Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene

Genomic DNA from 18 patients with combined pituitary hormone deficiency was screened for 2-bp deletion (A301,G302) in PROP1 gene by BcgI restriction e ndonuclease analysis of PCR-amplified exon 2 gene fragments. Two unrelated female patients were homozygous for this 2-bp deletion. Patient 1 presented at 8.8 yr with severe short stature (-2.9 so score), slightly enlarged sel la turcica at x-rays, and diffusely enlarged pituitary gland (height, 8 mm vs. 4.5 +/- 0.6 mm in matched controls) with hyperintense enhanced signal a t T1 weighted image at coronal and sagittal views at magnetic resonance ima ging (MRI). MRI repeated at age 15 yr revealed a marked reduction of pituit ary height (2 mm us. 5.3 +/- 0.8 mm in matched controls). Patient 2 present ed at 27 yr with short stature (-5.5 SD score) without pubertal development , normal sella turcica, and a pituitary gland of reduced size (height, 5 mm us. 6.1 +/- 0.3 mm in matched controls) of normal intensity at MRI. Both p atients had normal pituitary stalk and normally located neurohypophysis. Ho rmonal features were characterized by GH, TSH, PRL, LH, and FSH deficiencie s. Patient 1 had normal cortisol secretion at 8.8 yr, and at 16.6 yr had de veloped partial cortisol deficiency, whereas patient 2 maintained normal co rtisol secretion at 28.4 yr We conclude that 1) a large sella turcica and a n enlarged pituitary anterior lobe with hyperintense enhanced signal at T1 at MRI can be suggestive of PROP1 deficiency; 2) pituitary morphology can c hange during follow-up of patients with PROP 1 gene mutation; and 3) hormon al deficiencies could include the adrenal axis.