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Over a period of almost 10 yr, we carried out a prospective study of the neuropsychological development of the offspring of 16 women from a moderately iodine-deficient area (area A) and of 11 control women from a marginally iodine-sufficient area (area B) whose thyroid function had been monitored during early gestation. Attention deficit and hyperactivity disorder (ADHD) was diagnosed in 11 of 16 area A children (68.7%) but in none from area B. Total intelligence quotient score was lower in area A than in area B children (92.1 +/- 7.8 vs. 110 +/- 10) and in ADHD children when compared with both non-ADHD children from the same area and control children (88.0 +/- 6.9 vs. 99.0 +/- 2.0 and 110 +/- 10, respectively). Seven of 11 ADHD children (63.6%) were born to the seven of eight area A mothers who became hypothyroxinemic at early gestation, whereas only one of five non-ADHD children was born to a woman who was hypothyroxinemic at 20 wk of gestation. So far, a similar prevalence of ADHD has been reported only in children with generalized resistance to thyroid hormones. This might suggest a common ADHD pathogenetic mechanism consisting either of reduced sensitivity of the nuclear receptors to thyroid hormone (generalized resistance to thyroid hormones) or reduced availability of intracellular T3 for nuclear receptor binding. The latter would be the ultimate consequence of maternal hypothyroxinemia (due to iodine deficiency), resulting in a critical reduction of the source of the intracellular T3 available to the developing fetal brain.

Recombinant human TSH (rhTSH)-stimulated thyroglobulin (Tg) measurement and (131)I whole body scan (WBS) have been validated as informative tests in the postsurgical follow-up of differentiated thyroid carcinoma. We report the diagnostic accuracy of Tg measurement and diagnostic WBS, alone or in combination, after rhTSH stimulation in a retrospective, consecutive series of patients undergoing follow-up for differentiated thyroid cancer. Routine procedures also include neck ultrasound in every patient and post-therapy WBS when indicated. We studied 340 consecutive patients with differentiated thyroid carcinoma, previously treated with near-total thyroidectomy and (131)I thyroid ablation, scheduled for routine diagnostic tests. At baseline on L-T(4)-suppressive therapy, 294 patients had undetectable (<1 ng/ml) serum Tg and negative anti-Tg autoantibodies (TgAb), 25 patients had undetectable serum Tg and positive TgAb, and 21 patients had detectable serum Tg and negative TgAb. These patients were tested for the presence of active disease by rhTSH stimulation. The results of our study showed that rhTSH-stimulated Tg alone had a diagnostic sensitivity of 85% for detecting active disease and a negative predictive value (NPV) of 98.2%. After adding the results of neck ultrasound, sensitivity increased to 96.3%, and the NPV to 99.5%. rhTSH-stimulated WBS had a sensitivity of only 21% and a NPV of 89%. The combination of rhTSH-stimulated Tg and WBS had a sensitivity of 92.7% and a NPV of 99%. We conclude that the rhTSH-stimulated Tg test combined with neck ultrasonography has the highest diagnostic accuracy in detecting persistent disease in the follow-up of differentiated thyroid carcinoma. A detectable level of serum Tg on L-T(4), its conversion from undetectable to detectable after rhTSH, and/or a suspicious finding at ultrasound will allow the identification of patients requiring therapeutic procedures without the need for diagnostic WBS.

Introduction: After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. Objective: To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). Methods: We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. Results: Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P!0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. Conclusions: Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

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Total body weight is usually employed to calculate the amount of l-T(4) to be administered in patients with thyroid diseases. The aim of this study was to evaluate the effect of body composition on l-T(4) requirements. Body composition was assessed by dual energy x-ray absorptiometry in 75 patients on TSH-suppressive l-T(4) therapy after conventional thyroid ablation for differentiated cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3 mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There was a much stronger association between the l-T(4) dosage and lean body mass (P < 0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of regional tissue composition showed peripheral lean mass as the best correlate with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was observed with peripheral fat mass. In conclusion, individual l-T(4) requirements are dependent on lean body mass. Age- and gender-related differences in l-T(4) needs reflect different proportions of lean mass over the total body weight. An estimate of lean mass may be helpful to shorten the time required to attain a stable dose of l-T(4), particularly in subjects with high body mass index values that may be due either to increased muscular mass or to obesity.

Stimulation with recombinant human TSH (rhTSH) has been introduced in clinical practice as an effective alternative to thyroid hormone withdrawal for the diagnostic follow-up (Tg measurement and 131-iodine whole-body scan) of patients with differentiated thyroid cancer. The present study was specifically aimed to evaluate the utility of rhTSH-stimulated serum Tg measurements in patients with undetectable serum Tg values, on L-T(4) therapy, as the only test to differentiate patients with persistent disease from patients who are disease-free. We studied 72 consecutive patients with differentiated thyroid cancer, previously treated with near-total thyroidectomy and 131-I thyroid ablation. Admission criteria were: an undetectable (<1 ng/ml) serum Tg, on L-T(4) therapy, and negative anti-Tg antibodies. The study design consisted of a Tg-stimulation test after rhTSH, during L-T(4), followed by diagnostic WBS and serum Tg measurement off L-T(4). After rhTSH, serum Tg remained undetectable in 41 of 72 patients (56.9%). A negative rhTSH Tg test agreed with an undetectable hypo-Tg in 36 of 41 cases (87.8%), all without evidence of metastatic disease at hypo-WBS. In 5 of 41 cases (12.2%), hypo-Tg was detectable (1.1-7.8 ng/ml), in association with negative hypo-WBS or faint uptake in the thyroid bed. Serum Tg converted from undetectable to detectable after rhTSH in 31 of 72 patients (43.1%), with a peak Tg ranging between 1.2 and 23.0 ng/ml. Hypo-Tg was always detectable in these patients (100% concordance), and it was significantly higher than rhTSH-stimulated Tg (P < 0.0002). Hypo-WBS was positive in 23 of 31 patients (74.2%), showing thyroid residues in 12, cervical lymph nodes in 7, and lung metastases in 4 cases. In 8 of 31 cases, hypo-WBS was negative, despite detectable serum Tg. Thus, rhTSH-stimulated Tg was able to detect all cases of documented local or distant metastases. In conclusion, our data indicate that, in patients with undetectable basal levels of serum Tg, rhTSH-stimulated Tg represents an informative test to distinguish disease-free patients (not requiring WBS) from diseased patients (requiring further diagnostic and/or therapeutic procedures).

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