- Email: [email protected]
A fast end to a slow disease
Journal of Clinical and Translational Endocrinology: Case Reports 9 (2018) 9–11
Contents lists available at ScienceDirect
Journal of Clinical and Translational Endocrinology: Case Reports journal homepage: www.elsevier.com/locate/jctecasereports.com
A fast end to a slow disease Bilal Shaikh∗, Muneebah Sohaib, Raeda Alshantti, Francisco Barrera, Natia Murvelashvili Presence Saint Francis Hospital, 355 Ridge Avenue, Evanston, IL, 60202, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Myxedema coma Hypothyroidism Cardiac arrest Prolonged QTc
Severe untreated hypothyroidism has been shown to affect cardiovascular function. While there have been a few reports of life-threatening arrhythmias occurring as a direct result of the hypothyroid state, very few cases of cardiac arrest have been reported in the literature. We report one such case of a middle-aged man who suffered a cardiac arrest that was attributed to severe untreated hypothyroidism.
1. Introduction Myxedema coma (MC) is a rare life-threatening condition that represents physiological decompensation in patients with severe hypothyroidism. Cardiovascular manifestations include decrease in cardiac output, decreased myocardial contractility, pericardial effusion, sinus bradycardia, low voltage QRS complexes, prolongation of QT interval, ventricular tachycardia, Torsades de pointes (TDP), and ventricular fibrillation [1]. Here we describe the case of a middle-aged man with severe untreated hypothyroidism presenting with sudden cardiac arrest. 2. Case presentation A 50-year-old male with past medical history of Asthma, HIV, Hypertension and Hypothyroidism was brought to the emergency department (ED) by emergency medical services (EMS) following successful cardiopulmonary resuscitation (CPR). The EMS was alerted by a friend, who discovered him lying on the floor of his apartment, unresponsive. He received CPR for approximately ten minutes with 2 doses of Epinephrine, following which he achieved return of spontaneous circulation (ROSC). No anti-arrhythmic medications were given. No further information was available regarding the circumstances of his cardiac arrest. His home medications included: Levothyroxine 175 mcg daily, Efavirenz-Emtricitabine-Tenofovoir 600-200-300 mg tab daily, Budesonide-Formterol 160–4.5 mcg/puff inhaler, Albuterol inhaler and Amlodipine 10 mg daily. Initial assessment in the ED revealed he was bradycardic and hypothermic to 91.8F. Initial EKG (post-ROSC) revealed a prolonged QTc of 613 ms (Fig. 1). He was unresponsive to painful stimuli and immediately intubated for airway protection. He was admitted to the
∗
intensive care unit (ICU) for post-cardiac arrest targeted temperature management. Early workup revealed no apparent cause for his cardiac arrest. A CT angiogram of the chest ruled out pulmonary embolism. Serum electrolytes were in the normal ranges. Other pertinent laboratory findings are presented in Table 1. An echocardiogram revealed a low cardiac output state with a preserved ejection fraction and mild global pericardial effusion. Further evaluation revealed a markedly elevated TSH level of 92 mIU/L. Serum free T4 was 0.15 ng/dL. Based on prescription refill record obtained from his pharmacy, he had not filled his levothyroxine prescriptions in the preceding months, raising concern for non-compliance. One of the patient's friends also later attested to this fact. However, no information regarding the cause of hypothyroidism or his family history could be obtained from the patient due to his condition. No previous thyroid function tests were available. The patient was started on intravenous (IV) levothyroxine with a loading dose of 200 mcg for 4 days, and subsequently transitioned to 100 mcg daily. Stress dose of IV hydrocortisone was also given after sending a STAT serum cortisol level. Serum cortisol level was 18.9 μg/ dl. During the first 24 hours of ICU stay, serial EKGs showed progressive prolongation of QTc above 600 ms, but eventually returned to < 500 ms after rewarming. Serum free T4 notably improved to 0.59 μg/dl one week later. Despite targeted temperature management according to protocol, appropriate hemodynamic support and emergent treatment of myxedema crisis, the patient was unable to demonstrate any significant neurological recovery over the next few days. Subsequently all life support measures were withdrawn. The patient did not survive. 3. Discussion/conclusions Hypothyroidism can cause a myriad of effects on the heart leading to functional, structural or conduction abnormalities. It has been
Corresponding author. E-mail address: [email protected] (B. Shaikh).
https://doi.org/10.1016/j.jecr.2018.07.002 Received 6 June 2018; Received in revised form 3 July 2018; Accepted 16 July 2018 2214-6245/ © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Journal of Clinical and Translational Endocrinology: Case Reports 9 (2018) 9–11
B. Shaikh et al.
Fig. 1. EKG obtained post cardiac arrest. Please note prolonged QTc interval of 613 ms.
central nervous system effects were likely a result of anoxic brain injury rather than MC. Very few cases of hypothyroidism-related cardiac arrest have been reported in published literature. Table 2 presents patient characteristics from five case reports of cardiac arrest or life-threatening arrhythmias associated with severe hypothyroidism. Shojaie et al. and Schenck et al. have reported cases of patients with severe hypothyroidism, who presented with prolonged QT intervals and TDP, and responded well to treatment with Levothyroxine [2,4]. More recently, Lagan et al. reported a case of a 76-year-old woman who also presented with TDP and subsequent cardiac arrest, believed to be due to severe hypothyroidism [5]. In 2013, Muthu et al. reported a case of a 25-year-old female with history of central hypothyroidism following surgical hypophysectomy, and non-compliance with medications. She presented with sudden cardiac arrest also developing from prolonged QT interval that was not attributable to any other identifiable cause [6]. Notably, all these patients were females and all survived and improved after thyroid replacement therapy. Solario et al. reported a case of a 67-year old hypothyroid woman taking Amiodarone who presented with myxedema coma triggered by cardiac arrest but did not survive the event [7]. Our patient, a 50-year-old male presented with sudden cardiac arrest in the setting of severe untreated hypothyroidism. Regretfully, we were unable to speak with the patient himself to confirm his noncompliance with levothyroxine and learn his reasons for it. We could also not confirm if he was following the proper directions for taking it. According to our knowledge, none of the patient's other medications is known to significantly affect the bioavailability of levothyroxine. His presentation was significant for prolonged QTc > 613 on initial EKG, a low cardiac output state and pericardial effusion as evident on echocardiogram. These findings are consistent with cardiovascular effects expected in a patient with long-standing untreated hypothyroidism, which can potentially lead to malignant arrhythmias and sudden cardiac arrest. This patient's longstanding severe untreated hypothyroidism most likely contributed to both his hypothermic state and significantly prolonged QT interval, which in turn possibly triggered
Table 1 Pertinent laboratory findings on admission. Laboratory study:
Result
White blood cell count Hemoglobin Platelets Serum Potassium Serum Magnesium Serum Calcium Serum AST Serum ALT Serum ALP Serum Creatinine
11.1 × 1000/mm3 11.6 g/dL 221 × 1000/mm3 3.5 mmol/L 2.4 mg/dL 8.8 mg/dL 285 IU/L 152 IU/L 76 IU/L 1.72 mg/dL
hypothesized that decreased expression of tri-iodothyronine in cardiac myocytes due to hypothyroidism, results in a decreasing heart rate, worsening contractility and slowing of conduction. This may explain the bradycardia and prolonged QTc observed in such patients, which can subsequently lead to life-threatening arrhythmias including Torsades de pointes (TDP) [2]. Myxedema coma is a medical emergency with a very high mortality rate. Treatment with intravenous thyroid hormones needs to be initiated based on clinical suspicion without waiting for laboratory confirmation. Initial diagnosis in suspect patients with depressed mental status is based on history, physical exam findings and exclusion of other causes. Diagnosis is confirmed by measuring TSH, Free T4 and serum cortisol levels, prior to initiating therapy. A diagnostic scoring system has been proposed for early recognition of MC, based on a retrospective study of 21 patients to assess the frequencies of various characteristics associated with MC [3]. A score of > 60 is diagnostic for MC. Although it has potential use as a confirmatory tool in neurologically altered individuals with known or suspected hypothyroidism, it is certainly limited by the small patient population it was derived from. We also faced difficulties in using the scoring system to calculate an accurate score for our case. For example, at the time of our evaluation, the
Table 2 Cases reports of cardiac arrest and cardiac arrhythmias as a presenting feature of Myxedema Coma. Case
Age/sex
TSH
Free T4
Lagan et al. Muthu et al. Solorio et al. Salhan et al. [8] Shojaie et al.
76/F 25/F 67/F 62/M 50/F
> 150 mIU/L 1.890 μIU/mL 17 uIU/mL 43.730 uIU/mL 36 μIU/mL
2.6 pmol/L 0.22 ng/dL 1.23 ng/dL 0.1 ng/mL
Total T4
EKG findings
Outcome
< 0.5 mcg/dL 0.71 μg/dL
Prolonged QT, Sinus bradycardia, Torsades de Pointes Prolonged QTc, T wave inversions, low voltage Septal infarct, Bradycardia Prolonged QT, Bradycardia, Third degree heart block T wave inversions, Prolonged QTc, Torsades de pointes
Survived Survived Death Survived Survived
10
Journal of Clinical and Translational Endocrinology: Case Reports 9 (2018) 9–11
B. Shaikh et al.
References
ventricular arrhythmia and led to sudden cardiac arrest. It is possible his anti-HIV medication Efavirenz, which has been shown to induce QTc interval prolongation in certain genetically predisposed individuals, was conducive to this arrhythmia [9]. Albeit, without known recent addition of an interacting medication, it acting as the sole perpetrator seems unlikely. It is important to keep in mind that the QT interval shortened significantly, as noted on serial EKGs, following thyroid hormone replacement. Although uncommon, it is important to recognize and suspect untreated severe hypothyroidism as a potential reversible cause of sudden cardiac arrest.
[1] Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, Mukhopadhyay S, Chowdhury S. Myxedema coma: a new look into an old crisis. J Thyroid Res 2011;2011:493462. [2] Shojaie M, Eshraghian A. Primary hypothyroidism presenting with Torsades de pointes type tachycardia: a case report. Cases J 2008 Nov 6;1(1):298. [3] Popoveniuc G, Chandra T, Sud A, Sharma M, Blackman MR, Burman KD, Mete M, Desale S, Wartofsky L. A diagnostic scoring system for myxedema coma. Endocr Pract 2014 Aug;20(8):808–17. [4] Schenck JB, Rizvi AA, Lin T. Severe primary hypothyroidism manifesting with torsades de pointes. Am J Med Sci 2006 Mar;331(3):154–6. [5] Lagan J, Cutts L, Barker D, Currie P. Torsades de pointes cardiac arrest associated with severe hypothyroidism. Br J Cardiol 2014;21:79. [6] Muthu V, Luna B. Sudden cardiac death due to untreated hypothyroidism. J Innov Card Rhythm Manag 2013;4:1097–9. [7] Solorio FA, Abdel-aziz Y, Yoon Y. Myxedema coma presenting as a refractory cardiac arrest. B45. Critical care case reports: acid-base, electrolytes, endocrine, metabolic, and renal abnormalities 2018. A3366-A3366. [8] Salhan D, Sapkota D, Verma P, et al. Sudden cardiac arrest as a rare presentation of myxedema coma: case report. J Community Hosp Intern Med Perspect 2017;7(5):318–20. [9] Abdelhady AM, Shugg T, Thong N, et al. Efavirenz inhibits the human ether-a-go-go related current (hERG) and induces QT interval prolongation in CYP2B6*6*6 allele carriers. J Cardiovasc Electrophysiol 2016;27(10):1206–13.
Declarations of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
11
Contents lists available at ScienceDirect
Journal of Clinical and Translational Endocrinology: Case Reports journal homepage: www.elsevier.com/locate/jctecasereports.com
A fast end to a slow disease Bilal Shaikh∗, Muneebah Sohaib, Raeda Alshantti, Francisco Barrera, Natia Murvelashvili Presence Saint Francis Hospital, 355 Ridge Avenue, Evanston, IL, 60202, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Myxedema coma Hypothyroidism Cardiac arrest Prolonged QTc
Severe untreated hypothyroidism has been shown to affect cardiovascular function. While there have been a few reports of life-threatening arrhythmias occurring as a direct result of the hypothyroid state, very few cases of cardiac arrest have been reported in the literature. We report one such case of a middle-aged man who suffered a cardiac arrest that was attributed to severe untreated hypothyroidism.
1. Introduction Myxedema coma (MC) is a rare life-threatening condition that represents physiological decompensation in patients with severe hypothyroidism. Cardiovascular manifestations include decrease in cardiac output, decreased myocardial contractility, pericardial effusion, sinus bradycardia, low voltage QRS complexes, prolongation of QT interval, ventricular tachycardia, Torsades de pointes (TDP), and ventricular fibrillation [1]. Here we describe the case of a middle-aged man with severe untreated hypothyroidism presenting with sudden cardiac arrest. 2. Case presentation A 50-year-old male with past medical history of Asthma, HIV, Hypertension and Hypothyroidism was brought to the emergency department (ED) by emergency medical services (EMS) following successful cardiopulmonary resuscitation (CPR). The EMS was alerted by a friend, who discovered him lying on the floor of his apartment, unresponsive. He received CPR for approximately ten minutes with 2 doses of Epinephrine, following which he achieved return of spontaneous circulation (ROSC). No anti-arrhythmic medications were given. No further information was available regarding the circumstances of his cardiac arrest. His home medications included: Levothyroxine 175 mcg daily, Efavirenz-Emtricitabine-Tenofovoir 600-200-300 mg tab daily, Budesonide-Formterol 160–4.5 mcg/puff inhaler, Albuterol inhaler and Amlodipine 10 mg daily. Initial assessment in the ED revealed he was bradycardic and hypothermic to 91.8F. Initial EKG (post-ROSC) revealed a prolonged QTc of 613 ms (Fig. 1). He was unresponsive to painful stimuli and immediately intubated for airway protection. He was admitted to the
∗
intensive care unit (ICU) for post-cardiac arrest targeted temperature management. Early workup revealed no apparent cause for his cardiac arrest. A CT angiogram of the chest ruled out pulmonary embolism. Serum electrolytes were in the normal ranges. Other pertinent laboratory findings are presented in Table 1. An echocardiogram revealed a low cardiac output state with a preserved ejection fraction and mild global pericardial effusion. Further evaluation revealed a markedly elevated TSH level of 92 mIU/L. Serum free T4 was 0.15 ng/dL. Based on prescription refill record obtained from his pharmacy, he had not filled his levothyroxine prescriptions in the preceding months, raising concern for non-compliance. One of the patient's friends also later attested to this fact. However, no information regarding the cause of hypothyroidism or his family history could be obtained from the patient due to his condition. No previous thyroid function tests were available. The patient was started on intravenous (IV) levothyroxine with a loading dose of 200 mcg for 4 days, and subsequently transitioned to 100 mcg daily. Stress dose of IV hydrocortisone was also given after sending a STAT serum cortisol level. Serum cortisol level was 18.9 μg/ dl. During the first 24 hours of ICU stay, serial EKGs showed progressive prolongation of QTc above 600 ms, but eventually returned to < 500 ms after rewarming. Serum free T4 notably improved to 0.59 μg/dl one week later. Despite targeted temperature management according to protocol, appropriate hemodynamic support and emergent treatment of myxedema crisis, the patient was unable to demonstrate any significant neurological recovery over the next few days. Subsequently all life support measures were withdrawn. The patient did not survive. 3. Discussion/conclusions Hypothyroidism can cause a myriad of effects on the heart leading to functional, structural or conduction abnormalities. It has been
Corresponding author. E-mail address: [email protected] (B. Shaikh).
https://doi.org/10.1016/j.jecr.2018.07.002 Received 6 June 2018; Received in revised form 3 July 2018; Accepted 16 July 2018 2214-6245/ © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Journal of Clinical and Translational Endocrinology: Case Reports 9 (2018) 9–11
B. Shaikh et al.
Fig. 1. EKG obtained post cardiac arrest. Please note prolonged QTc interval of 613 ms.
central nervous system effects were likely a result of anoxic brain injury rather than MC. Very few cases of hypothyroidism-related cardiac arrest have been reported in published literature. Table 2 presents patient characteristics from five case reports of cardiac arrest or life-threatening arrhythmias associated with severe hypothyroidism. Shojaie et al. and Schenck et al. have reported cases of patients with severe hypothyroidism, who presented with prolonged QT intervals and TDP, and responded well to treatment with Levothyroxine [2,4]. More recently, Lagan et al. reported a case of a 76-year-old woman who also presented with TDP and subsequent cardiac arrest, believed to be due to severe hypothyroidism [5]. In 2013, Muthu et al. reported a case of a 25-year-old female with history of central hypothyroidism following surgical hypophysectomy, and non-compliance with medications. She presented with sudden cardiac arrest also developing from prolonged QT interval that was not attributable to any other identifiable cause [6]. Notably, all these patients were females and all survived and improved after thyroid replacement therapy. Solario et al. reported a case of a 67-year old hypothyroid woman taking Amiodarone who presented with myxedema coma triggered by cardiac arrest but did not survive the event [7]. Our patient, a 50-year-old male presented with sudden cardiac arrest in the setting of severe untreated hypothyroidism. Regretfully, we were unable to speak with the patient himself to confirm his noncompliance with levothyroxine and learn his reasons for it. We could also not confirm if he was following the proper directions for taking it. According to our knowledge, none of the patient's other medications is known to significantly affect the bioavailability of levothyroxine. His presentation was significant for prolonged QTc > 613 on initial EKG, a low cardiac output state and pericardial effusion as evident on echocardiogram. These findings are consistent with cardiovascular effects expected in a patient with long-standing untreated hypothyroidism, which can potentially lead to malignant arrhythmias and sudden cardiac arrest. This patient's longstanding severe untreated hypothyroidism most likely contributed to both his hypothermic state and significantly prolonged QT interval, which in turn possibly triggered
Table 1 Pertinent laboratory findings on admission. Laboratory study:
Result
White blood cell count Hemoglobin Platelets Serum Potassium Serum Magnesium Serum Calcium Serum AST Serum ALT Serum ALP Serum Creatinine
11.1 × 1000/mm3 11.6 g/dL 221 × 1000/mm3 3.5 mmol/L 2.4 mg/dL 8.8 mg/dL 285 IU/L 152 IU/L 76 IU/L 1.72 mg/dL
hypothesized that decreased expression of tri-iodothyronine in cardiac myocytes due to hypothyroidism, results in a decreasing heart rate, worsening contractility and slowing of conduction. This may explain the bradycardia and prolonged QTc observed in such patients, which can subsequently lead to life-threatening arrhythmias including Torsades de pointes (TDP) [2]. Myxedema coma is a medical emergency with a very high mortality rate. Treatment with intravenous thyroid hormones needs to be initiated based on clinical suspicion without waiting for laboratory confirmation. Initial diagnosis in suspect patients with depressed mental status is based on history, physical exam findings and exclusion of other causes. Diagnosis is confirmed by measuring TSH, Free T4 and serum cortisol levels, prior to initiating therapy. A diagnostic scoring system has been proposed for early recognition of MC, based on a retrospective study of 21 patients to assess the frequencies of various characteristics associated with MC [3]. A score of > 60 is diagnostic for MC. Although it has potential use as a confirmatory tool in neurologically altered individuals with known or suspected hypothyroidism, it is certainly limited by the small patient population it was derived from. We also faced difficulties in using the scoring system to calculate an accurate score for our case. For example, at the time of our evaluation, the
Table 2 Cases reports of cardiac arrest and cardiac arrhythmias as a presenting feature of Myxedema Coma. Case
Age/sex
TSH
Free T4
Lagan et al. Muthu et al. Solorio et al. Salhan et al. [8] Shojaie et al.
76/F 25/F 67/F 62/M 50/F
> 150 mIU/L 1.890 μIU/mL 17 uIU/mL 43.730 uIU/mL 36 μIU/mL
2.6 pmol/L 0.22 ng/dL 1.23 ng/dL 0.1 ng/mL
Total T4
EKG findings
Outcome
< 0.5 mcg/dL 0.71 μg/dL
Prolonged QT, Sinus bradycardia, Torsades de Pointes Prolonged QTc, T wave inversions, low voltage Septal infarct, Bradycardia Prolonged QT, Bradycardia, Third degree heart block T wave inversions, Prolonged QTc, Torsades de pointes
Survived Survived Death Survived Survived
10
Journal of Clinical and Translational Endocrinology: Case Reports 9 (2018) 9–11
B. Shaikh et al.
References
ventricular arrhythmia and led to sudden cardiac arrest. It is possible his anti-HIV medication Efavirenz, which has been shown to induce QTc interval prolongation in certain genetically predisposed individuals, was conducive to this arrhythmia [9]. Albeit, without known recent addition of an interacting medication, it acting as the sole perpetrator seems unlikely. It is important to keep in mind that the QT interval shortened significantly, as noted on serial EKGs, following thyroid hormone replacement. Although uncommon, it is important to recognize and suspect untreated severe hypothyroidism as a potential reversible cause of sudden cardiac arrest.
[1] Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, Mukhopadhyay S, Chowdhury S. Myxedema coma: a new look into an old crisis. J Thyroid Res 2011;2011:493462. [2] Shojaie M, Eshraghian A. Primary hypothyroidism presenting with Torsades de pointes type tachycardia: a case report. Cases J 2008 Nov 6;1(1):298. [3] Popoveniuc G, Chandra T, Sud A, Sharma M, Blackman MR, Burman KD, Mete M, Desale S, Wartofsky L. A diagnostic scoring system for myxedema coma. Endocr Pract 2014 Aug;20(8):808–17. [4] Schenck JB, Rizvi AA, Lin T. Severe primary hypothyroidism manifesting with torsades de pointes. Am J Med Sci 2006 Mar;331(3):154–6. [5] Lagan J, Cutts L, Barker D, Currie P. Torsades de pointes cardiac arrest associated with severe hypothyroidism. Br J Cardiol 2014;21:79. [6] Muthu V, Luna B. Sudden cardiac death due to untreated hypothyroidism. J Innov Card Rhythm Manag 2013;4:1097–9. [7] Solorio FA, Abdel-aziz Y, Yoon Y. Myxedema coma presenting as a refractory cardiac arrest. B45. Critical care case reports: acid-base, electrolytes, endocrine, metabolic, and renal abnormalities 2018. A3366-A3366. [8] Salhan D, Sapkota D, Verma P, et al. Sudden cardiac arrest as a rare presentation of myxedema coma: case report. J Community Hosp Intern Med Perspect 2017;7(5):318–20. [9] Abdelhady AM, Shugg T, Thong N, et al. Efavirenz inhibits the human ether-a-go-go related current (hERG) and induces QT interval prolongation in CYP2B6*6*6 allele carriers. J Cardiovasc Electrophysiol 2016;27(10):1206–13.
Declarations of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
11