Cited by 182Pituitary Gland Disorders and TreatmentsAdrenal and Paraganglionic TumorsAdrenal Hormones and Disorders

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Pre‐clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients

Leibowitz, Gil, Tsur, Anat, Chayen, Susan D., Salameh, Mohammad, Raz, Itamar, Cerasi, Erol, Gross, David J.·1996·Clinical Endocrinology

DOI 10.1046/j.1365-2265.1996.737558.x

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Abstract

OBJECTIVE: Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN: (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI > 25 kg/m2) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin > 9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (> 140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS: The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of "true' CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS: In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (< 140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle's test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1-9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 +/- 2.5 nmol/l (mean +/- SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS: The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.

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BackgroundResultInfluential
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BackgroundMethodInfluential
Hidden hypercortisolism: a too frequently neglected clinical condition
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“require a more meticulous investigation of CS in populations with features such as obesity, hypertension, diabetes and the polycystic ovarian syndrome [”
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Medical Management of Persistent and Recurrent Cushing Disease
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“[13] reported three patients with subCS in a study of 90 overweight patients (body mass index > 25 kg/m(2)) with poorly controlled diabetes (HbA1c > 9%).”
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Diagnosis, Classification, and Lifestyle Treatment of Diabetes
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Polycystic ovarian syndrome and Cushing's syndrome: a persistent diagnostic quandary
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When to Suspect Hidden Hypercortisolism in Type 2 Diabetes: A Meta-Analysis
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Hypercortisolism in Newly Diagnosed Type 2 Diabetes: A Prospective Study of 384 Newly Diagnosed Patients
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“3%) in a group of 2,381 diabetic patients from 12 studies (34-45).”
Background
Discovery of Cushing’s Syndrome After Bariatric Surgery: Multicenter Series of 16 Patients
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“6 % [13–16].”
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“[4] scanned 90 patients with type 2 diabetes for CS whose HbA1c [9 % and BMI [25, and 3 patients were diagnosed as CS (3.”
Method
Prevalence of subclinical hypercortisolism in type 2 diabetic patients from the Rio de Janeiro Type 2 Diabetes Cohort Study
Costa, D., Conceição, F. L., Leite, N. C., Ferreira, M. T., Salles, G. F., & Cardoso, C. R. L. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.05.006 · Cited by 22
Incidental and Metastatic Adrenal Masses
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Cushing's syndrome might be underappreciated in patients seeking bariatric surgery: a plea for screening
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Comorbidities in Mild Autonomous Cortisol Secretion – A Clinical Review of Literature
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Diagnostic efficacy of midnight cortisol and midnight ACTH in the diagnosis and localisation of Cushing’s syndrome
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“The clinical spectrum of Cushing’s disease (CD) is shifting as this rare diagnosis is being increasingly considered among different patient populations [1, 2]. Studies have shown that 2–3% of patients with poorly controlled type 2 diabetes mellitus have unrecognised CS [ 3 ].”
Background
Nonpeptide Corticotropin-Releasing Hormone Receptor Type 1 Antagonists and Their Applications in Psychosomatic Disorders
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“CRH and Endocrine ObesityObesity is a cardinal feature of Cushing’s hypercortisolism, and Cushing’s syndrome is a frequent consideration in the differential diagnosis of obesity [”
Background
Is it worthwhile to screen patients with type 2 diabetes mellitus for subclinical Cushing’s syndrome?
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Which type 2 diabetes mellitus patients should be screened for subclinical Cushing’s syndrome?
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Cushing′s surgery: Role of the anesthesiologist
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“[3] Leibowitz et al,[4] enrolled in their study 90 diabetic patients with a body mass index >25 and glycosylated hemoglobin >9%, definitely diagnosing CS in three patients (3.”
BackgroundInfluential
Role of salivary cortisol determinations in the diagnosis of Cushing syndrome
Raff, H. (2004) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/01.med.0000132655.69704.8c · Cited by 14
Low positive predictive value of midnight salivary cortisol measurement to detect hypercortisolism in type 2 diabetes
Steffensen, C., Thomsen, H. H., Dekkers, O. M., Christiansen, J. S., Rungby, J., & Jørgensen, J. O. L. (2016) · Clinical Endocrinology · doi:10.1111/cen.13071 · Cited by 14
Subclinical Cushing’s Syndrome
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“4 to 10 per million population [1], one small study suggests it may have a prevalence of up to 3% to 4% in the obese, uncontrolled diabetic population [2].”
Background
“Osler’s phenomenon”: misdiagnosing Cushing’s syndrome
De, P., Evans, L., Scanlon, M., et al. (2003) · Postgraduate Medical Journal · doi:10.1136/pmj.79.936.594 · Cited by 14
Budget impact of using midnight salivary cortisol in the diagnosis of hypercortisolism
León‐Justel, A., Mangas, M. Á., Fontan, R., Castro-Luque, J., Moreno, E. V., Madrazo‐Atutxa, A., del Rey, T. H., Martin‐Rodríguez, J. F., Soto‐Moreno, A., & Leal‐Cerro, A. (2011) · Clinica Chimica Acta · doi:10.1016/j.cca.2011.08.013 · Cited by 14
Incidence of Cushing’s syndrome in patients with significant hypercortisoluria
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Authors: Leibowitz, G., Tsur, A., Chayen, S. D., Salameh, M., Raz, I., Cerasi, E., & Gross, D. J.
Affiliations: Hebrew University of Jerusalem (IL)
Corresponding author: Gross, David J.
ORCID: Leibowitz, Gil
Tsur, Anat
Raz, Itamar
Cerasi, Erol
Venue: Clinical Endocrinology
Publisher: Wiley
Published: 1996-06
Volume: 44
Issue: 6
Pages: 717-722
ISSN: 0300-0664 (ISSN-L)
1365-2265
DOI: 10.1046/j.1365-2265.1996.737558.x
OpenAlex: W2019770879
Cited by: 180
References: 0
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 12 · 2014: 5 · 2013: 4 · 2012: 12
FWCI: 1.34
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2706 d)
Locations: Clinical Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: syndromes, uncontrolled diabetes, obesity, glycemic control, dexamethasone suppression test, prevalence, false positive rate, adrenalectomy, surgical treatment, screening test, glycosylated haemoglobin, hypercortisolism, adrenal incidentaloma
MeSH terms: Adult, Aged, Cross-Sectional Studies, Cushing Syndrome, Dexamethasone, Diabetes Mellitus, Female, Humans, Hydrocortisone, Male, Middle Aged, Obesity, Retrospective Studies, Prevalence

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Pre‐clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients

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