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PubMed1988

Apparent isolated elevation of serum triiodothyronine level in a patient with a thyroid nodule.

Cystic thyroid nodules most commonly occur with a euthyroid state and appear as cold lesions on radioactive iodine scan. I describe a 32-year-old woman who presented during the third trimester of her second pregnancy with a toxic cystic lesion of the thyroid. In studies performed post partum, the serum free thyroxine (T4) index was normal, while the triiodothyronine (T3) level was elevated and thyrotropin level was low and unresponsive to thyrotropin-releasing hormone stimulation. Iodine 123 thyroid scan demonstrated localized nonsuppressible uptake over the nodule. Multiple echo-free (fluid-filled) cavities were observed by ultrasound study. Thyroid lobectomy demonstrated a thyroid colloid nodule with areas of cystic degeneration containing hyperplastic papillary projections. Postoperatively, the patient developed transient hypothyroidism followed by spontaneous recovery to euthyroidism with normal function of the suppressed gland. Blood obtained from the venous effluent of the thyroid nodule had extremely high T3 and T4 concentrations: 359.1 nmol/L and 2420 nmol/L, respectively, while peripheral venous blood showed isolated elevation of T3, to 4.6 nmol/L (normal, 1.2 to 3.1 nmol/L), and a normal T4 level of 116 nmol/L (normal, 64 to 154 nmol/L). Serum T3 and T4 thyroidal/peripheral ratios were close to one in two euthyroid patients undergoing neck surgery. Thus, thyroid nodules may present with isolated elevation of serum T3 levels despite increased thyroidal release of T4.

Adult↗
PubMed1999

[Surgical treatment of benign thyroid nodules].

Benign thyroid nodules is a significant clinical problem since it involves more than 90% of all thyroid surgery. This has led the authors to perform a retrospective study of 190 patients suffering from this pathology out of 299 patients who underwent surgery from 1979 to 1995. 89 total thyroidectomies and 101 radical hemithyroidectomies were performed in patients suffering from benign thyroid nodules. Two cases of recurrent monolateral paralysis were found as well as 3 cases of permanent hypoparathyroidism in those patients who underwent total thyroidectomies. The results of numerous authors as well as the present case review indicate that more radical surgery does not significantly affect the degree of permanent complications. For this reason the authors are convinced that such radical surgery should be the treatment of choice, particularly in young patients whose life expectancy is long and where the likelihood of recurrence is greater.

Adult↗
PubMed2006

Subacute thyroiditis: fine-needle aspiration cytology of 14 cases presenting with thyroid nodules.

Subacute thyroiditis (SAT) is usually diagnosed clinically without the need for fine-needle aspiration. The cytologic literature on this condition is therefore rare. We report on 14 cases of SAT presenting with thyroid nodules. The majority of patients were women with a mean age of 46 yr. All had pain/tenderness in the thyroid area accompanied by fever or an elevated ESR. The salient cytologic features included cellular smears; multinucleated giant cells in 100% of cases, some ingesting colloid or neutrophils; fibrous fragments with enmeshed inflammatory cells were a constant feature; follicular cells were scant to absent in most cases. Granulomas were rare. Colloid, when present was thick, with central cracks and frayed edges. One case was suspicious for malignancy. We conclude that the cytologic features of SAT are predictable, particularly, in the appropriate clinical setting. FNA is also helpful in ruling out concomitant neoplastic conditions.

Adult↗
PubMed1993

[Physiopathology of the autonomous thyroid nodule].

"Autonomous" thyroid nodule is a localized nodular lesion of the thyroid gland characterized by growth, iodine uptake and function, all independent from TSH control. These nodules represent a heterogeneous anatomic and clinical entity. The clinical diagnosis is based upon a negative suppression of nodule iodine uptake and scan imaging by T3 administration. The nodule function is determined by high serum thyroid hormone levels and/or low TSH (measured by ultrasensitive assay). Etiology and pathogenesis of these nodules is not yet completely clarified. Both genetic and environmental factors determine nodule growth and function: thyroid cells, in fact, are genetically heterogeneous and may have intrinsic (congenital) characteristics that may promote the growth of cellular clones having mitotic and functional activity that is partially independent of TSH. In these particular cell clones, environmental factors like iodine deficiency or other goitrogens may favour the growth of autonomous nodules and also, by activating their function, may induce toxicity. The autonomous thyroid nodules need to be treated only when they become toxic: in this case both surgical excision or radioiodine may be used.

Humans↗
PubMed2005

High prevalence of suspicious cytology in thyroid nodules associated with positive thyroid autoantibodies.

OBJECTIVE: We assessed the association between thyroid autoimmunity and thyroid cancer in a retrospective series of unselected thyroid nodules submitted to fine-needle aspiration cytology (FNAC) to avoid the selection bias of surgical series. SUBJECTS AND METHODS: Ultrasound (US)-guided FNACs were obtained from 590 unselected consecutive patients with single thyroid nodules and positive (ATA + , n = 197) or negative (ATA - , n = 393) serum anti-thyroid antibody (ATA). Cytological results were classified in three classes of increased risk of malignancy: low risk or benign (class II); indeterminate risk (class III); and suspect or malignant (class IV). RESULTS: A higher prevalence of class III (28.9% vs 21.4%, P < 0.05) and class IV (18.8% vs 9.2%, P < 0.001) and lower prevalence of class II (52.3% vs 69.5%, P < 0.001) were found in ATA + vs ATA - nodules respectively. By multivariate logistic regression analysis ATA + conferred a significant risk (odds ratio (OR): 2.29 (95% confidence interval (CI): 1.39-3.76)) for class IV cytology independently from age and sex. In 106 patients where thyroidectomy was carried out, thyroid cancer was found in 54/61 (88.5%) patients with class IV nodules (with similar positive predictive value for cancer in ATA + (96.4%) and ATA- (81.8%) nodules), in 6/31 (19.3%) of class III nodules (all ATA - ) and in none of 14 class II nodules. Non-specific cytological atypias from hyperplastic nodules in lymphocytic thyroiditis probably accounted for the different prevalence of cancer in class III ATA + and ATA - nodules. Histologically proven thyroid cancer (mostly papillary) was then observed in a higher proportion (27/197 = 13.7%) of ATA + , when compared with ATA - nodules (33/393 = 8.4%, P = 0.044), but the significance of this finding is limited by the low number of class II nodules operated on. CONCLUSIONS: The presence of ATA + confers an increased risk of suspicious or malignant cytology in unselected thyroid nodules. Since ATA + is not responsible for increased false-positive class IV FNAC, our study provides indirect evidence supporting a significant association between thyroid carcinoma and thyroid autoimmunity, although further studies with a different design are needed for a definitive histological proof.

Adult↗
PubMed2003

[Thyroid nodules with calcification and thyroid carcinoma].

OBJECTIVE: To investigate the significance of thyroid calcification for diagnosis of thyroid carcinoma. METHODS: Retrospective analysis of 817 thyroid nodules' pre-operative ultrasonic and postoperative pathologic results. RESULTS: Total ultrasonic thyroid calcification ratio was 18.1% (148/817). Total pathologic thyroid calcification ratio was 19.6% (160/817), which in benign samples was lower than that in malignant samples (13.1% vs 53.5%, P < 0.01). Micro-calcification ratio in benign samples was lower than that in malignant samples (2.9% vs 38.6%, P < 0.01). CONCLUSIONS: Thyroid nodules with calcification especially micro-calcification is considered to be the most specific sign of thyroid carcinoma, so the detection of it should be an important diagnostic criterion.

Adolescent↗
PubMedDate not supplied

Localization of transferrin receptors (TFRs) in human non functioning thyroid nodules and in extranodular thyroid tissue.

In this research the TFR localization in non functioning human thyroid nodules and in the extranodular thyroid tissue, using an immunohistochemical technique, has been studied. For this study a monoclonal antibody (B3/25) against TFR and the peroxidase technique have been utilized. Moreover a morphometric comparative analysis was carried out based on the following parameters: 1) mean immunoreactive area for microscopic field, 2) mean value of immunoreactive follicular perimeter, 3) integrated optical density, 4) % of immunoreactive area on total examined area in nodular and extranodular tissue. The immunoreactivity was detected in some follicular cells in a number of follicles randomly distributed in the extra nodular tissue. As concern the non functioning thyroid nodules, the positivity was localized in the generality of the follicles both in the flattened epithelial cells of the larger follicles and in the cuboidal cells of the smaller ones. The morphometric parameters confirm a statistically significant difference of immunoreactivity between extranodular and nodular tissue. These results suggest that TF might play a role in the cellular proliferation of thyroid gland.

Cell Division↗
PubMed2002

Long-term follow-up of thyroid nodule growth.

Benign thyroid nodules are common in iodine deficient countries. Although many recent studies have addressed the molecular basis and short-term outcome of treatment in nodular thyroid disease, data on the long-term follow-up of thyroid nodule growth are widely lacking. The aim of the present study was to evaluate the long-term behaviour of benign thyroid nodules growth. We followed 109 consecutive patients seen at yearly intervals in our Outpatient Clinic for at least 3 years (range 3-12 years, mean 4.9 +/- 2.6 years) presenting with 139 benign nodules in uni- or multinodular goiters. The size of the nodules and thyroid glands was analysed retrospectively. The study included a spectrum of benign thyroid nodules, 86 functioning and 53 non-functioning. 27 patients were treated with levothyroxine, 8 with iodide and 16 with a combination of both. 58 patients were not treated mainly because of thyroid functional autonomy. Patients with overt hyperthyroidism or suspected malignancy by fine-needle aspiration were excluded from the study. The nodules and glands were assessed by ultrasonography at yearly intervals and documented by photoprints. Relevant growth was defined as an increase in nodule volume of at least 30%. For statistical analyses, Cox Proportional Hazard Model and life-table analyses according to Kaplan-Meier were performed. Most thyroid nodules grew slowly but continuously during follow-up. After about 3 years, half of the nodules had increased their volume by at least 30%. Growth of the nodules was significantly faster than of the corresponding thyroid glands (p < 0.0001). Age and sex of the patients and size or function of the nodules at initial presentation were not significantly related to their growth. Suppression of TSH did not affect growth of the nodules irrespective of the source of thyroid hormones, endogenous or by administration of levothyroxine. In conclusion, benign thyroid nodules have a slow intrinsic growth potential, which is apparently higher than that of the non-nodular tissue. In this study, not only nodular but even non-nodular goiter growth continues in the majority of patients. Exogeneous factors, including therapy with levothyroxine and/or iodide, appear to have little effect on the growth behaviour.

Adolescent↗
PubMed1994

Management of thyroid nodules.

Clinically apparent thyroid nodules occur in about 5 percent of the population. Because most patients with thyroid nodules present initially to their primary care physician, family physicians should have a thorough understanding of the diagnosis and treatment of thyroid nodules. The history and physical examination may be helpful in detecting thyroid nodules but are not useful in predicting malignancy. Furthermore, laboratory studies, ultrasonography and nuclear medicine scans do not reliably differentiate between benign and malignant thyroid nodules. In most cases, fine-needle aspiration biopsy can accurately identify malignant thyroid nodules. Fine-needle aspiration biopsy is safe and can be performed in an office setting.

Biopsy, Needle↗
PubMed2004

Lack of correlation for sodium iodide symporter mRNA and protein expression and analysis of sodium iodide symporter promoter methylation in benign cold thyroid nodules.

Cold thyroid nodules (CTNs) are characterized by a reduced iodide uptake in comparison to normal thyroid tissue. The sodium iodide symporter (NIS) is the first step in thyroid hormone synthesis and mediates the active iodide transport in the thyroid cells suggesting that decreased iodide uptake could be a result of changes in NIS expression or molecular defects in the NIS gene. In contrast to previous studies, an intraindividual comparison of NIS mRNA expression in CTNs and their corresponding surrounding tissue was performed using direct detection of NIS mRNA. A significant reduction in NIS mRNA expression was detected in 86% of the 14 investigated CTNs. We hypothesized that human sodium iodide symporter (hNIS) transcriptional failure could be caused by primary molecular NIS gene defects and/or methylation of DNA in the NIS promoter. However, no mutation in the NIS cDNA nor in the NIS promoter region upstream up to-443 bp from the ATG start codon was detected. Therefore, primary molecular NIS gene defects were excluded. However, in 50% of CTNs with reduced NIS mRNA expression, the promoter region was hypermethylated. NIS mRNA expression in these hypermethylated CTNs only reached a maximum of 30% of the corresponding surrounding tissue. Hence, methylation of CpG islands in the NIS promotor could be a regulatory mechanism of NIS transcription in CTNs. Immunoblot revealed absent hNIS protein expression in the total cell membrane fraction in 45% of investigated nodules. In the majority of the remaining CTNs NIS protein expression was decreased in the nodule tissue compared to the corresponding surrounding tissue. For investigating protein expression immunhistochemistry has two advantages. First, the whole nodule area can be investigated, and second, NIS expression can be detected in areas where an immunoblot of a cell membrane fraction is negative. Interestingly, immunhistochemistry revealed higher NIS expression in 50% of CTNs compared to their corresponding surrounding tissues and NIS staining was predominantly intracellular. These data demonstrate that NIS protein expression does not reflect NIS mRNA expression. Therefore, factors that affect targeting of NIS to the plasma membrane are likely to be affected.

Blotting, Western↗
PubMed2005

Two novel mutations in the sixth transmembrane segment of the thyrotropin receptor gene causing hyperfunctioning thyroid nodules.

Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

Adult↗
PubMed1992

Thyroid nodules associated with Hashimoto thyroiditis: assessment with US.

Sonographic findings in 109 thyroid nodules in 104 patients with Hashimoto thyroiditis were retrospectively analyzed. Sixty patients underwent ultrasound (US)--guided fine-needle aspiration (FNA) biopsy (65 nodules, 24 palpable, 27 surgically confirmed), 14 of whom also underwent palpation-guided FNA (14 nodules, all palpable, all surgically confirmed). Forty-four patients (44 nodules, 25 palpable) underwent diagnostic US followed up with surgery. US-guided FNA helped differentiate between benign (n = 11) and malignant (n = 16) diseases (sensitivity, 100%). Two papillary carcinomas were falsely diagnosed as Hashimoto thyroiditis with palpation-guided FNA. Eight malignancies were not palpable, and correct diagnosis was obtained with US-guided FNA. Hyperechoic nodules were usually benign, and isoechoic nodules had a low frequency (13%) of malignancy. Most carcinomas were found in hypoechoic masses, and almost all lymphomas were found in markedly hypoechoic masses. Lymphoma was indistinguishable from pseudotumor in Hashimoto thyroiditis or adenomatous hyperplasia at US. US-guided FNA is helpful in making the histologic diagnosis in thyroid nodules associated with Hashimoto thyroiditis. US-guided FNA is clinically beneficial because it can help select patients who need surgery, avoiding unnecessary surgery for patients with nonneoplastic disorders.

Adenoma↗
PubMed1985

[Diagnostic strategy for a thyroid nodule].

Solitary thyroid nodules present as localized tumefactions of the thyroid gland readily detectable clinically. They are frequent (2-5% of the general population) and due to a variety of causes, each requiring a specific treatment; hence the need for a systematized diagnostic approach. On scintigraphic grounds, one can distinguish between "warm" or "extinctive" nodules (10% and 20% of the cases respectively), which are a priori benign, and "cold" nodules (70%), which in 1 out of 10 cases correspond to a differentiated epithelioma with excellent post-operative prognosis. Three methodological data call for comments: (1) the images supplied by technetium may differ from those supplied by radioactive iodine, which remains the reference radioisotope; (2) there is no clinical criterion of malignancy, but fluid-containing nodules are almost invariably benign; (3) needle cytology is the best means of selecting nodules for surgery and histology which is the only reliable diagnostic examination. We therefore propose, albeit with due caution, a diagnostic approach based on the sequence scintigraphy-needle exploration and cytology and aimed at limiting surgery to purely therapeutic purposes.

Biopsy, Needle↗
PubMed1984

Prediction of malignancy in the solitary thyroid nodule by physical examination, thyroid scan, fine-needle biopsy and serum thyroglobulin. A prospective study of 100 surgically treated patients.

A prospective study was made of 100 consecutive patients selected for surgical treatment of a clinically solitary thyroid nodule. Anamnestic data and findings at physical examination, thyroid scan, fine-needle aspiration biopsy and measurement of serum thyroglobulin were correlated with the postoperative histologic diagnoses. The histologic findings were malignant in 18 cases and benign in 82. Familial occurrence of benign goiter was reported more frequently by patients with benign than by those with malignant histology (46 and 11%). Of the 11 nodules that were hard at palpation, 7 were malignant. All 12 scintigraphically "hot" nodules were benign, but 13 of 59 "solitary, cold" nodules were malignant. The cytologic specimens were reviewed and reclassified. The needle aspirate was insufficient for cytologic diagnosis in 11 cases. Papillary carcinoma was cytologically recognized in four cases. Of 36 lesions cytologically reported to be neoplasm of unspecified type, 12 were histologically shown to be malignant, 20 were follicular adenomas and 4 were colloid goiter. Benign lesion was the cytologic diagnosis in 47 cases. One diagnosis was false negative, but the cancer lay beneath the index nodule. The thyroglobulin level was significantly higher in patients with thyroid cancer than in those with benign disorders, but the test's predictive value was low. Thyroglobulin levels more than tenfold the upper limit of normal were found only in three patients with thyroid cancer and two with thyrotoxicosis. Although all of the mentioned investigative data were helpful in the management of solitary thyroid nodule, fine-needle biopsy was the best single method. When cytologic examination shows malignancy or unspecified neoplasm, surgery is indicated. For most patients with cytologically benign lesions, careful follow-up will suffice.

Adult↗
PubMed2000

Efficient evaluation of thyroid nodules by primary care providers and thyroid specialists.

OBJECTIVE: To determine whether primary care providers and thyroid specialists at Gundersen Lutheran Medical Center are evaluating thyroid nodules efficiently by following recently published clinical guidelines. STUDY DESIGN: One-year retrospective chart review. PATIENTS AND METHODS: We reviewed patient records from 1996 and tabulated the use of fine-needle aspiration cytology, radionuclide scanning, and thyroid ultrasonography by 49 primary care physicians evaluating 81 thyroid nodules and by 5 thyroid specialists evaluating 29 thyroid nodules. The results were compared with our previous findings and those recently reported by others. RESULTS: Fine-needle aspiration cytology was widely used by both groups of Gundersen Lutheran healthcare providers. Primary care physicians used imaging studies modestly and generated $106 per patient in unnecessary costs. Thyroid specialists occasionally used radionuclide scanning but did not use thyroid ultrasonography; they generated $41 per patient in unnecessary costs. Overall, the introduction of fine-needle aspiration cytology at our institution has reduced the use of radionuclide scanning from 90% to 12% and the use of thyroid ultrasonography from 30% to 10%. We also found that the frequency of surgery in patients with thyroid nodules fell substantially, yet detection of thyroid cancer in the operative specimens increased from 16% to 43% while the cost of removing a thyroid carcinoma decreased from $64,000 to $25,000. CONCLUSIONS: Fine-needle aspiration cytology, adopted as the initial test for diagnosing thyroid nodules by most of our healthcare providers, has reduced the use of imaging studies far below the frequency reported by others and has substantially decreased the cost of thyroid nodule management.

Adolescent↗