Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodide uptake in nontoxic nodular goiter

Abstract

Radioiodine (131I) is increasingly used as treatment for volume reduction of nontoxic, nodular goiter. A high dose of 131I is often needed because of low thyroid radioiodide uptake (RAIU). We investigated whether pretreatment with a single, low dose of recombinant human TSH (rhTSH; Thyrogen, Genzyme Transgenics Corp.) enhances RAIU in 15 patients with nontoxic, nodular goiter (14 women and 1 man; aged 61+/-11 yr). Four patients were studied twice, and 1 patient was studied 3 times. RAIU was measured both under basal conditions and after pretreatment (im) with rhTSH, given either 2 h (0.01 mg; n = 7) or 24 h [0.01 mg (n = 7) or 0.03 mg (n = 7)] before 131I administration (20-40 microCi). Serum levels of TSH, free T4 (FT4), and total T3 were measured at 2, 5, 8, 24, 48, 72, 96, and 192 h after rhTSH administration. After administration of 0.01 mg rhTSH, serum TSH rose from 0.7+/-0.5 to a peaklevel of 4.4+/-1.1 mU/L (P < 0.0001), FT4 rose from 16.0+/-2.6 to 18.5+/-3.7 pmol/L (P < 0.0001), and T3 rose from 2.10+/-0.41 to 2.63 - 0.66 nmol/L (P < 0.0001). After administration of 0.03 mg rhTSH, TSH rose from 0.6+/-0.4 to 15.8+/-2.3 mU/L (P < 0.0001), FT4 rose from 15.2+/-1.5 to 21.7+/-2.9 pmol/L (P < 0.0001), and T3 rose from 1.90+/-0.43 to 3.19+/-0.61 nmol/L (P < 0.0001). Peak TSH levels were reached at 5-8 h and peak FT4 and T3 levels at 8-96 h after rhTSH administration. Administration of 0.01 mg rhTSH 2 h before 131I increased 24-h RAIU from 30+/-11% to 42+/-10% (P < 0.02), 0.01 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 29+/-10% to 51+/-10% (P < 0.0001), and 0.03 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 33+/-11% to 63+/-9% (P < 0.0001). After administration of 0.01 mg rhTSH 2 h before 131I, 24-h RAIU did not increase in 1 patient, whereas the increase in 24-h RAIU was less than 10% in 2 other patients. In contrast, administration of rhTSH 24 h before 131I increased 24-h RAIU by more than 10% in all 14 patients (by >20% in 10 and by >30% in 6). In conclusion, pretreatment with a single, low dose of rhTSH in patients with nontoxic, nodular goiter increased RAIU considerably. Our observations hold promise that administration of rhTSH before 131I therapy for nontoxic, nodular goiter will allow treatment with lower doses of 131I in these patients.