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[Treatment of patients with nodular goiter].

The authors discovered nodular patterns in the thyroid gland of 18.8% of persons among many thousands subjected to periodical medical examination. The high detection rate of nodular patterns in the thyroid corresponds completely to the findings of post-mortem examinations. The number of nonpalpable nodules detected by the ultrasonic method exceeds the number of those palpated (55.2% and 44.8%, respectively). Ultrasonic examination with thin-needle aspiration biopsy followed by cytologic examination is the most informative method by which new malignant growths are identified. Patients with nonpalpable patterns measuring less than 1 cm in diameter which are revealed by ultrasound must be kept under active dynamic observation if there are no signs of malignancy. Patients with larger patterns and suspected cancer must be treated by operation.

Aged↗

[Fine needle puncture biopsy and methods to image the thyroid gland in the diagnosis of nodular goiter].

A retrospective analysis of the findings of fine needle puncture biopsy of the thyroid in 256 patients operated on for nodular goiter is presented. Cytologic findings coincided with the histologic in 84.8% of cases. The coincidences were the most frequent in (multiple) nodular colloid goiter and thyroid cysts (95.7 = 100%) and the least so in solitary adenoma (65.4%) predominantly of a follicular structure. In thyroid cancer the data correlated in 75% of cases. The presence of cystous changes in adenoma made the investigation less informative. Findings of ultrasonic examination of the thyroid coincided with operative findings in 87.5% of patients with (multiple) nodular goiter and in 86.1% of those with adenomas. Ultrasonography as a method for thyroid imaging is preferable to scintigraphy (scanning) and is an optimal supplement to puncture biopsy of the thyroid.

Adenoma↗

Nodular goiter: a histo-cytological study with some emphasis on pitfalls of fine-needle aspiration cytology.

A comprehensive comparative histo-cytological study of 48 nodular goiters from an endemic goiter region was undertaken. Practically all features observed on the biopsies were identified, although with less frequency, on the smears. In agreement with previous observations, characteristic components of nodular goiter (NG) in aspirates included small to medium size epithelial cells with regular round nuclei, honeycomb pattern, large follicles, papillae showing the previously mentioned epithelial features, oxyphilic cells, and moderate to abundant background colloid material and thyroid phagocytes (macrophages). All eight features occurred together in only 2% of the studied cases, seven in 6 (12.5%), six in 4 (8%), five in 6 (12.5%), four in 12 (25%), three in 6 (12.5%), two in 11 (23%), and one in 2 (4%) cases, respectively. Regardless of the number and combination of features present, specific identification of NG on the smears may not always be possible and diagnostic pitfalls include thyroid cyst, Hashimoto's thyroiditis, granulomatous lesions, and, more frequently, follicular neoplasia. Our findings suggest that thyroid aspirates should be analysed with critical clinico-pathological approach and surgery considered only for nodules that are clinically suspicious or unresponsive to hormonotherapy when a diagnosis of follicular neoplasia is made.

Biopsy, Needle↗

[Migration inhibition test with thyroid membrane antigen in Graves-Basedow disease and nodular goiter].

The evaluation of the migration inhibition test with thyroid membrane antigen was carried out in 20 patients with Graves' disease, 13 patients with neutral nodular goiter and 13 healthy subjects. A significant inhibition of migration by thyroid antigen as compared to the control group was demonstrated only in the patients with Graves' disease (the value of the migration index was 0.57 +/- 0.07). The respective value was 0.79 +/- 0.16 in patients with nodular goiter and 0.85 +/- 0.11 in healthy subjects. The results obtained indicate the practical value of the migration inhibition test in diagnosing the thyroid diseases having an autoimmune background.

Adult↗

[Percutaneous puncture thyroid cytology: cyto-histologic correlations in 136 nodular goiter surgical patients].

Percutaneous puncture for cytologic study was performed in 136 patients with nodular goiter. All patients were operated on and correlation of cytologic and histologic findings was obtained. Echographic study revealed a solid aspect in 72%, cystic aspect in 10% and mixed in 18%. The cytologic findings were classified as: benign--hyperplasia--, chronic thyroiditis, follicular neoplasm (adenoma and carcinoma), oxyphilic neoplasm (adenoma and carcinoma), papillary cancer, medullary cancer, anaplastic cancer and insufficient material. Surgery revealed cancer in 36 patients (26.5%). There were 3 false positives for cancer in the cytologic study. Percutaneous cytology was able to detect 88% of patients with cancer and 83% of patients with neoplasms. False negatives for cancer (n = 5) were due to insufficient sample (2), topographic error (2) and cytology error (1). No follicular cells were obtained in 13 patients with cystic follicular adenoma and the diagnosis was missed. Surgery confirmed that 24 of 25 patients with cystic aspect on echography had a basic underlying lesion. Thus, percutaneous cytology of the thyroid is useful in the evaluation of patients with cold nodules. Main limitations of the technique are found in patients with cystic lesions and follicular neoplasms.

Adolescent↗

[Nodular goiter and thyroid cancer].

The author analyzes 151 cases of differentiated carcinoma of the thyroid gland and 112 cases of nodular nontoxic goiter. In 83.5% of patients with carcinoma of the thyroid gland there was no "goiter anamnesis", in 71.5% of the carcinoma patients the tumoral node was located in the unchanged tissue of the thyroid gland, in 28.5% the nodular goiter was found in the contralateral lobe and only in 10% of observations carcinoma took place against the background of the nodular goiter and adenoma. There is no reason to consider the nodular goiter as pre-cancer, and the surgical treatment of the nodular goiter as prophylaxis of carcinoma of the thyroid gland. The indications to operation for benign nodular formations of the thyroid must be restricted.

Adenocarcinoma, Follicular↗

[The analysis of exercise efficiency and autonomic function in children with nontoxic nodular goiter during suppressive L-thyroxine therapy].

UNLABELLED: The aim of the study was the analysis of exercise efficiency and the function of the autonomic system in children with a nontoxic nodular goiter (NNG) subjected to TSH suppression. The study comprised 17 children, aged 11-18 years, with NNG treated with suppressive L-thyroxine doses for 6-36 months (mean 24 months). Exercise efficiency was examined on a moving track according to the protocol of Bruce. Analysis of the autonomic function was based on functional tests of the circulatory system and monitoring of the QTc interval. A group of healthy children with a negative heart and thyroid history served as control. Statistically significant acceleration of the heart rate (p<0.01) was found in NNG patients subjected to TSH suppression, compared with controls. The remaining results included a fall in exercise efficiency parameters:work load (p<0.001) and duration (p<0.003), metabolic equivalent (p<0.005), and the maximal oxygen consumption index Vo2 (p<0.005) at normal values of double product. A significant decrease was revealed in the ejection fraction during exercise (61+/-1.9 vs 67+/-5.9 p<0.001) in the group of children with nontoxic nodular goiter. CONCLUSIONS: 1. In the subclinical state of hyperthyroidism no functional disorders were observed in the autonomic system, which controls the circulatory system. 2. Exercise tolerance was reduced in patients with nontoxic nodular goiter subjected to TSH suppression. 3. A relationship was found between the level of thyroid hormones (TSH, FT4) indicating the subclinical state of hyperthyroidism and the acceleration of heart rate, reduction in the ejection fraction of the left ventricle of the heart after exercise and shortening of load test duration. 4. Higher rest values of heart rate were observed in children treated with suppressive doses of L-thyroxine, compared with controls.

English Abstract↗

Current treatment of nodular goiter with hyperthyroidism (Plummer's disease): surgery versus radioiodine.

BACKGROUND: First described 9 decades ago by H. S. Plummer, thyroidectomy and radioiodine remain the 2 therapeutic modalities for toxic nodular goiter. The aim of this study was to determine its optimal treatment. METHODS: The presentation, operative treatment, pathology, and clinical course of 362 consecutive patients treated at our institution for Plummer's disease from 1990 to 1999 were retrospectively reviewed. RESULTS: Three hundred forty-six patients (63 men and 283 women) were treated surgically (181, 53%), with radioiodine (RAI, 157, 45%), or a combination of both (8, 2%). Mean age was 62 years (surgical, 55 years; RAI, 69 years). Nearly half were symptomatic, 51 (15%) with airway or swallowing compromise and 110 (32%) with cardiac complications. The estimated goiter size was larger (60 g or greater) in surgical (72 patients, 38%) than medically treated (45 patients, 29%) patients. RAI treatment dose averaged 28 mCi; 10 patients (6%) required a second treatment, and 8 patients failed treatment and required subsequent thyroidectomy. Types of thyroidectomy included total (29 patients, 16%), near-total (47 patients, 26%), bilateral subtotal (46 patients, 25%), and unilateral (58 patients, 32%). One month after treatment, hyperthyroidism had resolved in 96% of the surgical patients but only 6% of the RAI patients (mean time to resolution, 5.4 months). Only 55 (38%) of the RAI patients' goiters reduced in size. Recurrent laryngeal nerve paralysis and hypoparathyroidism each occurred in 3 (2%) patients. CONCLUSIONS: Surgical treatment results in rapid, reliable resolution of hyperthyroidism and removal of the nodular goiter with low morbidity and no mortality. RAI is also safe and effective, usually requiring a single dose, but the results are delayed and it usually fails to resolve a goiter.

Adolescent↗

Treatment of recurrent nodular goiters with percutaneous ethanol injection: a clinical study of twelve patients.

Twelve patients who had previously undergone thyroid surgery received percutaneous ethanol injection (PEI) treatment because of recurrent nodular goiter (3 with a toxic [TN], 2 with a nontoxic cystic [NCN], and 7 with a nontoxic solid nodule [NSN]). Two of the 12 had recurrent nerve palsy contralateral to the nodule. Each patient received a mean total dose of 0.88 mL of ethanol per milliliter of nodular volume. Ethanol was injected in a mean of 3.5 sessions for solid and 3 sessions for NCN. In most cases, a slight to moderate burning pain was experienced during and for 12-48 hours after PEI treatment, and one patient experienced temporary hoarseness. One patient with TN and 2 patients with NSN became hypothyroid, 7 patients with nontoxic nodules remained euthyroid, 1 with TN became euthyroid, and a previously hyperthyroid patient with TN became subclinically hyperthyroid 1-year posttherapy. The nodule shrank by more than 50% of the pretreatment volume in all patients (8.6 +/- 2.6 vs. 2.9 +/- 1.2 mL in TN, and 12.3 +/- 4.9 vs. 4.16 +/- 2.54 mL in nontoxic nodules, pretreatment vs. 1 year posttreatment volume, respectively). With regard to the increased risk of reoperation, PEI treatment can be proposed for patients with recurrent nodular goiter requiring surgery.

Administration, Cutaneous↗

Molecular aspects of the pathogenesis of nodular goiters, thyroid nodules and adenomas.

One of the most significant results of recent molecular thyroid research on the pathogenesis of nodular goiters may be the finding that not only thyroid adenomas but also many thyroid nodules are clonal in origin and thus are true benign tumors. Both clonal and polyclonal nodules may coexist within the same nodular goiter. Since clonal nodules may secondarily acquire a heterogeneous phenotype, they can become morphologically indistinguishable from polyclonal lesions. The molecular mechanisms that generate thyroid nodules and adenomas are still poorly understood. Certainly, the recent detection of activating mutations in the TSH receptor and the Gs alpha gene in a subset of toxic thyroid adenomas and nodules may explain the generation of hyperfunction in these tumors, but there is strong evidence that these mutations are not the unique and primary cause of tumor formation. In this respect the concept of natural occurring heterogeneity of thyroid growth and function can provide a plausible explanation for the early stages of nodular transformation: If a thyrocyte has a high intrinsic growth potential or if it is affected by overexpression of a protooncogene or a growth factor or hit by an oncogene or other molecular events, the cell will outgrow and form a tumor. The inborn qualities of proliferating cells or the sequence of various genetic alterations in proliferating cells will in turn determine the phenotype and function of the tumor.

Adenoma↗

The lack of nocturnal serum thyrotropin surge in patients with nontoxic nodular goiter may predict the subsequent occurrence of hyperthyroidism.

TSH secretion, with particular regard to the nocturnal TSH surge, was evaluated in 115 subjects with non-toxic nodular goiter. All patients were clinically and biochemically euthyroid. After 18-36 months of follow-up (mean, 24 months), hyperthyroidism occurred in 21 (18%; group 1), while the remaining 94 remained euthyroid (82%; group II). The analysis of hormonal data at the time of first observation showed that the 2 groups had similar total and free T4 and T3 serum concentrations. Morning serum TSH values in group I were lower than those in group II patients (0.6 +/- 0.1 vs. 1.1 +/- 0.1 mU/L; P less than 0.001); this difference was even more striking for the nocturnal values (0.6 +/- 0.1 vs. 2.2 +/- 0.2 mU/L; P less than 0.0001); nocturnal values were significantly lower than morning values in group II, but not in group I. The mean peak TSH value after TRH was also significantly reduced in group I (5.5 +/- 0.4 vs. 9.2 +/- 0.7 mU/L; P less than 0.001). Morning TSH values in group II did not differ from those in controls (1.3 +/- 0.1 mU/L), whereas nocturnal and TRH stimulated peak TSH values were slightly but significantly lower. The nocturnal serum TSH values in control subjects were 62-390% higher than morning values. The nocturnal TSH surge was abolished in 18 of 21 (86%) group I patients and in 7 of 94 (8%) group II patients. TRH testing resulted in an absent or blunted TSH responses in 5 subjects in group I and 6 in group II. Analysis by the Galen and Gambino predictive model; comparing the abolition of the nocturnal TSH surge and the abnormal TRH test as predictors of the subsequent occurrence of hyperthyroidism, showed that the former had higher sensitivity (86% vs. 24%) and predictivity (72% vs. 45%). In conclusion, the results of the present study demonstrate that the evaluation of the nocturnal TSH surge may be useful in identifying patients with nontoxic nodular goiter in whom hyperthyroidism may eventually occur. Patients who lack the nocturnal serum TSH surge are more prone to develop thyroid hyperfunction; their thyroid status should, therefore, be more carefully and frequently monitored.

Adult↗

Use of fine-needle aspiration cytology and frozen section in the management of nodular goiters.

BACKGROUND: This study evaluates the role of frozen section (FS) in surgical decisions for nodular thyroid disease when a preoperative fine-needle aspiration cytology (FNAC) is available. MATERIAL AND METHOD: The charts of 113 patients who underwent thyroidectomy for nodular goiter were reviewed. Each patient underwent FNAC, FS, or both. Results were compared with the final pathologic examination to evaluate their effectiveness in predicting malignancy. RESULTS: The sensitivity and specificity of FNAC alone (49 patients) were 73% and 93.5%, respectively, and of FS (111 patients) 68% and 99%, respectively. The result of fine-needle aspiration cytology was: benign (n = 8), malignant (n = 13), indeterminate (n = 25), and nondiagnostic (n = 3). All cases diagnosed as benign on FNAC were benign on final pathology, but of the six FS performed in these cases, four were benign and two were suspect. Of the 13 FNAC that were interpreted as malignant, 11 and 10 proved to be malignant on final pathology and FS, respectively. The 25 indeterminate cases on FNAC were on final pathology benign (n = 21) and malignant (n = 4) and on frozen section were benign (n = 12), malignant (n = 2), and suspect (n = 11). CONCLUSION: When results of FNAC are interpreted as benign or malignant, FS is of little value, because it does not change the extension of thyroidectomy. FS proved useful in determining the extent of thyroidectomy only when results of the FNAC were suspect or atypical.

Adult↗

Prolactin secretion and nodular goiter. (Hypothetical correlations).

In a group of 129 female patients with nodular goiter, Graves' disease and primary hypothyroidism, the PRL and TSH secretions were studied in parallel. Concurrent changes in the two hormones were evident only in conditions of marked hyper- or hypothyroidism. In the patients with non-toxic nodular (single or multiple) goiter the TSH showed low or normal values, while the PRL appeared normal or elevated. From these results two important conclusions can be drawn: 1. the T3 and T4 levels interact with PRL secretion concomitantly with TSH only when they undergo a huge deviation from the normal range; 2. the goitrogenic action of PRL that has been reported in experimental animals cannot be excluded in man.

Adolescent↗

Fas and Bcl-2 protein expression in thyrocytes of patients with nodular goiter.

OBJECTIVE: The relative expression of the apoptotic protein Fas and the anti-apoptotic protein Bcl-2 were investigated in thyrocytes from patients with non-toxic nodular goiter (NTG, n=20) and Hashimoto's thyroiditis (HT, n=5), who underwent fine-needle aspiration biopsy for diagnostic reasons. On the basis of the clinical and cytological findings, the patients with NTG were sub-classified into the group of those with colloid nodules (n=9), degenerative nodules (n=6) and adenomatous nodules (n=5). METHODS: Fine-needle biopsy aspirates were examined by immunocytochemistry for Fas and Bcl-2 expression, using specific monoclonal antibodies. For the evaluation of Fas and Bcl-2 immuno-reactivity, an expression index, based on the number of cells with positive staining, was used: grade 1 included samples with positive staining in <20% of cells; grade 2 included samples with 20-50% positive cells; and grade 3 included samples with >50% positive cells. RESULTS: Fas protein expression was generally low (grade 1) in patients with nodular goiter, in contrast to patients with HT, in whom high expression was detected (grade 3). Only in aspirates from degenerative nodules (four out of six), and in which lymphocytes were also present, was Fas expressed at an intermediate level (grade 2). On the other hand, Bcl-2 protein was differentially expressed among the nodule subtypes. It was low in colloid and degenerative nodules (grade 1) but high in adenomatous ones (grades 2 and 3). Bcl-2 expression was also low in patients with HT (grade 1). CONCLUSION: It is concluded that in comparison to HT, where there is up-regulation of Fas and down-regulation of Bcl-2 protein, Fas expression is low in human goiter, indicating low apoptotic activity. The regulation of Bcl-2 protein differs between adenomatous and colloid nodules, suggesting that this protein may play a role in the differentiation of thyroid nodules.

Adult↗

Solitary nodular goiter. Review of cytomorphologic features in 441 cases.

OBJECTIVE: To study the cytomorphologic features of solitary nodular goiters (SNG). STUDY DESIGN: May-Grünwald-Giemsa-stained smears in 441 SNG diagnosed by ultrasonography and fine needle aspiration (FNA) and found to have optimum cellular material at review were subjected to detailed cytologic assessment. The age of the patients ranged from 11 to 75 years, with a median of 35. Male: female ratio was 69:372. The parameters for cytologic assessment included cellularity, colloid content, acinar formation, papillary formation, intranuclear cytoplasmic inclusions, nuclear grooves, marginal vacuoles, Hürthle cells and various inflammatory cells. Histopathology reports on thyroidectomy specimens were available in 27 cases from two Delhi hospitals. RESULTS: Hyperplastic nodules (68 cases) differed significantly from colloid goiters (269 cases) by having more cases with excessive cellularity, acinar formation and marginal vacuoles (P < .001). There was also a significant difference with respect to papillary formation and moderate-to-excessive colloid content (P < .001). As compared to hyperplastic nodules, neoplasms (60 cases) had a significantly higher number of cases with papillary formation, intranuclear inclusions and nuclear grooves but lower number of cases with marginal vacuoles (P < .01-.001). Among neoplasms, usual papillary carcinoma (19 cases) differed from follicular neoplasms (20 cases) with respect to acinar formation, papillary formation and nuclear grooves (P < .001). A significant difference was also observed with respect to colloid content and nuclear inclusions. Follicular variant of papillary carcinomas (FVPC) (10 cases) emerged as a distinct cytologic entity following review and differed from usual papillary carcinomas in having a higher number of cases with acinar formation, tubular formation and marginal vacuoles (P < .01-.001) and lower number of cases with nuclear grooves (P = .05). FVPC also differed from follicular neoplasms with respect to papillary formation, tubular formation, intranuclear inclusions and nuclear grooves (P < .01-.001). Overall cytohistologic agreement was achieved in 24 of 27 (88.9%) cases. CONCLUSION: Detailed cytologic assessment of FNA smears-in SNG was helpful in highlighting parameters that differentiate between various types of goiters.

Adolescent↗

Evaluation of routine basal serum calcitonin measurement for early diagnosis of medullary thyroid carcinoma in seven hundred seventy-three patients with nodular goiter.

The aims of the study were to identify medullary thyroid cancer (MTC) in its earliest stages by screening patients with basal calcitonin measurements and to determine whether basal serum calcitonin measurements should be a part of the routine evaluation of a nodular goiter. Basal serum calcitonin levels were obtained from 75 patients (female:male 57:18, mean age 42.8 years, range with 18-76 years) with nonnodular thyroid disease as controls. Their mean basal calcitonin level was 7.8+/-0.4 pg/mL with a range of 5-27 pg/mL. Seven hundred seventy-three patients with nodular goiter were included in the study (female:male 586:187) with the mean age of 46.1 years (range 17-78). Four patients had elevated basal serum calcitonin levels ranging between 150-1000 pg/mL. These 4 patients underwent surgery. MTC was confirmed by histopathology in all 4. One patient's mother and brother were also diagnosed as MTC as a result of family screening. Basal serum calcitonin levels were higher than 150 pg/mL in these patients. Fine needle aspiration biopsy (FNAB) of 2 of 4 MTC patients were incorrectly diagnosed as papillary carcinoma; another had malignant cytology and the fourth had benign cytology. None were diagnosed as MTC on the basis of FNAB. In conclusion, calcitonin measurement is an effective method for the diagnosis of MTC. Measurement of basal calcitonin levels in patients with malignant or suspicious FNAB may be a cost-effective approach to screen for MTC. High basal serum calcitonin levels increase the chance of curative therapy by diagnosing MTC in the early stages. It is superior to FNAB for diagnosis of MTC.

Adolescent↗