Hypocalcemia Following Thyroidectomy in a Patient With COVID-19: A Case Report and Literature Review

COVID-19 can lead to various complications, including severe respiratory symptoms. Both viral infections and total thyroidectomy are known to cause hypocalcemia, making a history of thyroidectomy a potential risk factor for hypocalcemia in COVID-19 patients. We present the case of a 34-year-old woman with Graves’ disease who developed hypocalcemia due to COVID-19 following a total thyroidectomy. The patient underwent an uneventful total thyroidectomy, with preservation of at least three of the four parathyroid glands. Postoperatively, her parathyroid hormone (PTH) levels were normal, and she was discharged without tetany. However, on postoperative day 90, she experienced mild hypocalcemia during a COVID-19 infection, although it was asymptomatic. By postoperative day 127, she presented with severe tetany and general malaise. Testing confirmed a reinfection with SARS-CoV-2 and hypocalcemia, while PTH levels remained normal. Treatment with intravenous calcium gluconate, oral calcium lactate, and alfacalcidol effectively resolved the hypocalcemia and tetany. The patient was subsequently discharged without tetany and has since been monitored without the need for calcium or vitamin D supplementation. This case highlights that the COVID-19 infection following a total thyroidectomy can cause hypocalcemia. Postoperative hypocalcemia is a common issue in head and neck surgery, and viral infections like COVID-19 should be considered in the differential diagnosis of hypocalcemia.


Introduction
The outbreak of COVID-19, caused by SARS-CoV-2, has profoundly impacted global medicine.Despite the development of vaccines, many individuals continue to experience COVID-19, which can lead to various serious complications.Beyond respiratory issues, endocrine disturbances, particularly hypocalcemia, have been documented as complications of COVID-19 [1].Additionally, total thyroidectomy is known to cause hypocalcemia, with reported incidence rates ranging from 2% to 83% [2].Here, we present a case of hypocalcemia following a total thyroidectomy, attributed to COVID-19.

Case Presentation
A 34-year-old woman with Graves' disease underwent medical treatment for a year at a private clinic.She was referred to our department for a total thyroidectomy due to inadequate control of thyroid function with thiamazole (20 mg/day) and potassium iodide (50 mg/day).The patient had a history of asthma and had not been vaccinated against SARS-CoV-2.At her initial visit to our department, the laboratory data were as follows: albumin: 4.5 g/dL; calcium: 9.2 mg/dL; phosphate: 3.4 mg/dL; free triiodothyronine: 2.58 pg/mL; free thyroxine: 0.78 ng/mL; thyroid-stimulating hormone: 14 μIU/mL; intact parathyroid hormone (PTH): 46.5 pg/mL; thyrotropin receptor antibody: 10.6 IU/L; anti-thyroglobulin antibody: 12.3 IU/mL; and antithyroid peroxidase antibody: 9 IU/mL (Table 1).

Measured value
Normal range Albumin 4.5 g/dL   We performed a total thyroidectomy through a transverse cervical incision under general anesthesia (Figure 2A).At least three out of four parathyroid glands were preserved, and the surgery was completed without complications.The excised thyroid gland weighed 125 g (Figure 2B).The patient received a calcium gluconate infusion for a few days post-surgery and was discharged with oral calcium lactate (3 g/day), alfacalcidol (2 μg/day), and levothyroxine.Follow-up blood tests showed normal levels of PTH and calcium without any signs of tetany, leading to the discontinuation of calcium lactate and alfacalcidol.The patient experienced an initial SARS-CoV-2 infection on postoperative day 90, with mild symptoms that resolved spontaneously.Although there was a slight decrease in calcium levels to 8.1 mg/dL, the PTH level remained normal, and no tetany was observed (Figure 3).

FIGURE 3: Postoperative course of corrected calcium and PTH levels
The PTH level gradually increased following total thyroidectomy, with calcium supplementation concluding one month after surgery.Despite normal PTH levels, severe hypocalcemia occurred following the COVID-19 reinfection.Calcium administration resolved the symptoms of reactive PTH downregulation.After recovery from COVID-19, both calcium and PTH levels remained within the normal range without supplementation.

PTH: parathyroid hormone
The patient was reinfected with SARS-CoV-2 on postoperative day 127, presenting with severe tetany, difficulty walking, general malaise, cough, and nasal discharge.Both SARS-CoV-2 antigen and PCR tests were positive, with a low PCR threshold cycle value of 23 indicating reinfection.A chest CT revealed no evidence of pneumonia (Figure 4).

FIGURE 4: CT scan of the chest
The chest CT scan revealed no evidence of pneumonia.

Discussion
Hypoparathyroidism, pseudohypoparathyroidism, vitamin D deficiency, and renal failure are the primary causes of hypocalcemia.Since Bossoni et al. reported the first case of severe hypocalcemia associated with COVID-19 in 2020 [3], the virus has been recognized as a potential inducer of hypocalcemia.The incidence of hypocalcemia among hospitalized COVID-19 patients ranges from 62.6% to 87.2% [4,5].Given that hypocalcemia may serve as a prognostic marker for ventilator requirements and mortality in COVID-19 patients [6], normalization of calcium levels is crucial for effective management.
Virus-dependent calcium influx into cells, vitamin D deficiency, functional hypoparathyroidism, and PTH resistance are considered causes of hypocalcemia in COVID-19 [5].Viruses utilize calcium signaling to enhance replication, with calcium playing a critical role throughout the viral life cycle, including viral structure formation, entry, gene expression, protein synthesis, fusion with host cells, and release of mature viruses [6].In enveloped viruses such as SARS-CoV and Ebola, calcium directly interacts with viral fusion peptides to promote replication [7].During the 2003 SARS and 2016 Ebola epidemics, hypocalcemia was observed in approximately 60% of affected patients [7].Additionally, patients with COVID-19 often experience vitamin D deficiency, which can contribute to hypocalcemia [8]; however, vitamin D levels in our patient were normal.Functional hypoparathyroidism and PTH resistance, which have been reported in critically ill patients, may also be relevant in COVID-19 cases [9].

PTH: parathyroid hormone
Of these patients, 46% (n = 6) were women.The median age was 53 years (range: 14-82 years).The median calcium level, adjusted for albumin, was 5.0 mg/dL (range: 2.6-6.9 mg/dL).Nine patients recovered, while four died from the infection.Notably, hypocalcemia with normal PTH levels (10-65 pg/mL) was observed in seven cases.It is possible that PTH levels were actually low but appeared normal due to the hypocalcemia.An additional six patients were diagnosed with hypoparathyroidism.
In Bossoni et al.'s case report, a patient who had undergone total thyroidectomy 19 years prior to the COVID-19 infection had normal calcium levels before the infection but developed hypocalcemia afterward [3], similar to our case.Our patient, who also underwent a total thyroidectomy, experienced hypocalcemia triggered by COVID-19.We observed that the initial COVID-19 infection caused mild hypocalcemia, which was exacerbated by a subsequent infection.Although most parathyroids were preserved and PTH levels seemed normal, it is plausible that parathyroid function was lower compared to patients who had not undergone total thyroidectomy.Hypocalcemia with normal PTH may be attributed to increased calcium demand due to virus-dependent calcium influx or PTH resistance.Clinicians should be aware that a history of thyroid surgery combined with viral infections, including COVID-19, may increase the risk of hypocalcemia, even when PTH levels are normal.Further research is needed to determine whether residual parathyroid function after thyroidectomy is adequate to maintain serum calcium levels during high calcium demands, such as during viral infections.

Conclusions
We report the case of a patient who developed hypocalcemia due to a COVID-19 infection following a total thyroidectomy.Despite normal vitamin D and PTH levels, COVID-19 was identified as the cause of hypocalcemia.While hypocalcemia is commonly observed after head and neck treatments, including total thyroidectomy, head and neck surgeons should be aware of viral infections as a potential contributing factor.

FIGURE 1 :
FIGURE 1: CT image of the thyroidThe thyroid gland was enlarged to a maximum width of approximately 7 cm.(A) Axial CT scan showing a diffusely enlarged thyroid gland.(B) Coronal CT scan displaying the same diffuse enlargement of the thyroid gland.

A
limitation of this study is the use of 1,25-(OH) vitamin D as a marker of vitamin D deficiency.While 1,25-(OH) vitamin D measures activated vitamin D, 25-(OH) vitamin D, which reflects the total amount of vitamin D, should also be assessed for a complete diagnosis of vitamin D deficiency.

TABLE 1 : Preoperative laboratory data CT
revealed a diffusely enlarged thyroid gland with a maximum width of approximately 7 cm (Figure1A, 1B).

TABLE 2 : Laboratory data during COVID-19 reinfection
Thyroid function remained normal with oral levothyroxine administration.Given the patient's hypocalcemia with normal PTH levels, renal function, and vitamin D levels, COVID-19 was considered the cause of hypocalcemia.Hypocalcemia and tetany improved immediately with intravenous calcium gluconate, oral calcium lactate (3 g/day), and alfacalcidol (3 μg/day).Her malaise gradually resolved, and she was discharged 17 days after admission.The doses of calcium lactate and alfacalcidol were tapered off, and PTH levels, which had decreased in response to calcium supplementation, normalized.One year after the COVID-19 infection, the patient showed no signs of tetany and maintained normal calcium and PTH levels without medication.