Hypoparathyroidism in adults with iron overload diseases (IOD): evidence of a subclinical phenotype

Purpose: To explore the prevalence of hypoparathyroidism (HPT), overt and subclinical, in a cohort of adults with Iron Overload Diseases (IOD). Secondary aim was to test the calcium (Ca)-to-phosphorus (P) ratio performance in identifying HPT. Methods: Single-center, prospective, case-control study. Sixty-five IOD, 40 with thalassemia major/intermedia (TMI) and 25 with hemochromatosis (HC), and 76 age-matched controls were included. Main outcomes (serum Ca, P, Ca/P ratio, intact parathyroid hormone (PTH), albumin) defined overt and subclinical HPT. Results: Albumin-adjusted Ca was lower (p = 0.004) and P higher (p = 0.002) comparing IOD to controls. Ca/P ratio was lower in IOD than controls (p < 0.001); PTH did not change. P was higher and Ca/P lower comparing TMI to HC and controls (p < 0.001); Ca did not change. A total of 28/65 IOD (43%) had HPT (9.2% overt, 33.8% subclinical) whose prevalence was higher in TMI than HC (p < 0.001). Ca/P ratio <2.32 had sensitivity 71.4% and specificity 83.9% in detecting overt/subclinical HPT. IOD with Ca/P ratio <2.32 (1.78 in SI) had an almost 12-fold increased likelihood to be affected by HPT (OR 12.92 [3.90–42.82]; p < 0.001). Ca/P (p = 0.002) was the only independent risk factor for HPT at multivariate analysis. Conclusions: HPT, especially non-classical subclinical HPT, is common in adult IOD with higher prevalence in TMI than HC. Ca/P ratio <2.32 is accurate to screen for overt/subclinical HPT and should be periodically evaluated in IOD to early detect an unbalanced mineral metabolism, and to monitor a possible evolution from subclinical to overt HPT.