Michelle Aparecida Ribeiro Borges

Ultrasonographic Differentiation Between Metastatic and Benign Lymph Nodes in Patients With Papillary Thyroid Carcinoma

The purpose of this study was to evaluate the ultrasonographic characteristics of metastatic lymph nodes in patients with papillary thyroid carcinoma.

Preparation with Recombinant Human Thyroid-Stimulating Hormone for Thyroid Remnant Ablation with 131I Is Associated with Lowered Radiotoxicity

Preparation with recombinant human thyroid-stimulating hormone (rhTSH) for thyroid remnant ablation results in lower extrathyroidal radiation than does hypothyroidism. The objective of this prospective study was to compare the damage caused by 131I (3.7 GBq) when these 2 preparations are used. Methods: Ninety-four consecutive patients who underwent total thyroidectomy and remnant ablation with 3.7 GBq of 131I were studied. Thirty patients (group A) received rhTSH, and 64 (group B) were prepared by levothyroxine withdrawal. Damage to salivary glands, ovaries, and testes; hematologic damage; and oxidative injury were evaluated by measurement of serum amylase, follicle-stimulating hormone (FSH), complete blood count, and plasma 8-epi-PGF2α before and after radioiodine. The 2 groups were similar in sex, age, and the results of baseline assessment. Results: The rate of successful ablation (stimulated thyroglobulin level < 1 ng/mL and negative findings on neck ultrasonography) was 90% in group A and 80% in group B. Considering only patients with a preablation thyroglobulin level greater than 1 ng/mL, these rates were 80% and 70.6%, respectively. Only 1 patient (3.3%) reported transient headaches with rhTSH. Elevated FSH levels after therapy were observed in 4 of 9 (44%) men in group A versus 16 of 18 (89%) in group B (P < 0.03), with a mean increase of 105% versus 236% (P < 0.001), respectively. In women, elevated FSH was observed in 1 of 13 (7.7%) patients in group A versus 6 of 30 (20%) in group B (P = 0.4), with a mean increase of 65% versus 125% (P < 0.001). Thrombocytopenia or neutropenia occurred in 2 of 28 (7%) patients in group A versus 12 of 56 (21.4%) in group B (P = 0.1), with a mean decrease of 20% versus 45% and 25% versus 52% (P < 0.01) for neutrophils and platelets, respectively. Hyperamylasemia and symptoms of acute sialoadenitis occurred in 11 of 30 (36.6%) versus 48 of 60 (80%) (P < 0.001) and in 9 of 30 (30%) versus 35 of 60 (58.3%) (P = 0.01), respectively. 8-Epi-PGF2α was found to be elevated after 131I in 14 of 25 (56%) patients in group A versus 45 of 45 (100%) in group B (P < 0.001), with a mean increase of 60% versus 125% (P < 0.001). Conclusion: The lower radiotoxicity with rhTSH, suggested in dosimetry studies, was confirmed in the present prospective investigation, and this advantage occurred without compromising the efficacy of treatment.

Is stimulation of thyroglobulin (Tg) useful in low‐risk patients with thyroid carcinoma and undetectable Tg on thyroxin and negative neck ultrasound?

Objective  To determine the usefulness of thyroglobulin (Tg) stimulation in low‐risk patients with undetectable Tg on T4 and negative neck ultrasound (US) after initial therapy of thyroid carcinoma.

Ultrasonographic differentiation of cervical lymph nodes in patients with papillary thyroid carcinoma after thyroidectomy and radioiodine ablation: a prospective study.

OBJECTIVE The objective of the present study was to validate an ultrasound (US) classification of cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC) after thyroidectomy and radioactive iodine (131I) ablation. METHODS We performed a prospective study in which the patients were submitted to thyroidectomy and 131I ablation and then followed until neck US revealed LN(s) ≥5 mm. A total of 288 LNs from 112 patients with PTC were evaluated. Patient management was based on LN characteristics grouped according to the classification system studied here. RESULTS The presence of microcalcifications and/or cystic degeneration of cervical LNs were highly suggestive of a metastatic etiology (specificity of 99.4%). In contrast, the most sensitive finding for LNs affected by PTC was the absence of an echogenic hilum (sensitivity of 100%). In the absence of these findings (microcalcifications, cystic degeneration, echogenic hilum), a metastatic etiology was the most likely in the case of a round LN (specificity of 89%). The differentiation of a spindle-shaped LN without a visible hilum by Doppler analysis permitted us to dichotomize an initial probability of metastases of 13% in 25% (with peripheral vascularization) versus 3.3% (without peripheral vascularization). CONCLUSIONS Our results confirm that the classification proposed for cervical LNs in patients with PTC is valid for determining patient management following initial therapy.

Malformations in the offspring of women with thyroid cancer treated with radioiodine for the ablation of thyroid remnants

RATIONALE Since ovarian function is only temporarily compromised by radioiodine therapy, many women with thyroid cancer treated with radioiodine can become pregnant. The present study evaluated the evolution of these pregnancies and the consequences for the offspring. PATIENTS AND METHODS We retrospectively analyzed 78 pregnancies of 66 women submitted to total thyroidectomy, followed by radioiodine therapy 3.75-5.5 GBq (131)I, mean 4.64 GBq). In all patients, conception occurred one year after ablative therapy (mean of 30 months). Age ranged form 19 to 36 years (mean of 30.6 years) at the time of radioiodine treatment and from 23 to 39 years (mean of 32.8 years) at the time of conception. RESULTS Four (5.1%) of the 78 pregnancies resulted in spontaneous abortions. Three (4%) of the 74 deliveries were preterm and there was no case of stillbirth. The birthweight was > 2500 g in 94.6% of the children (+/- SD: 3350 +/- 450 g) and only one infant (1.3%) presented an apparent malformation at birth (intraventricular communication). No difference in the age at the time of radioiodine therapy or conception or in radioiodine dose was observed between pregnancies with an unfavorable outcome and those with a favorable outcome. CONCLUSION We conclude that pregnancies that occur 12 months after ablative therapy are safe.

Is Doppler ultrasound of additional value to gray-scale ultrasound in differentiating malignant and benign thyroid nodules?

The objective of this study was to evaluate whether Doppler ultrasound (DUS) is of additional value to gray-scale ultrasound (GSUS) in predicting the benign or malignant nature of thyroid nodules. A total of 1,502 solid thyroid nodules ≥ 10 mm were evaluated. Suspicious vascularity (predominantly or exclusively central blood flow) was observed in only 5% of the nodules. This finding showed 96% specificity, but only 15% sensitivity. GSUS alone showed sensitivity and specificity of 88.7% and 68.2%, respectively, which did not improve with the addition of DUS (sensitivity of 89.4% and specificity of 66.4%). In non-suspicious nodules on GSUS, the type of vascularity on DUS did not modify the risk of malignancy, which was low. In suspicious nodules on GSUS, suspicious vascularity on DUS increased the risk of malignancy, but non-suspicious vascularity did not reduce this risk. DUS provided no additional value to GSUS in predicting the benign or malignant nature of thyroid nodules.

Elevated plasma factor VIII and von Willebrand factor in women with type 2 diabetes: inflammatory reaction, endothelial perturbation or else?

The association between type 2 diabetes and cardiovascular disease is long recognized. Although perturbations of haemostatic markers have been shown to be associated with macrovascular disease in patients with type 2 diabetes, it is unclear whether these are primarily due to endothelial dysfunction or a result of inflammation. The present study was undertaken to elucidate whether elevated levels of factor VIII (FVIII) and von Willebrand factor (vWF) in women with type 2 diabetes represent endothelial dysfunction, inflammation or an alternate mechanism. Sixty-four women with type 2 diabetes were evaluated using ultrasonography Doppler for carotid intima–media thickness (IMT) and were classified as group A – having no (<1 mm), group B – mild (≥1 mm and no plaque) and group C – moderate (≥1 mm and presence of plaque and stenosis) macrovascular disease. Several haemostatic markers including, FVIII, vWF and fibrinogen were assessed. In addition, thrombomodulin, a marker for endothelial damage, and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, were also measured. A significant association of elevated FVIII was found in group B and C patients (i.e. patients with IMT ≥1 mm and with plaque). Elevated fibrinogen and vWF levels were also found but confined to group C patients. No significant difference among subgroups was found for any other variable evaluated (hsCRP, thrombomodulin and FVII). In conclusion, plasma FVIII levels are elevated in women with type 2 diabetes and macrovascular disease. It also appears that this is not mediated by inflammation or endothelial injury and is likely to be due to an alternate mechanism.

Ablative treatment of thyroid cancer with high doses of 131I without pre-therapy scanning.

ObjectiveTo determine the success of ablative treatment using fixed high doses of 131I in patients with thyroid cancer. MethodsA retrospective study was conducted on 274 patients who received ablative treatment without previous scanning, with the dose being based on surgical staging: stage I patients (tumour restricted to the thyroid) received 3.7 GBq, and stage II (lymph node metastases) and stage III patients (extra-thyroid invasion) were treated with 5.5 GBq. Successful treatment was defined as a negative control scan. ResultsOne hundred and sixty patients were classified as stage I and 114 as stages II or III. Forty-six patients presented ectopic uptake on post-therapy scans (10% in stage I and 26% in stage II or III). Among stage I patients, the efficacy of treatment was 78.7%. A 47% failure rate was associated with metastases, and among patients without metastases who did not respond to treatment, thyroid bed uptake >5% on post-therapy scans was observed in 61%. Patients with stage II or III showed 62.2% efficacy. Twenty-three of the 43 (53%) unsuccessfully treated patients in this group had metastases and of the 20 patients without metastases, 14 (70%) presented thyroid bed uptake >5%. There were no differences between the responsive and non-responsive groups in terms of age, gender, histological type or size of the primary tumour. ConclusionEmpirical treatment presented 72% efficacy (higher in stage I) and failure was associated with the presence of metastases and large thyroid remnants; factors that can be evaluated by pre-therapy whole-body scanning.

PAI-1 and D-dimer in type 2 diabetic women with asymptomatic macrovascular disease assessed by carotid Doppler.

Asymptomatic diabetic patients with different degrees of macrovascular complications can present different hemostatic changes. At this study, plasminogen activator inhibitor-1 (PAI-1) and D-dimer were evaluated in 12 women without diabetes and 64 type 2 diabetic women. All patients were classified into 3 different categories according to the carotid intima-media thickness (IMT) assessed by Doppler: 25 with <1 mm (normal), 15 with >1 mm and without plaque (intermediate), and 24 with stenosis lower than 50% of the vessel lumen (plaque). The results showed increased plasma D-dimer in type 2 diabetic women with carotid plaque when compared to the other groups. High levels of PAI-1 were observed in all the 3 groups of diabetic women when compared to women without diabetes. Our results suggest that high levels of PAI-1 in type 2 diabetic women are only associated with diabetes and are not associated with macrovascular progression; however, it seems that D-dimer plasma levels are associated with carotid plaque.

Completion thyroidectomy in patients with thyroid carcinoma initially submitted to lobectomy

In their article entitled ‘Circulating ghrelin levels in the newborn are positively associated with gestational age’, Bellone et al . (2004) found no correlation between ghrelin levels in cord blood and anthropometric or biochemical parameters (GH, IGF-I, insulin, glucose and leptin levels) in adequate for gestational age newborns. I would like to point out some observations concerning this study. Endocrine activities of ghrelin are mediated by GH secretagogue receptor (GHSR)-1a, a G-protein-coupled receptor mainly expressed in the pituitary and hypothalamus, previously identified as the receptor for GH secretagogues, a group of molecules endowed with strong GH release activity (Howard et al ., 1996). Ghrelin may be esterified with octanoic acid on serine 3. Acylation of ghrelin is required for GHSR-1a activation, whereas des-acyl ghrelin, which is far more abundant than octanoylated ghrelin (Hosoda et al ., 2000), does not bind GHSR-1a and it is devoid of any pituitaric or pancreatic endocrine activity (Kojima et al ., 1999; Muccioli et al ., 2002; Torsello et al ., 2002; Broglio et al ., 2003). The polyclonal antibody used by the authors (Phoenix Pharmaceutical, Belmont, CA, USA) does not distinguish octanoylated and nonoctanoylated ghrelin. Therefore, the authors measured the total ghrelin levels in cord blood and they did not measure the levels of active ghrelin. I believe that the correlation of total ghrelin levels with anthropometric and biochemical parameters may be misleading because only octanoylated ghrelin and not total ghrelin has biological effects and in particular stimulates GH secretion. Interestingly, Linco Research (St Charles, MO, USA) produces an antibody that is specific for the biologically active form of ghrelin with the octanoyl group on serine 3 (cat. no. GHRA-88HK). The active form of ghrelin is very unstable and labile in plasma; as a consequence, special precautions must be taken. In particular, blood samples should be kept in ice and processed as quickly as possible after blood is withdrawn; in addition the plasma should be acidified. In the light of these considerations, the authors’ conclusion that ‘ghrelin levels are not associated to GH secretion or to IGF-I levels, suggesting that ghrelin is not involved in perinatal GH hypersecretion’ cannot be justified on the basis of the presented data. Further investigations are required to correlate the levels of octanoylated ghrelin levels in cord blood with those of GH, IGF-I, insulin, glucose and leptin.