TCM is characterized by a self-limiting myocardial dysfunction with complete recovery in most cases within weeks of diagnosis. Though the vast majority has an identifiable emotional or physical trigger prior to the illness, up to one-third have no specific trigger [1, 5]. The disease in general has good long-term prognosis with an in-hospital mortality of around 4%. The high-risk features include left ventricular ejection fraction < 45%, a left ventricular outflow gradient > 40 mm of Hg and the presence of cardiac arrhythmia. Most patients do not have associated coronary artery disease; however, the presence of a significant coronary artery disease does not exclude the diagnosis of TCM. The recurrence rate is maximum within the first year and is around 5% [1,2,3, 5, 9].
The International Takotsubo Diagnostic Criteria have been developed to aid in the diagnosis of TCM. The most important components of the criteria are transient left ventricular dysfunction, the presence of an emotional or physical trigger prior to the episode, new electrocardiographic abnormalities, moderately elevated cardiac biomarkers and no evidence of infectious myocarditis. Accordingly, an InterTAK clinical score was also developed to differentiate TCM from acute coronary syndromes [3, 9].
APS II is a rare endocrine disorder characterized by the coexistence of autoimmune thyroid disease with Addison’s disease and/or diabetes mellitus. Majority of the case of TCM complicating Addison’s disease have been reported in the pediatric age group. The exact pathogenesis of TCM remains elusive, but activation of sympathetic nervous system is believed to be the central theme. Excess catecholamines have deleterious effects on the heart resulting in acute myocardial dysfunction . The proposed theories for catecholamine-mediated myotoxicity include the overstimulation of beta-adrenergic receptors which results in a positive inotropic and chronotropic effect leading to imbalance in oxygen supply demand and resultant ‘functional’ hypoxia [7, 11]. Further, excessive stimulation of the alpha receptors on the coronary arteries causes vasospasm and vasoconstriction causing reduced blood supply and myocardial ischemia and dysfunction [6,7,8]. Other postulations include a downregulation of the beta-adrenergic receptors because of persistent stimulation eventually culminating in reduced myocyte function, oxidative stress, altered calcium homeostasis in the myocardial cells and mitochondrial dysfunction. The same is exemplified by the close association of TCM with pheochromocytoma— another condition in which catecholamine excess results in acute myocardial dysfunction .
Abundant literature points to the permissive effects of cortisol in synthesis of catecholamines as well as facilitating the action of catecholamines on heart and vascular smooth muscles. It enhances the inotropic actions of catecholamines and facilitates increased vasoconstriction by the sympathetic nervous system [7, 8]. Unsurprisingly, there has been association of TCM during induction of steroid therapy for unrelated illnesses reflecting the enhanced actions of catecholamines at alpha and beta receptors . This association can be explained by the improved sensitivity of the cardiac myocardium to the adrenergic system and an exaggerated catecholamine-induced myocardial dysfunction. Another similar association is the occurrence of TCM during administration of higher doses of levothyroxine among hypothyroid patients. The same is also attributable to the permissive effect of thyroid hormones in potentiating the action of catecholamines [4, 14].
The paradox in the index case is the development of TCM in a patient with adrenal insufficiency, wherein in the absence of steroid hormones, the toxic effects of sympathetic catecholamines were realized. Indeed, there have been only very few case reports documenting this association to date [15,16,17]. Pathophysiological mechanism of this association is largely unknown, but certain theories have been hypothesized. In adrenalectomized animal models, there was a toxic effect of catecholamines on the cardiac tissue when they were exposed to stress. The other theories include uncoupling of excitation–contraction in the myocardial cells in the absence of steroid hormones . Hence, the steroid hormones have variable actions on the sympathetic nervous system with both permissive and regulatory effects which is essential for positive inotropic and chronotropic effects on the myocardium in healthy individuals. Deviation from this finely balanced milieu results in myocardial dysfunction as seen in TCM.
TCM is usually a self-limiting disease, and treatment is aimed at achieving early resolution of myocardial dysfunction and preventing future recurrence. Angiotensin-converting enzyme inhibitors have shown promising results in this aspect and are indicated for most patients with TCM [1, 2]. Betablockers are not needed in the majority of cases though some evidence points toward its role in nullifying the sympathetic surge associated with TCM and may help in clinical improvement. In the index case, the induction of stress dose glucocorticoid therapy had a favorable effect on the myocardium. The same has been reported earlier although sparingly [15,16,17,18]. This may reflect the role of glucocorticoids in proper functioning of the membrane calcium transport chain in the sarcoplasmic reticulum which is essential for adequate myocardial contractility . However, one must remember that glucocorticoid therapy initiation is a double-edged sword and it may have an unfavorable effect on myocardial contractility in some patients as hypothesized above. To the best of our knowledge, this is only the 5th case report in the literature in which TCM was associated with APS II [19,20,21,22].