Thyroglobulin measurement in fine-needle aspiration biopsy of metastatic lymph nodes after rhTSH stimulation.

BACKGROUND: Thyroglobulin measurement in the washout of the needle used in fine-needle aspiration cytology (FNAC) has been proposed for the early detection of lymph node metastasis both in patients with or without serum thyroglobulin antibodies; however, up to now, there have been no reports that recombinant human thyrotropin (rhTSH) stimulation modifies thyroglobulin measurement in lymph node aspirates. METHODS: We described, after rhTSH stimulation, the switching from undetectable to detectable levels of thyroglobulin in fine-needle aspiration fluid from a suspected metastatic lymph node in 2 patients. RESULTS: We hypothesized that thyroglobulin levels in the lymph node increased after rhTSH stimulation. The excess thyroglobulin saturates all thyroglobulin antibody binding sites and becomes detectable, explaining why it was undetectable when TSH was suppressed. CONCLUSION: On the basis of our experience, we suggest submitting to thyroglobulin measurement in the washout of the needle used in FNAC all patients with detectable serum thyroglobulin antibody after rhTSH stimulation.

Morbid obesity in women is associated to a lower prevalence of thyroid nodules.

BACKGROUND: Few studies have recently showed functional and morphological changes of the thyroid gland in relation to obesity. To our knowledge, no data are available about the prevalence of thyroid nodules in female obese patients. The aim of this study was to investigate the prevalence of thyroid nodules in morbidly obese women. METHODS: One hundred eight consecutive female obese patients were selected from those referred to our medical and surgery outpatients providing that following criteria were satisfied: (1) affected by morbid obesity (body mass index (BMI) >40 kg/m(2)); (2) no previous diagnosis of thyroid disease; (3) biochemically proven euthyroid state at the time of recruitment. Ninety-seven control subjects, constituted by normo-weight and/or slightly overweight (BMI ≤ 30 kg/m(2)) women, should satisfy the above criteria 2 and 3. All the subjects were submitted to ultrasound investigation. RESULTS: The two groups of patients displayed no differences for age and fT4 levels. Obese patients clearly showed a lower prevalence of thyroid nodules [odds ratio 0.294, 95% confidence interval 0.206-0.382]. A single nodule was found in 23% of obese patients as compared to 65% of control subjects (p < 0.0001). No difference for age (year) was found between obese and non-obese subjects with nodules (40.5 ± 8.2 vs. 44.2 ± 8.9, respectively, p = 0.07). CONCLUSIONS: Our data clearly show a significantly lower prevalence of thyroid nodules in morbidly obese patients. Further studies are needed to confirm and to understand this first observation.

TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients.

OBJECTIVE: To assess the interplay between metformin treatment and thyroid function in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The acute and long-term effects of metformin on thyroid axis hormones were assessed in diabetic patients with primary hypothyroidism who were either untreated or treated with levothyroxine (L-T4), as well as in diabetic patients with normal thyroid function. RESULTS: No acute changes were found in 11 patients with treated hypothyroidism. After 1 year of metformin administration, a significant thyrotropin (TSH) decrease (P < 0.001) was observed in diabetic subjects with hypothyroidism who were either treated (n = 29; from 2.37 +/- 1.17 to 1.41 +/- 1.21 mIU/l) or untreated (n = 18; 4.5 +/- 0.37 vs. 2.93 +/- 1.48) with L-T4, but not in 54 euthyroid subjects. No significant change in free T4 (FT4) was observed in any group. CONCLUSIONS: Metformin administration influences TSH without change of FT4 in patients with type 2 diabetes and concomitant hypothyroidism. The need for reevaluation of thyroid function in these patients within 6-12 months after starting metformin is indicated.

Aggressive thyroid carcinoma showing thymic-like differentiation (CASTLE): case report and review of the literature.

Carcinoma showing thymic-like differentiation (CASTLE) is a rare tumour of the thyroid, which arises from ectopic thymic tissue or remnants of branchial pouches. A systematic review of English literature evidences less than thirty cases; from them, it clearly appears that CASTLE is considered an indolent slow-growing neoplasia even when lymph nodes metastasis are present. We describe a case of very aggressive CASTLE, which showed seeding along fine needle aspiration tract.

Reduced thyroid volume and nodularity in dyslipidaemic patients on statin treatment.

BACKGROUND: Little information is available concerning the possible antiproliferative effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on the thyroid gland. We have hypothesized that the antiproliferative effects of statins observed in thyroid cell lines in vitro may have a clinical counterpart that could be detected by investigating the prevalence and size of thyroid nodules in patients on long-term treatment with statins. METHODS: We retrospectively evaluated 135 dyslipidaemic patients receiving statin therapy continuously for at least 5 years, and 137 controls. All the subjects were submitted to ultrasound investigation of the thyroid gland, to establish prevalence, number and volume of thyroid nodules. RESULTS: Subjects treated with statins showed markedly lower prevalence of thyroid nodules (36.3%vs. 67.9%, P < 0.001), as well as reduced number and smaller total volume of lesions, as compared to the control group. A logistic regression analysis, taking into account age, sex, risk factors for the development of thyroid nodules and concomitant drug treatment, revealed that treatment with statins remained the only important predictor of the presence of thyroid nodules [odds ratio (OR) 0.312, 95% confidence interval (CI) 0.156-0.625, P < 0.001] besides risk factors. CONCLUSIONS: Our data provide the first circumstantial evidence of an association between HMG-CoA reductase inhibitor treatment and reduced prevalence, number and volume of thyroid nodules. This finding may be explained by an antiproliferative and/or pro-apoptotic effect of long-term statin treatment on thyroid cells, in vivo.

Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves' disease: a 120 months prospective study.

In most trials, at least 30-60% of patients with Graves' disease treated with antithyroid drugs relapse within 2 years after therapy withdrawal. At present, there are no prognostic parameters available early in treatment to indicate patients likely to achieve long-term remission. Because thyrotropin receptor autoantibodies (TRAb) are specific for Graves' disease, we evaluated the ability of their levels and of their rate of change to predict long-term prognosis. In our study 216 consecutive patients with newly diagnosed Graves' disease started a therapy with methimazole. Patients were treated until they achieved euthyroidism and TRAb were measured at 6-month intervals throughout a follow up of 120 months. Our study demonstrated that at the onset of hyperthyroidism patients' age, sex, fT4 levels and goiter size had no prognostic value in predicting long-term prognosis (respectively p = 0.79; p = 0.98; p = 0.83; p = 0.89). On the contrary, at the time of diagnosis TRAb titer was a good predictor of the final outcome (p<0.001); a titer equal to (or) more than 46.5 UI/L could identify patients who had never achieved long-term remission with a sensitivity of 52% and a specificity of 78%. Also fall rate of TRAb at 6 months of follow up and after therapy withdrawal were useful to predict the final outcome (p<0.001). At 6 months of follow up the time of therapy withdrawal, a decrease of TRAb lower than 52.3% or even its increase could identify patients who had never achieved permanent remission with a sensitivity of 55% and a specificity of 79.1%. No single parameter among TRAb, satisfactory identified a sub-set of patients who achieved long remission. Accordingly to our data, the best result in predicting long term remission is probably given by the presence of at least one of the two features evaluated at 6 months (TRAb titer and/or percentage of TRAb fall rate), with a sensitivity of 63% and specificity of 88%. TRAb titers evaluated both at the onset of hyperthyroidism that at 6 months of therapy or their rate of fall at 6 months and at ATD withdrawal are predictors of outcome. However, the presence of at least one, between titers of TRAb or their rate of fall at six months, resulted to be the best predictor of remission with the higher sensitivity and specificity.

Prognostic factors in well-differentiated thyroid carcinoma in patients treated and followed in the same institution.

AIM: To test the prognostic significant of clinicopathologic factors in patients affected by well-differentiated thyroid carcinoma (WDTC). METHODS: A retrospective review of patients treated for WDTC (thyroidectomy and a radioactive iodine (1131) thyroid ablation) at our Institute with a minimum of 10 years of follow-up was carried out. The unfavourable prognosis at the end of the follow-up was defined as persistence/recurrence of WDTC or death due to the cancer. RESULTS: 234 patients (162 female, 72 male), mean age of 47.6 +/- 166 years, were included in this study (mean follow-up 158.4 +/- 34.8 months): 78 (33.4%) subjects had persistence/recurrence of neoplasia while 5 (2.1%) died for cancer. The multivariate regression showed that prognostic factors were old age, size of cancer, detectable thyroglonulin levels six months after metabolic ablation, and DeGroot staging system. DISCUSSION: Our mortality rate is lower (2.1%) than reported in literature (10%): this could be explained by the different pathological classification and treatment. The mortality rate appears higher in patients treated with emitiroidectomy and TSH suppressive therapy than in those with total thyroidectomy and I131 ablation. Even if we have chosen an "aggressive" therapy and our mortality rate is lower, one third of patients have persistence/recurrence of cancer: it seems that tumour recurrence rate better reflects clinical problems related to cancer. CONCLUSION: WDTC has with a good disease-specific survival but a significant recurrence rate. The most important predictors are the old age and the size of lesion. We suggest a radical surgery followed by radiometabolic ablation in all patients with WDTC.

Thyroid nodule shape suggests malignancy.

OBJECTIVE: To evaluate if a nodule with shape taller than wide (anteroposterior/transverse diameter ratio, A/T > or = 1) is a good predictor of malignancy independent of the size. METHODS: We retrospectively examined the cytological and histological results of 7455 nodules (5198 patients) referred for ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from January 1991 to September 2004. RESULTS: A suitable FNAC was obtained from 6135 nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules, SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious lesions after FNAC. The size of carcinoma nodules was not significantly associated with the occurrence of extracapsular growth (large nodules (LN): 10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS). Malignant lesions showed microcalcifications more frequently than benign nodules (72.2 vs 28.7%; P < 0.001; (odds ratio, OR(confidence intervals, CI) = 9.9(7.2-13.4)). Similarly, A/T > or = 1 (76 vs 40%; P < 0.001; OR(CI) = 8.6(5.5-13.1)), blurred margins (52.8 vs 18.8%; P < 0.001; OR(CI) = 7.7(5.6-10.2)), solid hypo-echoic appearance (80.6 vs 52.4%; P < 0.001; OR(CI) = 3.2(2.2-4.3)) and intranodular vascular pattern (type 2) (61.6 vs 49.7%; P < 0.001; OR(CI) = 1.7(1.3-2.3)) were significantly more frequent in malignant than in benign nodules. CONCLUSIONS: Our data show that no single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC. We concluded that A/T > or = 1 with at least two of US features (microcalcification, blurred margins, hypo-echoic pattern) is today the best compromise between missing cancers and cost-benefit.

Outcome of patients surgically treated for various forms of hyperthyroidism with differentiated thyroid cancer: experience at an endocrine center in Italy.

PURPOSE: The incidence and aggressiveness of thyroid cancer associated with hyperthyroidism remains a subject of much controversy. The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid cancer, and to determine whether cancer becomes more aggressive with different forms of hyperthyroidism. METHODS: We retrospectively studied 2,449 patients assessed for hyperthyroidism between 1985 and 2001. All patients with a "cold" nodule on scintigraphy, such as those with Graves' disease and a concomitant solid nodule, underwent fine-needle aspiration biopsy (FNAB). Criteria for surgery were cytological findings indicative of malignancy, goiter with signs of tracheal or esophageal compression, side effects of antithyroid drug therapy, or Graves' disease with multiple relapses after therapy withdrawal or responsiveness to antithyroid drugs. RESULTS: Thyroid cancer was diagnosed more frequently in patients with Graves' disease (6.5%) than in those with uninodular toxic goiter (UTG) (4.4%) or multinodular toxic goiter (MTG) (3.9%). Lymph node involvement was found in 56% of the patients with Graves' disease, in 23% of those with MTG, and in none of those with UTG. Distant metastases were found in one patient with Graves' disease. CONCLUSIONS: Cancers associated with Graves' disease seems to be more aggressive than those associated with MTG or UTG. Thus, we suggest that patients with Graves' disease be carefully monitored for the detection of thyroid nodules. Ultrasonography seems to be the best modality to detect such nodules.

Is the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules a sonographic criteria for recommending fine-needle aspiration cytology?

BACKGROUND: As a consequence of the increasing application of ultrasound (US) technology, the detection of asymptomatic nonpalpable thyroid nodules has generally increased. The aim of our study was to assess if the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules (A/T) > or = 1 could be a sonographic criterion for recommending fine-needle aspiration cytology (FNAC). METHODS: From January 2002 to January 2004, 828 consecutive solid nonpalpable thyroid nodules were evaluated by ultrasonography, colour-Doppler and FNAC in our department. Cases were selected from 2217 patients, referred to our thyroid unit for US-guided FNAC from the greater Brescia area, an endemic zone for goitre. Entry criteria included the presence at US of a solid thyroid nodule that was nonpalpable at physical examination, euthyroid condition and no previous diagnosis of thyroid malignancy. All patients with suspicious or malignant cytology underwent surgery. RESULTS: One hundred and twenty-seven nodules with inadequate cytology were excluded from the study. Thyroid malignancy was observed in 67 (9.6%) nodules. At US, cancers presented a solid hypoechoic appearance in 79.1% of cases, blurred margins in 47.8%, microcalcification in 73.1%, intranodular vascular pattern in 56.7% and A/T > or = 1 in 83.6%. A hypoechoic appearance (OR 4.3), blurred margins (OR 2.6), microcalcification (OR 6.1), intranodular vascular pattern (OR 10.2) and A/T > or = 1 (OR 22.4) were independent risk factors of malignancy. CONCLUSIONS: A/T > or = 1 in conjunction with at least one other sonographic risk factor is able to detect the majority of carcinoma and, moreover, it limits the FNAC procedures to only 15.9% of all the nodules.

Long-term treatment of acromegaly with lanreotide: evidence of increased serum parathormone concentration.

The somatostatin analogue lanreotide is effective in reducing growth hormone levels in patients with acromegaly. Acromegaly is characterized by calcium homeostasis alterations. The aim of our study was to evaluate the effects of lanreotide on bone turnover markers in a group of acromegalic patients and to verify a possible increase of intact parathormone (iPTH) levels in a transient or persistent way. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before treatment and on months 3 and 24. In short-term treatment (3 months), lanreotide significantly decreased GH, IGF-I, serum calcium, osteocalcin and alkaline phosphatase levels, but increased iPTH level (49 +/- 16.7 vs pre-treatment 28.3 +/- 7.6 ng/L, p<0.001). During long-term study (24 months) GH and IGF-I were significantly still low; serum calcium and alkaline phosphatase levels returned to pre-treatment levels. iPTH level was significantly still higher compared with pre-treatment (46.4 +/- 9.2 vs 28.3 +/- 7.6 ng/L, p<0.05). No changes were seen in serum albumin, creatinine and vitamin D during short and long term treatment. The changes of most bone markers during lanreotide treatment can be explained by the decrease of GH and IGF-I. The increase of iPTH concentration suggests that lanreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the lanreotide could contribute to this "secondary" hyperparathyroidism. The clinical relevance of these long-standing effects needs to be further investigated.