cosyntropin and Adenoma

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

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

The diagnosis of central adrenal insufficiency (AI) continues to be challenging, especially when it is partial. We have recently demonstrated the value of measuring serum dehydroepiandrosterone sulfate (DHEA-S) in establishing the diagnosis of central AI. The current investigation examined the added value of measuring serum dehydroepiandrosterone (DHEA) levels during low-dose (1 μg) cosyntropin (LDC) stimulation in patients suspected to have central AI.. Baseline and LDC-stimulated cortisol, DHEA, and DHEA-S were measured preoperatively in 155 consecutive patients with pituitary masses and 63 healthy subjects. Hypothalamic-pituitary adrenal (HPA) function was normal (NL-HPA) in 97 of the patients and was impaired (impaired HPA) in 58 patients. Patients with NL-HPA underwent surgical removal of the sellar masses and received no glucocorticoids before, during, or after surgery.. Baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S in patients with NL-HPA were similar to those of normal subjects. In contrast, patients with impaired HPA had lower baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S levels. There were 18 subjects in the latter group whose LDC-stimulated serum cortisol levels were greater than 18.0 μg/dl. In those 18 subjects, baseline and LDC-stimulated DHEA and DHEA-S levels were similar to the whole group of patients with impaired HPA function. The molar ratio of cortisol to DHEA did not change with LDC stimulation in normal subjects and those with NL-HPA. In contrast, patients with impaired HPA had a higher baseline cortisol to DHEA molar ratio that increased further with LDC stimulation.. Patients with impaired HPA function have a more severe loss in DHEA secretion than that of glucocorticoids. Measurements of serum DHEA levels during LDC simulation provide additional valuable information that improves the diagnostic accuracy of LDC in patients suspected to have central AI. We recommend the inclusion of DHEA and DHEA-S measurements in the laboratory assessment of HPA function.

Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adrenal Insufficiency; Adult; Aged; Chemistry, Clinical; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diagnostic Techniques, Endocrine; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Prolactinoma; Reproducibility of Results

Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.. Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing's syndrome were excluded.. The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.. Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenalectomy; Adult; Aged; Cosyntropin; Cushing Syndrome; Dexamethasone; Endocrinology; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Pheochromocytoma; Postoperative Period; Retrospective Studies

We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA).. Multicenter retrospective study by Japan PA study.. We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria.. Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI.. Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Adrenocortical Adenoma; Adult; Aged; Cohort Studies; Cosyntropin; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Prognosis; Registries; Retrospective Studies; Sensitivity and Specificity; Treatment Outcome

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

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

Patients with non-hyperfunctioning adrenal adenomas often have an increased plasma 17-hydroxyprogesterone response to ACTH stimulation. The effects of adrenal surgery on this abnormality have rarely been investigated. One hundred and sixty-one patients with unilateral adrenal tumors (non-hyperfunctioning adenomas, 78; cortisol-producing adenomas, 8; aldosterone-producing adenomas, 37; adrenal cysts, 12; pheochromocytomas, 26) were studied. Patients before and after adrenal surgery as well as 60 healthy subjects underwent an ACTH stimulation test using 2 mg synthetic ACTH(1-24) (Cortrosyn Depot, Organon). Basal and ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations are reported. Before adrenal surgery, the basal plasma 17-hydroxyprogesterone concentrations were normal in patients with all types of tumors. However, the ACTH-stimulated plasma 17-hydroxyprogesterone levels were abnormally increased in 53% and 31% of patients with non-hyperfunctioning adenomas and aldosterone-producing adenomas, respectively. In addition, a few patients with adrenal cysts and pheochromocytomas also showed an increased ACTH-stimulated 17-hydroxyprogesterone response. After unilateral adrenalectomy, this hormonal abnormality disappeared in most, although not all patients with adrenal tumors. In patients with non-hyperfunctioning adrenal tumors, ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations significantly correlated with the size of the tumors. These results firmly indicate that the tumoral mass itself may be responsible for the increased plasma 17-hydroxyprogesterone and cortisol responses after ACTH stimulation in patients with non-hyperfunctioning and hyperfunctioning adrenal adenomas.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adolescent; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Aged; Aldosterone; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Pheochromocytoma

A 43-year-old female with a 24-years history of hypertension presented for further investigation and management of primary hyperaldosternoism. Postural studies were not conclusive and magnetic resonance (MR) imaging demonstrated a 27 x 18 mm lesion of the right adrenal gland which showed no signal loss during in and out of phase imaging. Although these appearances were considered to be atypical of those seen on MR in patients with aldosterone producing adrenal adenomas the patient underwent an adrenalectomy with removal of a 3 x 3 x 2 cm right adrenal mass. Post-operatively she became hypotensive and a 0900 hours serum cortisol was undetectable (< 50 nmol/l), consistent with adrenal insufficiency. Following the administration of hydrocortisone there was normalization of the blood pressure and subsequent adrenal stimulation tests confirmed the presence of functioning adrenal tissue albeit with an inadequate response. Cortisol measurement from preoperative samples revealed loss of normal diurnal rhythm whereas DHEAS levels both pre and postoperatively were undetectable, consistent with ACTH supression resulting from autonomous cortisol secretion in addition to aldosterone. Concurrent secretion of cortisol should always be considered in Conn's adenomas particularly when atypical radiological features are present.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Aldosterone; Cosyntropin; Female; Humans; Hydrocortisone; Magnetic Resonance Imaging; Neoplasm Proteins

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 reports have shown an exaggerated response of 17-hydroxyprogesterone in up to 70% of patients with incidentally detected adrenal adenomas ('incidentalomas'). This has been explained by pre-existing 21-hydroxylase deficiency which may be a pathogenetic factor in the development of adrenal tumours. However, other defects in steroidogenesis, such as mild 11 beta-hydroxylase deficiency, could also result in increased 17-hydroxyprogesterone secretion. We therefore studied the glucocorticoid and mineralocorticoid pathways in patients with adrenal 'incidentalomas' by measuring multiple adrenal steroids before and after 1-24 ACTH stimulation. Twenty patients with adrenal 'incidentalomas' (14 females, 6 males) and 27 healthy controls (14 females, 13 males) were studied. All subjects underwent a 1-24 ACTH stimulation test (250 micrograms i.v.) with determination of progesterone, 11-deoxycorticosterone, corticosterone, 17-hydroxyprogesterone, 11-deoxycortisol and cortisol at 0 and 60 min. All steroids were measured by RIA after extraction and HPLC. Patients with 'incidentalomas' had higher stimulated concentrations of 17-hydroxyprogesterone (21.6 +/- 8.4 vs 4.2 +/- 0.3 nmol/I; P < or = 0.001), 11-deoxycortisol (8.1 +/- 1.2 vs 3.6 +/- 0.3 nmol/I; P < or = 0.001), progesterone (8.28 +/- 2.82, vs 1.08 +/- 0.15 nmol/I; P < or = 0.001), and 11-deoxycorticosterone (2.1 +/- 0.39 vs 0.78 +/- 0.12 nmol/I; P = 0.002) compared with controls. In contrast, cortisol and corticosterone concentrations were not different. There was evidence for impairment of 11 beta-hydroxylase activity by an increased 11-deoxycortisol/ cortisol ratio (0.012 +/- 0.003 vs 0.005 +/- 0.001 in controls; P = 0.002) and 11-deoxycorticosterone/ corticosterone ratio (0.04 +/- 0.003 vs 0.015 +/- 0.003; P = 0.003). The conclusions reached were that patients with adrenal 'incidentalomas' have increased responses of precursors of the mineralocorticoid and glucocorticoid pathway including 17-hydroxyprogesterone after stimulation with ACTH. This seems to be caused by impairment of 11 beta-hydroxylase activity rather than by impaired 21-hydroxylase activity in these tumours.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Gland Neoplasms; Adult; Aged; Cortodoxone; Cosyntropin; Desoxycorticosterone; Female; Humans; Male; Middle Aged; Progesterone; Reference Values; Steroid 11-beta-Hydroxylase; Steroid 21-Hydroxylase

A case of Cushing's syndrome induced by the unilateral (right side) dominance of cortisol secretion in the face of bilateral adrenal tumors is reported. The adrenal tumor resected on the right side was a so-called black adenoma and histologically without any findings of nodular hyperplasia. After resection of the adrenal adenoma, no findings of cortisol hypersecretion from the remaining adrenal tumor on the left side were observed until the present, suggesting that the tumor of the left adrenal gland is a nonfunctioning adenoma. These data imply that the adrenal adenomas have primarily developed from the adrenal gland itself, rather than from micronodular hyperplasia by corticotropin stimulation, and that one of these tumors produces excess hormones initially by corticotropin stimulation, but the other remains in cell proliferation.

Topics: Adenoma; Adrenal Cortex Hormones; Adrenal Cortex Neoplasms; Adult; Cosyntropin; Cushing Syndrome; Dexamethasone; Follow-Up Studies; Growth Hormone; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Metyrapone

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

The effect of human atrial natriuretic peptide (hANP) on aldosterone, 18-OH-cortisterone, corticosterone, deoxycorticosterone, and cortisol secretion was examined in isolated human aldosteronoma cells from five patients with primary aldosteronism. hANP exerted a nearly identical inhibitory action on basal secretion of each of these steroids and antagonized also the stimulating effects of ACTH, serotonin, metoclopramide and vasoactive intestinal polypeptide. The results suggest that in human aldosteronoma cells hANP may be a non-selective inhibitor of corticosteroid biosynthesis and that the site of inhibition of steroidogenesis may be localized to the early pathway of steroid biosynthesis.

Topics: Adenoma; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Aldosterone; Atrial Natriuretic Factor; Cosyntropin; Humans; In Vitro Techniques; Kinetics; Metoclopramide; Vasoactive Intestinal Peptide

An adrenal tumour was incidentally discovered with no clinical signs of Cushing's syndrome. The endocrine evaluation revealed the unique hormonal constellation of an increased urinary cortisol excretion rate, unequivocal suppressibility of plasma and urinary cortisol by dexamethasone, but only to a residual level in the low normal range which probably reflected ACTH-independent 'autonomous' cortisol secretion. After removal of the adrenal mass, urinary cortisol secretion and dexamethasone suppressibility were normalized. In vitro, the tumour cells were as sensitive towards ACTH as 'normal' human adrenal cells, but showed a reduced cortisol production rate per cell. We suppose that the adrenal mass participated in the diurnal rhythm of ACTH-mediated cortisol secretion in vivo, which resulted in an increased cortisol secretion. During the night, when ACTH levels were low, the cortisol production decreased and the hormone levels were probably too low to suppress ACTH. We regard the hormonal findings in our patients as 'Pre-Cushing's syndrome', although the absence of clinical features of Cushing's syndrome remains unclear. We suggest that every patient with an incidentally discovered adrenal mass should have an endocrinological evaluation because the results may help to decide whether or not the adrenal tumour should be removed.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Angiotensin II; Cosyntropin; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Male; Middle Aged; Peptide Fragments

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Cosyntropin; Humans; Hyperaldosteronism; Male; Middle Aged

Data are presented concerning a case of female pseudohermaphroditism of unknown etiology. The child was born with labioscrotal fusion and clitoromegaly. From the age of 5 to the age of 25 there was no clinical evidence of a hormonal abnormality. At the age of 25 the patient presented with masculinization and Cushing's syndrome, and a left adrenal tumor was removed. The patient was restudied at the age of 29, when 21-hydroxylase deficiency was excluded. Other types of congenital adrenal hyperplasia are considered unlikely. The possible relationship between the ambiguous genitalia present at birth and the virilizing tumor diagnosed at the age of 25 is analyzed.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Cortex Neoplasms; Adult; Age Factors; Cortodoxone; Cosyntropin; Disorders of Sex Development; Female; Humans; Hydrocortisone; Hydroxyprogesterones

In vitro aldosterone, deoxycorticosterone, corticosterone and cortisol production of human adrenocortical cells derived from adenomas (Conn's syndrome, Cushing's syndrome), from hyperplastic adrenals (Cushing's syndrome) and from adrenals surrounding aldosteronoma are described. Cells from adenomas causing either Cushing's syndrome or Conn's syndrome harboured the highest basal and ACTH-stimulated corticosteroid production. Adrenocortical cells derived from micronodular hyperplasia causing Cushing's syndrome and cells from cortisol producing adenoma displayed predominantly cortisol and corticosterone secretion both under basal conditions and following stimulation with ACTH. Aldosteronoma cells showed highly variable aldosterone, deoxycorticosterone, corticosterone and cortisol response to ACTH. However, in aldosteronoma cell suspensions, the basal and ACTH-stimulated ratios of aldosterone to cortisol were increased when compared to ratios of steroids produced by cells from other adrenal tissues. Chronic treatment with spironolactone of patients with Conn's syndrome before surgery was associated with a decreased ratio of aldosterone to corticosterone, revealing that 18-hydroxylase in aldosteronoma cells may be inhibited during long-term therapy. Non-tumorous cells isolated from adrenals surrounding aldosteronoma displayed less aldosterone prior to and after stimulation with ACTH than aldosteronoma cells.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aldosterone; Corticosterone; Cosyntropin; Cushing Syndrome; Desoxycorticosterone; Humans; Hydrocortisone; Hyperaldosteronism; In Vitro Techniques

Systemic administration of the enkephalin analog FK 33.824 was previously shown to inhibit ACTH secretion in man. In this study, the direct action of this analog on cortisol release was studied. The enkephalin analog (1 microM and 10 microM) did not influence basal or ACTH-stimulated cortisol production by cultured isolated adrenocortical cells prepared from the hyperplastic adrenal glands from three patients with Cushing's disease. Naloxone (10 microM) had also no direct effect on cortisol release. It is concluded that the met-enkephalin analog used in this study and naloxone do affect the hypothalamo-pituitary-adrenal axis via a central effect.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Cells, Cultured; Cosyntropin; Cushing Syndrome; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Enkephalin, Methionine; Growth Hormone-Releasing Hormone; Hormones; Humans; Hydrocortisone; Naloxone

In vitro application of the morphinomimetic met-enkephalin resulted in inhibition of mineralocorticoid production by aldosterone-producing adenomas. Aldosterone, deoxycorticosterone, and corticosterone production by adrenocortical cells isolated from aldosteronomas has been studied under basal conditions and after stimulation with ACTH-(1-24). The blocking effect of met-enkephalin on the rate of aldosterone, deoxycorticosterone, and corticosterone release was significant at a concentration as low as 10(-11) M (P less than 0.001, P less than 0.01, and P less than 0.001, respectively). Dose-dependent inhibition of steroid biosynthesis became more apparent with increasing amounts of met-enkephalin in the incubation medium (10(-11)-10(-5) M); at a concentration of 10(-5) M, met-enkephalin decreased the production of aldosterone by 45%, that of deoxycorticosterone by 51%, and that of corticosterone by 44%. Increased steroid biosynthesis stimulated by ACTH-(1-24) was also significantly blocked by met-enkephalin. In a concentration of 10(-5) M, met-enkephalin produced significant decreases in aldosterone (P less than 0.001), deoxycorticosterone (P less than 0.05), and corticosterone (P less than 0.001) production compared to the peak values obtained after stimulation with 0.85 X 10(-10) M ACTH-(1-24). These data allow us to conclude that the inhibitory effect of met-enkephalin on mineralocorticoid production exerted at the level of the adrenals might be complementary to the factor(s) thought to be involved in the regulation of adrenal steroid production, playing a role similar to that of the biogenic amines originating in the adrenal medulla and regulating the adrenal cortex by a peripheral neurohumoral paracrine mechanism.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Aldosterone; Corticosterone; Cosyntropin; Desoxycorticosterone; Dose-Response Relationship, Drug; Endorphins; Enkephalin, Methionine; Enkephalins; Humans; Hydrocortisone; In Vitro Techniques; Mineralocorticoids

Topics: 18-Hydroxycorticosterone; Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Aldosterone; Angiotensin III; Corticosterone; Cosyntropin; Female; Humans; Male; Middle Aged

A case of fluctuating Cushing's syndrome due to an adrenal adenoma is described. Plasma corticosteroids were frequently low and urinary steroids fluctuated markedly over a 15-month period. Only the response to dexamethasone was consistently abnormal and indicative of Cushings's syndrome.

Topics: 11-Hydroxycorticosteroids; 17-Hydroxycorticosteroids; Adenoma; Adrenal Gland Neoplasms; Circadian Rhythm; Cosyntropin; Cushing Syndrome; Dexamethasone; Female; Humans; Metyrapone; Middle Aged; Time Factors