Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome

Abstract Objective Patients with Cushing’s syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. Design and methods Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. Results Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). Conclusions Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.

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Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome

Endocrine ◽

10.1007/s12020-016-0883-z ◽

2016 ◽

Vol 53 (1) ◽

pp. 63-70 ◽

Cited By ~ 6

Author(s):

Sean H. P. P. Roerink ◽

M. A. E. M. Wagenmakers ◽

J. W. A. Smit ◽

E. F. C. van Rossum ◽

R. T. Netea-Maier ◽

...

Keyword(s):

Risk Factors ◽

Glucocorticoid Receptor ◽

Cushing’S Syndrome ◽

Cardiometabolic Risk ◽

Cushing's Syndrome ◽

Cardiometabolic Risk Factors ◽

Glucocorticoid Receptor Polymorphisms

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Role for laparoscopic adrenalectomy in patients with Cushing's syndrome

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302007000800021 ◽

2007 ◽

Vol 51 (8) ◽

pp. 1349-1354 ◽

Cited By ~ 7

Author(s):

William F. Young, Jr. ◽

Geoffrey B. Thompson

Keyword(s):

Surgical Management ◽

Cushing’S Syndrome ◽

Patient Selection ◽

Laparoscopic Adrenalectomy ◽

Laparoscopic Approach ◽

Cushing's Syndrome ◽

Open Adrenalectomy ◽

The Past ◽

Tissue Handling

Laparoscopic adrenalectomy is one of the most clinically important advances in the past 2 decades for the treatment of adrenal disorders. When compared to open adrenalectomy, laparoscopic adrenalectomy is equally safe, effective, and curative; it is more successful in shortening hospitalization and convalescence and has less long-term morbidity. The laparoscopic approach to the adrenal is the procedure of choice for the surgical management of cortisol-producing adenomas and for patients with corticotropin (ACTH) dependent Cushing's syndrome for whom surgery failed to remove the source of ACTH. The keys to successful laparoscopic adrenalectomy are appropriate patient selection, knowledge of anatomy, delicate tissue handling, meticulous hemostasis, and experience with the technique of laparoscopic adrenalectomy.

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Factors predicting long-term comorbidities in patients with Cushing’s syndrome in remission

Endocrine ◽

10.1007/s12020-018-1819-6 ◽

2018 ◽

Vol 64 (1) ◽

pp. 157-168 ◽

Cited By ~ 2

Author(s):

Marie Helene Schernthaner-Reiter ◽

Christina Siess ◽

Alois Gessl ◽

Christian Scheuba ◽

Stefan Wolfsberger ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cushing's Syndrome

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Long-term low-dose ketoconazole treatment in bilateral macronodular adrenal hyperplasia

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-14-0083 ◽

2014 ◽

Vol 2014 ◽

Author(s):

Sophie Comte-Perret ◽

Anne Zanchi ◽

Fulgencio Gomez

Keyword(s):

Medical Therapy ◽

Cushing’S Syndrome ◽

Clinical Signs ◽

Cushing's Syndrome ◽

List Type ◽

Adrenal Hyperplasia ◽

Benign Condition ◽

Steroid Secretion ◽

Free Cortisol

Summary Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery. Learning points Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features. Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated. However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.

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Exogenous Cushing’s Syndrome with Subsequent Secondary Adrenal Insufficiency in Patients with Long Term Steroid Usage

Medico-Legal Update ◽

10.37506/mlu.v21i1.2401 ◽

2021 ◽

Cited By ~ 1

Keyword(s):

Adrenal Insufficiency ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Secondary Adrenal Insufficiency

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Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas

Acta Endocrinologica ◽

10.1530/eje-09-0957 ◽

2010 ◽

Vol 162 (4) ◽

pp. 779-785 ◽

Cited By ~ 45

Author(s):

R Giordano ◽

E Marinazzo ◽

R Berardelli ◽

A Picu ◽

M Maccario ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cumulative Risk ◽

Cushing's Syndrome ◽

Endocrine Function ◽

Adrenal Incidentalomas ◽

Term Outcome ◽

Long Term Outcome ◽

Significant Clinical Improvement

ObjectiveTo evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas.Design and methodsA total of 118 patients (77 F and 47 M; age 62.3±1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1–10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery.ResultsAt entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%,P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic–cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement.ConclusionsThe risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.

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