Endocrine Abstracts

Background: Primary bilateral bilateral macronodular adrenal hyperplasia is a cause of Cushing’s syndrome. It is characterised by a large enlargement of the adrenal glands at the expense of multiple non-pigmented nodules. There is inefficient steroidogenesis.

Summary of the case: A 58-year-old woman with a history of extreme obesity, type 2 diabetes mellitus, hypertension and dyslipidaemia was admitted to our hospital for cellulitis and anaemia secondary to a post-traumatic haematoma. The endocrinology department was consulted for hyperglycaemia. Clinical examinations revealed a Cushing’s phenotype. Blood hormone analysis revealed hypercortisolism, confirmed by elevated urinary cortisol. The primary origin was confirmed by the absence of basal cortisol suppression after dexamethasone 1 mg. An abdominal CT scan revealed enlargement of both adrenal glands consisting of multiple nodular hypodense lesions with low attenuation values. Associated hyperproduction of catecholamines, aldosterone and androgens, and 21-hydroxylase deficiency were ruled out. A 131-iodine-cholesterol scan was requested, which showed intense early bilateral uptake of both adrenals with a final diagnosis of bilateral adrenal hyperplasia scan. Genetic study detected the probably pathogenic variant c.394dup p.(Ala132Glyfs*55) in heterozygosis in the ARMC5 gene.Our patient was diagnosed with long-standing primary Cushing’s syndrome due to bilateral macronodular adrenal hyperplasia caused by a heterozygous mutation in the ARMC5 gene; associated with secondary complications: extreme obesity with severe functional limitation, arterial hypertension, type 2 diabetes mellitus, dyslipidaemia, chronic hypokalaemia and metabolic alkalosis, recurrent spontaneous haematomas and depressive syndrome. Surgical treatment was proposed, but was ruled out due to the maximum surgical risk due to her comorbidities. We therefore started medical treatment with ketoconazole, titrating the dose up to 800 mg per day, achieving disease control, after normalisation of hypercortisolism. During admission, functional limitation of the lower limbs was added, and an X-ray of the lumbar spine was performed, awaiting bone densitometry, which revealed vertebral crushing, and zolendronic acid was started. At present, our patient has been hospitalised for a year as a social problem. She remains functionally and cognitively limited due to persistent depression.

Conclusion: Primary bilateral macronodular adrenal hyperplasia as a cause of Cushing’s syndrome is rare. The initial management of this pathology is surgical, but there are patients with extensive comorbidity in whom this is not possible, and we have to opt for medical treatment. It is important to address all associated comorbidity as it is a pathology with a slow clinical course, but which greatly impairs the quality of life of patients.