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Background: Pituitary abscess (PA), a rare complication following transsphenoidal (TS) surgery for pituitary adenoma with an incidence of 0.2%, poses a significant risk; carrying potential morbidity, recurrence, and the necessity for reoperation. Timely suspicion, diagnosis, and treatment are imperative. Patients and Methods: We present two cases and provide a literature review on the symptoms, risk factors, diagnosis, treatment, and outcomes associated with secondary PAs following TS surgery for adenoma. Results: We identified 12 articles reporting a total of 45 cases, in addition to our 2 cases. The primary symptoms were headache and visual impairment, with no fever or specific infectious parameters observed. Predominant risk factors identified included cerebrospinal fluid (CSF) leakage and prior radiotherapy (RT). Our first patient, a 45-year-old male, presented 10 weeks after TS surgery with sudden-onset symptoms, whereas our second patient, a 64-year-old female, presented 22 years postoperatively. In the first case, intraoperative CSF leakage, with the patient's history of allergic rhinitis and frequent nasal irrigation possibly contributed to the development of abscess. In the second case, RT was considered a potential risk factor. Severe headache and subclinical signs of infection associated with a cystic lesion of the pituitary gland were common findings. Both patients underwent endoscopic TS drainage and received appropriate antibiotic therapy, resulting in complete recovery without recurrence. Conclusions: When faced with severe headaches in a patient with a history of TS surgery for a pituitary adenoma, coupled with radiological evidence showing a cystic appearance with peripheral enhancement, taking a proactive approach to promptly identify and intervene in secondary PAs is essential for mitigating potential complications and optimizing patient outcomes.

Objective: Anterior pituitary dysfunction is one of the major causes of disability and morbidity in patients suffering from traumatic brain injury (TBI). The present study was undertaken to evaluate the incidence of anterior pituitary dysfunction in cases of moderate and severe TBI, its value in long-term prognostication, and the factors that predispose to a higher incidence of anterior pituitary dysfunction in acute and chronic phases., Methods: This was a prospective cohort study wherein 216 patients with moderate and severe TBI were evaluated within 72 hours of TBI (acute phase) and at 6 months (chronic phase)., Results: At 6 months, out of the 216 patients, 95 patients had expired and 35 patients were lost to follow-up. The remaining 86 patients were evaluated at 6 months. In the acute phase, hypopituitarism was seen in 82.4% patients, thyroid axis deficiency was seen in 57.4% patients, gonadal axis deficiency in 54.2% patients, and adrenal axis deficiency in 13.8% patients. In the chronic phase, hypopituitarism was seen in 59.3% patients, thyroid axis deficiency was seen in 24.4% patients, gonadal axis deficiency in 32.6% patients, and adrenal axis deficiency in 23.3% patients. Patients with thyroid axis deficiency at admission had significant association with a bad modified Rankin Scale score at 6 months., Conclusions: Thyroid and gonadotropin axes were most commonly affected and deficiency of at least 1 axis was found in 82.4% patients in the acute phase and 59.3% in the chronic phase. Thyroid axis deficiency had a negative impact on prognosis in post-TBI patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Chronically transfused patients with sickle cell disease typically do not exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Pituitary dysfunction (PD) in granulomatosis with polyangiitis (GPA) is a rare manifestation of the disease with an incidence of 2% and tends to occur as the disease progresses. On very rare occasions, PD can be the initial presentation of GPA. From our literature review, only 6 such cases were documented., Case Presentation: We present a rare case of GPA in a 57-year-old female who primarily presented with PD and visual disturbance without any other systemic features of GPA. Her initial ANCA screen was negative and her MRI scan showed an enlarged pituitary gland with cystic changes. A pituitary biopsy confirmed the diagnosis and she was started on immunosuppressants. After completing her immunotherapy, her diabetic insipidus subsided and her vision markedly improved., Literature Review: A literature search on Pubmed, Cochrane, Open Grey, and SciELO with keywords 'granulomatosis', 'polyangiitis', and 'pituitary' was performed. A total of 72 articles were reviewed. 6 articles were identified where PD was the presenting complaint of GPA without other systemic involvement., Discussion: Secondary hypophysitis in GPA indicates pituitary inflammation resulting from systemic disease or pituitary near-lying lesions. PD in GPA tends to occur with concomitant active disease at other sites. Headache seemed to be a common presenting feature with diabetic insipidus being the most common type of PD. Tissue biopsy is essential to confirm diagnosis. Pituitary biopsy is rarely required as other organ involvement is available for safer tissue sampling. However, in our case, pituitary biopsy had a role in confirming diagnosis and avoiding treatment delay., Conclusion: PD as a primary manifestation in GPA without systemic involvement is very rare and poses a diagnostic challenge. Pituitary biopsy can aid in diagnosis, allowing prompt treatment and prevention of long-term complications of untreated GPA such as permanent pituitary dysfunction. Nevertheless, the risk and benefit of pituitary surgery in each case should be weighted.

Background: Pituitary insufficiency is a common toxicity of cranial radiotherapy received in childhood for central nervous system, head and neck, and hematological malignancies. There is a recognized deficiency pattern and correlation with prescribed radiotherapy dose; however, correlation with measured pituitary dose (which can be minimized with modern radiotherapy techniques) has not previously been assessed., Procedure: Retrospective analysis was carried out of measured pituitary dose and endocrine outcomes of patients receiving cranial, total body, or head and neck photon beam radiotherapy at a tertiary center from July 2008 to October 2019., Results: Complete data for 102 patients were available. Median (IQR) age at radiotherapy was 9.0 (6.0-12.0) and follow-up 5.7 years (3.5-9.1). Most patients received focal brain radiotherapy (36.3%) or total body irradiation (32.4%); most frequent diagnoses were acute lymphoblastic leukemia (25.5%) and medulloblastoma (17.6%). The majority developed pituitary insufficiency (64; 62.7%); 41% had one and 38% had two hormone deficiencies. Growth hormone deficiency (GHD) (58; 56.9%) and thyroid-stimulating hormone deficiency (TSHD) (32; 31.4%) were most common. Patients who developed pituitary insufficiency received higher maximum pituitary dose-median (IQR) Gy, 44.0 (20.4-54.0) vs 18.2 (14.4-52.6); P = 0.008. Doses of 40-49 Gy or >50 Gy led to a higher cumulative incident rate than <20 Gy (HR 4.07, P < 0.001 and HR 3.04, P < 0.001, respectively). However, even at lower dose bands, levels of pituitary insufficiency were significant with a five-year cumulative incidence of GHD for <20 Gy and TSHD for 20-29 Gy reaching >30%., Conclusions: Our findings confirm a correlation between measured pituitary dose and risk of insufficiency even at lower doses, despite modern radiotherapy techniques. These data highlight the importance of minimizing pituitary dose and early specialist endocrine follow-up., (© 2022 Wiley Periodicals LLC.)

Context: Data on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed., Objective: We aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort., Methods: The worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected., Results: A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels., Conclusion: These final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Pituitary autoimmunity is one of the principal causes of hypopituitarism. Additionally, hypophysitis is one of the immune-related adverse events associated with immunotherapy. Recent case-oriented research has revealed a novel type of autoimmune hypophysitis, anti-PIT-1 hypophysitis, related to isolated adrenocorticotropic hormone (ACTH) deficiency and immune checkpoint inhibitor-related hypophysitis, as a form of paraneoplastic syndrome. Under these conditions, the ectopic expression of pituitary antigens present in tumors evokes a breakdown of immune tolerance, resulting in the production of autoantibodies and autoreactive cytotoxic T cells that specifically harm pituitary cells. Consequently, an innovative clinical entity of paraneoplastic autoimmune hypophysitis has been purported. This novel concept and its underlying mechanisms provide clues for understanding the pathogenesis of autoimmune pituitary diseases and can be applied to other autoimmune diseases. This review discusses the etiology of paraneoplastic autoimmune hypophysitis and its future., Competing Interests: Declaration of competing interest Y.T. has been an advisory board member and consultant for Novo Nordisk, Versartis, and Ascendis Pharma and accepted a research grant from Novo Nordisk and Ono Pharmaceutical., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC)., Methods: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included., Results: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations., Conclusion: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease., (© 2021. Italian Society of Endocrinology (SIE).)

Objective: Childhood brain tumor survivors (CBTS) are at risk to develop hypothalamic-pituitary (HP) dysfunction (HPD). The risk for HPD may vary between different age groups due to maturation of the brain and differences in oncologic treatment protocols. Specific studies on HPD in infant brain tumor survivors (infant-BTS, 0-1 years at diagnosis) or toddler brain tumor survivors (toddler-BTS, ≥1-3 years) have not been performed., Patients and Methods: A retrospective nationwide cohort study in CBTS was performed. Prevalence and risk factors for HPD were compared between infant-, toddler-, and older-BTS. Subgroup analysis was performed for all non-irradiated CBTS (n = 460)., Results: In total, 718 CBTS were included, with a median follow-up time of 7.9 years. Overall, despite the less frequent use of radiotherapy (RT) in infants, no differences in the prevalence of HPD were found between the three groups. RT (OR: 16.44; 95% CI: 8.93-30.27), suprasellar tumor location (OR: 44.76; 95% CI: 19.00-105.49), and younger age (OR: 1.11; 95% CI: 1.05-1.18) were associated with HP dysfunction. Infant-BTS and toddler-BTS showed more weight gain (P < 0.0001) and smaller height SDS (P = 0.001) during follow-up. In non-irradiated CBTS, infant-BTS and toddler-BTS were significantly more frequently diagnosed with TSH-, ACTH-, and ADH deficiency, compared to older-BTS., Conclusion: Infant and toddler brain tumor survivors seem to be more vulnerable to develop HP dysfunction than older children. These results emphasize the importance of special infant and toddler brain tumor treatment protocols and the need for endocrine surveillance in children treated for a brain tumor at a young age.

The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.

Introduction: Pituitary hyperplasia following primary hypothyroidism in pediatric age group population is considered rare with reports of unnecessary neurosurgical intervention for this medically treatable condition. Given the paucity of information on this topic, it is timely to provide clinicians with a comprehensive summary of available research., Methods: A search of published studies in Pubmed, PsychInfo and Cochrane Database with the terms "pituitary hyperplasia" or "pituitary hypertrophy" and "hypothyroidism" was performed and the results filtered for English language, pediatric (0-18 years) population and CT or MRI confirmed findings. 55 studies met the inclusion criteria. Data for a total of 110 patients with pituitary hyperplasia following primary hypothyroidism were extracted. The study population included 29 males and 81 females (M: F= 0.35:1). Patient age varied from 3 weeks to 18 years with a mean age of 10.22 years., Results: The most common clinical presentations included growth retardation, constipation and features of myxedema which were present in 78, 36 and 18 percent of children included in our review. Neuroimaging showed the mean (SD) pituitary height being 13.48 mm (4.72 mm). All of the patients achieved resolution of their pituitary mass and clinical as well as biochemical abnormalities 1 to 26 months after initiation of thyroid hormone replacement therapy, with an average time interval of 7.22 months. Our review has tried to delve in the pathophysiology as well as clinical, biochemical and radiological aspects of pediatric pituitary hyperplasia secondary to primary hypothyroidism and provide recommendations for treatment and follow-up. This may help anyone concerned gain a substantial knowledge on this topic.

The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = -0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.

Background: To determine the impact of hypothalamic-pituitary (HP) disorders on health outcomes in children and adolescents who received conformal radiation therapy (RT) for central nervous system tumors., Procedure: Cohort study including 355 patients (age ≤25 years at diagnosis) treated with high-dose (50.4-59.4 Gy) RT using photons for low-grade glioma or ependymoma. Patients (median age, 6.4 years at RT) received systematic endocrine follow-up (median duration, 10.1 years; range, 0.1-19.6). Associations between HP disorders and adverse health outcomes were determined by multivariable analysis., Results: Prevalence was 37.2% for growth hormone deficiency (GHD), 17.7% for gonadotropin deficiency (LH/FSHD), 14.9% for thyroid-stimulating hormone deficiency (TSHD), 10.3% for adrenocorticotropic hormone deficiency (ACTHD), and 12.6% for central precocious puberty (CPP). Hypothalamus mean dose ≥ 36 Gy was associated with higher odds of any deficiency. GHD was associated with short stature (OR 2.77; 95% CI 1.34-5.70), low bone mineral density (OR 3.47; 95% CI 1.16-10.40), and TSHD with dyslipidemia (OR 5.54; 95% CI 1.66-18.52). Patients with ACTHD and CPP had lower intelligence quotient scores, and memory scores were impaired in patients with GHD (P = 0.02). Treatment of GHD was not associated with increased risk for tumor recurrence, secondary tumors, or mortality., Conclusions: HP disorders occur frequently in patients receiving high-dose RT and are related to physical and neurocognitive well-being. Future studies are needed to assess whether further optimization of endocrine management yields better health outcomes., (© 2020 Wiley Periodicals LLC.)

Introduction : Traumatic brain injuries (TBI) are reported to cause neuroendocrine impairment with a prevalence of 15% with confirmatory testing. Pituitary dysfunction (PD) may have detrimental effects on vital parameters as well as on body composition, cardiovascular functions, cognition, and quality of life. Therefore, much effort has been made to identify predictive factors for post-TBI PD and various screening strategies have been offered. Areas covered : We searched PubMed and reviewed the recent data on clinical perspectives and long-term outcomes as well as predictive factors and screening modalities of post-TBI PD. Inconsistencies in the literature are overviewed and new areas of research are discussed. Expert opinion : Studies investigating biomarkers that will accurately predict TBI patients with a high risk of PD are generally pilot studies with a small number of participants. Anti-pituitary and anti-hypothalamic antibodies, neural proteins, micro-RNAs are promising in this field. As severity of TBI has been the most commonly associated risk factor for post-TBI PD, we suggest prospective screening based on severity of head trauma until new evidence emerges. There is also a need for more studies investigating the clinical effects of hormone replacement in TBI patients with PD.

The objective of this study is to systematically review clinical studies that have reported on the prevalence of chronic post-traumatic brain injury anterior pituitary dysfunction (PTPD) 12 months or more following traumatic brain injury (TBI). We searched Medline, Embase, and PubMed up to April 2017 and consulted bibliographies of narrative reviews. We included cohort, case-control, and cross-sectional studies enrolling at least five adults with primary TBI in whom at least one anterior pituitary axis was assessed at least 12 months following TBI. We excluded studies in which other brain injuries were indistinguishable from TBI. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) score. We also considered studies that determined growth hormone deficiency and adrenocorticotrophic hormone reserve using provocation test to be at low risk of bias. Data were extracted by four independent reviewers and assessed for risk of bias using a data extraction form. We performed meta-analyses using random effect models and assessed heterogeneity using the I 2 index. We identified 58 publications, of which 29 (2756 participants) were selected for meta-analysis. Twelve of these were deemed to be at low risk of bias and therefore "high-quality," as they had NOS scores greater than 8 and had used provocation tests. The overall prevalence of at least one anterior pituitary hormone dysfunction for all 29 studies was 32% (95% confidence interval [CI] 25-38%). The overall prevalence in the 12 high-quality studies was 34% (95% CI 27-42%). We observed significant heterogeneity that was not solely explained by the risk of bias. Studies with a higher proportion of participants with mild TBI had a lower prevalence of PTPD. Our results show that approximately one-third of TBI sufferers have persistent anterior pituitary dysfunction 12 months or more following trauma. Future research on PTPD should differentiate between mild and moderate/severe TBI.

Pathologies involving the pituitary stalk (PS) are generally revealed by the presence of diabetes insipidus. The availability of MRI provides a major diagnostic contribution by enabling the visualization of the site of the culprit lesion, especially when it is small. However, when only an enlarged PS is found, the etiological workup may be difficult, particularly because the biopsy of the stalk is difficult, harmful and often not contributive. The pathological proof of the etiology thus needs to be obtained indirectly. The aim of this article was to provide an accurate review of the literature about PS enlargement in adults describing the differences between the numerous etiologies involved and consequent different diagnostic approaches. The etiological diagnostic procedure begins with the search for possible other lesions suggestive of histiocytosis, sarcoidosis, tuberculosis or other etiologies elsewhere in the body that could be more easily biopsied. We usually perform neck, thorax, abdomen, and pelvis CT scan; positron emission tomography scan; bone scan; or other imaging methods when we suspect generalized lesions. Measurement of serum markers such as human chorionic gonadotropin, alpha-fetoprotein, angiotensin converting enzyme, and IgG4 may also be helpful. Obviously, in the presence of an underlying carcinoma (particularly breast or bronchopulmonary), one must first consider a metastasis located in the PS. In the case of an isolated PS enlargement, simple monitoring, without histological proof, can be proposed (by repeating MRI at 3-6 months) with the hypothesis of a germinoma (particularly in a teenager or a young adult) that, by increasing in size, necessitates a biopsy. In contrast, a spontaneous diminution of the lesion is suggestive of infundibulo-neurohypophysitis. We prefer not to initiate steroid therapy to monitor the spontaneous course when a watch-and-see attitude is preferred. However, in many cases, the etiological diagnosis remains uncertain, requiring either close monitoring of the lesion or, in exceptional situations, trying to obtain definitive pathological evidence by a biopsy, which, unfortunately, is in most cases performed by the transcranial route. If a simple surveillance is chosen, it has to be very prolonged (annual surveillance). Indeed, progression of histiocytosis or germinoma may be delayed., (© 2020 S. Karger AG, Basel.)

Background: Craniopharyngioma (CP), despite being a malformational tumor of low histological grade, causes considerable morbidity and mortality mostly due to hypothalamo-pituitary dysfunction that is created by tumor itself or its treatment., Summary: Fluid-electrolyte disturbances which range from dehydration to fluid overload and from hypernatremia to hyponatremia are frequently encountered during the acute postoperative period and should be carefully managed to avoid permanent neurological sequelae. Hypopituitarism, increased cardiovascular risk, hypothalamic damage, hypothalamic obesity, visual and neurological deficits, and impaired bone health and cognitive function are the morbidities affecting the well-being of these patients in the long term. Key Messages: Timely and optimal treatment of early postoperative and long-term complications of CP is crucial for preserving quality of life of these patients., (© 2021 S. Karger AG, Basel.)

Context: Data on hypothalamic-pituitary (HP) disorders in systematically evaluated childhood cancer survivors are limited., Objective: To describe prevalence, risk factors, and associated adverse health outcomes of deficiencies in GH deficiency (GHD), TSH deficiency (TSHD), LH/FSH deficiency (LH/FSHD), and ACTH deficiency (ACTHD), and central precocious puberty (CPP)., Design: Retrospective with cross-sectional health outcomes analysis., Setting: Established cohort; tertiary care center., Patients: Participants (N = 3141; median age, 31.7 years) were followed for a median 24.1 years., Main Outcome Measure: Multivariable logistic regression was used to calculate ORs and 95% CIs for associations among HP disorders, tumor- and treatment-related risk factors, and health outcomes., Results: The estimated prevalence was 40.2% for GHD, 11.1% for TSHD, 10.6% for LH/FSHD, 3.2% for ACTHD, and 0.9% for CPP among participants treated with HP radiotherapy (n = 1089), and 6.2% for GHD, and <1% for other HP disorders without HP radiotherapy. Clinical factors independently associated with HP disorders included HP radiotherapy (at any dose for GHD, TSHD, LH/FSHD, >30 Gy for ACTHD), alkylating agents (GHD, LH/FSHD), intrathecal chemotherapy (GHD), hydrocephalus with shunt placement (GHD, LH/FSHD), seizures (TSHD, ACTHD), and stroke (GHD, TSHD, LH/FSHD, ACTHD). Adverse health outcomes independently associated with HP disorders included short stature (GHD, TSHD), severe bone mineral density deficit (GHD, LH/FSHD), obesity (LH/FSHD), frailty (GHD), impaired physical health-related quality of life (TSHD), sexual dysfunction (LH/FSHD), impaired memory, and processing speed (GHD, TSHD)., Conclusion: HP radiotherapy, central nervous system injury, and, to a lesser extent, chemotherapy are associated with HP disorders, which are associated with adverse health outcomes., (Copyright © 2019 Endocrine Society.)

Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality., Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years., Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment., Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases were the commonest cause of death soon after diagnosis, emphasizing the need for careful clinical vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.

Background: Parasellar meningiomas involving the cavernous sinus and Meckel's cave pose a management challenge because of invasion around neurovascular structures and the pituitary gland. The management options range from aggressive resection to focused radiotherapy alone. We present a strategy for these tumors that includes endonasal bony decompression, partial tumor removal, and stereotactic radiotherapy (SRT) in select cases., Methods: The tumor location, previous treatments, cranial neuropathies, pituitary dysfunction, tumor control rates, use of stereotactic radiosurgery, SRT, and complications were retrospectively evaluated., Results: Twenty patients (age range, 43-81 years; 65% women; 90% with World Health Organization grade I; median follow-up, 57 months; 14 without previous debulking and RT; 6 with previous debulking and RT) underwent endonasal bony decompression and partial tumor removal. The most common tumor locations were cavernous sinus (95%), Meckel's cave (95%), sella (75%), petroclival (60%), and optic canal/orbit (30%). Three patients with large meningiomas underwent staged transcranial and endonasal debulking. Of the 14 patients without previous debulking and RT, 11 had undergone postoperative SRT, with tumor shrinkage in 3 (27%). At the last follow-up examination, for these 14 patients and the 6 patients who had undergone previous surgery and RT, tumor control was 100% and 33% (P < 0.001) and the cranial neuropathies had improved in 57% and 33%, respectively. Major complications occurred in 2 patients: a permanent sixth cranial nerve palsy and cerebrospinal fluid leakage requiring reoperation., Conclusions: Endonasal bony decompression and selective tumor removal, followed by SRT, appears to be a reasonable treatment option for most previously untreated parasellar meningiomas. For patients who have undergone previous debulking and RT, new targeted treatment strategies are needed., (Copyright © 2019. Published by Elsevier Inc.)

Background: Arachnoid cysts are uncommon lesions of the sellar region, and only rarely require decompressive surgery to treat symptoms. Pituitary abscesses are another rare lesion, and are an uncommon complication of pituitary surgery. A previously healthy 45 year old woman presented with a new finding of bitemporal hemianopsia. Magnetic resonance imaging (MRI) showed a cystic sellar lesion with suprasellar extension and compression of the optic chiasm. Endoscopic transphenoidal surgery was performed and the lesion was found to be an arachnoid cyst. She was well immediately after the operation, but 1 week later presented with headaches, fever and worsening visual acuity. MRI showed a homogenous collection in the sellar region that was compressing the chiasm. The patient was treated with antibiotics, and a second transphenoidal operation was performed, with frank pus found in the pituitary fossa. Cultures of the fluid found during the operation grew Escherichia coli and Staphylococcus lugdunensis. Her symptoms resolved after the second operation, and formal visual fields and a pituitary hormone panel were normal at this time. We report on a rare case of a pituitary abscess complicating surgery for a sellar arachnoid cyst, and discuss management of these conditions., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Objective: To summarize the etiologies of pituitary stalk thickening (PST) and the natural course of indistinguishable PST., Methods: Clinical information, including the symptoms at onset and laboratory, imaging, operative, pathological, and follow-up data, of patients with MRI-confirmed PST at Peking Union Medical College Hospital from January 2014 to May 2017 was collected and reviewed., Results: Of 321 eligible patients with PST, 28.3% were ≤18 years old. Central diabetes insipidus was the initial symptom in 68.8% of patients. At least one anterior pituitary hormone deficit was found in 57.6% of patients. The adjusted OR of panhypopituitarism associated with hypothalamus involvement was 7.3 (95% CI, 3.0 to 17.8; P < 0.001). Confirmed diagnoses were established in 137 patients (42.7%), including neoplasms (75.2%), inflammation (13.1%), and congenital anomalies (11.7%). Intracranial germ cell tumors (66.7%) were the leading cause among children, whereas histiocytoses (20.0%) and malignant metastases (14.7%) were the most common causes in adults. Thirty-eight patients with indistinguishable PST underwent a second MRI at a median time of 4.4 months. Spontaneous remission was observed in 17 of these patients (44.7%) after a median 8.5 months, with complete remission in 14 (36.8%) and partial remission in three (7.0%); five (13.2%) patients exhibited progression, and the remaining 16 (42.1%) stabilized., Conclusion: PST is highly heterogeneous, and most confirmed cases are attributed to neoplasms. The etiological spectrum varies with age. Physicians must be familiar with the major differential diagnoses, necessary investigations, and follow-up. Biopsy is indicated when radiological progression and/or worsening of pituitary function is detected., (Copyright © 2019 Endocrine Society.)

Introduction: Treatment of childhood brain tumors, including surgical resection and especially external beam radiation, often results in endocrine complications manifested by hypopituitarism, which can involve growth hormone deficiency, hypothyroidism, adrenal insufficiency, disorders of puberty, diabetes insipidus, and hypothalamic obesity., Areas Covered: A comprehensive literature search was conducted on Medline (publications from the 1990s to 01/2019) including systematic reviews, meta-analyses, longitudinal controlled studies, retrospective cohort studies, and case reports. Herein, we present an up-to-date review of the current literature regarding endocrine sequellae of childhood brain tumor survivors., Expert Opinion: Late endocrine sequellae can arise many years after the initial treatment of tumor, so at least annual surveillance of growth, puberty, weight, development, and endocrine status is recommended for at least 10 years after tumor therapy. This follow up should encompass childhood and adulthood among survivors. If found early, outcomes of endocrinopathies are favorable when treated appropriately. Newer tumor therapy modalities, such as proton beam radiation, offer the potential for fewer endocrine complications, but such benefit has yet to be demonstrated, and more research into short- and long-term outcomes is needed.

Objective: Lymphocytic hypophysitis (LYH) is a rare autoimmune inflammatory disease of the pituitary gland. In this study, we aim to characterize LYH at presentation and focus on the management and prognosis of LYH., Methods: A retrospective study of patients with LYH was conducted between 2011 and 2018 at a single institute. The patients were included by pathologic conformation and strict exclusion criteria. Clinical profile, imaging, and management data were collected., Results: Twenty patients with LYH (16 women and 4 men) were included. Ten patients were diagnosed histologically and the remaining 10 patients were confirmed clinically of exclusion criteria. The median age at diagnosis was 37 years (range, 16-58 years). Presenting symptoms were followed by polyuria/polydipsia (11, 55%), vision changes (10, 50%), headache (8, 40%), menstrual irregularities and amenorrhea (4, 20%), diplopia (1, 5%), or sexual dysfunction (1, 5%). Eight patients had partial anterior pituitary hormone dysfunction. The thyroid-stimulating hormone axis was most involved. Ten patients received transsphenoidal surgery, 5 patients experienced steroid pulse therapy, and observation was performed on 5 patients. Only 5 patients (25%) showed improvement of anterior pituitary dysfunction after initial management. Recovery of diabetes insipidus occurred in 2 patients (18%). The overall recurrence rate was 22.2%., Conclusions: Nonoperative treatment is a better option for most patients with LYH because it is effective and noninvasive. Surgery is recommended for definitive diagnosis, severe or rapid progression of neurologic impairment, and glucocorticoid insensitivity. Periodic follow-up is mandatory in a patient's long-term management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Langerhans cell histiocytosis (LCH) is a rare disorder, characterised by a monoclonal proliferation of aberrant histiocytes that accumulate in and infiltrate into different organs. When the hypothalamic-pituitary axis is involved, central diabetes insipidus (CDI) can be its first manifestation. Three cases of LCH with central diabetes insipidus were retrospectively analyzed: Case 1 is a 41-year old female presenting with polyuria and polydipsia. Diabetes insipidus was diagnosed and treated with desmopressin. MRI pituitary showed hypophysitis. Subsequently, she developed bone lesions and a biopsy demonstrated LCH. Case 2 is a 51-year old female presenting in 2009 with polyuria and polydipsia. Diabetes insipidus was diagnosed and treated with desmopressin. MRI pituitary revealed hypophysitis. LCH was suspected because of known pulmonary histiocytosis. Coexisting bone lesions were biopsied and confirmed LCH. Case 3 is a 44-year old female presenting with diabetes insipidus. She was treated with desmopressin as well. MRI of the pituitary gland showed impressive thickening of the infundibulum. A few months later, she developed skin lesions and a biopsy revealed LCH. Conclusively, LCH is a rare, elusive and probably underdiagnosed disease with a broad disease spectrum. Due to infiltration of the hypothalamic-pituitary axis, CDI can be the first manifestation, even before LCH is diagnosed. Therefore, LCH should be considered in the diagnostic workup of CDI.

Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays a key role in GH secretion. In this review, we summarize the current state of knowledge regarding the physiology and molecular machinery of VGCCs in pituitary somatotrophs. We next discuss the possible involvement of Ca2+ channelopathies in pituitary disease and the potential use of Ca2+ channel blockers to treat pituitary disease. Various types of VGCCs exist in pituitary cells. However, because L-type Ca2+ channels (LTCCs) contribute the major component to Ca2+ influx in somatotrophs, lactotrophs, and corticotrophs, we focused on these channels. An increasing number of studies in recent years have linked genetic missense mutations in LTCCs to diseases of the human cardiovascular, nervous, and endocrine systems. These disease-associated genetic mutations occur at homologous functional positions (activation gates) in LTCCs. Thus, it is plausible that similar homologous missense mutations in pituitary LTCCs can cause abnormal hormone secretion and underlying pituitary disorders. The existence of LTCCs in pituitary cells opens questions about their sensitivity to dihydropyridines, a group of selective LTCC blockers. The dihydropyridine sensitivity of pituitary cells, as with any other excitable cell, depends primarily on two parameters: the pattern of their electrical activity and the dihydropyridine sensitivity of their LTCC isoforms. These two parameters are discussed in detail in relation to somatotrophs. These discussions are also relevant to lactotrophs and corticotrophs. High dihydropyridine sensitivity may facilitate their use as drugs to treat pituitary oversecretion disorders such as acromegaly, hyperprolactinemia, and Cushing disease.

Rationale: The transsphenoidal surgical (TS) approach to sellar masses is the preferred surgical route in most cases. Secondary pituitary abscess (PA) following TS is an extremely rare but serious postoperative complication with potentially high disability and mortality., Patient Concerns: We describe an uncommon case of secondary PA in a 42-year-old woman, who underwent uncomplicated transsphenoidal procedures without cerebrospinal fluid leak, to treat primary Rathke cleft cyst. Without obvious cause, the patient suffered recurrent meningitis with complaints of headache, hyperpyrexia, and chills from 1 month after the operation., Diagnosis: There were no significant imaging findings until a new rim-enhancement lesion was seen in the sellar region on magnetic resonance imaging during the 6th episode of meningitis 11 months after the initial surgery. A diagnosis of secondary PA was considered; INTERVENTIONS:: Therefore, she underwent a 2nd TS with pus evacuation and antibiotic treatment., Outcomes: She improved remarkably and had no recurrence of symptoms during the 9-month follow-up., Lessons: Our aim was to present this rare case and discuss the most likely etiologies and preventive measures for this condition. In patients with recurrent meningitis but dormant imaging manifestations after TS, the possibility of secondary PA should considered. Adequate surgical drainage with microbiology-guided antibiotic therapy is the 1st choice for treatment.

Traumatic brain injury(TBI)is a major cause of hypothalamopituitary dysfunction. TBI-related hypothalamopituitary dysfunction is more common in the acute phase. Disturbance of pituitary/gonadal axis and growth hormone axis,as well as posterior pituitary dysfunction including central diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion,are the most frequently seen. During the chronic phase of TBI,anterior hypopituitarism is the major concern,which affects the quality of life. Risk factors for hypothalamopituitary dysfunction following TBI include low Glasgow score,high body mass index,hypoxia,older age,longer intensive care unit stay and longer coma status,radiological evidence of acute brain injury,and increased intracranial pressure. Children and adolescents are in a crucial period of growth and development,and therefore TBI-related pituitary dysfunction during this period can substantially affect the cognition and behaviors. There is currently no reliable biochemical marker predicting hypothalamopituitary dysfunctions. Therefore,it is of great importance to evaluate the pituitary function and take appropriate hormone replacement for moderate-severe TBI patients or mild TBI patients with apparent symptoms,especially for patients with water-electrolyte disturbance and adrenal deficiency. Growth hormone and gonadal hormone replacement therapies are crucial for children and adolescents.

Objective: To formulate clinical practice guidelines for the endocrine treatment of hypothalamic-pituitary and growth disorders in survivors of childhood cancer., Participants: An Endocrine Society-appointed guideline writing committee of six medical experts and a methodologist., Conclusions: Due to remarkable improvements in childhood cancer treatment and supportive care during the past several decades, 5-year survival rates for childhood cancer currently are >80%. However, by virtue of their disease and its treatments, childhood cancer survivors are at increased risk for a wide range of serious health conditions, including disorders of the endocrine system. Recent data indicate that 40% to 50% of survivors will develop an endocrine disorder during their lifetime. Risk factors for endocrine complications include both host (e.g., age, sex) and treatment factors (e.g., radiation). Radiation exposure to key endocrine organs (e.g., hypothalamus, pituitary, thyroid, and gonads) places cancer survivors at the highest risk of developing an endocrine abnormality over time; these endocrinopathies can develop decades following cancer treatment, underscoring the importance of lifelong surveillance. The following guideline addresses the diagnosis and treatment of hypothalamic-pituitary and growth disorders commonly encountered in childhood cancer survivors.

Objective: Pituitary abscess (PA) is a rare but serious intrasellar disorder with potentially high disability and mortality. Secondary PA after transsphenoidal surgery (TS) is extremely rare, and only a few case reports have been identified in the literature. This study explored the salient clinical manifestations and etiologies to determine appropriate treatment., Methods: A retrospective review of 6832 consecutive patients who had undergone TS for pituitary diseases in Peking Union Medical College Hospital between 2003 and 2017 was performed. Demographics, previous medical and surgical history, clinical presentation, imaging features, and treatment details of 23 patients who had been diagnosed with secondary PA after TS among the cohort were reviewed., Results: Among these patients, the original pituitary lesion before TS included Rathke's cleft cyst (8 patients, 34.8%), nonfunctioning pituitary adenoma (11 patients, 47.8%), and somatotropic adenoma (4 patients, 17.4%). The diameter of the original pituitary lesion ranged from 11 to 47 mm. About 52% of secondary PAs occurred within a half a year after surgery. Based on the history of TS, clinical presentation, biochemical testing, and typical imaging features, the preoperative diagnosis rate was as high as 78%., Conclusions: Although rare, secondary PA should be included in the differential diagnosis of intrasellar lesions after TS. Patients with an initial diagnosis of Rathke's cleft cyst or pituitary macroadenoma were more likely to have PA after TS. Adequate surgical drainage combined with microbiology-guided antibiotic therapy is the first choice for treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pituitary pars intermedia dysfunction (PPID) is caused by an age-related degenerative disease of dopaminergic neurones. Despite its importance in equine practice, available information regarding its epidemiology is limited. This systematic review aimed to assess published literature to evaluate available evidence regarding the clinical presentation, prevalence and risk factors for PPID in horses and ponies. Electronic database searches were undertaken using a range of terms, and English language publications published prior to August 2016 were included. Both authors independently reviewed screened papers for inclusion, extracted data, and assessed the quality of reporting using predefined criteria. Data were extracted using modified critically appraised topic data collection forms. Meta-analysis was not undertaken due to marked between-study variations. Following removal of duplicate records, of 358 published papers yielded by the search, 97 abstracts were screened for eligibility and 29 publications meeting inclusion criteria were included in the review. Most studies reviewed were case series or cross-sectional studies, with considerable variation in study populations and PPID case definition. Hypertrichosis and/or other hair coat abnormalities, laminitis and epaxial muscle wastage or muscle atrophy are the most frequently reported clinical signs, with prevalence of these signs increasing with increasing horse age. The most robust prevalence estimates for PPID were 21.2% in horses and ponies aged ≥15 years and 2.9% amongst the general equine population. Findings regarding breed and sex predispositions were equivocal and only increasing age has been identified as a significant risk factor for PPID., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pituitary dysfunction, such as panhypopituitarism or diabetes insipidus(DI), is often found in patients with Rathke's cleft cyst. Patients were treated with transsphenoidal microscopic surgery; however, pituitary dysfunction did not usually recover. Recently, endoscopic transsphenoidal surgery(eTSS)has enabled minimally invasive surgery for patients with Rathke's cleft cyst. In this study, we analyzed 22 consecutive patients with Rathke's cleft cyst who underwent eTSS to determine if pituitary dysfunction recovered. The follow-up period ranged from 3 months to 19.25 years(mean, 4.75 years). Preoperative endocrinological evaluation showed impaired secretion of adrenocorticotropic hormone(ACTH)in 4 cases(18.2%), thyroid-stimulating hormone(TSH)in 2 cases(9.1%), hyperprolactinemia in 5 cases(22.7%), growth hormone(GH)in 9 cases(40.9%), and luteinizing hormone(LH)/follicle-stimulating hormone(FSH)in 11 cases(50%). In addition, preoperative DI was found in 2 cases(9.1%). We planned the site of fenestration for the cyst wall using preoperative sagittal magnetic resonance imaging. As a result, the recovery rate for ACTH, GH, and TSH secretion was 25%, 33.3%, and 50%, respectively. On the other hand, two patients with DI and other hormonal deficiencies did not recover pituitary function because of severe inflammation. Pituitary function might be preserved with minimally invasive surgery for Rathke's cleft cyst with mild inflammation.

OBJECTIVE Extracapsular resection of pituitary microadenomas improves remission rates, but the application of pseudocapsular techniques for macroadenomas has not been well described. In larger tumors, the extremely thin, compressed normal gland or its complete absence along the tumor's anterior surface limits the application of the traditional pseudocapsular technique that can be used for microadenomas. However, in the authors' experience, the interface between the pseudocapsule at the posterior margin of the adenoma and the compressed normal gland behind it is universally present, providing a surgical dissection plane. In mid-2010, the authors began using a new surgical technique to identify and use this interface for the resection of larger macroadenomas, a technique that can be used with the microscope or the endoscope. METHODS The authors performed a cohort study using prospectively collected preoperative imaging reports and operative details and retrospectively reviewed postoperative images and clinical follow-up of patients with a pituitary macroadenoma 20-40 mm in maximum diameter undergoing microscopic transsphenoidal resection. Since dissection of the tumor capsule only pertains to encapsulated tumor within the sella and not to tumor invading the cavernous sinus, assessment of tumor removal of noninvasive tumors emphasized the entire tumor, while that of invasive tumors emphasized the intrasellar component only. The incidence of residual tumor on postoperative imaging, new-onset endocrinopathy, and recovery of preoperative pituitary deficits was compared between patients who underwent surgery before (Group A) and after (Group B) implementation of the new technique. RESULTS There were 34 consecutive patients in Group A and 74 consecutive patients in Group B. Tumors in 18 (53%) Group A and 40 (54%) Group B patients had no evidence of cavernous sinus invasion on MRI. Use of the posterior pseudocapsule technique reduced the incidence of intrasellar residual tumor on postoperative MRI for tumors without cavernous sinus invasion (39% [Group A] vs 10%, p < 0.05) and in all tumors regardless of invasion (50% vs 18%, p < 0.005). The incidence of new endocrinopathy was less likely (25% vs 12%, p = 0.098) and the recovery of prior deficits more likely (13% vs 27%, p = 0.199) among patients treated using the pseudocapsule approach, although the differences are not statistically significant. CONCLUSIONS Use of the posterior pseudocapsule dissection plane can enhance the resection of pituitary macroadenomas.

Background/aims: The risk factors for pituitary hormone dysfunction (PHD) in children with optic nerve hypoplasia (ONH) are not well understood. This study identified the type, timing, and predictors of PHD in children with ONH., Methods: ONH patient charts were reviewed retrospectively. The incidence rate of PHD was calculated assuming a Poisson distribution. Predictors of PHD were identified through a multivariable Cox proportional hazards model., Results: Among 144 subjects with ONH, 49.3% (n = 71) developed PHD over 614.7 person-years of follow-up. The incidence was 11.55 (95% confidence interval [CI]: 9.02-14.57/100 person-years). The median time to first PHD was 2.88 (interquartile range: 0.02-18.72) months. Eighty-two percent developed their first PHD by their 5th and 90% by their 10th birthday, and 89% within 5 years of ONH diagnosis. Prematurity (adjusted hazard ratio [aHR]: 0.33; 95% CI: 0.1-1.07), blindness (aHR: 1.72; 95% CI: 1.03-2.86), maternal substance abuse (aHR: 1.51; 95% CI: 0.91-2.48), abnormal posterior pituitary (aHR: 3.8; 95% CI: 2.01-7.18), and hypoplastic/absent anterior pituitary (aHR: 2.52; 95% CI: 1.29-4.91) were significant predictors of PHD., Conclusions: The clinical predictors of PHD included blindness, pituitary gland abnormalities, and maternal substance abuse. These predictors help clinical decision-making related to the need for and frequency of hormone testing in pediatric patients with ONH., (© 2017 S. Karger AG, Basel.)

Introduction: Pituitary hyperplasia due to primary hypothyroidism is rare and underdiagnosed., Case Report: We report an 18-year-old patient referred for a pituitary mass revealing primary hypothyroidism. Biological parameters confirmed severe primary hypothyroidism and hyperprolactinemia. Outcome was favorable with l-thyroxin supplementation resulting in TSH and prolactin levels normalization and pituitary mass resolution., Conclusion: Pituitary hyperplasia due to primary hypothyroidism, although rare, should be recognized to avoid unnecessary surgery leading to irreversible complications., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

To improve the differential diagnosis of sellar region mass, 4 cases with sellar mass and misdiagnosed as lymphocytic hypophysitis (LYH) were reviewed retrospectively.The 4 patients (2 male and 2 female) aged 20-60 years old were all presented with symptoms of headache, polydipsia and polyuria.Biochemical studies confirmed the diagnoses of central diabetes insipidus and hypopituitarism.Head MRI scans showed LYH like image for all the cases, and, thus, high dose methylprednisolone pulse therapy (HDMPT) was applied to the patients.Their symptoms deteriorated and the sellar mass enlarged after a short period of partial improvement.Operations were performed in all the patients.Histology study showed craniopharyngioma with abscess, primary abscess, secondary hypophysitis caused by Wegener's granulomatosis, and germinoma with secondary hypophysitis, respectively.In conclusion, surgery or biopsy is necessary for those who presented with sellar region mass and was suspected to be with LYH, but with poor response or even worse after HDMPT.

Background: Pituitary metastases are a rare complication of generalized cancer. Metastases to the pituitary gland occur in only 1% of patients operated on for sellar tumor. The most common presenting symptom in patients with pituitary metastases is diabetes insipidus, whereas this is rare in those with pituitary adenoma., Material and Methods: This publication presents the cases of two patients with pituitary metastases and a systematic review of the literature. English-language publications related to pituitary metastases and published from 1957 to 2016 were identified using the PubMed database., Results: A total of 131 publications containing information about 259 patients (121 female and 138 male; mean age, 57.3 years) were identified. The most often metastasized breast carcinoma (24.6%) and lung carcinoma (23.8%), followed by thyroid carcinoma (11.3%), renal cell carcinoma (7.8%), hepatocellular carcinoma (4.3%), colorectal carcinoma (3.5%), and malignant melanoma (3.5%). The most frequent initial symptoms were manifestations of diabetes insipidus (39.6%), anterior pituitary deficiency (44.9%), perimeter disorders (51.6%), headache (37.6%), cranial nerve palsy (33.5%), and pseudoprolactinemia (16.7%). Radiotherapy (67.8%) and surgical treatment (63.9%) were the most frequently used treatment., Conclusion: The average survival time from the onset of metastatic disease was 11.8 months. Surgical therapy alone or in combination with radiation therapy does not prolong survival, but alleviates symptoms and improves quality of life.Key words: pituitary metastasis - diabetes insipidus - hypopituitarism - transsphenoidal surgery The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 1. 2017Accepted: 4. 4. 2017.

Lymphocytic hypophysitis(LH)has first been described as an autoimmune endocrinopathy by Goudie in 1962. In particular, lymphocytic adenohypophysitis(LAH)is usually associated with pregnancy and hypopituitarism due to insufficient endocrine of ACTH. However, several cases of LAH in pregnant patients showing only visual disturbances have recently been documented. We treated a patient with LAH presenting only the chiasma syndrome in the third trimester without hypopituitarism. A 27-year-old woman unexpectedly experienced visual disturbance starting in the 28th week of pregnancy. Her symptoms progressed rapidly. MRI revealed a pituitary mass lesion compressing the optic chiasma. In addition, ophthalmological examination revealed bitemporal hemianopsia. The patient underwent endoscopic transsphenoidal surgery(eTSS)during the 30th week of pregnancy. LH was diagnosed histologically during surgery. We performed decompression of optic chiasma. After surgery, the patient's visual field markedly widened and the pituitary mass regressed along with replacement of corticosteroids. In the 37th week of pregnancy, she delivered a healthy baby. We speculate that the reason for the absence of hypopituitarism during pregnancy in patients with LH, especially in the third trimester, might be that the placental endocrine system masks pituitary endocrinopathy. In summary, we report a case of LAH that did not present with hypopituitarism, and eTSS could be performed safely during pregnancy.

Purpose: Reports on long-term variations in pituitary function after traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) diverge. The aim of the current study was to evaluate the prevalence and changes in pituitary function during the first year after moderate and severe TBI and SAH and to explore the relation between pituitary function and injury variables., Methods: Adults with moderate and severe TBI or SAH were evaluated at 10 days, 3, 6 and 12 months post-injury/illness. Demographic, clinical, radiological, laboratory, including hormonal data were collected., Results: A total of 91 adults, 56 (15 women/41 men) with TBI and 35 (27 women/8 men) with SAH were included. Perturbations in pituitary function were frequent early after the event but declined during the first year of follow-up. The most frequent deficiency was hypogonadotrope hypogonadism which was seen in approximately 25 % of the patients. Most of the variations were transient and without clinical significance. At 12 months, two patients were on replacement with hydrocortisone, four men on testosterone and one man on replacement with growth hormone. No relations were seen between hormonal levels and injury variables., Conclusions: Perturbations in pituitary function continue to occur during the first year after TBI and SAH, but only a few patients need replacement therapy. Our study could not identify a marker of increased risk of pituitary dysfunction that could guide routine screening. However, data demonstrate the need for systematic follow-up of pituitary function after moderate or severe TBI or SAH., Competing Interests: The authors have no competing interests to declare. Ethical approval The study was approved by Regional Ethical Review Board in Stockholm (No: 2008/3:9 2008/1574-31/3). Informed Consent Our research involved human participants who had obtained informed consent.

Immune checkpoint inhibitors, used for cancer immunotherapy, show anti-tumor effects through T cell activations. Monoclonal antibodies against cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death (PD)-1, or PD-ligand 1 which is a ligand of PD-1 have been shown to be effective in the treatments of advanced cancers including malignant melanoma, non-small cell lung cancer, and renal cell carcinoma. However, these drugs also have immune-related adverse events (irAEs). The irAEs, which have unique characteristics different from those seen in conventional cytotoxic anti-tumor medicines, are observed in the several tissues such as skin, gastrointestinal tract, liver, lung, muscle, nerve and endocrine systems. To safely use immune checkpoint inhibitors, it is quite important to understand the characteristics of irAEs and to manage them in clinical practice. In this review, we focus on clinical characteristics and pathogenesis of adverse events in the pituitary gland.

To elucidate the pituitary function of Japanese patients after aneurysmal subarachnoid hemorrhage (aSAH) and implicative factors related to growth hormone deficiency (GHD) after aSAH. We evaluated basal pituitary hormone levels among 59 consecutive aSAH patients with a modified Rankin Scale (mRS) ⩽4 at 3months after aSAH onset. Patients with low insulin-like growth factor 1 (IGF-1) SD score (SDS) or who seemed to develop pituitary dysfunction underwent provocative endocrine testing during a period of 3-36months after SAH onset. The relationship between IGF-1 SDS and clinical factors of the patients such as severity of SAH, aneurysm location, and treatment modalities, were assessed. Six patients (10.2%) demonstrated their IGF-1 SDS less than -2. Multiple logistic regression analyses revealed that patients who underwent surgical clipping had a significantly lower IGF-1 SDS (<-1SD) than patients who underwent endovascular embolization with an odds ratio of 5.83 (p=0.032). Thirty-three patients took provocative tests and five (15.6%) patients were identified as having GHD. The mean IGF-1 SDS of these five GHD patients was 0.08 SD. The aneurysms in all GHD patients were located in internal carotid artery (ICA) or anterior cerebral artery (ACA). To the best of our knowledge, this is the first report describing the prevalence of GHD in Japanese patients after aSAH, and it was not as high as that of previous European studies. We recommend that screening pituitary dysfunction for aSAH survivors with their aneurysms located in ICA or ACA., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

New immunotherapies have significantly improved survival in certain advanced cancers in recent years, particularly metastatic melanoma and lung cancer. The most effective of these therapies are the immune checkpoint inhibitors (ICIs) such as ipilimumab, nivolumab and pembrolizumab. The use of ICIs will continue to increase in the coming years as evidence of their benefit in a range of other cancers builds. ICIs are associated with novel immune-related adverse events (irAEs), which can involve a wide range of organs. The most common irAEs involve the skin (rash, pruritus), gastrointestinal tract (diarrhoea, colitis) and endocrine system (thyroid, pituitary). While severity is generally mild, life-threatening complications can occur if not recognised and treated promptly. Due to the diverse manifestations of irAEs, patients may present to doctors who are not familiar with these drugs, which creates the potential for delays in management. Management of irAEs depends on severity and the organ affected. Systemic steroids are often required and ICI therapy may be withheld or discontinued. Additional immunosuppressive medications may be necessary in steroid-refractory cases. This review provides an overview of the potential toxicities and their management for general clinicians. Broader awareness of these issues among medical professionals will hopefully reduce unnecessary delays in diagnosis and treatment. Patient and carer education regarding irAEs is extremely important; patients and carers should be advised to seek urgent medical attention if required.

Background: The relationship between apathy and endocrine dysfunction, both frequent outcomes of neurological insult, has not yet been investigated in brain tumor survivors. The present study aimed to assess the relationship between pituitary disorders and apathy and other facets of executive function in long-term adult survivors of childhood brain tumors and to differentiate between apathy and depression in this population., Procedure: Seventy-six adult survivors of childhood brain tumors at least 5 years past diagnosis participated. An informant completed the Frontal Systems Behavior Scale (FrSBe), and 75 of the 76 participants completed a Structured Clinical Interview for the DSM-IV-TR (SCID). Information on neuroendocrine dysfunction was obtained through medical chart review., Results: Clinically significant levels of apathy on the FrSBe were identified in 41% of survivors. Pituitary dysfunction significantly explained 9% of the variance in apathy scores and affected whether an individual presented with clinical levels of apathy. Pituitary dysfunction predicted higher levels of executive dysfunction but did not impact whether a participant reached clinical levels of executive dysfunction. A past major depressive episode (MDE) significantly predicted current apathy but showed no relationship with pituitary disorders. Radiation treatment predicted pituitary dysfunction but not the differences in apathy or executive functions., Conclusions: Apathy and executive dysfunction in survivors of childhood brain tumors are strongly predicted by pituitary dysfunction, and individuals with pituitary dysfunction are more likely to present with clinical levels of apathy as adults. Clinical levels of apathy may present absent of current depression, and pituitary dysfunction impacts apathy uniquely., (© 2016 Wiley Periodicals, Inc.)

Purpose: Pituitary dysfunction is reported to be a common complication following aneurysmal subarachnoid hemorrhage (aSAH). The aim of this meta-analysis is to analyze the literature on clinical prevalence, risk factors and outcome impact of pituitary dysfunction after aSAH, and to assess the possible need for pituitary screening in aSAH patients., Methods: We performed a systematic review with meta-analysis based on a comprehensive search of four databases (PubMed/MEDLINE, ISI/Web of Science, Scopus and Google Scholar)., Results: A total of 20 papers met criteria for inclusion. The prevalence of pituitary dysfunction in the acute phase (within the first 6 months after aSAH) was 49.30 % (95 % CI 41.6-56.9), decreasing in the chronic phase (after 6 months from aSAH) to 25.6 % (95 % CI 18.0-35.1). Abnormalities in basal hormonal levels were more frequent when compared to induction tests, and the prevalence of a single pituitary hormone dysregulation was more frequent than multiple pituitary hormone dysregulation. Increasing age was associated with a lower prevalence of endocrine dysfunction in the acute phase, and surgical treatment of the aneurysm (clipping) was related to a higher prevalence of single hormone dysfunction. The prevalence of pituitary dysfunction did not correlate with the outcome of the patient., Conclusions: Neuroendocrine dysfunction is common after aSAH, but these abnormalities have not been shown to consistently impact outcome in the data available. There is a need for well-designed prospective studies to more precisely assess the incidence, clinical course, and outcome impact of pituitary dysfunction after aSAH.