Post Total Thyroidectomy Hypocalcaemia-Induced Cardiomyopathy: Case Presentation and Literature Review

Calcium ions play an important role in the contractility of cardiac muscle. Severe extracellular hypocalcaemia impairs cardiac contractility and results in ventricular dysfunction known as hypocalcemia induced cardiomyopathy. Hypocalcemia induced cardiomyopathy after total thyroidectomy is rare with only few cases reported in the literature. We report a case of post thyroidectomy Hypocalcaemia induced cardiomyopathy in a 45 years old lady who was successfully treated with calcium and vitamin D supplement with complete recovery of her left ventricular function.

She had a history of total thyroidectomy 3 years before admission for multinodular goiter and she was on levothyroxine 100 mg /day, calcium and vitamin D supplements but she was not compliant with medications. She had no history of hypertension, diabetes mellitus or other medical diseases.
On physical examination, she was fully conscious, oriented with normal oxygen saturation at room air. Her pulse rate was 90/min, blood pressure 110/70 mmHg, and temperature 37.5℃. On chest examination, there was basal crepitation, coarse breathing sounds on both lung fields, and a systolic murmur on the apex of the heart. Abdomen was soft and non-tender. There was trivial pedal edema.    The patient was treated with intravenous calcium gluconate, vitamin D and with aggressive treatment for congestive heart failure. She responded well to the treatment with improvement in cardiac symptoms. She was discharged home on calcium and vitamin D supplement (oral calcium carbonate 100 mg/kg/d in three divided doses and oral calcitriol 0.125 μg/daily) and advised to monitor her serum calcium weekly. She reported significant symptomatic improvement during her follow-up after discharge a month later. Serum calcium level at that time improved to1.96 mmol/L.

Discussion:
Calcium plays a key role in a wide range of biological functions including extra-and intracellular signaling, nerve impulse transmission, muscle contraction etc [1,2]. The vast majority of total body calcium (more than 99%) is present in the skeleton, and serves to provide skeletal strength, and represent a dynamic store to maintain the intra-and extracellular calcium pools [3,4].
Blood calcium represents less than 1% of total body calcium and approximately half of the total serum calcium is bound to protein (mainly albumin and globulin), with the remaining free ionized calcium represents the physiologically active calcium [5]. Serum ionized calcium is mainly regulated by parathyroid hormone, 1, 25-dihydroxy vitamin D, calcitonin and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone [4].
Parathyroid hormone (PTH) plays a major role in regulating ionized serum calcium. The hormone is secreted primarily by the chief cells of the parathyroid glands in response to hypocalcemia. It is a polypeptide containing 84 amino acids acts to increase serum calcium by mobilization calcium from bone, increase absorption of calcium from the small intestine and reduce calcium loss in urine by increasing calcium reabsorption by renal tubules.
Hypocalcemia is defined as a total serum calcium concentration less than the lower limit of the normal range ( 8.8 mg/dL / 2.20 mmol/L) in the presence of normal plasma protein concentrations or as a serum ionized calcium concentration less than (4.7 mg/dL / 1.17 mmol/L).
Vitamin D deficiency and hypoparathyroidism are the commonest cause of hypocalcaemia although it can be caused by many other conditions including renal disease, end-stage liver disease causing vitamin D inadequacy, Fanconi syndrome, and Hungry bone syndrome. It is also associated with many drugs, including bisphosphonates, cisplatin, anti-epileptics, and aminoglycosides, diuretics, and proton pump inhibitors [6].
Hypoparathyroidism is most commonly seen following inadvertent removal of or damage to the parathyroid glands or their vascular supply during a total thyroidectomy. Persistent hypocalcemia six months after surgery confirms the diagnosis of hypoparathyroidism in the presence of low or inappropriately normal PTH levels [7].
Total thyroidectomy is considered as the standard procedure in the management of thyroid cancer and increasingly used nowadays for benign thyroid diseases. The optimal surgical treatment of patients with multinodular goiters is still debatable. Although the recent European and American guidelines recommend total thyroidectomy for management of the multinodular due to increased reported safety of the procedure, subtotal thyroidectomy is still in common practice in several centers worldwide [8].
Some authors [9][10][11][12][13] advocates' subtotal thyroidectomy for surgical management of multinodular goiter as they believe that total thyroidectomy increases the rates of recurrent laryngeal nerve and parathyroid injuries in addition to the lifelong need for hormone replacement therapy. On the other hand, others advocate total thyroidectomy because of the significant risk of recurrence in patients undergoing thyroid surgery [14][15][16][17].
Recent European and American guidelines recommend total thyroidectomy for the treatment of multinodular goiter as it is the most reliable approach in preventing the high recurrence rate associated with a less invasive approach (18).
Although total thyroidectomy is a safe procedure under the skilled surgeon's hands, it carries a significant risk of morbidity associated with hypoparathyroidism and injury to the inferior laryngeal nerve.
Hypocalcemia remains a major postoperative complication of total thyroidectomy. The primary cause of post thyroidectomy hypocalcemia is damage to the parathyroid blood supply and/or inadvertent excision of one or more glands. [19]. Post thyroidectomy hypocalcemia can be transient or permanent.
Transient biochemical or symptomatic hypocalcemia is common after thyroid surgery. It is of not known or fully understood etiology and can occur despite careful preservation of the parathyroid glands and their blood supply. The reported incidence of post thyroidectomy transient hypocalcemia ranges between 6.9 and 49% [20-23]. It tends to develop during the first 24 to 48 hours after surgery, responds favorably to replacement therapy, and recovered during the first month in (79%) of the patients without serious consequences apart from delaying patient's discharge [24]. Although correction of serum calcium level can be achieved rapidly, restoration of myocardial function would take a few months, as restoration of intracellular calcium level is more important to restore cardiac function and usually takes time to be normalized [56].

Conclusions:
Hypocalcaemia is a rare treatable cause of CMP that should be suspected in all unexplained cases of severe LV systolic dysfunction in post thyroidectomy patients. Surgeons should be aware of this serious complication and pay more attention to careful identification, dissection, and preservation the parathyroid glands and their blood supply during thyroid surgery. Intraoperative, 1-24 hours postoperative measurement of (intact PTH) with or without serial measurement of the serum calcium in the first postoperative day is a sensitive predictor of the risk of post thyroidectomy hypocalcaemia. Early prediction of patients at high risk of hypocalcaemia is vitally important in making a decision about the early discharge of patients at low risk and commencement of replacement therapy on those at high risk. Early institution of appropriate replacement therapy together with regular follow up of patients at high-risk is the only safeguard against chronic post thyroidectomy hypocalcaemia and its serious cardiac complications.