Kazuro Kaise

Measurement of TSH in human amniotic fluid: diagnosis of fetal thyroid abnormality in utero

Using a highly sensitive immunoradiometric assay kit for human TSH, we measured TSH concentrations in unconcentrated amniotic fluids in normal pregnancies and those complicated for example by maternal hyper‐ and hypothyroidism, and compared them with those in maternal and cord sera. In normal pregnancies the mean concentration of TSH in amniotic fluid samples was 0·129 μU/ml, ranging from 0·065 to 0·278 μU/ml. In patients with premature delivery, the amniotic fluid TSH concentration was higher at 0·218 μU/ml. In four patients with abnormal thyroid function, TSH in amniotic fluid changed in parallel to that in cord serum, and there was a significant positive correlation between the two. No such correlation was observed between the concentrations of TSH in amniotic fluid and maternal serum. These results suggest that TSH in human amniotic fluid reflects fetal rather than maternal thyroid function and that the determination of TSH levels in amniotic fluid is useful in the diagnosis of abnormal thyroid function in fetuses.

THYROID FUNCTION IN PATIENTS WITH MYOTONIC DYSTROPHY

In order to investigate endocrine disturbances in patients with myotonic dystrophy (MD), 12 patients and 20 normal controls were studied. All patients were clinically euthyroid and there were no significant differences between circulating levels (mean±SD) of T4 (114.7±26.8 vs 129.9± 28.3 nmol/l), FT4 (16.6±4.5 vs 18.4±3.8 pmol/l), T3 (1.61±0.29 vs 1.86±0.33 pmol/l), TSH (2.7±1.3 vs 2.4±1.4 mU/l), TBG (26.7±5.5 vs 27.6±4.9 mg/l), T4/T3 (84.3±18.4 vs 82.1±15.3), and FT4/FT3 (0.28±0.05 vs 0.33±0.08). Serum FT3 (4.3±1.4 pmol/l) in patients were significantly lower than those (5.3±0.9 pmol/l) in normal controls (P<0.02). Thyroidal131 I‐uptakes (8.7±4.3%) in patients were significantly lower than those (25.8±7.4%) in controls (P<0.01). The mean maximal TSH responses following TRH stimulation were significantly less in patients with MD (11.4±4.5 vs 17.0±6.2 mU/l; P<0.02). Neither circulating thyroid microsomal nor thyroglobulin antibodies were detectable in the 11 patients tested. Serum thyroglobulin concentrations were within the normal range in all patients but one. In conclusion, it is suggested that normal levels of serum T4, T3, FT4, TSH, TBG, T4/T3 and FT4/FT3, slight but significant decrease of serum FT3, reduced TSH response to TRH and a decrease of thyroidal radioiodine uptake might be due to a slight functional failure of TSH secretion in patients with myotonic dystrophy.

EFFECT OF PREDNISOLONE AND SALICYLATE ON SERUM THYROGLOBULIN LEVEL IN PATIENTS WITH SUBACUTE THYROIDITIS

Twelve patients with subacute thyroiditis were divided into two groups and treated with prednisolone or salicylate. The initially elevated T4, T3, free T4 (FT4), free T3 (FT3) and erythrocyte sedimentation rate (ESR) were reduced during the early phase within about 4 weeks in both groups. The serum levels of thyroglobulin (Tg) were elevated in both groups treated with salicylate and prednisolone (252 ± SD 117 ng/ml and 233 ± SD 157 ng/ml, respectively) at initial examination. The serum level of Tg declined during the early phase with prednisolone treatment, and it reached normal values at the end of the early phase (17 ± SD 15 ng/ml). With salicylate treatment, the decline of levels of Tg was delayed and it was elevated (80 ± SD 34 ng/ml) despite normal levels of thyroid hormones and ESR at the end of early phase. The serum level of Tg at the end of the early phase of prednisolone treated was significantly lower than that of salicylate treatment (P<001). It is suggested that the effect of prednisolone on rapid decrease of Tg may be related to its inhibitory action of intrathyroid hydrolysis.

The Monodeiodination of Thyroxine to 3, 3^|^prime;, 5^|^prime;-Triiodothyronine in the Human Placenta

We investigated the characteristics of the monodeiodination of thyroxine to T3 and rT3 in human placentas which were obtained at normal delivery. The placentas were homogenized in a cold sucrose Tris-HCl buffer, pH 7.5. The microsomal fraction was incubated at 37 degrees C in air for 1 hr with 2 micrograms of T4 in the presence of 50mM DTT. The T3 and rT3 generated in the reaction mixture were extracted into cold ethanol and measured by RIA. Among the usal subcellular fractions of the placental homogenate, microsomes were the most potent in deiodinating T4 to rT3. In microsomes, production of rT3 increased with protein concentration, incubation temperature up to 37 degrees C, incubation time up to 120 min and T4 concentration up to 16 micrograms/tube. The production of rT3 from T4 was lost by prior heating of the microsomal fraction to 56 degrees C for 30 min. The net production rate of T4 to rT3 in the microsomal fraction was 17.9 ng/mg protein/micrograms T4/60 min at pH 7.5. RT3 production from T4 was maximal at pH 7.0. The production of T3 from T4 was negligible in the present system. Degradation of T3 in the placentas was rapid. Although the addition of anti-T3 antibody to the reaction mixture suppressed the degradation of T3, it had no effect on the net production of T3, suggesting that the obtained net T3 production rate had not been influenced by its degradation. Degradation of rT3 was negligible. These results indicate that the human placenta actively deiodinates T4 to rT3 enzymatically. This enzyme system might have some influence on the transplacental passage of the thyroid hormone from the mother to the fetus.

Complement Activities and Circulating Immune Complexes in Sera of Patients With Graves′ Disease and Hashimotofs Thyroiditis

In autoimmune thyroid diseases various immunological abnormalities were observed. Circulating immune complexes (CIC) have been detected in sera from patients with Graves′ disease(GD) and Hashimoto’s thyroiditis (HT). Intrathyroidal deposition of immune complexes was reported in these diseases. But the role of CIC in these diseases is not clear. Deposition of immune complexes induces activation of complement system and leads cells to lysis. In these process serum complements are consumed and its activities are reduced in some autoimmune diseases such as systemic lupus erythematodes and serum sickness. In such diseases serum complement activities were reported to correlate with the activity of the disease. In this report we studied about CIC and serum complement activities in patients with GD and HT to clarify the role of CIC and complement in these diseases.

[Two cases of hypothyroidism due to chronic thyroiditis preceding thyrotoxic Graves' disease].

慢性甲状腺炎による甲状腺機能低下症の治療中にBasedow病を発症した2症例を報告した.症例1は39才,症例2は46才の女性で,両者の血清T4, T3および症例1の131I摂取率は正常であつたが,血清TSHが高値であり,抗サイログロブリン抗体,および抗マイクロゾーム抗体が陽性のため,慢性甲状腺炎に伴うsubclinical hypothyroidismとしてl-thyroxineを投与していた.それぞれ2年半および1年後に, T4およびT3が高値となり, l-thyroxineを中止後も高値を持続した. 131I摂取率も高値となり, T3の投与にても抑制されず,ともにBasedow病を発症したものと思われた.症例2では眼症状も認められた.またこれらの例ではTSHリセプター抗体が陽性であつた.