Endocrine Abstracts

JOINT2388

Introduction: Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of rare disorders characterized by resistance to parathyroid hormone (PTH). PHP type 1A is associated with Albright’s osteodystrophy and resistance to multiple hormones (including TSH). In contrast, PHP type 1B develops PTH resistance over time, exhibiting mild clinical manifestations and low-level resistance to other hormones. The estimated prevalence of PHP is approximately 1 in 100,000 individuals. Thyroid agenesis, although rare, has been described in association with phospho-calcium metabolism disorders. However, its exact prevalence in patients with PHP remains unclear.

Case Report: A 21-year-old female has been followed since the age of 5 for hypothyroidism with positive antibody levels (antithyroid peroxidase > 2000mUI/mL and antithyroglobulin > 266mUI/mL), currently treated with levothyroxine (175 micrograms daily). Notably, neck ultrasound revealed thyroid agenesis of the right lobe. Her family history included hypothyroidism spanning three generations, but no other endocrinological disorders. At the time of hypothyroidism diagnosis, she also presented with markedly elevated PTH levels (296pg/mL), low serum calcium levels, phosphate in the upper limit of normal range and mildly increased urinary calcium excretion. She exhibited no clinical features or symptoms related to bone metabolism. After excluding more common causes for phospho-calcium abnormalities, genetic testing for PHP was performed. Methylation pattern analysis revealed changes across all differentially methylated regions (DMRs), a gain of methylation in NESP55 and loss of methylation in GNAS-AS1, GNASXL, and GNASAB, consistent with the diagnosis of PHP 1B. Subsequently, she has been treated with oral calcium, calcitriol and cholecalciferol, leading to normalization of both serum and urinary calcium and phosphate levels.

Discussion: Although PHP 1A is known to present with TSH resistance, PHP 1B is generally associated with minimal TSH resistance, which does not typically account for thyroid agenesis. Additionally, only a few cases of PHP 1B associated with Hashimoto’s thyroiditis have been reported in the literature. Given the high prevalence of Hashimoto’s thyroiditis, it has been assumed that its coexistence with PHP 1B is incidental.

Conclusions: This case highlights an unusual presentation of PHP 1B with concurrent thyroid agenesis and Hashimoto’s thyroiditis. While the link between PHP and thyroid agenesis remains unclear, this case suggests the need for further investigation into potential shared pathomechanisms. Genetic testing remains crucial for diagnosis and management in atypical cases.