A 43-year old woman was referred to the endocrinologist due to resistant arterial hypertension with a history of bilateral adrenal hypertrophy. The first medical contact with the patient dates back to 2012 when she was admitted to the urology department. A CT scan of the abdomen revealed a bilateral adrenal mass, hypodens lesions in the liver and a small left kidney. Further imaging with MRI showed similar findings. The liver lesions were described as hemangiomas. Because of high tensions during hospitalisation the patient was send to nephrology. Hormone balance showed a high to normal serum cortisol, low ACTH and an increased PAC/ARC ratio. A 24-hour urine collection showed no arguments for a pheochromocytoma. An oral salt loading test did not match with hyperaldosteronism. Six months after first imaging, a CT angiography of the renal arteries revealed a mass at the right kidney lower pole. At first the enlarged mass was described as a hemorrhagic cyst, but after further MRI imaging, the mass was suspected of malignancy A lesion in the fourth liver lobe, previously described as focal hepatic steatosis, was also suspected of malignancy. The patient never presented for consultation and was lost in follow-up. Untill four years later the family doctor send the patient to cardiology due to resistant arterial hypertension. Redo CT abdomen showed a new renal mass next to the known mass of the right kidney under pole and new bilateral adrenal nodules next to the known bilateral nodules as earlier described. Five years after the first contact, the patient was seen by an endocrinologist. A new hormonal balance showed an increased serum cortisol with a low ACTH. Control blood sample also revealed a detoriation of the kidney function and an elevated HbA1C (8.4%). Patient was admitted to the endocrinology department. A 48-hour low dose dexamethasone suppression test showed no suppression of serum cortisol. In summary, this case contains three main problems. The first problem being resistant hypertension. Adrenocortical causes of hypertension are primary hyperaldestoronism, hyperdeoxycorticosteronism and Cushing syndrome. Primary hyperaldosteronism was excluded by an oral salt loading test. Cushing syndrome was confirmed by an elevated free cortisol on a 24-hour urine collection, a 48-hour low dose dexamethasone suppression test and an elevated late night salivary cortisol. CT and MRI abdomen revealed bilateral macronodular adenoma which lead us to the diagnosis of macronodular hyperplasia. Secondly the patient has chronic renal failure stage four. Metabolic, we see a high to normal calcium with an elevated PTH. Thirdly, two renal masses and a liver lesion are suspected for malignancy wherefore a PET-CT was performed. This displayed an increased tracer uptake of the lesion in the fourth liver lobe. Liver biopsy withheld no arguments for malignancy. A partial right nephrectomy was proposed. Macronodular hyperplasia is an ACTH-independent Cushing syndrome with bilateral adrenal adenoma greater than one centimeter. It is a rare cause for Cushing syndrome. Macronodular hyperplasia occurs sporadically, however more than fifty percent of the patients are carrier of a mutation of the ARMC5 gene. Pathophysiology is not fully known but two important findings are: an aberrant expression of hormone receptors and a paracrine secretion of ACTH. Diagnosis is based on hormone balance and imaging. Screening for aberrant hormone receptors is indicated for luteinizing hormone (LH), human chorionic gonadotropin (hCG) and beta adrenergic receptors. Most patients have a mild form of Cushing syndrome, a unilateral adrenalectomy as treatment may be sufficient. Rather than surgery, drug treatment is an option for macronodular hyperplasia with aberrant LH, hCG or beta adrenergic receptors.
References: 1. Debillon E, Salenave S, et al. Unilateral adrenalectomy as a first-line treatment of Cushings syndrome in patients with primary bilateral macronodular adrenal hyperplasia. J Clin Endocrinol Metab. 2015. 100; 44174424.
2. Lefebvre H, Duparc C, et al. Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism. Front in endocrin. 2015. 6.
3. Louiset E, Gobet F, et al. ACTH-independent Cushings syndrome with bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma. J Clin Endocrinol Metab. 2010. 95; 1824.
4. Su HM, Dai J, et al. Classification, diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia. Can Urol Assoc. 2013. 7; 594597.
19 - 20 Oct 2018
Belgian Endocrine Society