Nobuaki Kuzuya

Increased Levels of Serum Angiotensin-Converting Enzyme Activity in Hyperthyroidism

Serum angiotensin-converting enzyme activity was significantly elevated in 21 patients with hyperthyroidism (65 +/- 18 U/mL) as compared with levels in healthy control subjects (30 +/- 9 U/mL). In eight patients treated with thionamide drugs, the enzyme activities decreased to a normal range as thyroid hormone concentrations returned to euthyroid levels. When two patients became hyperthyroid due to an insufficient maintenance dose of antithyroid drugs, the increase in the serum thyroid hormone concentration was followed by the re-elevation of serum angiotensin-converting enzyme levels with a time lag of about 2 weeks. Levels of this enzyme are increased reflecting the elevated serum thyroid hormone levels in hyperthyroidism. The hyperthyroid state should be considered when serum angiotensin-converting enzyme levels are high.

HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and remnant-like particle cholesterol in patients with type-2 diabetes

Patients with type 2 diabetes are known to have abnormalities in their remnant metabolism and low density lipoprotein (LDL) subfraction pattern, with a preponderance of small dense LDL. The effects of pitavastatin, a newly synthesized 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, on lipoprotein profiles in patients with type 2 diabetes were determined. Thirty-three patients were treated with pitavastatin with a daily dose of 2 mg for 8 weeks. After treatment, triglyceride, total and LDL cholesterol were significantly reduced by 28.7 +/- 36.7%, 25.2 +/- 14.3% and 36.1 +/- 14.3%, respectively. Remnant-like particle cholesterol (RLP-C), an independent risk factor for CAD which is known to be elevated in diabetic patients, was also significantly reduced (-30.9 +/- 30.5%) by the treatment and this decrease correlated well with the decrease in triglyceride level. The proportion of small dense LDL, which is known for its atherogenisity, decreased from 29.9 +/- 26.2% to 19.7 +/- 22.7% and the mean LDL particle size significantly increased from 26.36 +/- 1.13 nm to 27.10 +/- 1.36 nm. Pitavastatin, which is known to improve triglyceride levels and cholesterol levels, also improves RLP-C level and LDL subfraction profiles, and this in turn may reduce the cardiovascular risk in patients with type 2 diabetes and dyslipidemia.

Thyroid hormone secretion is more sensitive than thyroid cyclic AMP accumulation to stimulation with LATS in mice in vitro and in vivo

The effects of LATS-immunoglobulin G (IgG) on thyroid hormone secretion and on thyroid cAMP concentrations were investigated in mice and compared to those of TSH. In the in vitro experiments, thyroid lobes were incubated in Krebs-Ringer bicarbonate buffer with LATS-IgG or TSH for 3 h or 2 h and T3 concentrations in buffer and thyroid cAMP were measured by RIA. T3 in the buffer was increased with 1.5 mg/ml of LATS-IgG (A) or 2.5 mg/ml of LATS-IgG (B) (1000%/5 mg or 400%/5 mg in the McKenzie bioassay, respectively), whereas thyroid cAMP was elevated only after incubation with two to four times higher doses of LATS-IgG (A) or LATS-IgG (B). 0.03 mU/ml of TSH increased T3 concentrations, while a two fold higher dose of TSH was required to increase thyroid cAMP. I n the in vivo study, 5 mg of LATS-IgG (A) injected intravenously increased serum T4 concentrations but not thyroid cAMP. 2 mU of TSH increased serum T4, while 10 mU was needed to elevate thyroid cAMP. These results indicate that: i) thyroid hormone secretion is more sensitive than increases of thyroid cAMP to stimulation with LATS, which is similar to stimulation with TSH and that: ii) thyroid hormone secretion rather than increases of thyroid cAMP should be employed to detect serum thyroid stimulating activities when mouse thyroids are used.

Changes in Thyrotropin Binding Inhibiting Immunoglobulins (TBII) in sera of patients with Graves’ disease at the time of relapse or exacerbation

Thyrotropin Binding Inhibiting Immunoglobulins (TBII) were measured in sera of 240 patients with Graves’ disease who were followed 0–25 yr as a cross-sectioned study (21 untreated, 189 under therapy and 30 T3-suppressible and drug-discontinued patients) by using solubilized porcine thyroid TSH receptor. Assays were performed by using 50 μl of serum. All untreated 21 patients showed positive TBII. Frequency of positive patients decreased yearly with treatment although 36% of patients remained positive after 6 yr of therapy. After that time TBII were positive in 61 % of follow-up patients and in 16 positive patients who have been treated for more than 10 yr, drug therapy could not be stopped because of recurrence. TBII were positive in 6 of 30 T3-suppressible patients. As a longitudinal study changes in TBII were studied in 10 patients at the time of relapse or exacerbation. TBII increased in parallel with increases in thyroid hormone concentrations in 3 of 10 patients. Six of the others showed earlier or later TBII increases than those in thyroid hormones. One patient did not show any change in TBII, albeit thyroid hormone concentrations were found to be increased. Our observations suggest that abnormal IgGs detected as TBII in sera of patients with Graves’ disease by the present method do not explain the occurrence of hyperthyroidism.