PROP1Mutations Cause Progressive Deterioration of Anterior Pituitary Function including Adrenal Insufficiency: A Longitudinal Analysis

Antje Böttner, Eberhard Keller, Jürgen Kratzsch, Heike Stobbe, Johannes F. W. Weigel, Alexandra Keller, Wolfgang Hirsch, Wieland Kiess, Werner F. Blum, Roland W. Pfäffle
2004 Journal of Clinical Endocrinology and Metabolism  
Mutations in the PROP1 gene are the most frequent genetic defects in patients with combined pituitary hormone insufficiency. However, controversy exists about the timing and extent of pituitary insufficiency, and it remains unclear whether adrenal failure is a typical feature of this condition. We performed a retrospective longitudinal analysis of nine patients with PROP1 mutations who were under medical supervision at our clinic for 15.7 ؎ 3.4 yr. All patients initially presented with growth
more » ... ented with growth failure (height SD score, -3.7 ؎ 0.3) at a mean age of 4.9 ؎ 0.8 yr. They were first diagnosed with GH and TSH deficiency, and replacement therapy was instituted at 6.1 ؎ 1.1 and 6.8 ؎ 1.2 yr, respectively. All seven patients who reached pubertal age required sex hormone substitution at 15.0 ؎ 0.7 yr. Repeated functional testing of the anterior pituitary axes revealed a progressive decline with age in peak levels of GH, TSH, prolactin, and LH/FSH. All patients developed at least partial adrenal insufficiency, with a gradual decline of the function of the pituitary adrenal axis and eventually required substitution with hydrocortisone at a mean age of 18.4 ؎ 3.5 yr. It is concluded that anterior pituitary function in patients with PROP1 mutations deteriorates progressively and includes adrenal insufficiency as a feature of this condition, which has important clinical relevance in childhood and adolescence. (J Clin Endocrinol Metab 89: 5256 -5265, 2004)
doi:10.1210/jc.2004-0661 pmid:15472232 fatcat:kbc7lm2dbncr3b23rdp57fccvq