COMBINED PITUITARY DEFICIENCIES OF GROWTH-HORMONE, THYROID-STIMULATING HORMONE AND PROLACTIN DUE TO PIT-1 GENE MUTATION - A CASE-REPORT

A child exhibited postnatal obstipation and icterus together with seve re growth failure during the Ist year of life, a small facial skull an d a prominent forehead. Endocrine work-up established the diagnosis of combined pituitary deficiencies of growth hormone, TSH and prolactin. Subsequently, the Pit-1 gene was analysed in the patient and both par ents. A single point mutation was detected in exon 6 of the child: a C to G transversion on one allele, causing arginine in position 271 to be substituted by tryptophan (R271 W). This position is known as a ''h ot spot'' for mutations. The inheritance is autosomal-dominant, as the mutated gene product interferes with DNA-binding of the wild-type pro tein. In contrast, other mutations in the PIT-1 gene are inherited in an autosomal-recessive mode. Conclusion Diagnosing Pit-1 gene mutation s as a rare cause of combined pituitary deficiency is important both f or genetic counselling as well as for predicting the future course in the patient (spontaneous puberty, no glucocorticoid substitution neces sary during stress periods).