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Hypothalamic amenorrhea may be accompanied by low leptin levels. These investigators administered recombinant human leptin to eight women with hypothalamic amenorrhea. Six additional untreated subjects served as historical controls. Treatment with recombinant leptin increased mean luteinizing hormone levels and pulse frequency, improved ovarian variables, and resulted in ovulation in three women and in withdrawal bleeding in two. Leptin administration may improve reproductive, thyroid, and growth hormone function. Hypothalamic amenorrhea, either organic or functional, 1 is characterized by the absence of menstrual cycles, low estrogen levels, and low or normal levels of gonadotropins. It accounts for over 30 percent of cases of amenorrhea in women of reproductive age 2 and may lead to infertility and bone loss. 3 Functional hypothalamic amenorrhea occurs when a relative energy deficit (owing to weight loss, excessive exercise, or eating disorders) disrupts the secretion of hypothalamic gonadotropin-releasing hormone (GnRH) and other neuroendocrine axes. 4 – 7 However, the precise signal or signals indicating the availability of energy remain unknown. Leptin, a hormone secreted by adipocytes that regulates energy . . .

Data on hypothalamic-pituitary (HP) disorders in systematically evaluated childhood cancer survivors are limited. 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). Retrospective with cross-sectional health outcomes analysis. Established cohort; tertiary care center. Participants (N = 3141; median age, 31.7 years) were followed for a median 24.1 years. 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. 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). HP radiotherapy, central nervous system injury, and, to a lesser extent, chemotherapy are associated with HP disorders, which are associated with adverse health outcomes.

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.

Survivors of sellar/suprasellar tumors involving hypothalamic structures face a risk of impaired quality of life, including tumor- and/or treatment-related hypothalamic obesity (TTR-HO) defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment related damage of the hypothalamus. We analyze German claims data to better understand treatment pathways for patients living TTR-HO during the two years following the index surgical treatment. A database algorithm identified patients with TTR-HO in a representative German payer claims database between 2010 and 2021 (n = 5.42 million patients). Claims from 37 patients with TTR-HO were analyzed on a quarterly basis over 2 years. The analysis considered inpatient, outpatient, and prescription data. In the follow-up period, patients with TTR-HO are hospitalized 3.68 times on average; 37% of hospitalizations in year 1 and 31% in year 2 are due to TTR-HO. On average, patients see a general practitioner 12.27 times and various specialists 20.45 times. The need for complex neuroendocrine therapy develops quickly, with most patients having 2–3 neuroendocrine prescriptions in any given quarter. The management of patients with TTR-HO requires frequent inpatient and outpatient visits for tumor follow-up and management of incident comorbidities, and most patients with TTR-HO require intense polytherapy.

Chronic fatigue syndrome (CFS) is a disabling and medically unexplained condition with no readily demonstrable organic or psychiatric explanation. The bulk of evidence supports the presence of several factors related to hypothalamic–pituitary–adrenal axis dysfunction in patients with CFS. Here, the authors review the literature on CFS since 2003, put the new findings into context and evaluate progress against previously made recommendations. The weight of current evidence supports the presence of the following factors related to hypothalamic–pituitary–adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS): mild hypocortisolism; attenuated diurnal variation of cortisol; enhanced negative feedback to the HPA axis; and blunted HPA axis responsiveness. Furthermore, HPA axis changes seem clinically relevant, as they are associated with worse symptoms and/or disability and with poorer outcomes to standard treatments for CFS. Regarding etiology, women with CFS are more likely to have reduced cortisol levels. Studies published in the past 8 years provide further support for a multifactorial model in which several factors interact to moderate HPA axis changes. In particular, low activity levels, depression and early-life stress appear to reduce cortisol levels, whereas the use of psychotropic medication can increase cortisol. Addressing these factors—for example, with cognitive behavioral therapy—can increase cortisol levels and is probably the first-line approach for correcting HPA axis dysfunction at present, as steroid replacement is not recommended. Given what is now a fairly consistent pattern of findings for the type of HPA axis changes found in CFS, we recommend that future work focuses on improving our understanding of the cause and relevance of these observed changes. Key Points The bulk of evidence points to modest reductions in cortisol levels in some cohorts of patients with chronic fatigue syndrome (CFS), and these changes are more apparent in women than in men Underlying the reduction in cortisol levels is a hypothalamic–pituitary–adrenal (HPA) axis with attenuated diurnal variation, enhanced negative feedback and blunted response to challenges Low cortisol levels have clinical relevance as they might contribute to symptoms—along with other factors—and are associated with a worsened outcome of currently recommended treatments for CFS A multidimensional etiological model remains most probable, with low cortisol levels occurring at a later stage of the illness, moderated by factors such as activity levels, depression, early-life stress and psychotropic medication Cortisol levels can be increased by treatment with cognitive behavioral therapy, potentially because of reversal of some moderating factors Further improvements in research designs remain necessary to fully understand HPA axis dysfunction in CFS

Purpose Survivors of a pediatric suprasellar tumor may suffer from hypothalamic-pituitary dysfunction (HD), which may result in hypothalamic obesity (HO). The first step in HO treatment is lifestyle intervention (e.g. exercise). Our aim was to assess physical activity (PA), health-related fitness (HRF) and physical performance (PP) in a cohort of children with a suprasellar tumor. Methods Retrospective study on a national cohort including all children with a suprasellar tumor who were referred to the physiotherapy department 2018—2022. Data was collected on: PA defined as minutes of Moderate-to-Vigorous Physical Activity (MVPA) and number of steps per day, HRF defined as body composition, VO 2 peak percentage of predicted, mean power, and muscle strength, and PP based on the 10-m walk and run test, time up and down the stairs, and time to rise from the floor. Results Seventy-three children (mean age 11.09, mean body mass index SDS 2.36) were evaluated. In total, 24.1% reached the guideline of ≥ 60 min MVPA per day. The VO 2 peak percentage of predicted was 71.0% [IQR 57.0 – 82.8] and in 58.3% mean power was ≤ -2 SDS. Muscle strength was not decreased (median of -0.5 SDS). PP was found to be better than the norm. Conclusion and key findings PA and HRF are decreased in children with HD, however PP was not decreased. This implies that no PP restrictions are present to engage in PA and that a lifestyle coach can be involved to improve PA and HRF in these children.

Abstract BACKGROUND: Controversy persists regarding the optimal treatment of pediatric craniopharyngiomas. OBJECTIVE: We performed a meta-analysis of reported series of transcranial (TC) and transsphenoidal (TS) surgery for pediatric craniopharyngiomas to determine whether comparisons between the outcomes in TS and TC approaches are valid. METHODS: Online databases were searched for English-language articles reporting quantifiable outcome data published between 1990 and 2010 pertaining to the surgical treatment of pediatric craniopharyngiomas. Forty-eight studies describing 2955 patients having TC surgery and 13 studies describing 373 patients having TS surgery met inclusion criteria. RESULTS: Before surgery, patients who had TC surgery had less visual loss, more frequent hydrocephalus and increased intracranial pressure, larger tumors, and more suprasellar disease. After surgery, patients in the TC group had lower rates of gross total resection (GTR), more frequent recurrence after GTR, higher neurological morbidity, more frequent diabetes insipidus, less improvement, and greater deterioration in vision. There was no difference in operative mortality, obesity/hyperphagia, or overall survival percentages. CONCLUSION: Directly comparing outcomes after TC and TS surgery for pediatric craniopharyngiomas does not appear to be valid. Baseline differences in patients who underwent each approach create selection bias that may explain the improved rates of disease control and lower morbidity of TS resection. Although TS approaches are becoming increasingly used for smaller tumors and those primarily intrasellar, tumors more amenable to TC surgery include large tumors with significant lateral extension, those that engulf vascular structures, and those with significant peripheral calcification.

The surgical management of craniopharyngiomas includes transcranial approaches (TCAs) and endoscopic endonasal approaches (EEAs). The impact of these approaches on hypothalamic and endocrinological outcomes is controversial. Earlier systematic reviews showed contradictory results. This systematic review aims to clarify whether EEA is associated with lower postoperative hypothalamic and endocrinological morbidities than TCA. We conducted systematic literature search in PubMed and Embase following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Sixteen nonrandomized cohort studies that compared EEA and TCA were included in the meta-analysis. Postoperative hypothalamic morbidity, new-onset hypopituitarism, and diabetes insipidus (DI) were compared. Risk ratio (RR) was used to calculate effect sizes. Age (P = 0.28) and tumor volume on MRI (P = 0.20) at presentation were comparable between EEA and TCA. GTR was greater with EEA (RR: 0.84; P: 0.001). Incidences of postoperative hypothalamic morbidity (RR: 1.3; P = 0.18), new-onset hypopituitarism (RR: 1.10; P = 0.39), and DI (RR: 1.10; P = 0.40) were comparable between TCA and EEA. EEA resulted in less postoperative visual deterioration (RR: 3.48; P = <0.001) and a higher CSF leak after surgery (RR: 0.17; P = <0.001). The tumor recurrence was significantly higher after TCA (RR: 1.83; P < 0.001). However, the mean follow-up duration (P = 0.01) was relatively shorter with EEA. There was no significant difference in the requirement of CSF diversion for postoperative hydrocephalus (P = 0.91) between EEA and TCA. Postoperative hypothalamic morbidity and endocrinological outcomes are comparable between TCA and EEA. While EEA is associated with higher CSF leak, visual deterioration was more common with TCA postoperatively. EEA also reduces tumor recurrence on follow-up.

BackgroundFunctional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms.MethodsMedial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms.ResultsStructural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms.ConclusionsObesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.

Stress from many sources, including pain, fever, and hypotension, activates the hypothalamic-pituitary-adrenal (HPA) axis with the sustained secretion of corticotropin and cortisol. Increased glucocorticoid action is an essential component of the stress response, and even minor degrees of adrenal insufficiency can be fatal in the stressed host. HPA dysfunction is a common and underdiagnosed disorder in the critically ill. We review the risk factors, pathophysiology, diagnostic approach, and management of HPA dysfunction in the critically ill.