Search Results

Abstract

Objective—To investigate the in vitro effect of the combination of lignan enterolactone (ENL) or lignan enterodiol (END) with melatonin on steroid hormone secretion and cellular aromatase content in human adrenal carcinoma cells. Sample—Human adrenocortical carcinoma cells.

Procedures—Melatonin plus ENL or END was added to cell culture medium along with cAMP (100μM); control cells received cAMP alone. Medium and cell lysates were collected after 24 and 48 hours of cultivation. Samples of medium were analyzed for progesterone, 17-hydroxyprogesterone, androstenedione, aldosterone, estradiol, and cortisol concentration by use of radioimmunoassays. Cell lysates were used for western blot analysis of aromatase content.

Results—The addition of ENL or END with melatonin to cAMP-stimulated cells (treated cells) resulted in significant decreases in estradiol, androstenedione, and cortisol concentrations at 24 and 48 hours, compared with concentrations in cells stimulated with cAMP alone (cAMP control cells). The addition of these compounds to cAMP-stimulated cells also resulted in higher progesterone and 17-hydroxyprogesterone concentrations than in cAMP control cells; aldosterone concentration was not affected by treatments. Compared with the content in cAMP control cells, aromatase content in treated cells was significantly lower.

Conclusions and Clinical Relevance—The combination of lignan and melatonin affected steroid hormone secretion by acting directly on adrenal tumor cells. Results supported the concept that this combination may yield similar effects on steroid hormone secretion by the adrenal glands in dogs with typical and atypical hyperadrenocorticism.

Abstract

Objective—To compare the effects of 2 doses of cosyntropin (5 µg/kg vs 250 µg, IV) on serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates and determine the optimal sample collection time after adrenal stimulation with cosyntropin.

Animals—10 healthy, privately owned, neutered dogs.

Procedure—Dogs were randomly assigned to initially receive cosyntropin at 5 µg/kg or as a total dose of 250 µg, IV. Dogs received the alternate dose 1 to 2 weeks later. Serum was obtained from blood samples collected before (0 minutes) and 30, 60, 90, and 120 minutes after cosyntropin administration.

Results—Maximum stimulation of cortisol, androstenedione, progesterone, and 17-hydroxyprogesterone production was achieved at 60 minutes following IV administration of cosyntropin at 5 µg/kg or as a total dose of 250 µg. Serum estradiol concentration did not increase in response to either cosyntropin dose. For all hormones, no significant difference in serum hormone concentrations was found among sample collection times of 0, 30, 60, and 90 minutes when comparing the 2 doses of cosyntropin.

Conclusions and Clinical Relevance—Cosyntropin, when administered at 5 µg/kg, IV, effectively stimulated maximum production of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates at 1 hour after administration. (Am J Vet Res 2004;65:1631–1633)

Abstract

Objective—To evaluate the clinical and endocrine responses of ferrets with adrenocortical disease (ACD) to treatment with a slow-release implant of deslorelin acetate.

Animals—15 ferrets with ACD.

Procedure—Ferrets were treated SC with a single slow-release, 3-mg implant of deslorelin acetate. Plasma estradiol, androstenedione, and 17-hydroxyprogesterone concentrations were measured before and after treatment and at relapse of clinical signs; at that time, the adrenal glands were grossly or ultrasonographically measured and affected glands that were surgically removed were examined histologically.

Results—Compared with findings before deslorelin treatment, vulvar swelling, pruritus, sexual behaviors, and aggression were significantly decreased or eliminated within 14 days of implantation; hair regrowth was evident 4 to 6 weeks after treatment. Within 1 month of treatment, plasma hormone concentrations significantly decreased and remained decreased until clinical relapse. Mean time to recurrence of clinical signs was 13.7 ± 3.5 months (range, 8.5 to 20.5 months). In 5 ferrets, large palpable tumors developed within 2 months of clinical relapse; 3 of these ferrets were euthanatized because of adrenal gland tumor metastasis to the liver or tumor necrosis.

Conclusions and Clinical Relevance—In ferrets with ACD, a slow-release deslorelin implant appears promising as a treatment to temporarily eliminate clinical signs and decrease plasma steroid hormone concentrations. Deslorelin may not decrease adrenal tumor growth in some treated ferrets. Deslorelin implants may be useful in the long-term management of hormone-induced sequelae in ferrets with ACD and in treatment of animals that are considered at surgical or anesthetic risk. (Am J Vet Res 2005;66:910–914)

Abstract

Objective—To determine the effects of leuprolide acetate, a long-acting gonadotropin-releasing hormone analog, in ferrets with adrenocortical diseases.

Design—Case series.

Animals—20 ferrets with adrenocortical disease diagnosed on the basis of clinical signs and plasma sex hormone concentrations.

Procedure—Ferrets were treated with leuprolide (100 µg, IM, once), and plasma hormone concentrations were measured before and 3 to 6 weeks after treatment.

Results—Leuprolide treatment resulted in significant reductions in plasma estradiol, 17 α-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone concentrations and eliminated or reduced clinical signs associated with adrenocortical disease. Decreases in vulvar swelling, pruritus, and undesirable sexual behaviors and aggression were evident 14 days after treatment; hair regrowth was evident by 4 weeks after treatment. The response to treatment was transitory, and clinical signs recurred in all ferrets. Mean ± SEM time to recurrence was 3.7 ± 0.4 months (range, 1.5 to 8 months).

Conclusions and Clinical Relevance—Results suggest that leuprolide can be safely used to temporarily eliminate clinical signs and reduce sex hormone concentrations in ferrets with adrenocortical diseases. However, the safety of long-term leuprolide use in ferrets has not been investigated, and the long-term effects of leuprolide in ferrets with nodular adrenal gland hyperplasia or adrenal gland tumors are unknown. (J Am Vet Med Assoc 2001;218:1272–1274)

Abstract

Objective—To evaluate adrenal sex hormone concentrations in neutered dogs with hypercortisolemia.

Design—Case series.

Animals—11 neutered dogs with hypercortisolemia.

Procedure—Serum samples obtained before and 1 hour after administration of ACTH were evaluated for concentrations of cortisol, progesterone, testosterone, dehydroepiandrosterone sulfate or androstenedione or both, and 17-hydroxyprogesterone.

Results—For all dogs, concentrations of 1 or more adrenal sex hormones were substantially greater than reference range values before or after administration of ACTH. Testosterone concentration was not greater than reference range values in any of the dogs.

Conclusions and Clinical Relevance—Results emphasize the importance of ruling out hypercortisolemia before measuring adrenal sex hormone concentrations as a means of diagnosing adrenal hyperplasia syndrome (alopecia X) in dogs. (J Am Vet Med Assoc 2001;218:214–216)

Abstract

Objective—To characterize the physiologic response to IV bolus injection of glucose and insulin for development of a combined glucose-insulin test (CGIT) in horses.

Animals—6 healthy mares and 1 mare each with pituitary adenoma and urolithiasis.

Procedure—Horses were given a CGIT (glucose, 150 mg/kg; insulin, 0.1 U/kg); results were compared with a singular IV glucose tolerance test (GTT; 150 mg/kg) and a singular IV insulin sensitivity test (IST; 0.1 U/kg). Healthy horses were also given a CGIT after receiving xylazine and undergoing stress.

Results—Physiologically, the CGIT resulted in a 2-phase curve with positive (hyperglycemic) and negative (hypoglycemic) portions; the positive phase came first (250% of baseline at 1 minute). The descending segment declined linearly to baseline by approximately 30 minutes and to a nadir at 58% of baseline by 75 minutes. After a 35-minute valley, a linear ascent to baseline began. Addition of insulin in the CGIT increased glucose utilization by approximately 4.5 times during the positive phase but not during the negative phase. The diseases' effects and experimental inhibition of insulin secretion with xylazine and stress were detectable by use of the 2 phases of the CGIT. Only a single positive phase resulted from the GTT and a single negative phase from the IST.

Conclusions and Clinical Relevance—The CGIT resulted in a consistent, well-defined glycemia profile, which can be disrupted experimentally or by a disease process. The CGIT has clinical potential because it provides integrated information and more information than either the singular GTT or IST. (Am J Vet Res 2005;66:1598–1604)

Abstract

Objective—To determine causes of hyperphosphatasemia (high serum alkaline phosphatase [ALP] activity) in apparently healthy Scottish Terriers.

Design—Prospective case-controlled study.

Animals—34 apparently healthy adult Scottish Terriers (17 with and 17 without hyperphosphatasemia).

Procedures—Serum activities for 3 isoforms (bone, liver, and corticosteroid) of ALP were measured. Concentrations of cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, estradiol, and aldosterone were measured before and after cosyntropin administration (ie, ACTH; 5 μg/kg [2.27 μg/lb], IM). Liver biopsy specimens from 16 dogs (11 with and 5 without hyperphosphatasemia) were evaluated histologically.

Results—In dogs with hyperphosphatasemia, the corticosteroid ALP isoform comprised a significantly higher percentage of total ALP activity, compared with the percentage in dogs without hyperphosphatasemia (mean ± SE, 69 ± 5.0% and 17 ± 3.8%, respectively). In 6 dogs with hyperphosphatasemia, but none without, serum cortisol concentrations exceeded reference intervals after ACTH stimulation. Six dogs with and 15 without hyperphosphatasemia had increased concentrations of ≥ 1 noncortisol steroid hormone after ACTH stimulation. Serum ALP activity was correlated with cortisol and androstenedione concentrations (r = 0.337 and 0.496, respectively) measured after ACTH stimulation. All dogs with and most without hyperphosphatasemia had abnormal hepatocellular reticulation typical of vacuolar hepatopathy. Subjectively, hepatocellular reticulation was more severe and widespread in hyperphosphatasemic dogs, compared with that in nonhyperphosphatasemic dogs.

Conclusions and Clinical Relevance—Hyperphosphatasemia in apparently healthy Scottish Terriers was most likely attributable to hyperadrenocorticism on the basis of exaggerated serum biochemical responses to ACTH administration and histologic hepatic changes, but none of the dogs had clinical signs of hyperadrenocorticism.

Abstract

Objective—To evaluate the effect of a soy-based diet on general health and adrenocortical and thyroid gland function in dogs.

Animals—20 healthy privately owned adult dogs.

Procedures—In a randomized controlled clinical trial, dogs were fed a soy-based diet with high (HID; n = 10) or low (LID; 10) isoflavones content. General health of dogs, clinicopathologic variables, and serum concentrations of adrenal gland and thyroid gland hormones were assessed before treatment was initiated and up to 1 year later. Differences between groups with respect to changes in the values of variables after treatment were assessed by means of a Student t test (2 time points) and repeated-measures ANOVA (3 time points).

Results—No differences were detected between the 2 groups with respect to body condition and results of hematologic, serum biochemical, and urine analyses. Most serum concentrations of hormones did not change significantly after treatment, nor were they affected by diet. However, the mean change in serum concentration of total thyroxine was higher in the HID group (15.7 pmol/L) than that in the LID group (–1.9 pmol/L). The mean change in estradiol concentration after ACTH stimulation at 1 year after diets began was also higher in the HID group (19.0 pg/mL) than that in the LID group (–5.6 pg/mL).

Conclusions and Clinical Relevance—Phytoestrogens may influence endocrine function in dogs. Feeding soy to dogs on a long-term basis may influence results of studies in which endocrine function is evaluated, although larger studies are needed to confirm this supposition.

Abstract

Objective—To evaluate adrenal sex hormone concentrations in response to ACTH stimulation in healthy dogs, dogs with adrenal tumors, and dogs with pituitary- dependent hyperadrenocorticism (PDH).

Design—Prospective study.

Animals—11 healthy control dogs, 9 dogs with adrenal-dependent hyperadrenocorticism (adenocarcinoma [ACA] or other tumor); 11 dogs with PDH, and 6 dogs with noncortisol-secreting adrenal tumors (ATs).

Procedure—Hyperadrenocorticism was diagnosed on the basis of clinical signs; physical examination findings; and results of ACTH stimulation test, low-dose dexamethasone suppression test, or both. Dogs with noncortisol-secreting ATs did not have hyperadrenocorticism but had ultrasonographic evidence of an AT. Concentrations of cortisol, androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone were measured before and 1 hour after IM administration of 0.25 mg of synthetic ACTH.

Results—All dogs with ACA, 10 dogs with PDH, and 4 dogs with ATs had 1 or more sex hormone concentrations greater than the reference range after ACTH stimulation. The absolute difference for progesterone, 17-hydroxyprogesterone, and testosterone concentrations (value obtained after ACTH administration minus value obtained before ACTH administration) was significantly greater for dogs with ACA, compared with the other 3 groups. The absolute difference for androstenedione was significantly greater for dogs with ACA, compared with dogs with AT and healthy control dogs.

Conclusions and Clinical Relevance—Dogs with ACA secrete increased concentrations of adrenal sex hormones, compared with dogs with PDH, noncortisol-secreting ATs, and healthy dogs. Dogs with noncortisol-secreting ATs also have increased concentrations of sex hormones. There is great interdog variability in sex hormone concentrations in dogs with ACA after stimulation with ACTH. (J Am Vet Med Assoc 2005;226:556–561)