Longitudinal imaging reveals pituitary enlargement preceding hypoplasia intwo brothers with combined pituitary hormone deficiency attributable to PROP1 mutation

Mutations of the PROP-1 gene cause combined pituitary hormone deficiency. P rogressive ACTH/cortisol insufficiency is found in a few patients. Congenit al hypoplasia of the anterior pituitary gland is the most common magnetic r esonance imaging finding in patients with PROP-1 mutations. We present two brothers with compound heterozygosity for the two mutations 150delA and 301 -302delAG of the PROP-1 gene. Both showed combined pituitary hormone defici ency of GH, TSH, PRL, and gonadotropins, as is typical for PROP-1 deficienc y. We observed a developing insufficiency of ACTH and cortisol secretory ca pacity in both patients. Computed tomography revealed an enlarged pituitary in the older brother at 3.5 yr of age. Repeated magnetic resonance imaging after 12 yr showed a constant hypoplasia of the anterior pituitary lobe. S imilarly, magnetic resonance imaging of the younger brother showed a consta nt enlargement of the anterior pituitary gland until 10 yr. At the age of 1 1 yr, the anterior pituitary was hypoplastic. The reason for pituitary enla rgement in early childhood with subsequent decrease in pituitary size is no t known. We speculate that altered expression of early transcription factor s could be involved. Because both patients have the same PROP-1 mutations a nd an identical pattern of combined pituitary hormone deficiency, we sugges t that early pituitary enlargement may be the typical course in such patien ts in whom pituitary surgery is not indicated.