cosyntropin and Autoimmune-Diseases

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

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

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

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

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

The natural history and pathogenesis of lymphocytic hypophysitis remain poorly understood. We describe a 34-yr-old woman with postpartum thyroiditis and ACTH deficiency, studied at monthly intervals for 18 months after pregnancy. A significant titer of thyroid peroxidase autoantibodies was detected at 16 weeks gestation, and she was recruited into a prospective study of postpartum thyroid function. Four months postpartum she developed mild hyperthyroidism [free T4 (fT4), 27 pmol/L; TSH, less than 0.2 mU/L] and showed a rise in thyroid peroxidase and thyroglobulin autoantibodies. At 9 months postpartum, serum fT4 and fT3 levels were low normal (8.0 and 1.7 pmol/L, respectively), but TSH was not raised (0.4 mU/L). Subsequent investigation showed a low basal plasma cortisol level (28 nmol/L) in association with undetectable ACTH, and subnormal cortisol responses to depot Synacthen (535 nmol/L at 6 h) and hypoglycemia (peak, 145 nmol/L). FSH, LH, GH, and PRL function and computerized tomography of the pituitary were normal. Retrospective analysis of serum samples taken throughout the postpartum year showed developing hypocortisolemia between 3-9 months postpartum. Each sample was also tested for pituitary autoantibodies using a specific indirect immunofluorescent assay; none was detected. The ACTH deficiency recovered spontaneously, with normal cortisol responses to depot Synacthen (greater than 1380 at 6 h) and hypoglycemia (peak, 590) 14 and 18 months postpartum, respectively. This case illustrates that postpartum pituitary deficiencies are potentially reversible. The pattern of pituitary deficit and postpartum thyroiditis supported a diagnosis of autoimmune hypophysitis.

Topics: Adrenocorticotropic Hormone; Adult; Autoantibodies; Autoimmune Diseases; Cosyntropin; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Iodide Peroxidase; Pituitary Diseases; Pregnancy; Pregnancy Complications; Puerperal Disorders; Thyroiditis, Autoimmune; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

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

In both mammals and chickens, immunization with exogenous antigens results in a surge of serum glucocorticoid hormone levels concomitant with the antibody response. This effect is mediated by glucocorticoid-increasing factors (GIF) produced by cells of the immune system. In the avian system, GIF appear to act via the hypothalamo-pituitary axis and not directly on the adrenal gland. Interleukin 1 is the main active substance responsible for GIF activity, as shown by molecular sieve and immunoaffinity chromatography studies. In contrast to data from mammals, we found no evidence that interleukin 2 elevates chicken corticosterone. Obese strain chickens with spontaneous Hashimoto-like autoimmune thyroiditis are deficient in their in vivo GIF response. Because no differences were found between autoimmune and healthy chickens in the corticosterone response of the adrenal gland after ACTH administration, and since autoimmune animals are able to react normally to immobilization stress, it is assumed that this deficiency is due to a specific defect rather than a general disturbance in the endocrine system.

Topics: Adrenal Glands; Animals; Autoimmune Diseases; Chickens; Chromatography, Affinity; Corticosterone; Cosyntropin; Dexamethasone; Disease Models, Animal; Endocrine Glands; Feedback; Glucocorticoids; Hypothalamo-Hypophyseal System; Immune System; Pituitary-Adrenal System; Thyroiditis

Analysis of 24-h urinary steroid excretion was performed by capillary gas chromatography in six patients (five men, one woman) with adrenocortical insufficiency. Ten healthy subjects (five men, five women) served as controls. A complete absence of all 21-hydroxylated steroid metabolites was seen in patients with adrenocortical insufficiency, whereas the excretion of several steroids lacking hydroxylation in the 21-position (pregnenolone, pregnenetriol, and 11-ketoandrosterone) was markedly increased. In addition, the presence of 11 beta-hydroxyandrosterone was confirmed by mass-spectrometry in the urine of three patients. This pattern of steroid excretion was unchanged in patients with adrenocortical insufficiency, both after stimulation by 1-24 adrenocorticotropin (ACTH) and after short-term (3-d) suppression with dexamethasone. We conclude that patients with adrenocortical insufficiency present a pattern of steroid excretion characterized by the absence of 21-hydroxylated metabolites. In the absence of functional adrenocortical tissue, long-term pathologically elevated concentrations of ACTH apparently stimulate early steps of steroid synthesis, most likely in the gonads. In addition, the presence of 11-hydroxylated steroid metabolites (11-ketoandrosterone, 11 beta-hydroxyandrosterone) in the urine of patients with adrenocortical insufficiency demonstrates that chronic ACTH excess in this disorder may induce some activity of 11 beta-hydroxylase, an enzyme not found in the gonads under physiological conditions.

Topics: Adrenal Cortex Diseases; Adrenocorticotropic Hormone; Adult; Autoimmune Diseases; Chromatography, Gas; Cosyntropin; Cushing Syndrome; Dexamethasone; Female; Humans; Male; Middle Aged; Steroids

Topics: Adrenal Glands; Adult; Aged; Autoantibodies; Autoimmune Diseases; Circadian Rhythm; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Thyroiditis; Time Factors