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Last updated: 9/06/2023
Years published: 1986, 1989, 1993, 2004, 2019, 2023
NORD gratefully acknowledges Cara Molulon and Simon Padanilam, NORD Editorial Interns from the University of Notre Dame, and Inรฉs Castro-Dufourny, MD, PhD, Department of Endocrinology, Sureste University Hospital, Madrid Spain, for assistance in the preparation of this report.
Froehlich syndrome, also known as adiposogenital dystrophy, is a group of endocrine abnormalities believed to result from damage to the hypothalamus, a part of the brain that links the nervous system to the endocrine system via the pituitary gland. The hypothalamus regulates sleep cycles and body temperature and composition while stimulating the pituitary gland to release a variety of hormones that control growth, metabolism and body development. Thus, numerous pituitary gland hormones could be indirectly disrupted by damage to the hypothalamus. Unlike similar diseases such as Prader-Willi syndrome, Froehlich syndrome is acquired, not inherited, and is associated with tumors of the hypothalamus area or their surgical treatment, causing increased appetite and reduced secretion of gonadotropin. This syndrome affects males more often than females.
The more obvious and frequently encountered characteristics include delayed onset of puberty, short stature, small testes and obesity. Teenage boys with this disorder must be distinguished from those who have inherited growth delay disorders or Prader-Willi syndrome.
Froehlich syndrome is characterized by increased or excessive eating that leads to obesity, small testes and a delay in the onset of puberty. It is also common for children with Froehlich syndrome to experience the delay in physical growth and the development of secondary sexual characteristics. In addition to delayed growth and puberty, children with this syndrome tend to be short in stature. As a result of tumor growth, some children with Froehlich syndrome may also develop intellectual difficulties, poor vision due optic nerve damage, lower than normal body temperature (hypothermia), very delicate skin and infundibulo-tuberal syndrome. The infundibulo-tuberal syndrome may result in small testes, obesity, diabetes insipidus and drowsiness (somnolence).
Froehlich syndrome results from an injury to a part of the hypothalamus (arcuatus nucleus and ventromedial nueclei). The hypothalamus then fails to produce substances that stimulate the front portion (anterior) of the pituitary that is necessary for the onset of normal puberty and regulation of appetite.
The most frequent causes of Froehlich syndrome are a specific tumor of the pituitary-hypothalamus area, craniopharyngioma, an expanding hollow (cystic) lesion or injury of this area during surgery.
Lesions resulting from inflammation from an infection such as tuberculosis or an acute inflammation of the brain (encephalitis) can also be responsible for causing Froehlich syndrome.
Froehlich syndrome is a very rare condition that affects more males than females.
After a physician conducts a physical examination to identify characteristic signs of Froelich syndrome, laboratory analysis typically reveals low levels of pituitary hormones. This may suggest the presence of a lesion on either the pituitary gland or hypothalamus. Blood tests including TSH tests, FSH tests, LH tests, GH tests, prolactin level and ADH level tests are used to determine the level of hypothalamus and pituitary function.
If infection is suspected, blood cultures may be taken. In the event of a suspected lesion or abnormal growth, imaging studies of the brain are conducted. These may include CT scan of head region or MRI scan of the brain. Additional tests are needed to rule out Prader-Willi syndrome before a definite diagnosis of Froehlich syndrome can be made.
Treatment
If possible, tumors of the hypothalamus should be surgically removed.
Pituitary extracts may be given through hormone replacement therapy (HRT) to replace the missing hormones in patients with Froehlich syndrome. For males, this usually includes human chorionic gonadotropin to reach puberty followed up by testosterone. For females, HRT with estrogen is given during teenage years followed by complex estrogen-progestin therapy. Though appetite may be very difficult to manage, weight control depends on successful management. Some modern treatments can help to control obesity (GLP1 analogues).
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Reichlin S. Neuroendocrinology. In: Wilson JD, Foster DW. Eds. Textbook of Endocrinology. 8th ed. W.B. Saunders Company. Philadelphia, PA; 1992:192-93.
Styne Dm. Disorders of Puberty: Delayed Puberty. In: Sperling MA. Ed. Pediatric Endocrinology. 1st ed. W.B. Saunders Company. Philadelphia, PA; 1996:454-460.
JOURNAL ARTICLES
Castro-Dufourny I Obesidad hipotalรกmica tras intervenciรณn quirรบrgica de un craneofaringioma: tratamiento con un anรกlogo de glp-1. Endocrinol Diabetes Nutr. 2017 Mar; 64(3): 182-184. doi: 10.1016/j.endinu.2016.10.006. Epub 2017 Feb 27.
Castro-Dufourny I, Carrasco R, Prieto R, Pascual JM. Infundibulo-tuberal syndrome: the origins of neuroendocrinology in France. Pituitary 2015; 18: 838-843.
Castro-Dufourny I, Carrasco R, Prieto R, Barrios L, Pascual JM. The infundรญbulo-tuberal syndrome caused by craniopharyngiomas. Clinicopathological evidence from an historical French cohort (1705-1973). Pituitary 2015; 18: 642-657.
Ogura T, Tobe K, Mimura Y et al. Testosterone modulates serum leptin concentrations in a male patient with hypothalamic hypogonadism. J Endocrinol Invest. 2000;23:246-50.
Citron JT, Ettinger B, Rubinoff H, et al. Prevalence of hypothalamus-pituitary imaging abnormalities in impotent men with secondary hypogonadism. J Urol. 1996;155:529-33.
Schopohl J, Mojto J, Losa M, et al. Changes in anterior pituitary response in patients with idiopathic hypothalamic hypogonadism caused by pulsatile GnRH therapy and testosterone replacement. Exp Clin Endocrinol Diabetes. 1995;103:84-90.
Metyolkina L, Peresedov V. Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly. Stereotact Funct Neurosurg. 1995;65:184-86.
Frรถhlich A. Ein fall von tumor der hypophysis cerebri ohne akromegalie. Wien Klin Rundschau. 1901;15:883-886, 906-908.
Babinski J. Tumeur du corps pituitaire sans acromรฉgalie et avec arrรชt de dรฉveloppement des organes gรฉnitaux. Rev Neurol. 1900;8: 531-533.
INTERNET
Froelich syndrome. Genetic and Rare Diseases Information Center (GARD). Last updated: Feb 2023. https://rarediseases.info.nih.gov/diseases/6463/froelich-syndrome Accessed July 25, 2023.
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