Endocrine Abstracts

Introduction: Pseudohypoparathyroidism (PHP) type 1a is a genetic disorder associated primarily with resistance to parathyroid hormone (PTH). Its pathogenesis has been linked to dysfunctional G-protein-mediated signaling. Since the G unit is an ubiquitary protein, its mutation can lead to variable hormonal dysfunction. In this context we report the case of a patient followed in our department for multihormone resistance.

Case report: A 9 years old boy, born at term to healthy consanguineous parents, presented to our department for delayed growth. Medical history revealed congenital hypothyroidism and PHP diagnosed respectively at 3 and 5 years of age. He was under supplemental calcium, active vitamin D and thyroid hormone replacement. Physical examination revealed a short stature with a height of 90 cm (– 3 s.d), signs of Albright hereditary osteodystrophy (AHO) and a scoliosis. Hormonal investigations revealed a partial growth hormone (GH) deficiency (GH peak at 6.58 ng/mL after propranolol-glucagon test), a hypocalcemia (1.64 mmol/l) contrasting with high PTH levels (68 pg/ml). The pituitary magnetic resonance imaging (MRI) was normal. Regarding the AHO features and the multiple hormonal resistances, PHP type 1a was suspected. In line with this hypothesis, the GH deficiency would be due to GHRH resistance. Genetic assessment of the GNAS1 gene, encoding the α-subunit of the G protein (Gαs) confirmed the presence of a missense mutation in exon 1 (c.154G>A, p.Glu52Ly). Treatment with recombinant GH was initiated and resulted in 7 cm gain within 7 months. At the most recent visit at the age of 10, both calcemia and TSH were within normal ranges.

Conclusion: We report a patient with PHP type 1a displaying PTH, TSH and GHRH resistance. Our case highlights the importance of GH status evaluation in all patients with known mutation in Gαs gene and supports the hypothesis that this mutation is the basis for multiple hormone resistance in pseudohypoparathyroidism. Further studies will be necessary to determine the possible beneficial effects of GH replacement in these patients.