cosyntropin and Adrenocortical-Hyperfunction

The rapid cosyntropin stimulation test offers a simple means for detecting adrenal insufficiency. In contrast, assessment of suspected hypercortisolism (Cushing's syndrome) is difficult because cortisol levels fluctuate with intermittent release of corticotropin from the pituitary or from tumors. Also, a number of medications affect cortisol levels, leading to false-positive or false-negative results. The classic low-dose followed by high-dose dexamethasone test is cumbersome, and other, simpler studies, such as the overnight high-dose dexamethasone suppression test, may prove more practical and cost-effective. With both high and low levels of adrenal glucocorticoids, awareness and early recognition of the symptoms are important. An endocrinologist should be consulted when the overnight dexamethasone suppression test or the 24-hour urine cortisol collection is abnormal or if clinical suspicion is high despite normal results on screening tests.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Cosyntropin; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Patient Care Team

Lowering the cosyntropin dose needed for ACTH stimulation would make the test more economical.. To compare the cortisol response to 1 and 5 μg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism (HAC) and in dogs receiving trilostane or mitotane for pituitary-dependent HAC.. Healthy dogs (n = 10); client-owned dogs suspected of having HAC (n = 39) or being treated for pituitary-dependent HAC with mitotane (n = 12) or trilostane (n = 15).. In this prospective study, healthy dogs had consecutive ACTH stimulation tests to ensure 2 tests could be performed in sequence. For the first test, cosyntropin (1 μg/kg IV) was administered; the second test was initiated 4 hours after the start of the first (5 μg/kg cosyntropin IV). Dogs suspected of having HAC or being treated with mitotane were tested as the healthy dogs. Dogs receiving trilostane treatment were tested on consecutive days at the same time post pill using the low dose on day 1.. In dogs being treated with mitotane or trilostane, the 2 doses were pharmacodynamically equivalent (90% confidence interval, 85.1-108.2%; P = 0.014). However, in dogs suspected of having HAC, the doses were not pharmacodynamically equivalent (90% confidence interval, 73.2-92.8%; P = 0.37); furthermore, in 23% of the dogs, clinical interpretation of test results was different between the doses.. For dogs suspected of having HAC, 5 μg/kg cosyntropin IV is still recommended for ACTH stimulation testing. For dogs receiving mitotane or trilostane treatment, a dose of 1 μg/kg cosyntropin IV can be used.

Topics: Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Antineoplastic Agents; Case-Control Studies; Cosyntropin; Dihydrotestosterone; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Hormones; Hydrocortisone; Male; Mitotane

Increased peripheral metabolism of cortisol may explain compensatory ACTH-dependent adrenal steroidogenesis and hence hyperandrogenism in polycystic ovary syndrome (PCOS). Previous studies have described an increased 5alpha-reduction of cortisol or impaired regeneration of cortisol by 11beta-HSD1 in PCOS. However, these observations may be confounded by obesity. Moreover, the relationship between alterations in cortisol metabolism and the extent of adrenal androgen hyper-secretion in response to ACTH has not been established. This study aimed to examine the association between cortisol metabolism and ACTH-dependent adrenal hyperandrogenism in PCOS, independently of obesity.. We compared 90 PCOS women (age 18-45 yr) stratified by adrenal androgen responses to ACTH1-24 and 45 controls matched for age and body weight.. PCOS women were stratified as normal responders (NR), intermediate responders (IR), and high responders (HR) to 250 microg ACTH1-24: NR (no.=27) had androstenedione and DHEA responses within 2 SD of the mean in controls; IR (no.=43) had DHEA responses >2 SD above controls; HR (no.=20) had both androstenedione and DHEA responses >2 SD above controls.. All groups were similar for age, body weight, and body fat distribution. Basal testosterone, androstenedione, and 5alpha-dihydrotestosterone plasma levels were similarly elevated among the 3 groups of PCOS compared with controls, whereas basal DHEA-S was higher in HR (2.8+/-1.2 microg/ml) and IR (2.4+/-1.1 microg/ml) than in NR (1.8+/-0.8 microg/ml) and controls (1.7+/-0.6 microg/ml). The HR group had the lowest basal plasma cortisol levels (101+/-36 ng/ml vs IR 135+/-42 ng/ml, NR 144+/-48 ng/ml, and controls 165+/-48 ng/ml; all p<0.01), but the greatest cortisol response to ACTH1-24 (Delta(60-0)cortisol 173+/-60 ng/ml vs IR 136+/-51 ng/ml, NR 114+/-50 ng/ml, and controls 127+/-50 ng/ml; all p<0.01), and the highest urinary excretion of total and 5beta-reduced cortisol metabolites (eg 5beta-tetrahydrocortisol/ cortisol ratio 25.2+/-15.3 vs IR 18.8+/-10.7, NR 19.7+/-11.4, and controls 17.2+/-13.7; all p<0.05). There were no differences in urinary excretion of 5alpha-reduced cortisol metabolites or in 5alpha-dihydrotestosterone/testosterone ratio between groups.. Adrenal androgen excess in PCOS is associated with increased inactivation of cortisol by 5beta-reductase that may lower cortisol blood levels and stimulate ACTH-dependent steroidogenesis.

Topics: Adolescent; Adrenocortical Hyperfunction; Adult; Androstenedione; Basal Metabolism; Cosyntropin; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Hyperandrogenism; Middle Aged; Oxidoreductases; Pituitary-Adrenal Function Tests; Polycystic Ovary Syndrome; Up-Regulation; Young Adult

To compare adrenal gland stimulation achieved following administration of cosyntropin (5 microg/kg [2.3 microg/lb]) IM versus IV in healthy dogs and dogs with hyperadrenocorticism.. Clinical trial. Animals-9 healthy dogs and 9 dogs with hyperadrenocorticism.. In both groups, ACTH stimulation was performed twice. Healthy dogs were randomly assigned to receive cosyntropin IM or IV first, but all dogs with hyperadrenocorticism received cosyntropin IV first. In healthy dogs, serum cortisol concentration was measured before (baseline) and 30, 60, 90, and 120 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was measured before and 60 minutes after cosyntropin administration.. In the healthy dogs, serum cortisol concentration increased significantly after administration of cosyntropin, regardless of route of administration, and serum cortisol concentrations after IM administration were not significantly different from concentrations after IV administration. For both routes of administration, serum cortisol concentration peaked 60 or 90 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was significantly increased 60 minutes after cosyntropin administration, compared with baseline concentration, and concentrations after IM administration were not significantly different from concentrations after IV administration.. Results suggest that in healthy dogs and dogs with hyperadrenocorticism, administration of cosyntropin at a dose of 5 microg/kg, IV or IM, resulted in equivalent adrenal gland stimulation.

Topics: Adrenal Cortex Function Tests; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Area Under Curve; Cosyntropin; Cross-Over Studies; Dog Diseases; Dogs; Female; Hydrocortisone; Injections, Intramuscular; Injections, Intravenous; Male

We assess the effect of acute hypercortisolemia induced by ACTH stimulation on seizures and EEG interictal spike activity in patients with localization-related epilepsy (LRE) and stress-related seizures.. Seven patients (3 males, 4 females) with LRE and stress-related seizures were studied. All patients underwent ACTH stimulation with 0.25-0.75 mg Cosyntropin intravenously at 8 am. Serum cortisol and ACTH levels were monitored half- to one-hourly for 4 to 6 hours. Video/EEG monitoring was also performed.. ACTH injection induced hypercortisolemia in all patients. Hypercortisolemia was not associated with seizures or interictal spike facilitation in any patient. Two patients experienced seizures on the day of ACTH injection, one 8 hours after and another 15 and 12 hours after the injection, during a period when their cortisol levels had returned to normal.. No reproducible interictal EEG changes occurred in any of the patients following ACTH injection.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenocortical Hyperfunction; Adult; Cosyntropin; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Humans; Hydrocortisone; Male; Middle Aged; Seizures; Stress, Physiological; Time Factors

To determine whether low doses of synthetic ACTH could induce a maximal cortisol response in clinically normal dogs and to compare a low-dose ACTH stimulation protocol to a standard high-dose ACTH stimulation protocol in dogs with hyperadrenocorticism.. Cohort study.. 6 clinically normal dogs and 7 dogs with hyperadrenocorticism.. Each clinically normal dog was given 1 of 3 doses of cosyntropin (1, 5, or 10 micrograms/kg [0.45, 2.3, or 4.5 micrograms/lb] of body weight, i.v.) in random order at 2-week intervals. Samples for determination of plasma cortisol and ACTH concentrations were obtained before and 30, 60, 90, and 120 minutes after ACTH administration. Each dog with hyperadrenocorticism was given 2 doses of cosyntropin (5 micrograms/kg or 250 micrograms/dog) in random order at 2-week intervals. In these dogs, samples for determination of plasma cortisol concentrations were obtained before and 60 minutes after ACTH administration.. In the clinically normal dogs, peak cortisol concentration and area under the plasma cortisol response curve did not differ significantly among the 3 doses. However, mean plasma cortisol concentration in dogs given 1 microgram/kg peaked at 60 minutes, whereas dogs given doses of 5 or 10 micrograms/kg had peak cortisol values at 90 minutes. In dogs with hyperadrenocorticism, significant differences were not detected between cortisol concentrations after administration of the low or high dose of cosyntropin.. Administration of cosyntropin at a rate of 5 micrograms/kg resulted in maximal stimulation of the adrenal cortex in clinically normal dogs and dogs with hyperadrenocorticism.

Topics: Adrenal Cortex Function Tests; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Cohort Studies; Cosyntropin; Dog Diseases; Dogs; Evaluation Studies as Topic; Female; Hydrocortisone; Male

Topics: Adrenalectomy; Adrenocortical Hyperfunction; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Postoperative Period

Topics: Adrenalectomy; Adrenocortical Hyperfunction; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Postoperative Period

Although several lines of evidence suggest that the overall effects of the ACTH receptor, melanocortin 2 receptor (MC2-R), mediated signal transduction on adrenocortical growth and tumorigenesis are anti-proliferative, activation of MC2-R induces mitogens like jun, fos, and myc and activates the MAPK pathway. In vivo, potential effects of endogenous ACTH on adrenal tumori-genesis can not be separated from effects of other POMC derived peptides.. Murine adrenocortical tumor cells that lack MC2-R expression (Y6(pcDNA)) and Y6 cells stablely transfected with MC2-R (Y6(MC2-R)) were generated. Presence of functional MC2-R was demonstrated by RT-PCR and Western blot using an antibody for phosphorylated CREB. As a syngenic tumor model, LaHeF1/J mice simultaneously received 10(7) Y6(MC2-R) and Y6(pcDNA) subcutaneously, giving rise to MC2-R positive and negative tumors within the same animal. Animals were treated for 3 weeks in groups of 12 according to the following schedule: group A, control animals receiving saline injection; group B, animals receiving 5.7 ng/injection of a slow release formula of ACTH 1-24 administered i.p. three times a week (aiming at a low physiologic dose); and group C, animals receiving 57 ng/injection of ACTH 1-24 (high physiological dose).. Twenty days of ACTH 1-24 treatment did not significantly affect corticosterone levels, endogenous ACTH levels or adrenal and thymus weight compared with saline injection. However, ACTH 1-24 treatment of group B and C mice significantly reduced tumor weight in MC2-R positive tumors in a dose dependent manner (P = 0.03), while no significant difference in tumor mass was observed in MC2-R negative tumors. PCNA and TUNEL staining, together with morphological characterization, demonstrated that these in vivo effects were due to reduced proliferation, while apoptosis and cellular hypertrophy within the tumor remained unchanged.. MC2-R expression is associated with a less aggressive adrenal tumor phenotype and anti-proliferative effects can be amplified through stimulation with physiological doses of ACTH.

Topics: Adrenal Cortex Neoplasms; Adrenocortical Hyperfunction; Animals; Cell Growth Processes; Cell Line, Tumor; Corticosterone; Cosyntropin; Delayed-Action Preparations; Female; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mice; Organ Size; Proliferating Cell Nuclear Antigen; Receptor, Melanocortin, Type 2; Reverse Transcriptase Polymerase Chain Reaction; RNA; Transfection

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Animals; Cats; Cosyntropin; Dogs

Topics: Adrenal Insufficiency; Adrenocortical Hyperfunction; Animals; Cosyntropin; Dog Diseases; Dogs; Female; Hydrocortisone; Infusions, Intravenous; Leukocyte Count; Pilot Projects; Predictive Value of Tests; Reference Values

Topics: Adrenal Cortex Hormones; Adrenocortical Hyperfunction; Adult; Cosmetics; Cosyntropin; Female; Follow-Up Studies; Humans; Hydrocortisone; Skin Pigmentation; Time Factors

While hypercortisolemia is commonly observed in depression, exactly where in the hypothalamic-pituitary-adrenocortical (H-P-A) axis this dysfunction arises remains undefined. In attempting to distinguish between central or peripheral locus of dysfunction, we studied in 12 patients (10 females, two males) with primary major depression and eight age-matched controls (six females, two males) in their adrenal cortisol response to infused adrenocorticotropic hormone (ACTH) (cosyntropin 0.05 microg/kg bodyweight) while endogenous ACTH was suppressed with 1 mg of dexamethasone. Compared with the control group, pre-dexamethasone plasma baseline cortisol level was significantly higher in depressed patients while ACTH level remained normal. Post-dexamethasone responses of both hormones were greatly non-suppressed in the depressed group. Exogenous cosyntropin-elicited rise in plasma cortisol was significantly lower in depressed patients while the ACTH response was not significantly different. These findings suggest that an adrenal cortisol response to ACTH was significantly decreased during depression as compared with normals in Chinese depressed patients. Therefore, the central mechanism of hyperfunctioning H-P-A axis causing hypercortisolemia should be emphasized.

Topics: Adolescent; Adrenal Cortex; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Cosyntropin; Depressive Disorder, Major; Dexamethasone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Reference Values

A prospective study was undertaken to compare intravenous tetracosactrin at doses of 5 microg/kg and 250 microg for diagnosing hyperadrenocorticism in dogs. Both healthy dogs and dogs with pituitary-dependent hyperadrenocorticism were evaluated with the two doses of the drug, and serum cortisol concentrations were compared at 60 minutes post-stimulation. Some of the dogs had additional samples taken at 90 and 120 minutes. For four dogs with hyperadrenocorticism, timed samples were also obtained at 150, 180 and 240 minutes post-injection. Cortisol concentrations 60 minutes after stimulation with either 5 microg/kg or 250 microg intravenous tetracosactrin were similar for both healthy dogs and dogs with hyperadrenocorticism. The lower dose can therefore be used for diagnosing hyperadrenocorticism in dogs.

Topics: Adrenocortical Hyperfunction; Animals; Cosyntropin; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Hydrocortisone; Injections, Intravenous; Prospective Studies; Random Allocation; Reference Values; Time Factors

To evaluate whether ovarian function might have an influence on the adrenal hyperandrogenism present in patients with functional ovarian hyperandrogenism.. Controlled clinical study.. Tertiary institutional hospital.. Twenty-nine hirsute women with functional ovarian hyperandrogenism and 12 normal controls.. The ACTH and GnRH tests were performed before and during triptorelin-induced ovarian suppression in patients. The normal women served as controls for the ACTH test.. Basal and ACTH-stimulated steroid values.. All patients presented elevated T and free androgen index, which normalized after triptorelin. Patients with functional ovarian hyperandrogenism and adrenal hyperandrogenism, defined by elevated basal DHEAS (n = 10), presented enhanced delta 4-17, 20-lyase activity, which persisted during ovarian suppression. delta 4-17,20-lyase activity was normal in the functional ovarian hyperandrogenism patients without adrenal hyperandrogenism (n = 19). No correlation was observed between the any of the indexes of the adrenal enzymatic activities evaluated and plasma E2 or T.. Increased adrenal delta 4-17,20-lyase activity is present in functional ovarian hyperandrogenism women with adrenal hyperandrogenism. No influence of the excess ovarian androgens or estrogens was found on any of the adrenal enzymatic pathways explored.

Topics: Adolescent; Adrenocortical Hyperfunction; Adult; Androgens; Cohort Studies; Cosyntropin; Delayed-Action Preparations; Female; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Hyperandrogenism; Luteolytic Agents; Ovarian Diseases; Reference Values; Steroid 17-alpha-Hydroxylase; Steroids; Triptorelin Pamoate

To explore possible changes in adrenal steroid metabolism and androgenic-anabolic status in female endurance athletes as a mechanism for their hypercortisolism.. Adrenal steroids and androgenic-anabolic factors were studied during basal conditions and in response to ACTH stimulation related to menstrual status.. Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.. Thirteen female elite middle to long distance runners (six eumenorrheic, seven oligoamenorrheic) and seven regularly menstruating controls.. Blood samples were collected before and after an injection of 250 micrograms IV synthetic ACTH 1-24. Body weight, height, and body fat were measured.. Basal serum concentrations of cortisol, androstenedione (A), DHEA, DHEAS, 17 alpha-hydroxyprogesterone (17-OHP), T, steroid-binding proteins, and insulin-like growth factor I and ACTH-induced response (area under the curve) of cortisol, DHEA, and 17-OHP.. Oligoamenorrheic athletes had higher basal cortisol and A concentrations compared with healthy controls, whereas basal levels of DHEA and DHEAS were normal. Important findings in the oligoamenorrheic athletes were a significantly lower ratio between the ACTH-induced increments of DHEA and 17-OHP and an increased ratio between basal A and DHEAS. Insulin-like growth factor I was correlated negatively to sex hormone-binding globulin and to the amount of body fat in the combined material.. The results indicate a redistribution of adrenal steroid metabolism in favor of glucocorticoid production in female endurance athletes. We suggest that hypercortisolism in female endurance athletes is a physiological adaptation to maintain adequate blood glucose levels during a condition of energy deficiency.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Cortex Hormones; Adrenocortical Hyperfunction; Adult; Amenorrhea; Androstenedione; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Insulin-Like Growth Factor I; Physical Endurance; Running; Testosterone

Rats were treated with Synacthen, a synthetic corticotrophin analogue, to induce hypercorticism. The epididymal fat pad was selectively cannulated and perfused. In fasted rats acetone ether powder lipoprotein lipase (LPL) activity rose during treatment to levels found in fed controls. In fed animals no further rise in LPL activity was observed during Synacthen treatment. However, the heparin-elutable LPL activity did not change during this treatment in fasted nor fed animals. Pharmacologic levels of insulin in the perfusion medium caused an increase in heparin-releasable LPL activity as a percentage of total fat pad LPL activity (15% v 48%). Hydrolysis of chylomicrons was higher in fasted three days treated animals then in controls (10 +/- 4% v 2 +/- 2%). In this group a higher uptake of liberated free fatty acids was found (2.6 +/- 1.5% v 1.0 +/- 0.5% in controls). The increase in hydrolysis rate and uptake of fatty acids in the treated fasted animals could not be explained by an increase in releasable LPL activity. Fatty acid release from the fat pad was lower in treated animals than in controls (fasted and fed), basally as well as after adrenalin stimulation. The observation that the epididymal fat pad retains its weight during hypercorticism may therefore be ascribed to an increased influx of fatty acids from increased hydrolysis of TG-rich particles and to an inhibited efflux of fatty acids from the adipocyte. The discrepancy between the LPL activity extractable from an acetone ether powder and the heparin releasable LPL activity suggests impairment of the transport of LPL from the adipocyte to the heparin releasable pool at the endothelium.

Topics: Adipose Tissue; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Chylomicrons; Cosyntropin; Epinephrine; Fatty Acids; Hydrolysis; Lipid Metabolism; Lipoprotein Lipase; Male; Rats; Rats, Inbred Strains; Triglycerides

The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.

Topics: Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Hirsutism; Humans; Hydrocortisone; Hydroxyprogesterones; Testosterone

Topics: Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Corticosterone; Cosyntropin; Female; Humans; Male; Middle Aged; Rats