A sporadic case of pseudohypoparathyroidism type 1 and idiopathic primary adrenal insufficiency associated with a novel mutation in the GNAS1 gene

Abstract

OBJECTIVE: We report an atypical association of primary adrenal insufficiency and pseudohypoparathyroidism (PHP) and a novel GNAS1 gene mutation in a Caucasian female who initially presented with adrenal crisis. METHODS: A case report and literature review. RESULTS: A 37-year-old female presented with shock at 11 years of age, and investigations revealed primary adrenal insufficiency and pseudohypoparathyroidism (PHP). She had typical features of Albright hereditary osteodystrophy (AHO) and evidence of thyroid-stimulating hormone (TSH), growth-hormone-releasing hormone (GHRH), and gonadotrophin resistance fitting with the diagnosis of PHP type 1a/1c. She did not have a family history of any autoimmune disease or PHP. Her mother was phenotypically normal. Genomic DNA sequencing of those GNAS exons and adjacent intronic regions that encode the stimulatory guanine nucleotide-binding protein Gsalpha revealed a novel heterozygous mutation in exon 11, c.857-858delCT. CONCLUSION: The association of primary adrenal insufficiency and PHP has not been reported in literature and may prove an area for further research. The novel mutation in this case adds to the spectrum of mutations associated with these disorders.