Control of hypercalcaemia of parathyroid carcinoma by immunisation

Background Patients with parathyroid tumours can develop extreme hypercalca emia and osteitis fibrosa cystica. Clinical features result from the action of parathyroid hormone (PTH) on bone receptors. Because this hormone is pr oduced in microgram quantities, inhibition of its metabolic effects with po tent PTH antibodies should be possible. We tested whether an immunisation w ith synthetic human and bovine PTH peptides could stimulate autoantibodies against PTH. Methods A patient with metastatic parathyroid carcinoma in the lungs and pl eura developed severe bone disease and extreme; hypercalcaemia that proved resistant to conventional therapy. She was immunised with 200 mu g human an d bovine PTH peptides and 50 mu g human PTH. Booster doses were also given at 4 weeks and 11 weeks. The patient was then seen every week. Findings Antibodies against PTH were produced within 4 weeks of initial imm unisation and titres increased with repeated doses of immunogens. Total ser um calcium concentrations, which had ranged from 3.5 mmol/L to 4.2 mmol/L o ver the previous 18 months, fell to between 2.5 mmol/L and 3.0 mmol/L over 6 months of therapy. This fall was accompanied by striking clinical improve ment. Interpretation We believe this is the first use of immunotherapy to control remote, non-metastatic complications of malignant disease. B-cell toleranc e to human PTH was broken by immunisation with PTH peptides in adjuvant. Th is therapeutic approach could be used to control excess hormone production in several types of endocrine tumour and may have applications in other dis eases.