Thyroid dysfunction following pregnancy and implications for breastfeeding.

Subclinical autoimmune thyroiditis exacerbates after delivery through immune rebound mechanisms and results in 5 types of thyroid dysfunction. The prevalence of postpartum thyroid dysfunction is around 5% in mothers in the general population. Typically, an exacerbation induces destructive thyrotoxicosis followed by transient hypothyroidism, known as postpartum thyroiditis. Late development of permanent hypothyroidism is found frequently and patients should be followed up once every one to two years. Destructive thyrotoxicosis in postpartum thyroiditis should carefully be differentiated from post-partum Graves' disease. Postpartum thyroiditis typically occurs 1-4 months after parturition whereas Graves' disease develops at 4-12 months postpartum. Anti-TSH receptor antibodies (TRAb) are typically positive and thyroid blood flow is high in Graves' disease, whereas these features are absent in postpartum thyroiditis. Postpartum Graves' disease should be treated with antithyroid drugs.

Papillary thyroid carcinomas are highly obscured by inflammatory hypoechoic regions caused by subacute thyroiditis: a longitudinal evaluation of 710 patients using ultrasonography.

Subacute thyroiditis is a self-limited inflammatory disease and very few patients undergo ultrasonographic re-examination if no nodules are found at the initial examination. The objective of the study was to assess the diagnostic accuracy of ultrasonography in detecting nodular lesions in patients with subacute thyroiditis. We conducted a longitudinal study involving 710 patients with subacute thyroiditis who underwent ultrasonographic examinations in a single center between 2008 and 2018. These examinations were performed at initial diagnosis and during follow-up, with subsequent evaluation of nodules using fine needle aspiration cytology. Ultrasonographic examination used for the initial screening of thyroid nodules in patients with subacute thyroiditis showed a sensitivity of 72.4%, specificity of 89.0%, positive predictive value of 80.4%, and negative predictive value of 83.8%. Twenty-two patients (3.1%) had concomitant papillary thyroid carcinoma, 10 of whom underwent thyroidectomy while the remaining 12 opted for active surveillance owing to having low-risk microcarcinomas. Approximately 30% of papillary carcinomas (7/22) were identified during follow-up ultrasonography, but not during the initial scan. All tumors in this false-negative group were latently localized in the bilateral hypoechoic regions of the thyroid and showed no calcified components. Of the 15 tumors that were detected during both initial and follow-up examinations, 7 exhibited calcified components and 5 were located in unaffected areas apart from the inflammatory hypoechoic region. Subacute thyroiditis highly obscures any coexisting papillary carcinoma when inflammatory hypoechoic regions are present. Ultrasonographic re-examination after a sufficient interval is indispensable for patients with subacute thyroiditis.

Moderate Frequency of Anti-Thyroglobulin Antibodies in the Early Phase of Subacute Thyroiditis.

BACKGROUND: Subacute thyroiditis is generally believed to be induced by viral infection, and little attention has been paid to anti-thyroid antibodies. OBJECTIVES: Our study aimed to assess the prevalence of anti-thyroid antibodies in patients with subacute thyroiditis. METHODS: Anti-thyroglobulin (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were measured with 4 different immunoassay kits currently used in 40 patients in the early phase of subacute thyroiditis. RESULTS: The proportion of samples positive for TgAb was 52.5 ± 13.7% (mean of 4 kits), which was significantly (p < 0.05) higher than that positive for TPOAb (15.6 ± 6.5%). The prevalence of positive TgAb alone (negative TPOAb) was also significantly higher than that of TPOAb alone (negative TgAb). TgAb titers decreased or disappeared within 4 months to 6 years in 6 patients. CONCLUSIONS: Patient samples were moderately positive for TgAb initially, but the titer decreased or disappeared afterwards in subacute thyroiditis.

Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases.

It is generally believed that the detection of thyroid peroxidase antibodies (TPOAb) is superior to that of thyroglobulin antibodies (TgAb) for the diagnosis of Hashimoto's thyroiditis. However, limited data are available on the comparison of TgAb and TPOAb prevalence as a diagnostic measurement for Hashimoto's thyroiditis using sensitive immunoassays. We herein used five different current immunoassay kits (A-E) to compare the prevalence of TgAb and TPOAb in Hashimoto's thyroiditis (n = 70), Graves' disease (n = 70), painless thyroiditis (n = 50), and healthy control subjects (n = 100). In patients with Hashimoto's thyroiditis, positive TgAb was significantly more frequent than positive TPOAb in kits A-D (mean ± SD of the four kits: 98.6 ± 1.7 vs 81.4 ± 2.0%). In patients with Graves' disease, TgAb prevalence was almost equivalent to that of TPOAb in five kits. Patients with painless thyroiditis exhibited positive TgAb significantly more frequently than positive TPOAb in kits A-D (73.5 ± 4.1 vs 33.0 ± 3.4%). The prevalence of TgAb alone was significantly higher than that of TPOAb alone in both Hashimoto's thyroiditis and painless thyroiditis in kits A-D. In kit E, TgAb and TPOAb prevalence did not differ significantly for any disease, and TgAb distribution was different from other kits. In conclusion, the prevalence of TgAb was higher than that of TPOAb in patients with Hashimoto's thyroiditis and painless thyroiditis using commercially available kits. We suggest that TgAb immunoassay is the first choice of screening test for thyroid autoimmune abnormalities in Japan.

Comparative frequency of four different types of pregnancy-associated thyrotoxicosis in a single thyroid centre.

BACKGROUND: Pregnancy and delivery markedly influence thyroid function. However, the comparative prevalence of gestational thyrotoxicosis (GT), new onset of Graves' disease during pregnancy (GD during pregnancy), postpartum destructive thyrotoxicosis (PPT), and postpartum Graves' thyrotoxicosis (PPGD) has not yet been determined. METHODS: We prospectively registered and performed a review of 4127 consecutive non treated female patients with thyrotoxicosis, seen between August 2008 and December 2013 in our outpatient clinic of Kuma Hospital. 187 out of the 4127 women had new diagnosis of thyrotoxicosis during pregnancy or in the postpartum period. We investigated the prevalence of new diagnosis of GT, GD during pregnancy, PPT and PPGD and compared the characteristics of these types of thyrotoxicosis. The postpartum period is defined as twelve months after delivery. RESULTS: Out of 187 pregnant or postpartum women, we identified 30 (16.0%) with GT, 13 (7.0%) with GD during pregnancy, 42 (22.5%) with PPT, and 102 (54.5%) with PPGD. The onset time of thyrotoxicosis during pregnancy, i.e., both GT and GD during pregnancy, was delayed by a couple of weeks when hCG peaked at 10 gestational weeks. Seventy-six percent of patients with PPT developed thyrotoxicosis between delivery and 4 months postpartum; on the other hand, 83.3% of patients with PPGD developed thyrotoxicosis at 6 months postpartum or later. CONCLUSIONS: We named gestational thyrotoxicosis, new onset of Graves' disease during pregnancy, postpartum destructive thyrotoxicosis, and postpartum Graves' thyrotoxicosis as pregnancy-associated thyrotoxicosis. A clinically significant number of women developed Graves' disease in the postpartum period in a single thyroid centre.

Biochemical Markers Reflecting Thyroid Function in Athyreotic Patients on Levothyroxine Monotherapy.

BACKGROUND: Some investigators reported that among athyreotic patients on levothyroxine (LT4) monotherapy following total thyroidectomy, the patients with normal serum thyrotropin (TSH) levels had mildly low serum free triiodothyronine (fT3) levels, whereas the patients with mildly suppressed serum TSH levels had normal serum fT3 levels, and the patients with strongly suppressed serum TSH had elevated serum fT3 levels. The objective of the present study was to clarify which of these three patient groups is closer to their preoperative euthyroid condition. METHODS: A total of 133 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy were prospectively studied. The patients' serum levels of lipoproteins, sex hormone-binding globulin, and bone metabolic markers measured preoperatively were compared with the levels measured at postoperative LT4 therapy 12 months after the thyroidectomy. RESULTS: The postoperative serum sex hormone-binding globulin (p < 0.001) and bone alkaline phosphatase (p < 0.01) levels were significantly increased in the patients with strongly suppressed TSH levels (≤0.03 µIU/mL). The postoperative serum low-density lipoprotein cholesterol levels were significantly increased (p < 0.05), and the serum tartrate-resistant acid phosphatase-5b levels were significantly decreased (p < 0.05) in the patients with normal TSH (0.3 < TSH ≤5 µIU/mL). In the patients with mildly suppressed TSH (0.03 < TSH ≤0.3 µIU/mL) and fT3 levels equivalent to their preoperative levels, all metabolic markers remained equivalent to their preoperative levels. CONCLUSIONS: The serum biochemical markers of thyroid function in patients on LT4 following total thyroidectomy suggest that the patients with mildly suppressed TSH levels were closest to euthyroid, whereas those with normal TSH levels were mildly hypothyroid and those with strongly suppressed TSH levels were mildly hyperthyroid. These data may provide novel information on the management of patients following total thyroidectomy for thyroid cancer or benign thyroid disease.

A Novel Germline Mutation of KEAP1 (R483H) Associated with a Non-Toxic Multinodular Goiter.

BACKGROUND: A germline mutation of KEAP1 gene was reported as a novel genetic abnormality associated with familial multinodular goiter. That report was limited, and the pathogenic features were not well established. PATIENT FINDINGS: We report a 47-year-old Japanese woman who presented with hyperthyroidism and a large multinodular goiter. The family history was notable for a paternal history of goiter. Graves' disease was diagnosed based on positive TRAb, but scintiscan imaging showed that the patient's radioiodine uptake was restricted in the non-nodular areas, indicating largely cold nodules. A total thyroidectomy was performed. The resected thyroid tissue weighed 209 g, and subsequent pathological findings were benign. The patient had a germline heterozygous KEAP1 mutation, c. 1448 G > A, resulting in an amino acid substitution (p.R483H). A next-generation sequencing analysis covering all known genes associated with multinodular goiter showed no additional germline mutation. The nuclear accumulation of NRF2, a protein associated with KEAP1, was shown at much higher rates in the patient's nodules compared with nodules obtained from four unrelated patients with multinodular goiters. CONCLUSION: A novel germline mutation (R483H) of KEAP1 gene was associated with the development of a non-toxic multinodular goiter.

Partial prediction of postpartum Graves' thyrotoxicosis by sensitive bioassay for thyroid-stimulating antibody measured in early pregnancy.

Graves' disease often occurs after delivery. However, it has been difficult to predict who will develop Graves' hyperthyroidism. We attempted to predict postpartum onset of Graves' disease by measuring anti-TSH receptor antibodies (TRAb) and thyroid-stimulating antibodies (TSAb) in early pregnancy. TRAb was measured by a third generation assay and TSAb was measured by a newly developed sensitive bioassay. In 690 early pregnant women, 2 showed borderline TRAb positive reactions. However, none of them developed Graves' disease after delivery. Thirty-eight of 690 pregnant women were positive for anti-thyroid peroxidase antibodies (TPOAb) and 4 were positive for TSAb. Two of these 4 women developed postpartum Graves' hyperthyroidism. These findings indicate that the third generation TRAb assay was not useful, but that the sensitive TSAb bioassay was moderately useful for predicting the postpartum onset of Graves' hyperthyroidism.

Tumor protrusion with intensive blood signals on ultrasonography is a strongly suggestive finding of follicular thyroid carcinoma.

AIM: It is difficult to differentiate follicular carcinomas (FC) from follicular adenomas (FA) because ultrasonography and cytology provide very similar findings. FC is histopathologically diagnosed to have capsular and/or vascular invasion. In a few patients, tumor protrusions are observed by preoperative ultrasonography as large forms of capsular invasion of follicular carcinomas. The aim of the study was to clarify the predictive value of tumor protrusions on preoperative ultrasonography for follicular carcinomas. MATERIAL AND METHODS: A total of 531 patients (FC: 184 patients, FA: 347 patients) undergoing thyroid surgery were included in this study. A tumor protrusion on ultrasonography was defined as follows: 1) a solid tumor extending beyond a marginal line of capsular zone of the main tumor on B-mode ultrasonography; 2) intensive blood signals observed within the protrusion area on Doppler ultrasonography. The large form of capsular invasion was defined if the protrusion lesion was histopathologically diagnosed to be a capsular invasion of follicular carcinoma. RESULTS: The sensitivity of tumor protrusion was 0.071, specificity 0.994, positive predictive value 0.867, and negative predictive value 0.669 for FC diagnosis. For the large form of capsular invasion in FC the sensitivity of tumor protrusion was 0.813, specificity 0.982, positive predictive value 0.684, and negative predictive value 0.982. CONCLUSIONS: A tumor protrusion with intensive blood signals extending from the main tumor on ultrasonography strongly suggests a large form of capsular invasion of follicular carcinoma.

Kinetic analyses of changes in serum TSH receptor antibody values after total thyroidectomy in patients with Graves' disease.

We often recommend total thyroidectomy for patients with Graves' disease who wish to have a child in the near future in order to prevent fetal or neonatal hyperthyroidism, especially if the patients' serum thyrotropin receptor antibody (TRAb) values are high. The aim of this study was to analyze changes in serum TRAb values using a quantitative third-generation assay after total thyroidectomy and the half-lives of serum TRAb values to estimate the postoperative time needed to achieve the safe TRAb value for mothers. We retrospectively examined the records of 45 Graves' disease patients who underwent a total thyroidectomy and had high serum TRAb values. We also evaluated factors that prolonged the postoperative reduction of serum TRAb values. The serum TRAb values decreased rapidly in most of the patients, especially within the early postoperative (3-month) period. The presence of Graves' ophthalmopathy (GO) (p=0.001), smoking (p=0.004), and serum thyroglobulin values > 0.5 ng/mL at postoperative 12 months (p=0.039) were significantly associated with prolonged half-lives of the serum TRAb values. The median TRAb value half-life was 93.5 days in the patients without GO or smoking, 162.5 days in the patients with GO or smoking, and 357.4 days in the patients with both GO and smoking. Our findings indicate that using the half-life of patients' serum TRAb values determined by this third-generation assay would be effective to evaluate the reduction of serum TRAb values after total thyroidectomy and to estimate the postoperative time needed to achieve the maternal safe value.

Characteristic sonographic features of cribriform papillary thyroid carcinoma for differentiation from other thyroid nodules.

PURPOSE: The purpose of this paper is to clarify the sonographic features and differential diagnoses of the cribriform variant of papillary thyroid carcinoma (CV-PTC). METHODS: We retrospectively reviewed 24 nodules obtained from 22 CV-PTC cases. As control groups, we chose 50 cases each of conventional papillary carcinoma (C-PTC), follicular tumor, and nodular goiter. RESULTS: All of the cases were young women aged 35 years or younger. Serum thyroglobulin levels were normal or slightly elevated. The incidences of smooth or focal jagged margin, hypoechoic nodule, lateral shadow, posterior acoustic enhancement, poor marginal and internal vascularity, and no microcalcification were 100, 100, 91.7, 95.8, 100, and 95.8 %, respectively. The sensitivity and specificity of the requirement were 87.5 and 92.5 %, respectively. Sonographic findings of CV-PTC were similar to those of follicular tumor or nodular goiter rather than C-PTC. CONCLUSION: The criteria for suspecting CV-PTC we proposed provided high sensitivity and specificity. We should be aware that the sonographic findings of CV-PTC are similar to those of follicular tumor or nodular goiter rather than C-PTC. Clinical findings including gender, age, and serum thyroglobulin level may provide us with useful information.

Graves' Disease Patients with Persistent Hyperthyroidism and Diffuse Lymphoplasmacytic Infiltration in the Thyroid Show No Histopathological Compatibility with IgG4-Related Disease.

BACKGROUND: IgG4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and fibrosis into multiple organs. There is still controversy over whether some thyroid diseases are actually IgG4-related disease. The objective of this study was to elucidate the clinicopathological features of Graves' disease with diffuse lymphoplasmacytic infiltration in the thyroid. PATIENTS AND METHODS: Among 1,484 Graves' disease patients who underwent thyroidectomy, we examined their histopathological findings including the degree of lymphoplasmacytic and fibrotic infiltration and levels of IgG4-positive plasma cells in the thyroid. Their clinical pictures were defined by laboratory and ultrasonographic evaluation. RESULTS: A total of 11 patients (0.74%) showed diffuse lymphoplasmacytic infiltration in the stroma of the thyroid gland. Meanwhile, other patients showed variable lymphoid infiltration ranging from absent to focally dense but no aggregation of plasma cells in the thyroid gland. Based on the diagnostic criteria of IgG4-related disease, 5 of the 11 subjects had specifically increased levels of IgG4-positive plasma cells in the thyroid. Fibrotic infiltration was present in only 1 patient developing hypothyroidism after anti-thyroid drug treatment for 4 years, but not in the other 10 patients with persistent hyperthyroidism. Obliterative phlebitis was not identified in any of the 11 subjects. Thyroid ultrasound examination showed 1 patient developing hypothyroidism who had diffuse hypoechogenicity, but the other hyperthyroid patients had a coarse echo texture. CONCLUSIONS: In our study, Graves' disease patients with persistent hyperthyroidism who had diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells in the thyroid showed no concomitant fibrosis or obliterative phlebitis.

Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients.

OBJECTIVE: We and others recently reported that in total thyroidectomy (TT), serum triiodothyronine (T3) levels during levothyroxine (L-T4) therapy were low compared to the preoperative levels, suggesting that the presence of the thyroid tissue affects the balances of serum thyroid hormone levels. However, the effects of remnant thyroid tissue on these balances in thyroidectomized patients have not been established. METHODS: We retrospectively studied 253 euthyroid patients with papillary thyroid carcinoma who underwent a TT or hemithyroidectomy (HT). We divided the cases into the TT+supplemental L-T4 (+L-T4) group (n=103); the HT+L-T4 group (n=56); and the HT-alone group (n=94). We compared the postoperative serum levels of free T4 (FT4) and free T3 (FT3) and the FT3/FT4 ratio in individual patients with those of controls matched by serum TSH levels. RESULTS: The TT+L-T4 group had significantly higher FT4 (P<0.001), lower FT3 (P<0.01) and lower FT3/FT4 (P<0.001) levels compared to the controls. The HT+L-T4 group had FT4, FT3 and FT3/FT4 levels equivalent to those of the controls. The HT-alone group had significantly lower FT4 (P<0.01), equivalent FT3 (P=0.083), and significantly higher FT3/FT4 (P<0.001) ratios than the controls. CONCLUSIONS: The presence of the remnant thyroid tissue was associated with different thyroid hormone balances in thyroidectomized patients, suggesting that T3 production by remnant thyroid tissue has a substantial effect on the maintenance of postoperative serum T3 levels.

Occurrence of thyroxine tablet (Thyradin S(®)) - induced liver dysfunction in a patient with subclinical hypothyroidism.

A 54-year-old woman with subclinical hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) in tablet form (Thyradin S(®)) from 25µg to 50µg. Viral hepatitis, autoimmune hepatitis and NASH were ruled out with examinations. After cessation of levothyroxine in 50µg tablet form, liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in DDW-J 2004 workshop. Thyradin S(®) powder 0.01% (here in after referred to as L-T4 in powder form) was tried as an alternative, and liver enzymes have remained within normal range. As for Thyradin S(®) tablet, additives are different for each type of levothyroxine sodium content. The difference of additive is whether Fe2O3 is contained or not: it is not included in Thyradin S(®) 50µg tablet and powder form. Although there are two case reports in the Japanese literature and three case reports in the English literature of liver dysfunction suspected due to L-T4, we cannot find past reports about cases of drug induced liver dysfunction due to Fe2O3 free levothyroxine tablet form. This is a rare case report of drug induced liver injury due to Fe2O3 free levothyroxine tablet form, and administration of L-T4 in powder form may be useful for treatment of cases similar to this one.

Rapid bioassay for detection of thyroid-stimulating antibodies using cyclic adenosine monophosphate-gated calcium channel and aequorin.

BACKGROUND: Thyroid-stimulating antibodies (TSAb) are known to be responsible for hyperthyroidism in Graves' disease (GD). The conventional methods to measure TSAb depend on cell-based assays that require cumbersome procedures and a sterilized tissue culture technique. The aim of the present study was to develop a ready-to-use cell-based assay for measuring TSAb activity without requiring sterilized conditions. METHODS: We developed a new assay kit using a frozen Chinese hamster ovary cell line expressing the thyroid-stimulating hormone receptor, cyclic adenosine monophosphate (cAMP)-gated calcium channel and aequorin, tentatively named the aequorin TSAb assay. Activated stimulatory G-protein-coupled adenylate cyclase increases intracellular cAMP, which then binds to the cyclic nucleotide-gated calcium channel. Activation of this channel allows Ca(2+) to enter the cell, and the influx of Ca(2+) can be measured with aequorin, which is quantified by a luminometer. Results can be obtained in only 4 h without sterilized conditions. TSAb activities were expressed by international units using the NIBSC 08/204 standard. RESULTS: Positive results of aequorin TSAb were obtained in 197 of 199 (98.9%) of untreated patients with GD. Only 1 of 42 (2.3%) patients with painless thyroiditis had a weakly positive aequorin TSAb. All 45 patients with subacute thyroiditis and 185 normal subjects showed negative aequorin TSAb. As for chronic thyroiditis, all 52 euthyroid patients showed negative aequorin TSAb, but 8 of 50 (16.0%) hypothyroid patients had a positive reaction. However, these positive reactions were not induced by serum thyroid-stimulating hormone (TSH) and were thought to be induced by the stimulating activity of anti-TSH receptor immunoglobulins. Conventional porcine TSAb and Elecsys thyroid-stimulating hormone receptor antibodies were positive in 69.3 and 95.5% of GD, respectively. CONCLUSION: The aequorin TSAb assay was positive in 98.9% of GD and was more sensitive than the conventional assay. This assay can be conducted in only 4 h without sterilized conditions and is practically useful in general clinical laboratories.

Metastatic carcinoma to the thyroid gland from renal cell carcinoma: role of ultrasonography in preoperative diagnosis.

BACKGROUND: Patients with metastases to the thyroid from renal cell carcinoma (RCC) that need surgical management are not many and unfamiliar to clinicians and thyroid endocrinologists. Therefore, little information is available on ultrasonographic features of metastatic carcinoma in the thyroid. The strategic value of ultrasound in preoperative surgical planning for patients with thyroid nodules has become increasingly appreciated. The purposes of this article are to clarify the ultrasound characteristics of metastatic carcinoma to the thyroid from RCC by evaluating many patients in one institute, and to investigate the role of ultrasonography in preoperative diagnosis. METHODS: Ten patients with these carcinomas who had undergone surgical management were investigated clinically and ultrasonographically. Ultrasonographic features to be evaluated were the form of involvement in the thyroid, size, shape, pattern, calcifications, vascularity, and tumor thrombus. Clinical features were previous history of RCC, serum thyroglobulin levels, cytology, preoperative diagnosis, and surgery. RESULTS: Ultrasonographic features of these carcinomas were more likely to involve a solitary, irregular, and solid without calcifications, and prominent intra-tumoral vascularity and tumor thrombus in the vein. These patients tended to be older, and to have relatively late recurrence in the thyroid, RCC in the right kidney as the primary site, and relatively low serum thyroglobulin levels. CONCLUSIONS: Metastatic carcinomas to the thyroid from RCC presented highly characteristic features on ultrasonography. These ultrasonographic features combined with cytological findings and previous medical history of RCC can provide the optimal process for the preoperative diagnosis of such patients.

Thyroxine treatment may be useful for subclinical hypothyroidism in patients with female infertility.

Infertile women sometimes associated with subclinical hypothyroidism (SCH). The guidelines of the American Endocrine Society, and American Association of Clinical Endocrinologists and American Thyroid Association recommend treatment with thyroxine (T4) for patients with SCH who want to have children. We examined 69 female infertile patients with SCH and the effects of levothyroxine (l-T4) therapy on pregnancy rates and pregnancy outcomes were observed. Fifty-eight (84.1%) patients successfully conceived during the T4 treatment period (Group A), although 17 patients (29.3%) had miscarriage afterward. The remaining 11 patients continued to be infertile (Group B). The median TSH value in Group A before the T4 treatment was 5.46 µIU/mL (range 3.1-13.3) and this significantly decreased to 1.25 µIU/mL (range 0.02-3.75) during the treatment (p<0.001). The estimated duration of infertility before the T4 treatment was 2.8±1.7 years and the duration until pregnancy after the treatment was significantly shorter at 0.9±0.9 years (p<0.001). Shortening of the infertile period after the T4 therapy was observed not only in patients who were treated with assisted reproductive technology (ART) but also in patients who conceived spontaneously in Group A. Administered T4 dose was 54.3±14.2 µg before pregnancy and 68.5±22.8 µg during pregnancy (p<0.001). Anti-thyroid autoantibodies were identified in 42.0% of all patients and no significant difference was observed in positivity between Group A and Group B. High successful pregnancy rate and shorter duration of infertility until pregnancy after T4 treatment strongly suggest that T4 enhanced fertility in infertile patients with SCH.

Cytological characteristics of papillary thyroid carcinoma on LBC specimens, compared with conventional specimens.

BACKGROUND: The cytological findings in conventional specimens (C-S) and liquid-based cytology specimens (LBC-S) are not quite same. The aim of this article is to clarify the cytological findings of papillary thyroid carcinoma (PTC) characteristic of LBC-S. METHODS: Out of 5,971 cases diagnosed in a single institution from March to September in 2012, 161 PTC cases with both C-S and LBC-S were reviewed. Additionally, we compared the findings with those in LBC-S of 55 adenomatous or hyperplastic nodule (AN) and 21 follicular neoplasm (FN) cases. RESULTS: Compared to C-S, the incidences of trabecular and hobnail patterns, collagenous stroma, naked capillaries, intercellular spaces, convoluted nuclei, eosinophilic nucleoli, and perinucleolar halo were increased. Pale nuclei were observed in only one of 161 PTC cases. Specificity of convoluted nuclei and perinucleolar halo were 97.4% and 96.1%, respectively. CONCLUSION: Convoluted nuclei and perinucleolar halo might become a new indicator of PTC in LBC-S. Contrarily, we should be aware that pale nuclei are rarely observed in LBC-S.

Papillary thyroid microcarcinoma might progress during pregnancy.

BACKGROUND: Papillary thyroid cancer occasionally occurs in women of childbearing age. As papillary thyroid microcarcinoma (PTMC) rarely grows or becomes clinically apparent, observation without surgery is an appropriate strategy for patients with low-risk PTMC. Human chorionic gonadotropin possesses weak thyroid-stimulating activity. The aim of this study was to assess the effect of pregnancy on PTMC. METHODS: We studied 9 patients with PTMC who became pregnant between 2005 and 2011. Twenty-seven age-matched nonpregnant female PTMC patients from a database we used in our previous report served as controls. Tumor enlargement was defined as an increase in the diameter of the tumor of 3 mm or more. RESULTS: PTMC enlargement occurred in 44.4% (4/9 patients) of the pregnant subjects, whereas it occurred only in 11.1% (3/27 patients) of the controls (p=0.0497). Three of the pregnant patients who exhibited tumor enlargement underwent surgery after delivery. No relationship was detected between the changes in the serum thyroglobulin level, the serum thyrotropin level, and tumor size during pregnancy. Immunohistochemical examinations did not detect the estrogen receptor in the tumors of the three patients who underwent surgery. CONCLUSIONS: This study is an initial report indicating that the risk of PTMC enlargement might increase during pregnancy. PTMC should be carefully followed-up for possible disease aggravation during pregnancy. Even if a PTMC enlarges during pregnancy, the patient's prognosis will probably not worsen.