Takotsubo syndrome: hyperthyroidism, pheochromocytoma, or both? A case report
Authors: Marino Gaetano , Michielon Alberto , Musumeci Maria Beatrice , Autore Camillo 
Published: August 2021

Abstract

Background
Takotsubo syndrome (TTS) is a transient left ventricular dysfunction usually with apical akinesia (classical pattern). Other less frequent variants have been described: the mid-ventricular pattern is characterized by hypokinesia of the mid-left ventricle and hypercontractile apical and basal segments; the inverted or basal pattern is characterized by basal and mid-ventricular segment hypokinesia or akinesia with preserved contractility or hypercontractility of apical segments and finally the focal pattern. There are also biventricular variants and forms with exclusive involvement of the right ventricle. There is a correlation between endocrine disorders and TTS, the one most frequently described is with pheochromocytoma. Catecholamine-mediated myocarditis, focal and diffuse myocardial fibrosis, and myocardial dysfunction are described in pheochromocytoma.

Case summary
We describe a case of a 69-year-old patient with a recent diagnosis of hypertension and Graves’ disease, hospitalized for persistent chest pain, hypertensive crisis, tachycardia, dyspnoea, and diaphoresis. Thyroid hormones, antibodies to TSH receptors, and hs-troponin I were increased. Electrocardiogram showed sinus tachycardia at 130 b.p.m., first-degree atrioventricular block, signs of left ventricular hypertrophy with inverted T wave in V4–V6. Echocardiogram demonstrated left ventricular apical and para-apical akinesia. Coronary angiography ruled out an obstructive coronary artery disease. Computed tomography angiogram aortic dissection ruled out aortic dissection but incidentally revealed a left adrenal mass compatible with a pheochromocytoma. Plasma and urinary metanephrines were increased. A TTS secondary to pheochromocytoma and hyperthyroidism was diagnosed. Pharmacological treatment included nitrates, urapidil and esmolol IV and methimazole at high doses. Type 2 multiple endocrine neoplasia has been excluded. After a complete haemodynamic stability on 20th day of hospitalization, the patient underwent an adrenalectomy.

Discussion
High levels of catecholamines in pheochromocytoma can lead to myocardial dysfunction. Similarly, an excess of thyroid hormones with up-regulation of adrenergic system can lead to myocardial dysfunction. These two conditions, if both present, define a high haemodynamic risk profile. How do catecholamines interact with the thyroid gland? The clinical case is of interest as a relationship has been hypothesized between the incretion of plasma catecholamines and Graves’ disease. We suppose an imbalance of the immune system with a predominance of the T helper-type 2 (Th2)-mediated response. Predominance of Th2-mediated immune response may induce humoral immunity causing Graves’ disease. In addition Th2 cytokines are strong inducers of M2 macrophages (alternatively activated) that are involved in autoimmune diseases, myocarditis, and myocardial fibrosis. Knowing the interaction between the cardiovascular system, immune response, and endocrine glands can help define the patient's risk class, possible complications, and follow-up.