Tuula Helenius

THYROID FUNCTION TESTS IN PATIENTS ON LONG‐TERM TREATMENT WITH VARIOUS ANTICONVULSANT DRUGS

Thyroid function tests were studied in patients undergoing long‐term treatment with various anticonvulsant drugs. Previous reports that diphenylhydantoin induces a decrease in the serum concentrations of total and free thyroxine (T4) and tri‐iodothyronine (T3) without a change in the TSH concentration were confirmed. Diphenylhydantoin had no effect on reverse T3. Carbamazepine was also found to decrease serum T4, the free T4 index and T3 but, with the exception of T3, the decrease was smaller than that induced by diphenylhydantoin. Dipropylacetic acid did not influence the serum thyroid hormone concentrations, and neither did primidone. This demonstrates that the interaction between anticonvulsant drugs of different chemical structure and thyroid hormone metabolism is diverse. None of the drugs tested altered serum TSH or the T3 uptake test for the estimation of unsaturated thyroid hormone binding‐capacity in serum. These two tests are considered diagnostically more dependable than the measurement of thyroid hormones in serum when diphenylhydantoin and carbamazepine are administered.

SERUM LEVELS OF 25‐HYDROXYVITAMIN D, 24,25‐DIHYDROXYVITAMIN D AND PARATHYROID HORMONE IN PATIENTS WITH FEMORAL NECK FRACTURE IN SOUTHERN FINLAND

Serum concentrations of 25‐hydroxyvitamin D (25‐OHD), 24,25‐dihydroxy‐vitamin D [24,25(OH)2D] and immunoreactive parathyroid hormone (PTH) were determined in elderly patients with fracture of the femoral neck and in age‐matched controls during summer, winter and early spring in southern Finland. The expected seasonal variation in 25‐OHD values was observed in both patients and controls, though the patient group had significantly lower values during winter (P < 0.02) and spring (P < 0.01). The 24,25(OH)2D: 25‐OHD ratio remained constant in both patients and controls throughout the study. A significant negative correlation between PTH and 25‐OHD values was found in the patient group. Thus, vitamin D deficiency may contribute to the high incidence of femoral neck fractures in elderly people, and the increased PTH activity, observed in many patients with these fractures, is secondary to vitamin D deficiency.

Effect of fatty acids on thyroid function tests in vitro and in vivo.

Addition of long-chain fatty acids to serum increased thyroxine (T4), measured by a competitive protein binding assay, and triiodothyronine (T3) uptake by Sephadex or resin (T3U tests). This is compatible with the assumption that fatty acids compete with thyroxine for binding sites on T4-binding proteins. When equimolar concentrations of various saturated and unsaturated fatty acids were added to serum it was observed that the effectiveness in raising tests based on protein binding of thyroid hormones incrreased serum T3 determined by radioimmunoassay (RIA). T4(RIA) was not significantly influenced by either saturated or unsaturated fatty acids. Serum T4(CPB) rose during storage at 22degreesC and 37degreesC but was stable at 4degreesC and --20degreesC for periods up to two weeks. The proportional increase in T4(CPB) and free fatty acids (FFA) indicated that this phenomenon was due, at least partly, to the interference from FFA formed during storage of the serum. There was also a small, significant increase in T3U, T3(RIA) and CT4I (a free thyroxine estimate) after storage of serum at room temperature or higher for one to two weeks. Serum T4(RIA) did not alter during two weeks of storage. In five subjects with raised serum FFA after eating a fat meal followed by a heparin injection an increase in T4(CPB), T3U, T3(RIA) and CT4I that was proportional to the increase in FFA was observed. This effect on the thyroid tests was small until the increase in FFA concentration exceeded 2 mmol/l. T4(RIA) did not respond to the increase in FFA. In ten patients with raised levels of FFA due to uncontrolled diabetes T4(CPB), T4(RIA) and T3(RIA) decreased while T3U increased. These unexpected alterations were probably related to the severe, chronic illness in these patients. Increased FFA in vivo seem to be of little importance for the interpretation of thyroid tests in clinical practice.

ASSESSMENT OF THYROXINE SUPPRESSION IN THYROID CARCINOMA PATIENTS WITH A SENSITIVE IMMUNORADIOMETRIC TSH ASSAY

Serum TSH was determined with a sensitive radioimmunometric method (TSH IRMA) in 57 patients on suppression therapy with T4 after operation for differentiated thyroid carcinoma. When using a conventional RIA technique basal TSH was not detectable and remained so even after stimulation with TRH. With the TSH IRMA method 46 patients had a basal TSH below the detection limit (0·02 mU/l) (81 %) and in seven patients the values were between 0·02 and 0·05 mU/l (12%). In 23 of these patients there was a small increment of 0·01–0·15 mU/l. In two patients the basal TSH was 0·08 and 0·09 mU/l, and the increment after TRH was less than 0·7 mU/l. In two other patients with basal values close to 0·2 mU/l the increment after TRH was more than 1·0 mU/l. An undetectable basal TSH value did not thus predict an absent response to TRH. The responses were, however, in all but two cases, so small that they could be regarded as clinically insignificant. Therefore, the authors conclude that a basal TSH of 0·1 mU/l, as measured with a TSH IRMA method with a detection limit of 0·05, is a sufficient indication of TSH suppression in carcinoma patients on T4 therapy and that further testing with the TRH‐stimulation test is unnecessary.