A CASE REPORT AND LITERATURE REVIEW OF SUBCUTANEOUS LEVOTHYROXINE ABSORPTION TESTING IN A PATIENT WITH REFRACTORY PRIMARY HYPOTHYROIDISM

Abstract

INTRODUCTION/BACKGROUND

We present a case of refractory primary hypothyroidism in which the patient failed an oral levothyroxine (LT4) absorption test under optimised conditions. Given limited formulary options and the patient's complex clinical background, an off-label trial of subcutaneous LT4 was initiated as an alternative treatment strategy.

CASE

A 51-year-old male underwent total thyroidectomy with right central neck dissection and radioactive iodine ablation for papillary thyroid carcinoma. He was maintained on a supraphysiologic dose of oral LT4 (approximately 3.16 mcg/kg/day) with suppressed TSH 0.24 mIU/L and fT4 20.6 pmol/L. He was admitted for encapsulating sclerosing peritonitis, requiring two paracentesis, diagnostic laparoscopy, intravenous antibiotics and systemic corticosteroids. During admission, thyroid function progressively worsened (TSH >100 mIU/L and fT4 9.7 pmol/L) despite adherence to increasing oral LT4 doses. An oral LT4 absorption test confirmed malabsorption.

Given his ischemic heart disease, weekly high-dose intravenous or intramuscular LT4 posed a potential cardiac risk. Daily intravenous LT4 was logistically impractical, and daily intramuscular injections were deemed unsuitable due to patient discomfort and medication wastage.

A subcutaneous LT4 absorption test was performed using 100 mcg (1 mL) of IV LT4 (Fresenius Kabi) administered subcutaneously with a 25-gauge needle at a 45-degree angle. Free T4 levels were measured at baseline and 2-, 4-, 6-, and 48-hour post-injection (6.1, 8.7, 9.4, 12.4, and 7.2 pmol/L respectively). A peak increase in free T4 of 103.3% at 6 hours confirmed effective subcutaneous absorption. The LT4 dose was escalated to 150 mcg thrice weekly, resulting in biochemical improvement (TSH: 20.31 mIU/L; fT4: 9.1 pmol/L).

CONCLUSION

This case highlights subcutaneous LT4 as a viable off-label alternative in patients with confirmed malabsorption. Pharmacokinetic assessment revealed an estimated bioequivalence of 59.3% compared to intravenous LT4 (AUC calculated via trapezoidal method), consistent with findings from prior literature (Sharpe et al.).