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.
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