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Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitary hormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalk interruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to their similar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing to panhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor. She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably, menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism, hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights endocrinological landscape of transection of the pituitary stalk by acute trauma.

Objective: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center., Methods: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7-297.6) months., Results: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5-141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm 3 ) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm 3 ) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708-6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032-12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found., Conclusion: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm 3 ) and tumor progression were associated with new-onset hypopituitarism after a single GKRS., (© 2024. The Author(s).)

Background and Purpose: Multiple studies demonstrated hypothalamic-pituitary dysfunction in survivors of pediatric brain tumors. However, few studies investigated the trajectories of pituitary height in these patients and their associations with pituitary function. We aimed to evaluate longitudinal changes of pituitary height in children and adolescents with brain tumors, and their association with endocrine deficiencies., Materials and Methods: We conducted a retrospective analysis of 193 pediatric patients (54.9% male) diagnosed with brain tumors from 2002 to 2018, with a minimum of two years of radiological follow-up. Pituitary height was measured using MRI scans at diagnosis and at 2, 5, and 10 years post-diagnosis, with clinical data sourced from patient charts., Results: Average age at diagnosis was 7.6 ± 4.5 years, with a follow-up of 6.1 ± 3.4 years. 52.8% underwent radiotherapy and 37.8% experienced pituitary hormone deficiency. Radiation treatment was a significant predictor of decreased pituitary height at all observed time points (p = 0.016, p < 0.001, p = 0.008, respectively). Additionally, chemotherapy (p = 0.004) or radiotherapy (p = 0.022) history and pituitary height at 10 years (p = 0.047) were predictors of endocrine deficiencies. ANOVA revealed an expected increase in pituitary height over time in pediatric patients, but this growth was significantly impacted by radiation treatment and gender (p for interaction = 0.005 and 0.025, respectively)., Conclusion: Cranial irradiation in pediatric patients is associated with impairment of the physiologic increase in pituitary size; in turn, decreased pituitary height is associated with endocrine dysfunction. We suggest that pituitary gland should be evaluated on surveillance imaging of pediatric brain tumor survivors, and if small for age, clinical endocrine evaluation should be pursued., 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 B.V. All rights reserved.)

Summary: Background: Childhood-onset combined pituitary hormone deficiency (CPHD) has a wide spectrum of etiologies and genetic causes for congenital disease. We aimed to describe the clinical spectrum and genetic etiologies of CPHD in a single tertiary center and estimate the population-level incidence of congenital CPHD. Methods: The retrospective clinical cohort comprised 124 CPHD patients (48 with congenital CPHD) treated at the Helsinki University Hospital (HUH) Children's Hospital between 1985 and 2018. Clinical data were collected from the patient charts. Whole exome sequencing was performed in 21 patients with congenital CPHD of unknown etiology. Findings: The majority (61%;76/124) of the patients had acquired CPHD, most frequently due to craniopharyngiomas and gliomas. The estimated incidence of congenital CPHD was 1/16 000 (95%CI, 1/11 000-1/24 000). The clinical presentation of congenital CPHD in infancy included prolonged/severe neonatal hypoglycaemia, prolonged jaundice, and/or micropenis/bilateral cryptorchidism in 23 (66%) patients; despite these clinical cues, only 76% of them were referred to endocrine investigations during the first year of life. The median delay between the first violation of the growth screening rules and the initiation of GH Rx treatment among all congenital CPHD patients was 2·2 years, interquartile range 1·2–3·7 years. Seven patients harbored pathogenic variants in PROP1, SOX3, TBC1D32, OTX2, and SOX2, and one patient carried a likely pathogenic variant in SHH (c.676G>A, p.(Ala226Thr)). Interpretation: Our study suggests that congenital CPHD can occur in 1/16 000 children, and that patients frequently exhibit neonatal cues of hypopituitarism and early height growth deflection. These results need to be corroborated in future studies and might inform clinical practice. Funding: Päivikki and Sakari Sohlberg Foundation, Biomedicum Helsinki Foundation, and Emil Aaltonen Foundation research grants.

Purpose: This study was designed to assess the pituitary functions of patients with traumatic maxillofacial fractures and compare the results with healthy controls., Methods: Thirty patients (mean age, 38.14 ± 14.15 years; twenty-six male, four female) with a traumatic maxillofacial fracture at least 12 months ago (mean 27.5 ± 6.5 months) and thirty healthy controls (mean age, 42.77 ± 11.36 years; twenty-five male, five female) were included. None of the patients were unconscious following head trauma, and none required hospitalization in intensive care. Basal pituitary hormone levels of the patients were evaluated. All patients and controls had a glucagon stimulation test and an ACTH stimulation test to evaluate the hypothalamic-pituitary-adrenal axis and the GH-IGF-1 axis., Results: Five of thirty patients (16.6%) had isolated growth hormone (GH) deficiency based on a glucagon stimulation test (GST). The mean peak GH level after GST in patients with hypopituitarism (0.54 ng/ml) was significantly lower than those without hypopituitarism (7.01 ng/ml) and healthy controls (11.70 ng/ml) (P < 0.001). No anterior pituitary hormone deficiency was found in the patients, except for GH., Conclusion: Our study is the first to evaluate the presence of hypopituitarism in patients with traumatic maxillofacial fractures. Preliminary findings suggest that hypopituitarism and GH deficiency pose significant risks to these patients, particularly during the chronic phase of their trauma. However, these findings need to be validated in larger scale prospective studies with more patients., (© 2024. The Author(s).)

A 78-year-old man complained of subacute general fatigue and anorexia, following diplopia and gait disturbance. He demonstrated wide-based and small-stepped gait without objectively abnormal ocular movements. Brain ‍MRI showed enlargement of the pituitary stalk and gland with uniform contrast enhancement. PET-CT showed FDG ‍uptake in the pituitary gland, mediastinal lymph nodes, and left hilar lymph nodes. Blood investigations revealed panhypopituitarism and high serum IgG4 levels up to 265 ‍mg/dl. Histopathological examination revealed no IgG4-positive cell infiltration in the biopsied mediastinal lymph nodes. However, we suspected IgG4-associated hypophysitis based on the clinical symptoms and MRI findings, which were markedly resolved with steroid. Central masked diabetes insipidus was manifested, but was improved with oral desmopressin. We should pay close attention to the fact that IgG4-related hypophysitis may present with various symptoms regarded as indefinite complaints related to aging or underlying diseases, especially in elderly patients with multimorbidity.

Partial or complete deficiency of anterior or posterior pituitary hormone production leads to central hypoadrenalism, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency, or arginine vasopressin deficiency depending on the hormones affected. Hypopituitarism is rare and likely to be underdiagnosed, with an unknown but rising incidence and prevalence. The most common cause is compressive growth or ablation of a pituitary or hypothalamic mass. Less common causes include genetic mutations, hypophysitis (especially in the context of cancer immunotherapy), infiltrative and infectious disease, and traumatic brain injury. Clinical features vary with timing of onset, cause, and number of pituitary axes disrupted. Diagnosis requires measurement of basal circulating hormone concentrations and confirmatory hormone stimulation testing as needed. Treatment is aimed at replacement of deficient hormones. Increased mortality might persist despite treatment, particularly in younger patients, females, and those with arginine vasopressin deficiency. Patients with complex diagnoses, pregnant patients, and adolescent pituitary-deficient patients transitioning to adulthood should ideally be managed at a pituitary tumour centre of excellence., Competing Interests: Declaration of interests MF has received grants to Oregon Health and Science University from Ascendis and Novo Nordisk; occasional consulting fees from Ascendis, Novo Nordisk, and Pfizer; and has served (non-compensated) on the Pituitary Society and Endocrine Society board of directors. MC-C has received occasional kits for copeptin assays from ThermoFisher, speaking honoraria from Otsuka, and serves (non-compensated) on the European Society of Endocrinology board of directors. FL has received honoraria from Pfizer and Novo Nordisk, and served as Vice President of the Continuing Medical Education Committee for Association des Médecins Endocrinologues du Québec. MG has served on the advisory board of Novo Nordisk, received consulting and lecture presentation fees from Novo Nordisk, and has served (non-compensated) on the Pituitary Society board of directors. SM has received consulting fees from Novo Nordisk and serves (non-compensated) on the Pituitary Society board of directors., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: We describe a rare case of histopathologic-proven necrotizing infundibulo-hypophysitis (NIH)., Clinical History: A 40-year-old female presented with coexistence of central diabetes insipidus and hypopituitarism. Imaging disclosed a thickened infundibulum and a diffusely enlarged pituitary mass with gadolinium rim enhancement pattern. Microsurgical endonasal transsphenoidal resection was performed. The presence of extensive liquefactive necrosis, surrounded by lymphoplasmocytic inflammatory infiltrate, allowed for the diagnosis of NIH. Follow-up cranial imaging 10 months after surgery showed no evidence of reappearance of the lesion. There was no progression to panhypopituitarism., Conclusion: Surgery and histopathological confirmation are the key diagnostic feature in NIH. The current case is the fifth report of NIH and the first one with an indolent course and without progression to panhypopituitarism so far.

Hypopituitarism (HP) frequently occurs in patients presenting with sellar masses and despite recent advances in therapeutic options, HP patients consistently suffer from impaired quality of life due to psychological distress and cognitive dysfunction. These neurocognitive complications tend to persist in spite of surgical or biochemical remission of the disease making it especially challenging to segregate the effect of HP per se from other comorbidities such as the effect of tumour, surgery, radiation therapy, or complications caused by excess hormone production. Regardless, there is ample evidence to suggest that receptors for various pituitary hormones are abundantly expressed in key areas of central nervous system that are associated with memory and behaviour function and HP is also associated with poor sleep which can further exacerbate neurocognitive dysfunction. There is also evidence that hormonal replacement in HP patients partially restores these neurocognitive functions and improves sleep disorders. However, there is a need for creating better awareness among healthcare providers interacting with HP patients to enhance an earlier recognition of these disorder and their impact on quality of life despite initial remission. Importantly, there is a need to not only develop better and more cost-effective replacement therapies that would closely mimic the physiological hormonal release patterns, but also develop coping strategies for HP patients suffering from these complications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pituitary hormone deficiency, hypopituitarism, is a dysfunction resulting from numerous etiologies, which can be complete or partial, and is therefore heterogeneous. This heterogeneity makes it difficult to interpret the results of scientific studies with these patients.Adequate treatment of etiologies and up-to-date hormone replacement have improved morbidity and mortality rates in patients with hypopituitarism. As GH replacement is not performed in a reasonable proportion of patients, especially in some countries, it is essential to understand the known consequences of GH replacement in each subgroup of patients with this heterogeneous dysfunction.In this review on hypopituitarism, we will address some particularities regarding insulin resistance, which is no longer common in these patients with hormone replacement therapy based on current guidelines, metabolic syndrome and its relationship with changes in BMI and body composition, and to vascular complications that need to be prevented taking into account the individual characteristics of each case to reduce mortality rates in these patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The results of many studies in recent years indicate a significant impact of pituitary function on bone health. The proper function of the pituitary gland has a significant impact on the growth of the skeleton and the appearance of sexual dimorphism. It is also responsible for achieving peak bone mass, which protects against the development of osteoporosis and fractures later in life. It is also liable for the proper remodeling of the skeleton, which is a physiological mechanism managing the proper mechanical resistance of bones and the possibility of its regeneration after injuries. Pituitary diseases causing hypofunction and deficiency of tropic hormones, and thus deficiency of key hormones of effector organs, have a negative impact on the skeleton, resulting in reduced bone mass and susceptibility to pathological fractures. The early appearance of pituitary dysfunction, i.e. in the pre-pubertal period, is responsible for failure to achieve peak bone mass, and thus the risk of developing osteoporosis in later years. This argues for the need for a thorough assessment of patients with hypopituitarism, not only in terms of metabolic disorders, but also in terms of bone disorders. Early and properly performed treatment may prevent patients from developing the bone complications that are so common in this pathology. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The patient is a 41-year-old woman. She presented with vomiting and lightheadedness, and blood tests showed a generalized decrease in pituitary hormones and hyperprolactinemia. A head MRI showed increased signal intensity lesions on FLAIR image in the pituitary stalk, corpus callosum, periventricular area of the fourth ventricle, and superior cerebellar peduncle. The lesions were homogeneously enhanced, and a brain biopsy confirmed the diagnosis of primary diffuse large B-cell lymphoma of the central nervous system, and chemotherapy was started. Although the suprasellar region is a rare site for primary central nervous system lymphoma (PCNSL), it should be diagnosed early by biopsy.

Objective: Individuals with hypopituitarism (HPs) have an increased risk of developing non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) due to growth hormone deficiency (GHD). We aimed to investigate the possible mechanisms underlying the relationship between GHD and NAFLD using proteomic and metabolomic insights., Methods: Serum metabolic alternations were assessed in male HPs using untargeted metabolomics. A rat model of HP was established through hypophysectomy, followed by recombinant human growth hormone (rhGH) intervention. The mechanisms underlying GHD-mediated NAFLD were elucidated through the application of label-free proteomics and phosphorylation proteomics., Results: Metabolomic analysis revealed that biomarkers of mitochondrial dysfunction and oxidative stress, such as alanine, lactate, and creatine, were significantly elevated in HPs compared to age-matched controls. In rats, hypophysectomy led to marked hepatic steatosis, lipid peroxidation, and reduced glutathione (GSH), which were subsequently modulated by rhGH replacement. Proteomic analysis identified cytochrome P450s, mitochondrial translation elongation, and PPARA activating genes as the major distinguishing pathways in hypophysectomized rats. The processes of fatty acid transport, synthesis, oxidation, and NADP metabolism were tightly described. An enhanced regulation of peroxisome β-oxidation and ω-oxidation, together with a decreased NADPH regeneration, may exacerbate oxidative stress. Phosphoproteome data showed downregulation of JAK2-STAT5B and upregulation of mTOR signaling pathway., Conclusions: This study identified proteo-metabolomic signatures associated with the development of NAFLD in pituitary GHD. Evidence was found of oxidative stress imbalance resulting from abnormal fatty acid oxidation and NADPH regeneration, highlighting the role of GH deficiency in the development of NAFLD., 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 © 2024 Zhang, Chen and Fang.)

Purpose: To identify differences in the presentation and surgical outcomes between very large (30-39 mm) and giant (≥ 40 mm) (LARGE group) pituitary adenomas (PAs) compared to the smaller group (< 30 mm) (non-LARGE group)., Methods: Eighty patients with very large (n = 44) or giant (n = 36) PAs and 226 patients in the non-LARGE group who underwent tumor resection by pituitary surgery between 2008 and 2023 were studied. Hormonal, radiological, ophthalmological, and pathological data, and surgical outcomes were evaluated., Results: Preoperatively, patients of the LARGE group presented more frequently with visual impairment (82.5% vs. 22.1%, P < 0.001) and with pituitary apoplexy (15.0% vs. 2.7%, P < 0.001) than the non-LARGE group. Moreover, the LARGE group were more commonly associated with preoperative panhypopituitarism (28.8% vs. 6.2%, P < 0.001). This group presented cavernous sinus invasion more frequently (71.3% vs. 23.9%, P < 0.001). The non-LARGE group achieved surgical cure more often than the LARGE group (79.7% vs. 50.0%, P < 0.001), and the rate of major complications was higher in the latest (8.8% vs. 1.3%, P < 0.004)., Conclusions: PAs ≥ 30 mm are most frequently accompanied by hormonal dysfunction, cavernous sinus invasion, and visual impairment. All this implies lower resection rates and higher postoperative complications than the smaller adenomas, posing a real surgical challenge., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Although vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported., Case Presentation: An 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 μg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 μIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient's disease course was stable with continued thyroid and adrenal corticosteroid supplementation., Conclusions: Herein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination., (© 2024. The Author(s).)

Hypopituitarism is a relatively rare complication of hemorrhagic fever with renal syndrome. However, almost all available reported cases were total anterior pituitary hypofunction, isolated growth-hormone deficiency, or isolated gonadotropin deficiency. Here, we firstly describe a patient with partial hypopituitarism with ACTH deficiency as the main manifestation as a complication of hemorrhagic fever with renal syndrome., (© 2024. The Author(s).)

Objective: Assessment of posttraumatic hypothalamic-pituitary dysfunctions is expected to be the most relevant assessment to offer patients with severe intracranial affection. In this study, we aim to investigate the prevalence of hypopituitarism in patients with severe acquired traumatic brain injury (TBI) compared with nontraumatic brain injury (NTBI) and to relate pituitary insufficiency to functional and patient-reported outcomes., Design: This is a prospective study., Methods: We included patients admitted for inpatient neurorehabilitation after severe TBI (N = 42) and NTBI (N = 18). The patients underwent a pituitary function assessment at a mean of 2.4 years after the injury. Functional outcome was assessed by using Functional Independence Measure and Glasgow Outcome Scale-Extended (both 1 year after discharge from neurorehabilitation) and patient-reported outcome was assessed by using Multiple Fatigue Inventory-20 and EQ-5D-3L., Results: Hypopituitarism was reported in 10/42 (24%) patients with TBI and 7/18 (39%) patients with NTBI (P = .23). Insufficiencies affected 1 axis in 14/17 (82%) patients (13 hypogonadotropic hypogonadism and 1 growth hormone [GH] deficiency) and 2 axes in 3/17 (18%) patients (1 hypogonadotropic hypogonadism and GH deficiency, and 2 hypogonadotropic hypogonadism and arginin vasopressin deficiency). None had central hypoadrenalism or central hypothyroidism. In patients with both TBI and NTBI, pituitary status was unrelated to functioning and ability scores at 1 year and to patient-reported outcome scores at a mean of 2.4 years after the injury., Conclusion: Patients with severe acquired brain injury may develop long-term hypothalamus-pituitary insufficiency, with an equal occurrence in patients with TBI and NTBI. In both types of patients, mainly isolated deficiencies, most commonly affecting the gonadal axis, were seen. Insufficiencies were unrelated to functional outcomes and patient-reported outcomes, probably reflecting the complexity and heterogeneous manifestations in both patient groups., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer., Methods and Analysis: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis., Ethics and Disclosure: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal., Prospero Registration Number: CRD42021235163., 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.)

Background: Gamma knife radiosurgery (GKRS) is an established treatment option for residual and recurrent nonfunctioning pituitary adenoma (NFPA). This investigation assessed hormonal and radiologic outcomes after adjuvant and primary GKRS for NFPAs., Methods: This retrospective study included 252 patients with NFPA who underwent GKRS at a single center between 2005 and 2016. GKRS was performed as adjuvant procedure in 216 (85.8%) patients and as primary procedure in 36 (14.2%) patients. Characteristics of these two groups were compared., Results: Mean age was comparable between adjuvant and primary GKRS groups (48.3 ± 12.6 vs. 52.2 ± 13.2 years, respectively, p >  0.05). Adjuvant GKRS and primary GKRS groups were similar in terms of the mean prescribed radiation dose and tumor volume (15.1 ± 2.7 vs. 15.3 ± 1.9 Gy and 4.2 ± 3.6 vs. 3.1 ± 2.5 cm 3 , respectively, p >  0.05 for both). The rate of endocrine deficiency during 5-year follow-up showed similar trend in adjuvant and primary GKRS groups (3.7%, 8.7%, and 14.8% vs. 5.6%, 13.9%, and 27.8% at first, third, and fifth year time points, respectively). Tumor control rates were also similar (98.6%, 96.3%, and 93% vs. 100%, 97.3%, and 94.5% at first, third, and fifth year time points, respectively). In both groups, tumor volume >5 cm 3 was associated with higher rate of hypopituitarism and tumor progression., Conclusions: GKRS was effective both as adjuvant and primary procedure in patients with NFPA. Radiation dose of ≤13.5 Gy was associated with lower tumor control rate and tumor volume >5 cm 3 was associated with higher rates of hypopituitarism and tumor progression.

Objective: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS., Methods: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology., Results: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group., Conclusions: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Background: Lymphocytic hypophysitis is a rare autoimmune condition that usually presents during pregnancy and causes inflammation of the pituitary gland. Although the pathophysiology is not well understood, it often presents with headaches, visual disturbances, and symptoms of hypopituitarism. However, not all cases may present with hypopituitarism which can make this rare disease with an incidence of ~ 1 in 9 million much more difficult to diagnose., Case Presentation: We present a 35-year-old G4P4 woman with progressive vision loss and intermittent frontal headaches during her first trimester through 2 months postpartum. She presented with no symptoms of hypopituitarism and her hormone panel only showed elevated prolactin, possibly due to her breastfeeding. She was treated with a right pterional craniotomy with decompression of both optic nerves, partial resection of the suprasellar mass, and glucocorticoid therapy for headaches and visual disturbances., Conclusion: This case is notable for a presentation of lymphocytic hypophysitis without symptoms of hypopituitarism. This is important for outpatient providers to be aware of, especially those that care for pregnant patients so that unfavorable outcomes can be avoided., (© 2024. The Author(s).)

Introduction: Craniopharyngioma constitutes approximately 10% of primary brain tumors in children. It can cause considerable morbidity and mortality due to the local aggressiveness of the tumor itself or its management affecting the hypothalamus-pituitary axis and optic pathway involvement. There is very scarce data available from LMIC which makes the management controversial where multidisciplinary teams are already not available in most of the centers. This is a single-center cross-sectional retrospective review of 20-year record of 49 patients with craniopharyngioma treated between 2001 and 2020 at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan., Methods: We have assessed the epidemiological data of children presenting with the diagnosis of craniopharyngioma, treatment modalities used, and neurological, endocrine, and hypothalamic complications in these patients. The assessment involved a retrospective review of medical records and medical follow-up., Results: Out of a total of 49 patients, 26 (53%) were male, and 23 (46.9%) were female. The mean age was 9.5 years (SD ± 4.5 years). Most common symptoms at initial presentation were headache 41 (83.6%), visual deficit 40 (81.6%), nausea and vomiting 26 (53%), and endocrine abnormalities 16 (32%). Treatment modalities used at our center include gross total resection 11 (22%) and subtotal resection 38 (77%) out of total, while 6 (12.2%) patients received intracystic interferon. Histopathologic findings of the majority of patients (40 (81%)) revealed an adamantinomatous type of tumor. Only 23 (46.9%) children followed in clinic post-op. Median follow-up after craniopharyngioma presentation was 5 years (± 2.1 SD, range: 2-10 years). Pituitary hormone deficiencies (98%) and visual disturbances (75%) were the most common long-term health conditions observed., Conclusions: Since pituitary hormone deficiencies and visual disturbance were the most common long-term health conditions observed in our study, these patients require a multidisciplinary team follow-up to improve their quality of life., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

More and more clinical evidence confirms that hypopituitary dysfunction can lead to liver cirrhosis. The causes of hypopituitary dysfunction include sellarneoplastic diseases, hereditary diseases, perinatal adverse events, etc. Clinically, growth hormone deficiency (GHD) often the first cause in hypopituitary dysfunction.Hypopituitary dysfunction, especially GHD, can lead to liver cirrhosis, which in turn can result in damage to multiple organs such as the secondary lungs, spleen, and heart.Therefore, its clinical manifestations are complex, and the patients are first diagnosed in various departments.Reliable clinical observations have shown that GH replacement therapy at the early stage of the disease can effectively prevent and reverse the progression of cirrhosis, or even avoid inappropriate or unnecessary combined transplantation of liver or liver-related organs.Multidisciplinary collaboration and attention to the new findings that hypopituitary dysfunction can lead to liver cirrhosis will help to improve the accurate diagnosis and treatment of liver cirrhosis.

Introduction: A 27-year-old man presented due to unilateral leg pain. He had a history of diabetes insipidus and panhypopituitarism. Laboratory analysis revealed hormonal undersupply. MRI showed a large contrast medium-absorbing mass in the pituitary gland extending into the hypothalamus. FDG-PET/CT examination revealed a hypermetabolic soft tissue lesion around the left femoral shaft. After biopsy of the lesion, a diagnosis of multisystemic Langerhans cell histiocytosis was made., Competing Interests: Es bestehen keine Interessenskonflikte., (© 2024 Aerzteverlag medinfo AG.)

Aim: To share the surgical outcomes of 31 patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) at a single center., Material and Methods: This retrospective analysis of 31 craniopharyngioma cases (2013-2022) with a minimum 6-month follow-up included demographic data, preoperative findings, postoperative resection volumes, recurrence rates, pathological diagnoses, and complications., Results: Herein, 34 EETS surgeries were performed on 31 patients (12 males, 19 females). The presenting symptoms included visual loss (58%), hypopituitarism (54.8%), and diabetes insipidus (25.8%). Gross total resection was achieved in 87% of the patients, with 64.5% total and 22.5% near-total resection. Total resection prevented recurrences, contrasting with 75% recurrence in the subtotal resection patients (p=0.000). The primary patients showed 73.1% total resection, while only 20% of the recurrent patients achieved it (p=0.049). When comparing the first 16 cases with the last 15 cases in terms of surgical experience, the rates of resection (p=0.040) and recurrence-free survival (p=0.020) in the last 15 cases were statistically significant. Patients with preoperative visual loss demonstrated 94.4% improvement or stability postoperatively. Postoperative complications included hypopituitarism (71.4%), permanent diabetes insipidus (60.8%), worsening vision (6.5%), cerebrospinal fluid leakage (9.7%), meningitis (6.5%), and a 3.2% perioperative mortality rate., Conclusion: This study underscores the role of surgical resection in craniopharyngiomas, emphasizing the impact of surgical experience on recurrence-free survival. Primary surgery, with minimal complications and maximal resection, is crucial in managing recurrence challenges. Endoscopic endonasal transsphenoidal surgery, particularly in experienced centers, offers advantages such as panoramic vision and access to the third ventricle base, facilitating total and near-total resection and extending recurrence-free survival.

A previously fit and well male in his early 40s, presented to the emergency department, hypotensive, bradycardic and hypothermic with reduced levels of consciousness after being found diaphoretic and unwell at his home. Despite fluid resuscitation with warmed saline, he remained hypotensive and required vasopressor support leading to intensive care admission. Initially, the patient was managed for suspected meningoencephalitis but was later found to have hypopituitarism leading to secondary hypothyroidism and adrenal insufficiency. Subsequent investigations revealed it is due to empty sella syndrome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Patients with hypopituitarism often have no specific symptoms; that frequently results in missed diagnosis. An acute hypopituitarism crisis can be induced under stressful conditions. Here, we report a rare case of an acute pituitary crisis after lumbar surgery., Patient Concerns: We describe a 62-year-old female who presented with refractory electrolyte disorders after lumbar surgery. In addition, she developed anorexia, nausea, vomiting, chest cavity effusion, ascites, pericardial effusion, anemia, low blood pressure, bradycardia, and unconsciousness after surgery. MRI showed an empty sella turcica., Diagnoses: She was diagnosed with postoperative acute hypopituitary crisis., Interventions: The patient received hormone replacement therapy., Outcomes: Her symptoms improved significantly following the initiation of hormone replacement therapy and was well 6 months after surgery., Lessons: Refractory postoperative complications, including electrolyte disorders, infection, nausea, vomiting, circulatory collapse, anemia, and coma, indicate an acute postoperative hypopituitary crisis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Growth hormone (GH) deficiency (GHD) is one of the most prevalent deficiencies in patients with hypopituitarism and several cohort studies have demonstrated an increased mortality risk in hypopituitary patients with a presumed GHD. The cause of the excess mortality is most likely multifactorial, including the etiology of the hypopituitarism, non-physiological replacement therapies (mostly glucocorticoid), tumor treatment and its side effects as well as untreated GHD. Several years later, other cohort studies that investigated life expectancy in patients with hypopituitarism on GH replacement therapy (GHRT) that showed a normalized mortality. By comparison of the distribution of characteristics of interest between cohorts, we discuss the existing literature to answer the following question: does growth hormone replacement really improve mortality rates in adult patients with hypopituitarism and GHD? We also conducted a meta-analysis of these studies. Since the literature suffers from selection and time bias (improvement of tumor management and other pituitary hormone replacement therapies), there is no high-quality evidence that replacement therapy for GHD really improves mortality. However, the available data does suggest that GHRT plays a significant part in the normalization of the mortality in patients with hypopituitarism., Competing Interests: Declaration of Competing Interest DSO has served as a consultant for Ipsen, Pfizer, NovoNordisk, and Sandoz; has received research grants from Sandoz and Pfizer; and is an employee at AstraZeneca as of 30 August 2021. CCvB has no disclosures to report., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Growth hormone is among the most common hormones to be deficient in pituitary insult. It can occur either in isolation or combined with other hormone deficiencies. Growth hormone deficiency in adults (AGHD) can be due to causes acquired in adulthood or have a childhood-onset etiology, but the former is about three times more common. Usual causes of AGHD include mass effects due to a pituitary tumour, and/or its treatment (surgery, medical therapy, or radiotherapy), or radiotherapy to the head and neck region for non-pituitary lesions. The unusual or lesser-known causes of AGHD, are usually due to non-tumoral etiology and range from vascular and infective to inflammatory and miscellaneous causes. These not only expand the spectrum of AGHD but may also contribute to increased morbidity, adverse metabolic consequences, and mortality due to the primary condition, if unrecognised. The review features these lesser-known and rare causes of AGHD and highlights their clinical and diagnostic implications., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Pituitary adenomas (PA), comprising 10-20% of intracranial tumors, are classified as functioning and non-functioning and are further divided by size. Non-functioning tumors cause mechanical symptoms while functioning ones result in hormonal hypersecretion syndromes. Initial treatment involves surgery, with medical treatment for prolactinomas. Radiotherapy (RT) is employed as an adjuvant treatment, with various modalities including conventional, stereotactic radiosurgery (SRS), and fractionated stereotactic RT (FSRT). Although effective, RT is associated with complications and toxicities such as hypopituitarism, optic neuritis, secondary CNS tumors, and neurocognitive deficits., Aim: Describe the information on mortality from radiotherapy as treatment of functioning PA., Methods: A PubMed search spanning 2000-2017 was conducted for articles on pituitary RT., Results: Conventional RT entails high-energy radiation over multiple sessions, while SRS delivers precise high doses in a single session. FSRT offers enhanced precision using a linear accelerator, delivering multiple doses. Optic structure proximity and tumor volume dictate RT modality. Studies have shown SRS and FSRT's efficacy in tumor and endocrine control, with variable risks and complications. Mortality rates in pituitary adenomas treated with RT have been evaluated, revealing complexities. Acromegaly, associated with increased mortality due to cerebrovascular disease, may result from RT. Irradiation of non-functioning pituitary macroadenomas also elevates cerebrovascular risk, while radiotherapy-induced hypopituitarism is associated with increased cardiovascular mortality. RT-induced damage is attributed to microvascular lesions and arteriolar changes., Conclusion: Modern techniques mitigate complications, and although safer, long-term studies are needed. Multidisciplinary evaluation guides the treatment decision, optimizing efficacy and minimizing risk, ultimately improving the patient's quality of life., (Copyright © 2023 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) incurs substantial health and economic burden, as it is the leading reason for death and disability globally. Endocrine abnormalities are no longer considered a rare complication of TBI. The reported prevalence is variable across studies, depending on the time frame of injury, time and type of testing, and variability in hormonal values considered normal across different studies. The present review reports evidence on the endocrine dysfunction that can occur after TBI. Several aspects, including the pathophysiological mechanisms, clinical consequences/challenges (in the acute and chronic phases), screening and diagnostic workup, principles of therapeutic management, and insights on future directions/research agenda, are presented. The management of hypopituitarism following TBI involves hormonal replacement therapy. It is essential for health care providers to be aware of this complication because at times, symptoms may be subtle and may be mistaken to be caused by brain injury itself. There is a need for stronger evidence for establishing recommendations for optimum management so that they can be incorporated as standard of care in TBI management., (© 2023. The Author(s).)

Traumatic brain injury (TBI) is associated with hypopituitarism with a variable incidence, depending on the time and methods used to diagnosis, and on factors related to the trauma, such as its severity, its anatomical location and the drugs used in the acute phase. The pituitary gland can be damaged directly by the impact or secondary to factors such as ischemia, inflammation, excitotoxicity or immunity. In acute phases ACTH deficiency is the most relevant, since failure to detect and treat it can compromise the patient's life. Clinical manifestations are typical of each hormone deficient axes, although the combination hypopituitarism-trauma has been associated with cognitive deterioration, worse metabolic profile and greater impairment of quality of life. One of the clinical challenges is to determine which patients benefit from a systematic hormonal evaluation, and therefore from hormone replacement, and what is the appropriate time to do so and the most suitable diagnostic methods., (Copyright © 2023 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Nonfunctioning pituitary adenomas (NFPAs) constitute one of the most common tumours in the sellar region and are often discovered only when associated with compressive symptoms. With the frequent use of brain imaging, there has been an increase in the prevalence of incidentally discovered NFPAs., Aim: We aim to determine the prevalence of incidental diagnosis with NPAs observed over a decade and compare the analytical, clinical and treatment differences between those who were diagnosed either incidentally or symptomatically. We also intend to evaluate the pathology differences between both groups., Methods: We retrospectively analysed patients aged ≥18 years with an apparent NFPA, defined as a pituitary lesion compatible with pituitary adenoma which is not associated with the clinical or biochemical evidence of a hormone-secreting tumour. Inclusion criteria included normal prolactin level for lesions <9 mm or a prolactin level <100 ng/mL for lesions ≥10 mm in maximal tumour diameter., Results: We included 119 patients [53.8% males; mean age: 56.8 years (SD = 16.7)]. Diagnosis was incidental in 47.1% of patients, and many patients had unappreciated signs and symptoms of pituitary disease. In the symptomatic and incidental groups, 66.7% and 41.1% of patients had hypopituitarism, respectively (p = .005). Only 20.4% of patients incidentally diagnosed had microadenoma (p = .060). Hypopituitarism was present in 18.8% of those patients with microadenomas. Most tumours were macroadenomas (87.4%). Half of those patients diagnosed incidentally were submitted to surgery, compared with 75.8% of those who were diagnosed symptomatically (p = .004)., Conclusions: Nonfunctioning pituitary adenomas are commonly diagnosed incidentally, with many manifesting symptoms on examination. NFPAs incidentally diagnosed are more commonly macroadenomas and less frequently associated with hypopituitarism than symptomatic. Accordingly, if there was a greater level of knowledge and more suspicion about these pathologies, it might be possible to discover them earlier., (© 2023 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Context: Pathologies attributed to perturbations of the GH/IGF-I axis are among the most common referrals received by pediatric endocrinologists., Aim: In this article, distinctive cased-based presentations are used to provide a practical and pragmatic approach to the management of pediatric growth hormone deficiency (GHD)., Cases: We present 4 case vignettes based on actual patients that illustrate (1) congenital GHD, (2) childhood GHD presenting as failure to thrive, (3) childhood GHD presenting in adolescence as growth deceleration, and (4) childhood-onset GHD manifesting as metabolic complications in adolescence. We review patient presentation and a management approach that aims to highlight diagnostic considerations for treatment based on current clinical guidelines, with mention of new therapeutic and diagnostic modalities being used in the field., Conclusion: Pediatric GHD is diverse in etiology and clinical presentation. Timely management has the potential not only to improve growth but can also ameliorate or even mitigate adverse metabolic outcomes, which can be directly attributed to a GH deficient state., (© 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.)

Background: Non-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function., Objectives: To assess the incidence of hypopituitarism at presentation, the impact of treatment, and the likelihood of endocrine recovery during follow-up., Methods: All patients treated surgically with and without radiotherapy for NFPMs between 1987 and 2018 who had longer than six months follow-up were identified. Demographics, presentation, investigation, treatment, and outcomes were collected., Results: In total, 383 patients were identified. The median age was 57 years, with a median follow-up of 8 years. Preoperatively, 227 patients (227/375; 61%) had evidence of at least one pituitary deficiency. Anterior panhypopituitarism was more common in men (p = 0.001) and older patients (p = 0.005). Multiple hormone deficiencies were associated with large tumours (p = 0.03). Patients treated with surgery and radiotherapy had a higher incidence of all individual pituitary hormone deficiency, anterior panhypopituitarism, and significantly lower GH, ACTH, and TSH deficiencies free survival probability than those treated with surgery alone. Recovery of central hypogonadism, hypothyroidism, and anterior panhypopituitarism was also less likely to be reported in those treated with surgery and radiotherapy. Those with preoperative hypopituitarism had a higher risk of pituitary impairment at latest review than those presented with normal pituitary function (p = 0.001)., Conclusion: NFPMs are associated with a significant degree of hypopituitarism at time of diagnosis and post-therapy. The combination of surgery and radiotherapy is associated with a higher risk of pituitary dysfunction. Recovery of pituitary hormone deficit may occur after treatment. Patients should have regular ongoing endocrine evaluation post-treatment to assess changes in pituitary function and the need for long-term replacement therapy., (© 2023. Crown.)

Introduction: Rathke's cleft cysts are thought to have a benign clinical outcome apart from associated hypopituitarism and visual defects. Synchronous central nervous system lesions, including pituitary adenoma and intracerebral aneurysms, are rarely reported. Diagnosis of Rathke's cleft cyst after presenting with a subarachnoid hemorrhage due to a ruptured arterial aneurysm is reported only once before., Case Presentation: A 33-year-old Sri Lankan female presented with a subarachnoid hemorrhage due to a ruptured anterior communication artery aneurysm. She underwent pterional craniotomy and aneurysm clipping. She was found to have partial cranial diabetes insipidus and hypogonadotropic hypogonadism. She had a cystic lesion occupying enlarged sella turcica with characteristics of a Rathke's cleft cyst. Subsequently, she underwent trans-sphenoidal excision of the sellar lesion. Histology confirmed the diagnosis of Rathke's cleft cyst., Conclusions: Rare co-occurrence of a Rathke's cleft cyst and an anterior communicating artery aneurysm would have been missed if subtle manifestations atypical for subarachnoid hemorrhage were not further pursued. This could have led to progressive visual deterioration and hypopituitarism., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis)., Methods: The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected., Results: The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months)., Conclusions: Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.

Background: Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions., Methods: The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes., Results: From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed., Limitations: Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias., Conclusions: This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms., (© 2023. The Author(s).)

Abstract Traumatic brain injury (TBI) is increasingly recognized, with an incidence of approximately 110 per 100,000 in pediatric populations and 618 per 100,000 in adolescent and adult populations. TBI often leads to cognitive, behavioral, and physical consequences, including endocrinopathies. Deficiencies in anterior pituitary hormones (e.g., adrenocorticotropic hormone, thyroid-stimulating hormone, gonadotropins, and growth hormone [GH]) can negatively impact health outcomes and quality of life post-TBI. This review focuses on GH deficiency (GHD), the most common post-TBI pituitary hormone deficiency. GHD is associated with abnormal body composition, lipid metabolism, bone mineral density, executive brain functions, behavior, and height outcomes in pediatric, adolescent, and transition-age patients. Despite its relatively frequent occurrence, post-TBI GHD has not been well studied in these patients; hence, diagnostic and treatment recommendations are limited. Here, we examine the occurrence and diagnosis of TBI, retrospectively analyze post-TBI hypopituitarism and GHD prevalence rates in pediatric and adolescent patients, and discuss appropriate GHD testing strategies and GH dosage recommendations for these patients. We place particular emphasis on the ways in which testing and dosage recommendations may change during the transition phase. We conclude with a review of the challenges faced by transition-age patients and how these may be addressed to improve access to adequate healthcare. Little information is currently available to help guide patients with TBI and GHD through the transition phase and there is a risk of interrupted care; therefore, a strength of this review is its emphasis on this critical period in a patient's healthcare journey.

There is increased interest related to the impact of coronavirus disease 19 (COVID-19) on the endocrine system and in particular on the pituitary gland. Over the course of the severe infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are both acute and delayed effects on the pituitary, related to infection and/or treatment. Hypopituitarism, pituitary apoplexy and hypophysitis have been all reported, as well as arginine vasopressin deficiency (diabetes insipidus) and syndrome of inappropriate antidiuretic hormone secretion. Furthermore, patients with acromegaly, Cushing's disease and hypopituitarism are theoretically at increased risk of complications with COVID-19 and require close monitoring. Evidence regarding pituitary dysfunction in patients with COVID-19 continues to be gathered, as the breadth and depth of knowledge also continues to rapidly evolve. This review summarizes data analysis to date on the possible effects of COVID-19 and COVID-19 vaccination on patients with normal pituitary function and patients with known pituitary pathology. Though clinical systems were significantly affected, it seems there is no overall loss of biochemical control in patients with certain pituitary pathologies., Competing Interests: Disclosures The authors have no conflict of interest(s) to report regarding this topic., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.

Growth hormone deficiency (GHD) is a common complication in survivors of cancer and patients with tumors of the pituitary region. Growth hormone replacement therapy (GHT) has proven beneficial effects, including increased growth velocity, positive effects on body composition and skeletal integrity, and increased quality of life. However, due to known pro-proliferative, angiogenic, and anti-apoptotic properties of growth hormone, there are still some concerns about the safety of GHT in survivors. This narrative review aims to provide an overview of the long-term sequelae, and subsequently long-term safety, of GHT in survivors of (childhood) cancer and patients with tumors of the pituitary region. We identified predominantly reassuring results regarding the safety of survivors with GHT, although we must take into account the shortcomings of some studies and limited information on adult cancer survivors. Besides the already increased risk for second neoplasms, recurrences, or mortality in survivors due to host-, disease-, and treatment-related factors, we could not identify an increased risk due to GHT in particular. Therefore, we support the consensus that GHT can be considered in survivors after careful individual risk/benefit analysis and in open discussion with the patients and their families, taking into account the known morbidity of untreated GHD in cancer survivors and the positive effects of GHT.

Purpose: Hypopituitarism and tumor growth are rare in patients with non-functioning pituitary microadenomas (NFPmA). However, patients often present with non-specific symptoms. The aim of this brief report is to examine presenting symptomatology in patients with NFPmA compared to patients with non-functioning pituitary macroadenomas (NFPMA)., Methods: We performed a retrospective review of 400 patients (347 NFPmA and 53 NFPMA) who were conservatively managed; no patients had indications for urgent surgical intervention., Results: Average tumor size was 4.5 ± 1.9 and 15.5 ± 5.5 mm for NFPmA and NFPMA, respectively (p < 0.001). At least one pituitary deficiency was present in 7.5% of patients with NFPmA and 25% of patients with NFPMA. Patients with NFPmA were younger (41.6 ± 15.3 vs. 54.4 ± 22.3 years, p < 0.001) and more commonly female (64.6 vs. 49.1%, p = 0.028). There was no significant difference reported for similarly high rates of fatigue (78.4% and 73.6%), headache (70% and 67.9%), and blurry vision (46.7% and 39.6%). There were no significant differences in comorbidities., Conclusion: Despite smaller size and lower rate of hypopituitarism, patients with NFPmA presented with a high prevalence of headache, fatigue, and visual symptoms. This was not significantly different from patients with NFPMA who were conservatively managed. We conclude that symptoms of NFPmA cannot fully be attributed to pituitary dysfunction or mass effect., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Objective: How do subclinical hemorrhages into nonfunctioning pituitary adenomas (NFPAs) influence the hormonal status and surgical outcomes remains unclear, our study aim at evaluating its definite effects on pituitary gland function and surgical outcomes., Methods: All 103 consecutive patients who underwent initial endoscopic endonasal approach (EEA) for NFPAs resection from June 2016 to June 2018 were retrospectively reviewed, depending on magnetic resonance imaging (MRI), operative and pathological findings, patients were divided into the non-hemorrhagic NFPAs group and the subclinical hemorrhagic NFPAs group. A comparative analysis was conducted between these two groups to investigate the effects of subclinical hemorrhages in NFPAs on pituitary endocrine function and surgical outcomes., Results: The incidence of subclinical hemorrhage on NFPAs was 22.3% (23/103), which was more frequently observed in larger adenomas (28.9 ± 9.6 mm vs 19.2 ± 9.2 mm, p  = 0.001). The incidence of preoperative hypopituitarism was 69.6% (16/23) for subclinical hemorrhagic NFPAs group and 31% (25/80) for non-hemorrhagic NFPAs group ( p  = 0.001), a high incidence of hypopituitarism for subclinical hemorrhagic NFPAs finally was found to be owing to the large tumor rather than the intratumoral hemorrhage. All those NFPAs were resected via EEA with the technology of extra-pseduocapusual dissection in a standard elective fashion. Postoperatively, there were more than 75.6% of patients with preoperative hypopituitarism had at least one axis recovered, with hyperprolactinemia resolved in 91.7% of patients, 94.7% headaches and 90% visual symptoms resolved or improved after surgery, there was no significant difference between these two groups ( p  > 0.05), indicates there was no any surgical outcome difference between NFPAs with or without subclinical hemorrhage. A very low postoperative complication was achieved with new postoperative anterior pituitary failure occurred in 9.7% of patients and permanent diabetes insipidus (DI) occurred in 9.7% of patients, which advocated that EEA can be chosen as a safe surgical treatment for subclinical hemorrhagic NFPAs. Furthermore, with the technology of extra-pseduocapusual dissection, more than 87% subclinical hemorrhagic NFPAs had achieved gross total resection (GTR) with a low incidence of new postoperative hypopituitarism (14%)., Conclusion: Subclinical hemorrhage in NFPAs does not aggravate pituitary gland function. A surgical management strategy by EEA with the technology of extra-pseduocapusual dissection for the subclinical hemorrhagic NFPAs usually yields satisfactory endocrine and surgical outcomes, but it does not necessitate emergent tumor decompression.

Hypopituitarism, which refers to insufficiency of one or more hormones of the pituitary, can be due to myriad causes. The clinical and radiological spectrum of the condition is heterogeneous, based on the patient's age, gender, clinical setting, and/or other past medical history. Hypopituitarism includes central hypocortisolism, hypothyroidism, hypogonadism, and growth hormone deficiency. Both hypo- and hyperprolactinemia can be associated with hypopituitarism, with low prolactin signifying more extensive pituitary damage. Posterior pituitary insufficiency (arginine vasopressin deficiency) occurs either in isolation or with anterior pituitary hormone deficiency. Clinical symptomatology of hypopituitarism is usually nonspecific and insidious in onset and progression. Overall, the most common cause of hypopituitarism is a pituitary adenoma and/or its management (surgery, radiotherapy, pharmacotherapy, or a combination of these). However, it is this subset of patients which is more likely to be identified and managed in a timely manner, possibly alleviating the premature mortality associated with hypopituitarism. What is more challenging is the recognition of hypopituitarism in less common settings, which may be either due to direct involvement of the pituitary (infection, traumatic brain injury, or infiltrative causes) or indirectly as a consequence of the primary process (thalassemia, vasculotoxic snakebite, subarachnoid hemorrhage). These entities are often under-recognized, and increased awareness can help in greater recognition of the burden. Further, pituitary insufficiency in most of these settings is dynamic and may progress, or rarely, show recovery of function. This renders complexity to the problem, but makes it even more imperative to suspect, screen, and appropriately manage patients with less common causes of hypopituitarism., (© 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.)

Langerhans-cells Histiocytosis (LCH) is a rare disease characterized by the clonal proliferation of immature dendritic cells that locally or diffusely infiltrate different systems, mainly affecting children. We present the case of a 38-year-old man with a long-standing history of multiple tooth loss without association with trauma, smoking, or poor dental hygiene. Skull computed tomography (CT) showed multiple lytic jaw lesions. Jaw biopsy and immunohistochemical results were compatible with the finding of LCH. The patient evolved with polyuria, polydipsia, and nocturia, confirming the presence of diabetes insipidus and panhypopituitarism through hormonal studies. Magnetic resonance imaging (MRI) of the brain shows a hypothalamic neoplasm with infundibular involvement and an image suggestive of a pituitary granuloma. The treatment consisted of maxillobuccofacial defocusing, hormonal supplementation, chemotherapy, and radiotherapy with favorable evolution.