Hypocalcemia following Treatment for Hyperthyroidism

Summary

DOI: 10.1373/clinchem.2010.150375

A 17-year-old female was referred to the endocrinology clinic after blood test results suggestive of hyperthyroidism. She had mild symptoms of thyrotoxicosis, including menstrual disturbance with intermittent palpitations and tremor. On examination, the patient was normotensive, tachycardic (100 beats/min), and of slim build with poor dentition. She had a small diffuse goiter without retrosternal extension or bruit. There was conjunctival injection but no evidence of lid lag or proptosis. Auscultation of the precordium revealed murmurs in systole and diastole consistent with mixed aortic valve disease.

Student Discussion

Student Discussion Document (pdf)

Claire L. Meek,^1* Felicity Kaplan,² R. Scott Pereira,³ and Adie Viljoen¹

¹Departments of Chemical Pathology, ²Endocrinology, and ³Immunology, Lister Hospital, Stevenage, UK.
*Address correspondence to this author at: Department of Chemical Pathology, Lister Hospital, Corey’s Mill Lane, Stevenage SG1 4AB, UK. E-mail [email protected].

Case Description

The only child of healthy nonconsanguineous parents, the patient had previously been well. Her medical history included mild learning difficulties, a bicuspid aortic valve, recurrent urinary tract infections, and severe constipation as a child that required a colostomy, which was later reversed. Apart from an osmotic laxative, she received no other regular medication. A recent echocardiogram had demonstrated a bicuspid aortic valve with good flow and minor regurgitation.

Biochemically, the patient had an undetectable serum concentration of thyroid-stimulating hormone (TSH) (<0.03 mIU/L; reference interval, 0.3–5.6 mIU/L) and an increased concentration of free thyroid hormone (fT4) [43 pmol/L (3.3 ng/dL); reference interval, 7.5–21.1 pmol/L]. Her baseline serum concentrations of total calcium [2.27 mmol/L (9.08 mg/dL)] and phosphate [1.26 mmol/L (3.9 mg/dL)] were both within their reference intervals (2.20–2.60 mmol/L and 0.75–1.36 mmol/L, respectively).Theserum albumin concentration was 41 g/L (reference interval, 35–50 g/L), and the magnesium concentration was 0.71 mmol/L (reference interval, 0.74–1.00 mmol/L). The results of her other biochemical tests were unremarkable. An immunologic analysis demonstrated increased thyroid peroxidase antibodies (582 IU/L; reference interval, 0–60 IU/L) and increased TSH receptor antibodies (6.9 U/L; reference interval, 0–1.5 U/L), confirming Graves disease. Thyroid imaging revealed a diffusely enlarged thyroid gland, with no visible parathyroid tissue apparent on ultrasound and MRI evaluations.

After daily treatment with 30 mg carbimazole and 25 mg atenolol, the fT4 concentration in the patient decreased as expected (fT4, 19.2 pmol/L; TSH, 0.03 mIU/L). Concomitantly, the patient developed asymptomatic hypocalcemia [calcium, 1.72 mmol/L (6.88 mg/dL)]. The total 25-hydroxyvitamin D concentration was 38 nmol/L (reference interval, 15–100 nmol/L), and her serum magnesium concentration was 0.87 mmol/L (reference interval, 0.74–1.00 mmol/L). Both were within their respective reference intervals. The serum phosphate concentration was 1.28 mmol/L (reference interval, 0.9 –1.35 mmol/L), and the albumin concentration was 48 g/L (referenceinterval, 35–50 g/L). The parathyroid hormone (PTH) concentration was also within the reference interval [4.8 pmol/L (4.8 ng/L); reference interval, 1.6 –9.3 pmol/L] and thus inappropriately normal given the degree of hypocalcemia. A diagnosis of hypoparathyroidism was made, and the patient was treated with 0.5 _g alfacalcidol daily. The calcium concentration briefly normalized (Table 1).

After this improvement, the patient stopped complying with her carbimazole and alfacalcidol treatment regimen, and the results of thyroid function tests returned to near pretreatment concentrations [fT4, 58.4 pmol/L (4.5 ng/dL); TSH,<0.03 mIU/L; calcium, 2.34 mmol/L (9.36 ng/dL); Table 1]. With improved patient compliance, the fT4 results improved, approaching euthyroidism. The patient eventually achieved a normocalcemic state [fT4, 13.5 pmol/L (1.0 ng/dL); calcium, 2.35 mmol/L (9.4 mg/dL)]. More recently, compliance has been a concern with recurrent increased fT4 concentrations (Table 1).

The patient gave full written consent for the use of her clinical information and laboratory tests for the purposes of submission of a case report to the medical literature. She has very mild learning difficulties but was able to understand, process, and retain the information given.

Table 1. Chronological changes in the serum concentrations of total calcium and fT4 as treatement progressed

Questions to Consider

What effect does thyrotoxicosis have on serum calcium?
What other endocrine disorders affect serum calcium?
What genetic diseases can affect serum calcium?

Final Publication and Comments

The final published version with discussion and comments from the experts appears in the June 2011 issue of Clinical Chemistry, approximately 3-4 weeks after the Student Discussion is posted.

Educational Centers

If you are associated with an educational center and would like to receive the cases and questions 3-4 weeks in advance of publication, please email [email protected].

AACC is pleased to allow free reproduction and distribution of this Clinical Case Study for personal or classroom discussion use. When photocopying, please make sure the DOI and copyright notice appear on each copy.