Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal

Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 μg/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 μg/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 μg/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 μg/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and 131I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 μg/liter during THST.

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Serum thyroglobulin and 131I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer

Acta Endocrinologica ◽

10.1530/eje.0.1480019 ◽

2003 ◽

pp. 19-24 ◽

Cited By ~ 86

Author(s):

M Torlontano ◽

U Crocetti ◽

L D'Aloiso ◽

N Bonfitto ◽

A Di Giorgio ◽

...

Keyword(s):

Thyroid Cancer ◽

Lymph Node ◽

Thyroid Hormone ◽

Differentiated Thyroid Cancer ◽

Whole Body ◽

Whole Body Scan ◽

Serum Thyroglobulin ◽

Risk Patients ◽

Node Metastases

OBJECTIVE: The 'standard' postoperative follow-up of patients with differentiated thyroid cancer (DTC) has been based upon serum thyroglobulin (Tg) measurement and (131)I whole body scan ((131)I-WBS) after thyroid hormone (T(4)) treatment withdrawal. However, (131)I-WBS sensitivity has been reported to be low. Thyroid hormone withdrawal, often associated with hypothyroidism-related side effects, may now be replaced by recombinant human thyroid stimulating hormone (rhTSH). The aim of our study was to evaluate the diagnostic accuracy of (131)I-WBS and serum Tg measurement obtained after rhTSH stimulation and of neck ultrasonography in the first follow-up of DTC patients. DESIGN: Ninety-nine consecutive patients previously treated with total thyroidectomy and (131)I ablation, with no uptake outside the thyroid bed on the post-ablative (131)I-WBS (low-risk patients) were enrolled. METHODS: Measurement of serum Tg and (131)I-WBS after rhTSH stimulation, and ultrasound examination (US) of the neck. RESULTS: rhTSH-stimulated Tg was <or=1 ng/ml in 78 patients (Tg-) and >1 ng/ml (Tg+) in 21 patients, including 6 patients with Tg levels >5 ng/ml. (131)I-WBS was negative for persistent or recurrent disease in all patients (i.e. sensitivity = 0%). US identified lymph-node metastases (confirmed at surgery) in 4/6 (67%) patients with stimulated Tg levels >5 ng/ml, in 2/15 (13%) with Tg>1<5 ng/ml, and in 2/78 (3%) who were Tg-negative. CONCLUSIONS: (i) diagnostic (131)I-WBS performed after rhTSH stimulation is useless in the first follow-up of DTC patients; (ii) US may identify lymph node metastases even in patients with low or undetectable serum Tg levels.

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MANAGEMENT OF ENDOCRINE DISEASE: The role of rhTSH in the management of differentiated thyroid cancer: pros and cons

Acta Endocrinologica ◽

10.1530/eje-19-0149 ◽

2019 ◽

Vol 181 (4) ◽

pp. R133-R145 ◽

Cited By ~ 4

Author(s):

Luca Giovanella ◽

Leonidas H Duntas

Keyword(s):

Thyroid Cancer ◽

Thyroid Hormone ◽

Differentiated Thyroid Cancer ◽

Clinical Role ◽

Serum Thyroglobulin ◽

Thyroid Hormone Withdrawal ◽

Clinical Sensitivity ◽

Pros And Cons ◽

Recombinant Human Thyrotropin

The use of recombinant human thyrotropin (rhTSH) testing in the diagnosis and therapy of differentiated thyroid cancer (DTC) has been adopted over the last two decades as an alternative to the classical thyroid hormone withdrawal avoiding the threat of hypothyroidism. Serum thyroglobulin (Tg) measurement is crucial for monitoring DTC patients over time. Until about a decade ago, optimal sensitivity of Tg assays for the detection of smaller disease foci required Tg measurement after thyrotropin (TSH) stimulation, carried out following thyroid hormone withdrawal or rhTSH administration. In very recent years, significant improvements in assay technology have resulted in highly sensitive Tg (hsTg) assays, sufficiently sensitive to obviate the need for rhTSH stimulation in most DTC patients. The aim of this paper is to review and discuss, via a ‘pros and cons’ approach, the current clinical role of rhTSH to stimulate radioiodine (RAI) uptake for treatment and/or imaging purposes and to increase the clinical sensitivity of Tg measurement for monitoring DTC patients when high-sensitive Tg assays are available.

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A Comparison of Recombinant Human Thyrotropin and Thyroid Hormone Withdrawal for the Detection of Thyroid Remnant or Cancer1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.11.6094 ◽

1999 ◽

Vol 84 (11) ◽

pp. 3877-3885 ◽

Cited By ~ 1

Author(s):

Bryan R. Haugen ◽

Furio Pacini ◽

Christoph Reiners ◽

Martin Schlumberger ◽

Paul W. Ladenson ◽

...

Keyword(s):

Thyroid Cancer ◽

Thyroid Hormone ◽

Metastatic Disease ◽

Effective Means ◽

Thyroid Tissue ◽

Whole Body ◽

Serum Thyroglobulin ◽

Thyroid Hormone Withdrawal ◽

Recombinant Human Tsh ◽

Tsh Stimulation

Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

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