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The serum concentrations of calcium, phosphorus, parathyroid hormone, vitamin D₃ metabolites and their transport protein (DBP) were measured in 18 patients with the nephrotic syndrome (mean daily proteinuria 8.8 g). The glomerular filtration rate was normal in 13 patients while the remaining 5 had a mild degree of renal failure. The serum concentrations of total protein, albumin and DBP were significantly decreased in patients with the nephrotic syndrome. The serum calcium concentration was decreased but the calculated ionized calcium concentration remained normal. The serum concentrations of 25-hydroxycholecalciferol (5.3 ± 3.1 μg/l) and 1,25-dihydroxycholecalciferol [1,25-(OH)₂D₃ (20 ± 12 ng/l)] were significantly lower in patients with the nephrotic syndrome and normal glomerular filtration rates than in normal controls (14.4 ± 4 μg/l and 42 ± 13 ng/l, respectively). The free 1,25-(OH)₂D₃ index was also significantly below normal (0.9 ± 0.4 vs. 1.8 ± 0.4). Total and free 1,25-(OH)₂D₃ were still further reduced in patients with mild renal failure. The nephrotic syndrome thus results in mild vitamin D depletion with decreased free 1,25-(OH)₂D₃ concentrations but generally without secondary hyperparathyroidism.

Thirty-nine patients with progressive systemic sclerosis (PSS) in stable clinical conditions were extensively evaluated for the presence of thyroid disease. Two patients had previously undetected hypothyroidism while 7 additional patients had normal serum thyroid hormone levels but an exaggerated TSH response to thyrotropin-releasing hormone (TRH) administration, consistent with subclinical hypothyroidism. Four of the 9 subjects with abnormal TRH responses had positive antithyroid antibodies and of the remaining 5, 4 had been on chlorambucil or prednisone. Basal TSH and TSH response to TRH were significantly higher in PSS patients as a group when compared to a control group and increased with increasing duration of PSS. Serum antithyroid antibodies (antithyroglobulin and/or antimicrosomal antibodies) were positive in 18% and thyroid scans were abnormal in 18% of the patients. The euthyroid sick syndrome was not seen. Our findings indicate an increased frequency of, sometimes previously unsuspected, clinical and subclinical hypothyroidism in stable PSS patients which appears to be autoimmune in nature and becomes more prevalent with increased PSS duration. Careful and regular monitoring of the thyroid function in PSS patients is advisable.

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