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.

Primary adrenocortical micronodular adenomatosis causing Cushing's syndrome. Effects of ketoconazole on steroid production and in vitro performance of adrenal cells

1986 ◽  
Vol 113 (3) ◽  
pp. 370-377 ◽  
Author(s):  
W. Oelkers ◽  
V. Bähr ◽  
J. Hensen ◽  
H. Pickartz ◽  
P. Exner ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Plasma Cortisol ◽  
Venous Blood ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Urinary Cortisol ◽  
Adrenal Cells

Abstract. Mild Cushing's syndrome was diagnosed in a 35 year old woman. Elevated plasma and urinary cortisol levels were unsuppressible with up to 32 mg dexamethasone per day. Aldosterone, 18-OH-corticosterone and testosterone in plasma were normal and dehydroepiandrosterone-sulphate was low. No adrenal tumour was found by CT or adrenal venography, and bilateral cortisol secretion was demonstrated by steroid measurements in adrenal venous blood. A circadian rhythm of plasma cortisol was absent. Plasma ACTH was suppressed, even after injection of CRH, during insulininduced hypoglycaemia and after metyrapone administration, which led to a large fall in plasma cortisol but to a subnormal rise of plasma 11-deoxy-cortisol. The clinical diagnosis of primary micronodular adenomatosis of the adrenal gland was histologically confirmed, when the patient finally underwent bilateral adrenalectomy. In vitro, the adrenal cells did not produce more cortisol and aldosterone than adrenal cells from cadaver kidney donors. In vivo and in vitro, cortisol was slightly less than normally responsive to ACTH. Intermittent treatment of the patient with 800 mg/day of ketoconazole led to a rapid fall of cortisol secretion and clinical signs of adrenocortical insufficiency. Treatment for 7 weeks with 200–400 mg ketoconazole per day reduced plasma and urinary cortisol less dramatically into the normal range. This case unequivocally documents autonomous dysfunction of the adrenal cortex in this rare form of Cushing's syndrome and the efficacy of ketoconazole in the treatment of ACTH-independent hypercortisolism.

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.

scholarly journals Long term control of hypercortisolism with fluconazole: case report and in vitro studies

2006 ◽  
Vol 154 (4) ◽  
pp. 519-524 ◽  
Author(s):  
Michaela Riedl ◽  
Christina Maier ◽  
Georg Zettinig ◽  
Peter Nowotny ◽  
Wolfgang Schima ◽  
...  
Keyword(s):  
Case Report ◽  
Cell Line ◽  
Cushing’S Syndrome ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
Unilateral Adrenalectomy ◽  
Cortisol Excretion ◽  
Glucocorticoid Production

Objectives: To evaluate the efficacy of fluconazole as an alternative treatment for controlling hypercortisolism in Cushing’s syndrome and to determine its effect on glucocorticoid production in vitro. Design: Case report and in vitro study in a University Clinic. Case: An 83 year old patient presented with recurrence of Cushing’s syndrome due to pulmonary metastases three years after unilateral adrenalectomy. During a near fatal episode of sepsis she was started on fluconazole 200 mg/day intravenously which normalised cortisol excretion. The therapy was continued orally for 18 months. Upon temporary discontinuation and reintroduction of treatment, cortisol levels increased and normalized, respectively. At month 16, fluconazole had to be increased to a dose of 400 mg/day to keep cortisol excretion in the normal range. Disease progression was slow and no side effects occurred. In vitro results: Fluconazole in a concentration of 500 μM nearly abolished corticosterone production over 24 h from the adrenal adenoma cell line Y-1 (8.6 ± 0.5% compared with control, P < 0.0001) and significantly reduced corticosterone production in concentrations of 50 μM (48.3 ± 1.9% vs. control, P < 0.0001) and 5 μM (80.5 ± 8.5% vs. control, P < 0.05). Conclusion: These results demonstrate for the first time that fluconazole normalises cortisol concentrations in vivo in a patient with Cushing’s syndrome with adrenal carcinoma and inhibit glucocorticoid production in vitro in a cell line. Thus, fluconazole might be useful in controlling glucocorticoid excess in Cushing’s syndrome and because of its lower toxicity might be preferable to ketoconazole.

scholarly journals In Vivo and in Vitro Screening for Illegitimate Receptors in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Causing Cushing’s Syndrome: Identification of Two Cases of Gonadotropin/Gastric Inhibitory Polypeptide-Dependent Hypercortisolism

2005 ◽  
Vol 90 (3) ◽  
pp. 1302-1310 ◽  
Author(s):  
Jérôme Bertherat ◽  
Vincent Contesse ◽  
Estelle Louiset ◽  
Gaëlle Barrande ◽  
Céline Duparc ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Gastric Inhibitory Polypeptide ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Adrenal Hyperplasia ◽  
Adrenocortical Cells ◽  
Normal Cells ◽  
H1 Cells

In ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing’s syndrome, cortisol production can be controlled by illegitimate membrane receptors. The aim of the present study was to evaluate in vivo and in vitro the sensitivity of AIMAH to various regulatory factors to detect the expression of illegitimate receptors by the tissues. Four consecutive patients with AIMAH and hypercortisolism (H1–H4) preoperatively underwent a series of pharmacological and/or physiological tests. After adrenalectomy, in vitro studies were conducted to investigate the cortisol responses of cultured cells, derived from hyperplastic tissues, to various membrane receptor ligands. The adrenal tissues of the two patients who responded in vivo to food intake (H2 and H4) were stimulated in vitro by gastric inhibitory polypeptide. GnRH and human chorionic gonadotropin, but not FSH, stimulated cortisol secretion in patients H2 and H4. In these two cases, human chorionic gonadotropin but not GnRH stimulated cortisol production from cultured adrenocortical cells. Cisapride induced a significant increase in cortisol levels in patient H1. In addition, serotonin (5-HT) was more efficient to stimulate cortisol production in H1 cells than in normal adrenocortical cells. Upright stimulation test provoked an increase in cortisol levels in patients H1, H2, and H3. H1 and H2 cells were more sensitive to the stimulatory action of angiotensin II than normal cells. Similarly, arginine vasopressin (AVP) more efficiently activated steroidogenesis in H1 cells than in normal cells. In H1 tissue, immunohistochemical studies revealed the presence of 5-HT- and AVP-like immunoreactivities within clusters of steroidogenic cells, suggesting that these two factors acted through an autocrine/paracrine mechanism to stimulate cortisol secretion. The present study provides the first demonstration of primary adrenal Cushing’s syndrome dependent on both gonadotropin and gastric inhibitory polypeptide. Our data also show a hyperresponsiveness of hyperplastic adrenal tissues to 5-HT, angiotensin II, and AVP. Finally, they reveal for the first time the presence of paracrine regulatory signals in adrenal hyperplasia tissues.

scholarly journals TXNIP is highly regulated in bone biopsies from patients with endogenous Cushing's syndrome and related to bone turnover

2012 ◽  
Vol 166 (6) ◽  
pp. 1039-1048 ◽  
Author(s):  
Tove Lekva ◽  
Thor Ueland ◽  
Hege Bøyum ◽  
Johan Arild Evang ◽  
Kristin Godang ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Cushing’S Syndrome ◽  
Bone Cells ◽  
Cushing's Syndrome ◽  
Gene Encoding ◽  
Osteoclast Activity ◽  
Bone Biopsies ◽  
Before And After

ObjectivePatients with endogenous Cushing's Syndrome (CS), as long-time treated patients with exogenous glucocorticoids (GCs), have severe systemic manifestations including secondary osteoporosis and low-energy fractures. The aim of the present study was to investigate the functional role ofTXNIPin bone with focus on osteoblast (OB) differentiation and OB-mediated osteoclast activity and functionin vitro.Design and methodsNine bone biopsies from CS before and after surgical treatment were screened for expressional candidate genes. Microarray analyses revealed that the gene encodingTXNIPranked among the most upregulated genes. Subsequentin vitroandin vivostudies were performed.ResultsWe found thatTXNIPgene in bone is downregulated in CS following surgical treatment. Furthermore, ourin vivodata indicate novel associations between thioredoxin andTXNIP. Ourin vitrostudies showed that silencingTXNIPin OBs was followed by increased differentiation and expression and secretion of osteocalcin as well as enhanced activity of alkaline phosphatase. Moreover, treating osteoclasts with silenced TXNIP OB media showed an increased osteoclast activity.ConclusionsTXNIPexpression in bone is highly regulated during the treatment of active CS, and by GC in bone cellsin vitro. Our data indicate that TXNIP may mediate some of the detrimental effects of GC on OB function as well as modulate OB-mediated osteoclastogenesis by regulating the OPG/RANKL ratio.

scholarly journals cAMP signaling in cortisol-producing adrenal adenoma

2015 ◽  
Vol 173 (4) ◽  
pp. M99-M106 ◽  
Author(s):  
Davide Calebiro ◽  
Guido Di Dalmazi ◽  
Kerstin Bathon ◽  
Cristina L Ronchi ◽  
Felix Beuschlein
Keyword(s):  
Signaling Pathway ◽  
Cushing’S Syndrome ◽  
Cell Function ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
Camp Signaling ◽  
Common Finding ◽  
Adrenocortical Adenomas ◽  
Camp Signaling Pathway

The cAMP signaling pathway is one of the major players in the regulation of growth and hormonal secretion in adrenocortical cells. Although its role in the pathogenesis of adrenocortical hyperplasia associated with Cushing's syndrome has been clarified, a clear involvement of the cAMP signaling pathway and of one of its major downstream effectors, the protein kinase A (PKA), in sporadic adrenocortical adenomas remained elusive until recently. During the last year, a report by our group and three additional independent groups showed that somatic mutations of PRKACA, the gene coding for the catalytic subunit α of PKA, are a common genetic alteration in patients with Cushing's syndrome due to adrenal adenomas, occurring in 35–65% of the patients. In vitro studies revealed that those mutations are able to disrupt the association between catalytic and regulatory subunits of PKA, leading to a cAMP-independent activity of the enzyme. Despite somatic PRKACA mutations being a common finding in patients with clinically manifest Cushing's syndrome, the pathogenesis of adrenocortical adenomas associated with subclinical hypercortisolism seems to rely on a different molecular background. In this review, the role of cAMP/PKA signaling in the regulation of adrenocortical cell function and its alterations in cortisol-producing adrenocortical adenomas will be summarized, with particular focus on recent developments.

CONCURRENT 3β-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY IN ADRENAL AND SCLEROCYSTIC OVARY

1965 ◽  
Vol 48 (3) ◽  
pp. 392-412 ◽  
Author(s):  
Leonard R. Axelrod ◽  
Joseph W. Goldzieher ◽  
S. David Ross
Keyword(s):  
Cushing’S Syndrome ◽  
Dehydrogenase Deficiency ◽  
Clinical Manifestations ◽  
Regulatory System ◽  
Hydroxysteroid Dehydrogenase ◽  
Cushing's Syndrome ◽  
Hypothalamic Pituitary Adrenal ◽  
Relative Deficiency

ABSTRACT In vivo and in vitro studies were performed in a virilized patient with enlarged sclerocystic ovaries, in whom urinary corticoid excretion was not suppressed by dexamethasone. Both ovarian and adrenal tissues were incubated with 5-pregnenolone-4-14C and the metabolites isolated and definitively identified. Both tissues showed a relative deficiency of 3β-hydroxysteroid dehydrogenase. The ovarian aromatizing mechanism was intact. 5-Androstene-3β,17β-diol was the major adrenal biosynthetic product, and its metabolites were identified in the urine. The abnormality of the hypothalamic-pituitary-adrenal regulatory system resembled that seen in Cushing's syndrome, but the clinical manifestations were altered by the steroid enzyme abnormality.

scholarly journals Cushing’s Syndrome in a Patient with Bilateral Macronodular Adrenal Hyperplasia Responding to Cisapride: An in Vivo and in Vitro Study

2003 ◽  
Vol 88 (10) ◽  
pp. 4616-4622 ◽  
Author(s):  
Massimo Mannelli ◽  
Pietro Ferruzzi ◽  
Paola Luciani ◽  
Clara Crescioli ◽  
Lisa Buci ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
In Vitro Study ◽  
Cushing's Syndrome ◽  
Vitro Study ◽  
Adrenal Hyperplasia

scholarly journals IN VIVO AND IN VITRO STUDIES OF ADRENAL SECRETIONS IN CUSHING'S SYNDROME AND PRIMARY ALDOSTERONISM*

1963 ◽  
Vol 42 (4) ◽  
pp. 516-524 ◽  
Author(s):  
Edward G. Biglieri ◽  
Satoshi Hane ◽  
Paul E. Slaton ◽  
Peter H. Forsham
Keyword(s):  
Cushing’S Syndrome ◽  
Primary Aldosteronism ◽  
Cushing's Syndrome ◽  
In Vitro Studies
Sign in / Sign up

Export Citation Format

Share Document