Severe Hypercalcemia Secondary to Factitious Thyrotoxicosis
Article Outline
To the Editor:
A 32-year-old woman was admitted with a 4-week history of palpitations, insomnia, heat intolerance, weight loss, and excessive perspiration. She had similar episodes 7 years previously, following the birth of her child, when a provisional diagnosis of postpartum thyroiditis was made. She works as a health care assistant. Her mother suffers from hypothyroidism and is on thyroxin replacement. She denied ingestion of iodine or thyroid hormone. On examination she was restless and fidgety and had a pulse rate of 140 beats per minute, with tremor of both hands. She had no goiter or signs of ophthalmopathy. Thyroid function tests, done on admission and 2 weeks before that, showed thyrotoxicosis, free T4 (fT4) >108 pmol/L (normal, 10.6-21.0), free T3 (fT3) >44 pmol/L (normal, 10.6-21.0) and thyroid-stimulating hormone (TSH) <0.03 3 mIU/L (normal, 0.4-4.0) with negative thyroid peroxidase antibodies. Further investigations revealed severe hypercalcemia, adjusted serum calcium 14.2 mg/dL (normal, 8.4-10.4), with suppressed parathyroid hormone <0.32 pmol/L (normal, 0.45-5.00) and raised urinary calcium excretion, 16.5 mmol/24 hours (normal, 2.7-7.5). Serum protein electrophoresis, vitamin D, creatinine, and angiotensin-converting enzyme levels were all within normal range. Serum alkaline phosphatase was normal at 81 IU/L (normal, 40-120). Adrenocorticotropic hormone stimulation test, to exclude Addison's disease, also was normal. Chest radiograph and ultrasound of the thyroid and abdomen were unremarkable. A diagnosis of hypercalcemia secondary to thyrotoxicosis was made and she was treated with saline hydration and propylthiouracil, as she did not tolerate carbimazole.
After initial improvement of the hypercalcemia (serum calcium 10.08 mg/d) and thyroid function (fT4 33.5 pmol/L, fT3 5.1 pmol/L, TSH <0.03 mIU/L), she was discharged on propylthiouracil 150 mg three times per day 3 weeks postadmission, with an early outpatient follow-up. She missed the follow-up appointment and presented 3 weeks later with recurrence of her symptoms, with an increase in serum calcium (12.12 mg/dL), alkaline phosphatase (161 IU/L), and thyroid hormone levels (fT4 >108 pmol/L, fT3 >44 pmol/L, TSH <0.03 mIU/L). This worsening of her thyrotoxicosis despite ongoing antithyroid treatment raised the possibility of factitious thyrotoxicosis. Thyroglobulin level was low, 7.7 μg/L (normal, 0-40), and radioactive iodine uptake (RAIU) scan showed no thyroid or ectopic uptake, confirming the suspicion of factitious thyrotoxicosis. When confronted, she admitted buying Thyrotril (thyroid hormones) online. She also admitted to taking thyroid pills during her first episode 7 years ago. Antithyroid treatment was subsequently discontinued. Six months later, at outpatient follow-up, she was asymptomatic, with normalization of thyroid function (fT413.0 pmol/L, fT3 3.2 pmol/L, TSH1.92 mIU/L) and complete resolution of hypercalcemia (serum calcium 9.32 mg/dL).
Diagnosis of factitious thyrotoxicosis requires high index of suspicion, without which misdiagnosis and mismanagement are common. The work-up for diagnosis of factitious thyrotoxicosis should include careful history, physical examination, laboratory tests, and RAIU scan. The history needs to cover all medications, including herbal medicines and diet pills. Signs of Graves' disease and subacute thyroiditis are absent, and thyroid antibodies are typically negative. Serum thyroglobulin can be a useful, although not very sensitive, diagnostic marker; its value increases in hyperthyroidism and is suppressed in exogenous thyrotoxicosis. Absence of RAIU thyroid and ectopic uptake excludes hyperthyroidism and ectopic thyroid hormone production, respectively. In our case, on the first admission, factious thyrotoxicosis was not suspected, and RAIU scan and thyroglobulin level were not performed; this led to a delay in making a definitive diagnosis and to potentially harmful therapy with antithyroid medications. The patient missing the follow-up appointment led to a further delay.
Hypercalcemia secondary to thyrotoxicosis is common (11%-52%),1 but usually mild (<10.8 mg/dL) and rarely symptomatic.2 The direct effect of thyroid hormones, by stimulating the bone osteoclastic activity, leads to bone resorption and hence, hypercalcemia.1 Severe hypercalcemia has rarely been described in association with hyperthyroidism3, 4 and has never, to our knowledge, been reported in patients with factitious thyrotoxicosis. The present case is the first report of severe hypercalcemia due to factitious thyrotoxicosis.
References
- . Effects of thyroid hormones on bone and mineral metabolism. Endocrinol Metab Clin North Am. 1990;19(1):35–63
- Prevalence of primary hyperparathyroidism in 13,387 patients with thyroid diseases, newly diagnosed by screening of serum calcium. Exp Clin Endocrinol Diabetes. 1999;107:457–461
- . Symptomatic severe hypercalcemia: initial manifestation of hyperthyroidism. [Spanish] Rev Clin Esp. 1992;191(9):506
- . Life-threatening hypercalcemia in a case of thyrotoxicosis: clinical features and management (A case report). Acta Chir Scand. 1985;151(5):487–489
Funding: None.
Conflict of Interest: None.
Authorship: All authors meet the criteria for authorship, including acceptance of responsibility for the scientific content of the manuscript. We also confirm that all authors had access to the data and a role in writing.
PII: S0002-9343(09)00104-1
doi:10.1016/j.amjmed.2008.12.017
© 2010 Published by Elsevier Inc.
