Endocrine manifestations of the rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neural tumor syndrome in childhood

J Clin Endocrinol Metab. 2008 Oct;93(10):3971-80. doi: 10.1210/jc.2008-0238. Epub 2008 Jul 15.

Abstract

Context: Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neural tumor (ROHHADNET) is a newly described syndrome that can cause cardiorespiratory arrests and death. It mimics several endocrine disorders or genetic obesity syndromes during early childhood and is associated with various forms of hypothalamic-pituitary endocrine dysfunctions that have not yet been fully investigated.

Objective: The current report aspires to facilitate the earlier recognition and appropriate treatment of the ROHHADNET syndrome when children present with various endocrine manifestations, such as early obesity, growth failure, pseudo-Cushing's syndrome, glucocorticoid insufficiency, congenital hypopituitarism, or adrenal tumors. A more widespread knowledge of the syndrome will help characterize its molecular origin.

Design: Endocrine studies were performed in six patients admitted for seemingly common early-onset obesity associated with growth failure in five of them. The six patients later showed distinctive features of the ROHHADNET syndrome.

Results: Abnormalities of the pituitary adrenal axis ranged from a true Cushing-like profile (one of six), to glucocorticoid deficiency with normal ACTH (two of six). Complete GH deficiency with low IGF-I was observed in four of six, hypogonadotropic hypogonadism in four of six, hyperprolactinemia in six of six, and various degrees of TSH/T(4) abnormalities in five of five patients. All had increased natremia without diabetes insipidus. Five children had unilateral macroscopic adrenal ganglioneuroma. Two patients died at 8.5 and 12 yr of age.

Conclusions: Various hypothalamic-pituitary endocrine dysfunctions are associated with ROHHADNET, carrying a risk of misdiagnosis until other elements of the syndrome make it more easily recognizable. Given its severity, ROHHADNET syndrome should be considered in all cases of isolated, rapid, and early obesity.

Publication types

  • Case Reports

MeSH terms

  • Age of Onset
  • Autonomic Nervous System / physiopathology
  • Autonomic Nervous System Diseases / complications*
  • Autonomic Nervous System Diseases / physiopathology
  • Child
  • Child, Preschool
  • Endocrine System / physiopathology*
  • Female
  • Humans
  • Hypothalamic Diseases / complications*
  • Hypothalamic Diseases / epidemiology
  • Hypothalamic Diseases / physiopathology
  • Hypothalamus / physiopathology
  • Hypoventilation / complications*
  • Infant
  • Male
  • Nervous System Neoplasms / complications*
  • Nervous System Neoplasms / epidemiology
  • Nervous System Neoplasms / physiopathology
  • Obesity / complications*
  • Obesity / epidemiology
  • Obesity / physiopathology
  • Pituitary-Adrenal System / physiopathology