Case Reports of Severe Coronary Artery Spasm

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Thyroid 2014;24:383-9. 5. Nef HM, Mollmann H, Akashi YJ, Hamm CW. Mechanisms of stress (Ta- kotsubo) cardiomyopathy. Nat Rev Cardiol 2010;7:187-93. 6.
Soonchunhyang Medical Science 21(2):95-98, December 2015

pISSN: 2233-4289  I  eISSN: 2233-4297

CASE REPORT

Case Reports of Severe Coronary Artery Spasm Associated with Three Different Endocrine Hyperfunction Seung Hyun Hong1, Kyung Ae Lee1, Tae Sun Park1, Hong Sun Baek1, Heung Yong Jin1, Sung Yun Lee2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju; 2Department of Internal Medicine, Daerim Saint Mary’s Hospital, Seoul, Korea 1

Disorders of the endocrine system including hormone hyperfunction and hypofunction have multiple effects on cardiovascular system. However, in clinical practice, there are many cases of delayed or overlooked diagnosis of underlying endocrine dysfunction in patients presenting chest pain or other cardiac symptoms. Herein, we report three cases of endocrine hyperfunction presenting as coronary spasm; Graves’ hyperthyroidism, pheochromocytoma, and primary hyperparathyroidism. Chest pains disappear after treatment for these endocrine diseases. Endocrine hyperfunctions such as the three cases described above should be considered as possible diagnosis in patients with complaint of chest pain. High index of suspicion are needed. Keywords: Coronary artery spasm with hyperthyroidism; Pheochromocytoma; Hyperparathyroidism

INTRODUCTION

drug until 2 years ago. She stopped the medication herself. At arrival, her electrocardiogram (ECG) showed sinus tachycardia (120

Disorders of the endocrine system including hormone hyper-

bpm/min) with ST segment depression in precordial lead. Tropo-

function and hypofunction have multiple effects on cardiovascular

nin I (TnI) and creatine kinase muscle-brain fraction (CK-MB)

system. However, in clinical practice, there are many cases of de-

were elevated (TnI, 2.57 ng/mL [reference value, 0.16 ng/mL]; CK-

layed or overlooked diagnosis of underlying endocrine dysfunction

MB, 20.88 ng/mL [reference value, 4.94 ng/mL]). Echocardiogram

in patients presenting chest pain or other cardiac symptoms. Some

showed hypokinesia of the left ventricular (LV) apex and mild hy-

of these cases showed worsened clinical course. These patients had

pokinesia of mid posterior wall with normal LV systolic function.

serious morbidity and mortality. Herein, we report three cases of

Non ST segment elevation myocardial infarction was suspected.

endocrine hyperfunction presenting as severe coronary spasm. In

However, there was no occlusive lesion with relatively normal cor-

addition, we performed relevant literature review.

onary artery in coronary artery angiography (CAG). Laboratory results were: free T4 at 143.6 pmol/L (reference range, 11.5-22.7

CASE REPORTS

pmol/L), TSH < 0.01 μU/mL (reference range, 0.55-4.78 μU/mL), anti-TPO antibody titer at 215 IU/mL (reference value, 34 IU/mL),

1. Case 1: Coronary artery spasm due to Graves’

and thyroid stimulating immunoglobulin at 26.19 IU/mL (refer-

hyperthyroidism and impending thyroid storm after

ence value, 1.75 IU/mL). Thyroid ultrasound showed diffuse goiter

coronary angiography

with markedly increased vascularities (Fig. 1). After CAG, dyspnea

A 49-year-old female patient visited the emergency room (ER)

and orthopnea were developed. Chest X-ray showed pulmonary

with chief complaint of epigastric pain. Ten years ago, the patient

edema with bilateral pleural effusion. The patient’s state was con-

was diagnosed with hyperthyroidism. She maintained antithyroid

sidered as impending thyroid storm precipitated by CAG. High

Correspondence to:  Kyung Ae Lee Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea Tel: +82-63-250-2749, Fax: +82-63-254-1609, E-mail: [email protected] Received:  May 18, 2015 / Accepted after revision:  Jun. 22, 2015

© 2015 Soonchunhyang Medical Research Institute This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

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Hong SH, et al. • Hyperthyroidism, Pheochromocytoma, and Hyperparathyroidism Related Severe Coronary Artery Spasm

dose propylthiouracil and lugol solution were started to treat hy-

of substernal chest pain. This was the third time he visited our ER

perthyroidism. Heart failure management with loop diuretics was

with the same symptom for the past 10 years. In his two previous

done concurrently. Cardiac function and thyroid function of the

visits, blood pressures were high. ECGs revealed ST segment eleva-

patient were improved. Finally, the patient underwent total thy-

tion on S1-3. However, 1st CAG of the patient showed normal coro-

roidectomy. She has been free of symptoms.

nary artery. In his 2nd CAG, coronary spasm (variant angina) was confirmed using ergonovine provocation. But at the present visit,

2. Case 2: Recurrent coronary spasm due to

the patient still felt chest pain despite of treatment with anti-spasm

pheochromocytoma with markedly delayed diagnosis

medications. EKG showed sinus tachycardia with ST segment de-

A 62-year-old male patient visited the ER with chief complaint

pression and markedly elevated cardiac enzyme, with TnI at 7.25

-3.9 cm/sec

A

Right lobe

-3.9 cm/sec

Left lobe

B

Fig. 1. (A, B) Thyroid ultrasound of the patient. Thyroid ultrasound showed diffuse goiter with markedly increased vascularities.

A

B

C

Fig. 2. (A) Contrast enhanced computed tomography of abdomen (circle) and (B, C) tumor scan (I-123 MIBG, circle). This shows a 4.6-cm sized right adrenal mass with strong enhancement and central necrosis. MIBG accumulation was seen in marginal area of the tumor. MIBG, metaiodobenzylguanidine.

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Soonchunhyang Medical Science 21(2):95-98

Hyperthyroidism, Pheochromocytoma, and Hyperparathyroidism Related Severe Coronary Artery Spasm • Hong SH, et al.

ng/mL (reference value, 0.16 ng/mL) and CK-MB at 29.81 ng/mL

of coronary artery was observed. Laboratory tests results were: to-

(reference value, 4.94 ng/mL). Echocardiogram showed severe hy-

tal calcium at 11.6 mg/dL (reference range, 8.4-10.2 mg/dL), phos-

pokinesia of inferoposterolateral wall with mild LV systolic dys-

phorus at 2.3 mg/dL (reference range, 2.5-4.5 mg/dL), parathyroid

function (ejection fraction = 47%) and concentric LV hypertrophy.

hormone at 284.22 pg/mL (reference range, 11-62 pg/mL), and glo-

Third CAG was performed due to markedly elevated cardiac en-

merular filtration rate at approximately 44.4 mL/min/1.7. Neck ul-

zyme and newly developed wall motional abnormality. However,

trasonography showed about 2-cm sized well defined hypoechoic

CAG showed only non-significant stenosis. On the other hand,

mass below inferior pole of right thyroid gland. Technetium-me-

chest pain of the patient was episodic and accompanied with high

thoxyisobutylisonitrile single photon emission CT/CT showed

blood pressure, palpitation and headache. Therefore, hormonal

strong uptake of sestamibi (Fig. 3). Right parathyroidectomy was

studies and adrenal imaging were performed. Biochemical study

performed. Her serum calcium was normalized. The patient did

showed elevated plasma metanephrine at 1.47 nmol/L (reference

not feel chest discomfort after parathyroidectomy.

value, 0.50 nmol/L) and normetanephrine at 6.00 nmol/L (refer-

DISCUSSION

ence value, 0.90 nmol/L). Abdomeninal computed tomography (CT) showed 4.6-cm sized strong enhanced adrenal mass in right adrenal gland that was compatible with pheochromocytoma (Fig.

Disorders of the endocrine system have multiple effects on car-

2). The patient is going to have an adrenalectomy after alpha block-

diovascular system and may trigger cardiovascular risk factors.

er treatment.

Hyperthyroid state is associated with enhanced sympatho-adrenal activity due to increased adrenergic receptor sensitivity and in-

3. Case 3: A rare cause of coronary artery spasm:

creased receptor numbers. Consequently, stimulation of sympa-

primary hyperparathyroidism

thetic alpha-adrenergic receptors on coronary arteries leads to cor-

A 70-year-old female patient was referred to the endocrinology

onary vasospasm. In a retrospectively analysis of 325 patients diag-

department because of incidentally detected hypercalcemia. The

nosis with coronary spasm in Korea, Choi et al. [1] reported 8 pa-

patient had complaint of intermittent episode of dizziness, chest

tients (4.69%) had hyperthyroidism, including 5 young female pa-

discomfort, and muscle weakness. The admission ECG showed no

tients (age < 50 years old). On the other hand, there have been re-

abnormal findings except nonspecific T wave abnormality. During

ported cases of thyroid crisis after CAG with contrast medium [2].

hospitalization, the patient had complaint of sudden chest pain.

Therefore, under-diagnosed hyperthyroidism may lead to in-

ECG showed transient ST segment elevation, but her cardiac en-

creased morbidity and mortality in patients after CAG. On the oth-

zyme showed normal range. Echocardiogram showed normal LV

er hand, several endocrine abnormalities including hyperthyroid-

function with normal valvular function. Because the patient had

ism can also induced stress cardiomyopathy (also defined as Takot-

multiple risk factors for coronary artery disease such as diabetes,

subo cardiomyopathy), characterized by transient LV dysfunction

hypertension, and dyslipidemia, CAG was performed. However,

with chest symptoms, elevated cardiac enzymes, and electrocar-

there was no significant occlusive lesion. Only moderate stenosis

diogram changes that resemble myocardial infarction [3,4]. Patho-

30 min

1 hr

2 hr

A

B

Fig. 3. (A, B) Parathyroid single photon emission computed tomography (99m technetium+methoxyisobutylisonitrile) showed focal increased uptake below inferior pole of the right thyroid gland (circle). Soonchunhyang Medical Science 21(2):95-98

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Hong SH, et al. • Hyperthyroidism, Pheochromocytoma, and Hyperparathyroidism Related Severe Coronary Artery Spasm

physiological mechanisms have been suggested to explain the un-

In conclusion, normal endocrine function is essential to cardio-

usual features of this syndrome, including multivessel epicardial

vascular health. Disorders of the endocrine system have multiple

spasm, coronary microvascular impairment, and microvascular

effects on the cardiovascular system. Therefore, physicians must

spasm [5]. In our patient, initial presentation of chest pain was initi-

have awareness about the relationship between endocrine system

ated by coronary spasm that may worsen to stress cardiomyopathy

and cardiovascular system. Furthermore, high index of suspicion

during hospitalization. Therefore, because many patients with

and careful evaluation are needed. Endocrine hyperfunctions

acute coronary spasm need CAG, test of thyroid function is essen-

such as the three cases described above should be considered as

tial to reduce the procedural risk.

possible diagnosis in patients with complaint of chest pain.

Pheochromocytoma can present with a multitude of symptoms mimicking other diseases. The pathogenesis of pheochromocyto-

REFERENCES

ma-related cardiac complications is thought to be cardiotoxic effect of catecholamine. Excess catecholamine action can lead to stress cardiomyopathy, ischemic heart disease, coronary spasm, myocardial stunning, and rarely cardiogenic shock [6,7]. However, pheochromocytoma remains a frequently overlooked diagnosis compared to hyperthyroidism. It is well known that chronic hypercalcemia in primary hyperparathyroidism can cause hypertension, arrhythmias, ventricular hypertrophy, and calcifications of myocardium and cardiac valve. However, coronary spasm associated with hyperparathyroidism was rarely reported. One case study reported the occurrence of coronary spasm during spinal anesthesia in a patient with primary hyperparathyroidism [8]. Hypercalcemia is known as precipitating factor of intra-operative coronary spasm. Event in our patient, episode of acute chest pain with transient ST elevation, suggested that possibility of coronary artery spasm. However, unlike hyperthyroidism or pheochromocytoma, mechanism of coronary spasm in hyperparathyroidism is unclear. Further studies are needed to clarify the exact mechanism of coronary spasm.

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1. Choi YH, Chung JH, Bae SW, Lee WH, Jeong EM, Kang MG, et al. Severe coronary artery spasm can be associated with hyperthyroidism. Coron Artery Dis 2005;16:135-9. 2. Blum M, Kranjac T, Park CM, Engleman RM. Thyroid storm after cardiac angiography with iodinated contrast medium: occurrence in a patient with a previously euthyroid autonomous nodule of the thyroid. JAMA 1976;235:2324-5. 3. De Giorgi A, Fabbian F, Tiseo R, Parisi C, Misurati E, Molino C, et al. Takotsubo cardiomyopathy and endocrine disorders: a mini-review of case reports. Am J Emerg Med 2014;32:1413-7. 4. Eliades M, El-Maouche D, Choudhary C, Zinsmeister B, Burman KD. Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review of the literature. Thyroid 2014;24:383-9. 5. Nef HM, Mollmann H, Akashi YJ, Hamm CW. Mechanisms of stress (Takotsubo) cardiomyopathy. Nat Rev Cardiol 2010;7:187-93. 6. Rhee SS, Pearce EN. Update: Systemic Diseases and the Cardiovascular System (II): the endocrine system and the heart: a review. Rev Esp Cardiol 2011;64:220-31. 7. Di Maio M, Polito MV, Citro R, Piscione F. Stress-induced cardiomyopathy in pheochromocytoma: the way we treat and the way we think. Am J Emerg Med 2014;32:940-1. 8. Oguchi T, Kashimoto S, Kumazawa T. Coronary-artery spasm during spinal anaesthesia in a patient with primary hyperparathyroidism. Eur J Anaesthesiol 1991;8:69-70.

Soonchunhyang Medical Science 21(2):95-98