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Biomedical subjects

H K Kley

Publications and source records attributed to H K Kley.

At least 37 records · Page 2Linked to original sources

[Stability of steroids in plasma over a 10-year period].

In order to examine whether plasma samples may be used for steroid analysis after long periods of storage, cortisol, testosterone, oestrone and oestradiol were remeasured in samples, which had been analysed 1.3-10.8 years earlier. The method for the measurement of these steroids was unchanged over this period. The results demonstrate that at a temperature of -25 degrees C steroids remained stable. Only cortisol and testosterone concentrations showed a small, insignificant decrease (6-9%) after 3 to 4 years of storage. These differences are well within the range of the precision of the method (interassay variation), which over a period of 11 years was 9.4%, 8.0%, 10.0% and 9.5% for cortisol, testosterone, oestrone and oestradiol, respectively. It is concluded that steroid hormones in human plasma are stable in our laboratory, and that they might be analysed even after more than 10 years of storage at -25 degrees C.

Blood Preservation↗

[No effect of digitalis on sex and adrenal hormones in healthy subjects and in patients with congestive heart failure].

Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7 +/- 7.7 vs 35.4 +/- 3.2 pg/ml) nor estradiol (35.8 +/- 6.4 vs 32.2 +/- 3.9 pg/ml) nor testosterone (6.32 +/- 0.74 vs 6.45 +/- 0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55 +/0- 0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147 +/- 24 vs 142 +/- 19 pg/ml) and free estradiol (657 +/- 77 vs 615 +/- 78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128 +/- 18 to 389 +/- 18 ng/ml) and testosterone (from 5.96 +/- 0.90 to 10.33 +/- 1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150-210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took beta-methyldigoxin (n = 8), beta-acetyldigoxin (n = 20) and digitoxin (n = 7) from 1 to 9 (mean: 1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

The measurement of 4-androstene-3, 11, 17-trione (11-oxo-androstenedione) by radioimmunoassay in human plasma.

A radioimmunoassay (RIA) method is described for the determination of 4-androstene-3, 11, 17-trione (11-oxo-androstenedione) in human plasma. 4-androstene-3, 11, 17-trione 3-(0-carboxymethyl) oxime-bovine serum albumin conjugate was used to generate highly specific antiserum in rabbits. Cross reactivities of several other steroids with the antiserum were less than 4%. [1,2-3H] 4-androstene-3, 11, 17-trione was synthesized from [1,2-3H] 17 alpha, 21-dihydroxy-4-pregnene-3, 11, 20-trione. The intra- and interassay variation was 7.3% and 9.8%, respectively. The mean serum 4-androstene-3, 11, 17-trione level for healthy young subjects was 2.37 +/- 0.56 nM (X +/- SD) in males and 3.16 +/- 0.43 nM in females at 8 a.m. During the night, there was a marked decrease in serum level, giving at 11 p.m. 0.87 +/- 0.33 and 1.15 +/- 0.52 nM, respectively. During ACTH stimulation tests, 4-androstene-3, 11, 17-trione increased from 1.81 +/- 0.58 to 2.32 +/- 0.69 nM, while in dexamethasone suppression tests a decrease from 3.20 +/- 0.03 nM was seen. In contrast, HCG administration on 3 consecutive days did not influence plasma concentrations of 4-androstene-3, 11, 17-trione.

Adrenal Glands↗

The measurement of androst-4-en-17 beta-ol-3,11-dione (11-oxotestosterone) by radioimmunoassay in human plasma.

A radioimmunoassay was established for the measurement of androst-4-en-17 beta-ol-3,11-dione (11-oxotestosterone). Highly specific antiserum was raised in rabbits using androst-4-en-17 beta-ol-3,11-dione-3-bovine serum albumin conjugate as antigen. Cross reactivity with all steroids measured was less than 4%. [1,2-3H2]androst-4-en-17 beta-ol-3,11-dione was synthesized from [1,2-3H2]pregn-4-ene-17 alpha, 21-diol-3,11,20-trione in a two step reaction with [1,2-3H2]androst-4-ene-3,11,17-trione as intermediate. Purification of plasma androst-4-en-17 beta-ol-3,11-dione was performed by thin-layer chromatography. The intra- and interassay variation was 7.6% and 8.9%, respectively. Furthermore, the radioimmunological procedure was checked against the measurement of androst-4-en-17 beta-ol-3,11-dione in human plasma by gas chromatography/mass spectrometry. Mean plasma levels of androst-4-en-17 beta-ol-3,11-dione at 8 a.m. in healthy young subjects were 2.04 +/- 0.63 nmol/l (means +/- SD) in males and 2.18 +/- 0.89 nmol/l in females. In both groups there was a marked decrease during the night (p less than 0.01), becoming 0.96 +/- 0.33 and 0.96 +/- 0.40 nmol/l, respectively, at 11 p.m. Administration of human chorionic gonadotropin on 3 consecutive days did not influence the plasma concentrations of androst-4-en-17 beta-ol-3,11-dione, whereas both corticotropin (from 2.35 +/- 1.12 to 1.65 +/- 0.76 nmol/l; p less than 0.02) and dexamethasone (from 2.40 +/- 1.75 to 0.40 +/- 0.16 nmol/l; p less than 0.01) caused a significant decrease of androst-4-en-17 beta-ol-3,11-dione.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

[The effect of storage and temperature on the analysis of steroids in plasma and blood].

In the analysis of steroid hormones careful attention is usually paid to blood collection and plasma storage. However, the appropriate care of samples cannot always be assured in routine work with steroids. Therefore, the stability of cortisol, aldosterone, 17-hydroxyprogesterone, testosterone, androstenedione, dehydroepiandrosteronesulphate, oestrone, oestradiol, sex hormone binding globulin (SHBG) and, the binding of testosterone and cortisol to plasma proteins in blood and plasma were studied before and after various handling procedures. Ten cycles of alternate freezing and thawing of plasma did not significantly affect the levels of the steroids or their plasma binding. The greatest differences, compared with controls, were seen for aldosterone (-6.2%) and oestradiol (-5.3%). Plasma storage at -28 degrees C was hardly superior to a 4 days storage at 4 degrees C (refrigerator) or 22 degrees C (room temperature). Although androstenedione (-10.9%), oestrone (-10.2%) and oestradiol (-12.2%) levels decreased by more than 10%, the means of all analyses were still in the 2 SD range. Even SHBG and the steroid binding were only slightly affected by temperature. When whole blood was stored at 4 degrees C or 22 degrees C, the resulting values differed from those obtained with plasma, but the differences were usually less than 10%. Although the levels were within the 2 SD range, whole blood showed a decrease of 12.3% for aldosterone and 14.5% for androstenedione. In contrast, plasma binding of testosterone (25.9%) and cortisol (15.1%) were substantially affected by storage at 22 degrees C in whole blood. It is concluded that repeated freezing and thawing of plasma, or storage at various temperatures have only a small effect on the measured levels of steroids and their plasma binding. Although it is not advisable, even whole blood may be used for the analysis of steroid concentrations.

Blood Proteins↗

Cortisol excretion into gastric juice. Studies in health, in digestive ulcer disease, and in surgery stress.

Gastric juice cortisol concentrations in 36 healthy subjects in the basal state was 10.5 +/- 2.1 ng/ml. After stimulation with pentagastrin it was 11.5 +/- 3.2 ng/ml. There were no differences related to age or sex. Cortisol outputs were 25.9 +/- 12.1 ng/min in the basal state and 35.9 +/- 13.2 during pentagastrin stimulation. After stimulation with ACTH in 6 subjects gastric juice cortisol concentration increased 5.4 times while gastric cortisol output increased 19-fold. The plasma cortisol rose by a factor of 2.3 while the plasma free cortisol rose by a factor of 2.6. Gastric juice cortisol concentration increases correlated with concentrations of free and total plasma cortisol in plasma. When plasma levels of cortisol or dexamethasone were raised by intravenous infusions, the concentration in gastric juice depended on the free corticoid concentration in plasma. Gastric juice cortisol concentrations in 38 patients with gastric, duodenal, or combined gastric and duodenal ulcers were the same as in normal subjects. In 6 patients studied up to 6 days following abdominal surgery, both plasma and gastric cortisol concentrations were elevated but the increase in gastric juice cortisol was proportionally greater. This was not due to vagal stimulation, as shown by the failure of gastric juice cortisol concentrations to rise similarly during insulin hypoglycemia. Postsurgical increases in gastric juice cortisol may reflect the loss of protein-bound cortisol into the gastrointestinal tract as a result of injury to the gastric mucosa.

Adrenal Glands↗

Digoxin does not alter plasma steroid levels in health men.

Digoxin has been reported to induce feminizing effects in man. It does not compete for estradiol cytosol receptors in human breast carcinoma cells, however, and has no uterotrophic effect. We therefore investigated whether feminization might be due to digoxin action on plasma concentrations of sex steroids. Six healthy men (31.5 +/- 4 yr old) received therapeutic doses of digoxin for 43 days. We measured plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estrone, estradiol, progesterone, 17-hydroxyprogesterone, cortisol, and aldosterone. During 35 days on digoxin levels of these steroids remained in the normal range and there was no change from before-drug values. Digoxin was in the therapeutic range of 1.9 +/- 3 nmol/l throughout. After stimulation by adrenocorticotropic hormone or human choriongonadotropin, the rise in plasma steroids was in the same range as when digoxin was given, as well as 16 wk after it had been discontinued. A normal rise in luteinizing hormone after luteinizing hormone-releasing hormone showed that the hypothalamogonadal feedback was not altered by digoxin. Free testosterone, estradiol, and cortisol concentrations under basal conditions and after stimulation were also the same before and after drug. It is concluded that the estrogen-like activity of digoxin cannot be explained by altered steroid availability from plasma. Feminizing effects attributed to digoxin may be caused by other conditions known to influence sex steroid hormones that are common in patients with heart disease. Our data suggest that digoxin may be the preferred digitalis therapy to avoid feminizing effects.

Adrenal Cortex Hormones↗

Evidence for hypogonadism in massively obese males due to decreased free testosterone.

In obese male subjects with 160 - 200% of ideal body weight (IBW = 100%) the decrease in total plasma testosterone is biologically ineffective since SHBG is concomitantly decreased from 30.0 +/- 3.6 to 20.0 +/- 3.4 nM/l. Conversely, in massively obese males with greater than 250% of IBW, the decrease in SHBG (to 10.6 +/- 1.8 nM/l) is too small to compensate for total testosterone decrease (from 6.04 +/- 0.57 to 1.72 +/- 0.32 ng/Ml). Therefore, free testosterone is markedly less in the massively obese patients (55 +/- 8 vs. 127 +/- 15 pg/ml in the controls). Despite this significant difference in free testosterone concentrations (p less than 0.01), plasma LH is even lower in the obese (6.8 +/- 0.8 mU/ml) than in the controls (10.0 +/- 1.0 mU/ml). This may be an effect of free estradiol, which rises from 0.48 to 1.52 pg/ml in the massively obese subjects. These alterations are clearly demonstrated by the imbalance of the estradiol/testosterone ratios, which increase 10-fold and 7-fold for the total and for the free sex hormones, respectively. We conclude that the decrease in SHBG, which prevents obese males from developing hypogonadism, is not sufficiently effective in the massively obese patients to compensate the marked decrease in testosterone. This, in connection with the observed increase of free estradiol, may cause hypogonadism and hyperestrogenism in these subjects.

Adult↗

[Glucagon, growth hormone, and cortisol response to insulin-induced hypoglycemia in insulin-dependent diabetics (IDD) without autonomic neuropathy (author's transl)].

Insulin-induced hypoglycemias are a sign of non-sufficient counterregulation, in which different contra-insulinary hormones participate. The aim of the study was to investigate, whether there exists a difference between IDD and non-diabetics regarding secretion of glucagon, cortisol, and growth hormone during an insulin-induced hypoglycemia and further on pointing out, expecially, the importance of glucagon. Insulin-induced hypoglycemias are counterregulated in non-diabetics, not in IDD. The missing glucagon secretion during insulin-induced hypoglycemia in IDD seems to be independent from an autonomic neuropathy. Only after high doses of exogenous glucagon can one see a counterregulating increase of glucose. The STH secretion is similar in non-diabetics and IDD during an insulin-induced hypoglycemia and has evidently only a secondary effect in hypoglycemic counterregulation. The STH secretion may be the expression of a diencephal-triggered stress situation. The cortisol secretion is the same in both groups. The gluconeogenetic effect of cortisol is not sufficient to accomplish a fast compensation of hypoglycemia. This does not exclude long-term effects. When inhibiting the secretion of insulin and different contra-insulinary hormones with somatostatin, one is able to demonstrate that glucagon alone is a sufficiently counterregulatory hormone in insulin-induced hypoglycemias.

Adult↗

Relationship of plasma sex hormones to different parameters of obesity in male subjects.

Relationships between plasma sex hormones and different parameters of obesity (weight, ideal body weight [IBW], overweight, fat mass, and body surface) were investigated in 70 healthy nonobese and obese males, 20-40 yr of age and with a body weight of 85%-245% of IBW. Plasma sex hormones remained unaffected by weight up to approximately 160% of the IBW. Only in the massively obese subjects was plasma testosterone decreased to 40% of controls (from 6.2 to 2.5 ng/ml), whereas free testosterone remained almost constant. On the other hand, plasma estrone and estradiol exhibited significant increases in obese subjects, ranging from 31.5 +/- 52.3 +/- 5.8 pg/ml for estrone, and 25.4 +/- 5.4 increasing to 44.7 +/0 5.0 pg/ml for estradiol. Similarly, free estradiol was shown to significantly increase with obesity in men from 505 +/- 118 to 991 +/- 123 fg/ml (p < 0.001). The ratios of testosterone/androstenedione, as well as of estradiol/estrone, were not affected by obesity, suggesting that reduction of the 17-oxo-group of the steroids is not influenced by the amount of fat tissue. A significant (p < 0.001) correlation was found between IBW and estrone (r = 0.80) and estradiol (r = 0.75), as well as the ratios of estrone/androstenedione (r = 0.62) and estradiol/testosterone (r = 0.86). This is consistent in its evidence indicating that fat tissue may be able to aromatize androgens. In the obese subjects, there were significant correlations between plasma sex hormones (testosterone, estrone, estradiol, and free estradiol) and the parameters of obesity used. Among these, correlations were best with IBW, overweight, and fat mass (r = 0.74-0.89; p < 0.001); body weight and body surface were less favorable.

Adult↗

Enhanced conversion of androstenedione to estrogens in obese males.

In normal and obese young males [90--120% and > 160% of ideal body weight (IBW); IBW = 100%], plasma concentrations of testosterone, androstenedione, estrone, and estradiol were measured. Metabolic clearance and production rates of androstenedione and the conversion ratios of androstenedione to testosterone, estrone, and estradiol were determined using the constant infusion technique. In the obese subjects, IBW was inversely correlated (P < 0.001) with plasma concentrations of androstenedione (r = 0.81) and testosterone (r = 0.87), while the levels of estrone (r = 0.92) and estradiol (r = 0.95) increased with IBW (P < 0.001). Thus, when normal and obese subjects were compared as groups, plasma androstenedione decreased form 1.24 +/- 0.13 to 0.93 +/- 0.15 ng/ml (mean +/- SD) and plasma testosterone decreased from 5.89 +/- 0.82 to 3.29 +/- 0.92 ng/ml (P < 0.001), while estrone increased from 28.2 +/- 3.4 to 60.0 +/- 9.4 pg/ml, and estradiol increased from 21.7 +/- 3.5 to 43.9 +/- 5.3 pg/ml. The testosterone to androstenedione and the estradiol to estrone ratios were not different in obesity, but changes in IBW were positively correlated (P < 0.001) with differences in the estrone to androstenedione (r = 0.93) and estradiol to testosterone ratios (r = 0.93), indicating that fat tissue may aromatize androgens, whereas reduction of 17-oxo-steroid appears to be of minor importance. As the MCR of androstenedione increased with IBW (from 2156 to 2636 liters/day P < 0.05) while plasma levels decreased, the apparent production rate of androstenedione was not influenced by the degree of obesity. The conversion of androstenedione to estrone (r = 0.89) and of androstenedione to estradiol (r = 0.82) was enhanced in obese subjects (P < 0.001). We suggest that enhanced aromatization of androstenedione due to an increased adipose tissue mass may account for the high plasma estrogen levels observed in obese men.

Adult↗

Studies of heart rate oscillations in diabetics at rest.

Variation in electrocardiographic R-R intervals during rest was investigated as a measure of autonomic function and as a diagnostic tool in diabetes. Diabetics (106) of both sexes with different duration of the disease were compared with 116 metabolically healthy control subjects of the same age range. Diabetic retinopathy was diagnosed using fundus photography, and classified in stages O-II. Coefficient of variation (CV) of R-R intervals in controls is age-dependent. The negative correlation between CV and age in diabetics applied only when retinopathy was absent; in diabetics with late complications, CV was significantly lower (p less than 0.0001) than in the healthy or in uncomplicated diabetic state. The CV decreased with increasing severity of retinopathy permitting routine differentiation of progressive stages of retinopathy and peripheral neuropathy.

Adolescent↗

[Total and free testosterone in the male depending on body weight (author's transl)].

Total testosterone, the fraction of unbound testosterone and free testosterone were measured in 116 males of varying body weight in the range of 80 to 256% of the ideal weight. There are 3 groups for the establishment of normal ranges of testosterone. Testosterone and the fraction of unbound testosterone were fairly constant in group I (80--160% of the ideal weight). In group II (160--200% of ideal weight) there was a tendency towards lower values. The relatively wide normal range for testosterone was not reached in only 5 of these 20 patients. In contrast, in group III (more than 200% of ideal weight) clear-cut changes of total testosterone were demonstable reaching only 38% (P less than 0.001) of control values. Changes were also clear for unbound testosterone which increased from 2.24 to 3.9% (P less than 0.001). The concentration of free testosterone decreased to a lesser extent (P less than 0.01). Despite the low total testosterone hypogaonadism was not demonstable clinically in the extremely obsese patients. According to these results "normal values" for total testosterone, the fraction of unbound testosterone and free testosterone could be established depending on body weight.

Adult↗