Increased diagnostic probability of subclinical cushing’s syndrome in a population sample of overweight adult patients with type 2 diabetes mellitus

Endogenous Cushing’s Syndrome (CS) is unusual. Patients with subclinical CS (SCS) present altered cortisol dynamics without obvious manifestations. CS occurs in 2-3 percent of obese poorly controlled diabetics. We studied 103 overweight adult outpatients with type 2 diabetes to examine for cortisol abnormalities and SCS. All collected salivary cortisol at 23:00 h and salivary and serum cortisol after a 1 mg dexamethasone suppression test (DST). Patients whose results were in the upper quintile for each test (253 ng/dL, 47 ng/dL, and 1.8 mg/dL, respectively for the 23:00 h and post-DST saliva and serum cortisol) were re-investigated. Average values from the upper quintile group were 2.5-fold higher than in the remaining patients. After a confirmatory 2 mg x 2 day DST the investigation for CS was ended for 61 patients with all normal tests and 33 with only one (false) positive test. All 8 patients who had two abnormal tests had subsequent normal 24h-urinary cortisol, and 3 of them were likely to have SCS (abnormal cortisol tests and positive imaging). However, a final diagnosis could not to be confirmed by surgery or pathology. Although not confirmatory, the results of this study suggest that the prevalence of SCS is considerably higher in populations at risk than in the general population.

A síndrome de Cushing (SC) endógena é rara. Pacientes com SC subclínica (SCS) apresentam hipercortisolismo sem manifestações clínicas. SC ocorre em 2-3 por cento de diabéticos mal controlados. Estudamos 103 pacientes adultos obesos ambulatoriais com diabetes mellitus tipo 2 para avaliar alterações do cortisol e SCS. Todos coletaram cortisol salivar às 23:00 h e cortisol salivar e sérico após teste de supressão com 1 mg de dexametasona (DST). Pacientes cujos resultados de qualquer teste estavam no quintil superior (253 ng/dL, 47 ng/dL e 1,8 mg/dL, respectivamente para cortisol salivar 23:00 h e salivar e sérico pós-DST) foram reavaliados. Os valores médios desse grupo encontravam-se 2,5 vezes acima dos valores dos demais pacientes. Após um teste confirmatório com 2 mg x 2 dias DST, a investigação da SC foi encerrada para 61 pacientes com todos os testes normais e 33 com apenas um teste (falso) positivo. Todos os 8 pacientes com dois testes alterados apresentaram cortisol urinário normal, mas 3 deles mostraram maior probabilidade diagnóstica de SCS (hipercortisolismo e alterações em exames de imagem). Contudo, o diagnóstico final não pode ser confirmado por cirurgia ou patologia em nenhum deles. Embora não confirmatórios, os resultados deste estudo sugerem que a prevalência de SCS seja maior em populações de risco do que na população geral.

Estudio de 34 pacientes con incidentaloma suprarrenal / A study of 34 cases of adrenal incidentaloma

El incidentaloma suprarrenal, un tumor de dicha glándula descubierto por razones independientes de la sospecha de enfermedad adrenal, constituye un problema clínico frecuente. Aunque en la mayoría de los casos son benignos y no hiperfuncionantes, es importante identificar oportunamente la minoría de lesiones malignas o hiperfuncionantes de resolución quirúrgica. Si bien han sido diseñadas distintas estrategias de diagnóstico hay controversia alrededor de una serie de cuestiones. En el presente trabajo retrospectivo once (32%) de nuestros 34 pacientes presentaban masas adrenales hiperfuncionantes manifestadas por síndrome de Cushing subclínico en cuatro, feocromocitoma en tres, probable hiperaldosteronismo primario en dos y por hiperplasia adrenal congénita de origen tardío y carcinoma funcionante en los dos restantes. Las características de las imágenes por TAC y/o RM permitieron identificar los adenomas a la vez que decidir la cirugía tanto en dos pacientes con feocromocitomas bioquímicamente no funcionantes como en una paciente con un carcinoma adrenocortical primitivo, este diagnóstico también sugerido por un patrón mixto de hipersecreción de andrógenos y cortisol. En una paciente con síndrome de Cushing subclínico, hipertensa y diabética, ambas comorbilidades fueron resueltas por la cirugía. Los tumores no funcionantes fueron en su mayoría adenomas (87%), hallándose además histoplasmosis, pseudoquiste, hiperplasia suprarrenal idiopática y mielolipoma. Seis de los ocho pacientes operados tenían enfermedad maligna y/o hiperfuncionante. La condición asociada a los incidentalomas suprarrenales significó un amplio espectro de riesgo para los pacientes y reafirma la necesidad de una minuciosa evaluación clínica, bioquímica y de las imágenes a fin de adoptar conductas adecuadas.

Adrenal incidentaloma, a tumor discovered unexpectedly during imaging performed for non-adrenal related causes, has become a frequent clinical concern. Although in most cases they are benign and hormonally nonfunctioning, it is important to appropriately identify those few cases of malignant or hyperfunctioning lesions of surgical resolution. Although several proposals for an optimal diagnostic strategy have been designed, controversy over a series of questions still persists. In the present retrospective study we analyzed 34 patients with adrenal incidentaloma. Of these, 32% of the patients displayed hyperfunctioning pathologies that included subclinical Cushing's syndrome in four patients, probable primary hyperaldosteronism in two, late onset congenital adrenal hyperplasia in one, adrenocortical carcinoma in one and pheochromocytoma in three. CT and/or MRI permitted the identification of adenomas and were crucial to decide on surgery in two patients with nonfunctioning pheochromocytomas and in a patient carrying a primitive adrenocortical carcinoma, a diagnosis also suggested by a mixed pattern of hypersecretion of androgens and cortisol. In a diabetic and hypertensive patient with subclinical Cushing's syndrome both comorbidities were solved by surgery. Nonfunctioning tumors were mainly adenomas (87%) with individual cases of histoplasmosis, pseudocyst, idiopathic adrenal hyperplasia and mielolipoma. Six of the eight operated patients presented malignant and/or hyperfunctioning tumors. The pathology associated with incidentalomas represents a broad spectrum of risk for patients and reaffirms the necessity for a meticulous clinical, biochemical, and imaging evaluation in order to make appropriate decisions.