ESPE Abstracts

Pseudohypoparathyroidism (PHP) is a disorder caused by PTH resistance due to a genetic defect in imprinted GNAS cluster. It is characterized by high phosphorus, low to normal calcium and elevated PTH. It is classified into types 1a, 1b, 1c, pseudopseudohypoparathyroidism and type 2. Type 1a is often associated with Albright Hereditary Osteodystrophy (AHO) which is characterized by short stature, round facies, obesity, brachydactyly, ectopic calcifications and developmental delay. A 1-year-old boy presented to our clinic with obesity. Weight was 18 kg (+4.7 SD), length was 80 cm (1.2 SD). TSH was found to be 13.8 uIU/ml (normal: 0.7-6.4) and T4 was 5.9 mg /dl (normal 7.3-15). He was diagnosed as primary hypothyroidism and started Levothyroxine and diet plann. At 4 years old, subcutaneous calcifications were noticed on the dorsum of left foot, left side of neck and skull. Height was 107.0 cm (+1.0 SD), US/LS: 1.4, weight 30 kg (+3.9 SD) and BMI 33.2 (+5.6 SD). Patient had a notably round face and neurodevelopmental delay with IQ 80%. Lab studies revealed highly elevated PTH 307 pg/ml (normal: 15-65). Ca 8.9 mg/dl (N: 8.6-10.3), iCa 5.04mg/dl (N. 4.4 -5.4), Ph 5.5 mg/dl (n 4-7.0), ALP 138 U/l (n up to 644) and 25(OH)vit D 20ng/ml. Vitamin D and calcium supplementation were added till 25(OH) was normalized. However, PTH remained persistently elevated on repeated testing reaching 473 pg/dl despite of normalization of vit D. Plain Xray and soft tissue Ultrasound confirmed the presence of subcutaneous calcification in multiple locations. MRI brain and sella tursica revealed a diffusely thickened calvarium, multiple cutaneous & subcutaneous calcific spots. Our clinical diagnosis of pseudohypoparathyoidism was supported by the abundance of characteristic features as early onset obesity, hypothyroidism (TSH receptor resistance), stocky build, round face, neurodevelopmental delay, tissue calcifications and elevated PTH. However, the absence of hypocalcemia, hyperphosphatemia, normal urinary ca/creatinine ratio with high PTH and unusual normal height (+1 SD) were pointing us towards normocalcemic primary hyperparathyroidism. Confirmation was done via Whole Exome Sequencing. A heterozygous pathogenic variant was identified in GNAS associated with autosomal dominant Pseudohypoparathyroidism Ia (OMIM: 103580) Insufficient phenotypic features and lack of classical biochemical abnormalities should not exclude pseudohypoparathyroidism especially with metastatic calcification. Genetic testing should be considered to prevent false diagnosis.