Screening for Cushing’s syndrome: Is it worthwhile?

Posted on March 5, 2015 by MaryO

The data suggests that Cushing is not frequent enough to support the use of routine screening in patients with morbid obesity and type 2 DM. Also only 1 % of hypertensive patients have secondary hypertension due to CS. However, screening should be considered in young patients with resistant DM and/or hypertension. Among patients with osteoporosis and vertebral fractures up to 5 % were diagnosed with subclinical hypercortisolism; most of these had adrenal adenoma. Screening for CS is important in subjects with adrenal incidentaloma, and many studies show a high prevalence (~10 %) of Cushing or subclinical CS in these patients.

Abstract

Introduction

Cushing’s syndrome (CS) is a rare disease characterized by a collection of signs and symptoms, also common in the general population without elevated cortisol secretion. During the last years more patients with CS are identified earlier and with milder disease. Many of these patients are diagnosed during screening efforts performed for certain or isolated complaints like weight gain, diabetes mellitus (DM), hypertension, osteoporosis, elevated white blood cell counts and more.

Methods

In this review article the most popular screening test performed in the studies cited was the 1-mg dexamethasone suppression test.

Conclusions

Cushing is not frequent enough to support the use of routine screening in patients with morbid obesity and type 2 DM. Also only 1 % of hypertensive patients have secondary hypertension due to CS. However, screening should be considered in young patients with resistant DM and/or hypertension. Among patients with osteoporosis and vertebral fractures up to 5 % were diagnosed with subclinical hypercortisolism; most of these had adrenal adenoma. Screening for CS is important in subjects with adrenal incidentaloma, and many studies show a high prevalence (~10 %) of Cushing or subclinical CS in these patients.

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Subclinical Cushing’s syndrome and cardiovascular disease

Posted on May 2, 2014 by MaryO
Panagiotis Anagnostis a cEmail Address, Spyridon N Karras b, Vasilios G Athyros c, Dimitri P Mikhailidis d, Asterios Karagiannis c
Guido Di Dalmazi and colleagues1 reported that in patients with adrenal incidentalomas and either stable mild hypercortisolism or worsening of cortisol hypersecretion, all-cause and cardiovascular disease-specific mortality was higher compared with in those with adrenal incidentalomas that did not secrete cortisol, after a mean follow-up of 7·5 years. Moreover, cortisol concentrations measured after dexamethasone-suppression test were associated with all-cause mortality independent of the presence of traditional cardiovascular disease risk factors.
Subclinical Cushing’s syndrome is the most common hormonal abnormality in patients with adrenal incidentalomas (prevalence 1—29%).2 The proportion of adrenal incidentalomas that progress to subclinical Cushing’s syndrome is low (1·7%) and most are lesions of 3 cm or larger.2 Progression to overt Cushing’s syndrome is controversial (because both spontaneous normalisation of hypersecretion and stable disease have been reported during follow-up) and spontaneous normalisation of hypersecretion has been reported in 50% of cases.2 Results of the study by Di Dalmazi and co-workers1 are important because they show, for the first time, that patients with subclinical Cushing’s syndrome are at increased risk of cardiovascular disease and all-cause mortality (mainly attributable to cardiovascular disease). The association of cortisol with all-cause mortality might also be attributable to its potential role in the pathogenesis of metabolic syndrome.3
Findings of previous studies have shown an increased prevalence of cardiovascular disease risk factors in patients with subclinical Cushing’s syndrome, but data for optimum management are conflicting. Some criteria—such as large (>4—6 cm) adrenal incidentalomas, features suggestive of malignancy (eg, heterogeneity, irregular shape, calcification or necrosis, invasion to adjacent tissues), or potentially lethal hormonal hypersecretion (ie, pheochromocytomas)—support the need for adrenalectomy. However, universal surgical management of patients with subclinical Cushing’s syndrome has not been accepted.2, 4 Uncertainty about the most effective management strategy for subclinical Cushing’s syndrome is attributable to the variable definitions used, and the small sample size and retrospective nature of most studies.4 Only one prospective study has been published so far showing that laparoscopic adrenalectomy is more beneficial than is conservative management for the normalisation or improvement of cardiovascular disease risk factors, such as diabetes, dyslipidaemia, hypertension, and obesity.5
Prospective studies and registries are needed to document the effect of different approaches on the incidence of cardiovascular disease events and mortality in patients with adrenal incidentalomas and subclinical Cushing’s syndrome. Until then, individualised treatment seems prudent. Surgical management of subclinical Cushing’s syndrome can be suggested in young patients (age <50 years) and in those with cardiovascular disease risk factors or bone disease associated with hypercortisolism that are of recent onset, difficult to control with drugs, or show progression over time.4
Another message from Di Dalmazi’s study1 is that hormonal deterioration might develop even after 4—5 years, which most studies reported as a reasonable and safe follow-up.2 This possibility should be kept in mind for the management of patients with adrenal incidentalomas, especially if clinical signs of Cushing’s syndrome develop or if cardiovascular disease risk factors become evident or increase in severity (ie, hormonal hypersecretion).
We declare that we have no competing interests.

References

1 Di Dalmazi G, Vicennati V, Garelli S, et al. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing’s syndrome: a 15-year retrospective study. Lancet Diabetes Endocrinol 2014. published online Jan 29 http://dx.doi.org/10.1016/S2213-8587(13)70211-0.
2 Anagnostis P, Karagiannis A, Tziomalos K, Kakafika AI, Athyros VG, Mikhailidis DP. Adrenal incidentaloma: a diagnostic challenge. Hormones (Athens) 2009; 8: 163-184. PubMed
3 Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab 2009; 94:2692-2701. PubMed
4 Terzolo M, Pia A, Reimondo G. Subclinical Cushing’s syndrome: definition and management. Clin Endocrinol (Oxf) 2012; 76: 12-18. PubMed
5 Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E. Surgical versus conservative management for subclinical Cushing syndrome in adrenal incidentalomas: a prospective randomized study. Ann Surg 2009; 249: 388-391. PubMed
a Division of Endocrinology, Police Medical Centre, Thessaloniki, 54 640, Greece
b Department of Endocrinology and Metabolism, Agios Pavlos General Hospital, Thessaloniki, Greece
c Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
d Department of Clinical Biochemistry (Vascular Prevention Clinic) Royal Free Hospital Campus, University College London Medical School, University College London, London, UK

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