Diagnostic Approach to Cushing Disease

Bradley A. Gross, B.S.; Stefan A. Mindea, M.D.; Anthony J. Pick, M.D.; James P. Chandler, M.D.; H. Hunt Batjer, M.D.

Disclosures

Neurosurg Focus. 2007;23(3):E1 

In This Article

Abstract and Introduction

Abstract

In Cushing disease, a pituitary corticotroph neoplasm causes secondary adrenal hypercortisolism. This condition has known morbidity and mortality, underscoring the need for an efficient and accurate diagnostic approach. An 11 p.m. salivary cortisol level is a modern, simple initial screening tool for the diagnosis of Cushing syndrome. Confirmation with a 24-hour urinary free cortisol test and/or a low-dose dexamethasone suppression test may subsequently be performed. Patients with repeatedly equivocal results should be reevaluated after several months or undergo a corticotropin- releasing hormone (CRH) stimulation test following low-dose dexamethasone suppression to help rule out pseudo-Cushing states. The presence of low morning serum adrenocorticotropic hormone (ACTH) levels then distinguishes primary adrenal hypercortisolism from Cushing disease and the ectopic ACTH syndrome. Patients with moderate ACTH levels can undergo CRH stimulation testing to clarify the underlying disease because those with an ACTH-independent disorder have blunted subsequent ACTH levels. Once ACTH-dependent hypercortisolemia is detected, magnetic resonance (MR) imaging of the pituitary gland can be performed to detect a pituitary neoplasm. Normal or equivocal MR imaging results revealing small pituitary lesions should be followed up with inferior petrosal sinus sampling, a highly specific measure for the diagnosis of Cushing disease in experienced hands. If necessary, body imaging may be used in turn to detect sources of ectopic ACTH.

Introduction

Cushing disease, first described by Harvey Cushing in 1912 in his book entitled The Pituitary Body and its Disorders, is the most common cause of spontaneous Cushing syndrome, accounting for approximately two thirds of cases.[35,36] In this disease, neoplastic corticotroph hypersecretion of ACTH leads to excessive production of cortisol from the adrenal cortex. In contrast to their normal corticotroph counterparts, the neoplastic pituitary cells in this disease are relatively resistant to negative feedback from the resultant hypercortisolism and hence continue to produce excessive ACTH, perpetuating adrenal cortisol hypersecretion. Despite the considerable prevalence of hypertension and obesity in the general population, associated temporal fossa and supraclavicular fullness are somewhat specific findings that should prompt the physician to consider screening for Cushing syndrome.[11] Other associated symptoms include, but are not limited to, bruising, myopathy, glucose intolerance, and osteoporosis. Notably, the absence of bitemporal hemianopsia is not a strong negative predictive factor for Cushing disease because the majority of patients with this disease have pituitary microadenomas.[28]

Appropriate diagnosis and management of Cushing disease is important because the mortality rate in patients with this disease is at least fourfold that in the general population matched for age and sex.[42] Control of hypercortisolism leads to gradual improvement of bruising, myopathy, central obesity, glucose intolerance and hypertension, and rapid improvement of osteoporosis.[25] Although the initial presentation of a patient with such a constellation of symptoms is suggestive of Cushing syndrome, most symptoms characteristic of the disease are nonspecific, resting the burden of an accurate diagnosis on an appropriate diagnostic workup.

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