ESPE Abstracts

Background: Pseudohypoparathyroidism (PHP) refers to a group of rare diseases characterized by post-receptor resistance to parathyroid hormone and other protein hormones (TSH, GHRH, LH, FSH), due to defects in the Gsα protein. PHP can be associated with the phenotype known as Albright’s hereditary osteodystrophy (AHO), which includes round face, short stature, brachydactyly, ectopic ossifications and mental retardation. Diagnosis often stem out from hypocalcemia related symptoms (seizures or tetany), which are typically emerging later in childhood, contributing to delayed diagnosis; hypothyroidism may be evident earlier, through newborn screening, and can be the first sign of PHP.

Clinical case: A 13-year-old girl was initially diagnosed with congenital hypothyroidism by newborn screening (TSH at two weeks of life 26.5 microU/mL, ft4 3.13 ng/mL). She was started on replacement therapy with levothyroxine, with regular follow-up. On ultrasound the thyroid gland was in its normal position, with dimensions at the lower limits compared to the norm. The thyroid scintigraphy revealed diffuse uptake reduction in both thyroid lobes. Family history was unremarkable for significant pathologies. The girl had been overweight since her early years; the body mass index slightly improved with a dietary program but worsened during the peripubertal period. Pubertal development progressed normally, as well as her stature (at the 10th percentile for age and gender), although it remained at the lower end of the genetic target. At age of 12 a medical-sports examination revealed QTc prolongation, and a learning disorder was diagnosed. The clinical examination at the age of 13 revealed a round face and a short IV metacarpal. Blood tests showed asymptomatic hypocalcemia (ionic calcium 2.7 mg/dL), hyperphosphatemia (7.3 mg/dL) and increased parathyroid hormone (377 pg/mL). Suspicion of PHP1A was raised and genetic testing to verify is currently ongoing. She is undergoing treatment with activated form of vitamin D combined with oral calcium supplementation, blood levels of calcium and phosphorus are progressively returning to normal.

Conclusion: This case underscores the challenge in early diagnosis of PHP before the signs and symptoms of hypocalcemia appear. It is crucial to assess calcium-phosphorus metabolism in patients with mild TSH elevation, a thyroid gland in place and any sign of AHO. Some features of the AHO phenotype are quite subtle in early childhood and become more defined in later years (such as brachydactyly), while others may be present early but require careful physical examination and suspicion to detect (obesity and ectopic ossifications).