Management of an aggressive parathyroid tumour co-existing with vitamin D deficiency

Thein Htay1, Agnieszka Falinska1, Alison Wren 1,3, James Smellie2, Christopher Nutting 3 Daniel Morganstein1,3

1.  Endocrinology Department, Chelsea and Westminster Hospital Foundation Trust

2.  Endocrine  Surgery, Chelsea and Westminster Hospital Foundation Trust

3.  Head and Neck Unit, Royal Marsden Hospital NHS Trust



A seventy-six year old Caucasian lady was admitted with sudden onset severe lower abdominal pain. She had previous history of constipation but no history of renal stone. She had a history of osteoarthritis, essential hypertension and previous cholecystectomy. Physical examination was unremarkable. Initial biochemistry showed normal U&E, elevated adjusted calcium (2.87 mmol/L) and PTH (16.4 ng/L), low vitamin D (11.7 nmol/L). She had normal immunoglobulin with no abnormal paraprotein.  A CT scan of her chest, abdomen and pelvis was normal. The diagnosis of primary hyperparathyroidism with co-existing vitamin D deficiency was made. High urinary calcium: creatinine clearance ratio excluded FHH.

During her follow-up, she was asymptomatic from hypercalcaemia and repeated calcium was stable at 2.72 mmol/L. Ergocalciferol 20,000 units weekly without addition of calcium was commenced for eight weeks. The DEXA scan also confirmed that she had osteopenia, suggesting demineralisation related to primary hyperparathyroidism and Vitamin D depletion.

After eight weeks of vitamin D replacement, she developed further lower abdominal pain, intermittent urinary frequency, visual hallucination and confusion. Her calcium and PTH had risen to 3.1 mmol/L and 21.1ng/L respectively. Because of these distressing ongoing symptoms, emergency parathyroidectomy was planned.

During admission, visual hallucination persisted and her calcium went up to 3.48mmol/L. Sestamibi parathyroid scan and ultrasound did not localise a parathyroid adenoma. Intravenous saline infusion, intravenous low dose biphosphonate and cinacalcet lowered her calcium below 3mmol/L.  Subsequently, she underwent emergency open neck parathyroidectomy and her symptoms, especially visual hallucinations, remarkably resolved.  Her parathyroid histology was reported as showing atypical features on the background of a parathyroid adenoma, with some suspicion of vascular invasion and tumour at the resection margins. Although there were no absolute features of malignancy, after MDT discussion it was decided to manage as a parathyroid carcinoma due to the risk of local recurrence. She, therefore, went on to receive post operative radiotherapy to the neck.  Testing for HRPT2 gene mutations was negative. She remains in remission clinically and biochemically.

This case illustrates several challenges. Firstly, the dramatic rise in calcium following vitamin D replacement is unusual, being reported to occur in less than 5% of patients. Secondly, visual hallucinations are an unusual symptom of hypercalcaemia. Thirdly, the atypical histology and possible features of malignancy raised significant concerns about the risk of recurrence, leading the adjunctive radiotherapy.