Background: The common causes of adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome (CS) include Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis and lesion location of CD and EAS often bring great difficulties to clinical diagnosis and treatment. This article reports the localization diagnosis, treatment, and follow-up results of two patients with ACTH-dependent CS with different causes and reviews the literature.
Case description: Case 1: a 29-year-old female patient attended the clinic because of irregular menstruation, weight gain, and violaceous striae. The low dose dexamethasone suppression test (LDDST) was not suppressed, and the high dose dexamethasone suppression test (HDDST) suggested the results of serum cortisol and 24-h urine free cortisol were contradictory. Magnetic resonance imaging (MRI) indicated pituitary microadenoma, and bilateral inferior petrosal sinus sampling (BIPSS) indicated ACTH was centrally secreted. CD was diagnosed. The patient underwent transsphenoidal surgery, and the symptoms of CS were improved after the operation. A natural pregnancy occurred more than half a year after the surgery, and a healthy baby boy was delivered 9 months later. Case 2: a 29-year-old female patient complained of facial redness and elevated blood pressure. Examination showed refractory hypokalemia and abnormally elevated serum cortisol and ACTH. Androgens also increased. Neither LDDST nor HDDST was inhibited. Chest-to-pelvis computed tomography (CT) scan revealed a soft tissue mass in the anterior mediastinum, considered as a possible thymoma. EAS and thymoma were diagnosed. An anterior mediastinal mass resection was performed, and pathological results suggested thymic carcinoid weakly positive for ACTH. After the operation, hypertension and hypokalemia were relieved, and cortisol, ACTH and androgens returned to normal levels.
Conclusions: The differentiation between CD and EAS should be comprehensively evaluated in combination with the medical history, function tests, pituitary MRI, and other tests. If the function test results are discordant or pituitary MRI shows the lesion diameter is less than 6 mm, BIPSS should be further performed to confirm the diagnosis. The lesions of EAS are complex and diverse, and it is necessary to pay attention to imaging examinations of the neck-to-pelvis to locate lesion and provide direction for subsequent treatment.
Keywords: Adrenocorticotrophic hormone-dependent Cushing’s syndrome; Cushing’s disease (CD); bilateral inferior petrosal sinus sampling (BIPSS); case report; ectopic adrenocorticotrophic hormone syndrome (EAS).