Serum thyroglobulin measurement in the follow-up of patients treated for differentiated thyroid cancer.

Determination of thyroglobulin (Tg) in serum represents a key element in the follow-up of patients treated for differentiated thyroid cancer (DTC). The sensitivity and the specificity of the assay strongly affects the clinical impact. Most of patients are disease-free after thyroidectomy and iodine radioablation; 15% of them show over time persistent or recurrent disease; of these, 5% dies due to worsening of disease. This implies that the follow-up procedures should have a high negative predictive value to reduce as possible the unnecessary diagnostic tools and a high positive predictive value to identify the few patients with persistent/recurrent disease. The recent international guidelines are based on thyroglobulin measurement after thyroid-stimulating hormone (TSH) stimulation. More recent studies suggest that follow up based on serial measurements of basal (i.e. unstimulated) Tg show a higher predictive value than the single measurement after stimulation. Large and multicenter studies are necessary to modify the current guidelines.

The ovarian cycle as a factor of variability in the laboratory screening for primary aldosteronism in women.

Primary aldosteronism is increasingly investigated in hypertension being associated with an elevated cardiovascular risk. Aldosterone has been reported to increase in the luteal phase in normal women but to our knowledge the influence of the ovarian cycle on the first screening for primary aldosteronism (that is, on the levels of plasma aldosterone and its relationship to PRA levels) was never investigated. We measured hormonal levels during one cycle in 26 low-renin mild hypertensive outpatients. LH, FSH, 17 beta-estradiol, progesterone, aldosterone and PRA were assayed at the seventh, fourteenth, twenty-first and twenty-eighth days of the cycle after 30 min of recumbency. Aldosterone and PRA increased from the seventh (follicular phase) to twenty-first day (luteal phase) from 11.2 to 17.8 ng 100 ml(-1) and from 0.23 to 0.35 ng ml(-1) h(-1), respectively (both P=0.004) The proportion of patients with aldosterone >15 ng 100 ml(-1) significantly increased from the follicular to the luteal phase, (8/26 vs 19/25, P=0.018); a similar increase was found for Aldosterone-PRA Ratio >30 combined with either a minimum PRA value of 0.5 ng ml(-1) h(-1) or aldosterone >15 ng 100 ml(-1) (7/26 vs 16/25 and 7/26 vs 17/25 respectively, P<0.05). Aldosterone was positively related to PRA and progesterone. Higher aldosterone levels may be frequently encountered in the second part of the ovarian cycle in low-renin hypertensive women. This variability appears to be an important factor to be taken into account in the first-step laboratory screening for primary aldosteronism and should be considered in the process of standardization of the diagnostic work-up for this disease.

Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer.

OBJECTIVE: Serum thyroglobulin (Tg) represents a highly specific biomarker for detecting residual thyroid tissue/recurrence/metastases after treatment for differentiated thyroid cancer (DTC). We evaluated the clinical impact of a highly sensitive Tg assay during routine follow-up of DTC patients. DESIGN: Tg values were measured by a highly sensitive Tg assay during L-T4 suppressive therapy and after recombinant human thyrotropin (rh-TSH) stimulation and were compared with those obtained by using a routinely employed Tg assay. PATIENTS: One hundred and sixty consecutive DTC-treated patients (papillary carcinoma n = 124, follicular carcinoma n = 36) were studied. MEASUREMENTS: Measured variables included neck ultrasonography, (131)I whole body scanning, and Tg assayed by Immulite (Diagnostic Products Corporation, Los Angeles, CA) and by the highly sensitive Access assay (Beckman Coulter, Brea, CA). RESULTS: During L-T4 therapy, measurable Tg was found in only two patients (1% of total) by Immulite and in 23 patients (14% of total) by Access assay. Using the institutional cut-off of 2 microg/l after rh-TSH, a negative response was associated with undetectable Immulite Tg during L-T4 therapy in all patients (negative predictive value, NPV, 100%) and in 137 out of 152 patients with Access assay (NPV 90%). Measurable Tg during L-T4 therapy was found in 17% of positive patients with Immulite and in 100% of patients with Access, respectively. CONCLUSIONS: The use of a highly sensitive Tg assay may represent a useful diagnostic tool for improving the interpretation of Tg results during monitoring of DTC-treated patients for the early detection of recurrence and for optimizing the use of the more expensive rh-TSH test.

Serum thyroglobulin measurement: clinical background and main methodological aspects with clinical impact.

It is worldwide recognized that circulating thyroglobulin (Tg) measurement represents a fundamental tool in the follow-up of patients affected by differentiated thyroid cancer (DTC). In the last American and European Consensus Conferences, a surveillance guideline has been extended to the use of thyrotropin (TSH)-stimulated Tg levels for thyroidectomized patients without clinical evidence of residual tumor with Tg below 1 microg/l during TSH suppression. Therefore, sensitivity of the methods is critical to detect small amounts of Tg and/or to observe minimal changes in Tg concentration in the management of DTC patients. It has been proposed that only methods providing the greatest distinction between the lower limit of euthyroid reference range (approximately 3.0 microg/l) and the functional sensitivity limit (at least 1 microg/l) of the assay may offer a suitable clinical sensitivity for detecting small amounts of functioning thyroid tissue in TSH-suppressed state (1 g of normal thyroid tissue results in a serum Tg of approximately 1 microg/l when TSH is normal and about 0.5 microg/l when TSH is suppressed). In the last 30 years sensitivity of Tg measurements has been greatly improved, nowadays methods can achieve very good analytical and functional sensitivity to give reliable results also in the very low concentration range (between 0.1 and 1 microg/l). In addition, with the introduction of fully automated assays, results can be readily available to the clinician while patients are still in the ambulatory area. However, despite the large clinical use of Tg measurement, wide differences (by threefold) still remain between results produced in different laboratories due to poor standardization, heterogeneity of circulating Tg, interference from auto-antibodies, differences in the epitope recognition by antibodies used in the assays.

Diagnostic performance of a new highly sensitive thyroglobulin immunoassay.

The determination of serum thyroglobulin (Tg) is commonly used for detecting the presence of residual thyroid tissue or cancer recurrence in patients treated for differentiated thyroid cancer (DTC). The aim of the study was to evaluate the performance characteristics of a recently introduced fully automated chemiluminescent immunoassay, based on four monoclonal antibodies and which produces results in 40 min. Analytical sensitivity (0.01 micro g/l) was computed from 20 replicates of the zero calibrator and of the 'Tg-free' sample pool. Functional sensitivity (0.1 micro g/l at 20 coefficients of variation percent) was determined from the imprecision profile obtained by assaying ten serum pools. The reliability of the measurements in the low concentration range (Tg<1 micro g/l) has been checked by progressive dilution with the 'Tg-free' serum of a sample pool at 5.27 micro g/l; measured values were very close to the expected values (recovery 100-133%).Cut-off at the 99th percentile in DTC stage I 'disease-free' treated patients (n=53) was 0.16 micro g/l. Tg measurement in basal conditions during L-thyroxine suppression therapy and 5 days after recombinant human TSH stimulation was performed in 22 patients with DTC. In 80% of patients with basal Tg<0.1 micro g/l (12/15), Tg remained<0.1 micro g/l after stimulation, and in all of these Tg was<1 micro g/l. Our results have indicated the optimal analytical and clinical performance of this Tg immunoassay and encourage further studies on larger populations of patients with DTC.