Endocrine Abstracts

Background: The mechanisms regulating adrenarche have not been elucidated, although evidence supports a critical role for ACTH and possibly other unidentified pituitary or adrenal contributing factors. Absent adrenarche has been described in children with a variety of sellar tumors. We describe a case series of five adults with congenital hypopituitarism and absent adrenarche.

Cases: Three females and two males with “idiopathic” congenital hypopituitarism, median age 24 years, of which one male and one female were siblings. All patients had GH, gonadotropin and thyrotropin deficiencies and were diagnosed with hypopituitarism in childhood (median age 7). The two male patients opted to restart GH replacement several years after having been treated as children. None had a history of adrenal crisis. All but one female patient were treated with hydrocortisone. The patient not receiving hydrocortisone had subclinical ACTH deficiency, with normal morning ACTH and cortisol levels, but subnormal cortisol peak at 13.9 mcg/dl during an insulin tolerance test. One male patient had developed full body hair following consistent testosterone replacement since puberty, while the other male started developing axillary and pubic hair following re-institution of, and adherence to testosterone replacement. Associated abnormalities noted: the patients had skin dryness of various degrees and puffy hands and feet. One male was diagnosed with lichen planopilaris by skin biopsy taken from the scalp and had significant lymphedema at the lower extremities, one female has isolated dextrocardia, psoriasis and vitiligo. The two affected siblings have sinus bradycardia with a resting rate of 45 bpm; their unaffected brother also has sinus bradycardia. All patients had frankly low age and sex-adjusted serum levels of dehydroepiandrosterone sulphate (DHEAS).

Conclusions: This likely heterogenous group of adults with congenital hypopituitarism failed to demonstrate adrenarche. Androgen-dependent hair appeared only after testosterone replacement in the males. Genetic and metabolomic profiling is needed to enhance understanding of the interplay between pituitary hormonal stimuli, the intra-adrenal environment and even the specific follicle characteristics underlying the process of adrenarche.