Takotsubo cardiomyopathy and endocrine disorders: a mini-review of case reports
Contents lists available at ScienceDirect
American Journal of Emergency Medicine
journal homepage: locate/ ajem
Takotsubo cardiomyopathy and Endocrine disorders: a mini-review of case reports?,??
To the Editor,
Endocrine disorders may trigger cardiovascular (CV) risk factors [1]. Diabetes mellitus and pituitary [2,3], thyroid [4,5], and adrenal gland diseases [6,7] are associated with an increased risk of CV events. Takotsubo cardiomyopathy represents an uncommon clinical condition characterized by a clinical picture similar to that of acute myocardial infarction [8], but with no angiographical evidence of coronary vascular damage. It involves 1.7% to 2.2% of patients with Suspected acute coronary syndrome and is considered a typical postmenopausal disease after intense emotional stress [9]. The role of alterations of sexual hormones in Postmenopausal women is still a matter of debate. Estrogens have a protective effect on the heart during stress conditions by inhibition of vagal heart control and calcium-potassium modulation [10], in addition to a protective effect on vascular endothelium [11]. Estrogens may play a cardioprotective role against myocardial damage during ischemia/reperfusion [12] and can inhibit cardiac myofibroblast differentiation [13] and exert regulatory effect on the release of norepinephrine in the presynaptic cardiac sympathetic nerve fibers [14]. Different acute illnesses, such as infections [15], allergic reaction [16], and pulmonary disease [17] as well as several drugs [18], can induce stress responsible for TTC. Diagnosis of TTC is defined by the Mayo Clinic criteria [19], and screening for pheochromocytoma should be always considered in patients with TTC without obvious cause [20]. The aim of this study was to investigate the association between endocrine disorders and TTC, as documented by case reports.
We systematically explored PubMed and Embase medical
information source, with the following keywords: takotsubo cardiomyopathy; stress-induced cardiomyopathy; apical ballooning syndrome; endocrinopathy; thyroid, pituitary, and adrenal gland disease; and polyendrocrine syndrome. Author, year of publication, patients’ sex, age, triggers, therapy of acute events, and outcomes were recorded.
We identified 53 case reports (Table 1) [21-69]. Most patients were women (n = 42, 79.2%); the mean age was 58.6 +- 19.8 years. Takotsubo cardiomyopathy was more likely in the presence of thyroid (43.4%) or pituitary dysfunction (24.5%) and less likely in association with adrenal, pancreatic, and polyendocrine diseases (Table 2). Outcome is favorable in most cases, but 1 fatal event occurred, after terlipressin infusion. In 17 cases (32.1%), hyponatremia was reported.
? Funding support: Supported, in part, by a research grant “Fondo Ateneo Ricerca,” University of Ferrara, Italy.
?? Conflicts of interest: None.
Takotsubo cardiomyopathy is also defined as “stress cardiomyop- athy” because emotional stress is a valid trigger for its development. Cardiac damage in TTC is due to hypersecretion of catecholamines and their actions on ?-adrenoceptors [70]. In normal conditions, activation of ?1-adrenergic receptors has a positive inotropic effect, but in the case of pheochromocytoma, hyperactivation of ?1-adrenoceptor induces apoptosis of cardiomyocytes with negative inotropic effect [70]. Several endocrine abnormalities may be associated with TTC. Hyperthyroidism can cause transient ventricular dysfunction with a mechanism similar to the catecholamines cardiotoxicity. thyroid hormones increase peripheral oxygen consumption, heart contractil- ity, and heart rate but decrease systemic vascular resistance [71]. Moreover, high serum levels of thyroid hormones promote an exaggerated contractile and chronotropic response to catecholamines [72]. Hyperthyroidism can also induce Coronary vasospasm, especially in postmenopausal women (29% of cases), although prognosis is usually benign after treatment of endocrine disorder [73]. On the other hand, hypothyroidism is associated with increased CV risk, via the reduction of systolic and diastolic ventricular function, increased peripheral resistance, and risk of atherosclerosis and coronary events [74].
Hypothalamic-pituitary-adrenal axis dysfunction is associated with the development of TTC. Lack of adrenocortical hormone induces adrenal deficit, with consequent reduction of glucocorticoid-mediated cardio- protective effect [75-77]. Low circulating levels of corticosteroids are also associated with hypoglycemia and hyponatremia. Glucose has a protective effect on the myocardium, and hypoglycemia produces activation of the sympathetic nervous system [78]. Moreover, hypona- tremia is a risk factor for TTC. In our research, hyponatremia was present in 32.1% of cases of TTC. Pathophysiological mechanisms of hyponatremia to myocardial injury may depend on functional alteration of the pumps Ca++/Na+, and altered ionic concentrations contribute to inotropic state, systolic dysfunction, and arrhythmogenesis [79]. Hypothyroidism may be associated with hyponatremia because a reduction of 10 mUI/L in thyroid-stimulating hormone may cause a reduction of 0.14 mmol/L of serum sodium [80]. The importance of hyponatremia as a risk factor for the development of TTC has been recently underlined, and a series of clinical conditions characterized by inappropriate secretion of antidiure- tic hormone may associate with TTC [81]. On the other hand, hyperosmolarity is associated with myocardial cellular dehydration, consequent increase of Intracellular calcium concentration and cyclic adenosine monophosphate-mediated intracellular calcium, production of oxygen free radicals, inhibition of Na+/K+ pump activity, and intracellular alkalosis [82].
Several hormonal dysfunctions, not strictly limited to catecholamines,
may play important role in increasing susceptibility of patients, mainly women, to TTC in stress conditions. Patients presenting with suspected TTC are mostly evaluated by emergency department physicians, often staffing specific chest pain units [83]. Thus, it seems reasonable that they are sufficiently trained also in the diagnosis and treatment of endocrine diseases because therapeutical approach is based on supportive therapy associated with specific hormonal deficiency treatment.
0735-6757/(C) 2014
Table 1
Case reports of TTC and endocrine disorders
Table 1 (continued)
Cases associated with hyponatremia are highlighted.
Alfredo De Giorgi, MD
Clinica Medica, Department of Medicine Azienda Ospedaliera-Universitaria (AOU), Ferrara, Italy E-mail address: [email protected]
Fabio Fabbian, MD
Clinica Medica, Department of Medicine, AOU, Ferrara, Italy
E-mail address: [email protected]
Ruana Tiseo, MD
Clinica Medica, Department of Medicine, AOU, Ferrara, Italy
E-mail address: [email protected]
Claudia Parisi, MD
Clinica Medica, Department of Medicine, AOU, Ferrara, Italy
E-mail address: [email protected]
Elisa Misurati, MD
Clinica Medica, Department of Medicine, AOU, Ferrara, Italy
E-mail address: [email protected]
Table 2
Endocrine organ dysfunction associated with TTC
Endocrine organ No. of cases (%)
Christian Molino, MD Clinica Medica, Department of Medicine, AOU, Ferrara, Italy E-mail address: [email protected]
Marco Pala, MD
Clinica Medica, Department of Medicine, AOU, Ferrara, Italy
E-mail address: [email protected]
Raffaella Salmi, MD
Second Internal Medicine, Department of Medicine, AOU, Ferrara, Italy
E-mail address: [email protected]
Riccardo Volpi, MD
Department of Clinical and Experimental Medicine
University of Parma, Parma, Italy E-mail address: [email protected]
Roberto Manfredini, MD Clinica Medica, Department of Medicine, AOU, Ferrara, Italy E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2014.07.030
References
|
Thyroid |
23 (43.4%) |
[2] Webb SM, Mo D, Lamberts SW, Melmed S, Cavagnini F, Pecori Giraldi F, et al. |
|
Hypothyroidism |
2 (3.8%) |
Metabolic, cardiovascular, and cerebrovascular outcomes in growth hormone- |
|
Hyperthyroidism |
21 (39.6%) |
deficient subjects with previous Cushing’s disease or non-functioning pituitary |
|
Hypophysis |
13 (24.5%) |
|
|
Adenohypophysis |
10 (18.9%) |
[3] Duthie L, Reynolds RM. Changes in the maternal hypothalamic-pituitary-adrenal |
|
Neurohypophysis |
3 (5.6%) |
axis in pregnancy and postpartum: influences on maternal and Fetal outcomes. |
Neuroendocrinology 2013;98:106-15.
|
Pancreas, endocrine |
2 (3.8%) |
|
Adrenal glands |
7 (13.2%) |
|
Polyendocrine syndromes |
2 (3.8%) |
|
Drugs with endocrine effects |
6 (11.3%) |
Selmer C, Olesen JB, Hansen ML, von Kappelgaard LM, Madsen JC, Hansen PR, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab 2014;99: 2372-82.
Google Flu for forecasting influenza-like illness
To the Editor,
The report on “Google Flu for forecasting influenza-like illness”
[1] is very interesting. Araz et al [1] noted that “Google Flu Trends data statistically improve the performance of predicting ILI-related ED visits.” These authors also mentioned that the system could be “generalized to other communities” [1]. In fact, there are some reports confirming the advantage of Google Flu. Thompson et al [2] also noted that the system could provide real-time data and is useful in emergency department. Malik et al [3] also noted that the system “provided a good indication of weekly counts of laboratory- confirmed influenza cases.” It is clear that the system is useful, but there are many considerations. First, as an Internet-based system, it requires a computational network. Hence, limitations can be expected in any setting with restrictions on Internet access. Second, as a computer system, problems with internet safety and hacking are possible. The validation of data correctness must be systematically performed.
Viroj Wiwanitkit, MD Hainan Medical University, Hainan, China Faculty of Medicine, University of Nis, Nis, Serbia
Joseph Ayo Babalola University, Ikeji-Arakeji, Nigeria Surin Rajabhat University, Surin, Thailand Dr DY Patil Medical University, Pune, India Email-address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2014.08.021
References
- Araz OM, Bentley D, Muelleman RL. Using Google Flu Trends data in forecasting influenza-
- Thompson LH, Malik MT, Gumel A, Strome T, Mahmud SM. Emergency department and ‘Google flu trends’ data as syndromic surveillance indicators for seasonal influenza. Epidemiol Infect 2014:1-9 [Epub ahead of print].
- Malik MT, Gumel A, Thompson LH, Strome T, Mahmud SM. “Google flu trends” and emergency department triage data predicted the 2009 pandemic H1N1 waves in Manitoba. Can J Public Health 2011;102(4):294-7.
Korsakoff’s syndrome is preventable?
To the Editor,
Wernicke-Korsakoff syndrome (WKS) is a life-threatening neuro- psychiatric disorder caused by thiamine (vitamin B1) deficiency. Wernicke-Korsakoff syndrome is associated with mammillary body edema and small vessel ischemia. Many patients who develop WKS have a history of serious alcoholism and self-neglect. It is a common condition as around 15% of the alcoholics show specific WKS neuropathology. Originally, the syndrome was described as a triad of ataxia, eye Movement disorders, and Mental status change, but recent studies have suggested that patients frequently only show the mental status change [1].
Although it has been known for over 60 years that treatment with high doses of parenteral (intravenous or intramuscular) thiamine replacement therapy has the potency to improve the neuropsychiatric syndrome in the early stage of WKS [2], this is still uncommon medical practice. Recently published studies on treatment perspectives of WKS in general and psychiatric hospitals are alarming: European as well as American studies demonstrated that most patients did not receive thiamine at all or only received it orally in low doses [3,4]. Both types of treatment lead to unnecessary cases of chronic WKS (also Korsakoff’s syndrome) characterized by severe amnesia and lifelong impaired autonomy [4]. Based on the currently available literature, we suggest that any sign of mental confusion, cognitive defect, or change in mobility in an admitted alcoholic should alarm a clinician for treatable WKS. Parenteral thiamine replacement therapy is well tolerated and regularly ameliorates neuropathology in WKS. According to the European Federation of Neurological Societies and the Royal College of Physicians, parenteral thiamine should be given 200 mg up to 500 mg 3 times daily until symptoms of acute WKS resolute [5]. Importantly, in many cases, the benefit of treating WKS outweighs the risks of treating unnecessarily. The treatment is lifesaving and has the potential to reverse this acute neuropsychiatric syndrome. It is recommended to have a high suspicion of WKS in alcoholic patients and preventively treat them as such.
Erik Oudman, Msc
Slingedael Korsakoff Centre, Slinge 901, 3086 EZ Rotterdam
The Netherlands Utrecht University, Department of Experimental Psychology, Helmholtz
Institute, 3584 CS Utrecht, The Netherlands
Tel.: 31 10 29 31 555; fax: +31 10 293 1666
Tel.: +31 30 253 4281; fax: +31 30 253 4511
E-mail address: [email protected]
Jan W. Wijnia, MD
Slingedael Korsakoff Centre, Slinge 901, 3086 EZ Rotterdam
The Netherlands
Tel.: 31 10 29 31 555; fax: 31 10 293 1666
E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.08.017
like-illness related ED visits in Omaha, Nebraska. Am J Emerg Med 2014. http://dx.doi.
org/10.1016/j.ajem.2014.05.052 [pii: S0735-6757(14)00421-5, Epub ahead of print]. ? The authors have no conflict of interest. This correspondence was not funded.