Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants.

To examine steroidogenic responses of the different zones of the adrenal cortex to acute disease we determined the basal and adrenocorticotropin (ACTH)-stimulated levels of cortisol, dehydroepiandrosterone (DHEAS) and aldosterone in 16 infants aged 1-4 months with acute bronchiolitis. Fourteen of the infants were retested after recovery. During illness the mean basal levels of cortisol and DHEAS were twice as high as the levels after recovery (370 vs 180 nmol/l and 2.7 vs 1.3 mumol/l, respectively). The mean peak ACTH-stimulated levels of cortisol and DHEAS during illness were 1.5- and 2.5-fold higher, respectively, than the levels found after recovery. Although aldosterone secretion was stimulated > or = 3-fold by ACTH, illness was not associated with any change in aldosterone secretory capacity. The basal and stimulated levels of both cortisol and DHEAS during illness and after recovery were correlated significantly. Thus, the relative steroidogenic capacities for these two steroids were characteristic of the individual infant and showed constancy over a period of at least several weeks. While the levels of cortisol and aldosterone were not dependent on the age of the infants, both the basal and stimulated levels of DHEAS correlated strongly with age. We conclude that during acute disease the steroidogenic capacity selectively increases in the zones that secrete cortisol and DHEAS (only in infants < 3 months) but not in the zona glomerulosa that secretes aldosterone. The DHEAS response may be related to its putative effects to enhance immune responses.

Hyperinsulinaemia increases blood pressure in genetically predisposed spontaneously hypertensive rats but not in normotensive Wistar-Kyoto rats.

BACKGROUND: There is controversy in the literature concerning the effect of short-term insulin administration on blood pressure in different experimental situations, because in some experiments this association is clear, whereas in others it is nonexistent. OBJECTIVE: To investigate whether there is a difference in the effect of exogenous insulin administration on the blood pressure of normotensive Wistar-Kyoto (WKY) rats and hypertensive spontaneously hypertensive rats (SHR). METHODS: Hyperinsulinaemia was induced in normotensive WKY rats and in hypertensive SHR by the administration of long-acting insulin (insulin retard 0.4 U/kg body weight per day in one group and 0.8 U/kg body weight per day in another group) once a day, intraperitoneally, for 3 weeks. All of the rats drank a 10% sucrose solution, to prevent hypoglycaemia in those receiving insulin. RESULTS. Baseline serum levels were significantly higher in the SHR groups than in the WKY rat groups. At the end of the experiment, after 3 weeks' insulin therapy, systolic blood pressure measured by the tail-cuff method showed a significant increase in the SHR, but not in the WKY rats, possibly because of the genetic predisposition of the SHR to increase their blood pressure. The increase was similar in the SHR given 0.4 U/kg body weight per day insulin retard to that in those given 0.8 U/kg per day. CONCLUSIONS: Exogenous insulin increased systolic blood pressure in the SHR but not in the WKY rats. The rise was similar in rats receiving either 0.4 or 0.8 U/kg body weight per day insulin retard.

[Effect of low-dose amiodarone on thyroid function].

Thyroid function was examined periodically in a group of 85 patients treated with low-dose amiodarone, and followed for 1-13 years (mean 3.6). Biochemical hypothyroidism (elevated thyroid stimulating hormone (TSH) only) developed in 8 patients and clinical hypothyroidism in 3, while hypothyroidism developed in 5. In the first 11 cases amiodarone was continued but 1-thyroxine was added. In the 5 that became hyperthyroid, amiodarone was stopped and thyroid function became normal within a few months. In the 69 patients without thyroid dysfunction, elevated thyroxine (T4) and free thyroxine index (FTI) were found in 20% and 17%, respectively, and elevated free T4 (FT4) in 28%; all had normal total tri-iodothyronine (TT3) and TSH. In practically all patients, reverse T3 (rT3) rose more than 30% above initial levels. It is concluded that in patients treated with low dose amiodarone: 1) thyroid function should be followed closely; 2) elevated levels of TT4, FTI and FT4 do not necessarily imply hyperthyroidism; 3) hypothyroidism may be biochemical only, without progression to overt hypothyroidism, despite continued treatment; 4) both the hypo- and the hyperthyroidism induced are usually reversible; 5) amiodarone may be continued despite onset of hypothyroidism, provided replacement therapy is given.

[Elevated thyroid hormone levels in the absence of hyperactivity].

Elevated blood levels of thyroid hormones may be due to causes other than glandular hyperactivity. We have seen transient increases in total thyroxine (TT4), free thyroxine index (FTI), free thyroxine (FT4), and total triiodothyronine (TT3) in 12 women and 3 men with subacute thyroiditis and 2 women with painless (silent) postpartum thyroiditis. Elevated TT4, FTI, and FT4 were found in 11 of 85 patients treated with amiodarone. High TT4, but not FTI or FT4, was seen in 4 women using contraceptives, in 2 pregnant women and in 2 men with liver dysfunction. All hormones, except TSH, were elevated in a patient in whom thyrotoxicosis factitia was later proved. High FTI, TT4 or FT4 but not TT3 were detected in 11 of 20 patients treated with l-throxine after surgical thyroidectomy and in 10 of 68 treated for hypothyroidism. To avoid treating when thyroxicosis is not present and to avoid reducing or stopping vital drug treatment, familiarity with these states which alter blood hormone levels is important.

PIP: Elevation of the thyroid hormone levels might be induced by causes not reflecting overexpressivity of the gland. According to the authors' experience in Israel, mistakes have been encountered frequently in the averaging of the results, which on occasion brought about withdrawal of therapy without any justified reason, or therapy administration without need. 15 patients diagnoses with subcutaneous thyroiditis were treated with aspirin, prednisone, and propranolol, and reached normal levels of hormones in 6-8 weeks of time. In postpartum thyroiditis, normal levels of thyroid hormone were reached in 3-4 months without pharmacological intervention. Extrinsic overdose of iodine (aniodaron administration) was completed in all patients without any sign of thyroid overactivity. Alleged high levels of TT4 (total thyroxin) were diagnoses in women taking oral contraceptives and in men with cirrhotic liver disease but with normal levels of free thyroxin index and TT3. Overactivity of the thyroid gland was suspected in a patient receiving up to 100 mcg dose of eltroxin who tried to lose weight according to this method. Patients who used L-thyroxine after complete/partial thyroidectomy had high levels of TT4 but in all the TT3 and thyroid stimulating hormone levels were normal. The need for recognition of these cases is emphasized in order to avoid any over treatment which is harmful and depressive or from lowering the dose and halting the use of valuable drugs without obvious reason.

Effects of glibenclamide on serum lipids, lipoproteins, thromboxane, beta-thromboglobulin, and prostacyclin in non-insulin-dependent diabetes mellitus.

A study was conducted to determine the effects of glibenclamide on serum lipoproteins, apolipoproteins, thromboxane (TXA2), prostacyclin (PGI2), and beta-thromboglobulin (B-TGL) in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). In 20 NIDDM patients, aged 34 to 67 (mean, 53.6) years, without clinical signs of atherosclerotic disease and whose blood sugar level was over 140 mg/dl after four weeks of dietary treatment, fasting blood samples were taken before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glibenclamide treatment. Pretrial levels of total serum cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the diabetic patients did not differ from those in nondiabetic controls, whereas high-density lipoprotein cholesterol (HDL-C) levels and the percentage of TC bound to HDL (HDL-C%) were significantly lower in the patients than in controls. After combined dietary and glibenclamide treatment and the normalization of blood sugar, both HDL-C (mg/dl) levels and HDL-C% levels increased significantly. TC, TG, and LDL-C levels decreased. Levels of apolipoproteins A1 and A2 rose and apolipoprotein B fell, but differences were not significant. TXB2 and 6-keto-PGF1-alpha (the inert metabolites of TXA2 and PGI2) and B-TGL were determined by radioimmunoassay. TXB2 and B-TGL levels decreased significantly after glibenclamide administration, indicating attenuation of platelet aggregation. No changes in PGI2 were observed. The results demonstrate the favorable effect of glibenclamide on lipoproteins and apolipoproteins in NIDDM patients, especially in increasing HDL-C levels and HDL-C%, and in attenuating platelet aggregation as indicated by reduction of TXB2 and B-TGL.

Two methods for determination of renin secretion rates in rats.

1. Renin secretion rates in normal rats were determined with two different methods: (a) the product of renal plasma flow as measured by sodium p-aminohippurate and the difference between renal and peripheral vein renin activity; (b) the product of this latter difference and the renal plasma flow as calculated from the clearance and extraction of inulin. 2. The renin secretion rates, as calculated by these two methods, were not significantly different (P greater than 0-1) and were found to be highly correlated (r = 0-943; P less than 0-001).