hypothalamic diseases


Summary: Neoplastic, inflammatory, infectious, and other diseases of the hypothalamus. Clinical manifestations include appetite disorders; AUTONOMIC NERVOUS SYSTEM DISEASES; SLEEP DISORDERS; behavioral symptoms related to dysfunction of the LIMBIC SYSTEM; and neuroendocrine disorders.

Top Publications

  1. Marcus M, Loucks T, Berga S. Psychological correlates of functional hypothalamic amenorrhea. Fertil Steril. 2001;76:310-6 pubmed
    ..The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge. ..
  2. Kim D, Fenoglio K, Simeone T, Coons S, Wu J, Chang Y, et al. GABAA receptor-mediated activation of L-type calcium channels induces neuronal excitation in surgically resected human hypothalamic hamartomas. Epilepsia. 2008;49:861-71 pubmed
    ..Given the ready availability of L-type calcium channel blockers, our results have clinical ramifications for the treatment of seizures associated with HH lesions. ..
  3. Beggs J, Nakada S, Fenoglio K, Wu J, Coons S, Kerrigan J. Hypothalamic hamartomas associated with epilepsy: ultrastructural features. J Neuropathol Exp Neurol. 2008;67:657-68 pubmed publisher
  4. Kahane P, Ryvlin P, Hoffmann D, Minotti L, Benabid A. From hypothalamic hamartoma to cortex: what can be learnt from depth recordings and stimulation?. Epileptic Disord. 2003;5:205-17 pubmed
    ..Whether this proposal of secondary epileptogenesis is valid or not remains a major issue, since it could provide arguments on the moment to discuss surgery. ..
  5. Wu J, Dechon J, Xue F, Li G, Ellsworth K, Gao M, et al. GABA(A) receptor-mediated excitation in dissociated neurons from human hypothalamic hamartomas. Exp Neurol. 2008;213:397-404 pubmed publisher
    ..Taken collectively, we provide novel evidence for and mechanistic insights into HH epileptogenicity: GABA(A)R-mediated excitation. ..
  6. Palmini A, Van Paesschen W, Dupont P, Van Laere K, Van Driel G. Status gelasticus after temporal lobectomy: ictal FDG-PET findings and the question of dual pathology involving hypothalamic hamartomas. Epilepsia. 2005;46:1313-6 pubmed
    ..Ictal FDG-PET independently confirmed that gelastic seizures in patients with HH do originate in the diencephalic lesion. An HH may coexist with another epileptogenic lesion, in a context of dual pathology. ..
  7. Caronia L, Martin C, Welt C, Sykiotis G, Quinton R, Thambundit A, et al. A genetic basis for functional hypothalamic amenorrhea. N Engl J Med. 2011;364:215-25 pubmed publisher
    ..We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea...
  8. Welt C, Chan J, Bullen J, Murphy R, Smith P, Depaoli A, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004;351:987-97 pubmed
  9. Fohlen M, Lellouch A, Delalande O. Hypothalamic hamartoma with refractory epilepsy: surgical procedures and results in 18 patients. Epileptic Disord. 2003;5:267-73 pubmed
    ..To study the surgical procedures and results on seizures, in 18 patients with refractory epilepsy due to hypothalamic hamartoma...

More Information


  1. Fenoglio K, Wu J, Kim D, Simeone T, Coons S, Rekate H, et al. Hypothalamic hamartoma: basic mechanisms of intrinsic epileptogenesis. Semin Pediatr Neurol. 2007;14:51-9 pubmed
    ..These observations constitute the basis for future investigations aimed at elucidating the mechanisms of subcortical epileptogenesis. ..
  2. Leal A, Monteiro J, Secca M, Jordão C. Functional brain mapping of ictal activity in gelastic epilepsy associated with hypothalamic hamartoma: a case report. Epilepsia. 2009;50:1624-31 pubmed publisher
    ..The EEG/fMRI method has the spatial-temporal resolution to study the dynamics of seizure activity, with detailed demonstration of origin and propagation pathways. ..
  3. Coons S, Rekate H, Prenger E, Wang N, Drees C, Ng Y, et al. The histopathology of hypothalamic hamartomas: study of 57 cases. J Neuropathol Exp Neurol. 2007;66:131-41 pubmed
    ..Nodules of these small neurons were a universal feature of the microarchitecture of HH lesions associated with epilepsy. Characterization of these neurons may aid in understanding the mechanism of seizure development in HH. ..
  4. Kerrigan J, Ng Y, Chung S, Rekate H. The hypothalamic hamartoma: a model of subcortical epileptogenesis and encephalopathy. Semin Pediatr Neurol. 2005;12:119-31 pubmed
    ..Refractory epilepsy associated with HH is the premier human model for subcortical epilepsy and an excellent model for secondary epileptogenesis and epileptic encephalopathy. ..
  5. Elfers C, Ralston M, Roth C. Studies of different female rat models of hypothalamic obesity. J Pediatr Endocrinol Metab. 2011;24:131-7 pubmed
  6. Balbo S, Grassiolli S, Ribeiro R, Bonfleur M, Gravena C, Brito M, et al. Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat. Endocrine. 2007;31:142-8 pubmed
    ..Results suggest that increased fat accumulation is caused, at least in part, by high blood insulin concentration, and enhanced parasympathetic activity on MSG-obese rats. ..
  7. Polkey C. Resective surgery for hypothalamic hamartoma. Epileptic Disord. 2003;5:281-6 pubmed
    ..Alternate strategies include stereotactic radiosurgery and radiofrequency ablation under stereotactic control. ..
  8. Khan S, Wright I, Javed S, Sharples P, Jardine P, Carter M, et al. High frequency stimulation of the mamillothalamic tract for the treatment of resistant seizures associated with hypothalamic hamartoma. Epilepsia. 2009;50:1608-11 pubmed publisher
    ..An improvement in mood was reported by the patient's primary carers and demonstrated on quality of life questionnaires. ..
  9. Piccin A, Raimondi R, Laspina S, Marchi M, Rodeghiero F, Rovigatti U. Erythroleukaemia, diabetes insipidus and hypophyseal damage: Two case reports. Leuk Res. 2007;31:1135-9 pubmed
    ..These two cases show specific chromosomal/molecular alterations in EL with DI. The hypothesis of pituitary involvement in erythroleukemogenesis is discussed. ..
  10. Shimatsu A. [Hypothalamic syndrome]. Nihon Rinsho. 2006;Suppl 1:5-7 pubmed
  11. Berardelli R, Gianotti L, Karamouzis I, Picu A, Giordano R, D Angelo V, et al. Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea. Gynecol Endocrinol. 2011;27:753-8 pubmed publisher
    ..05) 24 h after CTX, without any rebound effect. One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration. ..
  12. Wilfong A, Curry D. Hypothalamic hamartomas: optimal approach to clinical evaluation and diagnosis. Epilepsia. 2013;54 Suppl 9:109-14 pubmed publisher
    ..Because use of SLA for HH is being adopted by other medical centers, further data will be acquired to help treat this difficult disorder. ..
  13. Garner J. Froelich, fertility and a French emperor. Commentary on 'Napoleon's sex life' by Maj Gen F M Richardson. J R Army Med Corps. 2003;149:344-7 pubmed
  14. Kuzniecky R, Guthrie B. Stereotactic surgical approach to hypothalamic hamartomas. Epileptic Disord. 2003;5:275-80 pubmed
    ..Epilepsy improved in 60% of patients with minimal morbidity. This approach was less successful in large lesions. These results indicate that this approach should be considered in patients with small/medium lesions. ..
  15. Andrew M, Parr J, Stacey R, Rosenfeld J, Hart Y, Pretorius P, et al. Transcallosal resection of hypothalamic hamartoma for gelastic epilepsy. Childs Nerv Syst. 2008;24:275-9 pubmed
    ..There were no adverse developmental effects of surgery. Transcallosal resection of HHs ameliorates resistant epilepsy syndromes associated with HH. ..
  16. Ng Y, Hastriter E, Wethe J, Chapman K, Prenger E, Prigatano G, et al. Surgical resection of hypothalamic hamartomas for severe behavioral symptoms. Epilepsy Behav. 2011;20:75-8 pubmed publisher
    ..HH resection can result in significant improvement in behavioral functioning, even in patients with relatively infrequent seizures. Further investigation under approved human research protocols is warranted. ..
  17. Baguley I. The excitatory:inhibitory ratio model (EIR model): An integrative explanation of acute autonomic overactivity syndromes. Med Hypotheses. 2008;70:26-35 pubmed
    ..Finally, minor modifications to this model provide a basis to begin to explain less severe, regional "overlap" syndromes. ..
  18. Samarasinghe S, Emanuele M, Mazhari A. Neurology of the pituitary. Handb Clin Neurol. 2014;120:685-701 pubmed publisher
    ..Management of pituitary tumors ranges from observation of nonfunctioning microadenomas through medical, surgical, and radiotherapeutic approaches dependent on tumor type, function, size, and invasiveness. ..
  19. Bunyaratavej K, Locharernkul C, Tepmongkol S, Lerdlum S, Shuangshoti S, Khaoroptham S. Successful resection of Hypothalamic Hamartoma with intractable gelastic seizures--by transcallosal subchoroidal approach. J Med Assoc Thai. 2006;89:1269-76 pubmed
    ..This appears to be the first report of this surgical approach for HH, which is less likely to disturb memory function compared to previously described interfoniceal approach. ..
  20. Freeman J. The anatomy and embryology of the hypothalamus in relation to hypothalamic hamartomas. Epileptic Disord. 2003;5:177-86 pubmed
    ..Potential environmental antecedents to HH development are discussed, and the significance for sporadic, isolated HH of several syndromes associated with HH is explored. ..
  21. Wethe J, Prigatano G, Gray J, Chapple K, Rekate H, Kerrigan J. Cognitive functioning before and after surgical resection for hypothalamic hamartoma and epilepsy. Neurology. 2013;81:1044-50 pubmed publisher
    ..This study provides Class IV evidence that single surgical resection for HH was associated with improvement in some subset measures of intellectual functioning, but not memory. Factors that predict better outcomes cannot be determined. ..
  22. Fukuhara Y, Takeshima T, Ishizaki K, Burioka N, Nakashima K. [Three Japanese cases of hypnic headache]. Rinsho Shinkeigaku. 2006;46:148-53 pubmed
    ..There were some patients with hypnic headache in Japan and neurologists should pay attentions to this form of benign headache, because some beneficial treatments are currently available. ..
  23. Kameyama S, Masuda H, Murakami H. Ictogenesis and symptomatogenesis of gelastic seizures in hypothalamic hamartomas: an ictal SPECT study. Epilepsia. 2010;51:2270-9 pubmed publisher
  24. Kumar Mandal P, Kumar Yadav S, Anand Saraswat V, Kumar Singh J, Upreti P, Singh R, et al. Mammillary body atrophy in acute liver failure and acute-on-chronic liver failure of nonalcoholic etiology. Metab Brain Dis. 2009;24:361-71 pubmed publisher
    ..We conclude that significant volume loss occurs in MBs in patients with ALF and ACLF of non-alcoholic etiology but not in CLF. This loss of MBs volume recovers substantially in patients with ALF who survive their illness. ..
  25. Perello M, Moreno G, Camihort G, Luna G, Cónsole G, Gaillard R, et al. Nature of changes in adrenocortical function in chronic hyperleptinemic female rats. Endocrine. 2004;24:167-75 pubmed
    ..Our study supports that adrenal leptin resistance could be responsible, at least in part, for enhanced glucocorticoid circulating levels in this phenotype of obesity. ..
  26. Sum M, Warren M. Hypothalamic amenorrhea in young women with underlying polycystic ovary syndrome. Fertil Steril. 2009;92:2106-8 pubmed publisher
  27. Kazlauskaite R, Evans A, Villabona C, Abdu T, Ambrosi B, Atkinson A, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab. 2008;93:4245-53 pubmed publisher
    ..94 and 0.85, respectively; P<0.001). Low-dose corticotropin test was superior to standard-dose test for diagnosing chronic HPAI, although it has technical limitations. ..
  28. Gil Antón J, Lopez Bayon J, López Fernández Y, Pilar Orive J. [Autonomic dysfunction syndrome secondary to tuberculous meningitis]. An Pediatr (Barc). 2004;61:449-50 pubmed
  29. Papayannis C, Consalvo D, Seifer G, Kauffman M, Silva W, Kochen S. Clinical spectrum and difficulties in management of hypothalamic hamartoma in a developing country. Acta Neurol Scand. 2008;118:313-9 pubmed publisher
    ..In five, an additional procedure was performed without any significant improvement. These series show the heterogeneous spectrum of this entity and the difficulties in its treatment in a developing country. ..
  30. Meccariello R, Chianese R, Cacciola G, Cobellis G, Pierantoni R, Fasano S. Type-1 cannabinoid receptor expression in the frog, Rana esculenta, tissues: a possible involvement in the regulation of testicular activity. Mol Reprod Dev. 2006;73:551-8 pubmed
    ..In conclusion, CB1 receptor is expressed in R. esculenta CNS and testis. As far as the gonad it concerns, our results suggest the involvement of the endocannabinoids in the control of reproductive function...
  31. Reynaud R, Leger J, Polak M, Tauber M, Sulmont V, Limal J, et al. [Idiopathic hypothalamic syndrome: retrospective study and literature review]. Arch Pediatr. 2005;12:533-42 pubmed
    ..This largest study ever reported of idiopathic hypothalamic syndrome emphasizes the need of a multidisciplinary coordination to provide the best care of these patients. ..
  32. Mitan L. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17:81-5 pubmed
    ..The neuroendocrine changes associated with menstrual abnormalities in underweight and weight recovered anorexia nervosa, recent research on osteopenia, and treatment recommendations are addressed. ..
  33. Vincent D, Alden T, Kamiryo T, Lopez B, Ellegala D, Laurent J, et al. The baromodulatory effect of gamma knife irradiation of the hypothalamus in the obese Zucker rat. Stereotact Funct Neurosurg. 2005;83:6-11 pubmed
    ..We hypothesize that this involves a resetting of the hypothalamic set point for body weight through an as yet uncharacterized neuromodulatory effect. ..
  34. Tzotzas T, Papazisis K, Perros P, Krassas G. Use of somatostatin analogues in obesity. Drugs. 2008;68:1963-73 pubmed
  35. Scholly J, Valenti M, Staack A, Strobl K, Bast T, Kehrli P, et al. Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis. Epilepsia. 2013;54 Suppl 9:123-8 pubmed publisher
    ..In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans. ..
  36. Maghnie M, Uga E, Temporini F, Di Iorgi N, Secco A, Tinelli C, et al. Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests. Eur J Endocrinol. 2005;152:735-41 pubmed
    ..Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re-assessment of adrenal function. ..
  37. Stabell K, Bakke S, Egge A. Cognitive and neurological sequelae after stereoendoscopic disconnection of a hypothalamic hamartoma. A case study. Epilepsy Behav. 2012;24:274-8 pubmed publisher
    ..The child also contracted a permanent oculomotor paresis. Our results are discussed in light of previous relevant findings. ..
  38. Genazzani A, Lanzoni C, Ricchieri F, Santagni S, Rattighieri E, Chierchia E, et al. Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea. J Endocrinol Invest. 2011;34:287-91 pubmed publisher
    ..01, respectively). No changes were observed in the normo-LH patients. Our data support the hypothesis of a specific role of ALC on counteracting the stress-induced abnormalities in hypo-LH patients affected by hypothalamic amenorrhea. ..
  39. Kerrigan J, Kruer M, Corneveaux J, Panganiban C, Itty A, Reiman D, et al. Chromosomal abnormality at 6p25.1-25.3 identifies a susceptibility locus for hypothalamic hamartoma associated with epilepsy. Epilepsy Res. 2007;75:70-3 pubmed
    ..8 Mb to 9.7 Mb. There are 38 RefSeq genes within the duplicated regions, and no known coding sequences within the deletion. This unique patient helps identify 6p25.1-25.3 as a possible susceptibility locus for sporadic HH. ..
  40. Martins A, Souza K, Shio M, Mathias P, Lelkes P, Garcia R. Adrenal medullary function and expression of catecholamine-synthesizing enzymes in mice with hypothalamic obesity. Life Sci. 2004;74:3211-22 pubmed
    ..We conclude that in MSG obesity the low total catecholamine content is directly related to a decrease of key catecholamine-synthesizing enzymes, which by its turn may lead to a defective catecholamine secretion. ..
  41. Mukherjee A, Ryder W, Jostel A, Shalet S. Prolactin deficiency is independently associated with reduced insulin-like growth factor I status in severely growth hormone-deficient adults. J Clin Endocrinol Metab. 2006;91:2520-5 pubmed
  42. Vescovi J, Jamal S, De Souza M. Strategies to reverse bone loss in women with functional hypothalamic amenorrhea: a systematic review of the literature. Osteoporos Int. 2008;19:465-78 pubmed publisher
  43. Vieira T, Chinen R, Ribeiro M, Nogueira R, Abucham J. Central precocious puberty associated with pituitary duplication and midline defects. J Pediatr Endocrinol Metab. 2007;20:1141-4 pubmed
    ..Sellar and cervical column MRIs revealed pituitary duplication and rudimentary intervertebral disks. We present the clinical and imaging observations of this case, and a thorough literature review of this rare developmental abnormality. ..
  44. Patterson B, Truxillo L, Wasilewski Masker K, Mertens A, Meacham L. Adrenal function testing in pediatric cancer survivors. Pediatr Blood Cancer. 2009;53:1302-7 pubmed publisher
    ..We recommend use of LDCT, not 8 a.m. serum cortisol to screen patients who received >30 Gy of radiotherapy and those with other central endocrinopathies. ..
  45. Singh G, Wei X, Hader W, Chan J, Bouffet E, Lafay Cousin L. Sustained response to weekly vinblastine in 2 children with pilomyxoid astrocytoma associated with diencephalic syndrome. J Pediatr Hematol Oncol. 2013;35:e53-6 pubmed publisher
    ..Despite the recognized more agressive clinical behavior of this histologic subtype, we report successful resolution of DS and sustained tumor response with prolonged use of single-agent vinblastine. ..
  46. Gordon C. Clinical practice. Functional hypothalamic amenorrhea. N Engl J Med. 2010;363:365-71 pubmed publisher
  47. Pleasure S, Guerrini R. Hypothalamic hamartomas and hedgehogs: not a laughing matter. Neurology. 2008;70:588-9 pubmed publisher
  48. Regis J, Scavarda D, Tamura M, Villeneuve N, Bartolomei F, Brue T, et al. Gamma knife surgery for epilepsy related to hypothalamic hamartomas. Semin Pediatr Neurol. 2007;14:73-9 pubmed
    ..The disadvantage of radiosurgery is its delayed action. Longer follow-up is mandatory for a reliable evaluation of the role of GKS. ..
  49. Moreno G, Perello M, Camihort G, Luna G, Console G, Gaillard R, et al. Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats. Int J Obes (Lond). 2006;30:73-82 pubmed
    ..Importantly, appropriate correction of the enhanced adrenocortical activity fully reversed these abnormal functions. ..
  50. Balercia G, Boscaro M, Lombardo F, Carosa E, Lenzi A, Jannini E. Sexual symptoms in endocrine diseases: psychosomatic perspectives. Psychother Psychosom. 2007;76:134-40 pubmed
    ..The endocrinologist, as an expert in body chemistry, is ideally positioned to identify and evaluate the full range of medical, physical, and psychiatric problems disrupting sexual function. ..
  51. Meczekalski B, Podfigurna Stopa A, Warenik Szymankiewicz A, Genazzani A. Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations. Gynecol Endocrinol. 2008;24:4-11 pubmed publisher
    ..Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA. ..
  52. de Pontual L, Trochet D, Caillat Zucman S, Abou Shenab O, Bougneres P, Crow Y, et al. Delineation of late onset hypoventilation associated with hypothalamic dysfunction syndrome. Pediatr Res. 2008;64:689-94 pubmed publisher
    ..We ruled out PHOX2B, ASCL1, and NECDIN as disease-causing genes by direct sequencing in our series of patients and discuss possible disease-causing mechanisms...
  53. Honda Y. [Clinical study on diencephalic mental disorders]. Seishin Shinkeigaku Zasshi. 2006;108:431-5 pubmed