Endocrine Abstracts

Introduction: Pseudohypoparathyroidism (PHP) is a group of heterogeneous disorders causing parathyroid hormone (PTH) resistance. The features could include Albright’s hereditary osteodystrophy phenotype (AHO) [brachydactyly, short stature, obesity, round face, ectopic ossifications, intellectual disability]. The condition is rare with an estimated prevalence of 0.34-1.1 in 100,000 and the clinical presentation can be variable. Herein, we present 8 patients with PHP from two centres (Alder Hey Children’s Hospital, UK and Endocrine Research Centre, Russia) with a wide variation in the clinical presentation.

Patients and methods: PTH resistance was established by the presence of high PTH with low/normal plasma calcium, high/normal plasma phosphate, and normal vitamin D. GNAS genetic testing was undertaken in 7/8 cases and positive in 5 patients.

Results: 5 girls and 3 boys with PHP were included. Five patients had PTH resistance and AHO (type 1a), two had only biochemical abnormalities (type 1b), and one had AHO and borderline laboratory results. Median age at presentationwas4 years (range 6 months - 14 years). Patients were referred with a range of symptoms: seizures, excessive weight gain and subcutaneous ossifications. Most patients (6/8) had hypocalcaemia and hyperphosphatemia. Interestingly, one of these children had temporary normalisation of calcium, phosphate and PTH levels. Two patients always had normal calcium and phosphate levels. TSH resistance was found in 7/8 cases. The features of AHO phenotype identified include brachydactyly (6/8), learning difficulty (6/8), round face (5/8), ectopic ossifications (3/8), overweight (3/8), and short stature (1/8). We also noted some uncommon features in our group, such as tall stature and advanced bone age. One child presented with medulloblastoma. 6/8 patients were treated with Alfacalcidol (0.6 - 8 mg/day).

Conclusion: Patients with PHP have heterogenous clinical and biochemical picture. Among phenotypical changes, brachydactyly, learning difficulties, and round face are most common ones in our group. Laboratory results can reveal normal calcium and phosphate levels in some patients. Due to overlapping symptoms, new classification of inactivating PTH/PTHrP signaling disorders might be beneficial.