Snapshot A 25-year-old obese woman presents to the urgent care center for twitching of her face for the past day. She reports that she has never had such prolonged symptoms before. On physical exam, there is contraction of her facial muscles with percussion to her cheeks bilaterally. Laboratory results show high parathyroid hormone levels, hypocalcemia, and hyperphosphatemia. Introduction Clinical definition pseudohypoparathyroidism (PHP) is a condition characterized by symptoms of hypoparathyroidism despite normal or elevated parathyroid hormone (PTH) levels due to end-organ resistance to PTH hypocalcemia hyperphosphatemia tetany seen in patients with Albright hereditary osteodystrophy Genetics autosomal dominant GNAS1 gene encodes α-subunit of Gs protein mutation the kidney to be resistant to PTH inherited via genetic imprinting from the mother Associated conditions pseudopseudohypoparathyroidism patients have physical exam features of Albright hereditary osteodystrophy but no symptoms of hypocalcemia patients have normal PTH levels and no end-organ PTH resistance when defective protein is inherited from the father not via genetic imprinting from the mother ETIOLOGY Pathogenesis actions of PTH ↑ bone resorption of calcium and phosphate ↑ kidney reabsorption of calcium ↓ kidney reabsorption of phosphate ↑ kidney calcitriol production causes ↑ serum calcium and ↓ serum phosphate resistance to PTH causes ↓ serum calcium ↑ serum phosphate Presentation Symptoms symptoms of hypocalcemia tetany Chvostek sign contraction of facial muscles with percussion of the facial nerve Contraction of Cheek = Chvostek Trousseau sign carpal spasm with occlusion of brachial artery with a blood pressure Tricep spasm = Trousseau sign Albright hereditary osteodystrophy shortened 4th and 5th digits short stature obesity developmental delay soft tissue calcification imaging Hand radiograph shortening of the bones, most severe in the 4th and 5th metacarpals calcifications and ossifications Studies Diagnostic testing studies serum studies ↓ calcium ↑ phosphate ↑ PTH administration of synthetic PTH no change in serum studies genetic testing GNAS1 gene mutation Differential Rickets distinguishing factors radiograph showing widened growth plates of the knee or wrist normal or ↓ calcium and ↓ phosphate Pseudopseudohypoparathyroidism distinguishing factors same physical exam features as seen in Albright hereditary osteodystrophy normal PTH, calcium, and phosphate levels DIAGNOSIS Diagnostic criteria confirmed with genetic testing Treatment Management approach targeted at normalizing calcium levels to suppress PTH levels First-line intravenous calcium indication severe symptomatic hypocalcemia oral calcium indication all patients calcitriol indication all patients Complications Chronically elevated PTH can cause increased bone remodeling