SUN-502 From Pseudohypoparathyroidism to Signaling Disorder

Abstract

Historically, pseudohypoparathyroidism (PHP) has been referred to a group of diseases characterized by resistance to parathyroid hormone. Patients with PHP typically exhibit hypocalcemia, hyperphosphatemia, and increased serum parathyroid hormone (PTH) due to GNAS gene mutation or methylation, which prompt signaling abnormality in PTH and parathyroid hormone-related peptide (PTHrP) receptors. Here, we describe a 40-year-old African-American male referred to our endocrinology clinic for hypocalcemia who had a round face and several subcutaneous nodules on his scalp, hands, and legs. Results of laboratory data revealed hypocalcemia, hyperphosphatemia, and elevated levels of intact PTH and TSH. X-ray of the hands showed brachydactyly of all metacarpal bones and soft tissue calcifications; and a CT scan of the brain demonstrated soft tissue calcifications in the scalp and dense calcifications in the subcortical region, bilateral basal ganglia, bilateral thalami, bilateral cerebellum, and vermis. The current guideline for diagnosis and classification of PTH resistance disorder relies on the presence of phenotypic features of Albright's hereditary osteodystrophy, hormone resistance, and urinary cAMP level in response to exogenous PTH along with genetic testing. However, there is significant overlap exists between the categories of that classification. Additionally, the cost and availability of those tests complicates definitive diagnosis and classification. In response, and to better reflect the disorder underlying pathophysiology, the EuroPHP network recommends using inactivating PTH/PTHrP signaling disorder (iPPSD) instead of PHP and has published a new approach for its diagnosis and classification consisting of simple physical features and biochemical tests and eliminates the need for measuring urinary cAMP. We applied the new diagnostic approach to the patient and he was diagnosed with iPPSD. The new diagnostic approach and cluster classification for PTH resistance disorder appears to be more incisive, and flexible compared with the traditional approach. Furthermore, it can be used as a quick and inexpensive screening tool for suspected patients and it is adaptable for additional genetic mutations related to this disorder.