cosyntropin and Hypopituitarism

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

Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic-pituitary-adrenal (HPA) axes using weight-based dosing for the GST.. To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively.. 28 Patients with hypothalamic-pituitary disease and 1-2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order.. Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = -0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST.. The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.

Topics: Adenoma; Adrenal Insufficiency; Adult; Aged; Blood Glucose; Body Weight; Case-Control Studies; Central Nervous System Cysts; Cosyntropin; Craniopharyngioma; Dose-Response Relationship, Drug; Female; Glucagon; Hormones; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemic Agents; Hypopituitarism; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System; Reference Values; Sensitivity and Specificity

Transsphenoidal surgery (TS) is the treatment of choice for many pituitary tumors. Because TS may cause pituitary insufficiency in some of these patients, early postoperative assessment of pituitary function is essential for appropriate endocrine management. The aim of our study was to evaluate the clinical relevance of the CRH-stimulation test in assessing postoperative pituitary-adrenal function. We performed a retrospective analysis of 144 patients treated by TS between January 1990 and November 2009, in whom a CRH-test and a second stimulation test was performed to assess adrenal function during follow-up. Patients with Cushing's disease were excluded. Hydrocortisone substitution was started if peak cortisol levels were <550 nmol/L. The cortisol response was insufficient in 42(29%) and sufficient in 102 patients at the postoperative CRH-test. Thirteen of 42(30%) demonstrated a normal cortisol response during a second cortisol stimulation test. In 75 of the 102 patients with a sufficient response to CRH repeat testing revealed an insufficient cortisol response in 14 patients (14%). All but one had concomitant pituitary hormone deficits. There were no cases of adrenal crises during follow-up. Additional pituitary insufficiency was significantly more present (P < 0.001) in the group of patients with an abnormal response to CRH directly after surgery. In this study a substitution strategy of hydrocortisone guided by the postoperative cortisol response to CRH appeared safe and did not result in any case of adrenal crises. However, the early postoperative CRH-test does not reliably predict adrenal function after TS for pituitary adenomas in all patients and retesting is mandatory.

Topics: Adenoma; Adolescent; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Corticotropin-Releasing Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Hypopituitarism; Insulin; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Postoperative Period; Retrospective Studies

It is widely accepted that the classical dose of 250.0 microg ACTH (1-24) (tetracosactin) is clearly supra-maximal while 1.0 and 0.03 microg have been shown as the maximal and the lowest stimulatory ACTH doses for cortisol (F) secretion in normal young subjects. Testing with low ACTH dose would better evaluate adrenal sensitivity to corticotropin. The aims of the present study were: a) to clarify the adrenal sensitivity to ACTH in patients with different duration of corticotroph insufficiency by testing with low and very low tetracosactin doses; and b) to evaluate diagnostic implication regarding the ability of ACTH tests to distinguish patients with corticotroph insufficiency from normal subjects. In 24 hypopituitaric patients (HYPOPIT, 15 male and 9 female, age 22-50 yr, BMI: 22-26 kg/m2) with corticotrophin deficiency we studied the F, DHEA and aldosterone (A) responses to challenges with low ACTH doses (0.06 or 0.5 microg iv at 0 min) followed by 250 microg iv (at +60 min). The results in HYPOPIT were compared with those recorded in 12 normal controls (NS, 6 male and 6 female, age 22-34 yr, BMI: 20-25 kg/m2). Basal F and DHEA levels in HYPOPIT were lower than in NS, while A levels were similar in both groups. The F responses to ACTH in HYPOPIT were dose-independent and markedly lower (p < 0.0001) than in NS. After the 0.06 and 0.5 microg ACTH dose, 16% of HYPOPIT patients showed AF peak within the range of normal response. No HYPOPIT showed AF peak within the normal range after 250 microg ACTH. The DHEA responses to ACTH in HYPOPIT were dose-independent and markedly lower than in NS (p < 0.0001). Overlap between individual DHEA responses in HYPOPIT and NS was present after 0.06 microg and 0.5 microg but not after 250 microg tetracosactin. The A responses in HYPOPIT were dose-dependent and overlapped with those in NS. The adrenal responses to ACTH in HYPOPIT were not associated with the duration of the disease. In conclusion, the present study shows that the mean F and DHEA but not the A responses to ACTH (1-24) are markedly impaired in hypopituitaric patients with corticotroph insufficiency independently of the duration of the disease. The impaired F and DHEA response to ACTH is also independent of the dose, suggesting the existence of relatively enhanced sensitivity of the fasciculata and reticularis adrenal zone to ACTH but meantime remarkable impairment of the adrenal function due to corticotrophin deficiency. In the present study, testing with sub

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Area Under Curve; Cosyntropin; Dehydroepiandrosterone; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Hypopituitarism; Male; Middle Aged

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

The short cosyntropin (synthetic ACTH) test is recognized as the best screening manoeuvre in the assessment of adrenocortical insufficiency. Recent data, however, suggest that i.v. administration of 250 microg cosyntropin could be a pharmacological rather than a physiological stimulus, losing sensitivity for detecting adrenocortical failure. Our objective was to compare 10 vs 250 microg cosyntropin in order to find differences in serum cortisol peaks in healthy individuals, the adrenocortical response in a variety of hypothalamic-pituitary-adrenal axis disorders and the highest sensitivity and specificity serum cortisol cut-off point values. The subjects were 83 healthy people and 37 patients, the latter having Addison's disease (11), pituitary adenomas (7), Sheehan's syndrome (9) and recent use of glucocorticoid therapy (10). Forty-six healthy subjects and all patients underwent low- and standard-dose cosyntropin testing. In addition, 37 controls underwent the low-dose test. On comparing low- and standard-dose cosyntropin testing in healthy subjects there were no statistical differences in baseline and peaks of serum cortisol. In the group of patients, 2 out of 11 cases of Addison's disease showed normal cortisol criterion values during the standard test but abnormal during the low-dose test. In our group of patients and controls, the statistical analysis displayed a better sensitivity of the low-dose vs standard-dose ACTH test at 30 and 60 min. In conclusion, these results suggest that the use of 10 microg rather than 250 microg cosyntropin i.v. in the assessment of suspicious adrenocortical dysfunction gives better results.

Topics: Addison Disease; Adenoma; Adrenal Glands; Adrenal Insufficiency; Adult; Aged; Area Under Curve; Cosyntropin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Hypopituitarism; Injections, Intravenous; Male; Middle Aged; Pituitary Neoplasms; Sensitivity and Specificity

The short Synacthen (tetracosactrin) test (SST) is an established method of assessing adrenocortical reserve, and is increasingly replacing the insulin tolerance test (ITT) for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis. However, there is no consensus on how the test is performed, and various time points and routes of administration are used. The present study was done, first, to determine whether there was any difference in cortisol responses when Synacthen was administered intramuscularly compared with intravenously and, secondly, to compare cortisol responses at 30 and 60 min. We found no significant difference between the two routes of administration. However, cortisol responses at 60 min were significantly higher than at 30 min (P < 0.05). Previous validations for the use of the SST in place of the ITT have used cortisol responses 30 min after Synacthen. We conclude that where the SST is used to assess the HPA axis, cortisol response at 30 min after intravenous Synacthen should be used.

Topics: Adult; Aged; Analysis of Variance; Cosyntropin; Female; Humans; Hypopituitarism; Hypothalamo-Hypophyseal System; Insulin; Linear Models; Male; Middle Aged; Pituitary-Adrenal System; Secretory Rate

Topics: ACTH Syndrome, Ectopic; Addison Disease; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Cosyntropin; Cushing Syndrome; Delayed-Action Preparations; Dexamethasone; Evaluation Studies as Topic; Humans; Hypopituitarism; Immunoradiometric Assay; Nelson Syndrome; Reagent Kits, Diagnostic; Reproducibility of Results; Sensitivity and Specificity

Topics: Atrophy; Azathioprine; Behcet Syndrome; Biomarkers; Colchicine; Cosyntropin; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Hypopituitarism; Luteinizing Hormone; Male; Middle Aged; Pituitary Gland; Prednisolone; Thyrotropin; Thyrotropin-Releasing Hormone

We present the endocrine parameters of two adult patients with partial hypopituitarism documented at 6 and 8 months after chemotherapy, single fraction total body irradiation (10.5 Gy) and autologous bone marrow transplantation. The hormone profiles demonstrate severe somatotroph insufficiency and impaired adrenocorticotroph secretory capacity, despite sparing of the gonadotroph compartment. We recommend stimulatory testing of hypothalamic-pituitary function from 3 months post-transplant, as basal hormonal concentrations may be equivocal, and supplementation may significantly improve quality of life.

Topics: Adult; Bone Marrow Transplantation; Cosyntropin; Hormones; Humans; Hydrocortisone; Hypopituitarism; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radioimmunoassay; Transplantation, Autologous; Whole-Body Irradiation

Short term suppression of ACTH by dexamethasone effects limited reduction in plasma deoxycorticosterone (DOC) while cortisol levels are almost completely suppressed in normal control subjects. The zona fasciculata (ZF) microsomal cytochrome P-450(21) appeared less influenced by lack of ACTH than mitochondrial cytochrome P-450(11 beta-18). Eleven patients with hypopituitarism were studied to quantitate basal ZF microsomal and mitochondrial derived steroids and their acute and extended responses to ACTH. Basal levels of 11-deoxycortisol (S) and DOC were modestly reduced (70% and 53%, respectively), while other ZF steroids were almost completely absent. Acute and prolonged ACTH treatment amplified the discrepancy in both plasma levels and production rates. DOC and S demonstrated prompt and sustained increases similar to those in normal controls, while cortisol, 18-hydroxydeoxycorticosterone, and corticosterone showed a slow subnormal recovery of steroid production. The preservation of microsomal cytochrome P-450(21) and P-450(17 alpha) to maintain DOC and S levels contrasts the reduced and delayed responses of steroids dependent on mitochondrial cytochrome P-450(11 beta-18), cortisol, corticosterone, and 18-hydroxydeoxycorticosterone. A greater effect of ACTH deficiency on mitochondrial over microsomal cytochrome P-450 activity is demonstrated, and in addition, the possibility is raised that other non-ACTH regulators sustain microsomal cytochrome P-450(21) and P-450(17 alpha) in a setting of reduced ACTH-stimulated factors.

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Cortodoxone; Cosyntropin; Desoxycorticosterone; Dexamethasone; Female; Humans; Hypopituitarism; Kinetics; Male; Middle Aged; Pituitary Neoplasms; Reference Values; Zona Fasciculata

One must consider the 17-DOS as a biosynthetic pathway with multiple regulatory factors. ACTH is its dominant regulator but in the absence of ACTH and in conditions where plasma renin activity is increased, this biosynthetic pathway maintains its sensitivity to exogenous ACTH. Suppression of the renin system delays the general recovery of aldosterone after the removal of an aldosterone producing adenoma but not of the 17-DOS: a pattern also showed after the removal of a DOC-producing adenoma. In addition to the possible role of the renin system there remain inexplicable situations in its regulation that cannot be explained by ACTH and renin. Our studies suggest that a non-renin, non-ACTH factor may influence the basal production of these steroids, and by its reduction, permits deviation of steroid substrate to cortisol production. This sequence may be operative in the "stress syndrome". Finally, one of the more interesting phenomenonologic patients who has been observed is a young male who has the biochemical findings and clinical signs of DOC excess with hypertension, hyperplasia, suppression of aldosterone and the RAS, and normal cortisol levels. All the 17-DOS are elevated and both adrenal veins have high concentrations. He represents excessive stimulation of this pathway by putative 17-deoxy regulator excess. The renin system is suppressed and ACTH levels are normal. Treatment with suppressive doses of glucocorticoid hormones diminishes the elevated 17-DOS and cortisol and ameliorates blood pressure. In summary, there seems to occur in clinical disorders and contrived experimental settings, suggestions that a non-renin, non-ACTH factor can regulate the 17-DOS, absence can explain some of the unusual conditions described (Fig. 1). The 17-DOS, while a vestigial pathway, may still cause disease, and provide clues to central organization of the adreno-cortical response to injury, stress, and disease.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Adrenal Gland Diseases; Biomarkers; Cosyntropin; Dexamethasone; Homeostasis; Humans; Hypopituitarism; Reference Values; Steroid Hydroxylases; Stress, Physiological; Zona Fasciculata

The effect of ACTH administration on plasma CRH levels was studied. In five patients with Addison's disease and three patients with hypopituitarism, bolus iv injection of 0.25 and 0.5 mg ACTH-(1-24) reduced plasma CRH levels (that had become elevated 48 h after discontinuation of corticosteroid replacement) to near-normal levels at 30-60 min in a dose-dependent manner. Plasma immunoreactive beta-endorphin levels were similarly decreased in patients with Addison's disease. ACTH-(1-24) (0.25 and 0.5 mg) injection failed to inhibit plasma CRH levels in five normal subjects. Basal CRH release from the rat hypothalamic median eminence in vitro was inhibited by 0.22 and 2.2 nM ACTH-(1-24) and ACTH-(1-39) in a dose-dependent manner. These results suggest that in the absence of negative feedback control of ACTH secretion by glucocorticoids, ACTH can regulate its secretion by inhibition of hypothalamic CRH release.

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; Aged; Animals; Corticotropin-Releasing Hormone; Cosyntropin; Feedback; Female; Humans; Hypopituitarism; Hypothalamus; Kinetics; Male; Median Eminence; Middle Aged; Rats

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adult; Aldosterone; Cosyntropin; Female; Humans; Hypopituitarism; Male; Metoclopramide; Middle Aged; Pituitary Gland, Anterior

In 30 resting normal persons, 5 ambulant normal persons and 3 patients with disorders of the pituitary-adrenal-system before and 30 minutes after intravenous injection of 0,25 mg synthetic adrenocorticotrophin (tetracosactid, Synacthen) plasma cortisol and aldosterone levels were evaluated. The evaluation of the corticoids was continued over 240 minutes in intervals of 30 minutes. The basal cortisol and aldosterone levels of the resting normal persons and ambulant persons ordinarily doubled 30 minutes after ACTH application. The plasma cortisol level of a steroid-treated patient with lupus erythematodes disseminatus rose subnormally but his aldosterone level increased normally. 2 patients with untreated hypopituitarism had subnormal plasma cortisol and normal aldosterone responses after ACTH administration. In contrast with patients with primary adrenal insufficiency, whose plasma aldosterone levels fail to rise, patients with secondary adrenal insufficiency had normal corticotrophin-stimulated aldosterone increments. Thus the extended ACTH test can be useful in differential diagnosis of primary and secondary adrenal insufficiency.

Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Cosyntropin; Diagnosis, Differential; Humans; Hydrocortisone; Hypopituitarism; Time Factors

Topics: 11-Hydroxycorticosteroids; Adolescent; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Adult; Child; Child, Preschool; Cosyntropin; Female; Humans; Hydrocortisone; Hypopituitarism; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary-Adrenal System; Prednisone

The promoting effect of ACTH on carnitine and lipid metabolism was studied in patients with various endocrine hypofunctions. The results were compared with those of normal subjects. In adrenocortical insufficiency, hypothyroidism and hypopituitarism urinary excretion of carnitine was significantly lower than in normal subjects. On intramuscular injection of synthetic beta1-24 ACTH-Z urninary excretion of carnitine in normal subjects increased sixfold on the day of the injection and returned to the pretreatment level on the third day. Serum concentrations of carnitine and FFA increase in parallel with carnitine excretion, while serum triglyceride was lowered in response to ACTH administration. These responses were totally lacking or substantially suppressed in patients with the above endocrine insufficiencies. In hypothyroid and hypopituitary patients substitution therapy restored the responses to ACTH in the same fashion as those in normal subjects. These findings suggest that the promoting effect of ACTH on carnitine and lipid metabolism requires the presence of intact adrenocortical and thyroid functions.

Topics: Addison Disease; Adrenalectomy; Adrenocorticotropic Hormone; Carnitine; Cosyntropin; Fatty Acids, Nonesterified; Humans; Hydrocortisone; Hypopituitarism; Hypothyroidism; Lipids; Prednisolone; Triglycerides; Triiodothyronine