Objective: The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome. Participants: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments. Conclusions: After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal inci...

The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.

I. Introduction II. Definitions and Etiology III. Diagnostic Overview IV. Clinical Features V. Biochemical Diagnosis of Cushing’s Syndrome A. Cardinal features B. Urinary free cortisol (UFC) C. Low-dose dexamethasone testing D. Circadian rhythm assessment E. Cyclical Cushing’s syndrome VI. ACTH-Dependent vs. ACTH-Independent Cushing’s Syndrome VII. Differential Diagnosis of ACTH-Dependent Cushing’s Syndrome A. Overview B. Basal testing C. Dynamic noninvasive testing D. Invasive testing VIII. Other Causes of Cushing’s Syndrome IX. Imaging A. Pituitary B. Adrenal C. Ectopic secretion X. Differentiation from Pseudo-Cushing’s States XI. Conclusions

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The Diagnosis and Differential Diagnosis of Cushing’s Syndrome and Pseudo-Cushing’s States

Plasma cortisol was analyzed every 20 minutes for 24 hours in six psychotically depressed patients and eight normal persons. The depressives, while ill, secreted substantially more cortisol, had more secretory episodes, and more minutes of active secretion; throughout day and night, cortisol concentration was markedly elevated both at the beginning and end of secretory episodes, and cortisol was actively secreted during late evening and early morning hours when normally secretion is minimal. After treatment, the patients' secretory patterns normalized. Biological half life of cortisol remained normal throughout. The data suggest an abnormal disinhibition during depressive illness of the neuroendocrine centers regulating adrenocorticotrophic hormone release. Such neuroendocrine activation has been produced in animals following depletion of brain biogenic amines; a similar mechanism may be involved in the hypersecretion of cortisol in certain depressed patients.

Disrupted 24-hour patterns of cortisol secretion in psychotic depression.

• The regulation of hypothalamopituitary-adrenal (HPA) function in depressed patients was studied by a midnight dexamethasone suppression test. By using an observation period of 24 hours postadministration of dexamethasone, a graded series of abnormal test responses was identified. Depressed patients show abnormal early escape from suppression rather than absolute resistance to HPA suppression by dexamethasone. With increasing severity of depression, this escape occurs progressively more early on the day after administration of dexamethasone. These abnormalities were strongly related to the presence of HPA hyperactivity before dexamethasone was given. The essential disturbance of neuroendocrine regulation in depression is a failure of the normal brain inhibitory influence on the HPA system. This disinhibition of HPA activity suggests that there is an abnormal limbic system drive on the HPA axis in primary depressive illness.

Neuroendocrine Regulation in Depression: I. Limbic System-Adrenocortical Dysfunction

Inhibition of gastrin and gastric-acid secretion by growth-hormone release-inhibiting hormone

Growth hormone release inhibiting hormone (GHRIH) was administered by constant infusion over 75 minutes to eight acromegalic patients at different doses. 100 to 1,000 mug were equally effective in reducing circulating growth hormone (GH) levels; 25 mug lowered GH levels in only five patients, and at this dose the extent of the fall was smaller than from doses of 100 mug or more. 10 mug was ineffective. Injection of single doses of 500 mug by intravenous, subcutaneous, and intramuscular routes caused only small and transient reductions in GH levels, though the effect was improved by injecting the hormone intramuscularly in 2 ml of 16% gelatin. Injection of a suspension of 4 mg GHRIH in 1 ml of arachis oil lowered growth hormone levels for between three and four hours.In four acromegalic patients an oral 50-g glucose tolerance test was performed during a continuous infusion of either saline or 1,000 mug GHRIH. The "paradoxical" rise in growth hormone seen in these patients during the saline infusion was suppressed by GHRIH. The blood glucose responses were, moreover, modified by GHRIH in that the peak was delayed and occurred at the end of the infusion in each case. A "normal" glucose tolerance curve was converted to a "diabetic" type of response in two patients. This effect could be accounted for by the inhibition of insulin secretion known to occur with large doses of GHRIH.We speculate that acromegaly may be primarily a hypothalmic disease due to deficiency of GHRIH resulting in excessive secretion of growth hormone from the pituitary and adenoma formation due to inappropriate and prolonged stimulation of the pituitary.

G.M. Besser

Papers

Inhibition of gastrin and gastric-acid secretion by growth-hormone release-inhibiting hormone

Growth Hormone Release Inhibiting Hormone in Acromegaly

Pituitary-adrenal function in severe depressive illness.

Glucagon control of fasting glucose in man

Inhibition of the plasma-aldosterone response to frusemide by bromocriptine