cosyntropin and Acromegaly

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

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

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

In order to elucidate the role of the dopaminergic system in the control of aldosterone secretion in acromegaly with arterial hypertension 10 patients and 10 healthy volunteers were studied. Plasma aldosterone and prolactin were determined by radioimmunological methods after dopaminergic receptor blockade with metoclopramide and sulpiride. Plasma aldosterone was also determined after adrenal stimulation with synthetic corticotrophin (Synacthen). In patients with acromegaly and hypertension, the aldosterone secretion in response to metoclopramide was completely inhibited whereas induced with corticotrophin was lower than in controls. Also prolactin secretion in response to metoclopramide or sulpiride was markedly lower as compared with that in controls. Sulpiride did not stimulate aldosterone secretion either in patients or in healthy controls. The results indicate that the dopaminergic control of aldosterone secretion in acromegaly with arterial hypertension is altered.

Topics: Acromegaly; Adrenocorticotropic Hormone; Adult; Aldosterone; Cosyntropin; Female; Humans; Hypertension; Male; Metoclopramide; Middle Aged; Prolactin; Receptors, Dopamine; Sulpiride