NORD gratefully acknowledges Cara Molulon and Simon Padanilam, NORD Editorial Interns from the University of Notre Dame, and Inés 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 constellation 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 depressed 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-, somnolence, and diabetes insipidus – known as Infundibulo-tuberal syndrome (Froehlich+somnolence+diabetes insipidus), lower than normal body temperature (hypothermia) and very delicate skin.
Froehlich syndrome (hypogonadism with obesity) results from an injury of a part of the hypothalamus (arcuatus nucleus and ventromedial nueclei. The hypothalamic gland is the endocrine gland that produces substances that stimulate the pituitary and regulate appetite. In Froehlich syndrome, the front portion (anterior) of the pituitary gland fails to secrete the hormones that are necessary for the onset of normal puberty.
The most frequent cause of Froehlich syndrome is a specific tumor of the pituitary-hypothalamus area, an expanding hollow (cystic) lesion (craniopharyngioma) or its surgical treatment (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 legion or abnormal growth, imaging studies of the brain are conducted. These may include x-ray of the skull, CT scan of head and neck region, or MRI scan of the brain. Additional tests such as methylation analysis are needed to rule out Prader-Willi syndrome before a definite diagnosis of Froehlich syndrome can be made.
Pituitary extracts may be administered through hormone replacement therapy (HRT) to replace the missing hormones in patients with Froehlich syndrome. For males, this usually includes administration of human chorionic gonadotropin to reach puberty followed up by testosterone. For females, HRT typically is the administration of estrogen during teenage years followed by complex estrogen-progestin therapy with age. If possible, tumors of the hypothalamus should be surgically removed if. Though appetite may be very difficult to manage, weight control depends on successful management. Some modern treatments can help to control obesity.
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:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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.
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 infundíbulo-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.
Fröhlich 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 acromégalie et avec arrêt de développement des organes génitaux. Rev Neurol. 1900;8: 531-533.
Froelich syndrome. Genetic and Rare Diseases Information Center (GARD). Last updated: 9/15/2010. https://rarediseases.info.nih.gov/diseases/6463/froelich-syndrome Accessed November 29, 2018.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100