Endocrine Abstracts

Summary: 59-year-old female diagnosed at the age of 41 in 2004 with pseudohypoparathyroidism (PHP) initially presenting with raised PTH 152 pmol/l (1.6-6.9), Phosphate 1.91 mmol/l (0.87-1.45), adjusted calcium 1.90 mmol/l (2.20-2.60), raised ALP 600 units/l (0-129) and low vitamin D 29 nmol/l. Since diagnosis started on alfacalcidol 1 mg daily and Calcichew-D3. Investigations by hepatology team in the view of persistently raised ALP showed normal liver ultrasound, Fibroscan and non-invasive liver screen, In June 2019 presented to the hospital with fall. A Trauma CT head & neck showed multiple skull lytic lesions with possibility of myeloma raised on the CT report, was referred to haematology team. Myeloma screen came back negative, low dose skeletal CT showed multiple lytic expansile lesions throughout the axial skeleton, which also confirmed on FDG PET CT. Bone biopsy histopathology reported as Brown tumour of secondary hyperparathyroidism. As PTH remined massively elevated over the last two years between 194 to 272 pmol/l, she started on Cinacalcet 30 mg twice/day in addition to alfacalcidol 1.75 mg and Calcichew four tablets daily. One week after Cinacalcet, biochemical improvement noted with PTH level improved from 193.3 to 172 pmol/l, ALP from 868 to 772 units/l. She currently undergoing a slow titration in Cinacalcet with regular blood checks in clinic.

Discussion: The unique features of this case:1. The massive elevation of PTH due PTH resistance (PHP 1b).2. The formation of extensive brown tumours due to chronic activation of osteoclastic activity by the elevated PTH in spite of the PTH resistance.Brown tumour, also known as osteitis fibrosa cystica and rarely as osteoclastoma, is one of the manifestations of hyperparathyroidism. It represents a reparative cellular process, rather than a neoplastic process. Increased PTH levels stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. Brown tumours have been described in small series of patients with pseudohypoparathyroidism. Despite PTH resistance in this condition, there is activation of osteoclastic activity. Cinacalcet is proposed to exert calcimimetic action through allosteric modulation of the calcium-sensing receptor (CaR) on the parathyroid cell surface. The primary role of the CaR is control of PTH secretion in response to extracellular calcium concentration. Cinacalcet acts to reduce circulating PTH concentration through activation of the CaR by increasing its sensitivity to extracellular calcium. We present early evidence that this treatment may act to suppress PTH secretion in PHP 1b.