Characterisation of parathyroid hormone concentration in extremely preterm or very low birthweight infants in routine clinical screening for metabolic bone disease: A service evaluation cohort study.

AIM: To characterise parathyroid hormone (PTH) concentrations in infants at high risk for metabolic bone disease, in order to assist clinical decisions around the use of PTH for screening. METHODS: Infants born under 28 weeks' postmenstrual age or with birthweight under 1.5 kg in a tertiary neonatal unit in the UK were included. Clinical guidance was to assess PTH concentration in the first 3 weeks after birth. Clinical information was extracted from prospective records. RESULTS: Sixty-four infants had mean birth gestation of 26 weeks and birthweight of 882 g. Median PTH (sent on median day 18 of life) was 9.2 pmol/L (interquartile range 5.3-17 pmol/L). Sixty-seven per cent of infants had a PTH greater than 7 pmol/L. For 22% of the infants, raised PTH was not accompanied by abnormal phosphate or alkaline phosphatase. Eighty-nine per cent of infants tested were insufficient or deficient for 25-hydroxyvitamin D. CONCLUSIONS: Universal screening highlights the high frequency of high PTH in this high-risk population, implying a need for calcium supplementation. A considerable number of infants would not be identified as showing potential signs of metabolic bone disease if the assessment excludes the use of PTH. The high level of 25-hydroxyvitamin D deficiency may be a confounder.

Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab.

OBJECTIVE: Hypercalcaemia is an important cause of increased morbidity and mortality in patients with parathyroid carcinoma. Surgical resection is the mainstay of treatment but, equally, managing hypercalcaemia is of paramount importance. At present, few therapies have been shown to be effective in the most severe cases. This report describes the efficacy of denosumab in a patient with parathyroid carcinoma when conventional therapies had been shown to be relatively ineffective.SUBJECT, METHODS AND RESULTS: A 50-year-old man presented with symptomatic hypercalcaemia 1 year after the surgery for his parathyroid carcinoma. Investigations revealed raised serum calcium and parathyroid hormone concentrations consistent with the recurrence of the disease. Imaging failed to localise any surgically remediable foci. Medical management with loop diuretics, calcimimetics and bisphosphonates failed to provide a sustained response. Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium concentrations with the values now persistently below 3 mmol/l. CONCLUSIONS: Denosumab, a fully human MAB that binds to the 'receptor activator of nuclear factor κB ligand (RANKL)', was shown to have a profound effect in modulating malignant hypercalcaemia. This medication should be considered as an effective option in patients with refractory hypercalcaemia secondary to parathyroid carcinoma.