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 severe growth failure during the 1st year of life, a small facial skull and 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 parents. 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 "hot spot" for mutations. The inheritance is autosomal-dominant, as the mutated gene product interferes with DNA-binding of the wild-type protein. In contrast, other mutations in the PIT-1 gene are inherited in an autosomal-recessive mode.

Diagnosing Pit-1 gene mutations as a rare cause of combined pituitary deficiency is important both for genetic counselling as well as for predicting the future course in the patient (spontaneous puberty, no glucocorticoid substitution necessary during stress periods).