cosyntropin and Hypoglycemia

The insulin tolerance test is considered the gold standard for assessing the hypothalamic-pituitary-adrenal and growth hormone (GH) axes, but its use varies considerably among different endocrine units. We recommend using the insulin tolerance test to assess the hypothalamic-pituitary-adrenal axis within 3 months of pituitary surgery, where adrenocorticotropic hormone 1-24 testing is equivocal, and to assess for GH deficiency where the patient is being considered for GH replacement therapy. We also discuss safety issues, how to ensure adequate hypoglycaemia and possible alternative tests, such as the overnight metyrapone test and glucagon test.

Topics: Adrenocorticotropic Hormone; Circadian Rhythm; Contraindications; Cosyntropin; False Negative Reactions; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypophysectomy; Hypopituitarism; Hypothalamo-Hypophyseal System; Insulin; Insulin-Like Growth Factor I; Metyrapone; Pituitary Function Tests; Pituitary-Adrenal System; Postoperative Complications

Adrenal insufficiency is known to be a complication of HIV infection, although estimates of its prevalence and severity vary. Adrenal insufficiency is the most serious endocrine complication that occurs in persons with HIV infection. Patients with acquired immune deficiency syndrome (AIDS) are considered to be at high risk for primary or secondary adrenal insufficiency. We describe 3 patients with AIDS who had clinical features suggestive of adrenal insufficiency, but their corticotropin (ACTH) stimulation tests were normal. Repeat testing confirmed the diagnosis in one patient, and further testing with the overnight metyrapone test revealed evidence of secondary adrenal insufficiency in the other patients. Persistent clinical improvement was evident on subsequent glucocorticoid therapy. A normal response to the ACTH stimulation test can be dangerously misleading. Patients with AIDS and suspected adrenal insufficiency who have normal screening by the ACTH stimulation test should undergo further testing for secondary adrenal disease.

Topics: Adrenal Glands; Adrenal Insufficiency; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Combined Modality Therapy; Cosyntropin; Cytomegalovirus Infections; Dexamethasone; False Negative Reactions; Fluid Therapy; HIV Infections; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Metyrapone; Mycobacterium avium-intracellulare Infection; Pituitary Gland; Pituitary-Adrenal System; Risk; Sarcoma, Kaposi; Stomach Neoplasms

Recent work has taught us that our conventional approach to corticosteroid replacement therapy requires review. Specifically, the doses of hydrocortisone we have used are probably too high for the majority, and should ideally be administered in three or more doses through the day. Nevertheless, there is not much hard evidence that excessive glucocorticoid replacement per se will lead to adverse effects such as osteoporosis, even though it may exacerbate any tendency in those who are predisposed to it for other reasons. As such, there is no compelling need for using determinations of either UFC excretion or of the serum cortisol profile in the routine management of patients on replacement therapy. Nevertheless, such measures may be considered in those thought to be at particular risk of osteoporosis, and in whom it is felt that special effort should be made to ensure that they are receiving the minimum dose possible. In such circumstances, a cortisol day curve is likely to be of more value than measurement of UFC.

Topics: 17-alpha-Hydroxyprogesterone; Addison Disease; Adrenal Cortex Hormones; Adrenal Gland Diseases; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cosyntropin; Cushing Syndrome; Glucocorticoids; Humans; Hydrocortisone; Hypoglycemia; Osteoporosis; Risk

Adrenocortical insufficiency causes difficulty in diagnosis and morbidity out of proportion to its rarity, because of the non-specific, multi-system nature of the clinical features. Most of these are due to cortisol deficiency. Prominent features are well-known ones such as weight loss and asthenia, and hypoglycaemia. Less prominent in recent accounts are those due to failure of cellular sodium export and to vasopressin excess, which are frequent and clinically significant. For this reason, the clinical features of isolated ACTH deficiency, isolated glucocorticoid deficiency and Addison's disease overlap greatly. In addition, cortisol deficiency has secondary endocrine effects, e.g. glucocorticoid-reversible hypothyroidism, hyperprolactinaemia and hypercalcaemia. Further overlap between the various steroid insufficiency syndromes occurs because of the association of various organ-specific autoimmune endocrinopathies with Addison's disease. Over 80% of Addison's disease is of the autoimmune type, though almost any systemic destructive process can cause similar steroid insufficiency. Demonstration of adrenal insufficiency requires various combinations of tetracosactrin adrenal stimulation tests, and hypoglycaemia or equivalent tests, if the cause is ACTH deficiency but the correct test can only be chosen to suit a firm clinical diagnosis. The treatment of adrenocortical insufficiency is described.

Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Androstenedione; Animals; Autoimmune Diseases; Blood Volume; Body Water; Calcium; Catecholamines; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Delayed-Action Preparations; Disease Models, Animal; Glomerular Filtration Rate; Glucocorticoids; Humans; Hypoglycemia; Hyponatremia; Hypotension; Hypothalamo-Hypophyseal System; Kidney; Posture; Prolactin; Regional Blood Flow; Skin Pigmentation; Thyroid Gland; Tomography, X-Ray Computed; Water-Electrolyte Balance

Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality.. The objective of this work is to investigate the role of the adrenocorticotropin (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1-24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day.. A double-blind, placebo-controlled, random-order, cross-over study was conducted.. This study took place in a clinical research center.. Participants included healthy men and women.. Interventions included an intravenous infusion of cosyntropin (70 μg/hour for 2.5 hours in the morning and again in the early afternoon) vs normal saline placebo.. Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions.. Cosyntropin infusion attenuated BRS (mm Hg/ms) as compared to placebo (baseline 17.8 ± 1.38 vs 17.0 ± 2.07; during 14.4 ± 1.43 vs 17.3 ± 1.65; and next day 14.8 ± 1.42 vs 18.9 ± 2.04; P < .05, time by treatment, analysis of variance). BRS was decreased during the final 30 minutes of the morning cosyntropin infusion as compared to baseline (P < .01) and remained suppressed the next day (16 hours after afternoon infusion) (P < .025). Placebo infusion did not significantly change BRS. Corrected QT interval was not affected.. ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.

Topics: Adult; Autonomic Nervous System Diseases; Baroreflex; Cosyntropin; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypoglycemia; Male

The efficacy of the standard high dose ACTH stimulation test (HDT), using a pharmacological 250-microg dose of synthetic ACTH-(1-24), in the diagnosis of central hypoadrenalism is controversial. The insulin hypoglycemia test is widely regarded as the gold standard dynamic stimulation test of the hypothalamo-pituitary-adrenal (HPA) axis that provides the most reliable assessment of HPA axis integrity and reserve. Alternatively, a prolonged infusion of ACTH causes a continuing rise in plasma cortisol levels that may predict the adrenals' capacity to respond to severe ongoing stress. In nine normal subjects, we compared plasma ACTH and cortisol levels produced by three i.v. bolus low doses of ACTH-(1-24) (0.1, 0.5, and 1.0 microg/1.73 m2; LDTs) with those stimulated by hypoglycemia (0.15 U/kg insulin) and with the cortisol response to a standard 250-microg dose of ACTH-(1-24). The normal cortisol response to an 8-h ACTH-(1-24) infusion (250 microg at a constant rate over 8 h) was determined using three modern cortisol assays: a high pressure liquid chromatography method (HPLC), a fluorescence polarization immunoassay (FPIA), and a standard RIA. In the LDTs, stepwise increases in mean peak plasma ACTH were observed (12.4 +/- 2.0, 48.2 +/- 7.2, 120.2 +/- 15.5 pmol/L for the 0.1-, 0.5-, and 1.0-microg LDTs, respectively; P values all <0.0022 when comparing peak values between tests). The peak plasma ACTH level after insulin-induced hypoglycemia was significantly lower than that produced in the 1.0-microg LDT (69.6 +/- 9.3 vs. 120.2 +/- 15.5 pmol/L; P < 0.0002), but was higher than that obtained during the 0.5-microg LDT (69.6 +/- 9.3 vs. 48.2 +/- 7.2 pmol/L; P < 0.02). In the LDTs, statistically different, dose-dependent increases in peak cortisol concentration occurred (355 +/- 16, 432 +/- 13, and 482 +/- 23 nmol/L; greatest P value is 0.0283 for comparisons between all tests). The peak cortisol levels achieved during the LDTs were very different from those during the HDT (mean peak cortisol, 580 +/- 27 nmol/L; all P values <0.00009. However, the mean 30 min response in the 1.0-microg LDT did not differ from that in the HDT (471 +/- 22 vs. 492 +/- 22 nmol/L; P = 0.2). In the 8-h ACTH infusion test, plasma cortisol concentrations progressively increased, reaching peak levels much higher than those in the HDT [995 +/- 50 vs. 580 +/- 27 nmol/L (HPLC) and 1326 +/- 100 vs 759 +/- 31 nmol/L (FPIA)]. Significant differences in the basal, 1 h, and peak cortisol levels

Topics: Adrenocorticotropic Hormone; Adult; Chromatography, High Pressure Liquid; Cosyntropin; Dose-Response Relationship, Drug; Female; Fluorescence Polarization Immunoassay; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Middle Aged; Radioimmunoassay; Reference Values; Single-Blind Method; Time Factors

Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic-pituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences.. In this study we evaluated the integrity of the HPA in 24 patients (age 4.2-31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency.. At a cortisol cut-off for a normal response of 550 nmol/l (20 microg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2-135.2 nmol/l (2.4-4.9 microg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST.. We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re-assessment of adrenal function.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Child, Preschool; Corticotropin-Releasing Hormone; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Human Growth Hormone; Humans; Hypoglycemia; Hypoglycemic Agents; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary Diseases; Pituitary-Adrenal System; Reproducibility of Results

A 6 year-old Chinese boy with Kabuki syndrome presented with hypoglycemic seizure. He was diagnosed to have isolated adrenocorticotropin deficiency. To our knowledge, this is the first case of Kabuki syndrome with isolated adrenocorticotropin deficiency in the literature.

Topics: Abnormalities, Multiple; Adrenocorticotropic Hormone; Child; Corticotropin-Releasing Hormone; Cosyntropin; Dermatoglyphics; Fingers; Hormones; Humans; Hypoglycemia; Hyponatremia; Intellectual Disability; Male; Seizures; Syndrome; Water-Electrolyte Imbalance

Topics: Adrenal Insufficiency; Coma; Cosyntropin; Humans; Hydrocortisone; Hypoglycemia; Hypopituitarism; Treatment Outcome

We tested the hypothesis that increased endogenous cortisol secretion reduces autonomic neuroendocrine and neurogenic symptom responses to subsequent hypoglycemia. Twelve healthy young adults were studied on two separate occasions, once after infusions of a pharmacological dose of alpha-(1-24)-ACTH (100 microg/h) from 0930 to 1200 and 1330 to 1600, which raised plasma cortisol levels to approximately 45 microg/dl on day 1, and once after saline infusions on day 1. Hyperinsulinemic (2.0 mU x kg(-1) x min(-1)) stepped hypoglycemic clamps (90, 75, 65, 55, and 45 mg/dl glucose steps) were performed on the morning of day 2 on both occasions. These markedly elevated antecedent endogenous cortisol levels reduced the adrenomedullary (P = 0.004, final plasma epinephrine levels of 489 +/-64 vs. 816 +/-113 pg/ml), sympathetic neural (P = 0.0022, final plasma norepinephrine levels of 244 +/-15 vs. 342 +/-22 pg/ml), parasympathetic neural (P = 0.0434, final plasma pancreatic polypeptide levels of 312 +/- 37 vs. 424 +/- 56 pg/ml), and neurogenic (autonomic) symptom (P = 0.0097, final symptom score of 7.1 +/-1.5 vs. 10.6 +/- 1.6) responses to subsequent hypoglycemia. Growth hormone, but not glucagon or cortisol, responses were also reduced. The findings that increased endogenous cortisol secretion reduces autonomic neuroendocrine and neurogenic symptom responses to subsequent hypoglycemia are potentially relevant to cortisol mediation of hypoglycemia-associated autonomic failure, and thus a vicious cycle of recurrent iatrogenic hypoglycemia, in people with diabetes mellitus.

Topics: 3-Hydroxybutyric Acid; Adrenal Medulla; Adult; C-Peptide; Cosyntropin; Epinephrine; Fatty Acids, Nonesterified; Female; Glucagon; Glucose Clamp Technique; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Neurosecretory Systems; Norepinephrine; Pancreatic Polypeptide; Parasympathetic Nervous System

Recent evidence suggests that 10 microg cosyntropin test has higher sensitivity for detecting hypothalamus-hypophysis-adrenal axis (HHA-A) dysfunction. Our objective was to determine prevalence of glucocorticoid insufficiency with the 10 microg cosyntropin test and the level of the HHA-A defect. One hundred and four HIV-infected patients underwent the 10 microg cosyntropin test. In abnormal and borderline respondents, insulin-induced hypoglycaemia test and human corticotropin releasing hormone test were used to confirm and localize the level of the HHA-A defect. Thirty-two patients with HIV infection and 72 with AIDS were identified. Prevalence of glucocorticoid insufficiency by the 10 microg cosyntropin test was 21.2%. By clinical categories, the frequency in AIDS and HIV infection patients was 26.4% and 9.4%, respectively. Confirmed glucocorticoid insufficiency by insulin-induced hypoglycaemia test was found in 16 out of 19 cases. Twelve cases had primary glucocorticoid insufficiency, 7 had secondary glucocorticoid insufficiency and 3 were false positive. In conclusion, adrenocortical dysfunction occurs in approximately 20% of the cases with HIV disease. Clinical findings commonly occurring in HIV disease as well as adrenocortical insufficiency are not reliable indicators for performing adrenocortical laboratory assessment. Our results suggest screening all AIDS patients with the 10 microg cosyntropin test.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Cosyntropin; Female; Glucocorticoids; HIV Infections; Humans; Hypoglycemia; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal System

Three patients who chronically abused alcohol were found to be hyponatraemic with normal plasma potassium. The first had been admitted with confusion and weight loss, the second with hypotension and sepsis, and the third with confusion and hypoglycaemia-induced seizures. All three patients had a subnormal cortisol response in the short synacthen test; however, the plasma cortisol after three days of tetracosactrin administration was greater than 550 nmol/L. Baseline corticotropin levels were less than 10 pg/mL in all three. No structural lesions of the hypothalamo-pituitary tract were found and there was no evidence of other endocrinopathies. Glucocorticoid replacement therapy led to the resolution of hyponatraemia and hypoglycaemia, where present, and to clinical improvement. The two surviving patients remained hypocortisolaemic in the long term, without recurrence of hyponatraemia or hypoglycaemia. The features of isolated corticotropin deficiency are easily confused with other effects of chronic alcohol abuse. In alcoholic patients with unexplained hyponatraemia, hypoglycaemia or haemodynamic instability, a short tetracosactrin test is advisable.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; Cosyntropin; Diagnosis, Differential; Female; Humans; Hypoglycemia; Hyponatremia; Male; Middle Aged

Hypothyroidism is known to lead to a certain degree of functional insufficiency of the adrenal gland by affecting both the hypophyseal axis and peripheral metabolism of cortisol. This study was conducted to evaluate hypothalamic, pituitary, and adrenal function in a homogeneous group of patients with long-standing major hypothyroidism.. Forty-five patients (32 females, 13 males; mean age 42.9 +/- 9.6 years; range 20-59) with major primary hypothyroidism known to be long-standing (> 1 year in 1 and for an undetermined duration of several years in all the others) were included. Twenty-nine age-matched subjects served as controls. Insulin-induced hypoglycaemia and oral metyrapone tests were performed before and after treatment had induced euthyroidism. Plasma ACTH and cortisol were measured every 20 min for 2 hours during the hypoglycaemia test and ACTH before and after the last dose of metyrapone. Plasma cortisol levels were determined before and 30 min after injection of tetracosactide.. Baseline ACTH and cortisol were not different in patients and controls and were unchanged by treatment. ACTH and cortisol response to hypoglycaemia were weaker in patients with ongoing hypothyroidism (p < 0.05 vs controls) and improved significantly (p < 0.05 vs baseline) after treatment. Adreno-cortical response to exogenous ACTH stimulation was weaker in patients with hypothyroidism (p < 0.05 vs controls) and returned to normal after treatment.. Modifications of the hypothalamic-pituitary-adrenal system resulting from hypothyroidism were minimal and evidenced only by dynamic exploration. Levels returned to normal after adequate treatment and the deficit restricted to the hypothalamus and pituitary might also involve the adrenal gland.

Topics: Adrenocorticotropic Hormone; Adult; Autoimmune Diseases; Cosyntropin; Female; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Hypothyroidism; Insulin; Male; Metyrapone; Middle Aged; Pituitary-Adrenal System; Reference Values

An insulin hypoglycemia test and a 30-min ACTH stimulation test was performed in 10 chronic alcoholic men, who had been abstinent from alcohol for at least one month. Attenuated serum cortisol responses were found in six of the patients despite a normal ACTH test. Four patients showed normal responses to both the insulin hypoglycemia test and the short ACTH test. No correlation was demonstrated between the cortisol response and the severity of alcoholism, cerebral atrophy, and peripheral neuropathy. It is concluded that in chronic alcoholism the short ACTH test may fail in disclosing hypofunction of the integrated hypothalamic-pituitary-adrenocortical (HPA) axis as assessed with the insulin hypoglycemia test.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; Blood Glucose; Cosyntropin; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal Function Tests

A corticotropin antiserum was obtained from rabbits immunized with synthetic 1--24 corticotropin conjugated with bovine serum albumin. The antiserum did not cross react with synthetic alpha-melanotropin or with synthetic beta-endorphin and had a cross reactivity of 0.23% with human beta-lipotropin. We developed a radioimmunoassay with the antiserum obtained, in which we used polyethylene glycol in conjunction with a second precipitating antibody for fast (15-min) separation of antibody-bound and free corticotropin. The assay had a sensitivity of 16 ng/L and was validated on patients with various pituitary and adrenal diseases. From 103 normal subjects, the median value for corticotropin in specimens collected during the morning was 34 ng/L of plasma; the upper 95% confidence limit of the normal range was 98 ng/L.

Topics: Adrenal Gland Diseases; Adrenocorticotropic Hormone; Animals; Cosyntropin; Cross Reactions; Female; Humans; Hypoglycemia; Immune Sera; Insulin; Iodine Radioisotopes; Male; Neoplasms; Rabbits; Radioimmunoassay; Reference Values

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Arthritis, Rheumatoid; Circadian Rhythm; Cosyntropin; Female; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Lysine; Male; Metyrapone; Middle Aged; Vasopressins