REVIEW URRENT C OPINION
Update on subclinical Cushing’s syndrome Lynnette K. Nieman
Purpose of review The present review summarizes recent findings in the diagnosis and treatment of subclinical Cushing’s syndrome, a condition of subtle cortisol dysregulation with a spectrum of clinical and biochemical abnormalities. Recent findings The diagnosis of subclinical Cushing’s syndrome is suggested by abnormal suppression to dexamethasone in a patient with an adrenal mass. The natural history of this disorder includes progression in a minority of cases, and increased cardiovascular disease in patients with more severe and progressive disease, much as is found in overt Cushing’s syndrome. In patients with an abnormal response to dexamethasone, additional biochemical and metabolic features increase confidence in the ability of adrenalectomy to reverse clinical abnormalities. In addition, bilateral masses and larger masses are more likely to be associated with hypercortisolism. Summary We review the recent literature on subclinical cortisol secretion and suggest that additional studies are needed to define optimal diagnostic and therapeutic approaches. Keywords adrenalectomy, hypercortisolism, subclinical Cushing’s syndrome
INTRODUCTION The concept of ‘subclinical’ Cushing’s syndrome refers to the presence of dysregulated cortisol physiology with mild hypercortisolism in a patient who does not exhibit the ‘classical’ or overt signs of Cushing’s syndrome [1–3]. One problem with this definition is that many people in the general population exhibit some signs of Cushing’s syndrome, such as weight gain, hypertension, diabetes, or psychiatric disturbances. Hence, many patients with ‘subclinical’ Cushing’s syndrome do have features of the syndrome, but lack those findings that are more often associated with severe hypercortisolism, such as wide purple striae, unusual infections, and proximal muscle weakness [3]. Dysregulated cortisol physiology is most often recognized during evaluation of an adrenal incidentaloma(s) to exclude Cushing’s syndrome. There is no consensus on how to establish the biochemical diagnosis. Another controversial area is the role of adrenalectomy as opposed to medical treatment of comorbidities. Emerging data suggest that morbidity and mortality are increased on a continuum with increasing number and degree of abnormalities in cortisol. However, these data have not been sufficiently refined on an individual patient level to www.co-endocrinology.com
allow for definitive recommendations. The present review will address recent findings in this area and suggest areas that require additional study.
DEFINITION OF SUBCLINICAL CUSHING’S SYNDROME (I.E., DYSREGULATED MILD CORTISOL EXCESS) One might argue to drop use of the term ’subclinical Cushing’s syndrome’ in favor of a more descriptive (but unwieldy) nomenclature: dysregulated mild hypercortisolism with metabolic and other abnormalities consistent with Cushing’s syndrome. The advantage of this approach is that it encapsulates the biochemical abnormalities and the reason to treat such patients to reduce morbidity and mortality. In this review, the term dysregulated Eunice Kennedy Shriver Institute of Child Health and Human Development, Bethesda, Maryland, USA Correspondence to Eunice Kennedy Shriver Institute of Child Health and Human Development, Building 10, CRC, 1 East, Room 1-3140, 10 Center Dr, MSC 1109, Bethesda, MD 20892, USA. Tel: +1 301 496 8935; fax: +1 301 402 0884; e-mail: [email protected] Curr Opin Endocrinol Diabetes Obes 2015, 22:180–184 DOI:10.1097/MED.0000000000000159 Volume 22 Number 3 June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Update on subclinical Cushing’s syndrome Nieman
Biochemical features of subclinical Cushing’s syndrome include suppressed ACTH (
Update on subclinical Cushing’s syndrome Lynnette K. Nieman
Purpose of review The present review summarizes recent findings in the diagnosis and treatment of subclinical Cushing’s syndrome, a condition of subtle cortisol dysregulation with a spectrum of clinical and biochemical abnormalities. Recent findings The diagnosis of subclinical Cushing’s syndrome is suggested by abnormal suppression to dexamethasone in a patient with an adrenal mass. The natural history of this disorder includes progression in a minority of cases, and increased cardiovascular disease in patients with more severe and progressive disease, much as is found in overt Cushing’s syndrome. In patients with an abnormal response to dexamethasone, additional biochemical and metabolic features increase confidence in the ability of adrenalectomy to reverse clinical abnormalities. In addition, bilateral masses and larger masses are more likely to be associated with hypercortisolism. Summary We review the recent literature on subclinical cortisol secretion and suggest that additional studies are needed to define optimal diagnostic and therapeutic approaches. Keywords adrenalectomy, hypercortisolism, subclinical Cushing’s syndrome
INTRODUCTION The concept of ‘subclinical’ Cushing’s syndrome refers to the presence of dysregulated cortisol physiology with mild hypercortisolism in a patient who does not exhibit the ‘classical’ or overt signs of Cushing’s syndrome [1–3]. One problem with this definition is that many people in the general population exhibit some signs of Cushing’s syndrome, such as weight gain, hypertension, diabetes, or psychiatric disturbances. Hence, many patients with ‘subclinical’ Cushing’s syndrome do have features of the syndrome, but lack those findings that are more often associated with severe hypercortisolism, such as wide purple striae, unusual infections, and proximal muscle weakness [3]. Dysregulated cortisol physiology is most often recognized during evaluation of an adrenal incidentaloma(s) to exclude Cushing’s syndrome. There is no consensus on how to establish the biochemical diagnosis. Another controversial area is the role of adrenalectomy as opposed to medical treatment of comorbidities. Emerging data suggest that morbidity and mortality are increased on a continuum with increasing number and degree of abnormalities in cortisol. However, these data have not been sufficiently refined on an individual patient level to www.co-endocrinology.com
allow for definitive recommendations. The present review will address recent findings in this area and suggest areas that require additional study.
DEFINITION OF SUBCLINICAL CUSHING’S SYNDROME (I.E., DYSREGULATED MILD CORTISOL EXCESS) One might argue to drop use of the term ’subclinical Cushing’s syndrome’ in favor of a more descriptive (but unwieldy) nomenclature: dysregulated mild hypercortisolism with metabolic and other abnormalities consistent with Cushing’s syndrome. The advantage of this approach is that it encapsulates the biochemical abnormalities and the reason to treat such patients to reduce morbidity and mortality. In this review, the term dysregulated Eunice Kennedy Shriver Institute of Child Health and Human Development, Bethesda, Maryland, USA Correspondence to Eunice Kennedy Shriver Institute of Child Health and Human Development, Building 10, CRC, 1 East, Room 1-3140, 10 Center Dr, MSC 1109, Bethesda, MD 20892, USA. Tel: +1 301 496 8935; fax: +1 301 402 0884; e-mail: [email protected] Curr Opin Endocrinol Diabetes Obes 2015, 22:180–184 DOI:10.1097/MED.0000000000000159 Volume 22 Number 3 June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Update on subclinical Cushing’s syndrome Nieman
Biochemical features of subclinical Cushing’s syndrome include suppressed ACTH (
