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Purpose: Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization., Results: OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% p value = 0.037 and in the whole area, at 5% p value = 0.028) and an increase in vascular density in the deep fovea (DVP) (at 10% p value = 0.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (p = 0.0002) and glucose values (p = 0.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, p value: 0.095) in the whole district., Conclusion: Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance., (© 2024. The Author(s).)

Objective: Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications., Methods: This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®., Results: All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24-26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported., Significance: This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases., (© 2024 International League Against Epilepsy.)

Functional Hypothalamic Amenorrhea (FHA) is a condition characterized by the absence of menstruation, which is increasingly affecting young women. However, specific recommendations for treating and preventing this condition are lacking. Based on a review of the available literature, this article provides practical and feasible dietary management recommendations for healthcare professionals and researchers in women's health and nutrition. It answers the question of what interventions and nutritional recommendations are necessary to restore menstrual function in women struggling with FHA. Physicians recommend an energy availability threshold of 30 kcal/kg FFM/day to prevent FHA. Also, energy availability below and above this threshold can inhibit LH pulsation and cause menstrual disorders. In addition, the risk of menstrual disorders increases with a decrease in the caloric content of the diet and the duration of the energy deficit, and women with FHA have significantly lower energy availability than healthy women. It is essential to ensure that adequate kilocalories are provided throughout the day (regular meals that are a source of proper glucose) to avoid a negative energy balance, as glucose has been proven to affect LH pulses and T3 and cortisol concentrations in the body. Dietary intervention should focus on increasing the caloric content of the diet, thus increasing energy availability and restoring energy balance in the body. Treatment and diagnosis should also focus on body composition, not just body weight. An increase in body fat percentage above 22% may be required to restore menstrual function. In women with FHA, even an increase in body fat mass of one kilogram (kg) increases the likelihood of menstruation by 8%. It is advisable to reduce the intensity of physical activity or training volume, while it is not advisable to give up physical activity altogether. It is also important to ensure adequate intake of micronutrients, reduce stress, and incorporate cognitive-behavioral therapy.

It is widely known that estrogen has a fundamental role to play in skeletal homeostasis. In the most reductionist sense, the action of estrogen can be surmised as anti-resorptive. Estrogen prevents the break-down of bone. It therefore follows that estrogen deficiency states, such as the menopause and functional hypothalamic amenorrhoea (FHA), are often characterised by increased bone remodelling and disrupted skeletal homeostasis. FHA is the cessation of menstruation secondary to abnormal signalling between the hypothalamus and pituitary gland due to deficient pulsatile secretion of Gonadotrophin Releasing Hormone (GnRH). Functional hypothalamic amenorrhoea is frequently a consequence of women suffering with eating disorders. The development of FHA secondary to eating disorders is an evolutionary adaptive response to chronic metabolic energy deficiency. Fundamentally, preservation of life is biologically prioritised over dispensable physiological process such as reproduction. Consequently, the hypothalamic-pituitary-ovarian (HPO) axis fails, which disrupts menstrual function and ovulation, culminating in a state of estrogen deficiency. One of the most important and long-lasting deleterious consequences of FHA is disrupted skeletal homeostasis and bone loss. Estrogen replacement, most commonly in the form of combined hormone replacement therapy (HRT) or the combined oral contraceptive pill (COCP), is advised for women with an early menopause to prevent bone loss. Arguably, estrogen replacement should also be utilised in the context of FHA. However, the optimum estrogen regime for women with FHA remains under-researched and so management is not evidence-based., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS)., Methods: A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging., Results: Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS (p = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD (p = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%; p = 0.095 and p = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic-pituitary-adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%; p = 0.007 and p = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy., Conclusions: MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: To describe a rare seizure semiology originating from a hypothalamic hamartoma in a child, along with unusual ictal onset and connectivity pattern, and provide a review of the pathophysiology of epilepsy associated with hypothalamic hamartoma and management., Methods: A detailed retrospective chart review and literature search were performed using Pubmed and Embase., Results: We present a case of a three-year-old male who presented with dyscognitive seizures with onset at age 22 months. Stereoelectroencephalography exploration confirmed the onset in hypothalamic hamartoma with rapid propagation to the temporal-parietal-occipital association cortex and precuneus. The patient's epilepsy was cured with laser ablation of the hamartoma., Conclusion: Published literature mostly describes a more anterior frontal or temporal epileptic network with primarily gelastic seizures being the hallmark type of seizures associated with hypothalamic hamartoma. We highlight a rare posterior cortex network with an atypical presentation of focal nonmotor seizures with impaired awareness in the setting of a hypothalamic hamartoma. Stereotactic laser ablation of the hamartoma rendered seizure freedom. Early diagnosis and appropriate treatment can lead to seizure freedom., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

The post-surgical outcome for Hypothalamic Hamartoma (HH) related epilepsy in terms of seizure freedom (SF) has been extensively studied, while cognitive and psychiatric outcome has been less frequently reported and defined. This is a systematic review of English language papers, analyzing the post-surgical outcome in series of patients with HH-related epilepsy (≥5 patients, at least 6 months follow-up), published within January 2002-December 2022. SF was measured using Engel scale/equivalent scales. We looked at the outcome related to different surgical techniques, and HH types according to Delalande classification. We evaluated the neuropsychological and neuropsychiatric status after surgery, and the occurrence of post-surgical complications. Forty-six articles reporting 1318 patients were included, of which ten pediatric series. SF was reported in 686/1222 patients (56,1%). Delalande classification was reported in 663 patients from 24 studies, of which 70 were type I HH (10%), 320 were type II HH (48%), 189 were type III HH (29%) and 84 were type IV HH (13%). The outcome in term of SF was reported in 243 out of 663 patients. SF was reported in 12 of 24 type I HH (50%), 80 of 132 type II HH (60,6%), 32 of 59 type III HH (54,2%) and 12 of 28 type IV HH (42,9%). SF was reached in 129/262 (49,2%) after microsurgery, 102/199 (51,3%) after endoscopic surgery, 46/114 (40,6%) after gamma knife surgery, 245/353 (69,4%) after radiofrequency thermocoagulation, and 107/152 (70,4%) after MRI-guided laser interstitial thermal therapy. Hyperphagia/weight gain were the most reported surgical complications. Others were electrolyte alterations, diabetes insipidus, hypotiroidism, transient hyperthermia/poikilothermia. The highest percentage of memory deficits was reported after microsurgery, while hemiparesis and cranial nerves palsy were reported after microsurgery or endoscopic surgery. Thirty studies reported developmental delay/intellectual disability in 424/819 (51,7%) patients. 248/346 patients obtained a global improvement (72%), 70/346 were stable (20%), 28/346 got worse (8%). 22 studies reported psychiatric disorders in 257/465 patients (55,3%). 78/98 patients improved (80%), 13/98 remained stable (13%), 7/98 got worse (7%). Most of the patients had non-structured cognitive/psychiatric assessments. Based on the available data, the surgical management in patients with HH related epilepsy should be individualized, aiming to reach not only the best epilepsy result, but also the optimal cognitive and psychiatric outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea (FHA)., Methods: A retrospective cohort study was conducted to summarize the clinical and endocrine characteristics of 58 patients with FHA at initial diagnosis and to follow up the recovery of ovulation and spontaneous menstruation in the patients to investigate these biochemical indicators and their effects on recovery outcomes., Results: Among patients with FHA, 13.8% (8/58) and 15.5% (9/58) had above moderately severe depressive and severe anxiety symptoms respectively, and 25.9% (15/58) were at high risk for eating disorders. 34.5% (20/58) were included assessed as having recovered. The non-recovered group had higher scores on the Patient Health Questionnaire (PHQ-9) ( p  = .022) and higher scores on the Eating Attitude Test-26 (EAT-26) ( p  = .03) as well as bulimia and food preoccupation ( p  = .041). Follicle diameter >5 mm at initial diagnosis was an independent factor influencing recovery of reproductive axis function (odds ratio = 7.532; 95% confidence interval, 1.321-42.930; p  = .023)., Conculsions: Mood disorders and a certain risk of eating disorders were present in FHA.These, together with weight loss, endocrine and follicle size, could influence the outcome.

Purpose: The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea., Methods: Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients' group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol., Results: SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes (p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH., Conclusion: When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular "compaction" could be a first phase of hypoestrogenism adaptation., (© 2024. The Author(s).)

Background: Hypothalamus hamartomas (HHs) are rare, congenital, tumor-like, and nonprogressive malformations resulting in drug-resistant epilepsy, mainly affecting children. Gelastic seizures (GS) are an early hallmark of epilepsy with HH. The aim of this study was to explore the disease progression and the underlying physiopathological mechanisms of pathological laughter in HH., Methods: We obtained clinical information and metabolic images of 56 HH patients and utilized ictal semiology evaluation to stratify the specimens into GS-only, GS-plus, and no-GS subgroups and then applied contrasted trajectories inference (cTI) to calculate the pseudotime value and evaluate GS progression. Ordinal logistic regression was performed to identify neuroimaging-clinical predictors of GS, and then voxelwise lesion network-symptom mapping (LNSM) was applied to explore GS-associated brain regions., Results: cTI inferred the specific metabolism trajectories of GS progression and revealed increased complexity from GS to other seizure types. This was further validated via actual disease duration (Pearson R = 0.532, P = 0.028). Male sex [odds ratio (OR) = 2.611, P = 0.013], low age at seizure onset (OR = 0.361, P = 0.005), high normalized HH metabolism (OR =  - 1.971, P = 0.037) and severe seizure burden (OR =  - 0.006, P = 0.032) were significant neuroimaging clinical predictors. LNSM revealed that the dysfunctional cortico-subcortico-cerebellar network of GS and the somatosensory cortex (S1) represented a negative correlation., Conclusions: This study sheds light on the clinical characteristics and progression of GS in children with HH. We identified distinct subtypes of GS and demonstrated the involvement of specific brain regions at the cortical-subcortical-cerebellar level. These valuable results contribute to our understanding of the neural correlates of GS., (© 2023. The Author(s).)

Achieving favorable seizure outcomes is challenging in patients with seizures resulting from hypothalamic hamartoma. Although minimally invasive and non-invasive surgical procedures are used to treat this population, these procedures have limitations. Therefore, we analyzed the outcomes of patients with hypothalamic hamartoma following direct resection. We included 159 patients with hypothalamic hamartoma who underwent direct resection using the transcallosal interforniceal approach between 2011 and 2018. The relationships between clinical parameters and seizure outcomes were analyzed. In total, 55.3% achieved gross total resection and 25.2% underwent near-total resection. Of all patients, 79.2% were overall seizure-free at one year, but this number dropped to 77.0% at more than five years. Moreover, 88.4% (129/146) reached gelastic seizure (GS)-free status at one year and this number increased to 89.0% (97/109) at more than five years. Seventy-one patients took antiseizure medication (ASM) long-term, 68 took it for one year, and 11 took it for one-half year. The duration of ASM consumption (p < 0.001) and extent of hypothalamic hamartoma resection (p = 0.016) were significant independent predictors of long-term overall seizure-free survival, while the duration of ASM consumption (p = 0.011) and extent of hypothalamic hamartoma resection (p = 0.026) were significant independent predictors of long-term GS-free survival. Most patients' behavior, school performance, and intelligence were not affected after surgery. Direct resection is effective and safe strategy for patients with hypothalamic hamartomas. Hypothalamic hamartomas should be removed as completely as possible, and patients should take ASM long-term following surgery to reach long-term overall seizure-free or GS-free status., (© 2024. The Author(s).)

Objectives: Sarcoidosis is a multi-system granulomatous disease of unknown origin. It is mainly thought of as a lung disease but it can affect any organ system. Sinus and endocrine dysfunctions are described but are rare and seldomly linked with sarcoidosis., Methods: Here we describe a case of a young Caucasian man who already visited multiple care givers for sinusitis, erectile dysfunction and anorexia. He presented at the emergency department with fever and emaciation, polyuria and polydipsia. The results of the blood sampling revealed a hypercalcaemia as well as abnormal thyroid function., Results: After biochemical, radiological and histopathological workup, he was diagnosed with pulmonary sarcoidosis. Treatment with corticosteroids resulted in resolution of the sinusitis and normalisation of the calcemia, as well as the thyroid function while the impotence, polydipsia and polyuria remained. Elaboration revealed extra-pulmonary involvement of the sarcoidosis with dysfunction of the hypothalamic-pituitary axis with hypogonadotropic hypogonadism and diabetes insipidus due to a sellar mass., Conclusion: This is a rare case of systemic sarcoidosis with both thoracic and extra thoracic manifestations, with pituitary and sinus involvement. It shows that sarcoidosis can affect any organ system and diagnosis can be difficult in case of extrapulmonary manifestations.

Functional hypothalamic amenorrhea (FHA) is one of the most common causes of both primary and secondary amenorrhea in women of reproductive age. It is characterized by chronic anovulation and the absence of menses that appear as a result of stressors such as eating disorders, excessive exercise, or psychological distress. FHA is presumed to be a functional disruption in the pulsatile secretion of hypothalamic gonadotropin-releasing hormone, which in turn impairs the release of gonadotropin. Hypoestrogenism is observed due to the absence of ovarian follicle recruitment. Numerous neurotransmitters have been identified which play an important role in the regulation of the hypothalamic-pituitary-ovarian axis and of which the impairment would contribute to developing FHA. In this review we summarize the most recent advances in the identification of contributing neuroendocrine disturbances and relevant contributors to the development of FHA., (© 2023. The Author(s).)

Background: Nonalcoholic steatohepatitis (NASH) is an important etiology of hepatocellular carcinoma (HCC), and there is no established therapy for this syndrome. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD(NET)) is an extremely rare syndrome considered to be life-threatening, with death occurring around 10 years of age. We present the oldest known autopsy case of this syndrome that developed HCC. This case provided important information on not only improving the course of this syndrome, but also understanding the natural history and therapeutic modalities of NASH and HCC., Methods: The patient was diagnosed with ROHHAD(NET) syndrome in childhood, and liver cirrhosis due to NASH was diagnosed at age 17. HCC was detected at age 20, and embolization and irradiation were performed. At age 21, she died from accidental acute pancreatitis and subsequent liver failure and pulmonary hemorrhage., Results: Rapid onset of obesity, hypoventilation, and hypothalamic disturbance appeared in childhood and was diagnosed as this syndrome. At age 17, liver cirrhosis due to NASH was diagnosed by liver biopsy, and at age 20, HCC was diagnosed by imaging. Transarterial chemoembolization and irradiation were performed, and the HCC was well controlled for a year., Conclusion: At age 21, she died from accidental acute pancreatitis, subsequent liver failure and pulmonary hemorrhage. Autopsy revealed that the HCC was mostly necrotized. This case was valuable not only for other ROHHAD(NET) syndrome cases, but also in improving our understanding of the natural history of NASH and HCC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Status gelasticus is a rare form of status epilepticus characterized by prolonged and/or clustered gelastic seizures. The review encompasses an analysis of cases reported in the literature, focusing on causes, clinical-electroencephalographic features, and therapeutic interventions. The study reveals the challenges in defining and understanding status gelasticus due to its diverse etiologies and limited reported cases. The association with hypothalamic hamartomas and other brain abnormalities underscores the importance of thorough evaluations. The review also discusses new treatments, including medications and less invasive surgeries. While progress has been made, the study points out challenges in diagnosing and managing this complex condition, highlighting the importance of ongoing research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep-wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin-melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long-term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future., (© 2024 John Wiley & Sons Ltd.)

Introduction: Hypothalamic hamartomas (HHs) are deep-seated congenital lesions that typically lead to pharmacoresistant epilepsy and a catastrophic encephalopathic syndrome characterised by severe neuropsychological impairment and decline in quality of life. A variety of surgical approaches and technologies are available for the treatment of HH-related pharmacoresistant epilepsy. There remains, however, a paucity of literature directly comparing their relative efficacy and safety. This protocol aims to facilitate a systematic review and meta-analysis that will characterise and compare the probability of seizure freedom and relevant postoperative complications across different surgical techniques performed for the treatment of HH-related pharmacoresistant epilepsy., Methods and Analysis: This protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data guidelines. Three major databases, PubMed, Embase and Scopus, will be systematically searched from database inception and without language restrictions for relevant articles using our predefined search strategy. Title-abstract and full text screening using inclusion and exclusion criteria created a priori will be performed by two independent reviewers to identify eligible articles. Conflicts will be resolved via discussion with a third team member. Following data extraction of both study-level and individual patient data (IPD), a study-level and IPD meta-analysis will be performed. Study-level analysis will focus on assessing the degree of heterogeneity in the data and quantifying overall seizure outcomes for each surgical technique. The IPD analysis will use multivariable regression to determine perioperative predictors of seizure freedom and complications that can guide patient and technique selection., Ethics and Dissemination: This work will not require ethics approval as it will be solely based on previously published and available data. The results of this review will be shared via conference presentation and submission to peer-reviewed neurosurgical journals., Prospero Registration: CRD42022378876., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Children with acquired hypothalamic obesity, e.g. following treatment for pediatric craniopharyngioma are at great risk for metabolic syndrome, cardiovascular health problems and premature mortality. Treatment for acquired hypothalamic obesity has thus far been disappointing. Several interventions were reported to be partially successful, including dextro-amphetamine and GLP-1R agonists, although results in acquired hypothalamic obesity are conflicting. Disruption of signaling through the melanocortin-4 receptor (MC4R) pathway results in hyperphagia and severe early-onset hypothalamic obesity. Recently, the MC4R agonist setmelanotide has shown promising results in children with genetic forms of hypothalamic obesity; POMC, PCSK1 and LEPR. Patient quotes such as "we have our family life back" illustrate the magnitude of the effect. Targeted hormone replacement therapy with a MC4R agonist for acquired hypothalamic obesity could be a game-changer. Preliminary results of setmelanotide treatment in 14, mostly pediatric, patients with acquired hypothalamic obesity are promising. The FDA has recommended that a prospective, randomized, blinded trial be conducted over a 12 months treatment period, comparable to pivotal trials for other obesity drugs. It may be discussed whether setmelanotide should be regarded as an obesity drug or whether it may be envisioned as an agent for hypothalamic substitution therapy. In this commentary we discuss the trial that is currently recruiting patients with acquired hypothalamic obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Prof. HM, Dr. CD, and Dr. HvS have received travel and accommodation costs for an international meeting from Rhythm Pharmaceuticals. The Princess Máxima Center has received funding for the organization of the 6th Post-graduate course Craniopharyngioma in 2023 from the companies Rhythm Pharmaceuticals, Novo Nordisk and Pfizer. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 van Santen, Denzer and Müller.)

Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

Context: Endothelial dysfunction is a preclinical cardiovascular disease (CVD) marker. Due to various neuroendocrine aberrations, functional hypothalamic amenorrhea (FHA) may be a sex-specific risk factor for CVD in young women., Objective: To investigate endothelial function in women with FHA, compared with eumenorrheic controls and recently menopausal women., Methods: We performed a cross-sectional analysis among women with FHA (n = 30), eumenorrheic controls (n = 29), and recently menopausal women (n = 30). FHA was defined as amenorrhea ≥3 consecutive months, estradiol <50 pg/mL, follicle-stimulating hormone (FSH) < 10 mIU/mL, and luteinizing hormone (LH) < 10 mIU/mL, excluding other etiologies. Participants were recruited through obstetrics and gynecology referrals, social media advertising, and review of electronic health records. Preclinical CVD was measured using EndoPAT 2000 to calculate reactive hyperemic index (RHI). RHI ≤1.67 indicates endothelial dysfunction., Results: Mean estradiol levels in women with FHA, as compared with eumenorrheic controls and recently menopausal women, were 29.0 ± 18.1, 46.4 ± 15.7, and 10.9 ± 14.4 pg/mL (P < .0001), respectively. Women with FHA had lower insulin (P = .0095) and higher cortisol (P = .0004) compared with controls. RHI was significantly lower in women with FHA compared with eumenorrheic controls and recently menopausal women (1.8 ± 0.5 vs 2.2 ± 0.5 vs 2.2 ± 0.6, respectively; P = .008), and 35% of women with FHA had RHI ≤1.67, consistent with endothelial dysfunction., Conclusion: These results demonstrate endothelial dysfunction in 1 out of 3 young women with FHA. FHA may be a contributor to preclinical CVD, and it is not explained by hypoestrogenemia alone., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Several surgical options are available for treating hypothalamic hamartoma-related epilepsy but their respective efficacy and safety profiles are poorly defined., Methods: A literature search identified English-language articles reporting series of patients (minimum 3 patients with a follow-up ≥12 months) operated on by either microsurgery, endoscopic surgery, radiosurgery, radiofrequency thermocoagulation or laser interstitial thermal therapy for hypothalamic hamartoma-related epilepsy. The unit of analysis was each selected study. Pooled rates of seizure freedom and of neurological and endocrinological complications were analyzed using meta-analysis to calculate both fixed and random effects. The results of meta-analyses were compared., Results: Thirty-nine studies were included. There were 568 and 514 participants for seizure outcome and complication analyses, respectively. The pairwise comparison showed that: i) the proportion of seizure-free cases was significantly lower for radiosurgery as compared to microsurgery, radiofrequency thermocoagulation and laser ablation, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation; ii) the proportion of permanent hypothalamic dysfunction was significantly higher for microsurgery as compared to all other techniques, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation and laser ablation; iii) the incidence of permanent neurological disorders was significantly higher for microsurgery as compared to endoscopic surgery, radiosurgery and radiofrequency thermocoagulation, and significantly lower for radiosurgery as compared to laser ablation., Conclusions: Minimally invasive surgical techniques, including endoscopic surgery, radiofrequency thermocoagulation and laser ablation, represent an acceptable compromise between efficacy and safety in the treatment of hypothalamic hamartoma-related epilepsy. Microsurgery and radiosurgery should be considered in carefully selected cases., Competing Interests: Declaration of Competing Interest Michele Rizzi served as paid consultant testimony for WISE srl in the last 2 years. None of the other Authors has any conflict of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The relevance of secondary epileptogenesis for human epilepsy remains a controversial subject decades after it was first described in animal models. Whether or not a previously normal brain region can become independently epileptogenic through a kindling-like process has not, and cannot, be definitely proven in humans. Rather than reliance on direct experimental evidence, attempts to answering this question must depend on observational data. In this review, observations based largely upon contemporary surgical series will advance the case for secondary epileptogenesis in humans. As will be argued, hypothalamic hamartoma-related epilepsy provides the strongest case for this process; all the stages of secondary epileptogenesis can be observed. Hippocampal sclerosis (HS) is another pathology where the question of secondary epileptogenesis frequently arises, and observations from bitemporal and dual pathology series are explored. The verdict here is far more difficult to reach, in large part because of the scarcity of longitudinal cohorts; moreover, recent experimental data have challenged the claim that HS is acquired consequent to recurrent seizures. Synaptic plasticity more than seizure-induced neuronal injury is the likely mechanism of secondary epileptogenesis. Postoperative running-down phenomenon provides the best evidence that a kindling-like process occurs in some patients, evidenced by its reversal. Finally, a network perspective of secondary epileptogenesis is considered, as well as the possible role for subcortical surgical interventions., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively., Methods: Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate., Results: The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%., Conclusion: This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Miao, Fan, Peng, Li, Chen, Bai, Wei, Deng, Zhao, Wu, Ge, Gong and Wu.)

Hypothalamic obesity (HO) is a complex and rare disorder affecting multiple regulatory pathways of energy intake and expenditure in the brain as well as the regulation of the autonomic nervous system and peripheral hormonal signaling. It can be related to monogenic obesity syndromes which often affect the central leptin-melanocortin pathways or due to injury of the hypothalamus from pituitary and hypothalamic tumors, such as craniopharyngioma, surgery, trauma, or radiation to the hypothalamus. Traditional treatments of obesity, such as lifestyle intervention and specific diets, are still a therapeutic cornerstone, but often fail to result in meaningful and sustained reduction of body mass index. This review will give an update on pharmacotherapies of HO related to hypothalamic injury. Recent obesity drug developments are promising for successful obesity intervention outcomes., Competing Interests: CR has received compensation for consulting, advisory board participation, and speaking engagements from Rhythm Pharmaceuticals. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Roth and Zenno.)

Purpose: To determine long-term outcome for seizure control and clinical predictors for seizure freedom in patients undergoing surgical treatment for epilepsy associated with hypothalamic hamartoma (HH)., Methods: 155 patients underwent surgical treatment for HHs and treatment-resistant epilepsy at one center (Barrow Neurological Institute at St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA) between February 2003 and June 2010. Data collection included medical record review and direct follow-up interviews to determine seizure outcome. Statistical analysis included descriptive summaries of patient characteristics and time-to-event analysis for seizure freedom., Results: Long-term survival with follow-up of at least five years since first surgical treatment was available for 108 patients (69.7% of the treatment cohort). The surgical approach for first HH intervention consisted of transventricular endoscopic resection (n = 57; 52.8%), transcallosal interforniceal resection (n = 35; 32.4%), pterional resection (n = 7; 6.5%), and gamma knife radiosurgery (n = 9; 8.3%). Multiple surgical procedures were required for 39 patients (36.1%). There were 10 known deaths from all causes in the treatment cohort (6.5%). Of these, one (0.6%) was related to immediate complications of HH surgery, three (1.9%) were attributed to Sudden Unexpected Death in Epileptic Persons (SUDEP), and one (0.6%) to complications of status epilepticus. For surviving patients with long-term follow-up, 55 (50.9%) were seizure-free for all seizure types. Univariable analysis showed that seizure-freedom was related to 1) absence of a pre-operative history for central precocious puberty (p = 0.01), and 2) higher percentage of HH lesion disconnection after surgery (p = 0.047). Kaplan-Meier survival analysis shows that long-term seizure outcome following HH surgery is comparable to short-term results., Summary: These uncontrolled observational results show that long-term seizure control following HH surgical treatment is comparable to other forms of epilepsy surgery. Late relapse (at least one year after surgery) and SUDEP do occur, but in a relatively small number of treated patients. These results inform clinical practice and serve as a comparable benchmark for newer technologies for HH surgery, such as magnetic resonance imaging-guided laser interstitial thermal therapy, where long-term outcome results are not yet available., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Hypothalamic hamartomas are benign lesions associated with drug resistant epilepsy. Surgical treatment has become an increasingly utilised approach with promising results. This study aims to evaluate seizure outcome and complications after surgery in a population-based series of patients with intractable epilepsy and hypothalamic hamartoma., Methods: All patients with hypothalamic hamartoma treated with epilepsy surgery in Sweden since 1995 with at least two years of follow-up were included. Preoperative, two-, five- and ten-year prospective longitudinal data were collected from The Swedish National Epilepsy Surgery Register. Data included seizure types and frequency, duration of epilepsy, clinical characteristics, neurological deficits, cognitive level and complications. In a subgroup from Gothenburg, we also analysed data not included in the register such as classification of hamartomas, surgical procedures and gelastic seizures., Results: Eighteen patients were operated on during the period 1995-2020. The median age at epilepsy onset was 6 months and age at surgery 13 years. Four were seizure free and another four had ≥75% reduction in seizure frequency at the two-year follow-up. Two of the 13 patients with a long-term follow-up (five or ten years) were seizure-free and four had ≥75% reduction in seizure frequency. Three had an increased seizure frequency. No major complications were seen. Five had minor complications. In the Gothenburg subgroup all had open pterional disconnection or intraventricular endoscopic disconnection. Six of 12 were free from gelastic seizures at the two-year follow-up and six of eight at the long-term follow-up., Conclusion: This study supports surgical treatment of hypothalamic hamartomas as a safe method with a low risk of permanent complications. The seizure reduction seems to be persistent over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Objective: To assess seizure semiology and disease evolution in a large number of hypothalamic hamartoma (HH) patients., Methods: Seizure semiology and associated medical records for 78 patients with HH-related epilepsy were retrospectively reviewed. Potential predictors of seizure types were assessed through univariate and binary logistic regression analyses., Results: 57 (73.1%) patients presented with gelastic seizures at the onset of epilepsy, of whole 39 (68.4%) experienced additional seizure types with a mean latency interval of 4.59 years. Automatism, version, and sGTCs were increasingly common with disease evolution. The intraventricular size of HH was significantly negatively correlated with the disease evolution interval (r = -0.445, p = 0.009). A significantly higher rate of patients with automatism in the DF-II group relative to the DF-III group was found in both χ 2 (X = 6.07, p = 0.014) and logistic regression analyses (B = 3.196, p = 0.020)., Interpretation: Gelastic seizures are the most common initial seizure type in HH patients, but variable semiologies occur with disease evolution. The intraventricular HH lesion size is an important determinant of epilepsy evolution. DF-II HH lesions contribute to a higher chance of automatism evolution. The present study furthers our understanding of the dynamic organization of the seizure network affected by HH., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Craniopharyngioma is a benign tumor originating from the sellar region. Damages in this area caused by the tumor itself, surgery, or radiotherapy may result in severe hypothalamic-pituitary dysfunction (HPD) and eventually lead to a significant impairment in the long-term quality of life of patients. This study aimed to investigate the characteristics of HPD in patients with adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) and to identify the factors affecting HPD after surgery., Methods: In this single-center retrospective study, a total of 742 patients with craniopharyngioma were included. The neuroendocrine function of these patients before and after surgery was investigated. The differences in hypothalamic-pituitary function between the ACP and PCP groups were compared. The factors influencing the aggravation of HPD after surgery were identified., Results: The median follow-up after surgery was 15 months. Before surgery, the proportion of patients with diabetes insipidus (DI) and hyperprolactinemia in the PCP group was significantly higher than that in the ACP group ( P <0.01), and the proportion of patients with adrenocortical hypofunction in the PCP group was significantly lower than that in the ACP group ( P =0.03). Most cases of ACP originated in the sellar region, while most cases of PCP originated in the suprasellar region ( P <0.01). More patients experienced adenohypophyseal hypofunction, DI, and hypothalamic obesity at postoperative follow-up than at onset in both the ACP and PCP groups (both P <0.01), with a higher increase observed in the ACP group ( P <0.01). Older age at CP onset, tumor recurrence or progression, and ACP type were risk factors for postoperative aggravation of HPD in CP patients., Conclusion: Surgical treatment significantly aggravated HPD in both the ACP and PCP groups, but the specific characteristics and risk factors leading to aggravation were different between the two groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Pei, Li, Li, Gui, Ni, Liu, Zhang and Zhong.)

Purpose: To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents., Methods: The literature (1965-2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause., Results: ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions., Conclusion: ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Russel described a rare clinical entity known as diencephalic syndrome (DS) in 1951, which was traditionally caused by a neoplasm in the hypothalamic-optic chiasmatic region. DS is characterized by severe emaciation despite adequate or slightly reduced caloric intake, locomotor hyperactivity, euphoria and other minor features. Current evidence suggests that a rare population of children with a similar phenotype may have their tumor located in the posterior fossa instead, defining the DS-like presentation, a rare entity with few cases reported in the literature., Methods: A thorough search of three databases (PubMed, Ovid Medline, and Ovid Embase) was conducted to identify relevant papers reporting children with DS associated with brainstem tumors. To our knowledge, only seven cases have been documented in the literature. Moreover, we present four of our own cases, focusing on the unusual clinical presentation, the diagnosis process, and the lag time between the initial symptoms and the definitive diagnosis., Results: In this review, the mean lag time between the onset of symptoms and diagnosis was 20.9 months (median: 16 months; range: 1.5-72 months), whereas in our series of cases, the time was 32.5 months (median: 33 months; range: 7-57 months)., Conclusion: Despite recent significant advances in neuro-oncology diagnostic tools, this mean lag time did not improve when compared with the previous literature review from 1976. Throughout these data, we aim to raise awareness in the hopes of detecting intracranial neoplasms earlier in cases of children with profound emaciation of unknown cause., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypothalamic hamartoma is a less common condition characterized by the several types of epileptic seizures including the gelastic type. It is reported that gelastic seizures are resistant to medical treatment with anticonvulsants, while stereotactic thermocoagulation or Gamma Knife radiosurgery are effective for seizure control. Here, we report an individual case where direct surgical resection disconnecting hypothalamic hamartoma from mammillothalamic tract resulted in complete disappearance of gelastic seizures without deterioration of cognitive function. A 6-year-old boy developed gelastic seizures at the age of 2 and suffered from precocious puberty. Anticonvulsants including carbamazepine and zonisamide failed to control seizures. The patient underwent direct division of the mammillothalmic tract by removal of hypothalamic hamartoma partially via anterior interhemispheric approach. It was observed that gelastic seizures disappeared completely after the surgical treatment without any endocrine and cognitive dysfunction for a follow-up period of 14 years. The mammillothalamic tract which connects anterior nucleus of thalamus and mammillary bodies plays a key role in gelastic seizures related to hypothalamic hamartoma. In this case, we disconnected the hamartoma specifically from the mammillary bodies and not from the rest of hypothalamus. Effectively, it enabled permanent control of seizures. This result shows that fibers connecting other hypothalamic structures and the dorsomedial nucleus of thalamus are not involved in gelastic seizure propagation from the hypothalamic hamartoma. When surgical treatment of hypothalamic hamartomas is performed it has high morbidity associated with hypothalamic disorders. Therefore, disconnection between hypothalamic hamartoma and mammillary bodies presents a possibility of reducing hypothalamic damage. Surgical disconnection between hamartoma and mammillothalamic tract carries minimal hypothalamic injury risk and our results suggest that it has the potential of seizure control for intractable gelastic seizures with less complications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypothalamic obesity (HO) is defined as abnormal weight gain due to physical destruction of the hypothalamus. Suprasellar tumors, most commonly craniopharyngiomas, are a classic cause of HO. HO often goes unnoticed initially as patients, families, and medical teams are focused on oncologic treatments and management of panhypopituitarism. HO is characterized by rapid weight gain in the first year after hypothalamic destruction followed by refractory obesity due to an energy imbalance of decreased energy expenditure without decreased food intake. Currently available pharmacotherapies are less effective in HO than in common obesity. While not a cure, dietary interventions, pharmacotherapy, and bariatric surgery can mitigate the effects of HO. Early recognition of HO is necessary to give an opportunity to intervene before substantial weight gain occurs. Our goal for this article is to review the pathophysiology of HO and to discuss available treatment options and future directions for prevention and treatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Prencipe, Marinelli, Varaldo, Cuboni, Berton, Bioletto, Bona, Gasco and Grottoli.)

The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gelastic seizures are rare epileptic manifestations characterized by laughter or a smile. The main etiology is represented by hypothalamic hamartoma, but also focal localization of the epileptogenic zone is described. We reviewed a group of patients with gelastic seizures to describe the semiology and to establish any difference related to diverse epilepsy etiologies. Thirty-five seizures from 16 patients (6 females) were reviewed. The study confirms that hypothalamic hamartoma is the more frequent etiology associated with gelastic seizures. Laughter represented the majority of gelastic ictal signs, while the ictal smile was less frequent. In 87.5% of patients, the manifestation of laughter or smile was the only ictal phenomenon, or the first and the most important clinical sign. Interestingly, it has been observed that patients with a lesion localized in the hypothalamic region had more frequently laughter with emotional involvement and that laughter was the only manifestation of the seizure. On the contrary, patients with lesions localized outside the hypothalamic region had more often seizures with laugh without emotional involvement, resembling a more mechanical action, and associated with other semeiological signs. It, therefore, seems possible to assume that the emotional involvement and the expression of mirth during the seizure, especially in children, are more frequently associated with hypothalamic hamartoma. On the contrary, when the semiology includes less conveyed emotion similar to a mechanical action and other symptoms, an extra hypothalamic localization should be considered., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Psychological factors have been found to be associated with functional hypothalamic amenorrhea (FHA); however, their role in the onset or persistence of FHA is still understudied. The study aims to assess the associations of psychological factors with the presence vs the absence of FHA., Methods: A systematic literature search has been conducted across the major databases (PubMed, PsycINFO, Scopus, and Embase) to explore the psychological factors associated with FHA. The search was limited to English-written articles published from 2000 onwards. Articles were selected based on stringent inclusion/exclusion criteria. After data extraction, meta-analysis and meta-synthesis were conducted., Results: Of 349 retrieved articles, eight studies were included. Findings indicate that the main psychological factors associated to FHA seem to be depression and eating attitudes, especially drive for thinness. FHA women present higher levels of anxiety, sleep disorders, dysfunctional attitudes, and alexithymia. The meta-analysis on drive for thinness revealed that the pooled MD across the studies was statistically significant both in the fixed 0.63 (95% CI: 0.31-0.95) and random model 0.70 (95% CI: 0.13-1.26). Likewise, as for depression, the pooled MD across the studies was statistically significant both in the fixed 0.60 (95% CI: 0.36-0.84) and random model 0.61 (95% CI: 0.20-1.01)., Discussion: Findings showed the association of psychological factors and FHA and recognized their involvement in the persistence of the disorder. A multidisciplinary approach should involve a collaborative process between gynecologists, clinical psychologists, and psychiatrists, from diagnosis to treatment. Longitudinal studies should be implemented with a comparison/control group or by including clinical psychologists in the psychological assessment and study design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bonazza, Politi, Leone, Vegni and Borghi.)

Objective: Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the "circumstances of" nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA)., Materials and Methods: One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay., Results: Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p  = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-β-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels., Conclusions: This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.

Objective: Young patients with hypothalamic hamartomas (HHs) often present with intractable epilepsy. Currently there are no established management guidelines for HH. The authors retrospectively reviewed their single-institution experience to delineate the role of stereotactic radiosurgery (SRS)., Methods: Seven patients with HHs (4 females; median age 13.7 years, range 2.5-25 years) with no prior resection underwent SRS between 1987 and 2022. The clinical history, epilepsy profile, radiographic findings, and neurological outcomes were characterized. HH topographical types were classified according to the Régis classification. Outcome measures included Engel seizure classification, HH response, and the need for additional surgical interventions., Results: All patients had Engel class IV epilepsy. A Leksell Gamma Knife was used to deliver a median margin dose of 18 Gy (range 16-20 Gy) to a median hamartoma volume of 0.37 cm3 (range 0.20-0.89 cm3). Seizure reduction was confirmed in 6 patients, and 2 patients had regression of their hamartoma. Two patients underwent resection and/or laser interstitial thermal therapy after SRS. At follow-up, 1 patient was seizure free, 4 patients achieved Engel class II, 1 patient had Engel class III, and 1 patient had Engel class IV seizure outcomes., Conclusions: SRS as the initial management option for HH was associated with a low risk of adverse effects. In this institutional series reviewing small-volume HHs treated with SRS, no adverse radiation effect was detected, and the majority of patients experienced seizure reduction. SRS should be considered as the first-line treatment for seizure control in patients with small-volume HHs.

In the original definition by Klinefelter, Albright and Griswold, the expression "hypothalamic hypoestrogenism" was used to describe functional hypothalamic amenorrhoea (FHA). Given the well-known effects of estrogens on bone, the physiopathology of skeletal fragility in this condition may appear self-explanatory. Actually, a growing body of evidence has clarified that estrogens are only part of the story. FHA occurs in eating disorders, overtraining, and during psychological or physical stress. Despite some specific characteristics which differentiate these conditions, relative energy deficiency is a common trigger that initiates the metabolic and endocrine derangements contributing to bone loss. Conversely, data on the impact of amenorrhoea on bone density or microarchitecture are controversial, and reduced bone mass is observed even in patients with preserved menstrual cycle. Consistently, oral estrogen-progestin combinations have not proven beneficial on bone density of amenorrheic women. Low bone density is a highly prevalent finding in these patients and entails an increased risk of stress or fragility fractures, and failure to achieve peak bone mass and target height in young girls. Pharmacological treatments have been studied, including androgens, insulin-like growth factor-1, bisphosphonates, denosumab, teriparatide, leptin, but none of them is currently approved for use in FHA. A timely screening for bone complications and a multidisciplinary, customized approach aiming to restore energy balance, ensure adequate protein, calcium and vitamin D intake, and reverse the detrimental metabolic-endocrine changes typical of this condition, should be the preferred approach until further studies are available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Indirli, Lanzi, Mantovani, Arosio and Ferrante.)

Objective: Hypothalamic hamartoma (HH) is a rare, nonmalignant, heterotopic developmental malformation that consists of a mixture of normal neurons and glial cells. Resection of HHs has been associated with high rates of mortality and morbidity. Therefore, minimally invasive ablation methods could be the best treatment option for HH. The most frequently used minimally invasive options for HH ablation are radiofrequency thermocoagulation (RFT), laser ablation (LA), and stereotactic radiosurgery., Methods: To investigate three minimally invasive procedures in the treatment of refractory seizures related to HH, the authors conducted a systematic search in March 2022 in the MEDLINE, Embase, Scopus, and Web of Science databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seizure freedom was the primary outcome of interest. The authors defined seizure freedom as Engel class I or International League Against Epilepsy class 1 or 2 or as the reported term "seizure freedom." The secondary outcome was long-term complications reported in studies. Both random- and fixed-effects models were used to calculate the pooled proportion of seizure freedom and complication rate with 95% confidence intervals. A modified version of the Joanna Briggs Institute (JBI) Critical Appraisal to assess the risk of bias was used., Results: The authors included 15 studies with 422 patients (RFT, n = 190; LA, n = 171; and Gamma Knife Radiosurgery [GKRS], n = 61). Generally, the mean incidences of overall seizure freedom after minimally invasive procedures were 77% (95% CI 0.74-0.81) and 68% (95% CI 0.57-0.79) using fixed- and random-effects models, respectively. The mean incidence of overall seizure freedom after RFT was 69% (95% CI 0.63-0.75), and the mean incidences of overall seizure freedom after LA and GKRS were 87% (95% CI 0.82-0.92) and 44% (95% CI 0.32-0.57), respectively. The total complication rate with minimally invasive procedures was 13% (95% CI 0.01-0.26). The complication rate in each treatment was as follows: 5% (95% CI 0.0-0.12) for RFT, 20% (95% CI 0.0-0.47) for LA, and 22% (95% CI 0-0.65) for GKRS. Meta-regression analysis showed an association between older age and higher complication rates in the LA group., Conclusions: In this meta-analysis, LA showed superiority in seizure freedom over the other two methods. The complication rate associated with RFT was less than those in the other two methods; however, this difference was not statistically significant.

Objective: We aimed to determine the prevalence of epilepsy and neurodevelopmental disorders, including autism spectrum disorder, in children and adolescents with hypothalamic hamartoma (HH). We also sought to explore the relationship between these neurodevelopmental comorbidities and epilepsy and to establish the predictive value of structural characteristics of the hamartoma itself., Methods: We retrospectively studied a cohort of 62 children with HH, with neuroimaging reviewed at Great Ormond Street Hospital (GOSH) between 2008 and 2018. Clinical records were reviewed, cognitive and language data analysed, and MRI scans studied., Results: We confirmed a high burden of epilepsy (56%), autism (19%) and other neurodevelopmental disorders. Although rates of some neurodevelopmental disorders were significantly higher in those with epilepsy, autistic features and/or early developmental concerns often predated the onset of seizures, in particular generalized seizures, or occurred independently of seizures. We found a significant correlation between certain structural characteristics of the hamartoma itself and both epilepsy and certain neurodevelopmental comorbidities., Significance: These findings suggest that although seizure burden clearly contributes to the cognitive and behavioural phenotypes seen, the hamartoma itself, and particular characteristics of it, are likely to be primary determinants of both the epilepsy and neurodevelopmental profiles. It is also probable that the underlying aetiology, likely genetic, directly contributes to the clinical profile, with epilepsy, neurodevelopmental impairment and the hamartoma itself representing markers of this aetiology. We propose that atypical neurodevelopmental profiles in HH could best be conceptualized as a developmental and epileptic encephalopathy. These findings have implications for counselling, monitoring and treatment.

Purpose: Hypothalamic hamartomas (HH) are malformations responsible for drug-resistant epilepsy. HH are usually isolated or part of a genetic syndrome, such as Pallister-Hall. Exceptionally they can be associated with other brain malformations such as polymicrogyria (PMG) and periventricular nodular heterotopia (PNH). We discuss the origin of the seizures associated with this combination of malformations, through electrophysiological studies, and review the literature on this rarely reported syndrome., Methods: We retrospectively reviewed the patients with HH who had surgery between 1998 and 2020 and selected those with associated focal PMG and PNH, detected on MRIs. All patients had comprehensive clinical evaluation and surface video-EEG and one underwent stereoelectroencephalography (SEEG)., Results: Three male patients out of 182 were identified with a mean age at surgery of 7.5 years. MRI showed unilateral focal PMG (fronto-insulo-parietal, fronto-insulo-parieto-opercular, and fronto-insular, respectively) and multiple PNH homolateral to the main HH implantation side. In two patients, there were strong clinical and scalp EEG arguments for seizure onset within the HH. In the third, due to abnormalities on scalp video-EEG in the same area as PMG and the lack of gelastic seizures, SEEG was indicated and demonstrated seizure onset within the hamartoma. With a mean follow-up of 6 years, two patients were seizure-free., Conclusion: Our results show that HH is the trigger of epilepsy, which confirms the high epileptogenic potential of this malformation. In patients such as ours, as in those with isolated HH, we recommend to begin by operating the HH independently of seizure semiology or electrophysiological abnormalities., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Snakebite envenomation (SE) is an important tropical disease in India, causing significant morbidity and mortality among patients. The hormonal deficiencies due to the involvement of the pituitary in case of SE can present in either acute or delayed setting. Hypopituitarism (HP) is often an underrecognized and relatively rarely reported complication of this neglected disease., Methods: We present here the data of 15 patients diagnosed to have HP following systemic SE and are being currently followed-up in the Endocrinology outpatient department of a tertiary care hospital of South India. The study was approved by the Institute ethics committee, and informed onsent was taken from all the study patients. The study was a record-based retrospective analysis of the patients with HP following SE. Clinical data including lag time in diagnosis and type of snake were determined. Further, hormonal data including all the anterior pituitary functions (thyroid stimulating hormone, free T4, cortisol, insulin-like growth factor (IGF-1) luteinizing hormone, follicular-stimulating hormone, testosterone; prolactin) and water deprivation test to determine diabetes insipidus (DI) in patients with polyuria on follow-up were extracted from the records and the hospital information system. An experienced neuroradiologist examined the magnetic resonance imaging (MRI) findings of the pituitary., Results: The mean age of the patients was 43 ± 9 years and 80% were male. Around 90% of patients belonged to upper-lower socioeconomic status according to the modified Kuppuswamy scale. The commonest snake species reported was Russell's viper. Thirteen patients had delayed HP. The median duration from snakebite to onset of HP symptoms was 1 year (range 0.33-10 years). However, the median time from snakebite to the diagnosis of HP was 7 years (range 1-13 years). Central hypothyroidism and hypogonadism were present in all subjects. However, central hypocortisolism was noted in 93% of patients. Low IGF-1 was noted in all the six patients where data were available. One patient had partial central DI. Thirteen out of 15 patients had reduction of pituitary volume in MRI., Conclusion: HP in patients with SE can appear slowly and the diagnosis is frequently delayed for years. Following snakebite, multiple pituitary hormone deficiencies associated with radiological abnormalities like a significant reduction in the pituitary volume are common., Competing Interests: None

Background: Disconnection surgery for the treatment of epileptic hypothalamic hamartomas (HHs) is strategically difficult in cases with complex-shaped HHs, especially with bilateral hypothalamic attachments, despite its effectiveness., Objective: To evaluate the feasibility of a new approach for stereotactic radiofrequency thermocoagulation (SRT) using penetration of the third ventricle (SRT-TT) aiming to disconnect bilateral hypothalamic attachments in a single-staged, unilateral procedure., Methods: Ninety patients (median age at surgery, 5.0 years) who had HHs with bilateral hypothalamic attachments and were followed for at least 1 year after their last SRT were retrospectively reviewed., Results: Thirty-three patients underwent SRT-TT as initial surgery. Of the 58 patients after mid-2013 when SRT-TT was introduced, 33 underwent SRT-TT and 12 (20.7%) required reoperation (ReSRT), whereas 20 of 57 patients (35.1%) without SRT-TT underwent reoperation. Reoperation was required in significantly fewer patients after mid-2013 (n = 12 of 58, 20.7%) than before mid-2013 (n = 15 of 32, 46.9%) ( P = .01). Final seizure freedoms were not different between before and after mid-2013 (gelastic seizure freedom, n = 30 [93.8%] vs n = 49 [84.5%] and other types of seizure freedom, n = 21 of 31 [67.7%] vs n = 32 of 38 [84.2%]). Persistent complications were less in SRT-TT than in ReSRT using the bilateral approach, but not significantly. However, hormonal replacement was required significantly more often in ReSRT using the bilateral approach (4 of 9, 44.4%) than in SRT-TT (3 of 32, 9.4%) ( P = .01)., Conclusion: SRT-TT enabled disconnection of bilateral attachments of HHs in a single-staged procedure, which reduced the additional invasiveness of reoperation. Moreover, SRT-TT reduced damage to the contralateral hypothalamus, with fewer endocrinological complications than the bilateral approach., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: A giant hypothalamic hamartoma (GHH) is a rare congenital malformation only reported in a few cases in the literature and is often associated with precocious puberty, gelastic seizures, or less commonly, Pallister-Hall syndrome. Persistent syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare in infancy, and most patients with GHH do not develop persistent SIADH, usually only transient electrolyte disturbances postoperatively. Previous cases of GHH have not been associated with persistent derangements in antidiuretic hormone levels., Case Description: A 7-month-old male infant presented to our hospital with a history of an intracranial cystic lesion diagnosed at 23 weeks gestational age (GA), later impressed as a solid-cystic mass at 37 weeks GA by ultrasound prenatally. Postnatal MRI after birth showed a large mass with a dorsal cyst occupying the hypothalamus, causing hydrocephalus and brainstem compression. The patient started to have subtle seizures on the seventh day after birth and eventually developed dacrystic seizures. Hyponatremia with persistent SIADH was observed at 3 months of age before surgery. He received long-term oral sodium supplementation, polytherapy of anti-epileptic medications, ventriculocystostomy for progressive enlargement of the cystic cavity, and later surgical treatment for disconnection and partial resection which confirmed a histological diagnosis of hypothalamic hamartoma., Conclusion: In this case study, we present a novel association of GHH with persistent SIADH and a rare presentation of a cystic component at the dorsal part of the tumor. Clinicians should be aware of this potential endocrine derangement and provide emergent treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Functional hypothalamic amenorrhea is a state of reversible hypogonadism common in adolescents and young women that can be triggered by energy deficit or emotional stress or a combination of these factors. Energy deficit may be a consequence of (i) reduced caloric intake, as seen in patients with eating disorders, such as anorexia nervosa, or (ii) excessive exercise, when caloric intake is insufficient to meet the needs of energy expenditure. In these conditions of energy deficit, suppression of the hypothalamic secretion of gonadotrophin-releasing hormone (with resulting hypoestrogenism) as well as other changes in hypothalamic-pituitary function may occur as an adaptive response to limited energy availability. Many of these adaptive changes, however, are deleterious to reproductive, skeletal, and neuropsychiatric health. Particularly, normoestrogenemia is critical for normal bone accrual during adolescence, and hypoestrogenemia during this time may lead to deficits in peak bone mass acquisition with longstanding effects on skeletal health. The adolescent years are also a time of neurological changes that impact cognitive function, and anxiety and depression present more frequently during this time. Normal estrogen status is essential for optimal cognitive function (particularly verbal memory and executive function) and may impact emotion and mood. Early recognition of women at high risk of developing hypothalamic amenorrhea and its timely management with a multidisciplinary team are crucial to prevent the severe and long-term effects of this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pedreira, Maya and Misra.)

Hypothalamic hamartoma with gelastic seizures is a well-established cause of drug-resistant epilepsy in early life. The development of novel surgical techniques has permitted the genomic interrogation of hypothalamic hamartoma tissue. This has revealed causative mosaic variants within GLI3, OFD1 and other key regulators of the sonic-hedgehog pathway in a minority of cases. Sonic-hedgehog signalling proteins localize to the cellular organelle primary cilia. We therefore explored the hypothesis that cilia gene variants may underlie hitherto unsolved cases of sporadic hypothalamic hamartoma. We performed high-depth exome sequencing and chromosomal microarray on surgically resected hypothalamic hamartoma tissue and paired leukocyte-derived DNA from 27 patients. We searched for both germline and somatic variants under both dominant and bi-allelic genetic models. In hamartoma-derived DNA of seven patients we identified bi-allelic (one germline, one somatic) variants within one of four cilia genes-DYNC2I1, DYNC2H1, IFT140 or SMO. In eight patients, we identified single somatic variants in the previously established hypothalamic hamartoma disease genes GLI3 or OFD1. Overall, we established a plausible molecular cause for 15/27 (56%) patients. Here, we expand the genetic architecture beyond single variants within dominant disease genes that cause sporadic hypothalamic hamartoma to bi-allelic (one germline/one somatic) variants, implicate three novel cilia genes and reconceptualize the disorder as a ciliopathy., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma., Methods: The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression., Results: Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%., Conclusions: Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO., (© 2022 The Obesity Society.)

Background: A standardized approach for identifying and treating hypothalamic obesity (HO) in children with hypothalamic tumours is lacking., Objectives: To describe children with hypothalamic tumours at risk for obesity, assess outcomes of a novel HO clinical algorithm, and identify factors associated with weight gain., Methods: Retrospective analysis of youth with hypothalamic and suprasellar tumours, seen at a paediatric tertiary care centre from 2010 to 2020., Results: The study cohort (n = 130, 50% female, median age at diagnosis 5 [range 0-17]y) had a median duration of follow up of 5 (0.03-17)y. At last recorded body mass index (BMI) measurement, 34% had obesity, including 17% with severe obesity. Median onset of overweight and obesity after diagnosis was 6.2 (0.3-134) and 8.9 (0.7-65) months, respectively. After algorithm implementation (n = 13), the proportion that had an early dietitian visit (within 6 months) increased from 36% to 54%, (p = 0.498) and weight management referrals increased from 51% to 83% (p = 0.286). Higher BMI z-score at diagnosis was associated with overweight and obesity development (p < 0.001)., Conclusion: Patients with hypothalamic tumours commonly develop obesity. Use of a clinical algorithm may expedite recognition of HO. Further research is needed to identify predictors of weight gain and to develop effective treatment., (© 2022 World Obesity Federation.)