Serum levels of
procollagen III N-
peptide (
PIIINP) and
hyaluronic acid (HA) reflect secretion of
procollagen III and HA from fibroblasts, a cell type sensitive to
thyroid hormones. Serum
PIIINP and HA concentrations were measured in different thyroid function states, the former by two different assays, one detecting intact and aggregated
PIIINP (
PIIINP assay) and another detecting low mol wt degradation products of
PIIINP as well (Fab-
PIIINP assay). Two thirds of 28
hyperthyroid patients had elevated serum
PIIINP values (mean, 192% in the
PIIINP assay and 243% in the Fab-
PIIINP assay) compared to age- and sex-matched controls (P less than 0.001). Normalization was seen after medical treatment (n = 16). In contrast, serum HA levels increased from 49 +/- 30 to 68 +/- 37 ng/mL (P less than 0.01) when a euthyroid state was achieved. Hypothyroid patients (n = 23) had increased serum HA levels (mean, 162%; P less than 0.05), which normalized after L-T4 treatment (71 +/- 50 before and 41 +/- 20 ng/mL
after treatment (n = 16; P less than 0.02). L-T4 treatment also increased serum
PIIINP levels significantly. Subjects with
familial dysalbuminemic hyperthyroxinemia (n = 8), representing a situation with elevated circulating levels of T4 due to enhanced protein binding, and patients with nontoxic
goiter with serum TSH levels ranging from 3.6-0.05 mU/L had normal serum levels of
PIIINP and HA. Our data suggest that the secretion of
procollagen III and that of HA from fibroblasts are influenced differently by
thyroid hormones, since the secretion of
procollagen III seems enhanced by
thyroid hormones, whereas the secretion of HA seems reduced. Neither euthyroidism with enhanced serum T4 levels (
familial dysalbuminemic hyperthyroxinemia) nor euthyroidism with reduced serum TSH levels (nontoxic
goiter) seems associated with alterations at the connective tissue level.