AUTOSOMAL RECESSIVE DEFICIENCY OF COMBINED PITUITARY-HORMONES (EXCEPTACTH) IN A CONSANGUINEOUS BRAZILIAN KINDRED

Familiar hypopituitarism represents a clinically and genetically heter ogeneous disorder. In a subset of these families, defects in Pit-1, a transcription factor essential for proper pituitary development have b een identified as underlying molecular cause. These patients present e xtreme short stature, GH, PRL and TSH deficiency but intact ACTH, LH a nd FSH secretion. The pituitary is usually hypoplastic. In this report we describe a consanguineous family (the parents are first cousins) w ith thirteen siblings. Of the ten living siblings, four (two males and two females) have panhypopituitarism with severe growth failure. They had evidence of growth hormone, prolactin and gonadotropin deficienci es and developed central hypothyroidism late in life. ACTH secretion w as normal. Bone age was retarded and dual-photon bone densitometry ind icated severe osteoporosis. Combined provocative tests for pituitary h ormones indicated blunted responses for GH, LH, FSH and a modest rise in serum PRL and TSH. A clonidine-test failed to induce pituitary GH r esponse. A corticotropin-releasing factor (CRF) provocative test was c onducted after 6 months without the use of prednisone with a normal AC TH response after CRF in the affected sibling. Plasma IGF-I and IGF-BP 3 were below normal levels. Serum E2 (females) and serum testosterone (males) levels were very low. MRI evaluation of the pituitary indicate d pituitary aplasia in all subjects. The phenotype described in this k indred is different from families reported with Pit-1 mutations. Howev er, it resembles previously published kindreds with similar clinical a nd biochemical findings. The relative preservation of ACTH suggests a genetic defect early in pituitary gland development. (J. Endocrinol. I nvest. 21: 386-391, 1998) (C)1998, Editrice Kurtis.