cosyntropin and Addison-Disease

The silent pheochromocytoma, a hidden form of pheochromocytoma, exposes the patient to an increased risk of mortality if the diagnosis is not established on time. Biological diagnosis of pheochromocytoma can be difficult. Catecholamine secretion is dependent on tumor size and a large number of physiological, pharmacological, lifestyle modifications and sampling conditions influence the measurement of urinary and plasma metanephrines. The prevalence of pheochromocytoma is 2% among adrenal incidentaloma smaller than 3 cm (2/3 of tumors). Recent studies suggest the almost zero risk of pheochromocytoma among these tumors if they are hypodense (<10 housefield units) on adrenal tomography. Addison's disease is a pathology affecting about 1 in 8000. Immunopathology is still unknown, but some elements advocated the hypothesis of a predominant cell-mediated immunity in particular Interferon-gamma production by CD4 T lymphocytes in the presence of an epitope from the 21-hydroxylase, as well as IgG1 subtype produced by activated B lymphocytes, autoantibodies do appear to be a simple marker of the disease. Subclinical Addison's disease is defined by the presence of anti-21-hydroxylase autoantibodies, without clinical symptoms. It evolves faster to the clinical phase in young subjects, male, having high levels of autoantibodies and with an initially impaired adrenal function. Dosage of ACTH, plasma renin active, and basal cortisol and after Synacthen allow to discriminate the subjects with low or high risk of evolution and establish an appropriate monitoring.

Topics: Addison Disease; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; Autoantibodies; CD4-Positive T-Lymphocytes; Cosyntropin; Humans; Hydrocortisone; Immunity, Cellular; Interferon-gamma; Male; Metanephrine; Pheochromocytoma; Renin; Steroid 21-Hydroxylase

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

We describe a case of a 42 year old male who presented with Addison's disease resulting from primary lymphoma of the adrenals. Our case and a review of the literature indicates that this distinct entity has some unique clinical and radiologic features. In this entity, the lymphoma tends to be extranodal and have a poor prognosis. In addition, the computed tomography (CT) images have the unique appearance of enlargement of the adrenal gland with maintenance of the adreniform shape. We suggest that primary adrenal lymphoma is a distinct clinical entity and should be considered in patients with an elevated serum lactate dehydrogenase, characteristic CT findings and Addison's disease.

Topics: Addison Disease; Adrenal Cortex Neoplasms; Adrenal Gland Diseases; Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cosyntropin; Cyclophosphamide; Dexamethasone; Diagnosis, Differential; Doxorubicin; Etoposide; Eye Neoplasms; Fatal Outcome; Humans; Hydrocortisone; Hyperkalemia; Ifosfamide; L-Lactate Dehydrogenase; Lymphoma, T-Cell; Male; Methotrexate; Neoplasm Proteins; Oculomotor Muscles; Prednisone; Tomography, X-Ray Computed; Tuberculosis, Endocrine; Vincristine

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

Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis.. To determine frequencies and clinical features of residual corticosteroid production in patients with AAD.. Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography-tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test.. Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = -0.487; P < 0.001).. In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.

Topics: Addison Disease; Adrenal Cortex Hormones; Adult; Cosyntropin; Cross-Sectional Studies; Female; Humans; Male; Middle Aged

Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility.. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease.. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility.. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy.. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study.. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement.. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.

Topics: Addison Disease; Adolescent; Adrenal Cortex Hormones; Adrenal Glands; Adult; Aged; Cosyntropin; Female; Humans; Infusion Pumps; Male; Middle Aged; Remission Induction; Treatment Outcome; Young Adult

To determine the lowest ACTH dose that would induce a significant increase in serum cortisol concentration and identify the time to peak cortisol concentration in healthy neonatal foals.. Prospective randomized crossover study.. 11 healthy neonatal foals.. Saline (0.9% NaCl) solution or 1 of 4 doses (0.02, 0.1, 0.25, and 0.5 μg/kg [0.009, 0.045, 0.114, and 0.227 μg/lb]) of cosyntropin (synthetic ACTH) was administered IV. Serum cortisol concentrations were measured before and 10, 20, 30, 60, 90, 120, 180, and 240 minutes after administration of cosyntropin or saline solution; CBCs were performed before and 30, 60, 120, and 240 minutes after administration.. Serum cortisol concentration was significantly increased, compared with baseline, by 10 minutes after cosyntropin administration at doses of 0.1, 0.25, and 0.5 μg/kg. Serum cortisol concentration peaked 20 minutes after administration of cosyntropin at doses of 0.02, 0.1, and 0.25 μg/kg, with peak concentrations 1.7, 2.0, and 1.9 times the baseline concentration, respectively. Serum cortisol concentration peaked 30 minutes after cosyntropin administration at a dose of 0.5 μg/kg, with peak concentration 2.2 times the baseline concentration. No significant differences were detected among peak serum cortisol concentrations obtained with cosyntropin administration at doses of 0.25 and 0.5 μg/kg. Cosyntropin administration significantly affected the lymphocyte count and the neutrophil-to-lymphocyte ratio.. Results suggested that in healthy neonatal foals, the lowest dose of cosyntropin to result in significant adrenal gland stimulation was 0.25 μg/kg, with peak cortisol concentration 20 minutes after cosyntropin administration.

Topics: Addison Disease; Animals; Animals, Newborn; Cosyntropin; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Horse Diseases; Horses; Hydrocortisone; Male; Reproducibility of Results; Time Factors

To evaluate by echocardiography the cardiac structure and function in patients with primary adrenocortical insufficiency.. Two-dimensionally guided M-mode echocardiograms and spectral Doppler studies were performed in seven consecutive patients with newly diagnosed autoimmune primary adrenal failure before and 4-8 months after an adequate regimen of steroid substitution. Echocardiographic parameters were also studied in ten healthy controls.. In the cases with untreated Addison's disease, both left ventricular end-systolic and end-diastolic dimensions were significantly reduced in comparison with those in controls (P<0.01). Four patients had echocardiographic signs of mitral valve prolapse (MVP) at the anterior leaflet, with no evidence of mitral regurgitation by Doppler echocardiography. Systolic clicks characteristic of MVP were present on auscultation in two of these cases. Left ventricular chamber size normalized, i.e. significantly increased (P<0.01), and both echocardiographic and physical signs of MVP resolved after steroid substitution in all patients. All other echocardiographic indices were normal before and after treatment.. Patients with untreated Addison's disease have cardiac abnormalities which regress after steroid substitution. A valvular-ventricular disproportion due to the hypovolemic state could explain these findings.

Topics: Addison Disease; Adult; Cardiovascular Abnormalities; Cosyntropin; Echocardiography; Female; Hemodynamics; Hormone Replacement Therapy; Hormones; Humans; Male; Mitral Valve Prolapse; Stroke Volume

During a Phase I trial of suramin, a novel antineoplastic agent with activity against hormone-refractory prostate carcinoma, the authors observed two patients with clinical mineralocorticoid insufficiency in spite of hydrocortisone replacement therapy.. The authors retrospectively assessed adrenal cortical function in 20 such patients via adrenocorticotropic stimulation testing, measuring both cortisol and aldosterone responses, either at the time or treatment of immediately after discontinuation of treatment.. Two of 9 patients (22%) treated at relatively low dose levels (< or = 1200 mg/m2 on Day 1) demonstrated adrenal cortical insufficiency, as compared with 9 of 11 patients (32%) treated with relatively high doses (> 1200 mg/m2 on Day 1) (P = 0.03 by 1-tailed Fisher's exact test). There appeared to be a cumulative dose-response relationship to the development of glucocorticoid insufficiency, with no instances being observed at doses < 4.8 g/m2 and uniform toxicity occurring at doses > 7.6 g/m2. Long term glucocorticoid insufficiency was present in 1 of 5 patients (20%) tested at an interval of > 90 days after discontinuation of suramin treatment. All instances of glucocorticoid insufficiency were associated with mineralocorticoid insufficiency. Suramin did not affect the absorption or excretion of exogenously administered glucocorticoid in one patient.. Suramin causes both primary mineralocorticoid and primary glucocorticoid insufficiency. This may occur in a dose-dependent manner. Long term glucocorticoid insufficiency appears to occur in a minority of patients treated with low doses of suramin. Patients receiving high doses of suramin for treatment of advanced carcinoma should receive at least physiologic replacement doses of both mineralocorticoid and glucocorticoid. Higher doses of glucocorticoid may be required in selected patients.

Topics: Addison Disease; Adrenal Cortex Diseases; Adrenocorticotropic Hormone; Aged; Aldosterone; Antineoplastic Agents; Cosyntropin; Drug Administration Schedule; Humans; Hydrocortisone; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Suramin

Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.. Cross-sectional study.. We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH.. Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively).. We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.

Topics: Addison Disease; Biomarkers; Cardiovascular Diseases; Cosyntropin; Cross-Sectional Studies; Extracellular Matrix Proteins; Female; Glucocorticoids; Humans; Inflammation; Leptin; Male; Neoplasm Proteins; Quality of Life

There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link is established. There are reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19. We describe the first pediatric report of adrenal insufficiency and autoimmune hypothyroidism after COVID-19.. A 14-year-old previously healthy girl, with vitiligo, presented in shock following 1 week of fever, lethargy, diarrhea, and vomiting. Three weeks prior, she had congestion and fatigue and known familial exposure for COVID-19. Labs were remarkable for sodium 129 mmol/L, K 4.3 mmol/L, creatinine 2.9 mg/dL, hemoglobin 8.3 g/dL, and positive COVID-19 PCR and SARS-CoV-2 IgG. She was resuscitated with normal saline and required pressor support. EKG showed abnormal repolarization presumed secondary to myocarditis. She met the criteria for multisystem inflammatory syndrome in children (MIS-C), received intravenous immune globulin and IL-1R antagonist and was admitted for intensive care. Persistent hypotension despite improved inflammatory markers and undetectable cortisol led to initiation of hydrocortisone. She was then able to rapidly wean off pressors and hydrocortisone within 48 h. Thereafter, tests undertaken for persistent bradycardia confirmed autoimmune hypothyroidism with TSH 131 μU/mL, free T4 0.85 ng/dL, and positive thyroid autoantibodies. Basal and stimulated cortisol were <1 μg/dL on a standard 250 μg cosyntropin stimulation test, with baseline ACTH >1,250 pg/mL confirming primary adrenal insufficiency. Treatment was initiated with hydrocortisone, levothyroxine, and fludrocortisone. Adrenal sonogram did not reveal any hemorrhage and anti-adrenal antibody titers were positive. The family retrospectively reported oligomenorrhea, increased salt craving in the months prior, and a family history of autoimmune thyroiditis. The cytokine panel was notably different from other cases of MIS-C.. This is the first pediatric report, to our knowledge, of primary adrenal insufficiency and hypothyroidism following COVID-19, leading to a unique presentation of autoimmune polyglandular syndrome type 2. The initial presentation was attributed to MIS-C, but the subsequent clinical course suggests the possibility of adrenal crisis. It remains unknown if COVID-19 had a causal relationship in triggering the autoimmune adrenal insufficiency and hypothyroidism.

Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Adult; Autoantibodies; Child; Cosyntropin; COVID-19; Creatinine; Cytokines; Female; Fludrocortisone; Hashimoto Disease; Humans; Hydrocortisone; Hypothyroidism; Immunoglobulins, Intravenous; Retrospective Studies; Saline Solution; SARS-CoV-2; Sodium; Systemic Inflammatory Response Syndrome; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine

We report here a woman in her 70s presenting with adrenal insufficiency secondary to a primary adrenal lymphoma. The patient had a previous history of aphthous ulcers on dexamethasone and was referred to endocrinology with symptoms of fatigue and orthostasis. Subsequent Cosyntropin stimulation showed primary adrenal insufficiency and adrenal CT demonstrated large infiltrative masses. Adrenal biopsy confirmed the diagnosis of primary adrenal lymphoma of the B-cell type. This case demonstrates the importance of including lymphoma in the differential diagnosis of adrenal insufficiency, particularly in the elderly population and in the setting of negative 21-hydroxlyase antibody results.

Topics: Addison Disease; Adrenal Gland Neoplasms; Adrenal Insufficiency; Aged; Cosyntropin; Dexamethasone; Female; Humans; Lymphoma; Lymphoma, B-Cell; Tomography, X-Ray Computed

In autoimmune Addison's disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion. Patients on long-term steroid replacement have increased morbidity, reduced life expectancy, and poorer quality of life.. The objective of this article is to restore adrenocortical steroidogenic function in recent-onset AAD.. An open-label, multicenter trial of immunotherapy and trophic stimulation in new-onset AAD was conducted. Serial measurement of serum and urine corticosteroids at baseline and throughout a 72-week follow-up period was performed.. This study was conducted at the.. endocrine departments and clinical research facilities at 5 UK tertiary centers.. Thirteen participants (9 female, 4 male; age 19-64 years) were included with AAD confirmed by high adrenocorticotropin, low circulating cortisol (basal < 100 nmol/L or post-tetracosactide < 300 nmol/L), and positive serum 21-hydroxylase antibodies.. All participants received dual therapy with B-lymphocyte-depleting immunotherapy (rituximab 1 g given twice) and repeated depot tetracosactide (1 mg on alternate days for 12 weeks).. Restoration of normal GC secretion (stimulated cortisol > 550 nmol/L) at week 48 was the main outcome measure.. Ten of 13 (77%) participants had detectable stimulated serum cortisol (26-265 nmol/L) at trial entry. Following intervention, 7 of 13 (54%) had an increase in stimulated cortisol measurement, with a peak response of 325 nmol/L at week 18 in 1 participant. Increased steroid metabolites, assayed by urine gas chromatography-mass spectrometry at week 12 and week 48, was detected in 8 of 13 (62%) individuals, reflecting an increase in endogenous steroidogenesis. Four of 13 had residual adrenal function at 72 weeks.. Combined treatment with rituximab and depot tetracosactide did not restore normal adrenal function. Nevertheless, adrenocortical plasticity is demonstrated in some patients, and this has the potential to be exploited to improve adrenal function.

Topics: Addison Disease; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Biomarkers; Cosyntropin; Drug Therapy, Combination; Female; Follow-Up Studies; Hormones; Humans; Hydrocortisone; Immunologic Factors; Male; Middle Aged; Quality of Life; Rituximab; Young Adult

The natural history of adrenal function in autoimmune Addison disease once diagnosed and treated has not been systematically studied, but several case reports of recovery from established adrenal failure suggest it may not be uniform.. To ascertain steroidogenic function in autoimmune Addison disease immediately following diagnosis and during prolonged treatment.. We studied peak serum cortisol in response to ACTH1-24 in 20 newly diagnosed autoimmune Addison disease patients at first presentation and then again within a month. We also studied 37 patients with established Addison disease (for between 7 months and 44 years) in a medication-free state, measuring peak serum cortisol responses to ACTH1-24 and the urine LC-MS steroid metabolome.. Adrenal steroidogenesis declined rapidly after steroid replacement treatment for newly diagnosed Addison disease was started, with a peak serum cortisol falling from 138 ± 19 nmol/L (SEM) at presentation to 63 ± 13 nmol/L over 4 weeks (P < 0.003).Six of 37 participants (16%) with established Addison disease had detectable serum cortisol and urine glucocorticoid and mineralocorticoid metabolites during repeat testing, indicating variable degrees of residual adrenal function.. Autoimmune Addison disease is a heterogeneous condition, showing a rapid decline in adrenal steroidogenesis during the first few weeks following diagnosis, but low-level residual function in a minority of patients, which appears to persist for many years.

Topics: Addison Disease; Adolescent; Adrenal Glands; Adult; Autoimmune Diseases; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Young Adult

During a clinical trial of regular tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antitetracosactide (ACTH1-24 ) antibodies.. Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves' disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera.. Bands at approximately 4 and 6 kDa, corresponding to ACTH1-24 and full-length ACTH1-39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P < 0·001 compared to controls) and 1 isolated ACTH deficiency patient (7% of 15). These sera also recognized native ACTH in human pituitary sections.. Our study demonstrates that repeated administration of depot tetracosactide can lead to anti-ACTH1-24 autoreactivity. In addition, a significant number of patients with AAD and GD also had similar, spontaneous, anti-ACTH reactivity. The presence of these antibodies could mediate some of the adverse effects or explain the well-described phenomenon of resistance to chronic ACTH therapy.

Topics: Addison Disease; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Antibodies; Antibody Affinity; Antibody Specificity; Cosyntropin; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Immunoblotting; Immunohistochemistry; Male; Middle Aged; Pituitary Gland; Young Adult

Serum free cortisol (SFF) responses to cosyntropin simulation test (CST) may more accurately assess adrenal function than total cortisol (TF).. The objective of the study was to evaluate the diagnostic utility of SFF responses during a 250-μg CST.. We recruited healthy volunteers (HV; n = 27), patients with primary and secondary adrenal insufficiency (n = 19 and n = 24, respectively), and subjects with Child-Pugh class A cirrhosis (CH; n = 15). Each received 250 μg cosyntropin with measurement of ACTH and corticosteroid binding globulin (CBG) at time 0 and TF and SFF at 0, 30, and 60 minutes. Salivary cortisol was measured at all time points in CH subjects.. Peak SFF and TF were significantly higher in HVs vs both AI groups (P < .05). Peak SFF and TF (6.8 μg/dL vs 2.2 μg/dL; [188 nmol/L vs 62 nmol/L]; P < .01) were significantly higher in the secondary adrenal insufficiency vs primary adrenal insufficiency patients. The optimal peak SFF criterion to identify adrenal insufficiency patients vs HV was 0.9 μg/dL (25 nmol/L) (sensitivity of 95%, specificity of 100%). Mean CBG and albumin levels were similar among all four groups. CH patients had a higher peak SFF than HV (2.4 vs 2.0 μg/dL; P = .02. In the CH patients, peak salivary cortisol levels correlated well with peak SFF (rs = 0.84, P = .005). CBG levels were similar among the groups.. We provide normative data for SFF values in HV and AI during the CST. Normal CBG levels in mild cirrhosis did not affect the interpretation of the CST.

Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Hepatitis, Viral, Human; Humans; Hydrocortisone; Liver Cirrhosis; Male; Middle Aged; Saliva; Transcortin

A 15 year-old girl with three days of upper abdominal pain was admitted to hospital. Vital parametres were within normal limits. Blood samples and abdominal computed tomography were normal. As pain increased diagnostic laparoscopy was performed and mesenteriel lymphadenitis was found. Thorough examinations were performed including laparotomy. A synachtentest showed an insufficient level of cortisol. The patient was diagnosed with Addison's disease and responded well to treatment with cortisone. Symptoms of adrenal insufficiency can be vague, and it is important to keep the diagnosis in mind in patients with unexplained abdominal pain.

Topics: Abdomen, Acute; Addison Disease; Adolescent; Cosyntropin; Diagnosis, Differential; Female; Humans; Hydrocortisone

The validity of low-dose 1 microg cosyntropin test (LDT) is reported mainly for the assessment of secondary adrenocortical insufficiency (AI). Likewise the hypothalamic-pituitary disorders, early diagnosis of the initial or partial stages of primary AI has an important role.. The aim of study was to: 1) establish the normal cut-off level at which the stimulated plasma cortisol (FP) in LDT excludes primary AI; 2) compare the results in elderly subjects to those in younger ones; 3) compare the results between normal and obese subjects; and 4) verify the established cut-off values on the sample of patients suspected to have primary AI.. 110 subjects (99 women and 11 men, aged 19-80 years, mean 46.2+/-16.1 years, without suspicion for impairment of the hypothalamo-pituitary-adrenal axis were recruited to undergo the LDT in standard conditions. Control group consists of 30 patients (22 women and 8 men, aged 7-58 years, mean 38.4+/-10.6 years) evaluated in whom for suspicion of primary AI as suggested by LDT was confirmed by supplemental investigations (elevated ACTH levels, positive autoantibodies against 21-hydroxylase, mutational analysis of corresponding genes).. The mean peak FP level at 30 min (FP (30)) of the subjects was 675+/-85 nmol/L (95% CI=659 to 691 nmol/L), thus reference values expressed as mean+/-2 SD were 505-845 nmol/L. There was a significant negative correlation between basal FP values (FP (0)) (434+/-105 nmol/L) and the absolute FP incremental (FP (Delta)) response varying from 52 to 553 nmol/L (median 230 nmol/L) (r=-0.71; P<0.001). FP (30) was higher in elderly subjects (n=27) in comparison to younger subjects (n=25) (689+/-88 nmol/L vs. 642+/-63 nmol/L, u=2.11, P<0.05) due to higher FP (Delta) (274+/-116 nmol/L vs. 175+/-112 nmol/L; u=4.02, P<0.01) ; FP (30) levels in obese subjects (n=27) did not differ from those with normal BMI (n=33) (694+/-100 nmol/L vs. 667+/-65 nmol/L, u=1.31, P>0.05). We did not find any correlation between body weight or body surface area and FP (0), FP (30) or FP (Delta). Post-stimulation FP (30) levels in the control group varied from 0 to 354 nmol/L with median 64 nmol/L (25 (th) percentile 10 nmol/L; 75 (th) percentile 165 nmol/L) and were entirely distinctive from those of the subjects without adrenal impairment ( P<0.001).. Taking the mean -2 SD result as a threshold, FP value of 500 nmol/L can be consider as cut-off at 30 min in the LDT for defining the intact adrenocortical function, independently of age and body weight, body surface area.

Topics: Addison Disease; Adult; Aged; Aged, 80 and over; Body Surface Area; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Steroid 21-Hydroxylase; Young Adult

We present the first national audit of the Short Synacthen Test (SST), identifying the clinical, analytical and interpretative procedures adopted by 89 laboratories.. The SST has replaced the insulin stress test as the first-line test to assess adrenal insufficiency and has received considerable attention regarding its sensitivity and specificity. Concerns regarding this test include the bias of cortisol methods, cut-off values used, contraindications and the limitations of the test in diagnosing recent, mild secondary adrenal insufficiency. The audit took into consideration the protocols used by laboratories, the advice provided prior and after the SST and the analytical bias of the methods used.. A web-based questionnaire using Microsoft FrontPage(TM) was prepared to collect data from laboratories and provided drop-down lists and other form-field elements to capture additional comments. The resultant data were exported to Microsoft Excel(TM) for data clean-up and analysis.. The workloads were highly variable; however, most laboratories were in general agreement to the indications, contraindications, timing and reference ranges. In contrast, there was variability in the bias of the cortisol methods, which had not been translated to the cut-off values used by the majority of laboratories.. The audit has shown that though the preanalytical procedures were similar in most laboratories, there is a requirement to recognize the effect that method bias may have on the reference ranges and consequently on the diagnosis of adrenal insufficiency. There is a need to develop consensus guidelines, which can aid both clinicians and laboratories.

Topics: Addison Disease; Adrenal Insufficiency; Cosyntropin; Hematologic Tests; Humans; Laboratories; Medical Audit; Reference Values; Surveys and Questionnaires; United Kingdom

Topics: Addison Disease; Adrenal Insufficiency; Adult; Cosyntropin; Female; Humans; Hydrocortisone; Male; Reference Values; Young Adult

Topics: Addison Disease; Adrenal Cortex; Adrenocorticotropic Hormone; Cosyntropin; Early Diagnosis; Hormones; Humans; Hydrocortisone; Patient Education as Topic

An eighty-year-old man who had complained of skin pigmentation and weight loss was referred to our hospital. Upon physical examination, marked hyperpigmentation was found on the whole body including oral mucosa, tongue and fingernails. Endocrinological findings showed increased ACTH (126 pg/ml) and normal serum cortisol (15.4 microg/dl). First, we used a 250 microg cosyntropin stimulation test which is valid to diagnose Addison's disease, resulting in an adequate cortisol response. Second, we performed 1 microg cosyntropin stimulation test, and the cortisol response was blunted. Since the diagnosis of Addison's disease was fairly certain, he was treated with hydrocortisone 15 mg/day, and improvement of his skin pigmentation and an increase in body weight were observed. To our knowledge, this is the first report that 1 mug cosyntropin stimulation test was helpful to make diagnosis as having Addison's disease rather than the 250 microg cosyntropin stimulation test, although it is established that the 1 mug cosyntropin stimulation test is useful in secondary or relative adrenal insufficiency.

Topics: Addison Disease; Adrenal Cortex Function Tests; Aged, 80 and over; Cosyntropin; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Male; Skin Pigmentation

Topics: Addison Disease; Cosyntropin; Female; Humans; Middle Aged; Transaminases

X linked adrenoleucodystrophy (X-ALD) is considered to be a rare cause of Addison's disease, although several small series suggest a high incidence in young Addisonian males. A survey in the south west of England identified 12 male patients diagnosed with Addison's disease in the period 1987-99. In 10 of these (83%) X-ALD was the underlying cause; the other two were of autoimmune aetiology. Five boys had developed Addison's disease subsequent to the diagnosis of X-ALD. Of the remaining five, in three boys the diagnosis of X-ALD was considerably delayed (by six months to two years from that of Addison's disease) and in two it was only made as a result of this survey. We also identified a patient who presented with Addison's disease at the age of 5 years but was only diagnosed as having X-ALD at the age of 34 years; in the interim his diagnosis of adrenomyeloneuropathy had been missed. Our experience highlights the absolute necessity of measuring very long chain fatty acids in all males with idiopathic Addison's disease.

Topics: Addison Disease; Adolescent; Adrenoleukodystrophy; Adult; Age of Onset; Child; Child, Preschool; Cosyntropin; Humans; Male

Addison's disease may present with diverse and non-specific clinical and biochemical features. Contentious issues include the appropriate criteria for the interpretation of the ACTH stimulation test and the necessary extent of investigation to identify a specific aetiology for the hypoadrenalism. The experience of Addison's disease at a South African teaching hospital was reviewed to (1) record the aetiology and spectrum of presentation, (2) examine the performance of the ACTH stimulation test and (3) determine the utility of adrenal CT scan and biopsy.. Retrospective study of patients admitted to a South African teaching hospital from 1980 to 1997 with a diagnosis of acute Addison's disease.. Fifty patients presenting with acute Addison's disease were identified by a search of hospital records. Pretreatment biochemical and haematological parameters were recorded. The cortisol response at 20 and 60 min to an intravenous injection of 250 micrograms synacthen (Cortrosyn) was analysed. In a subgroup of affected subjects, the bone mineral density (BMD) in the lumbar spine and femoral neck was measured during long-term follow-up.. Presenting features included hyperpigmentation (86%), weight loss (67%), abdominal pain (20%) and diarrhoea (16%). Thirty-nine patients (78%) were hyponatraemic, while 26 (53%) were hyperkalaemic. Nine patients (18%) were hypoglycaemic and 21% had hypercalcaemia. The mean basal cortisol was 148 nmol/l (range 10-487) and 16 patients (40%) had a normal basal cortisol. The mean cortisol 20 min after ACTH stimulation was 172 nmol/l (range 19-588). There was no significant increase in serum cortisol following ACTH stimulation (P > 0.05). Adrenal CT scans were performed in only 24 patients (48%) and were normal in 10, while abnormalities were detected in 14 patients (bilateral enlargement in 11, calcification in two and atrophic adrenals in one). Eight patients had a DEXA scan performed during follow-up--four were osteopaenic in the lumbar spine and five at the femoral neck. The probable aetiology of Addison's was idiopathic in 42%, related to active TB in 18%, old TB in 16%, autoimmune in 12% and malignancy with metastases in 6%--single cases were due to sarcoid, iron overload and adrenoleukodystrophy. Adrenal biopsy was performed in two patients and was diagnostic of malignancy in both cases. The mortality within the first month after hospitalization was 12%.. In our experience, Addison's disease is frequently idiopathic, presents with protean manifestations and should be considered in patients with unexplained hyperpigmentation or gastrointestinal complaints, particularly when associated with hyponatraemia and hyperkalaemia. A normal basal cortisol does not exclude the diagnosis which requires ACTH stimulation testing.

Topics: Abdominal Pain; Acute Disease; Addison Disease; Adolescent; Adult; Aged; Bone Density; Child; Cosyntropin; Diarrhea; Female; Follow-Up Studies; Hospitals, Teaching; Humans; Hydrocortisone; Hyperpigmentation; Male; Middle Aged; Retrospective Studies; South Africa

It has been suggested that endogenous ouabain-like substance (OLS) is of adrenal origin and the secretion of OLS may be ACTH dependent. To determine if OLS is influenced by the pituitary-adrenal axis, we studied the effect of adrenal stimulation (0.25 mg Synacthen) and suppression (1 mg Dexamethasone) on two separate groups of nine subjects. Serum OLS was measured by a radioimmunoassay (RIA) developed in our lab, and cortisol and ACTH were measured by commercial assay kits. Dexamethasone significantly (P< 0.001) suppressed serum cortisol and ACTH concentrations, without effecting endogenous OLS concentration (0.64+/-0.17 vs 0.85+/-0.18nmol/l). Synacthen increased the concentration of cortisol in serum (p < 0.001) over the test period; OLS concentration, again, remained unchanged (0.45+/-0.04 vs 0.43+/-0.05 nmol/l). In further studies, serum concentrations of cortisol and OLS were compared between left (LAV) and right (RAV) adrenal veins with that from the inferior vena cava (IVC). Concentration of cortisol in the LAV and RAV was five-fold greater than that in IVC. However, there was no difference in OLS concentration at the corresponding sites. In addition, serum OLS concentrations in patients having undergone bilateral adrenalectomy or diagnosed with Addison's disease (0.62+/-0.19 nmol/l) were similar to concentrations in healthy subjects (0.67+/-0.21 nmol/l). Examination of bovine adrenal, liver, kidney, heart and human placenta demonstrated that OLS content of bovine adrenal was comparable with other tissues analysed. HPLC studies of human serum and bovine adrenal gland produced identical elution profiles, resolving a single peak which coincided with the retention time observed for standard ouabain. We conclude that the adrenal is unlikely to be the source of endogenous OLS, the secretion of which appears to be independent of ACTH.

Topics: Addison Disease; Adrenal Glands; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Animals; Cattle; Chromatography, High Pressure Liquid; Cosyntropin; Dexamethasone; Female; Humans; Hydrocortisone; Kidney; Male; Middle Aged; Ouabain; Placenta; Pregnancy; Veins

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

Nonneoplastic Lambert-Eaton Myasthenic Syndrome (LEMS) is rare. A 27-year-old man as initially having the diagnosis of Addison's disease was admitted to the hospital because of fatigue, dry-mouthness and proximal limb weakness for 1 year. A diagnosis of LEMS was made from electrophysiological studies. Clinical and laboratory studies revealed no malignancy. We report the first case of Addison's disease associated with non-neoplastic LEMS. It is possible that subclinical LEMS might be present in patients with Addison's disease more frequently than currently believed, since the prominent symptoms of LEMS may be confused with symptoms of Addison's disease.

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; Aldosterone; Cosyntropin; Dehydroepiandrosterone Sulfate; Electrophysiology; Fatigue; Humans; Hydrocortisone; Lambert-Eaton Myasthenic Syndrome; Male; Xerostomia

Topics: Addison Disease; Adolescent; Anti-Inflammatory Agents; Anuria; Child; Cosyntropin; Cough; Diplopia; Female; Fludrocortisone; Headache; Humans; Hydrocortisone; Male; Mineralocorticoids; Muscle Weakness; Pseudotumor Cerebri; Syncope; Vomiting; Weight Loss

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

Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.

Topics: 17-alpha-Hydroxyprogesterone; Addison Disease; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Autoantibodies; Autoimmune Diseases; Corticotropin-Releasing Hormone; Cosyntropin; Diabetes Mellitus, Type 1; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Hypothyroidism; Kinetics; Middle Aged; Thyroiditis, Autoimmune

Topics: Addison Disease; Adrenal Cortex Function Tests; Adult; Cosyntropin; Humans; Male; Predictive Value of Tests

We report the case of a 70 year old man who presented with physical and biochemical features suggestive of Addison's disease, but had a normal short tetracosactrin (Synacthen) test. Six months later he re-presented with similar clinical features but with an abnormal response to tetracosactrin confirming the diagnosis of Addison's disease. We recommend that if adrenal insufficiency is strongly suggested further investigation should be performed to exclude this diagnosis.

Topics: Addison Disease; Aged; Cosyntropin; False Negative Reactions; Humans; Male

Topics: Addison Disease; Cosyntropin; False Negative Reactions; Humans

Sixteen cases of newly diagnosed Addison disease were studied by CT scan. An initial diagnosis was performed according to the clinical data of each patient, and a second diagnosis after examining the abdominal CT scan. According to the second diagnosis there were six patients with primary adrenal failure of probable autoimmune origin, six tuberculosis, two metastatic, one undetermined and one hemorrhagic. The second diagnosis coincided with the first one in 10 cases (62.5%), but was different in six cases (37.5%). Information obtained by CT scan modified the therapeutic attitude in 4 cases (25%). The main morphologic patterns of adrenal glands in CT scan (atrophy, calcification and enlargement) are commented as well as the importance of CT scan in the study of the more common etiologies of Addison's disease (tuberculosis, autoimmune, neoplastic metastasis and hemorrhage). It is concluded that the information obtained by CT scan is important in the etiological diagnosis of Addison disease and it is advised to perform it in all newly diagnosed cases.

Topics: Addison Disease; Adolescent; Adrenal Glands; Adult; Aged; Autoimmune Diseases; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Tomography, X-Ray Computed

beta-Endorphin and ACTH are secreted concomitantly in baseline conditions and in response to physiological and pharmacological stimuli. However, few and contradictory data are available on their feedback inhibition mechanisms. To investigate this aspect, the effects of exogenous ACTH1-24 and glucocorticoids on endogenous ACTH1-39 and beta-endorphin were tested in 18 patients with Addison's disease. Two main experimental protocols were employed: (1) 7 patients were given ACTH1-24 50 micrograms as an intravenous bolus followed by a 50-micrograms infusion in 90 min. Blood samples for beta-endorphin, ACTH and cortisol were obtained at 0, 15, 30, 45, 60, 90, 120 min. Six other patients were given oCRH 100 micrograms i.v. plus ACTH1-24, as described above. (2) In 5 other patients, hydrocortisone 37.5 mg was administered i.v. in 90 min. Blood samples for beta-endorphin, ACTH and cortisol were drawn at 0, 15, 30, 45, 60, 90, 120 min. One week later, the same patients were given oCRH 100 micrograms i.v. and hydrocortisone 37.5 mg, as described above. ACTH1-24 administration caused a significant (p less than 0.01) decrease in endogenous ACTH but not in beta-endorphin. oCRH injection significantly stimulated both ACTH and beta-endorphin. The response of both ACTH and beta-endorphin was inhibited by exogenous ACTH1-24. There was a potent inhibition by hydrocortisone on both basal and stimulated beta-endorphin, confirming that the feedback mechanism of glucocorticoids concomitantly inhibits ACTH and beta-endorphin. On the other hand, only CRH-stimulated but not basal secretion of beta-endorphin seems affected by ACTH ultrashort feedback, suggesting an intrapituitary regulation.

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Cosyntropin; Feedback; Female; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Gland

The existence of feedback inhibition of ACTH on its own secretion has been postulated. To investigate its existence in man, the effects of synthetic ACTH 1-24 on endogenous ACTH secretion were tested in 13 patients with Addison's disease. Plasma ACTH was measured using an immunoradiometric assay, specific for endogenous ACTH 1-39. Ten patients were given 50 micrograms ACTH 1-24 as a bolus iv dose followed by a 50-microgram infusion in 90 min. Blood samples for ACTH and cortisol assay were obtained at 0, 15, 30, 60, 90, and 120 min. As a control, a saline infusion was given 2 days earlier. Three other patients were given 100 micrograms ovine corticotropin-releasing hormone (oCRH) iv and ACTH 1-24 as described above. Blood samples for ACTH and cortisol assay were drawn every 15 min for 2 hours. A CRH test was performed during saline infusion as a control 2 days earlier. In all patients steroid replacement therapy was maintained during the studies. ACTH 1-24 caused a significant decrease (P less than 0.01) in endogenous plasma ACTH at 15 min compared to saline. oCHR administration markedly stimulated ACTH release in the three patients tested, and the ACTH response to oCRH was completely inhibited by the simultaneous administration of ACTH 1-24. These findings strongly support the presence of ACTH autoregulation in man. The complete inhibition of the ACTH response to oCRH by exogenous ACTH 1-24 provides evidence for ultra-short feed-back inhibition at the pituitary level.

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cosyntropin; Female; Homeostasis; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Gland; Radioligand Assay; Reference Values

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: Addison Disease; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Humans; Hydrocortisone; Platelet Aggregation

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

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

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; Aldosterone; Angiotensin II; Cosyntropin; Humans; Male; Middle Aged; Theophylline; Xanthinol Niacinate

The increase in plasma-fluorogenic-corticosteroids in response to a single injection of tetracosactrin depot was measured in eleven patients with suspected acute renal insufficiency who were treated simultaneously with prednisolone and deoxycorticosterone acetate (D.O.C.A.). Acute adrenal insufficiency was excluded in seven patients within 24 hours. There was no response in the remaining four patients, and prolonged corticotrophin stimulation tests confirmed the diagnosis of Addison's disease.

Topics: 11-Hydroxycorticosteroids; Acute Disease; Addison Disease; Adult; Aged; Cosyntropin; Desoxycorticosterone; Drug Therapy, Combination; Female; Humans; Hydrocortisone; Male; Middle Aged; Prednisolone; Stimulation, Chemical

Raised plasma immunoreactive corticotrophin (ACTH) levels were found in five boys with the sex-linked disorder progressive leucodystrophy associated with adrenal insufficiency (Addison-Schilder's disease) and in a symptom-free brother of one of them. Similar ACTH concentrations were found using two antisera, one against the N-terminal part of the ACTH molecule and the other against the C-terminal part. In one patient the circulating ACTH had normal biological activity as measured using the cytochemical ACTH bioassay. Immunoreactive beta/-melanocyte-stimulating hormone was also determined in one patient and found to be raised.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Addison Disease; Adrenocorticotropic Hormone; Child; Child, Preschool; Cosyntropin; Diffuse Cerebral Sclerosis of Schilder; Humans; Immune Sera; Male; Melanocyte-Stimulating Hormones; Sex Factors

Topics: 17-Ketosteroids; Addison Disease; Adolescent; Adrenal Cortex; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenalectomy; Adrenocorticotropic Hormone; Cosyntropin; Cushing Syndrome; Hypertrichosis; Hypoadrenocorticism, Familial; Pituitary-Adrenal Function Tests; Urine