Evaluation of the role of thyroid scintigraphy in the differential diagnosis of thyrotoxicosis.

OBJECTIVE: A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. METHODS: We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. RESULTS: Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves' disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). CONCLUSIONS: Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.

Bidirectional association between alopecia areata and thyroid diseases: a nationwide population-based cohort study.

Alopecia areata (AA) has long been associated with thyroid diseases; however, the temporality of their association remains unclear. This study aimed to investigate the bidirectional association between AA and thyroid diseases. In analysis 1, we included 5929 AA patients and 59,290 matched controls to assess the risk of thyroid diseases. In analysis 2, we included 35,071 patients with thyrotoxicosis, 19,227 patients with Graves' disease, 5460 patients with thyroiditis, 3352 patients with Hashimoto's thyroiditis, and their matched controls (1:10) to assess the risk of AA. Incidence of thyroid diseases and AA were the outcomes in analysis 1 and analysis 2, respectively. After adjusting the potential confounders, AA patients had an increased risk of all thyroid diseases, including toxic nodular goiter, (aHR 10.17; 95% confidence interval [CI] 5.32-19.44), nontoxic nodular goiter (aHR 5.23; 95% CI 3.76-7.28), thyrotoxicosis (aHR 7.96; 95% CI 6.01-10.54), Graves' disease (aHR 8.36; 95% CI 5.66-12.35), thyroiditis (aHR 4.04; 95% CI 2.12-7.73), and Hashimoto thyroiditis (aHR 4.35; 95% CI 1.88-10.04). On the contrary, a significantly increased risk of developing AA was observed among patients with thyrotoxicosis (aHR 9.29; 95% CI, 7.11-12.14), Graves' disease (aHR 8.66; 95% CI 6.03-12.42), and thyroiditis (aHR 6.42; 95% CI 3.15-13.11) but not in patients with Hashimoto's thyroiditis. In conclusion, our study found a bidirectional association between AA and thyroid diseases, suggesting shared biological mechanisms underlying these two diseases.

Thyroid Dysfunction in Relation to Immune Profile, Disease Status, and Outcome in 191 Patients with COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2-related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers. METHODS: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from July 21 to August 21, 2020, were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3), and antithyroid antibodies were measured on admission. RESULTS: Among 191 patients with COVID-19 (mean age 53.5 ±â€…17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. Abnormal thyroid function was seen in 13.1%. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in 2 of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing nonthyroidal illness syndrome. Lower SARS-Cov-2 polymerase chain reaction cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (P = .030) and low fT3 (P = .007), respectively. A decreasing trend of fT3 with increasing COVID-19 severity (P = .032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes. CONCLUSION: Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance.

Immune Checkpoint Inhibitor-induced Thyroid Dysfunction Is Associated with Higher Body Mass Index.

CONTEXT: Obesity is a proinflammatory metabolic state that may play a role in the development of immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy. OBJECTIVE: To characterize the association between body mass index (BMI) and thyroid irAEs. METHODS: We performed a single-center, retrospective analysis of 185 cancer patients treated with anti-PD-1/L1 from January 2014 to December 2018. Patients with normal thyroid function at baseline and available BMI were included. MAIN OUTCOME MEASURES: The primary endpoint was difference in BMI in patients who developed overt thyroid dysfunction versus those who remained euthyroid following anti-PD-1/L1 initiation. Additional endpoints included any (overt or subclinical) thyroid dysfunction, overt thyrotoxicosis or overt hypothyroidism, and time to development of dysfunction according to BMI. RESULTS: Any thyroid dysfunction developed in 72 (38.9%) patients and 41 (22.1%) developed overt thyroid dysfunction. Mean BMI was higher in those with overt thyroid dysfunction versus euthyroid (27.3 ±â€…6.0 vs 24.9 ±â€…4.5, P = .03). Development of overt thyrotoxicosis versus remaining euthyroid was associated with higher BMI (28.9 ±â€…5.9 vs 24.9 ±â€…4.5; P < .01), whereas overt hypothyroidism was not (26.7 ±â€…5.5 vs 24.9 ±â€…4.5, P = .10). Overt thyrotoxicosis developed within 57.5 (interquartile range [IQR] 31.8-78.8) days of treatment in the low-normal BMI group, 38.0 (IQR 26.8-40.5) days in the overweight group, and 23.0 (IQR 21.0-28.0) days in the obese group (P = .02). CONCLUSIONS: Patients treated with PD-1/L1 inhibitors were more likely to develop thyroid irAEs, specifically overt thyrotoxicosis, with increasing BMI. Overt thyrotoxicosis occurred earlier in obese versus leaner patients. These data highlight the complex interplay between obesity and immune response in immune checkpoint inhibitor-treated patients.

Thyrotoxicosis in patients with COVID-19: the THYRCOV study.

OBJECTIVE: This study assessed thyroid function in patients affected by the coronavirus disease-19 (COVID-19), based on the hypothesis that the cytokine storm associated with COVID-19 may influence thyroid function and/or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly act on thyroid cells, such as previously demonstrated for SARS-CoV-1 infection. DESIGN AND METHODS: This single-center study was retrospective and consisted in evaluating thyroid function tests and serum interleukin-6 (IL-6) values in 287 consecutive patients (193 males, median age: 66 years, range: 27-92) hospitalized for COVID-19 in non-intensive care units. RESULTS: Fifty-eight patients (20.2%) were found with thyrotoxicosis (overt in 31 cases), 15 (5.2%) with hypothyroidism (overt in only 2 cases), and 214 (74.6%) with normal thyroid function. Serum thyrotropin (TSH) values were inversely correlated with age of patients (rho -0.27; P < 0.001) and IL-6 (rho -0.41; P < 0.001). In the multivariate analysis, thyrotoxicosis resulted to be significantly associated with higher IL-6 (odds ratio: 3.25, 95% confidence interval: 1.97-5.36; P < 0.001), whereas the association with age of patients was lost (P = 0.09). CONCLUSIONS: This study provides first evidence that COVID-19 may be associated with high risk of thyrotoxicosis in relationship with systemic immune activation induced by the SARS-CoV-2 infection.

Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-tolymphocyte ratio in different etiological causes of thyrotoxicosis

Background/aim: The most common causes of thyrotoxicosis include Graves' disease (GD), toxic multinodular goiter (TMNG), toxic adenoma (TA), and subacute granulomatous thyroiditis (SAT). In our study, we aimed to see whether neutrophil­to­lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet­to­lymphocyte ratio (PLR), and mean platelet volume (MPV) may be helpful in the differential diagnosis of these diseases. Materials and methods: We retrospectively analyzed the hospital records of the Endocrinology Clinic of our hospital between 2016 and 2019. We included data from 66 GD, 37 TA, and 35 SAT patients. We compared the data with those of 35 healthy subjects as controls. Results: NLR, MLR, and PLR were found to be higher in the SAT group when compared to other groups. The post hoc analysis of comparison of NLR, MLR, and PLR in each group showed that NLR and PLR were significantly different in the SAT group when compared to the GD, TA, and controls groups (P < 0.001, P = 0.003, and P < 0.001 for NLR respectively and P < 0.001 for PLR in all groups). MPV levels were different between groups (P = 0.007). However, the intergroup analysis (Tukey's test) failed to show a statistically significant difference for any of the groups. In patients with SAT, PLR and NLR were significantly higher than in the GD, TA, and control groups. MLR was also higher in SAT when compared to other groups, but the difference was not statistically significant. Conclusion: High PLR and NLR may be helpful to differentiate SAT from GD and TA, the other common causes of thyrotoxicosis.

Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab.

Thyroid dysfunction (TD) induced by immune checkpoint inhibitors is not sufficiently understood. The purpose of this retrospective observational study was to identify risk factors and the clinical course of TD induced by nivolumab. Patients with advanced solid tumors who were treated with nivolumab from March 2009 through to March 2016 at the National Cancer Center Hospital (Tokyo, Japan) were included. Thyroid function and antithyroid Abs from serum samples among all patients were evaluated at baseline and during nivolumab treatment. Overt hypothyroidism was defined as low serum-free T4 together with elevated thyroid-stimulating hormone (TSH) >10 µIU/mL. Thyrotoxicosis was defined as low TSH with elevated free T4 and/or free T3. We defined thyroid autoimmunity as the presence of antithyroid Abs at baseline, including antithyroid peroxidase Abs and antithyroglobulin Abs (TgAb). Twenty-three (14%) of a total of 168 patients developed TD, including 17 cases of hypothyroidism and 20 of thyrotoxicosis. Thyrotoxicosis followed by hypothyroidism occurred in 14 cases. Fourteen of 35 patients (40%) with thyroid autoimmunity developed TD vs 9 of 133 (7%) without (odds ratio 9.19; 95% confidence interval [CI], 3.53-23.9). In multivariate analysis, elevated TSH and TgAb at baseline were significantly associated with the development of TD, with odds ratio of 7.36 (95% CI, 1.66-32.7) and 26.5 (95% CI, 8.18-85.8), respectively. Association between TD and elevated antithyroid peroxidase Abs at baseline was not significant. These results suggest that patients with pre-existing TgAb and elevated TSH at baseline are at high risk of TD.

POSITIVE THYROTROPIN RECEPTOR ANTIBODIES IN PATIENTS WITH TRANSIENT THYROTOXICOSIS.

OBJECTIVE: Thyrotropin (TSH) receptor antibody (TRAb) testing is considered accurate for the diagnosis of Graves disease (GD) and has been identified rarely in thyrotoxic patients without GD. We describe 4 patients with transient thyrotoxicosis and positive TRAb to highlight this clinical possibility. METHODS: Patient demographics, symptoms, laboratory findings, and time to resolution of thyrotoxicosis are summarized. TRAb testing was performed by either a third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) competitive-binding assay or a thyroid-stimulating immunoglobulin (TSI) bioassay from either Mayo Clinic Laboratory or Quest Diagnostics. RESULTS: Four patients with transient thyrotoxicosis and positive TRAb testing were identified. Of these, three were female, and the median age was 44 years (range, 25 to 49 years). Median symptom duration at evaluation was 6.5 weeks (range, 3 to 12 weeks). No patient had any clinical manifestations unique to GD or exposure to biotin, thyroid hormone, supplements, iodine, or relevant medications. The TSH was <0.1 mIU/L in all patients. Three patients had a positive TSI, which was elevated less than twice the upper limit of the reference range in all cases, and 1 patient had a strongly positive TBII. None of the patients were treated with thionamides or radioactive iodine. Spontaneous resolution occurred in all patients at a median of 5.5 weeks (range, 2 to 14.4 weeks). CONCLUSION: These cases demonstrate that TSI or TBII may be present in thyrotoxic patients with transient thyrotoxicosis. For clinically stable patients presenting without pathognomonic evidence of GD, mildly elevated TRAb results may require cautious interpretation, and alterative diagnostic testing or close monitoring should be considered. ABBREVIATIONS: cAMP = cyclic adenosine monophosphate; FT4 = free thyroxine; GD = Graves disease; TBII = thyrotropin-binding inhibitory immunoglobulin (also known as TBI); TRAb = thyrotropin receptor antibody; TSH = thyrotropin; TSHR = thyrotropin receptor; TSI = thyroid-stimulating immunoglobulin; TT3 = total triiodothyronine; TT4 = total thyroxine.

Maternal Thyrotropin Receptor Antibody Concentration and the Risk of Fetal and Neonatal Thyrotoxicosis: A Systematic Review.

BACKGROUND: In pregnant women with Graves' disease, maternal thyrotropin receptor antibodies (TRAb) can cross the placenta and induce fetal or neonatal thyrotoxicosis. Symptoms of fetal thyrotoxicosis are tachycardia, intrauterine growth restriction, and intra-uterine death. Recommendations on an upper limit of TRAb concentrations below which intensive fetal monitoring can be safely omitted vary between different guidelines. The objective of this study was to define an evidence-based cutoff level for maternal TRAb necessitating additional fetal monitoring during pregnancy. METHODS: A literature search was performed to identify studies on pregnant women with Graves' disease and fetal and/or neonatal thyrotoxicosis. Only studies that reported TRAb were included. RESULTS: From a total of 229 identified titles, 20 articles could be included in the analysis. A total of 53 cases of fetal and/or neonatal thyrotoxicosis were described. The lowest level of maternal TRAb leading to neonatal thyrotoxicosis was 4.4 U/L, which corresponds to 3.7 times the upper limit of normal. The level of evidence for this threshold is moderate to low. CONCLUSION: In women with Graves' disease, intensive fetal monitoring is recommended when maternal TRAb concentrations are >3.7 times the upper limit of normal. This cutoff level should be interpreted with caution, since evidence is limited.

Reversible and unilateral corticospinal tract disease secondary to autoimmune free-T3-thyrotoxicosis.

68-year-old female patient with no significant medical history presents with a 3-month history of progressive neurological symptoms, which began with left eye ptosis, blurred vision and non-painful jaw discomfort, followed by left spastic weakness and hyper-reflexia with positive Babinski and Hoffman signs. An elevated T3 level, a positive peroxidase and an antigraves antibody level led to an ultrasound, which confirmed a sub acute-chronic autoimmune thyroiditis. A nerve conduction studies/electromyogram showed normal motor and sensory velocity conduction with a small amplitude compound motor action potential, indicative of likely axonal damage. Following treatment with carbimazole, the neurological symptoms greatly improved. The authors concluded that the left pyramidal syndrome was secondary to autoimmune free T3-thyrotoxicosis.

[Psycho-immuno-endocrinology of the thyroid gland]. / Psycho-imuno-endokrinologie stítné zlázy.

Historically endocrinologists and psychiatrists are aware that disturbances in thyroid disease in beginning or even in clinically intensified states of thyrotoxicosis or hypothyroidism exhibit pathological mental manifestations, masking or potentiating the underlying disease. Immune system disorders cause thyroid organ-specific autoimmune process. This autoimmune thyroid disease binds with a number of disorders in both endocrine or non-endocrine organs. This appears in vascular, neurological, skin, connective tissue, gastrointestinal tract and mental pathology. These disorders are part of autoimmune polyglandular syndromes (APS) type I -III, especially the APS type III. Originally it was assumed that these mental disorders are caused by direct exposure to excess or deficiency of thyroid hormones. Recently, however, it appears that these psycho-immune-endocrine disorders have common etiologic mechanisms of formation and on cellular and molecular level they involve similar, if not in some cases, common mechanisms.Key words: antithyroid peroxidase antibody - autoimmune polyglandular syndrome type I., II., III. - autoimmune thyroid disease - bipolar disorder - depression - Hashimotos encephalopathy - postpartum psychosis - psycho-immuno-endocrinology - schizophrenia.

[The choice of surgery in patients with diffuse toxic goiter]. / Vybor ob''ema operatsii u bol'nykh diffuznym toksicheskim zobom (s kommentariem).

AIM: to define clear individual indications for different operations for diffuse toxic goiter by research of immunological markers of thyrotoxicosis recurrence probability. MATERIAL AND METHODS: Long-term results of survey and treatment of 215 patients with diffuse toxic goiter are presented. Patients were divided into 2 groups. The 1st group consisted of 31 patienrs who underwent conventional partial thyroidectomy. Group 2 included 184 patients. They were divided into 2 subgroups depending on type of surgery. Subgroup A included 59 patients after partial thyroidectomy and subgroup B - 125 patients after total thyroidectomy. In group 2 surgery was defined based on only level of antibodies against TSH-receptors. RESULTS: Recurrence incidence was 16 and 0% in groups 1 and 2 respectively. CONCLUSION: In patients with diffuse toxic goiter partial thyroidectomy is possible if normal titer of antibodies against TSH-receptors is present (<1.5 U/l). Total thyroidectomy is advisable in titer ≥1.5 U/l.

The presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) does not exclude the diagnosis of type 2 amiodarone-induced thyrotoxicosis.

PURPOSE: It is widely accepted that type 2 amiodarone-induced thyrotoxicosis (AIT) generally occurs in patients with a normal thyroid gland without signs of thyroid autoimmunity. However, it is currently unknown if the presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) in AIT patients without other signs of an underlying thyroid disease may impair the response to glucocorticoid therapy. METHODS: We performed a pilot retrospective cohort study with matched-subject design and an equivalence hypothesis, comparing the response to glucocorticoid therapy between 20 AIT patients with a normal thyroid gland, low radioiodine uptake, undetectable TSH receptor antibodies and positive TgAb and/or TPOAb (Ab+ group), and 40 patients with the same features and absent thyroid antibodies (Ab- group). RESULTS: The mean cure time was 54 ± 68 days in the Ab+ group and 55 ± 49 days in the Ab- group (p = 0.63). The equivalence test revealed an equivalent cure rate after 60, 90 and 180 days (p = 0.67, 0.88 and 0.278, respectively). The occurrence of permanent hypothyroidism was higher in the Ab+ group than in the Ab- group (26.3 vs 5.13 %, p = 0.032). CONCLUSIONS: The presence of TgAb and/or TPOAb does not affect the response to glucocorticoid therapy, suggesting that the patients with features of destructive form of AIT should be considered as having a type 2 AIT irrespective of the presence of TGAb or TPOAb. These patients have a higher risk of developing hypothyroidism after the resolution of thyrotoxicosis and should be monitored accordingly.

Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies.

CONTEXT: Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described. CASE DESCRIPTION: We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months. CONCLUSIONS: Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.

Thyroid function and prevalence of anti-thyroperoxidase (TPO) and anti-thyroglobulin (Tg) antibodies in outpatients hospital setting in an area with sufficient iodine intake: influences of age and sex.

In order to examine the prevalence of thyroid disease in a hospital outpatient setting, in an area of sufficient iodine intake, serum levels of TSH, T4, T3, anti-Tg and anti-TPO antibodies were examined in 909 individuals with an age range of 12.4 to 88.5 years, participating in a checkup outpatient setting. The study was conducted in Henry Dynant Hospital located in the metropolitan area of Athens, Greece, during a 2 year period. Hormonal parameters were determined by chemiluminescence immunoassay. Overt thyrotoxicosis was found in 4.95% of the total population and subclinical thyrotoxicosis in 5.5%. Overt hypothyroidism was found in 1.43% and subclinical hypothyroidism in 4.51%. In male population, overt thyrotoxicosis was found in 4.4 % and subclinical thyrotoxicosis was also found in 4.4%. On the other hand, overt hypothyroidism was found in 1.4% and subclinical hypothyroidism was found in 3.7% in males. In female population, overt thyrotoxicosis was found in 5.2% whereas subclinical thyrotoxicosis was found in 6.0%. Overt hypothyroidism was found in 1.5% and subclinical hypothyroidism was found in 4,9% in females. Positive anti-TPO antibodies were detected more often (30.4%) than anti-Tg (15.4%) in the tested population. The positivity in both anti-TPO and anti-Tg antibodies was correlated with abnormally high TSH concentrations after the age of 50 years, especially in female population. In conclusion distinct profile of thyroid hormonal parameters was observed in inhabitants in the metropolitan area of Athens, with overt thyrotoxicosis strikingly overcome overt hypothyroidism while subclinical forms of each dysfunction also exhibit analogous results.

Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations.

Autonomously functioning thyroid nodules (AFTN) are known to receive an increased blood influx necessary to sustain their high rate of growth and hormone production. Here, we investigated the expression of hematic and lymphatic vases in a series of 20 AFTN compared with the contralateral non-tumor tissues of the same patients, and the transcript levels of proteins involved in the control of vascular proliferation, including the vascular endothelial growth factor (VEGF) and platelet-derived growth factors (PDGF) and their receptors and the endothelial nitric oxide synthase (eNOS). In parallel, the expression of the differentiation markers sodium/iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (Tg), and TSH receptor (TSHR) was also investigated. The data were further analyzed comparing subgroups of tumors with or without mutations in the TSHR gene. Analysis by means of CD31 and D2-40 immunostaining showed in AFTN an increased number of hematic, but not lymphatic, vessels in parallel with an enhanced proliferation rate shown by increased Ki67 staining. Quantitative RT-PCR analysis revealed an increase of VEGF, VEGFR1 and 2, PDGF-A, PDGF-B, and eNOS expression in tumor versus normal tissues. Also, higher transcript levels of NIS, TPO, and Tg were detected. Comparison of the two subgroups of samples revealed only few differences in the expression of the genes examined. In conclusion, these data demonstrate an increased expression of angiogenesis-related factors associated with an enhanced proliferation of hematic, but not lymphatic, vessels in AFTNs. In this context, the presence of TSHR mutations may only slightly influence the expression of pro-angiogenic growth factors.

[Silent thyroiditis and subacute thyroiditis].

Silent thyroiditis and subacute thyroiditis are important causes of transient thyrotoxicosis from rapidly progressive tissue injury, followed by the release of thyroid hormone into the circulation. The most striking differences between them are severe pain and extreme tenderness in the thyroid region. Although the etiology of these diseases is not clarified, silent thyroiditis is basically occurred in autoimmune thyroiditis. The most difficult differential diagnosis of silent thyroiditis is Graves' disease. TSH receptor antibody (TRAb) is useful, but TRAb is rarely positive in silent thyroiditis. A low thyroid radioiodine uptake value is most useful in identified silent thyroiditis.

[Concept and management of postpartum thyroid dysfunction].

Postpartum thyroid dysfunction is found in 5-10% of women within one year after delivery. Dysfunction is developed from subclinical autoimmune thyroiditis through immune rebound mechanism and divided into 5 types. Most frequent one is destructive thyrotoxicosis, named as postpartum thyroiditis, which occur in early postpartum period and usually followed by transient hypothyroidism. Some of them progress into permanent hypothyroidism. Graves' disease is also developed mainly after 4 months postpartum and found in one out of 200 postpartum women in general population. Treatment of this dysfunction is principally the same as ordinal thyroid disease except for transient hypothyroidism.