Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve adult males with documented active Cushing's disease were studied. Mean plasma testosterone (T) was significantly decreased: 1.8 +/- 0.3 (SEM) ng/ml (N=6.8 +/- 0.5); gonadotropin measurements in 8 patients, in basal conditions and under LH-RH iv, showed a significant decrease in both FSH and LH. A further study of 11 patients in remission of Cushing's disease indicated a significant increase in plasma T and gonadotropins up to the normal range. One patient with an initial low T value had a normalized T while in remission, then a dramatic decrease when the disease relapsed. We conclude: a hypogonadotropic hypogonadism is found in male Cushing's disease; it disappears as early as hypercortisolism is suppressed. Some possible mechanisms are discussed.
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PMID:Reversible gonadotropin deficiency in male Cushing's disease. 19 24

Using a specific radioimmunoassay, serum hydrocortisone values were measured in dogs. Between 9:00 AM and 10:00 AM, the base-line hydrocortisone value for 56 clinically normal dogs ranged from 6.0 to 28.5 ng/ml, with a mean value of 17.8 +/- 1.32 ng/ml (mean +/- SEM). Marked differences due to age, sex, body weight, or breed were not observed in the hydrocortisone values. In 11 dogs with definitive hyperadrenocorticism, serum hydrocortisone values were from 32 to 148 ng/ml. In 2 dogs with hyperadrenocorticism, the values were 4.5 and 3.1 ng/ml. The estimation of serum hydrocortisone values by radioimmunoassay is simple and precise, and can be utilized to aid in the diagnosis of adrenopathy in dogs.
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PMID:Serum hydrocortisone (cortisol) values in normal and adrenopathic dogs as determined by radioimmunoassay. 62 43

A urine cortisol:creatinine (c:c) ratio, determined from a free-catch morning sample, was evaluated in each of 83 dogs as a screening test for hyper-adrenocorticism. The dogs evaluated were allotted to 3 groups, including 20 healthy dogs, 40 dogs with confirmed hyperadrenocorticism (HAC), and 23 dogs with polyuria and polydipsia not attributable to HAC (polyuria/polydipsia group; PU/PD). Overlap in the urine c:c ratios (mean +/- SEM), comparing results from the healthy dogs (5.7 x 10(-6) +/- 0.9) with those from the HAC dogs (337.7 x 10(-6) +/- 72.0) was not found. However, 11 (64%) of the 18 values from the PU/PD dogs (42.6 x 10(-6) +/- 9.4) were above the lowest ratio in the HAC group and 50% of the HAC group had a urine c:c ratio below the highest value in the PU/PD group. When the mean urine c:c ratio (+/- 2 SD) for the group of healthy dogs was used as a reference range, 100% of the HAC dogs and 18 (77%) of 23 dogs in the PU/PD group had abnormal urine c:c ratios. The sensitivity of the urine c:c ratio to discriminate dogs with HAC was 100%. The specificity of the urine c:c ratio was 22% and its diagnostic accuracy was 76%. On the basis of our findings, a urine c:c ratio within the reference range provides strong evidence to rule out HAC. However, abnormal urine c:c ratios are obtained from dogs with clinical diseases other than HAC. Therefore, measurement of a urine c:c ratio should not be used as the sole screening test to confirm a diagnosis of HAC.
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PMID:Urine cortisol:creatinine ratio as a screening test for hyperadrenocorticism in dogs. 142 51

Subjects with Cushing's disease have diminished growth hormone (GH) response to growth hormone-releasing hormone (GHRH). The aim of our study was to investigate the underlying mechanism of this diminished GH response in these patients using pyridostigmine (PD), an acetylcholinesterase inhibitor, which is reported to increase GH secretion by reducing somatostatin tone. Eight subjects with untreated Cushing's disease (caused by a pituitary adenoma) and 6 control subjects received GHRH 100 micrograms in 1 ml of saline, as intravenous bolus injection 60 min after (1) placebo (2 tablets, p.o.) or (2) PD (120 mg, p.o.). After GHRH plus placebo, the GH peak (mean +/- SEM) was significantly lower in subjects with Cushing's disease (2.4 +/- 0.5 micrograms/l) compared to control subjects (25.1 +/- 1.8 micrograms/l, p less than 0.05). After GHRH plus PD, the GH peak was significantly enhanced both in subjects with Cushing's disease (7.1 +/- 2.3 micrograms/l, p less than 0.05) and in control subjects (42.3 +/- 4.3 micrograms/l, p less than 0.05). In patients with Cushing's disease, the GH response to GHRH plus PD was lower with respect to the GH response to GHRH alone in normal subjects. We conclude that hypercortisolism may cause a decrease in central cholinergic tone which is in turn hypothesized to be responsible of an enhanced somatostatin release from the hypothalamus. However, other metabolic or central nervous system alterations may act synergistically with hypercortisolism in causing GH inhibition in patients with Cushing's disease.
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PMID:Pyridostigmine enhances even if it does not normalize the growth hormone responses to growth hormone-releasing hormone in patients with Cushing's disease. 180 75

Acute activation of the hypothalamic-pituitary axis with CRH has been reported to suppress gonadotropin secretion in women of reproductive age. In this study we specifically examined the effects of increasing doses of human CRH (hCRH) on circulating concentrations of ACTH, cortisol, and gonadotropins in five agonadal women, aged 46-65 (mean, 51.2) yr. The subjects had undergone either natural menopause or surgical removal of their ovaries at least 1 yr before study. Each woman was studied on four separate occasions and received either saline or hCRH at a dose of 0.5, 1.0, or 2.0 micrograms/kg BW through an indwelling iv catheter in a randomized, single blind fashion. During each experiment, five sequential iv injections of the same dose of hCRH or saline were administered at 90-min intervals over an 8-h period, followed by a 10-micrograms iv bolus of GnRH to test for pituitary gonadotropin responsiveness. Blood samples for measurement of LH, FSH, PRL, ACTH, and cortisol were obtained at 15-min intervals through an indwelling iv in the contralateral arm. Episodic pulses of LH secretion were analyzed using the Cluster computer program. Transverse mean LH, FSH, and PRL levels did not change with increasing hCRH doses. Mean (+/- SEM) LH pulse frequency [saline, 5.2 +/- 0.4/8 h; hCRH, (0.5 micrograms/kg), 4.8 +/- 0.2; hCRH (1 microgram/kg), 5.2 +/- 0.2; hCRH (2 micrograms/kg), 5.4 +/- 0.2] and amplitude [saline, 14.4 +/- 4.2 IU/L; hCRH (0.5 microgram/kg), 14.0 +/- 2.4; hCRH (1 microgram/kg), 15.8 +/- 2.5; hCRH (2 micrograms/kg), 17.2 +/- 2.9] did not differ among groups. Although the transverse mean levels of ACTH [saline, 8.7 +/- 0.2 pmol/L; hCRH (0.5 microgram/kg), 12.4 +/- 0.3; hCRH (1 microgram/kg), 11.5 +/- 0.4; hCRH (2 micrograms/kg), 12.8 +/- 0.4] did not change with increasing doses of hCRH, the duration of cortisol peaks after hCRH was longer and accounted for the increased transverse mean at each dose [saline, 152.8 +/- 4.1 nmol/L; hCRH (0.5 microgram/kg), 265.4 +/- 10.5; hCRH (1 microgram/kg), 329.7 +/- 14.3; hCRH (2 micrograms/kg), 348.2 +/- 12.1]. These findings suggest that ever larger doses of pulsatile hCRH continue to increase adrenal output of cortisol secondary to more sustained ACTH responses. However, hCRH-induced acute hypercortisolism does not alter gonadotropin secretion in agonadal women.
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PMID:Dose-response effects of exogenous pulsatile human corticotropin-releasing hormone on adrenocorticotropin, cortisol, and gonadotropin concentrations in agonadal women. 185 Nov 83

Erythrocyte insulin receptor binding measurements were evaluated in 8 dogs with spontaneous hyperadrenocorticism. These dogs had normal serum glucose concentration, with normal to high serum insulin concentration (range, 45 to 1,400 pmol/L; normal, 40 to 170 pmol/L). Dogs with hyperadrenocorticism had significant (P less than 0.01) decrease in mean +/- SEM percentage of maximal binding for erythrocyte insulin receptors (2.25 +/- 0.21%), compared with results in 11 clinically normal pet dogs (4.29 +/- 0.42%). The decrease in erythrocyte receptor binding was attributed to significant (P less than 0.01) decrease in high-affinity receptor sites in dogs with hyperadrenocorticism (14.5 +/- 2.8), compared with clinically normal dogs (31.2 +/- 4.3). Significant differences in receptor affinity were not apparent between the 2 groups. Percentage of maximal binding for erythrocyte insulin receptors for dogs with hyperadrenocorticism was inversely correlated with serum insulin concentration (r = -0.85, P less than 0.01). Results indicate that the observed decrease in erythrocyte insulin receptor binding could contribute to insulin resistance and hyperinsulinemia associated with hyperadrenocorticism. Alternatively, decreased binding of insulin receptors in animals with hyperadrenocorticism may result from down-regulation secondary to hyperinsulinemia itself caused by insulin resistance at a postreceptor site (decreased responsiveness).
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PMID:Erythrocyte insulin receptors in dogs with spontaneous hyperadrenocorticism. 188 96

Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usually does not produce clinical manifestations. This report describes primary cortisol resistance in a boy with isosexual precocity. A 6 7/12-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) tests. There were no features of glucocorticoid excess. Serum androstenedione and dehydroepiandrosterone concentrations were 4.7 +/- 0.3 nmol/L (mean +/- SEM of four measurements; normal less than 1.2) and 13.5 nmol/L (single measurement; normal, 1.0-2.2), respectively. The serum testosterone concentration was 0.9 nmol/L (normal, less than 0.7), and FSH and LH were normal. Serum cortisol concentrations were 1590 +/- 110 nmol/L (normal, 190-630) and 580 +/- 60 nmol/L (normal, 50-410) at 0800 and 2000 h, respectively. Serum cortisol responded normally to insulin-induced hypoglycemia. Glucocorticoids and adrenal androgens were resistant to suppression by dexamethasone. The Kd of [3H]dexamethasone binding to the glucocorticoid receptors of mononuclear leukocytes was increased (6.4 +/- 0.8 nM; mean +/- SEM of four determinations; normal, 1.4-3.4; P less than 0.001), but the binding capacity was normal. This patient with isosexual precocity has PCR, as indicated by functionally abnormal glucocorticoid receptors and hypercortisolism without other clinical or biochemical manifestations of Cushing's syndrome. Excessive adrenal stimulation by ACTH caused increased secretion of both cortisol and adrenal androgens, and the latter caused the clinical manifestations. PCR should be considered in other male children with isosexual precocity or female children with heterosexual precocity.
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PMID:Primary cortisol resistance presenting as isosexual precocity. 210 34

Thyroxine (T4), 3,5,3'-triiodothyronine (T3), and cortisol frequently are quantified in canine serum or plasma samples to aid in the diagnosis of hypothyroidism, hypoadrenocorticism, and hyperadrenocorticism. Many laboratories have established reliable references values for concentrations of these hormones in blood of clinically normal animals. However, nonpathologic factors that affect thyroidal and adrenocortical secretion may lead to misinterpretation of test results when values for individual animals are compared with reference values. The objective of the study reported here was to identify effects of age, sex, and body size (ie, breed) on serum concentrations of T3, T4, and cortisol in dogs. Blood samples were collected from 1,074 healthy dogs, and serum concentrations of the iodothyronines and cortisol were evaluated for effects of breed/size, sex, and age. Mean (+/- SEM) serum concentration of T4 was greater in small (2.45 +/- 0.06 micrograms/dl)- than in medium (1.94 +/- 0.04 micrograms/dl)- or large (2.03 +/- 0.03 micrograms/dl)-breed dogs, the same in females (2.11 +/- 0.04 micrograms/dl) and males (2.08 +/- 0.04 micrograms/dl), and greater in nursing pups (3.04 +/- 0.05 micrograms/dl) than in weanling pups (1.94 +/- 0.05 micrograms/dl), rapidly growing dogs (1.95 +/- 0.04 micrograms/dl), and young adult (1.90 +/- 0.06 micrograms/dl), middle-aged adult (1.72 +/- 0.05 micrograms/dl), or old adult (1.50 +/- 0.05 micrograms/dl) dogs. Dogs greater than 6 years old had lower mean serum T4 concentration than did dogs of all other ages, except middle-aged adults. Mean serum T3 concentration in medium-sized dogs (1.00 +/- 0.01 ng/ml) was greater than that in small (0.90 +/- 0.01 ng/ml)- and large (0.88 +/- 0.01 ng/ml)-breed dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of age, sex, and body size on serum concentrations of thyroid and adrenocortical hormones in dogs. 231 25

The effects of Ketoconazole (600 mg/day) were evaluated in 10 patients with Cushing's syndrome during a mean period of 4.5 weeks (range 1-12). The urinary free cortisol excretion (UFC) decreased by 21 +/- 15% (mean +/- SEM) (p less than 0.01) on day 1; 54 +/- 8% (p less than 0.0001) on day 2; 60 +/- 15% (p less than 0.0001) on day 3 and 87 +/- 3% (p less than 0.0001) on day 8 compared to baseline. Salivary cortisol at 0800 h decreased similarly. On day 3, 7 patients showed normal UFC values and on day 8, only 1 patient, with the ectopic ACTH syndrome, had persistent hypercortisolism. The cortisol decrease was associated with an increase in desoxycorticosterone values (p less than 0.01) and a decrease in dehydroepiandrosterone sulfate (p less than 0.001), delta 4 androstenedione (p less than 0.05) and testosterone (p less than 0.05). No significant variations were observed in ACTH, 11 desoxycortisol, aldosterone, plasma renin activity, corticosteroid-binding globulin and sex hormone-binding globulin. Side effects were few: mild clinical adrenal insufficiency (n = 5), oedema (n = 3) and reversible hepatic toxicity (n = 1). We conclude that Ketoconazole is an effective inhibitor of cortisol and androgens synthesis. It is well tolerated, rapidly effective and its efficacy persists unchanged for at least one month in all forms of Cushing's syndromes. For these reasons Ketoconazole may be a valuable drug for preoperative treatment of Cushing's syndrome.
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PMID:[Short term effects of ketoconazole in Cushing's syndrome]. 269 87

We studied the effects of glucocorticoid excess on calcium and phosphorus homeostasis in relation to vitamin D metabolites and parathyroid hormone (PTH) in seven patients with spontaneous ACTH-dependent Cushing's syndrome. Remission of hypercortisolism resulted in a significant increase in tubular reabsorption of phosphate [from 76 +/- 4% to 89 +/- 2% (mean +/- SEM); P less than 0.01] and serum phosphorus (from 3.1 +/- 0.1 to 4.2 +/- 0.2 mg/dl; P less than 0.005). Serum calcium did not change, although there was a reduction in daily urinary calcium excretion from 0.23 +/- 0.02 to 0.107 +/- 0.02 mg calcium/mg creatinine. Serum immunoreactive PTH (iPTH) levels were normal during Cushing's syndrome (34 +/- 5 microleq/ml), but fell significantly after remission to 22 +/- 2 microleq/ml (P less than 0.05). This small decrease in iPTH did not correlate with the improvement of phosphate homeostasis. Plasma 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH2)D] concentrations in Cushing's syndrome did not differ from measurements in 97 normal subjects. After treatment, 25OHD did not change, but 1,25-(OH)2D fell in each patient from a mean of 44 to 22 pg/ml (P less than 0.02). 1,25-(OH)2D was inversely correlated with serum phosphorus (r = 0.59; P less than 0.01), but did not correlate with iPTH. The known impairment of intestinal calcium absorption in Cushing's syndrome cannot be attributed to a decrease in the circulating levels of 1,25-(OH)2D. Endogenous hypercortisolism decreases tubular phosphate reabsorption and serum phosphorus, increase tubular phosphate reabsorption and serum phosphorus, increases iPTH, and results in an increase in 1,25-(OH)2D. These events may contribute to the severe loss of bone mass in such patients and may account for the calciuria and phosphaturia of Cushing's syndrome.
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PMID:Vitamin D metabolites and parathyroid hormone in Cushing's syndrome: relationship to calcium and phosphorus homeostasis. 697 49


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