Pitfalls in the diagnosis of Cushing's syndrome

Abstract

Among endocrine disorders, Cushing's syndrome (CS) is certainly one of the most challenging to endocrinologists due to the difficulties that often appear during investigation. The diagnosis of CS involves two steps: confirmation of hypercortisolism and determination of its etiology. Biochemical confirmation of the hypercortisolaemic state must be established before any attempt at differential diagnosis. Failure to do so will result in misdiagnosis, inappropriate treatment, and poor management. It should also be kept in mind that hypercortisolism may occur in some patients with depression, alcoholism, anorexia nervosa, generalized resistance to glucocorticoids, and in late pregnancy. Moreover, exogenous or iatrogenic hypercortisolism should always be excluded. The three most useful tests to confirm hypercortisolism are the measurement of 24-h urinary free cortisol levels, low-dose dexamethasone-suppression tests, and determination of midnight serum cortisol or late-night salivary cortisol. However, none of these tests is perfect, each one has different sensitivities and specificities, and several are usually needed to provide a better diagnostic accuracy. The greatest challenge in the investigation of CS involves the differentiation between Cushing's disease and ectopic ACTH syndrome. This task requires the measurement of plasma ACTH levels, non-invasive dynamic tests (high-dose dexamethasone suppression test and stimulation tests with CRH or desmopressin), and imaging studies. None of these tests had 100% specificity and their use in combination is usually necessary. Bilateral inferior petrosal sinus sampling is mainly indicated when non-invasive tests do not allow a diagnostic definition. In the present paper, the most important pitfalls in the investigation of CS are reviewed. Entre as doenças endócrinas, a síndrome de Cushing (SC) é certamente uma das mais desafiadoras para o endocrinologista, devido às dificuldades que comumente surgem durante a investigação. O diagnóstico de SC envolve dois passos: a confirmação do hipercortisolismo e a determinação de sua etiologia. A confirmação bioquímica do excesso de cortisol precisa ser estabelecida antes de qualquer tentativa de diagnóstico diferencial; caso contrário, poderá resultar em diagnóstico incorreto, tratamento impróprio e manejo insuficiente. Deve também ser lembrado que hipercortisolismo pode ocorrer em certos pacientes com depressão, alcoolismo, anorexia nervosa, resistência generalizada aos glicocorticóides e no final da gravidez. Além disso, hipercortisolismo exógeno ou iatrogênico deverá ser sempre excluído. Os três testes mais úteis para a confirmação do hipercortisolismo são: a medida do cortisol livre em urina de 24 h, os testes de supressão com dexametasona (TSD) em doses baixas e a determinação do cortisol sérico à meianoite ou do cortisol salivar no final da noite. Contudo, nenhum deles é perfeito, cada um com sua sensibilidade e especificidade, sendo vários deles usualmente necessários para fornecer uma melhor acurácia diagnóstica. O ma...

Performance of salivary cortisol in the diagnosis of Cushing's syndrome, adrenal incidentaloma, and adrenal insufficiency

“…In light of this, physicians may be called to exclude the different forms of CS from the most common ones in the general population: obesity, depression, hirsutism, and metabolic syndrome (3). UFC collection and the 1 mg DST are simple, but neither is able to make a certain diagnosis of CS (15,20,21). The LNSC test, as proposed recently (5,6,7,10,11,12,14), is a reliable, noninvasive, stress-free, and low-cost procedure to diagnose CS.…”

Incidental and Metastatic Adrenal Masses

“…46 Some investigators have shown that elevated midnight salivary cortisol levels are a useful and simple screening test for hypercortisolism, with a sensitivity and specificity reaching 90% to 95%. 47 In patients without clearly diagnostic laboratory results, a classical DST (Liddle test: 2 mg/d oral dexamethasone for 2 days) may be performed.…”

A rare case of Cushing syndrome by cyclic ectopic-ACTH

“…Diagnosis of ACTH ectopic secretion involves two basic steps that cannot be omitted to prevent misdiagnosis: confirmation of hypercortisolism and determination of its etiology (differential diagnosis) (4). After confirmation of hypercortisolism in ACTH-dependent matter, bilateral sinus sampling (BIPSS) is the best single test to differentiate between a central and a peripheral source of ACTH (2,5).…”

“…Once EAS is confirmed, identification of the site of the primary tumor may begin with chest high-resolution computerized tomography (CT) scan. If results are normal, extensive abdominal CT should be carried out (4). In the case of negative scans, somatostatin receptor scintigraphy (SRS) or fluorine-18-fluorodeoxyglucose positron emission tomography scan ([18-F]-FDG-PET) may be used.…”

“…The rationale for SRS is the presence of large number of high-affinity somatostatin receptors in many neuroendocrine tumors. The potential advantage in relation to conventional radiology is that it gives information about the whole body, enabling primary and metastatic lesions to be visualized (4). Fluorine-18-fluorodeoxyglucose PET is widely used to identify malignant (high metabolism) tumors.…”