Dexamethasone Suppression Tests for the Differential Diagnosis of Hypercortisolism

Abstract

Dexamethasone suppression tests (DST) are practical, cheap and safe tests which are used to evaluate endogenous hypercortisolism. They are based on the principle that glucocorticoids exogenously given at supraphysiological doses suppress the production of CRH, ACTH and cortisol by binding to central glucocorticoid receptors. Lack of suppression of cortisol production suggest endogenous hypercortisolism. Additionally, DST may be used in the diagnosis of glucocorticoid remediable hyperaldosteronism. Due to strong glucocorticoid activity, lack of mineralocorticoid activity and lack of cross-reaction with the measurement of cortisol, dexamethasone is the preferred drug for the tests. As a screening tool in endogenous hypercortisolism, overnight 1 mg DST is used. If screening test is negative, hypercortisolism is excluded; but if the test is positive, 2-day 2 mg DST should be performed to confirm the diagnosis of Cushing’s syndrome. If endogenous hypercortisolism is confirmed, plasma ACTH should be measured. Undetectable plasma ACTH level suggest ACTH-independent Cushing’s syndrome, but inappropriately normal or high plasma ACTH level suggest ACTH-dependent Cushing’s syndrome. High dose DST (overnight 8 mg or 2-day 8 mg) should be performed to discriminate pituitary or extra-pituitary cause in the patients with ACTH-dependent Cushing’s syndrome. In the presence of pituitary Cushing’s disease, because of relatively preserved negative feedback mechanism, high dose dexamethasone may suppress ACTH. In ectopic ACTH secretion, due to lack of a normal negative feedback mechanism, ACTH cannot be suppressed by high dose dexamethasone. Extraordinarily, ectopic ACTH production in some neuroendocrine tumors may be suppressed by high dose dexamethasone, but no suppression may be observed in some patients with pituitary Cushing’s disease. When applying DST, serum and plasma samples should be collected in appropriate route, and they should be transferred by true collection tubes and in right storage conditions.

Keywords

• Dexamethasone
• Dexamethasone Suppression Test
• Hypercortisolism
• Cushing Syndrome

Deksametazon Süpresyon Testlerinin Hiperkortizolizm Ayırıcı Tanısında Kullanımı

Abstract

Deksametazon supresyon testleri (DST) endojen hiperkortizolizmin değerlendirilmesinde kullanılan pratik, ucuz ve güvenli testlerdir. Suprafizyolojik dozda ekzojen verilen sentetik glukokortikoidlerin, santral glukokortikoid reseptörlerine bağlanarak CRH, ACTH ve kortizol üretimini baskılaması ilkesine dayanır. Kortizol üretiminin baskılanmaması endojen hiperkortizolizmi düşündürür. Ayrıca DST, glukokortikoid yanıtlı hiperaldosteronizm tanısında da kullanılır. Güçlü glukokortikoid aktivitesinin olması, mineralokortikoid aktivitesinin olmaması ve kortizol ölçümlerine girmemesi sebebiyle deksametazon tercih edilir. Endojen hiperkortizolizm “tarama testi” olarak gecelik “1 mg DST” kullanılır. Tarama testi negatif çıkarsa (<1.8 mcg/dL) hiperkortizolizm dışlanır. Pozitif çıkarsa, yani kortizol düzeylerinde baskılanma olmazsa ≥1.8 mcg/dL) endojen hiperkortizolemiyi doğrulamak için “düşük doz deksametazon süpresyon testi” - 2 gün 2 mg DST- yapılır. Serum kortizol düzeylerinde baskılanma olmaz (≥1.8 mcg/dL) ve Cushin g Sendromu tanısı doğrulanırsa hiperkortizoleminin kaynağını saptamak için plazma ACTH ölçülür. Plazma ACTH ölçülemeyecek seviyedeyse ACTH bağımsız Cushing sendromu, plazma ACTH düzeyi uygunsuz olarak normal veya yüksek ise ACTH bağımlı Cushing sendromu düşünülür. ACTH bağımlı Cushing sendromu düşünülen hastalarda hipofizer veya hipofiz dışı bir patoloji ayırımı için yüksek doz DST (gecelik 8 mg veya 2 gün 8 mg) kullanılır. Hipofizer Cushing varlığında glukokortikoid negatif geri besleme kısmen korunduğundan yüksek doz deksametazon ile ACTH suprese olabilir. Ektopik ACTH salınımında ise glukokortikoid negatif geri besleme yanıtı kaybolduğundan yüksek doz deksametazon ile baskılanma olmaz. İstisna olarak, bazı nöroendokrin tümörlerdeki ektopik ACTH üretimi yüksek doz deksametazon ile baskılanabilirken, bazı hipofizer Cushing vakalarında baskılanma izlenmez. DST uygulanırken, sağlıklı sonuç alabilmek için, serum ve plazma örneklerinin uygun bir şekilde alındığından, doğru tüplerde ve saklama koşullarında taşındığından emin olunmalıdır.

Keywords

• Deksametazon
• Deksametazon Süpresyon Testi
• Hiperkortizolizm
• Cushing Sendromu

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