Yoshiyuki Fuwa

A case of Graves’ disease associated with polymyositis

A patient with Graves’ disease associated with severe muscle weakness who was finally diagnosed as polymyositis by pathological examination of the muscle is reported. A 28-year-old women was incidentally found to have hyperthyroidism when she consulted a hospital for the evaluation and treatment of anemia in 1979. She was treated with methimazole for approximately a month when she stopped the medication by herself. Approximately two yr later (Nov. 4, 1981) she consulted another hospital with complaints of palpitation and muscle weakness. Diagnosis of hyperthyroidism due to Graves’ disease and thyrotoxic myopathy were made, followed by the treatment with radioiodine (4 mCi of 131I). She was further treated with propylthiouracil (PTU). Four yr after the treatment, serum thyroid hormone concentration declined to the lower level than normal and serum TSH concentration increased. She was subsequently treated with synthetic I-T4. Despite the fact she became euthyroid with the treatment, muscle weakness as well as elevated concentrations of muscle enzymes were not improved. Muscle biopsy was made in July 1983, and she was diagnosed as immune polymyositis and treatment with prednisolone and cyclophosphamide in addition to PTU or I-T4, was started. With the treatment, serum LDH decreased to the normal range. However she still has muscle weakness and serum concentrations of CPK and aldolase are still in higher levels than normal range.

Measurement of plasma free steroids by direct radioimmunoassay of ultrafiltrate in association with the monitoring of free components with [14C]glucose

We describe a modified method of centrifugal ultrafiltration using the Grace MPS-3 device for the measurement of plasma free (unbound) steroids (cortisol, testosterone, estradiol, and prednisolone). Plasma was incubated with [14C]glucose to monitor the movement of free components, applied to the MPS-3 and centrifuged. Steroid concentration of ultrafiltrate was directly measured by radioimmunoassay, and multiplied by the ratio of [14C]glucose count (dpm) in plasma to [14C]glucose count (dpm) in ultrafiltrate. The data by this method correlated well with those obtained by equilibrium dialysis. Our results of free steroid in healthy volunteers and patients with various diseases were comparable with the previously reported values. This procedure showed the advantages of small sample volume, rapid separation and the ability to process a large number of samples in a single run.

プレドニゾロン (PSL) 隔日投与時の総及び遊離PSL薬物動態

To determine the pharmacokinetic changes of prednisolone associated with an alternate-day regimen, 12 patients with various diseases were studied longitudinally. There were 9 patients (6 with systemic lupus erythematosus, 2 with sarcoidosis and one with polymyositis), who were treated with prednisolone (daily period) and subsequently put on an alternate-day regimen (alternate-day period). In 2 of the other patients (one with systemic lupus erythematosus and one with multiple sclerosis), the alternate-day regimen was preceded by the daily regimen, and subsequently an intermittent regimen consisting of 4 consecutive days on therapy and 3 days off therapy was followed. In the remaining patient with systemic lupus erythematosus, the treatment with the alternate-day regimen was initiated and followed throughout the treatment period. The mean duration and the mean total administered dose during the study were 1.1 months and 1.9 g in the daily period, and 7.8 months and 7.7 g in the alternate-day period. The test was done and blood was drawn for 6 hours after an intravenous administration of 20 mg prednisolone (0.36 mg/kg on the average) at the end of the respective regimen periods. In the daily period and the on-day of the alternate-day regimen, the pharmacokinetic study of iv prednisolone injection was done before the ingestion of oral prednisolone. The off-day test was done the next morning of the on-day. Plasma total and free prednisolone concentrations were measured by RIA. On-day and off-day tests in the alternate-day period were performed during the same week. The mean half life of both total and free prednisolone was prolonged significantly in the daily period and during the on-day and off-day of the alternate-day regimen compared with the pretreatment values. The mean metabolic clearance rates (MCR) of both total and free prednisolone decreased significantly in the daily period and during the on-day and off-day of the alternate-day period in comparison with the pretreatment values. No significant difference was found between either mean half life or MCR during the on-day and off-day of the alternate-day period. These findings were in contrast with our previously observed prednisolone pharmacokinetics during the intermittent regimen (4 days on therapy and 3 days off therapy within one week), in which pharmacokinetic parameters during the on-day (after 3 days of prednisolone ingestion) and off-day (after 3 off-days of prednisolone ingestion) periodically changed and were similar to those in the pre-treatment period and during the daily therapy period, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)