Toshio Shinoda

Disappearance of Thyrotropin-Blocking Antibodies and Spontaneous Recovery from Hypothyroidism in Autoimmune Thyroiditis

BACKGROUNDnHypothyroidism may result from the production of antibodies that block the actions of thyrotropin. How often these thyrotropin-blocking antibodies are a cause of hypothyroidism and whether their production may cease, causing hypothyroidism to disappear, have not been extensively studied.nnnMETHODSnWe determined the frequency with which thyrotropin-blocking antibodies were present in 172 hypothyroid patients with goitrous autoimmune thyroiditis (Hashimotos disease) and 64 hypothyroid patients with atrophic autoimmune thyroiditis (idiopathic primary hypothyroidism). For 6 to 11 years we then followed 21 of these patients who were found to have thyrotropin-blocking antibodies. They received levothyroxine therapy for 3.5 to 8 years, after which it was discontinued. At frequent intervals during this time we measured the patients serum concentrations of thyroxine, triiodothyronine, thyrotropin, and thyrotropin-blocking antibodies (measured as immunoglobulins that inhibit thyrotropin binding and immunoglobulins that inhibit thyrotropin bioactivity).nnnRESULTSnThyrotropin-blocking antibodies were detected in 9 percent of the patients with goitrous autoimmune thyroiditis and in 25 percent of those with atrophic autoimmune thyroiditis. Among the 21 patients studied serially while receiving levothyroxine, thyrotropin-blocking antibodies disappeared in 15 (group 1), 7 of whom had goiter initially, and persisted in 6 (group 2), none of whom had goiter initially. Levothyroxine therapy was subsequently discontinued in these 21 patients. Six of those in group 1 (four with goiter) remained euthyroid (mean follow-up after discontinuation of therapy, 2.1 years), and nine became hypothyroid again within 3 months. All six patients in group 2 remained hypothyroid.nnnCONCLUSIONSnHypothyroidism in some patients with autoimmune thyroiditis may be due to thyrotropin-blocking antibodies. The production of thyrotropin-blocking antibodies may subside, producing remissions of hypothyroidism. Chronic autoimmune thyroiditis may therefore cause transient as well as permanent hypothyroidism.

Alteration of renal function in hyperthyroidism : increased tubular secretion of creatinine and decreased distal tubule delivery of chloride

In 77 untreated patients (16 males and 61 females, aged 12 to 65 years) with hyperthyroid Graves disease, and in 107 control subjects (36 males and 71 females, aged 13 to 78 years), blood urea nitrogen (BUN), serum creatinine (Scr) levels, and BUN to Scr ratios (BUN/Scr) were determined. In 53 patients, the determinations were performed before treatment and after restoration of euthyroidism by treatment with an antithyroid drug. In addition, in seven untreated patients and seven normal subjects, renal clearances of creatinine (Ccr), urea nitrogen (Cun), inulin (Cin), and p-aminohippurate (CPAH) were also determined. The distal tubule delivery of chloride (DTD) and the distal fractional chloride reabsorption (DFCR) were also measured in these subjects: DTD = (CH2O + Ccl)/Cin x 100, and DFCR = CH20/(H20 + Ccl) x 100, where CH20 and Ccl stand for clearances of H2O and chloride, respectively. BUN was significantly elevated, while Scr was significantly depressed, in untreated patients with hyperthyroid Graves disease. Accordingly, the BUN/Scr was markedly elevated. Restoration of euthyroidism accompanied the normalization of all these abnormalities. Ccr and Cun were significantly elevated, but Cin (glomerular filtration rate [GFR]) was slightly, but insignificantly, elevated in the patients. As a result, the ratios Ccr/Cin and Cun/Cin were significantly greater in the patients than in controls (Ccr/Cin, 1.42 v 1.00; Cun/Cin, 0.92 v 0.68). The amounts of urinary creatinine and urea nitrogen (UN) excretion were decreased and increased, respectively, and DTD was significantly depressed, but DFCR was unchanged in the patients. We conclude that BUN is elevated, Scr is depressed, and the BUN/Scr is increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Polycystic kidney of autosomal dominant inheritance, polycystic liver and congenital hepatic fibrosis in a single kindred

A family with clear evidence of concomitant congenital hepatic fibrosis, polycystic liver and adult-type polycystic kidney is reported. The autosomal dominant inheritance of polycystic kidney in association with either liver cyst or hepatic fibrosis in this family suggests that various combinations of hepatic and renal fibrocystic lesions are possible to occur. Additionally, in the proband a very rare association of congenital hepatic fibrosis and cerebral aneurysm was present.

Hyperuricemia in patients with hyperthyroidism due to graves' disease

The effects of hyperthyroidism on uric acid metabolism were investigated. First, the serum uric acid level was measured in 92 patients with hyperthyroidism due to Graves disease, eight patients with subacute thyroiditis, six patients with hypothyroidism, and 70 sex- and age-matched controls. Second, the correlation between serum thyroxine (T4) and serum uric acid was obtained in hyperthyroid Graves disease patients before and during antithyroid drug therapy. Finally, uric acid clearance (CUA) was determined in untreated patients with hyperthyroidism due to Graves disease. Serum uric acid was significantly elevated in patients with hyperthyroidism, and the elevation correlated well with serum T4 before treatment as a group and during treatment in each patient. A significant elevation of serum uric acid was not present in patients with a transient mild thyrotoxicosis due to subacute thyroiditis. Serum uric acid was significantly decreased in patients with hypothyroidism. Renal excretion of uric acid clearly increased in hyperthyroid patients, and CUA also increased. The increase in CUA corresponded to the increase in renal plasma flow (RPF), which was measured by p-aminohippuric acid clearance. The fractional excretion of uric acid as determined by CUA/glomerular filtration rate (GFR) was similar and within the normal range in hyperthyroid patients and normal controls. A significant inverse correlation between CUA and serum uric acid concentration was present in hyperthyroid patients as in normal controls, indicating that the renal handling of uric acid in the tubule affected uric acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of calcium antagonists and nitroglycerin on atrial natriuretic peptide in normal subjects and patients with essential hypertension.

Acute effects of coronary vasodilators (nifedipine, nicardipine, and nitroglycerin) on atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system were studied in normal subjects and patients with essential hypertension. Nifedipine lowered blood pressure both in normal subjects and in patients and elevated ANP, plasma renin activity, and angiotensin II in normal subjects but not in hypertensive patients. Nicardipine lowered blood pressure but failed to elevate ANP and angiotensin II in normal subjects. Nitroglycerin failed to elevate ANP in normal subjects.

Co-occurrence of Hypercalciuria and Hypouricaemia in Type 2 Diabetic Patients

The relationship between the urinary excretion of calcium (Ca2+) and uric acid was investigated in 151 Type 2 diabetic patients and 48 normal subjects. In the diabetic patients, uric acid clearance/creatinine clearance (Clurate/Clcr) was higher and the serum level of uric acid was lower than in the normal subjects (Clurate/Clcr: 10.9 ± 5.8 vs 8.1 ± 2.6%, p < 0.001; serum uric acid: 304 ± 86 vs 357 ± 89 μmol l−1, p < 0.001). Calcium clearance/Clcr (Clca/Clcr) also increased in the diabetic patients, as did urinary excretion rate, but the serum Ca2+ level was not different to normal control subjects (Clca/Clcr: 2.29 ± 1.59 vs 1.56 ± 0.98%, p < 0.001; Ca2+ excretion rate: 2.24 ± 1.67 vs 1.63 ± 1.11 mmol day−1, p < 0.01; serum Ca2+ level: 2.34 ± 0.11 vs 2.33 ± 0.08 mmol l−1). In the diabetic patients, Clcr positively and the serum uric acid negatively correlated with the urinary excretion of Ca2+ (p < 0.001 for both correlations in the multivariate regression analysis). These data suggest that the diabetic patients have increased fractional excretion of both Ca2+ and uric acid.

Hypouricemia in NIDDM Patients

I n the epidemiological survey conducted by Herman et al. (1), serum uric acid levels were significantly lower in non-insulin-dependent diabetic (NIDDM) patients than in normal subjects. Gotfredsen et al. (2) also reported a decrease in serum uric acid levels in insulin-dependent diabetic patients, and increases in urinary uric acid excretion and uric acid clearance (Curate). In this study, we investigated the serum and urinary uric acid levels in NIDDM patients and discuss the mechanism of hypouricemia in diabetic patients. Two hundred and four nonnephrotic NIDDM patients (95 men, 109 women) and 44 normal controls (20 men, 24 women) were studied. All participants were admitted to the hospital between January 1984 and September 1987. Diagnosis of diabetes was based on the 1982 Japan Diabetes Society criteria (3). Patients with >25 mg/dl of proteinuria in morning urine samples, measured with a Combistix (Ames-Sankyo, Tokyo), were excluded from the study. Patients whose insulin dosage was >0.6 U/kg of body weight and who were receiving diuretics, antigout or antituberculous agents, antibiotics, aspirin, or anti-inflammatory agents were also excluded. Forty-nine of the diabetic patients were treated with insulin with the mean dosage consisting of 22.7 U/day. Forty-five patients received oral hypoglycemics, and the remainder were treated by diet therapy. Ageand body-weight-matched subjects with no major diseases were used as control subjects. Medical problems were either thyroid adenoma or simple goiter with normal thyroid function. Diabetic patients maintained their prescribed diets containing 25-30 kcal/kg of ideal body weight with 17% protein, 23% fat, and 60% carbohydrate. Control subjects maintained a normal hospital diet containing 2200 kcal/day with the same composition of protein, fat, and carbohydrate as diabetic patients. Blood and urine samples were collected at 0800 after at least 10 h of fasting. A 2-h postprandial plasma glucose level was measured at 1030. In 100 of the diabetic patients (49 men, 51 women) and all the controls, urine samples were collected for 3 days after the blood sampling day. From the 3-day measurements, the average data per 24 h were used for analysis. Serum and urinary uric acid levels were measured by a colorimetric procedure using an enzymatic (uricase) method, and plasma and urinary glucose levels were measured by the glucose oxidase method. Other serum chemicals were analyzed by an autoanalyzer (SMAC, Technicon Japan, Tokyo). Table 1 shows 13 clinical parameters in NIDDM patients and controls. Diabetic patients had a signifi-

Abnormal molecular weight profile of urinary protein in rats with streptozotocin-induced diabetes

A quantitative analysis of the molecular weight (MW) profile of urinary protein by SDS-PAGE was performed in streptozotocin (STZ)-injected, non-ketotic diabetic rats (DM group), diabetic rats receiving dipyridamole (DM-DIP group), normal rats (C group) and STZ-injected rats with near-normal glycemia due to insulin treatment (DM-INSULIN group). In the DM group, decrease of a small MW protein (SMWP) (MW 19.5 k) was found at 2.5 weeks, and an increase of larger MW proteins (LMWP) (MW 68 [albumin], 55 and 29 k) together with a decrease of SMWPs (MW 19.5 and 15 k) was found at 15 weeks, as compared to the C group: the MW profile of urinary protein in the DM-INSULIN and C groups was indistinguishable. At 15 weeks, creatinine clearance (Ccr) was significantly depressed and an increase in the mesangial matrix with electron dense deposits was evident in the DM group. The urinary protein abnormalities were partially corrected and the reduction of Ccr was absent in the DM-DIP group with no effect on glomerular morphology. STZ-induced diabetes in rats is accompanied by a reduction of urinary SMWP, and a subsequent increase of LMWP and depression of Ccr: dipyridamole ameliorates urinary protein abnormalities and prevents the reduction of Ccr.

Case Report: ACTH Deficiency and TSH Hypersecretion in a Patient with Empty Sella Turcica

In a 49-year-old woman with empty sella syndrome, corticotropin (ACTH) deficiency and various abnormalities, including increased thyrotropin (TSH) secretion, growth hormone (GH) deficiency, and inappropriately high insulin with early phase hypoglycemia, during an oral glucose tolerance test were found. Existence of serum antipituitary antibody suggested that the empty sella and ACTH deficiency may be caused by an autoimmune destruction of the pituitary gland. All of the accompanying abnormalities except for increased TSH secretion were corrected with glucocorticoid supplement. Thyroidal responses to an increase and decrease of endogenous TSH were qualitatively normal, indicating that the patients TSH was biologically active and the set point of hypothalamic-pituitary feedback regulation for TSH secretion was shifted.

An adult case of rheumatic fever complicated by acute renal failure.

急性リウマチ熱に急性腎不全を合併し, 腎不全発症時の原因として急性糸球体腎炎の併発が考えられた成人例を報告する. 症例は23歳の男性. 感冒様症状の約10日後, 発熱, 関節痛, 呼吸困難のため入院となった. 入院時, 軽度の高血圧, 扁桃腫大, 全身の関節腫脹がみられた. 検尿では蛋白尿, 血尿, 顆粒円柱を認め, 血液検査では高度の白血球増多, 血沈値亢進, CRP強陽性, ASO価上昇, 軽度の腎機能障害を認めた. 扁桃炎に対し抗生物質が投与されたが, 心膜摩擦音が聴取されるようになり, 腎不全も進行した. 胸部X線, 心電図, 心エコー検査で心膜炎, 心筋炎の所見を認めたためJonesの診断基準により急性リウマチ熱と診断し, これに急性腎不全が合併したものと考えられた. 血液透析, ペニシリン系抗生物質およびステロイド剤の投与により両病態とも軽快した. 第30病日の腎生検ではメサンギウムのごく軽度の拡大と, 糸球体への好中球の軽度浸潤が主体であったが, 一部の糸球体に半月体形成を伴った硝子化像およびその周囲の高度の線維化, 細胞浸潤が認められ, 急性腎不全発症時の原因として急性糸球体腎炎の併発が示唆された.