Refractory hypercalcaemia due to ectopic PTH secretion
Jaimini Cegla1, Meera Nandhabalan2, Conrad Lewanski2 and Karim Meeran1
1 Dept of Metabolic Medicine, 2 Dept of Oncology, Charing Cross Hospital, London, UK
We report a rare case of ectopic PTH secretion in a non-smoking 29 year old female with metastatic squamous cell carcinoma of the lung. This lady was treated with radical intent having presented with haemoptysis after diving. Biopsy and staging investigations revealed a T3 N1 M0 squamous cell carcinoma of the right lung. She maintained a good clinical and radiological response to cytoreductive chemotherapy and consolidation radiotherapy.
Six months later, she was admitted with abdominal pain. Her serum calcium on admission, however, was 3.52 mmol/l (2.15-2.60). Concomitant liver and bone profile was as follows: alanine transaminase 15 IU (0-31), alkaline phosphatase 373 IU (30-130), bilirubin 10 umol/l (0-17) and phosphate 0.58 mmol/l (0.80-1.40). CT was unremarkable and bone scan showed no bony metastases. Intravenous fluids were started immediately along with 90mg of pamidronate. Her calcium further rose to 4.37 mmol/l the following day. This continued to rise to over 6 mmol/l as depicted, despite fluid and electrolyte replacement, multiple administrations of pamidronate, frusemide and dexamethasone.
A concomitant PTH level was found to be 281.4 (1.1-6.8 pmol/l). This was measured by a two-site immunoassay and was therefore deemed to be true PTH rather than PTH-related peptide. The differential diagnosis for this autonomous PTH secretion was parathyroid carcinoma or ectopic PTH secretion from the squamous cell lung carcinoma. Despite aggressive therapy, the patient passed away before further radiological investigation could be performed. Post-mortem revealed extensive tumour and no parathyroid carcinoma was identified. The lung carcinoma did not stain for parathyroid hormone and this was attributed to its rapid degradation and secretion into the circulation.
Ectopic PTH secreting tumours are rare. Squamous cell lung carcinomas commonly secrete PTH-related peptide, however, only a few cases of squamous cell lung carcinomas secreting PTH are reported. The rapid and aggressive rise of serum calcium in this patient is unusual. This case also illustrates the severe refractoriness to high-dose bisphosphonate infusion of patients with a raised PTH, even in an oncology setting.