Endocrine Abstracts

Primary hyperparathyroidism is a common endocrine condition; 80% due to a parathyroid adenoma. We present an unusual case of a 69-year old white European female, who presented first in 2012 with mild hypercalcaemia (< 2.8 mmol/l), osteoporosis, hypertension and type 2 diabetes. Pharmacotherapy included Bendroflumethiazide, but no phosphate supplements. Investigations revealed primary hyperparathyroidism and dual-modality scanning showed no evidence of an adenoma, although hyperplasia was suggested on ultrasound. Molecular analysis showed no CASR mutation, making familial hypocalciuric hypercalcaemia unlikely. She was discharged to follow-up in primary care with advice to refer if the plasma adjusted calcium was above 2.9 mmol/l consistently, which was the practice prior to UK NICE 2019 guidance. There had been no other change to her health; she had normal vitamin D level without supplementation and no renal disease. She presented 8 years later with severe hypercalcaemia (peak plasma adjusted calcium 3.5 mmol/l), but with few symptoms. Plasma PTH was 30 pmol/l and the concern was of malignant transformation. Treatment included IV 0.9% sodium chloride, sc calcitonin, IV pamidronate and then PO cinacalcet; the thiazide was stopped. The hypercalcaemia was fairly resistant to cinacalcet, which she found difficult to tolerate. Dual modality imaging showed similar findings for the Sestamibi scan to the previous scan: no tracer retention to suggest an adenoma. The ultrasound scan showed evidence of thyroiditis on the right and possible right inferior parathyroid adenoma. She underwent four-gland exploration which was complicated by a severe nodular thyroiditis but demonstrated significant enlargement of the left superior (2 g) and right inferior (1 g) parathyroids (both excised) and a normal left inferior parathyroid. Histological features were more consistent with hyperplasia than adenoma and with features seen in tertiary hyperparathyroidism. The patient’s biochemistry normalised postoperatively. This case illustrates an unusual progression of primary hyperparathyroidism hyperplasia progressing to more autonomous parathyroid hormone production. The histopathology would be seen usually in tertiary hyperparathyroidism associated with severe nephropathy, but this patient had normal renal function. This progress can also be seen in secondary hyperparathyroidism due to chronic hypovitaminosis D, but our patient was vitamin D replete. Thiazide-associated hypercalcaemia tends to be seen in older females and persists after drug withdrawal. We may speculate whether the lack of response to cinacalcet points to thiazide-associated renal PTH resistance, leading to increased PTH and promotion of hyperplasia; but the association of thiazides with hyperparathyroidism is inconsistent, some studies showing no effect on PTH levels.