ABSTRACT
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.
Subject(s)
Hypothyroidism/complications , Scleroderma, Systemic/complications , Thyroid Gland/physiopathology , Adult , Aged , Autoantibodies/analysis , Autoimmune Diseases , Female , Humans , Hypothyroidism/immunology , Hypothyroidism/physiopathology , Male , Microsomes/immunology , Middle Aged , Prospective Studies , Scleroderma, Systemic/physiopathology , Thyroglobulin/antagonists & inhibitors , Thyroid Gland/immunology , Thyroid Hormones/blood , Thyrotropin/blood , Thyrotropin-Releasing HormoneABSTRACT
Tiflamizole is a fluorinated diarylamidazole sulfone nonsteroidal anti-inflammatory drug not metabolized or excreted in urine. Its mean (+/- SD) elimination t 1/2 from plasma was 21.6 +/- 9 days (range 11.8 to 49.5 days) in 17 subjects with rheumatoid arthritis, and appeared to be first order in most of them. Plasma elimination t 1/2 was loosely related (r = -0.67) to stool frequency in eight subjects for whom stool frequency data were available. In one, cholestyramine decreased t 1/2 to 4.1 days. In two patients, synovial fluid total tiflamizole concentrations were approximately one-third of simultaneous plasma concentrations, but elimination t 1/2s from synovial fluid were of the same order as those from plasma. Even with infrequent dosing, the longer t 1/2 may help sustain the anti-inflammatory effects of this drug.
