Abstract
Ectopic ACTH syndrome (EAS) accounts for 10–20% of endogenous Cushing’s syndrome (CS). Hardly any cases of adrenal medullary hyperplasia have been reported to ectopically secrete adrenocorticotropic hormone (ACTH). Here we describe a series of three patients with hypercortisolism secondary to ectopic production of ACTH from adrenal medulla. Cushingoid features were absent in case 1 but evident in the other two cases. Marked hypokalemia was found in all three patients, but hyperglycemia and osteoporosis were present only in case 2. All three patients showed significantly elevated serum cortisol and 24-h urinary cortisol levels. The ACTH levels ranged from 19.8 to 103.0pmol/L, favoring ACTH-dependent Cushing’s syndrome. Results of bilateral inferior petrosal sinus sampling (BIPSS) for case 1 and case 3 confirmed ectopic origin of ACTH. The extremely high level of ACTH and failure to suppress cortisol with high dose dexamethasone suppression test (HDDST) suggested EAS for patient 2. However, image studies failed to identify the source of ACTH secretion. Bilateral adrenalectomy was performed for rapid control of hypercortisolism. After surgery, cushingoid features gradually disappeared for case 2 and case 3. Blood pressure, blood glucose and potassium levels returned to normal ranges without medication for case 2. The level of serum potassium also normalized without any supplementation for case 1 and case 3. The ACTH levels of all three patients significantly decreased 3-6 months after surgery. Histopathology revealed bilateral adrenal medullary hyperplasia and immunostaining showed positive ACTH staining located in adrenal medulla cells. In summary, our case series reveals the adrenal medulla to be a site of ectopic ACTH secretion. Adrenal medulla-originated EAS makes the differential diagnosis of ACTH-dependent Cushing’s syndrome much more difficult. Control of the hypercortisolism is mandatory for such patients.
Highlights
Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome can be classified as either Cushing’s disease or ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS)
Our case series suggest that severe Cushing’s syndrome can be induced by ectopic production of ACTH caused by adrenal medulla hyperplasia, supported by a drastic decrease of ACTH level after bilateral adrenalectomy, positive ACTH staining in adrenal medulla cells, and the number of ACTH positive cells in proportion to serum ACTH level
Back in 1980s, researchers showed the presence of immunoreactive ACTH and corticotropin-releasing hormone (CRH) in adrenals by radioimmunity assay, immunoaffinity chromatography, and gel filtration chromatography [11]
Summary
Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome can be classified as either Cushing’s disease or ectopic ACTH syndrome (EAS). 70mmHg. ACTH level significantly decreased at the latest follow-up (3 months after surgery, Table 2), indicating adrenal glands to be the origin of excess ACTH. ACTH and CRH staining were both negative for the tumor, whereas histopathology showed an increased adrenal medullary cell mass and diffuse hyperplasia of the medullary cells in both adrenal glands (Figures 2A, B). Physical examination revealed a blood pressure of 130/90 mmHg, weight of 99 kg, and height of 177 cm (BMI 31.6 Kg/ m2) He showed cushingoid features including moon face, supraclavicular fat accumulation, buffalo hump, facial and truncal acne, ecchymoses and striae. BIPSS showed that there was no evidence of a central-to-peripheral gradient of ACTH at baseline or after desmopressin stimulation According to these findings, the patient was diagnosed with EAS. In order to suppress ACTH secretion, we added dexamethasone 0.1875mg at 10PM
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