Considering these results a diagnosis of adrenocortical adenoma with mixed nodules enriched in adrenaline-type secretory granules was made.
The patient was discharged medicated with irbesartan 150 mg/day, amlodipine 5 mg/day, and hydrochlorothiazide 12.5 mg/day.
At 6 months follow up, the patient's 24-hours urinary metanephrines levels were normalized (143 μg/24 h) and the transthoracic echocardiography after surgery showed a reduction of end-diastolic intraventricular septum thickness (14 mm) (Table 2) associated to normalization of BP values (130/80 mm Hg).
This is a unique case, to our knowledge, of a catecholamine-induced HCM induced by a cortical adrenal adenoma with adrenaline-neurosecretory granules inside. The appearance of these metabolites, stored into nodules enriched in multiple secretory granules, explains the strongest uptake of the left adrenal lesion in 123I-MIBG scintigraphy. Previously, false-positive results of MIBG imaging were reported in adrenal adenomas showing augmented tracer uptake.[6,7,8] We support that our case cannot be listed in those previously described because we demonstrated, by using electron microscopy, the existence of a complex network of neurosecretory granules, that are directly responsible of this clinical scenario.
Left ventricular endomyocardial biopsy has been crucial, in this case, to testify catecholamine-induced LVH. Use of endomyocardial biopsy in HCM is still controversial and is recommended only in infiltrative or storage diseases. In patients with true HCM, left ventricular endomyocardial biopsy can be specifically useful to analyze the underlying causes of cardiac deterioration, to demonstrate histological changes during the course of the disease, and finally to provide myocardial tissue for research purposes.
Catecholamine-induced cardiomyopathy is defined by a reversible left ventricular dysfunction without evidence of obstructive coronary artery disease. Acute and chronic myocardial damage are the results of an exogenous or endogenous catecholamine excess.
Overactivation of the sympatho-adrenergic system is an essential process to support cardiovascular system during stressful conditions in critical illnesses. Although, its prolonged and excessive stimulation is detrimental to cardiovascular system. Abnormal amounts of catecholamines, via the beta-1 adrenoceptor transduction pathway, induce directly intracellular calcium overload in cardiomyocytes. Furthermore, these metabolites can also indirectly damage the heart, in particular via their oxidation during stressful situations, which generate oxygen radicals that provoke coronary artery spasm, arrhythmias and cardiac dysfunction. On the other hand, long-term exposure to catecholamines down-regulate the expression of beta-adrenergic receptors, inducing the suboptimal function of myofibers and decreasing the number of contracting units. As the consequent result, PHEO-associated cardiomyopathy is histologically characterized by contraction band necrosis, neutrophil infiltration, and fibrosis.
Similar mechanisms of myocardial toxicity, which originate from a hyper catecholaminergic state, have been described in case of cocaine abuse, including marked oxidative stress and mitochondrial dysfunction. Instead, chronic use of cocaine may results in various degrees of systolic and diastolic dysfunction, cardiac hypertrophy and dilatation. Histological features, such as in those cases of endogenous excess of catecholamines, include loss of myofibrils, multiple foci of band contraction necrosis and fibrosis.
Treatment of PHEO-associated cardiomyopathy is curative surgical resection of catecholamine-producing tumor. After the appropriate excision of PHEO, cardiomyopathy may definitely reverse.
In summary, we have described a rare case of catecholamine–induced cardiomyopathy due to an adrenal adenoma mixed with nodules enriched in epinephrine-type secreting granules. The patient has provided informed consent for publication of this case report.
Data curation: Federica Olmati, Gaia Oliviero, Maria Bonvicini, Antonio Ciardi, Gino Iannucci.
Investigation: Vincenza Saracino, Martina Mezzadri.
Methodology: Valeria Bisogni, Antonio Concistré.
Supervision: Giorgio de Toma, Claudio Letizia.
Validation: Giorgio de Toma, Andrea Frustaci, Claudio Letizia.
Writing – original draft: Luigi Petramala, Andrea Frustaci, Claudio Letizia, Federica Olmati.
Writing – review & editing: Luigi Petramala, Federica Olmati.
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Keywords:Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
adrenal adenoma; catecholamine–induced cardiomyopathy; endomyocardial biopsy; pheochromocytoma