THE METABOLISM OF [4-14C]CORTISOL IN A PATIENT WITH CUSHING'S SYNDROME

1962 ◽  
Vol 24 (2) ◽  
pp. 199-214 ◽  
Author(s):  
C. H. GRAY ◽  
J. M. GREENAWAY ◽  
N. J. HOLNESS ◽  
D. A. SHAW
Keyword(s):  
Cushing’S Syndrome ◽  
Metabolic Pathways ◽  
Cushing's Syndrome ◽  
Secretion Rate ◽  
Cortisol Secretion ◽  
Cortisol Metabolism ◽  
Excretion Rates ◽  
Hydroxy Metabolites

SUMMARY The metabolism of [4-14C]cortisol in a patient with Cushing's syndrome has been studied by the isolation, identification and measurement of the specific radioactivities of the major metabolites. The results show that the metabolism of cortisol was not abnormal in the aspects studied. The biological half-lives of cortisol and of the tetrahydrocorticosteroid metabolites were found to be normal. Data obtained on excretion rates of metabolites indicated that the metabolic pathways of cortisol were normal. There was no evidence for an increased conversion of cortisol to 6β-hydroxycortisol when the excretion of the latter was expressed as a fraction of the cortisol production. The overall pattern was one of an abnormally high secretion of cortisol by the adrenals, resulting in a proportionally high excretion of tetrahydrocortisone, tetrahydrocortisols, cortolones, cortols, 11-oxygenated 17-oxosteroids, 6β-hydroxycortisol, cortisone and cortisol. Apart from an increased ratio of 11β-hydroxy-metabolites to 11-oxo-metabolites, each metabolite, expressed as a fraction of the cortisol secreted, was excreted in a normal proportion. Hence, in spite of the grossly elevated cortisol secretion rate, the major pathways available for cortisol metabolism were not overloaded and there was no evidence of increased metabolism via minor pathways. Evidence for an increased secretion of corticosterone by the adrenals was obtained by the isolation of abnormal amounts of tetrahydrocorticosterone.

Cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion: a new variant of Cushing's syndrome

1985 ◽  
Vol 110 (3) ◽  
pp. 289-295 ◽  
Author(s):  
Hans-Udo Schweikert ◽  
Horst Lorenz Fehm ◽  
Rudolf Fahlbusch ◽  
Rainer Martin ◽  
Rainer Kolloch ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Normal Tissue ◽  
Plasma Cortisol ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Normal Response ◽  
New Variant ◽  
Marked Suppression

Abstract. A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy. Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF. The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.

Values for Urinary Free Cortisol during Treatment with Amino-Glutethimide for Cushing’s Syndrome

1973 ◽  
Vol 19 (9) ◽  
pp. 1067-1068 ◽  
Author(s):  
Karl W Schmitt ◽  
Roger Juselius ◽  
James Hanlon ◽  
David Steed
Keyword(s):  
Cushing’S Syndrome ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Sensitive Indicator ◽  
Cortisol Secretion ◽  
Clinical Correlation ◽  
Free Cortisol ◽  
Amino Glutethimide

Abstract Of the chemical tests used, we found that values for urinary free cortisol had the best clinical correlation and were the most sensitive indicator of cortisol secretion in a patient with Cushing’s syndrome who was treated with amino-glutethimide.

scholarly journals Phase-shifted Diurnal Rhythm of Cortisol Secretion in a Patient with Cushing's Syndrome due to Adrenocortical Adenoma.

1988 ◽  
Vol 35 (2) ◽  
pp. 261-266
Author(s):  
AKIRA SHIMATSU ◽  
YUZURU KATO ◽  
HIDETA SAKAMI ◽  
YOSHIKATSU NAKAI ◽  
HIROO IMURA
Keyword(s):  
Cushing’S Syndrome ◽  
Diurnal Rhythm ◽  
Cushing's Syndrome ◽  
Adrenocortical Adenoma ◽  
Cortisol Secretion

scholarly journals Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing’s syndrome

Pituitary ◽  
2012 ◽  
Vol 16 (3) ◽  
pp. 363-369 ◽  
Author(s):  
Roberta Giordano ◽  
Rita Berardelli ◽  
Ioannis Karamouzis ◽  
Valentina D’Angelo ◽  
Andreea Picu ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Gaba Receptors ◽  
Cushing's Syndrome ◽  
Acute Administration ◽  
Cortisol Secretion

Incidentally discovered ACTH-dependent adrenal adenoma presenting as 'Pre-Cushing's syndrome'

1986 ◽  
Vol 111 (1) ◽  
pp. 89-92 ◽  
Author(s):  
U. Bogner ◽  
U. Eggens ◽  
J. Hensen ◽  
W. Oelkers
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Mass ◽  
Adrenal Adenoma ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Adrenal Tumour ◽  
Urinary Cortisol

Abstract. 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.

scholarly journals Food-Dependent Cushing’s Syndrome: Possible Involvement of Leptin in Cortisol Hypersecretion*

1999 ◽  
Vol 84 (10) ◽  
pp. 3817-3822 ◽  
Author(s):  
François P. Pralong ◽  
Fulgencio Gomez ◽  
Louis Guillou ◽  
François Mosimann ◽  
Sebastiano Franscella ◽  
...  
Keyword(s):  
Food Intake ◽  
Cushing’S Syndrome ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Adrenal Hyperplasia ◽  
Adrenal Cells ◽  
Patient Reported ◽  
Stimulation Of

Abstract Stimulation of cortisol secretion by food intake has been implicated in the pathogenesis of some cases of ACTH-independent Cushing’s syndrome, via an aberrant response of the adrenal glands to gastric inhibitory polypeptide (GIP). We report here a novel case of food-dependent Cushing’s syndrome in a patient with bilateral macronodular adrenal hyperplasia. In this patient we were able to confirm a paradoxical stimulation of cortisol secretion by GIP in vivo as well as in vitro on dispersed tumor adrenal cells obtained at surgery. In addition to GIP, in vitro stimulation of these cultured tumor adrenal cells with leptin, the secreted product of the adipocyte, induced cortisol secretion. By comparison, no such stimulation was observed in vitro in adrenal cells obtained from another patient with bilateral macronodular adrenal hyperplasia and Cushing’s syndrome that did not depend on food intake, in tumor cells obtained from a solitary cortisol-secreting adrenal adenoma, and in normal human adrenocortical cells. These results demonstrate that as in previously described cases of food-dependent Cushing’s syndrome, GIP stimulated cortisol secretion from the adrenals of the patient reported here. Therefore, they indicate that such a paradoxical response probably represents the hallmark of this rare condition. In addition, they suggest that leptin, which normally inhibits stimulated cortisol secretion in humans, participated in cortisol hypersecretion in this case. Further studies in other cases of food-dependent Cushing’s syndrome, however, will be necessary to better ascertain the pathophysiological significance of this finding.

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