Coexistence of hypocalciuric hypercalcaemia and interstitial lung disease in a family: a cross-sectional study

In a prospective investigation, a large kindred (twenty-one subjects) with unexplained association of familial hypocalciuric hypercalcaemia and idiopathic interstitial lung disease was studied. Serum calcium was increased in fifteen patients (the youngest being 7 years old) and was associated with hypo- or normocalciuria. The abnormalities were not age-dependent. The serum concentrations of parathyroid hormone, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and calcitonin were normal. In twelve patients the diffusing capacity (DLCO) and/or DLCO per unit lung volume was less than 75% predicted. This was often accompanied by a vital capacity of less than 80% predicted, and increased Tiffeneau index, and a reticulo-micronodular pattern with high diaphragm on chest X-ray. The decrease in DLCO was more pronounced in older non-smoking as well as smoking subjects (P less than 0.02) suggesting a progressing interstitial disease with age. The fibrosing alveolitis, which had been confirmed by open lung biopsy in three subjects, could not be attributed to sarcoidosis, collagen-vascular disease, or exogenous causes. The disturbances in the calcium homeostasis and in the diffusing capacity of the lung coexisted in seven of the twenty-one patients. Apparently, both abnormalities were inherited following an autosomal-dominant pattern but with a different penetration in each person, and seemed not be causally related to each other.