Presence Of Lymphocytic Thyroiditis Research Articles

The Association between Lymphocytic Thyroiditis and Papillary Thyroid Cancer Harboring Mutant BRAF: A Systematic Review and Meta-Analysis.

Background: Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harboring BRAFV600E (PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC. Objective: We compared the prevalence of PTC-BRAF with and without LT. The risk of adverse pathological features in (i) PTC in the presence and absence of BRAF mutation, irrespective of LT status, was compared to (ii) PTC in the presence and absence of LT, irrespective of BRAF status. Methods: We searched PubMed, Embase, and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features, and the quality assessment tool were extracted by two reviewers. The study was registered with PROSPERO (CRD42023437492). Results: Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated that the odds of PTC-BRAF were significantly lower in the presence of LT compared to its absence (odds ratio [OR] 0.53, 95% confidence interval [CI]: 0.48-0.58, p < 0.00001). In PTC-BRAF patients, there was a positive association of central neck nodal disease (CNND), PTC > 1 cm, extra-thyroidal extension, American Joint Committee on Cancer (AJCC) Stage 3-4, and multifocality with pooled ORs of 1.54 (95% CI: 1.16-2.04), 1.14 (95% CI: 0.82-1.58), 1.66 (95% CI: 1.40-1.97), 1.53 (95% CI: 1.35-1.75), and 1.24 (95% CI: 1.11-1.40) respectively, compared to wild-type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled ORs of 0.64 (95% CI: 0.51-0.81) for CNND, 0.83 (95% CI: 0.73-0.95) for PTC > 1 cm, 0.71 (95% CI: 0.58-0.86) for ETE, 0.84 (95% CI: 0.75-0.94) for AJCC Stage 3-4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT, with pooled ORs of 1.12 (95% CI: 0.66-1.90, p = 0.67) and 0.60 (95% CI: 0.28-1.30, p = 0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set. Conclusion: The odds of PTC-BRAF are significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and whether this is relevant to the role of immunotherapy in advanced thyroid cancer.

The role of vascular endothelial growth factor in the development of papillary thyroid carcinoma in patients with lymphocytic thyroiditis.

Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of autoimmune chronic inflammatory conditions and papillary thyroid carcinoma (PTC). We hypothesized that, as VEGF expression is increased both in PTC and in lymphocytic thyroiditis (LT), it may stimulate the development of PTC in patients with LT. To evaluate this, we examined both tumor and adjacent non-tumoral tissues of PTC patients with and without LT. A total of 50 patients with PTC (52.50±7.41 years) and 17 patients with nodular goiter (NG) (50.47±10.38 years) were included in the study. According to the presence of LT, patients with PTC were further divided into two groups. Immunohistochemical analyses of VEGF were conducted in all patients and for PTC patients, both tumor tissue and adjacent non-tumoral tissue were evaluated. The scores for intensity of staining and percentage of labeled thyrocytes for VEGF were found to be significantly higher in the PTC patients than in the NG patients (p<0.001, p<0.001, respectively). The tumor tissue revealed similar scores for PTC patients with LT and without LT. However, the scores in adjacent non-tumoral tissue were higher in PTC patients with LT than in patients without LT (p=0.004, p=0.01, respectively). To the best of our knowledge, our results are the first to demonstrate that the expression of VEGF in adjacent non-tumoral tissue were higher in PTC patients with LT than in those without, which shows a possible role of VEGF expression in the progression of PTC in the presence of LT.

Transcriptome analysis discloses dysregulated genes in normal appearing tumor-adjacent thyroid tissues from patients with papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The molecular characteristics of histologically normal appearing tissue adjacent to the tumor (NAT) from PTC patients are not well characterized. The aim of this study was to characterize the global gene expression profile of NAT and compare it with those of normal and tumor thyroid tissues. We performed total RNA sequencing with fresh frozen thyroid tissues from a cohort of three categories of samples including NAT, normal thyroid (N), and PTC tumor (T). Transcriptome analysis shows that NAT presents a unique gene expression profile, which was not associated with sex or the presence of lymphocytic thyroiditis. Among the differentially expressed genes (DEGs) of NAT vs N, 256 coding genes and 5 noncoding genes have been reported as cancer genes involved in cell proliferation, apoptosis, and/or tumorigenesis. Bioinformatics analysis with Ingenuity Pathway Analysis software revealed that “Cancer, Organismal Injury and Abnormalities, Cellular Response to Therapeutics, and Cellular Movement” were major dysregulated pathways in the NAT tissues. This study provides improved insight into the complexity of gene expression changes in the thyroid glands of patients with PTC.

Is Vitamin D Deficiency Associated with Chronic Lymphocytic Thyroiditis?

Objectives:Vitamin D deficiency is a very common global health problem. Evidence from recent studies focuses on the extraskeletal effects of vitamin D (Vit D) deficiency. Chronic lymphocytic thyroiditis (or Hashimoto’s thyroiditis) is an autoimmune disease of the thyroid. Although there are many studies reporting that autoimmune thyroid diseases may be associated with Vitamin D deficiency, this is still a controversial issue that has not yet been proven. In this study, we aimed to appraise whether there is a relationship between lymphocytic thyroiditis diagnosed by histopathological evaluation and Vitamin D deficiency.Methods:Data of 256 patients whom were operated by a single surgeon in a single center between 2012 and 2017 and whose preoperative vitamin D tests and thyroid pathologies have been collected, were retrospectively evaluated. Due to the pathological examination, two groups were formed considering the presence of lymphocytic thyroiditis (Group 1), and the absence of lymphocytic thyroiditis (Group 2). Vitamin D deficiency was defined as the level <20 ng/mL (50 nmol/L) and Vitamin D insufficiency was defined as the level 21–29 ng/mL (525–725 nmol/L).Results:There were 108 (92F/16M) patients in Group 1, and 148 (116F/32M) patients in Group 2, and the mean age was lower in Group 1 (p=0.053). The mean vitamin D levels (16.6±15.2 vs. 14±10, p=0.409) and vitamin D deficiency rates (67.6% vs. 72.3%, p=0.416) were found similar between the Groups 1 and 2. No positive significant correlation was found between lymphocytic thyroiditis and vitamin D level or vitamin D deficiency rates. There was a positive correlation between lymphocytic thyroiditis and age, preoperative thyroid-stimulating hormone level, preoperative anti-thyroglobulin ,and anti-thyroid peroxidase levels, but no significant relationship was found with Vitamin D level.Conclusion:According to our results, lymphocytic thyroiditis was not associated with either Vitamin D deficiency or Vitamin D level.

An Approach to Macroscopic Central Lymph Nodes Detected during Surgery in Patients with Thyroid Micropapillary Carcinoma: Should We Resort to Dissection?

Background. High-resolution ultrasonography and the ability to perform fine-needle aspiration biopsy even for nodules smaller than three millimeters have considerably increased the detection rate of thyroid micropapillary carcinoma (TMPC). Despite favorable prognosis, the prevalence of cervical lymph node metastases in patients with TMPC is approximately 30%. Aim. In this study, we aimed to determine the central lymph node metastasis rate and its relation to the characteristics of the tumor. Methods. One hundred nine patients who underwent surgery due to TMPC between December 2009 and January 2014 were analyzed retrospectively. Patients were divided into two groups according to whether they underwent lymph node dissection and the two groups were then compared with respect to tumor size and multicentricity, age, and presence of lymphocytic thyroiditis. Results. There were no statistically significant differences between the two groups of patients in terms of tumor size, tumor multicentricity, age, and presence of lymphocytic thyroiditis. When the patient group that received lymph node dissection was further analyzed, it was found that patients with lymphocytic thyroiditis had a significantly lower number of metastatic lymph nodes. Conclusion. Central lymph node dissection in TMPC patients with macroscopic lymph node detected intraoperatively would ensure accurate staging without an increase in morbidity.

Association of lymphocytic thyroiditis and papillary thyroid carcinoma: a retrospective study done at a tertiary care centre in Kerala, India

Background: The incidences of thyroid malignancies are rising across many parts of the world, due to various reasons. Among all the thyroid malignancy, Papillary Carcinoma of Thyroid (PTC) is the most common type, but fortunately if follows a slow course with excellent survival statistics. Papillary Thyroid Cancer has varied presentations and it has been observed that PTC is commonly found in association with Lymphocytic thyroiditis. In this study, we aim to analyse the mode of presentation of PTC, along with the diagnostic modalities and its relationship with Lymphocytic thyroiditis. Methods: A total of 80 patients who were operated at a tertiary care hospital in south Kerala and had a histopathological diagnosis of Papillary Carcinoma of thyroid were included in the study. The presenting complaints, clinical signs, pre-operative thyroid function tests, ultrasonography findings, FNAC reports and pathology reports were obtained from the patient records. Results: Mean ages of the participants were 44.6 years and vast majorities (80%) were females. All the participants had a neck swelling at the time of presentation while 6.2% of the participants presented with hyperthyroid/thyrotoxicosis symptoms and 23.1% had symptoms suggestive of hypothyroidism. Fifty percent of the participants had an associated lymphocytic thyroiditis. Conclusions: The mode of initial clinical presentation of this malignancy is varied and can range from hypothyroidism to thyrotoxicosis to a neck swelling. Biochemically also, we have found that the Thyroid Function Tests can yield a result in any part of the wide spectrum between hypothyroidism and hyperthyroidism. Also, it was found that no clinical or a laboratory finding was associated with the presence of lymphocytic thyroiditis in patients with Papillary Carcinoma of thyroid.

Pathologic spectrum of lymphocytic infiltration and recurrence of papillary thyroid carcinoma.

PurposeThe aim of this study was to investigate the prognosis of papillary thyroid carcinoma (PTC) patients according to different pathologic grades of lymphocytic thyroiditis (LT).Materials and MethodsThis study included 144 PTC patients who underwent total thyroidectomy with radioactive iodine remnant ablation therapy. Pathologic grades of LT were separated at two points, chronic lymphocytic thyroiditis (CLT) and Hashimoto thyroiditis (HT). Patients were divided into two groupings according to the presence of the diseases (Grouping 1; patients with CLT or HT and without CLT or HT, Grouping 2; patients with HT and without HT). The groupings were compared according to recurrence, clinicopathologic and ultrasound (US) characteristics, and disease free survival.ResultsOf 144 patients, 41 had CLT and 19 had HT. There were 10 patients (6.9%) with tumor recurrence. In both groupings, the presence of calcification was more frequently associated with patients with LT (p=0.041 and 0.047, respectively). In Grouping 2, the mean age at diagnosis was older in patients without HT compared to patients with HT (p=0.032). On multivariate analysis, the presence of LT was not an independent predictor of recurrence in both groupings. For both groupings, pathologic tumor size and taller than wide shape on US were independent predictors of recurrence. The presence of LT in PTC patients did not affect recurrence.ConclusionThere was no relationship between PTC prognosis and different grades of LT. Pathologic tumor size and taller than wide shape on ultrasound were independent predictors of PTC recurrence regardless of concurrent LT.

CXCR4 expression correlates with the degree of tumor infiltration and BRAF status in papillary thyroid carcinomas

Emerging evidence indicates that interactions between chemokine receptors and their ligands may have a critical role in several steps of tumor development, including tumor growth, progression, and metastasis. In this report, we retrospectively evaluated CXCR4 expression in a consecutive series of 200 papillary thyroid carcinomas. We investigated the relationship between the clinicopathological features of the tumors and mutations in the BRAF gene to verify whether overexpression of CXCR4 is linked to more aggressive behavior in thyroid tumors. CXCR4 protein expression was evaluated by immunohistochemical staining. A final staining score was calculated by adding the score representing the percentage of positive cells to the intensity score. The CXCR4 expression of each papillary thyroid carcinoma sample was normalized by calculating the z score for each final staining score. Univariate analysis was used to correlate CXCR4 expression with the papillary thyroid carcinoma variant, the degree of neoplastic infiltration, the American Joint Commission on Cancer stage, the presence of lymphocytic thyroiditis and the mutation status of the BRAF gene. Multiple regression analysis confirmed a strong association between CXCR4, BRAF mutation and the degree of neoplastic infiltration. These data clearly indicate that the chemokine receptor expression induced by oncogenic activation could be the major determinant of the local aggressiveness of neoplastic cells. In conclusion, our data indicate that CXCR4 expression and BRAF mutation status could cooperatively induce and promote a more aggressive phenotype in papillary thyroid carcinoma through several pathways and specifically increase the tumors' spread outside of the thyroid gland.

Role of Lymphocytic Thyroiditis in Metastasis of Papillary Thyroid Carcinoma

Objective: The role of chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) is unclear. Studies have failed to demonstrate correlation of CLT with lymph node metastases (LNM) in part due to lack of standardized central lymph node dissection (CND). We investigate the incidence of LNM in specimens with CLT. Method: All OHSU patients who underwent total thyroidectomy with comprehensive ipsilateral CND for PTC between 2005 and 2010 were included. All specimens underwent genomic mutation analysis using a panel of known mutations. Reports were reviewed for tumor type, presence of lymphocytic thyroiditis, extracapsular extension, angiolymphatic invasion, and nodal metastasis. Results: A total of 139 patients met the selection criteria for this study. The overall rate of chronic lymphocytic infiltrate was 43.8%. The overall rate of central node positivity was 63%. There was a significantly higher proportion of central node positivity in the non-CLT patients (74% vs 49%, P = .003). There was also a higher rate of angiolymphatic invasion in the non-CLT patients (31% vs 15% P &lt; .05). There was no significant difference in mean age, tumor size, and extracapsular extension. Molecular genotyping did not reveal a significant difference in the types of mutations found in both groups. Conclusion: Our data indicates a lower incidence of LNM in those with CLT ( P = .003), suggesting a potential protective role in tumor spread. The equal distribution of mutations in tumors with and without CLT argues against mutation-specific inflammation. Further research is needed to characterize the role of autoimmunity in thyroid cancer.

Features of Papillary Thyroid Microcarcinoma in the Presence and Absence of Lymphocytic Thyroiditis

It is known that the prevalence of lymphocytic thyroiditis (LT) is higher in patients with papillary thyroid carcinoma (PTC), that gender influences this association, and that certain features of PTC occur more frequently in patients who also have LT. These relationships have not been studied in patients with papillary thyroid microcarcinomas (PTMC), however. Therefore, we performed a study to compare the clinical and pathological features of patients with PTMC who did and did not have LT. We collected the 323 consecutive patients following excision of PTMC diagnosed as papillary carcinoma on preoperative needle aspiration cytology. We analyzed the demographic, serologic, and pathologic data of those cases with categorization into four groups based on presence of LT and neck lymph node metastasis. In all PTMC, the presence of LT did not influence the frequency of lymph node metastasis (27 of 105 [25.7%] vs. 48 of 218 [22.0%]). Among the patients with metastatic PTMC, LT was noted significantly more often in female than male patients (95.2% vs. 79.8%). In metastatic PTMC, multifocality and bilaterality was more frequent in with LT than without LT (44.4% vs. 29.2%; 29.6% vs. 14.6%). Both the presence of serum thyroglobulin antibody (TgAb; p = 0.016) and serum microsomal antibody (p = 0.013) were highly correlated with the presence of LT. Twenty-seven of 105 patients (25.7%) with PTMC with LT had nodal metastasis. Co-existing LT was noted predominantly in women, influenced more often multifocality and bilaterality of tumors, and higher frequency of metastasis to lateral compartment lymph nodes.

Is Lymphocytic (Hashimoto) Thyroiditis Associated With Suicide?

The histologic diagnosis of lymphocytic (Hashimoto) thyroiditis requires lymphocytic inflammation of the thyroid gland in combination with Hourthle cell metaplasia of follicular epithelial cells. Clinically, this autoimmune process has been associated with hypothyroidism and psychiatric conditions including depression. This retrospective study was designed to quantify the incidence and severity of lymphocytic thyroiditis in a series of nonconsecutive suicides compared with a cohort of motor vehicle accident victim controls. Eighty-one suicide victims (61 male, 20 female; age range 13-79 years, average 43) were compared with 88 age and gender matched controls (64 males, 24 females; age range 19-85 years, average 36). The degree of lymphocytic inflammation of the thyroid gland was graded on a scale of 0 to 3 (0 = no inflammation, 1 = mild inflammation, 2-3 moderate-to-marked inflammation with Hourthle cell metaplasia). Slides from each case were reviewed while blinded to the cause and manner of death in each case. Of these 169 total cases, 8 (4.7%) received a score of 3, whereas additional 7 (4.1%) received a grade of 2. Eighty-six percent of all of the cases showed no significant inflammation and recorded a score of 0. Of the 81 suicides, 3 had a score of 3, and 3 had a score of 2 (combined incidence of 7.4%). Within the control group, 5 of 88 cases scored 3 and another 4 scored 2 (combined incidence = 10.2%). Three males and 5 females scored 3 with an age range of 23 to 63 years, average 42. Incidental data tabulated showed that 19% of suicide victims were on psychoactive medications compared with 6% in the motor vehicle accident control group. No one on this study was on thyroid hormone replacement therapy. Depression is strongly linked to suicide and lymphocytic thyroiditis may be a cause of depression. Based on this study, however, the presence of lymphocytic thyroiditis cannot be used as a histologic adjunct to discriminate between suicide and accident in problematic cases (ie, overdose deaths). This diagnosis is rendered with essentially equal frequency in suicide victims versus controls.

Características de presentación del microcarcinoma papilar del tiroides: Experiencia retrospectiva de los últimos 12 años

Thyroid microcarcinoma is a tumor of 10 mm or less, that should have a low risk of mortality. However, a subgroup of these carcinomas is as aggressive as bigger tumors. To describe the pathological presentation of these tumors, and compare them with larger tumors. All pathological samples of thyroid carcinoma that were obtained between 1992 and 2003, were studied. In all biopsies, the pathological type, tumor size, the focal or multifocal character, the presence of lymph node involvement and the presence of lymphocytic thyroiditis or thyroid hyperplasia, were recorded. One hundred eighteen microcarcinomas and 284 larger tumors were studied. The mean age of patients with microcarcinoma and larger tumors was 42.7+/-14 and 49.3+/-16 years respectively (p <0,001) and 83% were female, without gender differences between tumor types. Mean size of microcarcinomas was 8.6 mm and 116 (98%) were papillary carcinomas. Of these, 109 (94%) were well differentiated and seven (6%) were moderately differentiated. Thirty six (31%) were multifocal and in 10 (8,6%), there was lymph node involvement. The mean size of larger tumors was 23.8 mm and 241 (85%) were papillary carcinomas. Of these, 200 (83%) were well differentiated, and 41 (17%) were moderately differentiated. Eighty five (35%) were multifocal and in 44 (18%) there was lymph node involvement. The prevalence of thyroiditis and hyperplasia was significantly higher among microcarcinomas than in larger tumors (15 and 2.5%, respectively, p <0.001, for the former; 32.4 and 1.7%, respectively, p <0.001, for the latter). In this series, one third of microcarcinomas were multifocal and 10% had lymph node involvement. Therefore, the aggressiveness of these tumors is higher than what is reported in the literature and they should be treated with total thyroidectomy.

Influence of lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma.

Both the association between lymphocytic thyroiditis (LT) and papillary thyroid carcinoma (PTC), and the prognostic significance of lymphocytic infiltrate in patients with thyroid malignancy, remain controversial. We examine the above relationships by retrospectively reviewing our series of patients treated for differentiated nonmedullary thyroid carcinoma at University of California-San Francisco over a 25-yr period (1970-1995). Of the 631 patients with complete data for analysis, 128 patients (20.3%) showed concomitant histologic evidence of LT and 503 patients (79.7%) had no evidence of LT. Prognostic outcome was assessed using Kaplan-Meier survival plots and analysis of risk factors by Cox's proportional-hazard modeling. The cohort with LT revealed a higher frequency of PTC (97.7% vs. 87.3%) and female patients (85.2% vs. 66.8%), a lower frequency of extrathyroidal invasion (7.8% vs. 23.3%) and nodal metastases (25.8% vs. 43.3%), and absence of distant metastases (0% vs. 4.8%), respectively, compared with those without LT. At initial surgery, a significantly greater proportion of patients with LT belonged to lower pathological tumor-node-metastasis stages, compared with those without LT (stage 1, 86.7% vs. 73%; stage 2, 4.7% vs. 8.3%; stage 3, 8.6% vs. 15.3%; and stage 4, 0% vs. 3.4%). Over a mean +/- SE follow-up period of 11.1 +/- 0.4 yr, patients with LT had significantly lower cancer recurrence rate (6.3% vs. 24.1%; P < 0.0001) and cancer mortality rate (0.8% vs. 8.0%; P = 0.001), respectively, compared with those without LT. In summary, our series showed a relatively common occurrence of LT in patients with PTC, and we believed that lymphocytic infiltration developed mainly in response to the tumor itself. We also found a more favorable course of PTC in the presence of LT; this supports the hypothesis that lymphocytic infiltration represents a form of immune reaction to control tumor growth and proliferation.

The pathogenicity of spontaneously-occurring thyroglobulin-reactive T lymphocytes from BB/WOR rats.

Autoantigen-reactive T lymphocytes have been implicated in the pathogenesis organ-specific autoimmune disease. Thyroglobulin (Tg) is one of the primary autoantigens associated with autoimmune lymphocytic thyroiditis (LT). These experiments investigated the pathogenicity of a lymphocyte line derived from spontaneously-occurring Tg-reactive T lymphocytes isolated from unprimed NB line BB/Wor rats which have nearly a 100% incidence of spontaneous LT. Adoptive transfer of LT was accomplished by injecting 1.0 x 10(5) Tg-reactive lymphocytes into the tail vein of MHC compatible, non LT-prone BB line BB/Wor rats. All of the Tg-reactive cell line recipients (5/5) developed LT compared to only 20% (1/5) of the control rats given a parallel tetanus toxoid-reactive T cell line (p < 0.05, Fisher's exact test). Furthermore, despite the presence of LT, only one Tg-reactive cell line recipient developed insulitis. When Tg-reactive lymphocytes were incubated with an MHC compatible Wistar rat thyrocyte line at increasing effector: target ratios, the T cell line lysed thyrocytes in a dose-response fashion (r = 0.99, p < 0.05, linear regression), but did not lyse smooth muscle cell targets. FACS analysis established that this cell line is CD8 predominant. This is the first study to demonstrate that spontaneously-occurring Tg-reactive T lymphocytes from a nonimmunized animal model for LT are pathogenic. Further investigations into the repertoire of Tg-reactive lymphocytes in BB/Wor rats should provide insight into the pathogenesis of autoimmune thyroid disease and provide a basis for targeted immunotherapy.

The effect of iodide ingestion on the development of spontaneous lymphocytic thyroiditis in the diabetes-prone BB/W rat.

It has been suggested that the incidence of Hashimoto's thyroiditis is increased in the presence of high iodide intake. The diabetes-prone BB/W rat develops spontaneous histological autoimmune lymphocytic thyroiditis (LT) without functional hypothyroidism between 60 and 120 days of age. Studies were carried out to determine whether iodine administration to BB/W rats would affect the incidence and severity of LT and induce hypothyroidism. Iodide (0.05% in water) or tap water (C) was administered ad libitum to 42 10-month-old BB/W rats and 71 30-day-old BB/W rats for 8 weeks. For control purposes, 0.05% iodide or tap water (C) was also administered ad libitum to 42 30-day-old nondiabetic and non-LT-prone BB/W genetically equivalent rats (W-line) for 12 weeks and 41 21-day-old Wistar rats for 7 weeks. In a separate experiment, weanling BB/W rats were fed a low iodine diet, a control iodine-sufficient (C) diet, or Purina chow (P) and tap water ad libitum for 8 weeks. In each experiment, blood was obtained at the time of death for the measurement of serum T4, T3, TSH, and antithyroglobulin antibody (anti-Tg Ab), and the thyroids were removed for histological evaluation (0 = no LT; 1-4 = LT). Iodide administration (0.05%) induced a significant increase in the incidence of LT in 30-day-old BB/W rats (I, 77%; C, 30%, P less than .001). Thyroid weight and serum T4, T3, and anti-Tg Ab concentrations were not affected by iodide administration. However, the presence of LT was associated with a significant increase in thyroid weight and anti-Tg Ab concentrations. BB/W rats subjected to a low iodine diet exhibited a significantly decreased incidence of LT (low I, 8.6%; C, 47.3%; P less than 0.01), but no statistically significant difference in anti-Tg Ab levels. Increased iodide intake did not significantly affect the incidence of LT in adult BB/W rats and did not induce LT or affect thyroid function in W-line or Wistar rats. These data show that iodine intake significantly affects the incidence of spontaneous LT in young, genetically predisposed rats.