Case of coronary vasospasm caused by hypocalcaemia post parathyroidectomy mimicking ST-elevation myocardial infarction

Abstract

A man in his 30s with primary hyperparathyroidism underwent an elective four-gland parathyroid exploration with intraoperative parathyroid hormone monitoring. On the fourth postoperative day (POD), the patient presented to the emergency department with severe symptomatic hypocalcaemia. ECG findings were in keeping with inferior–posterior ST-elevation myocardial infarction (STEMI); however, he was asymptomatic with no chest pain. Biochemistry revealed elevated serial troponin levels. Coronary angiogram and transthoracic echocardiogram were normal, suggesting coronary vasospasm, mimicking STEMI on ECG because of severe hypocalcaemia post parathyroidectomy. This is an uncommon and unreported complication of parathyroid surgery. The patient was successfully managed with intravenous calcium and discharged on oral calcium replacement on the tenth POD.

Background

Primary hyperparathyroidism (PHPT) is a common clinical condition for which parathyroidectomy is the only definitive management. Hypocalcaemia is a common complication of parathyroid surgery. In our centre, low-risk patients are routinely discharged on postoperative day (POD) 1, provided they are clinically well and biochemical markers including serum calcium are normal. This case highlights an important potential complication caused by severe symptomatic hypocalcaemia. It also underlines the importance of having a high index of suspicion of cardiac events in patients with severe electrolyte abnormalities.

Case presentation

A man in his 30s was admitted to the ear, nose and throat (ENT) unit for an elective parathyroidectomy on a background of PHPT. Preoperative imaging (including ultrasound, sestamibi and 4D CT scanning) failed to localise any definite adenoma. After the endocrinology multidisciplinary meeting, the decision was made to proceed to a four-gland parathyroid exploration with intraoperative parathyroid hormone (ioPTH) monitoring.

Preoperatively, the patient had a parathyroid hormone (PTH) of 71 pg/mL (10 to 55 pg/mL), thyroid stimulating hormone (TSH) of 3.06 mIU/L (0.27 to 4.20 mIU/L) and adjusted calcium of 2.83 mmol/L (2.17–2.51 mmol/L) (table 1).

Table 1.

Preoperative investigations

Test	Result	Normal range
Adjusted calcium (mmol/L)	2.83	2.17–2.51
Potassium (mmol/L)	4.6	3.3–5.1
TSH (mIU/L)	3.06	0.27–4.20
Parathyroid hormone (pg/mL)	71	10–55
White cell count (×109/L)	4.8	4.0–11.0

Bilateral parathyroids were explored intraoperatively. The left inferior parathyroid gland was removed in the first instance as it was found to be moderately enlarged; however, the ioPTH levels failed to normalise following excision. The left superior parathyroid gland was identified in normal anatomical position and was normal in appearance. The right side of the neck was subsequently explored, and the right superior parathyroid gland was found to be enlarged and adenomatous in nature and, hence, was excised. Excision precipitated a drop of more than 50% in serum PTH levels, and subsequent histology confirmed a parathyroid adenoma with focal atypical features including fibrosis and focal mitotic figures; however, there was no evidence of carcinoma. His immediate postoperative course was uneventful.

On POD 1, he was clinically well with no signs or symptoms of electrolyte abnormalities, and his serum PTH was 6 pg/mL (10–55 pg/mL) and adjusted calcium was 2.22 mmol/L (2.17–2.51 mmol/L). The patient was monitored and then discharged with simple analgesia, and follow-up in the ENT outpatient clinic was scheduled in 3 weeks’ time.

The patient re-presented to the ED on POD 4 with a 1-day history of severe paraesthesia, which had started periorally with a adjusted calcium of 1.52 mmol/L (2.17–2.51) (table 2). He was afebrile with observations within normal limit. The parathesia initially involved the patient’s fingertips, and eventually spread to his both upper and lower limbs. He also reported having difficulty with speech and slurring of his words. He reported no neck swelling, dyspnoea, chest pain, palpitations or changes in his mental state. On examination, he was alert and orientated, and his vitals were stable. Cardiovascular, respiratory and abdominal examinations were unremarkable; neurological examination was normal, with no motor abnormalities or muscle spasm. Chvostek and Trousseau signs were negative.

Table 2.

Readmission investigations

Test	Result	Normal range
Adjusted calcium (mmol/L)	1.52	2.17–2.51
Potassium (mmol/L)	4.6	3.3–5.1
Magnesium (mmol/L)	0.62	0.65–1.05
Inorganic phosphate (mmol/L)	1.73	0.87–1.45
White cell count (×109/L)	5.1	4.0–11.0
Estimated glomerular filtration rate (eGFR) (mL/min)	>90	60–160
Anti-TSH receptor antibody (IU/L)	<0.8	0.0–1.8

ECG showed mild ST elevation in leads II, III and aVF with left axis deviation (figure 1).

Figure 1.

Admission ECG (postoperative day 4) showing sinus rhythm with left axis deviation and subtle ST elevation in leads II, III and aVF, raising suspicion and leading to further investigation with serial troponins and repeat ECG.

Treatment

Blood tests showed a troponin of 1480 ng/L on POD 4, on the day of readmission (table 3). An urgent coronary angiogram was performed which revealed normal coronary arteries with no obstructive or occlusive disease (figures 2 and 3). The patient also underwent a transthoracic echocardiogram, which was also normal. He had normal inflammatory markers with a white cell count of 5.1×10⁹/L (4.0–11.0×10⁹/L).

Figure 2.

Normal coronary angiogram.

Figure 3.

Normal coronary angiogram.

ECG on POD 5 showed worsening ST elevation in leads II, III and aVF with reciprocal ST depression in I, aVL and V1–V3 (figure 4). On day 6 postoperatively, ventricular tachycardia (VT) was detected on telemetry (figure 5). He was asymptomatic with no chest pain, shortness of breath or syncope, and his most recent adjusted calcium was 1.71 mmol/L (table 3). The patient was transferred to the coronary care unit where he experienced further episodes of VT with associated ST elevation in leads II and III and ST depression in the lead V1 (figure 5).

Figure 4.

Postoperative day 5, worsening ST-elevation in leads II, III and aVF with reciprocal ST depression in I, aVL and V1–V3.

Figure 5.

Postoperative day 6, 17 beat run of ventricular tachycardia. Patient was asymptomatic with no palpitations, chest pain or shortness of breath.

Table 3.

Relationship between troponin-T and adjusted calcium

POD	Troponin (<14 ng/L)	Adjusted calcium (2.17–2.51 mmol/L)
4 (readmission)	1480 ng/L	1.52
5	2142→1939→2072 ng/L	1.49
6	3061 ng/L	1.66
7	1853 ng/L	2.09
8	1270→72 ng/L	2.43
9	382 ng/L	2.45

POD, postoperative day.

Calcium was corrected using continuous intravenous 10 mL 10% calcium gluconate followed by 40 mL 10% calcium gluconate, which had an additional advantage of stabilising the cardiac membranes considering the severe hypocalcaemia. This was supplemented with oral alfacalcidol (3 μg and verapamil 2.5 mg daily. Serum calcium was monitored closely and checked every 2 hours initially and then subsequently six times a day. The patient had ongoing perioral paraesthesia until calcium homeostasis was achieved on PODs 7 and 8 with a calcium of 2.43 mmol/L, which correlates to the down-trending troponin within the same day.

Bisoprolol 2.5 mg and ramipril 2.5 mg were administered for cardioprotection, along with continuous intravenous calcium replacement. Adjusted calcium levels were monitored every 8 hours and then subsequently every 12 hours after the patient’s calcium stabilised on POD 12. The serum troponin level began to downtrend on POD 7 (day 4 of admission) reducing to 382 ng/L on POD 9 (table 3).

The patient had a T4 >100 mIU/L with a TSH of 0.07 mIU/L (0.27–4.20 mIU/L); however, the patient was not clinically thyrotoxic. TSH receptor antibodies were normal at <0.8 IU/L (0.0–1.8 IU/L), which further supported the likelihood of thyroiditis secondary to surgical manipulation causing thyrotoxicosis. This was managed with initiating carbimazole 20 mg (three times a day) and prednisolone 40 mg (once a day for 5 days) and close monitoring of thyroid function tests (TFTs) during admission and as an outpatient for follow-up. The TFTs normalised 10 days post discharge with continued use of carbimazole.

The patient was monitored for an additional 48 hours following stabilisation of calcium levels before discharge. He was clinically asymptomatic with resolving ST-elevation on ECG (figure 6) and discharged on alfacalidol, carbmiazole, bisoprolol and ramipril.

Figure 6.

Postoperative day 9, resolved ST elevation with T-wave inversion in leads I, II, III, aVF and V3–V6.

Outcome and follow-up

The patient was followed up in cardiology, endocrinology and ENT clinics. His bisoprolol was stopped and is due for a repeat echocardiogram in 3 months to monitor the long-term sequalae of myocardial injury.

The endocrinology department is regularly following up the patient’s calcium levels and titrating the alfacalcidol accordingly. He remains asymptomatic to date.

Discussion

Parathyroidectomy is the definitive surgical treatment for PHPT. PHPT is most frequently diagnosed incidentally when hypercalcaemia is identified on biochemical assays.¹ Surgical intervention is recommended for symptomatic patients, and patients with familial disease and select asymptomatic patients, like our patient. Surgical intervention is also recommended when serum calcium levels are over 0.25 mmol/L above the upper normal limit. Asymptomatic patients may report improvement in quality of life indices post parathyroidectomy as symptoms such as fatigue, memory impairment, depression and difficulty in concentrating can be difficult to identify prior to surgical intervention.²

Approximately 85% of PHPT is caused by a single adenoma. The two main surgical approaches for parathyroidectomy in patients with a parathyroid adenoma are standard bilateral exploration (BE) and focused, image-guided (minimally invasive) parathyroidectomy. Minimally invasive surgery is indicated for patients who are suspected clinically or via imaging to have a single parathyroid adenoma. In BE, all parathyroid glands are identified intraoperatively to differentiate a single hyperfunctioning adenoma from multiple gland disease.³ In our case, preoperative imaging failed to localise an adenoma; therefore, a BE approach was used.

Although bleeding and airway compromise are the most concerning postparathyroidectomy complications, monitoring calcium in hypocalcaemic patients is an important cause for hospitalisation in this cohort.³ Transient hypocalcaemia can occur postoperatively in 7%–35% of patients following parathyroidectomy for PHPT.^{4 5} Up to 10% of patients may experience a delay in normalisation of their calcium levels for up to 2 weeks postoperatively.⁶ In addition, transient or permanent symptomatic hypocalcaemia can be caused by the removal of parathyroid glands. Another interesting aspect of our case was the slow optimisation of calcium despite adequate standard management dictated by protocol. This could be attributed to the most common cause of hypocalcaemia (post parathyroidectomy) and damage to the inferior thyroid artery, which supplies the parathyroid glands. This is limited and influenced by the degree of surgical manipulation.^7–9 This can help explain the potentiation of hypocalcaemia caused by hyperthyroidism resulting in an increased calcium reabsorption in bone and increased losses via the kidney.

Surgical approach can influence the incidence of hypocalcaemia post parathyroidectomy. An increased incidence of hypocalcaemia was demonstrated in patients who underwent BE like our case when compared with unilateral exploration.^{8 10} Moreover, two studies found that postoperative hypocalcaemia is more common in total parathyroidectomy than subtotal parathyroidectomy due to the quantity of parathyroid tissue removed at the time of surgery.^{11 12} Subtotal parathyroidectomy is usually favoured over total parathyroidectomy for PHPT as it results in similar rates of recurrence but a lower risk of postoperative hypoparathyroidism and hypocalcaemia.^12–14 A recent multi-institutional study comparing surgical outcomes following index and revision parathyroidectomies showed that 1.7% of patients following index parathyroidectomies had hypocalcaemia at 180 days postoperatively compared with 10.6% in the revision group.¹⁵ With respect to biochemical markers predictive of postoperative hypocalcaemia, one study found a reduction of ioPTH greater than 85% postremoval as the only significant predictive factor of postoperative hypocalcaemia.⁴

Severe symptomatic hypocalcaemia post parathyroidectomy requiring admission is rare.³ In a prospective study of 3000 patients post parathyroidectomy, only 0.2% required admission for intravenous calcium replacement for symptomatic hypocalcaemia.¹⁶ There are no clear definitions of severe hypocalcaemia in literature, which makes it difficult to ascertain the incidence of this complication postoperatively. However, symptoms such as tetany usually occur when the serum calcium falls below 1.9 mmol/L. While classical teaching suggests that Chvostek and Trousseau’s signs are indicative of hypocalcaemia, our literature review revealed that neither is a fully reliable sensitive or specific sign. Chvostek’s sign can be absent in one-third of patients with hypocalcaemia, and one study showed that it could be an indicator of hypercalcaemia as opposed to hypocalcaemia.^{17 18} Trousseau’s sign, while more sensitive than Chvostek’s, can be present in 1%–4% of normocalcaemic patients.¹⁹ Other life-threatening complications of hypocalcaemia include seizures, arrhythmias, congestive cardiac failure and cardiomyopathies, and less commonly, acute psychiatric complications such as hallucinations and psychosis.^{20 21}

A less frequent mechanism causing postoperative hypocalcaemia is hungry bone syndrome, which results in rapid uptake of calcium into bones postoperatively with hypomagnesaemia and hypophosphatemia.²² In our case, there was mild hypomagnesaemia and a high phosphate. This is consistent with a postoperative hypoparathyroidism picture seen in parathyroidectomy, where decreased levels of PTH influence homeostasis of phosphate and magnesium.²³ Damage to the vasculature is the suspected cause behind severe symptomatic hypocalcaemia mimicking ST-elevation infarcts on ECGs.

VTs such as Torsades Du Point associated with calcium electrolyte abnormalities and subsequent QT prolongation are a well-established phenomenon in literature.^{20 21 24} However, there are no published cases to our knowledge of postoperative severe hypocalcaemia due to a subtotal parathyroidectomy causing an ST-elevation picture on ECGs. There have been cases in literature of severe hypocalcaemia mimicking the pattern of ST-elevation myocardial infarctions on ECG; however, the patients have complex medical histories and significant comorbidities such as secondary renal failure confounding the findings.^{22 25 26}

Calcium ions are essential in the regulation of cardiac muscle contractions, and this is the mechanism by which we believe hypocalcaemia caused the coronary artery vasospasm in our patient.^{27 28} This is supported by the localisation of the ischaemic changes to the areas perfused by the right coronary artery, ‘rise and fall’ pattern of serial troponin-T, and a normal coronary angiogram and echocardiogram. A normal coronary angiogram in the presence of ST-elevation secondary to coronary vasospasm is a well-documented phenomenon in literature.²⁹

Hypomagnesaemia has the potential to cause vasospasm as well and is often associated with severe hypocalcaemia.³⁰ In our case, the degree of hypocalcaemia was much greater than the hypomagnesaemia, which resolved within a day of admission despite ECG changes persisting and evolving. A similar case described ST-segment elevation associated with chest pain in a patient with primary hypoparathyroidism and subsequent hypocalcaemia who was admitted with tonic–clonic seizures.³¹ Unlike this case, our patient had no seizures or cardiac symptoms associated with ischaemia and normal left ventricular function.

In conclusion, we present a unique case of hypocalcaemia-induced ST elevation on electrocardiograph with a working diagnosis of coronary artery vasospasm. Our case is unique compared with similar published cases as the hypocalcaemia was secondary to parathyroidectomy; the coronary angiogram and echocardiogram were normal; and there was no significant prior cardiac or renal history. Our patient had no cardiac symptoms and minimal changes in the initial ECG. There have been numerous cases where hypocalcaemia caused cardiac events and where parathyroidectomy caused hypocalcaemia; however, based on our literature review, this is a rarely reported phenomenon in these surgeries. This highlights the importance of conducting serial investigations including troponin-T and ECGs in the presence of severe electrolyte abnormalities. The decision to discharge a patient post parathyroidectomy should be made after taking the intraoperative events and biochemical results into consideration as delayed hypocalcaemia may occur and could potentially lead to life-threatening complications.

Learning points.

• With parathyroidectomy, severe hypocalcaemia causing coronary vasospasm is an important and potentially life-threatening complication that is essential to be aware of regardless of the type of resection.

• Intraoperative events, biochemical markers and the patient’s medical history must be considered carefully to weigh the risk of delayed hypocalcaemia prior to discharge.

• Coronary artery vasospasm induced by severe hypocalcaemia can mimic ST-elevation myocardial infarctions and patients should undergo coronary angiograms to rule out obstructive coronary artery disease.

• Further investigations with serial troponin measurement, ECGs and cardiac monitoring should be considered, in the presence of severe electrolyte abnormalities and mild ECG changes, even if patients are asymptomatic from a cardiac perspective.

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