The 4Ds of ectopic ACTH syndrome: diagnostic dilemmas of a difficult disease

Abstract

Cushing's syndrome (CS) is an uncommon condition that leads to high morbidity and mortality. The majority of endogenous CS is caused by excessive ACTH secretion, mainly due to a pituitary tumor-the so-called Cushing's disease (CD)-followed by ectopic ACTH syndrome (EAS), an extrapituitary tumor that produces ACTH; adrenal causes of CS are even rarer. Several methods are used to differentiate the two main etiologies: specific laboratory tests and imaging procedures, and bilateral inferior petrosal sinus sampling (BIPSS) for ACTH determination; however, identification of the source of ACTH overproduction is often a challenge. We report the case of a 28-year-old woman with clinical and laboratory findings consistent with ACTH-dependent CS. All tests were mostly definite, but several confounding factors provoked an extended delay in identifying the origin of ACTH secretion, prompting a worsening of her clinical condition, with difficulty controlling hyperglycemia, hypokalemia, and hypertension. During this period, clinical treatment was decisive, and measurement of morning salivary cortisol was a differential for monitoring cortisol levels. This report shows that clinical reasoning, experience and use of recent methods of nuclear medicine were decisive for the elucidation of the case.

Síndrome de Cushing: Revisao Integrativa

“…Quanto à Doença de Cushing (DC) refere-se ao hipercortisolismo causado pela secreção excessiva de hormônio adrenocorticotrófico (ACTH) por lesão hipofisária, sendo esta a causa mais frequente de SC 2,3 . O principal glicocorticoide produzido pelo córtex da glândula suprarrenal é o cortisol.…”

“…Em indivíduos saudáveis, a homeostase fisiológica dos corticotróficos é ajustada por fatores hipotalâmicos estimulatórios e inibitórios e pelo ciclo de feedback negativo dos glicocorticóides das glândulas supra-renais. No entanto, o tumor produtor de ACTH presente na DC é insensível às inibições que ocorreriam normalmente, resultando, assim, em um sistema incapaz de se autorregular e, consequentemente, em níveis aumentados de glicocorticóides causando o hipercortisolismo 3,4 .…”