Abstract
A 56-year-old Afro-Caribbean lady was found to have incidental hypercalcaemia on routine GP investigations. Tiredness was the only elicitable hypercalcaemic symptom and aside from early menopause at age 40, she had no significant past medical or family history. Examination was unremarkable. Blood results showed a raised adjusted calcium 2.68mmol/L (2.2–2.6), normal phosphate 1.06mmol/L (0.80–1.50), raised parathyroid hormone (PTH) 14.1pmol/L (1.6–7.2) and low 25-hydroxyvitamin D 28.1nmol/L (70–150).
She had osteopaenia of the femora and left radius on DEXA scan but no nephrocalcinosis on renal ultrasound. On initial investigation, her urinary calcium output was low at 1.55mmol/day resulting in a 24h calcium:creatinine ratio (UCCR) of 0.0065. Although suggestive of Familial Hypocalciuric Hypercalcaemia (FHH), her notable Vitamin D deficiency was considered to contribute to the observed hypocalciuria. After Vitamin D repletion, a repeat UCCR improved to 0.012, however, remained in the indeterminate range. No known pathogenic variant was identified on genetic analysis for FHH.
Her PTH and Calcium levels remained persistently high within 9.7–17.1pmol/L and 2.65-2.82mmol/L respectively, suggestive of Primary Hyperparathyroidism (PHPT) given the end organ damage and negative genetic studies. Based on her symptom of fatigue, osteopaenia at a young age and hypercalcaemia, localisation studies were arranged which showed no definitive evidence of a parathyroid adenoma and explorative surgery was planned.
The negative genetic testing, PTH level 17.1pmol/L, osteopaenia, low-normal magnesium and phosphate level collectively support a diagnosis of PHPT in this case, despite a low UCCR which however is observed in some PHPT patients. Indeed, a lower UCCR ratio has been reported in the healthy Afro-Carribean population across all age groups, as well as in Afro-Carribean patients with PHPT [1]. The underlying mechanism for this is yet to be determined but may be due to increased renal sensitivity to PTH or altered activity of the tubular calcium reabsorptive pathways. One can further speculate regarding an evolutionary reason behind a protective homeostatic system favouring renal calcium reabsorption over excretion in this frequently vitamin D deficient population.
Clinical practice relies heavily on the use of UCCR in aiding the biochemical differentiation of PHPT and FHH. However, as this case highlights, its use can be misleading in Afro-Carribean patients and therefore should be interpreted within an ethnic context.
References: Taha W., Singh N., Flack J. M., Abou-Samra A. B. Low urine calcium excretion in African American patients with Primary Hyperparathyroidism. Endocr Pract. 2011; 17: 867–872
Combined vitamin D and calcium supplementation in vitamin D inadequate patients with urolithiasis: Impact on hypercalciuria and de novo stone formation
