Endocrine Abstracts

Subcutaneous ossifications (SCO) represent a recognized manifestation of pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP), posing significant morbidity to affected individuals. This report details the case of a 37-year-old woman with PHP1A with extensive scalp calcifications, an unusual and unexpected finding. The patient presented with multiple firm skin nodules on the right knee and dorsum of both hands. Having been diagnosed with hypothyroidism and hypocalcemia five years prior, she was receiving levothyroxine (50 μg/day), alfacalcidol (1 μg/day), and calcium carbonate (1 g/day). Despite a stature of 148 cm and displaying typical Albright hereditary osteodystrophy (AHO) features, she maintained regular menstrual cycles. Genetic analysis identified a c.85C>T mutation in the GNAS, confirming the suspicion of PHP1A. To assess extraskeletal calcifications (ESO), a brain CT scan was conducted, revealing basal ganglial calcifications and unexpectedly extensive scalp SCO. Notably, the patient remained asymptomatic with regard to these calcifications. A skin biopsy from a knee nodule confirmed osteoma cutis. Subsequently, the patient’s identical twin daughter, born three years later, exhibited hypocalcemia and seizures, leading to the identification of PHP1A. Genetic testing revealed a shared GNAS mutation in both the patient and her daughters. This case aligns with previous observations suggesting that patients with frameshift and nonsense mutations in GNAS tend to manifest more severe SCO compared to those with missense mutations. The identification of SCO in conjunction with AHO phenotypes underscores the importance of GNAS mutation analysis, not only for diagnostic purposes but also for facilitating genetic counseling. This emphasizes the need for a comprehensive approach in managing patients with SCO and AHO phenotypes, ensuring a more accurate diagnosis and informed genetic guidance.