# Humoral Hypercalcemia of Malignancy Caused by Parathyroid Hormone-Related Protein-Secreting Medullary Thyroid Carcinoma: A Case Report

## TL;DR

A rare case of medullary thyroid carcinoma caused severe hypercalcemia through the production of parathyroid hormone-related protein, highlighting the importance of PTHrP testing in similar cases.

## Contribution

This paper presents a rare case of hypercalcemia in medullary thyroid carcinoma caused by PTHrP secretion.

## Key findings

- The patient had severe hypercalcemia due to PTHrP production by medullary thyroid carcinoma.
- Postoperative PTHrP levels normalized, and the patient showed no recurrence at 8 months.
- PTHrP measurement is recommended for diagnosing hypercalcemia in thyroid cancer patients.

## Abstract

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor arising from the parafollicular C cells, accounting for approximately 1.5% of all thyroid cancers. Although calcitonin secreted by the MTC typically lowers calcium levels, serum calcium concentrations usually remain within the normal range due to compensatory parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy is broadly categorized as humoral hypercalcemia of malignancy (HHM), mediated by parathyroid hormone-related protein (PTHrP), or local osteolytic hypercalcemia. We report a rare case of HHM caused by a PTHrP-secreting MTC.

A 60-year-old woman visited our hospital with weight loss, fatigue, and a large right-sided neck mass. Laboratory tests revealed marked hypercalcemia (16.5 mg/dL), hypophosphatemia, and renal dysfunction. The intact PTH level was within the normal range, whereas the PTHrP level was elevated to 5.7 pmol/L, consistent with HHM. Tumor marker analysis revealed marked increases in carcinoembryonic antigen and calcitonin levels. Imaging studies revealed a large mass in the right thyroid lobe without evidence of regional or distant metastasis. Fine-needle aspiration confirmed the diagnosis of MTC. Genetic testing was negative for rearranged during transfection mutations and multiple endocrine neoplasia 2A, supporting a sporadic form. Hypercalcemia was managed with intravenous hydration (saline solution, 2 L/day for 10 days), elcatonin (80 units/day for 9 days), and a single dose of zoledronic acid. The patient underwent a right thyroid lobectomy. Histopathological analysis confirmed MTC without extra-thyroidal extension or lymph node metastasis (Union for International Cancer Control pT3aN0M0 stageII). Postoperatively, the serum PTHrP levels decreased to normal, and the patient recovered without complications. At the 8-month follow-up, no evidence of recurrence was observed.

Herein, we present a rare case of MTC that caused hypercalcemia via PTHrP production. Although HHM is uncommon in thyroid cancer, the condition can cause severe hypercalcemia requiring prompt diagnosis and treatment. HHM should be considered in patients with thyroid cancer with hypercalcemia, and PTHrP measurement may aid in the diagnosis.