Evaluation and Treatment of Patients With Hypercortisolism

Abstract

lthough different across races and ethnicities, the incidence of hypercortisolism ranges from 0.2 to 5.0 cases per million per year with an estimated prevalence of 39 to 79 cases per million in various populations. [1][2][3][4] However, considerable underdiagnosis is likely, especially in the case of mild autonomous cortisol secretion (MACS, formerly known as subclinical Cushing syndrome). The incidence of MACS in patients with adrenal incidentalomas ranges from 5% to 30%. 5,6 In patients with hypertension, diabetes, obesity, and osteoporosis, the incidence of MACS reaches 10%. Chronic diseases, such as hypertension, diabetes, obesity, and osteoporosis, affect nearly half of the US population, are costly, and are among the nation's leading causes of death and disability. 7 The need to limit development and unrecognized persistence of these potentially curable conditions that lead to chronic disease is of great importance and should be a focus of attention.Surgeons often encounter patients with hypertension, type 2 diabetes, obesity, and bone density loss. These common comorbidities are associated with increased morbidity and mortality in patients undergoing surgery. In some, hypercortisolism is the underlying cause of these comorbidities. Depending on the origin, site, and degree of excess cortisol production, hypercortisolism may be classified as Cushing disease, Cushing syndrome, ectopic Cushing syndrome, or MACS. An understanding of the outcomes, challenges in diagnosis, and management of hypercortisolism will assist surgeons in caring for these patients. With knowledge of the adverse outcomes of hypercortisolism and strategies to mitigate these, improved surgical outcomes may follow. Enhanced preoperative evaluation and preparation of patients for surgery and incorporation of intraoperative tactics to minimize bleeding, infection, anastomotic leak, and wound dehiscence are important to optimize outcomes in these patients. Postoperative pathways to optimize recovery are often overlooked but are vital to long-term functional status.This review examines hypercortisolism from a surgeon's viewpoint and considers the present and future state of disease management. Included with a basic review of pathophysiology, evaluation, and general management of hypercortisolism is a discussion of specific organ system outcomes, pitfalls in the diagnosis of hypercortisolism, and preoperative, perioperative, and postoperative management considerations. Population health outcomes and the potential role surgeons can play in treating patients with MACS are also discussed. Higher-level considerations are put forth to encourage a long-term view of future work needed to optimally care for these patients. PathophysiologyCorticotropin-releasing factor is produced in the hypothalamus and stimulates production of adrenocorticotropin hormone (ACTH) IMPORTANCE With the potential for severe adverse effects of hypercortisolism, the need to limit the development and unrecognized persistence of sequelae from cortisol excess is of great importan...

Common Pitfalls in the Interpretation of Endocrine Tests

“…• A Cushing's syndrome diagnosis will be confirmed when at least two first-line (screening) tests are positive (21). • To improve the diagnostic sensitivity of screening test, the upper reference value of > 145 ng/dL for salivary cortisol is used.…”

“…• If the screening test are normal in patients with low clinical suspicion, it is unlikely the disease is present unless mild or cyclical hypercortisolism is present. If two negative results in two different tests are observed, no other tests are recommended (21). • Nocturnal serum cortisol: A value of > 7.5 mcg/dL is necessary for a Cushing's syndrome diagnosis (Sens = 96%, Spe = 100%).…”

“…The CRH stimulation test shows a complete lack of response if it is of adrenal origin or on the other side, if there is an elevation of ACTH, a diagnosis of ACTH-dependent Cushing's syndrome may be considered (22). • In cases of ACTH-dependent hypercortisolism, a pituitary cause should be initially evaluated; studies are aimed at identifying a possible corticotropic adenoma with MRI or performing an inferior petrosal sinus sampling (IPSS) (21,23). If ACTH production is ectopic, studies should be performed to identify the etiology, such as: CT chest, abdomen, pelvis, or consider gallium-68 DOTATATE scan or, depending on availability, 18 F-Dopa positron emission tomography PET-CT. An alternative approach in cases of ACTH-dependent hypercortisolism is to perform the SSDT at 11:00 p.m. at high doses with 8 mg of dexamethasone -80% of pituitary tumors will be suppressed and will present a decrease of greater than 50% in subsequent cortisol.…”

“…In patients with chronic kidney disease with glomerular filtration rate less than 30 ml/minute, 1 mg dexamethasone suppression test is recommended over urinary cortisol (Table2). In patients with epilepsy, urinary cortisol or salivary cortisol is recommended, as many anticonvulsants increase dexamethasone clearance(12,21).• The main protein involved in cortisol transport is the cortisol binding globulin (CBG). Methods used for cortisol measurement do not distinguish protein-bound cortisol (90%) from free cortisol (10%).…”

“…Methods used for cortisol measurement do not distinguish protein-bound cortisol (90%) from free cortisol (10%). Therefore, plasmatic cortisol values should be interpreted carefully in situations that could alter CBG concentrations(21,23). • This way, if a reduction in CBG synthesis occurs (liver disease, hypothyroidism, sepsis) or if renal losses are increased…”