cosyntropin and Pituitary-Neoplasms

To describe the current indications for adrenal vein sampling (AVS), variability in institutional protocols for performing the procedure, shortage of expert interventional radiologists trained in this procedure, pitfalls in technique and strategies to improve success. A major emphasis of the review will focus on the interpretation of the AVS results.. Published protocols for performance of the AVS procedure and variability in the diagnostic criteria differentiating aldosterone-producing adenoma from bilateral adrenal hyperplasia vary significantly. Inability to catheterize the right adrenal vein is the major reason for technical failure of AVS. Preplanning computed tomography, stat intraprocedural cortisol levels and cone-beam computed tomography are helpful in identifying the right adrenal vein. The administration of adrenocorticotropic hormone stimulation during AVS varies significantly between different studies.. More interested interventional radiologists need to acquire the necessary technical expertise for AVS due to increased demand for the procedure, which is the diagnostic reference standard for primary aldosteronism. Unresolved issues include variability in the AVS procedure protocol, use of adrenocorticotropic hormone stimulation and standardization of the interpretation of the results. Despite all these variables, many different approaches still appear to be clinically successful, as indicated by the extensive published reports.

Topics: Adenoma; Adrenal Glands; Adrenocorticotropic Hormone; Aldosterone; Catheterization; Clinical Competence; Cosyntropin; Diagnosis, Differential; Humans; Hydrocortisone; Hyperplasia; Pituitary Neoplasms; Radiology; Veins; Workforce

The first half of this manuscript is devoted to a review of the methods used and the results obtained in the published measurements of the normal responses to tests of the three main types of hypothalamic-pituitary-adrenocortical (HPA) activity in man. These are, I, basal, unstressed activity leading to appropriate levels of total daily production of cortisol in the characteristic circadian pattern; II, responses to feedback stimulation of HPA activity by metyrapone administration; and III, responses to tests of the effects of stress on the HPA system including the effects of hypoglycemia, induced fever, vasopressin administration, and ACTH injections and infusions. The advantages and shortcomings of each type of procedure are discussed. The second half of this paper describes the authors' attempts to establish the limits of normality of standard and modified methods of evaluating the HPA system. The defined limits of normality have been used to assess the HPA function in 158 patients with known or suspected disorders of the HPA system. In normal controls, halfhourly plasma cortisol determinations established the normality of circadian and postprandial fluctuations and of mean plasma cortisol concentration, 6.2 +/- 0.3 (SEM) micrograms/dl, which were closely approximated by determinations every 6 h. Metyrapone, given in a dose of 500 mg every 2 h for 24 h increased urinary 17-OHCS excretion to 10.5-32.6 mg/day or to 1.7-7.8 times basal excretion rate. Increasing rates of insulin infusion disclosed significant relationships between resulting plasma glucose and cortisol concentrations. The slopes of the delta cortisol/delta glucose responses were similar after insulin infusions (0.46 +/- 0.05) and after insulin injections, 0.15 U/kg (0.43 +/- 0.09), and were always greater than 0.20 micrograms/mg. This index provides a useful objective measure of the normality of responses to hypoglycemic stress, 0.20-0.87 micrograms/mg. Adrenocortical responses to iv infusions of ACTH (cosyntropin 0.25 mg) may be equivocal at 2 h but are clear cut at 4, 6 and 8 h. Of 158 patients in whom hypopituitarism was known or suspected because of the presence of a pituitary tumor, acromegaly, hyperprolactinemia, or clinical features, HPA function was found to be entirely normal in 88 patients and partially or severely abnormal in the remaining 70 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: 17-Hydroxycorticosteroids; Acromegaly; Adenoma, Chromophobe; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Blood Glucose; Child; Circadian Rhythm; Cosyntropin; Cushing Syndrome; Feedback; Female; Glucocorticoids; Humans; Hydrocortisone; Hypophysectomy; Hypothalamic Neoplasms; Hypothalamo-Hypophyseal System; Infusions, Parenteral; Injections, Intravenous; Insulin; Lypressin; Male; Metyrapone; Middle Aged; Pituitary Diseases; Pituitary Neoplasms; Pituitary-Adrenal System; Prolactin; Pyrogens; Stress, Physiological

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

Observational methods can be used in conjunction with the comparative effectiveness research (CER) paradigm to inform decisions between alternative patient management strategies in real-world clinical settings.. To present a brief review of current observational research regarding 3 strategies for predicting normal hypothalamic-pituitary-adrenal (HPA) axis function after surgical resection of pituitary tumors and to apply the CER model to compare these management alternatives.. We designed and conducted 2 prospective observational studies involving 183 patients undergoing microsurgical resection for pituitary tumors. These investigations yielded a comprehensive database comprising longitudinal data from multiple clinical domains. We investigated 3 potential strategies to predict normal postoperative HPA axis function in this cohort, including preoperative adrenocorticotrophic hormone stimulation testing and measurement of serum cortisol levels immediately after surgery or on the first postoperative day. We performed a focused comparative effectiveness review to help inform the decision between the 3 potential clinical management strategies.. This investigation illustrates the use of observational research methods in conjunction with CER methodology as one means of informing clinical management decisions. Of the 3 strategies for assessing postoperative HPA axis function studied, preoperative and immediate postoperative adrenocorticotrophic hormone stimulation testing had the highest sensitivity, accuracy, and positive predictive value for normal HPA axis function postoperatively. The preoperative strategy was also the most cost-effective approach (12% reduction vs benchmark).. The decision to use any of the 3 strategies outlined requires attention to a specific patient's clinical situation, but this decision may be aided by the results of this CER analysis.

Topics: Comparative Effectiveness Research; Cosyntropin; Hematologic Tests; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Microsurgery; Neurosurgical Procedures; Pituitary Neoplasms; Pituitary-Adrenal System; Postoperative Complications; Reference Values; ROC Curve; Sensitivity and Specificity

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the IL-6 family that activates the hypothalamic-pituitary-adrenal axis and promotes corticotrope cell differentiation during development. The aim of this study was to investigate the expression of LIF and its receptor (LIFR) in the canine pituitary gland and in corticotrope adenomas, and to perform a mutation analysis of LIFR. Using immunohistochemistry, immunofluorescence, and quantitative expression analysis, LIF and LIFR expression were studied in pituitary glands of control dogs and in specimens of corticotrope adenoma tissue collected through hypophysectomy in dogs with pituitary-dependent hypercortisolism (PDH, Cushing's disease). Using sequence analysis, cDNA was screened for mutations in the LIFR. In the control pituitary tissues and corticotrope adenomas, there was a low magnitude of LIF expression. The LIFR, however, was highly expressed and co-localized with ACTH(1-24) expression. Cytoplasmatic immunoreactivity of LIFR was preserved in corticotrope adenomas and adjacent nontumorous cells of pars intermedia. No mutation was found on mutation analysis of the complete LIFR cDNA. Surprisingly, nuclear to perinuclear immunoreactivity for LIFR was present in nontumorous pituitary cells of the pars distalis in 10 of 12 tissue specimens from PDH dogs. These data show that LIFR is highly co-expressed with adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in the canine pituitary gland and in corticotrope adenomas. Nuclear immunoreactivity for LIFR in nontumorous cells of the pars distalis may indicate the presence of a corticotrope adenoma.

Topics: ACTH-Secreting Pituitary Adenoma; alpha-MSH; Animals; Cell Nucleus; Cosyntropin; Cytoplasm; DNA, Complementary; Dog Diseases; Dogs; Female; Fluorescent Antibody Technique; Immunohistochemistry; Leukemia Inhibitory Factor; Male; Mutation; Pituitary Gland; Pituitary Neoplasms; Polymerase Chain Reaction; Receptors, OSM-LIF; Sequence Analysis, DNA

One microgram short synacthene test is widely recommended as a screening test for evaluation of hypothalamo-pituitary-adrenocortical axis in patients with secondary adrenal insufficiency. Information on adequacy of cortisol response to this dose at different periods of the day in patients with hypothalamic-pituitary disorders is not available. Hence, this study was designed to assess the adequacy of cortisol response to 1 microg 1-24 adrenocorticotropin (ACTH) at 0800 h and 1600 h in patients with sellar and suprasellar mass lesions.. Thirty five consecutive patients with sellar and suprasellar mass lesions with mean age of 43.0+/-14.4 yr and 36 healthy controls with mean age of 32.3+/-9.0 yr were studied after obtaining informed consent. Maintenance doses of glucocorticoids in these patients were discontinued appropriately. On day 1, prestimulated and stimulated plasma cortisol samples at 0800 h and at 30 and 60 min following i.v. bolus of 1 microg 1-24 ACTH were collected. While on day 3, plasma cortisol samples were similarly collected at 1600 h. Cortisol estimation was done by a sensitive and specific radioimmunoassay. Stimulated plasma cortisol of 500 nmol/l or higher was defined as a normal response.. In healthy controls, the prestimulated and peak cortisol levels at 0800 h (377.5+/-93.3 and 729.1+/-183.2 nmol/l) were higher (P<0.001 and P<0.01) than those at 1600 h (230.1+/-75.7 and 665.8+/-138.6 nmol/l). All subjects had a cortisol response of 500 nmol/l or higher in response to 1 microg 1-24 ACTH both at 0800 and 1600 h. In the patients' group, the prestimulated plasma cortisol at 0800 h (250.3+/-169.7 nmol/l) was higher (P<0.001) than that at 1600 h (166.3+/-128.9 nmol/l), while the peak cortisol response was comparable (P>0.05) in the morning as well as in the evening (490.9+/-309.4 vs 464.8+/-318.4). In 27 patients (77%) the morning and evening stimulated cortisol response to 1 microg 1-24 ACTH was consistent (normal in 13 and subnormal in 14) but was discrepant in the remaining 8 (23%). In 7 of these 8 patients, cortisol response was normal at 0800 h but not at 1600 h, while in only one, normal response was seen at 1600 h but not at 0800 h.. The demonstration of normal peak cortisol response to 1 microg 1-24 ACTH at 0800 h but not at 1600 h in substantial number of patients with sellar and suprasellar mass lesions suggests preference to morning for performing this test.

Topics: Adolescent; Adult; Aged; Circadian Rhythm; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System

Since 1988, when a retrospective study of patients attending this unit was published, we have advocated the use of the short synacthen test (SST) as the primary screening investigation to detect ACTH deficiency. However, others have published comparisons of SST and insulin tolerance tests that suggest a significant false negative rate with SST, leading to concern that some patients who pass the SST are in danger from the clinical consequences of ACTH deficiency. To address this, we audited biochemical results and clinical outcome in 63 patients who did not have ACTH deficiency detected (i.e. who passed the test) by SST after pituitary surgery. Twelve of the 63 patients who passed a SST after pituitary surgery became ACTH-deficient later as diagnosed by SST: 4 within the first year, 2 of whom had received postoperative radiotherapy (3 had symptoms of tiredness and 1 was admitted to the hospital with a viral infection); 8 in yr 3-5, 7 of whom had received postoperative radiotherapy (all had either no symptoms or symptoms of tiredness alone). Thus, the predictive value of the SST in excluding ACTH deficiency is approximately 97% (2 of 63 patients who initially passed the SST were found to be ACTH-deficient within 12 months without having received postoperative radiotherapy). Only 1 patient was ill enough to require hospital admission. Setting the risk of false negatives with SST against the morbidity and manpower implications associated with insulin tolerance tests, SST remains the primary screening test for ACTH deficiency in our practice. However, a high index of clinical suspicion to detect false negative results must be maintained.

Topics: Acromegaly; Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Cosyntropin; Craniopharyngioma; False Negative Reactions; Female; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Sensitivity and Specificity

Tetracosactin [corticotropin-(1-24)] is used for clinical testing of adrenocortical responsiveness. The usual dose [high dose test (HDT)] is 250 micrograms. With this test, patients with mild secondary adrenal insufficiency are usually not identified, thus putting them at risk of an adrenal crisis in stressful situations. It was recently reported that a tetracosactin test with approximately 1 micrograms [low dose test (LDT)] identifies patients with mild forms of pituitary-adrenal insufficiency. We performed both the HDT and the LDT in 35 control subjects and in 44 patients with pituitary disease, mostly pituitary tumors. In these patients, more sensitive reference tests for evaluating the pituitary-adrenal axis (insulin-induced hypoglycemia, metyrapone, and CRH tests) were also performed. In the HDT, plasma cortisol was measured 30 and 60 min after tetracosactin injection; in the LDT (0.5 microgram/m2 body surface area), plasma cortisol was measured 20, 30, 40, 50, and 60 min postinjection. In 6 control subjects, tetracosactin plasma levels were also measured after injection. In the HDT, the correlation between 30 and 60 min cortisol levels was extremely high (r = 0.991; P < 0.0001), but the correlation of the LDT with the HDT at 30 min was also highly significant (r = 0.948; P < 0.0001). The lower normal limit of cortisol responses (means of controls minus 2 SD) at 30 min was lower in the LDT by 3.1 micrograms/dL (85 nmol/L) than in the HDT. Compared with the reference tests, the diagnostic sensitivities of the HDT and the LDT were almost identical. Both tests identified patients with moderately to severely pathological insulin and metyrapone tests, but not those with slightly pathological reference tests. In the HDT, plasma tetracosactin rose to more than 60,000 pg/mL shortly after injection. In the LDT, it rose to 1,900 pg/mL. Both concentrations stimulate cortisol (supra-) maximally. Together, these data show that in pituitary disorders the results of the LDT and the HDT are almost identical. Plasma tetracosactin levels in the LDT still rise to levels that maximally stimulate the adrenal. Tetracosactin testing with low or high doses cannot generally replace the more expensive and cumbersome insulin or metyrapone tests.

Topics: Adult; Aged; Aged, 80 and over; Corticotropin-Releasing Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Insulin; Kinetics; Male; Metyrapone; Middle Aged; Pituitary Diseases; Pituitary Neoplasms

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

Recent data suggest that recovery of anterior pituitary function promptly follows surgical decompression and that hypothalamic-pituitary-adrenal axis assessment need not be delayed following transsphenoidal pituitary surgery. We hypothesized that one protocol for both glucocorticoid supplementation and axis investigation prior to discharge may be applied to all transsphenoidal pituitary surgery patients. The protocol examined the merits of preoperative testing and of basal and hypoglycaemia-stimulated cortisol and ACTH measurements in post-operative axis evaluation.. Rapid tetracosactrin stimulation testing classified patients according to preoperative adrenal integrity. All patients received tapered doses of hydrocortisone beginning on the morning of surgery and discontinued after 48 hours.. Of 28 consecutive patients with various pituitary tumours, 19 completed all aspects of the protocol. All evaluable information from the other 9 was incorporated into the final conclusions and recommendations.. Morning serum cortisol was measured 24 hours after the last hydrocortisone dose. Plasma ACTH and serum cortisol were measured during insulin tolerance testing within 8 days after surgery. Patients received clinical evaluations and repeat testing as clinically indicated during 6-30 months of follow-up.. Both peak serum cortisol > 550 nmol/l and peak plasma ACTH of > 4.4 pmol/l during insulin tolerance testing were 100% sensitive and specific in predicting sustained hypothalamic-pituitary-adrenal axis integrity after surgery. For patients entering surgery with normal tetracosactrin tests, an initial morning serum cortisol > 270 nmol/l provided 100% specificity for preserved axis integrity, but a low cortisol did not indicate axis dysfunction. For patients entering surgery with cortisol deficiency, an initial morning cortisol < 60 nmol/l indicated sustained axis failure, but higher values proved inconclusive. However, the basal cortisol, but not ACTH, on the day of insulin tolerance testing conclusively defined axis status in 18 of 19 study patients (95%).. We conclude that (1) a 48-hour perioperative hydrocortisone reducing regimen may be used in all uncomplicated transsphenoidal pituitary surgery cases regardless of pituitary-adrenal axis status before surgery; (2) preoperative adrenal testing aids interpretation of the initial morning serum cortisol and may be used to direct further testing; (3) a single morning serum cortisol drawn 24 hours after glucocorticoid withdrawal suffices for pituitary-adrenal axis investigation if result suggest no change in axis function, as occurred in most study patients; (4) while insulin tolerance testing 5-8 days after surgery is 100% accurate in determining the need for sustained glucocorticoid replacement due to clinically significant hypopituitarism, repeat morning cortisol measurement obviates provocative testing in 95% of cases; and (5) basal and stimulated plasma ACTH values provide no information additional to serum cortisol measurements in post-operative axis evaluation.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Anti-Inflammatory Agents; Cosyntropin; Female; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Postoperative Period

The best dynamic test for the assessment of the hypothalamic-pituitary-adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic-pituitary-adrenal axis.. Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed.. Programmed Investigation Unit.. Fifty-seven healthy volunteers and 166 patients.. Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycemia (plasma glucose < 2 mmol/l) during an IST.. From normal data the mean-2SD 30-minute value during the SST was 392 nmol/l and 60-minute value was 497 nmol/l. The maximal cortisol response (mean - 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission.. Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

Topics: Adrenal Cortex Function Tests; Adult; Cost-Benefit Analysis; Cosyntropin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Medical Audit; Pituitary Neoplasms; Pituitary-Adrenal System; Predictive Value of Tests; Reference Values; Stimulation, Chemical; Time Factors

Topics: Cosyntropin; Humans; Insulin; Pituitary Neoplasms

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

Corticotropin deficiency may occur after pituitary surgery, and, if unrecognized and untreated, it can be fatal. In this study the insulin tolerance test was used to assess hypothalamic-pituitary-adrenal reserve five to seven days after pituitary surgery, and postoperative morning serum cortisol concentration was compared with the insulin tolerance test for predicting corticotropin deficiency. In 35 patients with pituitary tumors studied prospectively, 27 had normal insulin tolerance test results five to seven days after pituitary surgery; in these patients, the morning serum cortisol concentration two to three days after surgery was 250 nmol/L (9 micrograms/dL) or greater. Eight patients had subnormal insulin tolerance test results or clinical evidence of adrenal insufficiency; the morning serum cortisol concentration in these patients was 80 nmol/L (3 micrograms/dL) or less. Postoperative adrenal insufficiency was transient (one to three months) in five of these eight patients. We retrospectively identified 45 patients whose postoperative morning serum cortisol values were 200 nmol/L (7 micrograms/dL) or greater; none of these patients had clinical evidence of adrenal insufficiency. We conclude that a morning serum cortisol level obtained two to three days after surgery and 24 hours after the discontinuation of hydrocortisone accurately predicts postoperative corticotropin reserve.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Postoperative Period; Prospective Studies; Retrospective Studies

A simple, short and sensitive direct radio-immunoassay technique for the determination of salivary cortisol concentration was employed to assess saliva as a medium for evaluating cortisol response during endocrine testing in 9 controls and 40 patients. Results in controls suggested that an adequate salivary cortisol response to insulin hypoglycaemia was an increase of 150% above the basal value with a minimum peak of 15 nmol/l. Thirty-three patients were classified as being either good or poor responders to insulin hypoglycemia on the basis of criteria for plasma cortisol levels. When the defined salivary cortisol response was used for assessment, all 33 patients were correctly categorized into the same response groups. The salivary cortisol response to intramuscular tetracosactrin in 3 patients and an intravenous dexamethasone infusion in 4 patients confirmed the value of saliva as an assay medium. These studies show that the salivary cortisol response parallels that of total plasma cortisol in all cases. However, with sampling at short intervals a lag in secretion of the free fraction from the plasma into the saliva becomes apparent. The relative change in cortisol levels from the basal value is greater in saliva than in plasma.

Topics: Adult; Cosyntropin; Cushing Syndrome; Dexamethasone; Dose-Response Relationship, Drug; Evaluation Studies as Topic; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Radioimmunoassay; Saliva

Topics: Adenoma, Basophil; Adrenocorticotropic Hormone; Adult; Cosyntropin; Cytoplasm; Cytoplasmic Granules; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Lysosomes; Male; Pituitary Neoplasms; Pituitary-Adrenal System; Staining and Labeling