summary Pseudohypoparathyroidism is a rare genetic metabolic bone disease caused by a defect in the GNAS1 protein that leads to a decreased response to PTH. Patients present with characteristic findings of short 4th and 5th metacarpals, round facies, short stature, and symptoms of hypocalcemia. Diagnosis is made based on physical examination findings, serum labs, and results of the Ellsworth-Howard test. Treatment is medical management with oral calcium and 1alpha-hydroxylated vitamin D metabolites. Etiology Mechanism PTH resistance decreased target cell response to PTH Classification Type 1a - Albright hereditary osteodystrophy defect in GNAS1 (Gsα protein) defective gene from mother upstream defect login to view 1 more bullet skeletal defects short 4th, and 5th metacarpals and metatarsals or short 4th metacarpal only login to view 7 more bullets brachydactyly exostoses round facies obesity short stature diminished intelligence Type 1b defect in GNAS1 (Gsα protein) normal appearance Type 2 unknown gene defect downstream defect distal to formation of cAMP normal appearance Presentation Symptom symptoms of hypocalcemia paresthesia login to view 1 more bullet abdominal pain, biliary colic muscle cramps, tetany dyspnea (laryngospasm, bronchospasm) convulsions mental status changes login to view 1 more bullet Physical exam findings of tetany Trousseau's Sign login to view 4 more bullets Chvostek's Sign login to view 1 more bullet dermatologic fungal nail infections hair loss blotchy skin login to view 1 more bullet Evaluation Laboratory high PTH low calcium high phosphate low vit D Ellsworth-Howard test method to differentiate type 1 and type 2 by administering exogenous PTH Type 1 login to view 1 more bullet Type 2 login to view 1 more bullet Differential Causes of hypocalcemia renal osteodystrophy (low Ca, high PTH, high phosphate, high ALP) hypoparathyrodism (low Ca, low PTH, high phosphate) pseudopseuodohypoparathyroidism mechanism login to view 2 more bullets genetics login to view 2 more bullets skeletal defects login to view 2 more bullets laboratory login to view 4 more bullets decreased vitamin D3 Labs Type Appearance PTH Calcium Phos Vitamin D Response to PTH administration Genetics Hypoparathyroidism Normal ↓ ↓ ↑ ↓ Pseudohypoparathyroidism Type 1a Skeletal defects ↑ ↓ ↑ ↓ No increase in urinary cAMP or phosphate GNAS1 (maternal defect, upstream) Pseudohypoparathyroidism Type 1b Normal ↑ ↓ ↑ ↓ GNAS1 and STX16 Pseudohypoparathyroidism Type 2 Normal ↑ ↓ ↑ ↓ Increased urinary cAMP and phosphate GNAS1 (downstream) Pseudopseudohypoparathyroidism Skeletal defects N N N N GNAS1 (paternal defect) Treatment Nonoperative oral calcium and 1alpha-hydroxylated vitamin D metabolites indications login to view 1 more bullet IV calcium replacement indications login to view 1 more bullet