Hypercalcitoninaemia has been described in patients with pseudohypoparathyroidism (PHP) type 1A and 1B. Elevated calcitonin levels are thought to result from impaired Gsα receptorial signaling, leading to multiple hormone resistance. Evidence on the risk of me-dullary thyroid carcinoma (MTC) or C-cell hyperplasia in PHP patients with hypercalcitoninaemia is lacking.

We describe a case that will provide further insights on this topic.

Case presentation: A caucasian 43-year-old man referred to our Endocrinology Clinic for chronic hypocalcemia associated with elevated serum parathormone levels, and a single cystic thyroid nodule. The patient did not show skeletal deformities and screening for concomitant hormone resistances was negative, except for the presence of elevated serum calcitonin levels. The workup led to a molecular diagnosis of sporadic PHP1B. Fine needle aspiration of the thyroid nodule was not diagnostic. Calcium stimulation test yielded an abnormal calcitonin response. Given the scarcity of data on the risk of thyroid malignancy in PHP and calcium stimulation test results, total thyroidectomy was performed. Histological examination revealed a cystic papillary thyroid cancer in a background of diffuse C-cell hyperplasia.

To our knowledge, we are the first to describe a rare form of thyroid cancer combined with C-cell hyperplasia in a patient with PHP and hypercalcitoninaemia. In this intriguing case, a mere receptorial resistance might not fully explain the elevated calcitonin levels, suggesting that hypercalcitioni-naemia should be carefully evaluated in PHP patients, especially in case of concomitant thyroid nodules. Further studies on larger cohorts are needed to elucidate this topic.