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Cited by 0Pituitary Gland Disorders and TreatmentsElectrolyte and hormonal disordersHypothalamic control of reproductive hormones

Approach to the patient with acquired hypothalamic syndrome

Open access
Grishman, Ellen K, McCormack, Shana E·2026·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/clinem/dgag197PMC PMC13466942
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Abstract

The hypothalamus integrates signals from the body and the environment and coordinates homeostatic responses in multiple physiologic processes, including water balance, stress response, temperature regulation, energy balance, feeding behavior, sleep-wake cycles, and reproduction. Endocrinologists care for individuals for whom hypothalamic injury, whether from tumors, their treatment, or other causes, impairs pituitary hormone production and secretion. The extent of other symptoms in affected individuals is also influenced the extent of hypothalamic injury. “Acquired hypothalamic syndrome” refers to this broader collection of problems attributable to hypothalamic injury, variably including not only pituitary hormone deficiencies, but also hypothalamic obesity (or rarely, diencephalic syndrome), sleep and circadian disruption, temperature dysregulation, and behavioral issues (including memory problems and impulse control). Our goal is to present a pragmatic guide to the multidisciplinary, collaborative evaluation and management of hypothalamic syndrome.

AI snapshot

Written from the paper’s full text.

TL;DR

This is a pragmatic clinical review of acquired hypothalamic syndrome, covering its diagnostic criteria, pathophysiology, and multidisciplinary management across pituitary hormone deficiencies, hypothalamic obesity, cardiovascular, sleep/circadian, temperature, and behavioral domains. It uses an illustrative pediatric craniopharyngioma case and cites evidence for treatments including GLP1RAs and setmelanotide.

Key findings

  • Acquired hypothalamic syndrome includes pituitary hormone deficiencies plus variable hypothalamic obesity, sleep/circadian disruption, temperature dysregulation, and behavioral problems; hypothalamic injury leads to acquired hypothalamic syndrome in approximately 80% of individuals, depending largely on tumor characteristics.
  • In a survey of 353 individuals with acquired hypothalamic dysfunction, obesity was the most frequently reported health problem at 50.7%, followed by fatigue at 48.2%; 25.2% felt they had not received adequate nutritional advice when attempting weight loss.
  • In a 2024 case series, 25 of 26 individuals with hypothalamic obesity lost weight on semaglutide, with mean weight loss of 13.4 kg after 12 months; in a phase 3 trial of setmelanotide in acquired hypothalamic obesity, mean BMI change at 52 weeks was −16.5% with setmelanotide vs +3.3% with placebo.
  • Excessive daytime sleepiness has been reported in 25% to 100% of individuals with craniopharyngioma depending on cohort and tools; in one study, 82% met objective criteria for excess daytime sleepiness while only 29% endorsed it on the modified Epworth Sleepiness Scale.
  • In the illustrative case, BMI increased from approximately 132% to approximately 148% of the 95th percentile in the first approximately 9 months after definitive tumor treatment; after starting semaglutide at age 12 years, BMI decreased by 14%, from 148% to 124% of the 95th percentile over approximately 6 months.

Methods

  • Narrative clinical review and pragmatic management guide, not a systematic review or original study; it synthesizes diagnostic criteria, hypothalamic nuclei functions, radiographic scoring systems, hormone replacement, obesity pharmacotherapy, cardiovascular, sleep, temperature, and behavioral management.
  • Uses an illustrative case of a 10-year-old child with adamantinomatous craniopharyngioma, multiple pituitary hormone deficiencies, postoperative obesity, and multidisciplinary care, followed through semaglutide treatment.
  • Includes tables summarizing hypothalamic nuclei/functions and a brief clinical visit checklist; no formal sample, randomization, or statistical analysis is reported.

Limitations

  • Stated in the paper: the visit checklist is “not intended to be comprehensive”; evidence is incomplete; for some manifestations, such as disordered temperature regulation, there are few studies demonstrating effective approaches; more research is needed for oxytocin replacement, glucocorticoid replacement details, and optimal obesity pharmacotherapy strategy.
  • Stated in the paper: many hypothalamic functions are less well characterized or yet to be discovered, and manifestations can change over time.
  • Evident from the text: this is a narrative review without systematic search or quality appraisal, and it relies on heterogeneous evidence including small case series, retrospective studies, and a single illustrative case, limiting generalizability.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/clinem/dgag197

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

68 of 121 cited sources checked · 37 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    A growing body of evidence supports the heterogeneity of acquired hypothalamic syndrome, with individuals experiencing many distinct and unique combinations of problems.

    “A growing body of evidence supports the heterogeneity of this condition, with individuals experiencing many distinct and unique combinations of problems (3).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] van Roessel, 2025, The many different clinical faces of acquired hypothalamic dysfunction: a retrospective cohort study in The Netherlands, EClinicalMedicine source
  • Premisecitation

    In prepubertal age children, hypothalamic injury can also disrupt typical pubertal timing and precipitate early or precocious puberty.

    “in prepubertal age children, hypothalamic injury can also disrupt typical pubertal timing and precipitate early or precocious puberty (13)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] Reichlin, 1989, Neuroendocrinology of the pituitary gland, Toxicol Pathol source

      The Abstract (page unavailable) says hypothalamic lesions affect pituitary function and identifies hypothalamic factors that stimulate gonadotropin secretion. Neither it nor the other retrieved passages addresses pubertal timing or precocious puberty in prepubertal children (searched: precocious puberty, hypothalamic injury, puberty and hypothalamic lesions). (LLM, conf=0.72)

      Experimental — accuracy not yet measured
  • Premisecitation

    Recent guidelines suggest initiation of GH as early as 3 months post completion of therapy in individuals with craniopharyngioma.

    “suggesting initiation as early as 3 months post completion of therapy in individuals with craniopharyngioma.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [29] Boguszewski, 2022, Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement, Eur J Endocrinol source

      The section on timing GH therapy after tumour treatment says initiation as early as 3 months is reasonable for some children with craniopharyngioma. The claim extends that timing to individuals generally, but the consensus limits it to children with radiologically stable disease and relevant growth or metabolic concerns; it discusses adults separately. No page number is provided in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [30] van Iersel, 2025, Growth hormone replacement therapy in childhood-onset craniopharyngioma, Best Pract Res Clin Endocrinol Metab source
  • Premisecitation

    Ongoing accumulating evidence supports the safety of GH replacement.

    “Ongoing accumulating evidence of the safety of GH replacement has led to more recent guidelines (29) and other reviews (30)”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [29] Boguszewski, 2022, Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement, Eur J Endocrinol source
    • cites [30] van Iersel, 2025, Growth hormone replacement therapy in childhood-onset craniopharyngioma, Best Pract Res Clin Endocrinol Metab source
  • Premisecitation

    Healthful nutrition and physical activity are rarely sufficient to address weight gain in hypothalamic obesity.

    “but are rarely sufficient to address weight gain”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [36] Roth, 2024, Acquired hypothalamic obesity: a clinical overview and update, Diabetes Obes Metab source
    • cites [37] Argente, 2025, Hypothalamic obesity: from basic mechanisms to clinical perspectives, Lancet Diabetes Endocrinol source
  • Classified as probably not a substantial claim. 22
  • May combine two claims. 32
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In one survey of 353 individuals with acquired hypothalamic dysfunction, obesity was the most frequently reported health problem, affecting 50.7%.

    “In one survey of 353 individuals with acquired hypothalamic dysfunction, obesity was the most frequently reported health problem, affecting 50.7%”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] van Roessel, 2023, Acquired hypothalamic dysfunction in childhood: ‘what do patients need?’ - an endo-ERN survey, Endocr Connect source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    Hypothalamic syndrome represents a substantial burden for patients and families.

    “Hypothalamic syndrome represents a substantial burden for patients and families (5-8), and correspondingly, poses a considerable challenge to clinicians.”
    Quote in the paperNot a substantial claim4 of 4 sources checked
    • cites [5] Craven, 2022, A survey of patient-relevant outcomes in pediatric craniopharyngioma: focus on hypothalamic obesity, Front Endocrinol (Lausanne) source

      The Introduction describes impaired quality of life and challenges for affected individuals and families, and the Discussion reports reduced social functioning and caregiver concerns. These passages concern hypothalamic obesity and other sequelae in survivors of pediatric craniopharyngioma; they do not establish the burden of hypothalamic syndrome generally. No page numbers are available in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [6] Marshall, 2023, Retrospective dataset and survey analyses identify gaps in data collection for craniopharyngioma and priorities of patients and families affected by the disease, Neoplasia source
    • cites [7] van Roessel, 2023, Acquired hypothalamic dysfunction in childhood: ‘what do patients need?’ - an endo-ERN survey, Endocr Connect source
    • cites [8] Kayadjanian, 2023, Caregiver burden and its relationship to health-related quality of life in craniopharyngioma survivors, J Clin Endocrinol Metab source

      The Discussion reports that symptoms of hypothalamic dysfunction in craniopharyngioma survivors were linked to high caregiver burden and negatively affected survivors’ quality of life. This supports a substantial burden for those patients and their families, but the paper studies craniopharyngioma survivors rather than hypothalamic syndrome across patient populations. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Deficiencies of these hypothalamic and/or pituitary hormones result in central adrenal insufficiency (AI), GH deficiency (GHD), central hypothyroidism, and hypogonadotropic hypogonadism.

    “Deficiencies of these hypothalamic and/or pituitary hormones result in central adrenal insufficiency (AI), GH deficiency (GHD), central hypothyroidism, and hypogonadotropic hypogonadism”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] Reichlin, 1989, Neuroendocrinology of the pituitary gland, Toxicol Pathol source
    • Rests on an assumption: The hypothalamus controls pituitary hormone production by producing vasopressin, corticotrophin-releasing hormone, thyrotropin-releasing hormone, GH-releasing hormone, and gonadotropin-releasing hormone.

  • May combine two claims.

    Premisecitation

    Testosterone replacement in boys with hypogonadism increases muscle mass, which influences resting energy expenditure.

    “testosterone replacement in boys with hypogonadism increases muscle mass, which influences resting energy expenditure (32)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [32] van Iersel, 2019, Pathophysiology and individualized treatment of hypothalamic obesity following craniopharyngioma and other suprasellar tumors: a systematic review, Endocr Rev source

      In “Interventions targeting hypopituitarism” (page unavailable), the review says testosterone replacement improves muscle mass in males, citing adult hypopituitarism guidelines; it separately says testosterone therapy induces puberty in boys. “Domain 6: hypopituitarism” (page unavailable) says testosterone influences resting energy expenditure by increasing muscle mass. The review does not specifically establish that replacement increases muscle mass in boys with hypogonadism. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Guidelines propose total daily hydrocortisone doses of 15 to 20 mg per day in 2 or 3 divided doses, with the highest dose in the morning, with a view to approximating typical circadian patterns.

    “In adults, guidelines propose total daily hydrocortisone doses of 15 to 20 mg per day in 2 or 3 divided doses, with the highest dose in the morning, with a view to approximating typical circadian patterns”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] Fleseriu, 2016, Hormonal replacement in hypopituitarism in adults: an endocrine society clinical practice guideline, J Clin Endocrinol Metab source

      The Glucocorticoid Replacement recommendation gives a usual total hydrocortisone dose of 15–20 mg/day and specifies the highest morning dose for two- or three-dose regimens. It also allows a single daily dose, which the claim omits. The Circadian rhythm–multiple daily dosing section discusses the normal rhythm but cautions that available regimens do not accurately simulate it. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Healthful nutrition and physical activity, as well as other aspects of lifestyle modification, are critical aspects of treatment, especially to prevent or mitigate obesity-related health problems.

    “Healthful nutrition and physical activity, as well as other aspects of lifestyle modification, are critical aspects of treatment, especially to prevent or mitigate obesity-related health problems”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [36] Roth, 2024, Acquired hypothalamic obesity: a clinical overview and update, Diabetes Obes Metab source
    • cites [37] Argente, 2025, Hypothalamic obesity: from basic mechanisms to clinical perspectives, Lancet Diabetes Endocrinol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the same survey, fatigue was reported by 48.2%.

    “followed by fatigue, reported by 48.2% (7)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] van Roessel, 2023, Acquired hypothalamic dysfunction in childhood: ‘what do patients need?’ - an endo-ERN survey, Endocr Connect source

  • May combine two claims.

    Premisecitation

    The timing of pubertal induction is individualized, with many individuals starting at typical ages (ie, 11 years in girls and 12 years in boys).

    “The timing of pubertal induction is individualized, with many individuals starting at typical ages (ie, 11 years in girls and 12 years in boys) (31)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] Nordenstrom, 2022, Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline, Eur J Endocrinol source

      The Abstract (page not provided) says pubertal induction should be individualized and considered at 11 years in girls and 12 years in boys. That supports the ages as guidance, but not the claim that many individuals actually start at those ages; the boys’ section describes varied practice instead. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In primary hypothyroidism, the addition of twice-daily 3,5,3′-triiodothyronine (T3) replacement to levothyroxine is considered, especially if T3 levels are low, if individuals have persistent symptoms that could be related to hypothyroidism.

    “In primary hypothyroidism, the addition of twice-daily 3,5,3′-triiodothyronine (T3) replacement to levothyroxine is considered, especially if T3 levels are low, if individuals have persistent symptoms that could be related to hypothyroidism (22).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Taylor, 2024, Hypothyroidism, Lancet source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Historically, a theoretical concern for risk of primary tumor recurrence or secondary neoplasia related to GH use led to caution, and delays of a year following treatment for some brain tumors.

    “historically, a theoretical concern for risk of primary tumor recurrence or secondary neoplasia related to GH use led to caution, and delays of a year following treatment for some brain tumors (28)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [28] Sklar, 2018, Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline, J Clin Endocrinol Metab source

  • May combine two claims.

    Premisecitation

    In a retrospective study, dextroamphetamine demonstrated favorable benefits with respect to weight loss (or attenuation of weight gain) while also achieving decreases in hyperphagia and improved energy.

    “In a retrospective study, dextroamphetamine (50) has demonstrated favorable benefits with respect to weight loss (or attenuation of weight gain) while also achieving decreases in hyperphagia and improved energy (50).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [50] van Schaik, 2022, Dextroamphetamine treatment in children with hypothalamic obesity, Front Endocrinol (Lausanne) source

  • May combine two claims.

    Premisecitation

    In a 2024 case series, 25 of 26 individuals with hypothalamic obesity lost weight in response to semaglutide, with a mean weight loss of 13.4 kg after 12 months.

    “in 2024, a case series demonstrated that 25 of 26 individuals with hypothalamic obesity lost weight in response to semaglutide, with a mean weight loss of 13.4 kg after 12 months (42).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [42] Svendstrup, 2024, Semaglutide treatment of hypothalamic obesity - a real-life data study, Pituitary source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the previously cited patient survey, 25.2% of respondents felt they had not received adequate nutritional advice when attempting to lose weight.

    “In the previously cited patient survey, 25.2% of respondents felt they had not received adequate nutritional advice when attempting to lose weight (7).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] van Roessel, 2023, Acquired hypothalamic dysfunction in childhood: ‘what do patients need?’ - an endo-ERN survey, Endocr Connect source

      The Results section (Unmet needs and rating of current care for hypothalamic dysfunction) reports that 25.2% of patients identified dietary help as an unmet need. It does not say those respondents were attempting to lose weight or that they had received inadequate nutritional advice; a separate 23.8% rated their dietitian’s support as insufficient. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Adverse cardiac remodeling is evident even in the youngest survivors of craniopharyngioma, and worsens with increasing age and by adulthood, also with obesity.

    “Adverse cardiac remodeling is evident even in the youngest survivors, and worsens with increasing age and by adulthood, also with obesity (66).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [66] Sowithayasakul, 2021, Cardiac remodeling in patients with childhood-onset craniopharyngioma-results of HIT-Endo and KRANIOPHARYNGEOM 2000/2007, Eur J Pediatr source

      The Results (page unavailable) report that all echocardiographic parameters were normal in the pediatric subgroup except for increased wall thickness in one extremely obese patient. The Abstract and Discussion associate remodeling with BMI and disease duration, but this cross-sectional study does not show that remodeling is evident in the youngest survivors or worsens as individuals age into adulthood. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In Prader-Willi syndrome, extended-release diazoxide treatment resulted in stable body fat mass and increased lean body mass.

    “while body fat mass remained stable, lean body mass increased (47).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [47] Miller, 2024, Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study, Obesity (Silver Spring) source

  • May combine two claims.

    Premisecitation

    Some individuals with brain tumors develop obsessive compulsive symptoms, but these manifestations seem infrequent enough that they were described in a case report.

    “Some individuals with brain tumors develop obsessive compulsive symptoms, but these manifestations seem infrequent enough that they were described in a case report (82).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [82] Saroj, 2024, A case report of obsessive-compulsive disorder in craniopharyngioma: moderating effect of tumor, Indian J Psychiatry source

      The case report describes a patient with obsessive-compulsive symptoms after surgery for a craniopharyngioma, and its introduction says brain tumors can produce such symptoms. It does not establish that these manifestations are infrequent; the authors also acknowledge that this patient's symptoms might have resulted from surgery rather than the tumor itself. The supplied copy has no page numbers. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Individuals with hyperphagia spend more time "talking or engaging with food" than those without hyperphagia, and food interferes with daily functioning.

    “Individuals with hyperphagia spend more time “talking or engaging with food” than those without hyperphagia, and food interferes with daily functioning (84).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [84] Hinton, 2024, Evaluating eating behaviour, energy homeostasis, and obesity in childhood-onset craniopharyngioma: a feasibility study, Horm Res Paediatr source

      The Results section ('Preliminary Data with Matched Controls') reports more time spent talking or engaging with food and greater interference with daily functioning in patients with childhood-onset craniopharyngioma than in matched controls. It also reports greater hyperphagia in the patient group, but it does not compare individuals classified as having hyperphagia with those without it. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Fatigue in individuals with hypothalamic syndrome could potentially be related to disordered signaling from GABAergic neurons in the suprachiasmatic, ventrolateral, and preoptic nuclei.

    “Commonly reported fatigue (72, 73) could potentially be related to disordered signaling from γ-aminobutyric acid (GABA)-ergic neurons in the suprachiasmatic, ventrolateral, and preoptic nuclei (74, 75).”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [72] Romigi, 2021, Sleep disorders in patients with craniopharyngioma: a physiopathological and practical update, Front Neurol source

      The Classification and Pathogenesis section links damage to the suprachiasmatic nucleus and preoptic areas with disrupted sleep–wake regulation and daytime somnolence. It describes melatonin and orexin pathways, however, not disordered GABAergic signaling as a potential cause of fatigue. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [73] Muller, 2010, Increased daytime sleepiness in patients with childhood craniopharyngioma and hypothalamic tumor involvement: review of the literature and perspectives, Int J Endocrinol source

      The paper’s Abstract links hypothalamic injury, including possible suprachiasmatic nucleus dysfunction, to increased daytime sleepiness in patients with childhood craniopharyngioma. It does not attribute that symptom to disordered GABAergic signaling in the suprachiasmatic, ventrolateral, and preoptic nuclei; its discussion instead focuses on melatonin and orexin. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [74] Gallopin, 2000, Identification of sleep-promoting neurons in vitro, Nature source
    • cites [75] Donlea, 2017, Neuronal substrates of sleep homeostasis; lessons from flies, rats and mice, Curr Opin Neurobiol source

  • May combine two claims.

    Premisecitation

    Peer relationships pose a challenge for many individuals with hypothalamic syndrome; those with obesity fare even worse than those without, and more than is accounted for by weight gain alone.

    “Peer relationships also pose a challenge for many individuals with hypothalamic syndrome; those with obesity fare even worse than those without, and more than is accounted for by weight gain alone (5).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [5] Craven, 2022, A survey of patient-relevant outcomes in pediatric craniopharyngioma: focus on hypothalamic obesity, Front Endocrinol (Lausanne) source

      The Discussion (page unavailable) reports impaired peer relationships in youth with craniopharyngioma, worse scores among those with obesity, and scores below those reported for children with obesity without craniopharyngioma. It proposes additive effects of craniopharyngioma and obesity, but does not establish that the difference exceeds what weight gain alone accounts for. The study also does not establish the finding for individuals with hypothalamic syndrome generally. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The effect of hyperphagia behaviors is decreased quality of life for affected individuals and increased burden for caretakers; obesity without hyperphagia does not have the same effects.

    “The effect of these hyperphagia behaviors is decreased quality of life for affected individuals and increased burden for caretakers; obesity without hyperphagia does not have the same effects (84).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [84] Hinton, 2024, Evaluating eating behaviour, energy homeostasis, and obesity in childhood-onset craniopharyngioma: a feasibility study, Horm Res Paediatr source

      The Discussion (page not provided) reports that parents rated quality of life lower for young people with greater hyperphagic behaviours, but the young people’s own ratings did not show that relationship. The paper does not establish that hyperphagia causes lower quality of life, measure increased caretaker burden, or compare these effects with obesity without hyperphagia. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The limbic system affects emotional regulation and is integrally connected to the hypothalamus.

    “The limbic system affects emotional regulation and is integrally connected to the hypothalamus (86), so when the connection between the two is impaired, emotional lability can occur.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [86] Rajmohan, 2007, The limbic system, Indian J Psychiatry source

  • Probably not a substantial claim: may not pass S4 (based). The quote only partly states this claim.

    Findingnone given

    Individuals who consume a diet with plenty of lean protein, healthful fat, vegetables and other high-fiber, complex carbohydrates, with limited amounts of simple and/or added sugars, are most successful (in weight management).

    “Our observation is that individuals who consume a diet with plenty of lean protein, healthful fat, vegetables and other high-fiber, complex carbohydrates, with limited amounts of simple and/or added sugars, are most successful.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Once the child turned 12 years, semaglutide was obtained for the obesity indication, and led to some initial weight loss, including a 14% decrease in BMI, representing a decrease from 148% of the 95th percentile BMI to 124% of the 95th percentile BMI.

    “Once the child turned 12 years, semaglutide was obtained for the obesity indication, and led to some initial weight loss, including a 14% decrease in BMI, representing a decrease from 148% of the 95th percentile BMI to 124% of the 95th percentile BMI (Fig. 3).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Alanine transaminase decreased from a peak of 3 to 4 times the upper limit of the reference range to approximately 2 times the upper limit of the reference range.

    “Liver function tests varied, but overall alanine transaminase decreased from a peak of 3 to 4 times the upper limit of the reference range to approximately 2 times the upper limit of the reference range;”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After the patient turned age 12 years, approval for semaglutide for obesity was obtained, with a decrease to 124% of the 95th percentile over the first approximately 6 months of treatment.

    “After the patient turned age 12 years, approval for a glucagon-like peptide 1 agonist (semaglutide) for obesity was obtained, with a decrease to 124% of the 95th percentile over the first approximately 6 months of treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Prior to initiation of semaglutide, magnetic resonance elastography showed steatosis, with fat fraction between 12% and 14%, and increased liver stiffness, reflecting congestion and/or fibrosis, at 4.8 kPa.

    “prior to initiation of semaglutide, magnetic resonance elastography showed steatosis, with fat fraction between 12% and 14%, and increased liver stiffness, reflecting congestion and/or fibrosis, at 4.8 kPa.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    A selective serotonin reuptake inhibitor was initiated for anxiety with good effect.

    “A selective serotonin reuptake inhibitor was initiated for anxiety with good effect.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    The child continued to undergo MRI surveillance at intervals and was without tumor recurrence.

    “The child continued to undergo MRI surveillance at intervals and was without tumor recurrence.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    Diagnostic biopsy was declined, and a presumptive diagnosis of metabolic-associated steatotic liver disease was made.

    “Diagnostic biopsy was declined, and a presumptive diagnosis of metabolic-associated steatotic liver disease was made.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    BMI already exceeded the 95th percentile at diagnosis, and quickly increased to a peak of 148% of the 95th percentile within 9 months.

    “BMI already exceeded the 95th percentile at diagnosis, and quickly increased to a peak of 148% of the 95th percentile within 9 months.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The extent of other symptoms in affected individuals is influenced by the extent of hypothalamic injury.

    “The extent of other symptoms in affected individuals is also influenced the extent of hypothalamic injury.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The diagnostic criteria include assessment of background risk from radiologic assessment of the hypothalamus and/or risk for a genetic disorder associated with hypothalamic syndrome, and then assessment of multiple clinical domains: status of pituitary hormone function, including AVP-D with or without thirst; appetite and weight trajectory; sleep and circadian function; temperature regulation; and

    “These criteria include assessment of background risk from radiologic assessment of the hypothalamus and/or risk for a genetic disorder associated with hypothalamic syndrome, and then assessment of multiple clinical domains: status of pituitary hormone function, including AVP-D with or without thirst; appetite and weight trajectory; sleep and circadian function; temperature regulation; and behavior”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] van Santen, 2023, Diagnostic criteria for the hypothalamic syndrome in childhood, Eur J Endocrinol source

  • May combine two claims.

    Premisecitation

    Other highly morbid symptoms of hypothalamic syndrome include abnormal sleep and circadian function, temperature dysregulation, and behavior changes.

    “Clinicians caring for such patients have also appreciated the presence of other highly morbid symptoms, including abnormal sleep and circadian function, temperature dysregulation, and behavior changes (2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Muller, 2022, Hypothalamic syndrome, Nat Rev Dis Primers source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The range of effects of hypothalamic injury follow from the essential roles of the hypothalamic nuclei.

    “The range of effects of hypothalamic injury follow from the essential roles of the hypothalamic nuclei, as illustrated in Fig. 2 and accompanying Table 1.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Formal diagnostic criteria, including common symptoms and a scoring system, were proposed to encompass both acquired and congenital forms of hypothalamic syndrome.

    “Formal diagnostic criteria, including the common symptoms and a scoring system (1), were proposed to encompass both acquired and congenital forms of hypothalamic syndrome.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] van Santen, 2023, Diagnostic criteria for the hypothalamic syndrome in childhood, Eur J Endocrinol source

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The hypothalamus integrates signals from the body and the environment and coordinates homeostatic responses in multiple physiologic processes, including water balance, stress response, temperature regulation, energy balance, feeding behavior, sleep-wake cycles, and reproduction.

    “The hypothalamus integrates signals from the body and the environment and coordinates homeostatic responses in multiple physiologic processes, including water balance, stress response, temperature regulation, energy balance, feeding behavior, sleep-wake cycles, and reproduction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    Hypothalamic syndrome poses a considerable challenge to clinicians.

    “Hypothalamic syndrome represents a substantial burden for patients and families (5-8), and correspondingly, poses a considerable challenge to clinicians.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    Increasing both patient/family and clinician awareness of hypothalamic syndrome is expected to lead to increased use of available interventions, including supportive measures, and to catalyze new investigations.

    “Regardless, increasing both patient/family and clinician awareness of hypothalamic syndrome is expected to lead to increased use of available interventions, including supportive measures, and to catalyze new investigations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The hypothalamus regulates energy expenditure and eating behaviors.

    “The hypothalamus regulates energy expenditure and eating behaviors”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Klages, 2022, Health-related quality of life, obesity, fragmented sleep, fatigue, and psychosocial problems among youth with craniopharyngioma, Psychooncology source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The preoptic nucleus produces gonadotropin-releasing hormone and thus regulates puberty.

    “As an illustration, the preoptic nucleus produces gonadotropin-releasing hormone, and thus regulates puberty, so individuals with injury to this area can have hypogonadotropic hypogonadism requiring pharmacologic replacement.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In hypothalamic syndrome, disorders of water balance are common, variably including AVP-D, syndrome of inappropriate AVP secretion (either transient or permanent), reset osmostat, or absent thirst (adipsia).

    “In hypothalamic syndrome, disorders of water balance are common, variably including AVP-D, syndrome of inappropriate AVP secretion (either transient or permanent), reset osmostat, or absent thirst (adipsia).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Chasseloup, 2024, Diabetes insipidus: vasopressin deficiency, Ann Endocrinol (Paris) source
    • Rests on an assumption: Vasopressin is produced in the paraventricular and supraoptic nuclei of the hypothalamus and promotes retention of free water in response to hyperosmolality and hypotension.
    • Rests on an assumption: The hypothalamus affects volume status by regulating thirst in response to hyperosmolality and hypotension.

  • May combine two claims.

    Interpretationreasoning

    Diazoxide has risk for side effects, which extend beyond hyperglycemia to fluid retention, and modest, if any, anticipated benefit for weight loss in acquired hypothalamic obesity.

    “Based on the experience to date, and the risk for side effects, which extend beyond hyperglycemia to fluid retention, and modest, if any, anticipated benefit for weight loss, we do not recommend using diazoxide for acquire hypothalamic obesity outside the research setting.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Sleep disruption is expected in hypothalamic syndrome because the hypothalamus plays a critical role in maintaining healthful sleep-wake cycles.

    “Sleep disruption is expected in hypothalamic syndrome because the hypothalamus plays a critical role in maintaining healthful sleep-wake cycles.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The hypothalamus plays a critical role in maintaining healthful sleep-wake cycles.

  • May combine two claims.

    Premisecitation

    In one study, 82% of children with craniopharyngioma met objective criteria for excess daytime sleepiness on multiple sleep latency testing, while only 29% endorsed this symptom on the modified Epworth Sleepiness Scale.

    “For example, one study screened children with craniopharyngioma using multiple sleep latency testing, and 82% met these objective criteria for excess daytime sleepiness, while only 29% endorsed this symptom on a validated questionnaire, the modified Epworth Sleepiness Scale (68).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] Crabtree, 2019, Sensitivity and specificity of the modified Epworth sleepiness scale in children with craniopharyngioma, J Clin Sleep Med source

  • May combine two claims.

    Interpretationcitation

    Setmelanotide has a favorable risk-benefit balance and holds promise for treatment of acquired hypothalamic obesity.

    “On balance, the favorable risk-benefit balance of this medication thus holds promise for treatment of acquired hypothalamic obesity.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: In the phase 3 study of setmelanotide for acquired hypothalamic obesity, the most common side effects were hyperpigmentation, nausea, and vomiting.
    • Rests on an assumption: Setmelanotide causes hyperpigmentation because of off-target cross-reactivity at the melanocortin 1 receptor in melanocytes.
    • Rests on an assumption: Hyperpigmentation typically appears within a few weeks of setmelanotide treatment initiation.
    • Rests on an assumption: Preexisting nevi can become darker, and new melanocytic nevi may appear during setmelanotide treatment.
    • Rests on an assumption: Hyperpigmentation is expected to reach a plateau, and fade if setmelanotide is discontinued.
    • Rests on an assumption: Nausea and vomiting typically appear soon after setmelanotide treatment initiation.
    • Rests on an assumption: More gradual uptitration of setmelanotide can help with tolerability.

  • May combine two claims.

    Interpretationreasoning

    Continuous positive airway pressure use avoids frequent apneic episodes and potential sequelae of untreated obstructive sleep apnea, including pulmonary hypertension.

    “its use remains strongly recommended because it avoids frequent apneic episodes and potential sequelae of untreated obstructive sleep apnea, including pulmonary hypertension.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Much of the related literature on behavioral problems originates from studies in individuals with PWS, so not all phenomena necessarily translate to acquired hypothalamic syndrome.

    “Much of the related literature originates from studies in individuals with PWS, so not all phenomena necessarily translate to acquired hypothalamic syndrome.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These deficits translate into impaired functional capabilities relative to healthy control cohorts, and portend worse academic performance and lower quality of life.

    “These deficits translate into impaired functional capabilities relative to healthy control cohorts, and portend worse academic performance and lower quality of life.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88] Ozyurt, 2014, Neuropsychological outcome in patients with childhood craniopharyngioma and hypothalamic involvement, J Pediatr source

  • May combine two claims.

    Interpretationcitation

    For persistently elevated temperature, strategies from individuals with traumatic brain injury, including administration of chlorpromazine, may be effective, although there is not substantial literature specifically in hypothalamic syndrome.

    “For persistently elevated temperature, strategies from individuals with traumatic brain injury, including administration of chlorpromazine, may be effective, although there is not substantial literature specifically in hypothalamic syndrome (81).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [81] Chatzisotiriou, 2004, Delayed persistent hyperthermia after resection of a craniopharyngioma, Pediatr Neurosurg source
49 of 49

  • The paper relies on this without support.

    Nononcologic processes, including traumatic brain injuries, can also cause acquired hypothalamic syndrome.

    “Nononcologic processes, including traumatic brain injuries, can also cause acquired hypothalamic syndrome.”

  • The paper relies on this without support.

    Manifestations of hypothalamic syndrome can change over time.

    “Relevant to clinicians monitoring such patients, manifestations can also change over time.”

  • The paper relies on this without support.

    For several manifestations of hypothalamic syndrome, such as obesity, there are now evidence-supported therapies.

    “For several of the manifestations of hypothalamic syndrome (eg, obesity), there are now evidence-supported therapies, whereas for others (eg, disordered temperature regulation), there are few studies demonstrating effective approaches.”

  • The paper relies on this without support.

    For other manifestations of hypothalamic syndrome, such as disordered temperature regulation, there are few studies demonstrating effective approaches.

    “For several of the manifestations of hypothalamic syndrome (eg, obesity), there are now evidence-supported therapies, whereas for others (eg, disordered temperature regulation), there are few studies demonstrating effective approaches.”

  • The paper relies on this without support.

    The hypothalamus controls pituitary hormone production by producing vasopressin, corticotrophin-releasing hormone, thyrotropin-releasing hormone, GH-releasing hormone, and gonadotropin-releasing hormone.

    “The hypothalamus controls corresponding pituitary hormone production by producing vasopressin (released by the posterior pituitary), corticotrophin-releasing hormone (for adrenocorticotropin), thyrotropin-releasing hormone (for thyrotropin), GH–releasing hormone (for GH), and gonadotropin-releasing hormone (for luteinizing hormone and follicle-stimulating hormone).”

  • The paper relies on this without support.

    Vasopressin is produced in the paraventricular and supraoptic nuclei of the hypothalamus and promotes retention of free water in response to hyperosmolality and hypotension.

    “Vasopressin is produced in the paraventricular and supraoptic nuclei of the hypothalamus and promotes retention of free water in response to hyperosmolality and hypotension.”

  • The paper relies on this without support.

    The hypothalamus affects volume status by regulating thirst in response to hyperosmolality and hypotension.

    “The hypothalamus also affects volume status by regulating thirst in response to these signals.”

  • The paper relies on this without support.

    Inadequately controlled AVP-D often results in nighttime awakenings to drink and/or urinate, which exacerbate fatigue in individuals who may already have disordered sleep.

    “Inadequately controlled AVP-D often results in nighttime awakenings to drink and/or urinate, which exacerbate fatigue in individuals who may already have disordered sleep.”

  • The paper relies on this without support.

    Individuals with intact thirst are at risk to drink sweet beverages to excess, which could precipitate hyponatremia if they are also taking a vasopressin analogue.

    “They should not be permitted ad libitum sweet beverages, though, since they are at risk to drink these to excess, which could precipitate hyponatremia if they are also taking a vasopressin analogue.”

  • The paper relies on this without support.

    Individuals with AVP-D may also be deficient in oxytocin.

    “Individuals with AVP-D may also be deficient in oxytocin, another hormone produced in the posterior hypothalamus.”

  • The paper relies on this without support.

    Untreated central AI can lead to adrenal crisis.

    “Treatment of central AI is essential to prevent adrenal crisis.”

  • The paper relies on this without support.

    Overtreatment of central AI can contribute to weight gain in individuals of all ages and poor linear growth in children.

    “However, overtreatment can contribute to weight gain in individuals of all ages and poor linear growth in children.”

  • The paper relies on this without support.

    Acute illness or procedures require stress-dose steroids to avoid adrenal crisis.

    “Acute illness or procedures require “stress-dose” steroids to avoid adrenal crisis.”

  • The paper relies on this without support.

    Thyrotropin levels are not reliable in patients with secondary hypothyroidism.

    “Thyrotropin levels are not reliable in patients with secondary hypothyroidism and should no longer be used to guide treatment after the diagnosis is made.”

  • The paper relies on this without support.

    Individuals with untreated GHD often have impaired lipid profiles and increased visceral adiposity.

    “Individuals with untreated GHD often have impaired lipid profiles and increased visceral adiposity, and often report decreased energy and diminished quality of life.”

  • The paper relies on this without support.

    Individuals with untreated GHD often report decreased energy and diminished quality of life.

    “Individuals with untreated GHD often have impaired lipid profiles and increased visceral adiposity, and often report decreased energy and diminished quality of life.”

  • The paper relies on this without support.

    Some individuals start pubertal induction later if maximizing linear growth is a consideration in those with short stature who warrant additional time for growth to permit attainment of height potential.

    “but some starting later if, for example, maximizing linear growth is a consideration in those with short stature who warrant additional time for growth to permit attainment of height potential.”

  • The paper relies on this without support.

    Public health guidelines typically recommend a combination of aerobic and resistance training.

    “Public health guidelines typically recommend a combination of aerobic and resistance training that may initially be out of reach for individuals with hypothalamic obesity who are deconditioned.”

  • The paper relies on this without support.

    It is challenging to conduct rigorous trials of nutrition interventions, especially in hypothalamic obesity.

    “It is challenging to conduct rigorous trials of nutrition interventions, especially in hypothalamic obesity”

  • The paper relies on this without support.

    Fewer data are available on GLP1RA use in children with hypothalamic obesity than in adults.

    “Fewer data are available in children with hypothalamic obesity, even though GLP1RAs are approved for obesity in the United States for children as young as 12 years, and as young as 10 years for other indications.”

  • The paper relies on this without support.

    Access to GLP1RAs remains challenging, especially for children.

    “However, as in adults, access remains challenging, especially for children, for whom there are fewer currently approved other indications (eg, metabolic-associated liver disease, obstructive sleep apnea) compared to adults.”

  • The paper relies on this without support.

    Adverse effects of GLP1RAs can be more severe in individuals with multiple pituitary hormone deficiencies who must take oral medications and maintain hydration.

    “Additionally, dosing must be individualized to address adverse effects, which can be more severe in individuals with multiple pituitary hormone deficiencies who must take oral medications and maintain hydration.”

  • The paper relies on this without support.

    In the phase 3 study of setmelanotide for acquired hypothalamic obesity, the most common side effects were hyperpigmentation, nausea, and vomiting.

    “As when used for other forms of hypothalamic obesity, the most common side effects were hyperpigmentation, nausea, and vomiting.”

  • The paper relies on this without support.

    Setmelanotide causes hyperpigmentation because of off-target cross-reactivity at the melanocortin 1 receptor in melanocytes.

    “Setmelanotide causes hyperpigmentation because of off-target cross-reactivity at the melanocortin 1 receptor in melanocytes.”

  • The paper relies on this without support.

    Hyperpigmentation typically appears within a few weeks of setmelanotide treatment initiation.

    “Hyperpigmentation typically appears within a few weeks of treatment initiation.”

  • The paper relies on this without support.

    Preexisting nevi can become darker, and new melanocytic nevi may appear during setmelanotide treatment.

    “Preexisting nevi can become darker, and new melanocytic nevi may appear; thus, regular dermatologic monitoring is appropriate.”

  • The paper relies on this without support.

    Hyperpigmentation is expected to reach a plateau, and fade if setmelanotide is discontinued.

    “Hyperpigmentation is expected to reach a plateau, and fade if medication is discontinued.”

  • The paper relies on this without support.

    Nausea and vomiting typically appear soon after setmelanotide treatment initiation.

    “Nausea and vomiting also typically appear soon after treatment initiation; more gradual uptitration can help with tolerability.”

  • The paper relies on this without support.

    More gradual uptitration of setmelanotide can help with tolerability.

    “Nausea and vomiting also typically appear soon after treatment initiation; more gradual uptitration can help with tolerability.”

  • The paper relies on this without support.

    Empiric data on combined phentermine and topiramate in individuals with hypothalamic obesity are limited.

    “One ongoing trial is testing combined phentermine and topiramate in individuals with hypothalamic obesity (NCT06299891); empiric data are limited, but this oral agent already approved in the United States for adolescents age 12 years and older with obesity could be considered with careful individualization of the risk-benefit profile, including attention to potential cardiac effects of stimulants,”

  • The paper relies on this without support.

    Phentermine/topiramate is approved in the United States for adolescents age 12 years and older with obesity.

    “One ongoing trial is testing combined phentermine and topiramate in individuals with hypothalamic obesity (NCT06299891); empiric data are limited, but this oral agent already approved in the United States for adolescents age 12 years and older with obesity could be considered with careful individualization of the risk-benefit profile, including attention to potential cardiac effects of stimulants,”

  • The paper relies on this without support.

    Metformin may be useful to address insulin resistance or type 2 diabetes mellitus.

    “While not a first-line choice to achieve weight loss in hypothalamic obesity, based on minimal anticipated benefit, metformin may be useful to address insulin resistance or type 2 diabetes mellitus, and is inexpensive, so may be an option for individuals for whom GLP1RAs, for example, are not a choice.”

  • The paper relies on this without support.

    Stimulants can help address excess weight gain while also improving attention and energy.

    “Stimulants should be strongly considered in individuals with excess appetite who also have other indications for stimulants such as inattention, attention deficit hyperactive disorder (ADHD), and/or excess daytime fatigue, as stimulants can help address excess weight gain while also improving attention and energy.”

  • The paper relies on this without support.

    At the time of writing, tesofensine is not approved for clinical use.

    “Finally, a small trial using tesofensine plus metoprolol (the latter to avoid potential adverse cardiovascular effects of tesofensine) resulted in weight loss in hypothalamic obesity (52), but at the time of this writing, tesofensine is not approved for clinical use.”

  • The paper relies on this without support.

    The autonomic nervous system supports the cardiovascular response to exercise.

    “The autonomic nervous system also supports the cardiovascular response to exercise.”

  • The paper relies on this without support.

    The autonomic nervous system is essential in maintaining hemodynamic stability in response to stresses such as illness, injuries, or operative procedures.

    “The autonomic nervous system is also essential in maintaining hemodynamic stability in response to stresses such as illness, injuries, or operative procedures.”

  • The paper relies on this without support.

    Excess daytime sleepiness is likely underreported in individuals with craniopharyngioma, in part because of underrecognition even among affected individuals and their families.

    “Consensus exists that excess daytime sleepiness is likely underreported, in part because of underrecognition even among affected individuals and their families.”

  • The paper relies on this without support.

    The hypothalamus plays a critical role in maintaining healthful sleep-wake cycles.

    “Sleep disruption is expected in hypothalamic syndrome because the hypothalamus plays a critical role in maintaining healthful sleep-wake cycles.”

  • The paper relies on this without support.

    Untreated sleep-disordered breathing can contribute to excess daytime sleepiness.

    “Untreated sleep-disordered breathing, which is more common but not exclusively seen in individuals with obesity, can also contribute to excess daytime sleepiness.”

  • The paper relies on this without support.

    Behavioral problems are common in individuals with hypothalamic syndrome.

    “Behavioral problems are common in individuals with hypothalamic syndrome.”

  • The paper relies on this without support.

    Cognitive impairment is reported in individuals with hypothalamic syndrome.

    “Cognitive impairment is also reported in individuals with hypothalamic syndrome.”

  • The paper relies on this without support.

    The limbic system is implicated in the development of ADHD.

    “The limbic system has also been implicated in the development of ADHD, which may explain symptoms of inattention and difficulty focusing that may develop in individuals with hypothalamic syndrome.”
42 of 42

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Phillip, 2002, Growth without growth hormone, J Pediatr Endocrinol Metab, 15, 1267

Cited by

Still being checked.

Authors
Grishman, E. K., & McCormack, S. E.
Affiliations
  • St. Jude Children's Research Hospital (US)
  • Children's Hospital of Philadelphia (US)
ORCID
McCormack, Shana E
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2026-05-11
Volume
111
Issue
9
Pages
2692-2703
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/clinem/dgag197
PMC
PMC13466942
OpenAlex
W7160837313
Semantic Scholar
16d3ede3623909fef1764061fc8528b41bf2ce51
Cited by
0
References
90
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
Children’s Hospital of Philadelphia (R01KD135211)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
hypothalamic injury, hypothalamic obesity, diencephalic syndrome, pituitary hormone deficiency, impulse control disorders, memory impairment, multidisciplinary management, hypothalamic tumors, homeostasis
MeSH terms
Humans, Hypothalamic Diseases, Hypothalamus, Obesity, Syndrome

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-21.

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