Table 2.
Studies of Thyroglobulin Testing—Intervention and Test Characteristics
| Study, year | Surgery type | RAI | TSH level | Tg testing timing (from surgery) | TgAb status | Duration of follow-up | Reference standard |
|---|---|---|---|---|---|---|---|
| Tg testing following partial thyroidectomy | |||||||
| Alzahrani, 2002 (7) | Lumpectomy: 7.9% Unilateral lobectomy: 36% Hemithyroidectomy: 35% Bilateral partial thyroidectomy: 7.9% Subtotal thyroidectomy: 13.9% Unilateral modified neck dissection: 3.0% Cervical lymph node sampling: 8.9% |
None | Not described; median TSH 3.25 mU/L | Unclear | Not routinely performed; negative in 30 patients with at least 1 Tg level >20 ng/mL | Median 3.2 months (time to completion surgery) | Pathological (completion surgery, with modified neck dissection in 89%) |
| Park, 2018 (30) | Lobectomy: 100% | None | Not described; mean TSH not reported | 3–6 Months after lobectomy, then every 6–12 months | Excluded if TgAb positive | Median 6.9 years | Neck US, histology |
| Ritter, 2020 (33) | Lobectomy: 100% | None | Not described; mean TSH not reported | At least 3 months after surgery, then annually | 11% had TgAb (mean 438 IU/mL) | Mean 78 months | Not described |
| Vaisman, 2013 (39) | Lobectomy with or without isthmusectomy | None | TSH <0.5 mIU/L | Every 6 months during the first year, then at 6–12-month intervals | Excluded if TgAb positive | 6–13 Months | Cytology/histology, neck US |
| Tg testing following total or near-total thyroidectomy without RAI therapy | |||||||
| Durante, 2012 (9) | Total or near-total thyroidectomy Central neck dissection: 12% |
None | 24% had TSH >1 mU/L | Not reported (varied) | Negative: 100% | Median 5 years (range 2.5–22 years) | Clinical, ultrasonography, and Tg findings |
| Janovsky, 2016 (14) | Total thyroidectomy | None | (a) TSH <0.05 mIU/L | 3 Months | No patients developed anti-TgAb | (a) 3 Months | 123I total body scan and neck US |
| (b) Stimulated Tg (TSH level not reported) | (b) 6 Months | ||||||
| (c) TSH 0.5–2.0 mIU/L | (c) 18 Months | ||||||
| (d) TSH 0.5–2.0 mIU/L | (d) 24 Months | ||||||
| Matrone, 2020 (24) | Total thyroidectomy | None | On thyroid replacement | Median 5 months, then every 12–18 months | Excluded for TgAb >8 IU/mL | Median 73 months | Neck US and other imaging (CT, MRI, and/or PET) as indicated |
| Nascimento, 2013 (27) | Total thyroidectomy Central neck dissection: 3% Central and ipsilateral neck dissection: 50% Central and bilateral neck dissection: 3% |
None | Not reported | Mean 9 months, then at discretion of physician (timing of repeat Tg not reported) | 12% with detectable postoperative TgAb | Median 2.5 years | Neck US and other imaging (CT, MRI, and/or PET) as indicated |
| van Wyngaarden, 1997 (40) | Subtotal or near-total thryoidectomy: 83% Lobectomy with or without isthmusectomy: 17% |
None | On thyroid replacement | Not described | Not described | Mean 60 months | Not described |
| Postoperative Tg testing before RAI therapy | |||||||
| Caballero-Calabuig, 2008 (8) | Total lymph node dissection not reported |
Tg obtained before RAI | TSH >30 mU/mL | 4–6 Weeks | Excluded for positive Tg antibodies and negative Tg | 4–6 Weeks | 131I total body scan |
| Giovanella, 2008 (10) | Total central neck dissection: 41% |
Tg obtained before RAI | No (on T4) | 4–6 Weeks | Excluded for TgAb levels >60 U/mL and/or recovery <80% or >120% | 4–6 Weeks | 131I total body scan |
| Grunwald, 1996 (11) | Thyroidectomy, not otherwise described | Tg obtained before RAI | TSH >30 mU/mL | 4–5 Weeks | Excluded for positive Tg antibodies or recovery <80% or >120% | 4–5 Weeks | 131I upper thorax scintigraphy |
| Hasbek, 2014 (12) | Thyroidectomy, not otherwise described | Tg obtained before RAI | Thyroid hormone withdrawal for 4 weeks (TSH not reported) | Not reported | Excluded if anti-TgAb positive | 8 or 9 Days | 131I total body scan |
| Heemstra, 2007 (13) | Thyroidectomy, not otherwise described | Tg obtained before RAI | Thyroid hormone withdrawal (duration and TSH not reported) | Not reported | Excluded if anti-TgAb positive | Within 1 year | Pathological or radiological evidence of tumor presence |
| Kim, 2013 (15) | Total thyroidectomy | Tg obtained before RAI | TSH >30 mU/mL | Not reported | 44% had increasing TgAb levels | Median 54 months | Cytology/pathology |
| Kim, 2005 (16) | Total thyroidectomy | Tg obtained before RAI | TSH >30 mU/mL | 5–6 Weeks | 25% had elevated TgAb levels | 7–13 Months (6–12 months following remnant ablation) | Cytology/pathology, 131I total body scan |
| Krajewska, 2016 (17) | Total thyroidectomy | Tg obtained before RAI | TSH ≥25 uIU/mL | Not reported | Not reported | Not reported (median freedom from progression 155 months) | 131I total body scan, neck US, and stimulated Tg level |
| Latrofa, 2016 (18) | Total thyroidectomy | Tg obtained before RAI | Thyroid hormone withdrawal (mean 54.0 mIU/L) | 3 Months | 12–24% had positive TgAb, depending on assay used | 3 Months | 131I total body scan and CT |
| Ledwon, 2021 (19) | Total or near-total thyroidectomy | Tg obtained before RAI | Nonstimulated | Median 2.7 months | 14% had elevated TgAb levels | Median 6 years | Neck US with confirmatory biopsy, CT, MRI, or [18F]FDG PET/CT for metastatic disease |
| Lima, 2002 (20) | Total thyroidectomy | Tg obtained before RAI | Appears to be nonsuppressed | 3 Weeks | Excluded if TgAb positive | 3 Weeks | Not reported |
| Lin, 2011 (21) | Total thyroidectomy | Tg obtained before RAI | No thyroid replacement or withdrawal | 3–8 Weeks | Excluded if TgAb positive | 3–8 Weeks | 131I total body scan and CT |
| Makarewicz, 2006 (22) | Thyroidectomy, not otherwise described | Tg obtained before RAI | Thyroid hormone withdrawal (median 48.2 mIU/L) | 17–98 Days | Excluded if TgAb >60 U/mL | 6 Months | Imaging, 131I total body scan |
| Makarewicz, 2006 (23) | Thyroidectomy, not otherwise described | Tg obtained before RAI | Not reported | Unclear | Excluded if TgAb >60 U/mL | At least 18 months | Imaging, 131I total body scan |
| Matrone, 2017 (25) | Total thyroidectomy | Tg obtained before RAI | On thyroid replacement | 3–4 Months | Excluded if TgAb ≥20 ng/mL | 3–4 Months | 131I total body scan, neck US, cytology |
| Matthews, 2016 (26) | Total thyroidectomy | Tg obtained before RAI | Not reported | Not reported | Excluded if TgAb positive | Not reported (at least 12 months after RAI therapy) | Not reported |
| Ng, 2000 (28) | Total or near-total thyroidectomy | Tg obtained before RAI | Thyroid replacement withdrawal for at least 5 weeks | Not reported | 25% had TgAb levels >0.3 U/mL | 1 Week before RAI therapy | (a) 131I whole body scan (b) 99mTc-sestamibi whole body scan |
| Oyen, 2000 (29) | Total thyroidectomy | Tg obtained before RAI | No thyroid replacement | Not reported | Not reported | 4–6 Weeks | Histology or 131I total body scan and Tg level; with clinical follow-up, CT, and/or ultrasonography in some cases |
| Polachek, 2011 (31) | Total or near-total thyroidectomy | Tg obtained before RAI | Suppressed (on thyroid hormone treatment, TSH <0.1 mU/L) and stimulated (TSH >30 ng/mL after thyroid hormone withdrawal) | Not reported | Excluded if TgAb positive | 2 Years | Imaging, cytology, and/or RAI uptake, and suppressed Tg |
| Prabhu, 2018 (43) | Total thyroidectomy | Tg obtained before RAI | Mean 106 ng/mL (stimulated) | Not reported | Excluded if TgAb positive (defined as >100 IU/mL) | 2–6 Weeks | 131I whole body scan |
| Ren, 2021 (32) | Total thyroidectomy | Tg obtained before RAI | Thyroid replacement withdrawal for at least 4 weeks with TSH >30 ng/mL | Not reported | Excluded if TgAb positive (defined as >115 IU/mL) | 5–7 Days | 131I whole body scan, other imaging, with pathology confirmation |
| Ronga, 1999 (34) | Total thyroidectomy | Tg obtained before RAI | Tg obtained before starting therapy | ∼40 Days | Not reported | Within 18 months | 131I whole body scan, other imaging and clinical evaluation if 131I scan negative and Tg high |
| Rosario, 2011 (35) | Total thyroidectomy | Tg obtained before RAI | Thyroid hormone withdrawal before Tg testing (TSH target not reported) | 3–6 Months | Excluded if TgAb positive | 3–6 Months | Imaging and 131I whole body scan |
| Szujo, 2021 (36) | Total or near-total thyroidectomy | Tg obtained before RAI | Nonstimulated | Not reported | Excluded if TgAb positive | Median 4.5 years | Not reported |
| Torlantano, 2006 (37) | Near-total thyroidectomy | Tg obtained before RAI | rhTSH stimulated | 6–12 Months | Excluded if TgAb positive | 6–12 Months | Ultrasonography |
| Toubeau, 2004 (38) | Total or near-total thyroidectomy | Tg obtained before RAI | Thyroid hormone withdrawal before Tg testing (TSH target not reported) | Mean 2.7 months | Excluded if TgAb positive or not measured | 6–12 Months | Imaging modalities or surgery |
| Zerva, 2006 (41) | Total or near-total thyroidectomy | Tg obtained before RAI | TSH >30 IU/mL | Not reported | Excluded if TgAb positive | 15 Months following RAI therapy | 123I whole body scan |
| Zhao, 2017 (42) | Total or near-total thyroidectomy | Tg before RAI | Thyroid hormone withdrawal (TSH >30 mIU/mL) | Not reported; serial Tg at median interval 8 days | Excluded if TgAb >46 IU/mL | Not reported (at time of RAI therapy) | 131I whole body scan with SPECT in patients with negative WBS |
CT, computerized tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; RAI, radioactive iodine; rhTSH, recombinant human thyrotropin; SPECT, single-photon emission computerized tomography; Tg, thyroglobulin; TgAb, thyroglobulin antibody; TSH, thyrotropin; US, ultrasound; WBS, whole body scan.