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Biomedical subjects

A W Meikle

Publications and source records attributed to A W Meikle.

At least 73 records · Page 4Linked to original sources
PubMed1985

Factitious Cushing's syndrome.

A woman with pituitary-dependent Cushing's disease remained hypercortisolemic after bilateral adrenalectomy. A search for an adrenal remnant by venous catheterization study suggested persistent cortisol-secreting tissue in the left adrenal bed. During ACTH stimulation, plasma corticosterone concentrations remained low and cortisol remained high, suggesting the cortisol was of exogenous origin. Cushingoid features resolved after confronting the patient with this evidence. Plasma corticosterone concentrations played a novel role in the diagnosis of factitiously induced Cushing's syndrome in this patient.

Adrenocorticotropic Hormone↗
PubMed1984

Increased levels of nuclear androgen receptors in hyperplastic prostate of aging men.

Several publications indicate the dihydrotestosterone content of hyperplastic prostatic tissue from man and dog is increased. There is limited information concerning an abnormality in the androgen receptor content in this disorder. In men, we determined the androgen receptor concentration in cytosol, nuclei, the nuclear matrix, and nuclease solubilized salt extract fractions from benign prostatic hyperplasia (BPH) and normal prostate. Nine BPH cases (age 61 +/- 7, mean +/- SD) and seven controls (age 29 +/- 10.6) were compared. Prostates were obtained during autopsy performed within 12 h after death and frozen at -70 degrees C until analysis. Four grams of tissue were homogenized and centrifuged for separation of nuclei and cytosol. Androgen receptors were estimated with an improved assay procedure. The androgen receptor content per mg of DNA in whole nuclei and in the salt extract fraction (P less than 0.01 and less than 0.05 respectively) was higher in BPH cases than in controls. Cytosol did not show a significant difference. For both groups, receptors were undetectable in the nuclear matrix. We speculate that increased androgen receptor bound to chromatin of hyperplastic tissue may be causally related to the development of BPH in aging man.

Adult↗
PubMed1984

Hypogonadism in hemochromatosis: reversal with iron depletion.

Gonadal function was evaluated in 64 persons homozygous for the HLA-linked hemochromatosis allele. Of 41 men, 10 had reduced libido or impotence and 6 had testicular atrophy. Before treatment, 5 men had below normal testosterone concentrations, 4 of whom also had low gonadotrophin levels. Four hypogonadal men were reevaluated after iron depletion treatment. In 2, 1 with primary and another with secondary hypogonadism, testosterone levels returned to normal after phlebotomy and were accompanied by a return of normal sexual function. None of 23 women with hemochromatosis had loss of libido or had a natural menopause before age 45. Our findings indicate that in some men with hereditary hemochromatosis and hypogonadism of either testicular or central origin, sexual function and sex hormone concentrations can be restored to normal after iron depletion therapy.

Adolescent↗
PubMed1984

Cushing's disease with 'normal suppression' due to decreased dexamethasone clearance.

Suppression of urinary corticosteroids during low-dose dexamethasone testing (0.5 mg every six hours eight times) has commonly been recognized as a response that excludes the diagnosis of Cushing's syndrome. Although "normal suppression" has been reported previously in Cushing's disease, rarely has an explanation been provided for this aberrant response. We report a case of proven Cushing's disease in which normal suppression was observed with low-dose dexamethasone testing. Further study suggested that this phenomenon, which is not widely recognized, was related to an abnormally decreased clearance of dexamethasone. We therefore suggest that whenever responses to testing appear discordant with the clinical index of suspicion, simultaneous plasma dexamethasone and cortisol levels should be obtained to exclude abnormalities in dexamethasone clearance.

Adrenocorticotropic Hormone↗
PubMed1984

Adrenal corticoid hyperresponsiveness in hirsute women.

Data are limited on the existence of adrenal hyperplasia or cortisol oversecretion in women with hirsutism. Supranormal responses of cortisol (greater than 20 micrograms/dl) were observed at 15 and 30 minutes after the 8:00 A.M. adrenocorticotropin (0.5 U) injection (performed after 1 mg of dexamethasone taken orally at midnight) in 6 of the 12 hirsute women (hirsute I) and in all 4 women with Cushing's disease. Baseline plasma levels of corticoids, androgens, and gonadotropins, body weight, menstrual history, and degree of hirsutism were all indistinguishable between the two hirsute groups. The mean plasma levels of cortisol and 17-hydroxyprogesterone were both significantly greater in the hirsute I group and in those with adrenal hyperplasia caused by Cushing's disease than in normal subjects. Our data indicate that adrenal hyperplasia is a common abnormality in women with hirsutism. We speculate that this abnormality may contribute to the pathogenesis of hirsutism and ovarian dysfunction in many hirsute women.

Adolescent↗
PubMed1982

Dexamethasone suppression tests: usefulness of simultaneous measurement of plasma cortisol and dexamethasone.

The effect of oral dexamethasone on the plasma content of cortisol and dexamethasone was investigated in 175 patients suspected of having Cushing's syndrome. Plasma concentrations of cortisol and dexamethasone were measured by specific radioimmunoassays at 08.00 h following administration of either a low-low (0.5 mg), low (1.0 mg), high (4.0 mg) or high-high (8.0 or more mg) dose of dexamethasone at midnight. All seventeen patients with documented Cushing's syndrome exhibited resistance to the action of low-low and/or low dose dexamethasone on suppression of 08.00 h plasma cortisol content. Nine of twelve patients with pituitary dependent Cushing's syndrome had plasma cortisol values of less than 166 nmol/l following high-high dose testing. In 157 patients with suspected Cushing's syndrome, standard dexamethasone testing was considered unsatisfactory in at least 20%. After low-low or low dose tests 11% had supranormal cortisol values, but plasma cortisol content overlapped with values observed in patients with Cushing's syndrome only when plasma dexamethasone content was less than 5.6 nmol/l. Twelve per cent of patients suspected of having Cushing's syndrome had sufficient elevation of plasma dexamethasone values after low dose testing so that marked reduction of plasma cortisol might be expected even in patients with pituitary dependent Cushing's syndrome. Four patients receiving anticonvulsants had subnormal plasma levels of dexamethasone for the dose administered, but all exhibited normal suppression when plasma levels of dexamethasone and cortisol were correlated simultaneously. In summary, there is considerable variation in the plasma content of dexamethasone following oral doses. Simultaneous measurement of both plasma levels of dexamethasone and cortisol has proved most useful in identifying patients with unsatisfactory dexamethasone suppression tests.

Adolescent↗
PubMed1982

Familial prostatic cancer risk and low testosterone.

We investigated whether familial factors influence 1) the incidence of prostatic cancer and 2) the plasma content of sex steroids. A 4-fold higher relative risk for the development of prostatic cancer was observed for brothers (n = 257) of prostatic cancer cases (n = 150) compared to their brothers-in-law (n = 202) and males in the general population of the state Utah. The intraclass correlation for plasma testosterone content [intraclass correlation coefficient (r1) = 0.51; P less than 0.01] and the apparent free testosterone concentration (r1 = 0.54; P less than 0.01) were highly significant in nonendocrinologically treated cases and their brothers. Further, sons and their fathers had significant intraclass correlations for both plasma dihydrotesterone (r1 = 0.83; P less than 0.01) and the ratio of testosterone to dihydrotestosterone (r1 = 0.46; P less than 0.05). Probands and their brothers, and sons of the patients with the disease had significantly lower plasma testosterone levels than controls of comparable age. This is the first documentation indicating that familial (possibly genetic) factors are potent risk factors for predisposing men to the development of prostatic cancer and in regulating the plasma content of androgens. Our results indicate that plasma androgen levels in families with prostatic cancer are clustered in the lower range of the normal population. They also suggest that plasma androgen content is more similar within each family with the cancer than among the families without cancer.

Dihydrotestosterone↗
PubMed1982

Familial effects on plasma sex-steroid content in man: testosterone, estradiol and Sex-hormone-binding globulin.

We investigated whether familial factors influence the plasma content of sex-steroids and sex-hormone-binding globulin (SHBG) in 98 adult males of 66 families. They had no apparent endocrine dysfunction, The 0800-1100 hr plasma levels of testosterone, 5 alpha-dihydrotestosterone (DHT), estradiol-17 beta (E2) and estrone (E1) were measured by radioimmunoassay. The free fractions of E2 and testosterone were determined by equilibrium dialysis, and binding capacity of SHBG was also calculated. The data were analyzed by analysis of variance. We observed that the differences in the plasma content of testosterone (p = .02). SHBG binding capacity (p = 0.1), and E2 (p = 0.3), free E2 index (p = .05) were all substantially less variable within groups of brothers than among non-brothers. The variability of the plasma concentration of DHT, free testosterone and E1 was not significantly less within brothers than among non-brothers. The correlation between either plasma testosterone content (r = .14) or SHBG binding capacity (r = .12) and percent of ideal body weight was not significant statistically. Age had no effect on the results. Our data suggest that genetic and/or environmental factors may affect the plasma content of testosterone, E2 and SHBG binding capacity.

Adult↗
PubMed1981

Effect of smoking on prednisone, prednisolone, and dexamethasone pharmacokinetics.

The pharmacokinetics of oral prednisone and oral dexamethasone were examined in 18 healthy male adults. Eight subjects also received intravenous prednisolone and intravenous dexamethasone. Half of each group were cigarette smokers as confirmed by plasma thiocyanate concentrations. Plasma and urine concentrations of prednisone and prednisolone were assayed by high performance liquid chromatography, while plasma dexamethasone was measured by radioimmunoassay. There were no statistically significant differences between smokers and nonsmokers in the systemic availability of prednisolone (75 versus 84%), oral dose clearance of prednisone (29 verus 27 ml/min/kg), systemic prednisolone clearance (2.8 versus 2.9 ml/min/kg), or in the interconversion rates, volumes of distribution, or urinary recoveries of prednisone and prednisolone. Similarly, the pharmacokinetics of dexamethasone were unaffected by smoking. A limited correlation (r = 0.55) was found between the high oral dose clearances of prednisone and the lower values of dexamethasone (6.73 and 5.71 ml/min/kg in smokers and nonsmokers). A two- to threefold variability occurred in oral dose clearances of each steroid with partial intrasubject covariance. Unlike the anticonvulsants, which markedly induce corticosteroid metabolism, smoking has no effect on their pharmacokinetics and should not complicate therapy with these drugs.

Adult↗
PubMed1980

Acute and chronic methyl mercury poisoning impairs rat adrenal and testicular function.

Animals poisoned with methyl mercury (CH3Hg) exhibit stress intolerance and decreased sexual activity, which suggest both adrenal and testicular dysfunction. Adrenal and testicular function was studied in male rats after treatment with CH3Hg. In animals treated chronically, the adrenal glands were markedly hyperplastic with enlargement of the zona fasiculata. The mean basal serum levels of corticosterone were similar in experimental (17.8 micrograms/dl) and control (16.8 micrograms/dl) groups. However, with ether stress, experimental animals had a subnormal response, and the mean serum levels of corticosterone increased to only 23.9 micrograms/dl compared to 40.6 micrograms/dl in the controls. Exogenous ACTH stimulation produced a mean level of 19.0 micrograms/dl in the CH3Hg-treated animals and 49.7 micrograms/dl in the controls. In vitro studies demonstrated a defect in the conversion of cholesterol to pregnenolone. A profound impairment in swimming was partially reversed with glucocorticoid therapy. In animals treated with CH3Hg, serum testosterone was lower than normal in the basal state. Human chorionic gonadotropin stimulation increased the mean serum concentration of testosterone to 23.4 ng/ml in controls, but it was only 4.50 ng/ml in experimental animals. The data indicate that CH3Hg poisoning impairs adrenal and testicular steroid hormone secretion, which accounts in part for the diminished stress tolerance and decreased sexual activity observed in CH3Hg-intoxicated animals.

Adrenal Glands↗
PubMed1980

Supranormal nuclear content of 5 alpha-dihydrotestosterone in benign hyperplastic prostate of humans.

We investigated the concentration of nuclear and cytosolic 5 alpha-dihydrotestosterone and 3 alpha-androstanediol in benign prostatic hyperplasia (BPH) in men. The endogenous content of the androgens was quantitated by radioimmunoassay after isolation of the nuclear and cytosolic fractions by classical differential centrifugation techniques. The mean dihydrotestosterone content was about four-fold higher (P < .01) than normal in the nuclear fraction and two-fold higher (P = .05) in the cytosolic fraction in periurethral tissue from hyperplastic prostates. The mean 3 alpha-androstanediol values were approximately one-third of normal in both the nuclear (P < .01) and cytosolic (P < .01) fractions in glands with BPH. In BPH tissue the ratios of dihydrotestosterone to androstanediol content in both the nuclear and cytosolic fractions was significantly higher (P < .01) than the ratio in normal prostate. Our data suggest that elevated intranuclear dihydrotestosterone but not 3 alpha-androstanediol may be causally related to the development of BPH in aging men.

Aged↗