The incidence of thyrotoxicosis accompanied by overt diabetes has been reported to be 2 to 3%. Several workers have suggested the possible role of immunological and inherited factors in the occurrence of thyrotoxic patients with overt diabetes. We investigated, therefore, the clinical characteristics, backgrounds, and HLA antigens in thyrotoxic patients with overt diabetes.
In nine thyrotoxic patients with overt diabetes (group DM) (3 men and 6 females, average age of 45.8±2.9yr), mean levels of free-triiodothyronine (FT₃) and free thyroxine (FT₄) were 8.2±0.8pg/ml and 4.9±0.4ng/dl, respectively. Although these levels were extremely high, they were significantly lower than those levels in forty thyrotoxic patients without overt diabetes (group ND) (8 men and 32 females, average age 35.1±4.5yr). Mean levels of both thyrotrophin receptor-antibody (TR-Ab) and thyroid simulating antibody (TS-Ab) in group DM were relatively lower than those in group ND. Mean titers of both antithyroid antibody (TGHA) and antimicrosomal antibody (MCHA) in group DM were also relatively lower than those in group ND, respectively. Regarding the clinical features in thyrotoxic patients with overt diabetes, mean duration of diabetes mellitus was 4.1±2.5 years with mean levels of fasting plasma glucose (FPG), HbAic, and serum fructosamine 208.1±34.0mg/dl, 10.6±0.6%, and 3.9±0.9mmol/L, respectively. Seven patients in group DM frequently had ketosis or ketoacidosis in their histories, and they had been treated with insulin injection. However, the diabetic complications in group DM were moderate or severe. The occurrence of the thyrotoxicosis preceding overt diabetes mellitus was observed in two of 9 patients with 3 others who had been treated as diabetes mellitus until the thyrotoxicosis was discovered. The nearly simultaneous occurrence of thyrotoxicosis and diabetes mellitus was found in four.
In the analysis of HLA-antigens, the frequency of A24 (9), BW54, BW55 (W22), BW61 and CW1 among patients in group-DM was significantly greater than those in group ND (p<0.01 or p<0.05). The frequency of DR4 antigen in patients in group-DM (88.9%) was significantly greater than that in group-ND (p<0.01).
These results suggest that some genetic factors may play a role in the occurrence of overt diabetes in thyrotoxic patients.

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The utility of urinary 17α-hydroxyprogesterone (U-17-OHP) in the diagnosis and management of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21- OHD) was evaluated in 16 patients with 21-OHD. The normal values for U-17-OHP in relation to age and other physiological conditions were investigated in 96 normal subjects and 7 low birth weight infants. Levels of U-17-OHP, serum 17-OHP (S-17-OHP) and urinary free cortisol (U-FC) were simultaneously determined using enzyme-linked immunosolvent assay (ELISA) combined with fractionation by high performance liquid chromatography (HPLC). Pregnanetriol (PT) levels in the same urine specimens were determined using glass capillary gas chromatography (GC).
The results were as follows:
1) Normal subjects and low birth weight infants. A significant correlation between U-17-OHP excretions corrected for body surface area (BSA) in 2-h urine specimens and S-17-OHP concentrations at the midpoint of the urine sampling period was observed in normal subjects (r=0.768, p<0.01). Circadian U-17-OHP excretion in 6 adult males was synchronous with that of U-FC. Age-related changes in actual U-17-OHP excretions (Mean±SD ng/day) were as follows: neonates: 31.9±10.3, children aged 2 to 4 years old: 29.1±14.5, 5 to 8 years old: 68.6±29.9, 9 to 11 years old: 151.3±50.0, 12 to 15 years old: 222.7±82.0, adult males: 400.1±62.5, adult females (luteal phase): 339.1±109.7, and adult females (follicular phase): 185.6±72.3, respectively. Correlation between U-17-OHP and PT excretions in 24-h urine specimens from normal subjects greater than 2 years of age was highly significant (r=0.871, p<0.01). Although U-17-OHP values were measurable in neonates, those of PT were not detectable by GC in the same specimens because of low conversion of 17- OHP to PT.
2) Cases of 21-OHD. In 4 cases of 21-OHD diagnosed in the neonatal period (aged 11 to 15 days, all were of the salt-losing type), the U-17-OHP concentration in a single urine specimen was significantly higher than that of age-matched controls, whereas the PT concentration in one case was low and therefore had no diagnostic value. In 12 patients with 21-OHD receiving suppressive therapy, correlation between S-17-OHP concentrations and 24-h U-17-OHP excretions corrected for BSA was significant (r=0.847, p<0.01). Both correlated significantly with plasma renin activity (PRA) (the former: r=0.431, p<0.05; the latter: r=0.427, p<0.05, respectively) and serum testosterone (T) concentrations (the former: r=0.482, p<0.05; the latter: r=0.491, p<0.05, respectively) to the same respective degree. In the well -controlled cases with S-17-OHP concentrations less than 2ng/ml, U-17-OHP excretions correlated inversely with those of U-FC (r=-0.598, p<0.01), though the S-17-OHP concentrations did not correlate significantly with them (r=-0.101, p>0.10). There was one case in which the nocturnal morning U-17-OHP excretion was higher than normal with a normal daytime S-17-OHP value. There was a significant correlation between urinary PT and U-17-OHP excretions in the same 24-h urine specimens (r=0.896, p<0.01). PT values correlated significantly with those of S-17-OHP (r=0.853, p<0.01), PRA (r=0.432, p<0.05) and T (r=0.467, p<0.05), and correlated inversely with those of U-FC (r=-0.572, p<0.01).
These findings suggest that 1) U-17-OHP reflects the level of non-protein-bound S-17-OHP in plasma, and its excretion rate provides an integrated parameter of diurnal secretion, as is the case with U-FC, 2) U-17-OHP is a useful parameter in the diagnosis and management of CAH due to 21-OHD, and 3) U-17-OHP is superior to PT in the diagnosis of early neonatal 21-OHD and applicable to the management of 21-OHD without blood sampling.

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To verify the role of the dopaminergic mechanism in the control of gonadotropin secretion and aging of this mechanism in men, we studied serum gonadotropin response to LH-RH (100μg i. v.) in basal condition and during dopamine infusion (DA 4μg/kg/min). Seven young males (24-29yr.) and twenty aged males (50-80yr.) without endocrinological diseases were included in the present study.
Aged male subjects were divided into hyperresponders, in whom maximal LH response to LH-RH without DA infusion exceeded 153.5mIU/ml (mean+2SD of young male subjects), and non-hyperresponders, in whom maximal LH responses to LH-RH without DA infusion were less than 153.5mIU/ml. In hyperresponders, serum LH response at 30 minutes after LH-RH administration was significantly (p<0.05) suppressed by DA infusion. In non-hyperresponders and young male subjects, however, serum LH response to LH-RH was not affected by DA infusion. Basal levels of serum LH and FSH in hyperresponders tended to be higher than that of non-hyperresponders. Total serum testosterone, free testosterone and estradiol levels of hyper and non-hyperresponders failed to reveal any significant differences.
These observations suggest that 1) DA directly suppresses gonadotroph responsiveness to LH-RH, 2) in aging men, inhibitory tone imposed on gonadotrophs by DA is decreased, and 3) this decline of DA system can cause hypergonadotropism in aging men, independent of serum sex steroids levels.

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Sarafotoxin S6B (SRT), a peptide in snake venom, has a high degree of sequence homology with endothelin (ET) and both are potent vasoconstrictors. In order to determine whether SRT acts via the ET receptor, we performed autoradiographic binding studies on rat tissues using the radioligands, ¹²⁵I-ET-1 and ¹²⁵I-SRT and computerized in vitro autoradiography. In the heart, a high density of ET binding was found in the atria, and moderate density was found in the ventricles. A high density of ET-1 was found in the heart. In the kidney, ET-1 binding occurred in association with glomeruli, outer cortex, and inner stripe and inner medulla. In the adrenal, a high density of ET-1 binding occurred in the medulla as well as the zona glomerulosa. The binding affinity constant (K_A) for ET-1 binding in these sites ranged from 1-10×10⁹M^-1. Although SRT was 5-100 fold weaker than ET-1 in displacing ¹²⁵I-ET-1 from these sites, 1μM unlabelled SRT completely abolished ¹²⁵I-ET-1 binding in all sites. Other venom peptides or unrelated peptides did not affect ¹²⁵I-ET-1 binding. Moreover, the pattern of ¹²⁵I-SRT binding in rat tissues by in vitro autoradiography was identical with that of ¹²⁵I-ET-1 binding, and both unlabelled SRT and unlabelled ET-1 fully competed with ¹²⁵I-SRT for binding. These results provide evidence that SRT binds to the ET binding sites in a range of rat tissues.

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The aim of the present study was to investigate the role of insulin on the renal mechanism of hyperuricemia in overweight patients with essential hypertension. Thirty-four essential hypertensives (EHT), receiving a regular diet containing 120mEq of sodium, 75mEq of potassium and 2000 killocalories daily, were divided into two groups of non-obese (NHT) and obese (OHT) EHT. NHT as categorized as a body mass index (BMI) less than, and OHT as a BMI equal to or more than, 25kg/m2 in male patients and 24kg/m2 in female patients. In the early morning after overnight fast,renal uric acid and sodium clearance were examined while the patients remained in a supine position, During the two-hour clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), immunoreactive insulin (IRI), serum uric acid (SUA), fractional excretion of uric acid (FEUA) and sodium (FENa) were measured.
Although there were no significant differences in age, MAP, FIR, Ccr, nor SUA between the two groups, a higher ratio of female to male patients was found in OHT than in NHT. On the other hand, higher SUA and IRI and lower FEUA and FENa were observed in OHT than in sex-and Ccr-matched NHT. SUA was negatively correlated with FEUA in all patients (r=-0.392, p<0.05) and in NHT (r=-0.553, p<0.05), unlike in OHT. A significant negative correlation between BMI and FEUA was revealed in all EHT (r=-0.441, p<0.01) and in OHT(r=-0.597, p<0.01) but not in NI-IT. FEUA was positively correlated with FENa in all EHT (r=0.554, p<0.001) as well as in NHT (r=0.548, p<0.05) and OHT (r=0.507, p<0.05). Moreover, there was a significant negative correlation between IRI and FENa in all EHT (r=-0.361, P<0.05) and in OHT (r=-0.470, p<0.05). However, no significant relation was demonstrated between WI and SUA or FEUA in NHT or OHT.
From these results, it is concluded that an attenuated renal excretion of uric acid related to natriuretic ability may play an important role in hyperuricemia in EHT. However, the role of hyperinsulinemia, which contributes to the blunting of natriuresis, might be relatively small in the renal mechanism of hyperuricemia in EHT, particularly in OHT.

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