Severe hypercalcaemia associated with Graves' disease
SN Ali, K Wynne and K Meeran
Imperial Centre for Endocrinology
We present a case of a 25 year old lady, who presented with a six-month history of symptoms suggestive of thyrotoxicosis; weight loss, anxiety, palpitations, heat intolerance and lethargy. Of note, she had also had symptoms of thirst, polyuria and nocturia. On examination, she had a tremor, was tachycardic and had a moderately enlarged smooth goitre with an associated thyroid bruit.
Blood tests performed in clinic confirmed thyrotoxicosis: a suppressed TSH<0.05mU/L (NR 0.3-4.2mU/L), free T3 >46.1pmol/L (NR 2.5-5.7pmol/L) and free T4 69.1pmol/L (NR 9.0-26.0pmol/L). TSH receptor antibody was positive at >30.0u/mL (NR 0-0.4u/mL). Of note, corrected calcium was significantly raised at 3.35mmol/L (NR 2.15-2.60mmol/L), phosphate was 1.50mmol/L (NR 0.8-1.4mmol/L) and parathyroid hormone was non-suppressed but low-normal: 2.1pmol/L (NR 1.1-6.8pmol/L). Alkaline phosphate remained normal throughout. Other causes of hypercalcaemia were excluded.
She was admitted and the severe hypercalcaemia was treated with aggressive intravenous fluids. She was concurrently started on carbimazole 20mg tds and propranolol 40mg tds. She was discharged home when the corrected calcium fell to 2.79mmol/L and was followed up closely in the outpatient setting.
Remarkably, biochemical results were significantly better two weeks after aggressive treatment of the Gravesí disease, including resolution of the hypercalcaemia (TSH<0.05mU/L, fT4 16.0pmol/L, fT3 4.2pmol/L, corrected Ca 2.14mmol/L, phosphate 0.87mmol/L, PTH 2.5pmol/L). It was therefore felt that this severe hypercalcaemia was due to thyrotoxicosis as opposed to primary hyperparathyroidism. Interestingly, this lady was seen in clinic two months later and due to five weeks of noncompliance with Carbimazole, she was once again thyrotoxic and hypercalcaemic.
Thyrotoxicosis is commonly associated with abnormalities in bone metabolism, however the resultant hypercalcaemia is usually mild and asymptomatic. If hypercalcaemia is severe and symptomatic, there is often an alternative cause. In support of severe hypercalcaemia due to thyrotoxicosis is the reversal of hypercalcaemia with treatment of the hyperthyroidism. This case is interesting as thyrotoxicosis with such marked hypercalcaemia is uncommon and is one of the highest recorded corrected calcium levels found in the literature.