ESPE Abstracts

A PROP1 homozygous mutation was found in an 8 years old boy who was referred for fatigue, general slowness, dry skin, normal weight and slow growth. His T4 and TSH were low, while tests of pituitary reserve were normal as well as the concentrations of ACTH and cortisol. FSH/LH/T/E were in the pre-pubertal range. TRH test resulted in no increased TSH and T4, confirming the pituitary origin of the defect. MRI of the pituitary hypothalamic region revealed an enlargement of the anterior pituitary gland, a mass lesion of 10 mm. The pituitary stalk was normal and neurohypophyses was normally located. Substitution with sodium L-thyroxine resulted in increased growth velocity. Control MRI of the pituitary hypothalamic region after 6 years revealed a pituitary mass of 2mm. At the age of 14 years, the boy had testicle size of 2ml and no signs of puberty. At the age of 15 years, GnRH test resulted in unresponsive FSH/LH and testosterone. Substitution with chorionic gonadotropins resulted in increased growth velocity, testicle size and pubarche. At the age of 16 years the ACTH serum concentrations were 25.8 pg/ml (0.0-46.0), while cortisol serum concentrations were 3.09 mg /dL (6.7-22.6). Corticotropin realizing hormone test is pending. At the age of 16 years GH was low at two tests of pituitary reserve (<0.5 ng/ml). IGF-1 was low, IGFBP-3 had normal values for age and gender. His height is 164 cm (mother 158, father 172), his bone maturity is 13 years and he started GH treatment. Clinical exome sequencing revealed that the proband is a PROP1 compound heterozygote with c.358C>T (P.Arg120ys) inherited from the mother, and the c.301_302del (P.(Leu102CysfsTer8) inherited from the father. The sequential pituitary hormone deficiency unusually begun with TSH deficiency, continued with gonadotropin deficiency, followed by GHD and finished with central hypoadrenocorticism.

Key words: combined pituitary deficiency, PROP1, pituitary mass.