Background The effects of moderate variations in dietary iodine intake on maternal and fetal thyroid function are poorly understood. Recent studies question the usefulness of neonatal screening of congenital hypothyroidism as a tool for monitoring iodine deficiency. We proposed to test the hypothesis of an association between iodine intake during the last trimester of pregnancy and fetal thyroid function at the time of birth. Methods The study was undertaken at term in 233 healthy pregnant women (29.75.6 years) and in their newborn. Inclusion of women in the study was done within the 24 hours prior to delivery. Results The median maternal urinary iodine concentration was 126.5 g/L. The maternal FT3, although not TSH and FT4, correlated significantly with the urinary iodine concentration (r=0.17, p=0.013). The cord blood TSH, FT4 and FT3 correlated positively with the maternal urinary iodine concentration at the time of delivery (r=0.24, p=0.001; r=0.16, p=0.032 and r=0.24, p=0.003, respectively). The cord blood and heel blood TSH correlated positively with the amniotic fluid iodine concentration (r=0.21, p=0.015 and r=0.15, p=0.036). The cord blood TSH correlated positively with the cord blood FT4 (r=0.21, p=0.022) and FT3 (r=0.32, p=0.017). The maternal TSH correlated significantly with the cord blood TSH (r=0.22, p=0.014) and with the heel blood TSH (r=0.13, p=0.050). Conclusions The results of this study show the presence of a positive association of TSH-FT4 at the time of delivery, which may be modulated by the amount of iodine consumed by the mother during pregnancy.

Background:

Distant metastasis, generally to lung and bone, is rare in differentiated thyroid carcinoma (DTC) and the prognosis is still elusive. We investigated long-term outcomes of lung metastasis in DTC patients and its prognostic factors.

Methods:

A retrospective review was performed of 4,572 patients who underwent surgery for DTC from 1962 to 2009 at Seoul National University Hospital. Among them, 164 patients were identified with lung metastasis and 152 patients were enrolled in the final analysis. Poor prognosis was defined as progressive disease or death.

Results:

Of these 152 patients, overall survival rates at 10 and 20 years were 85.0% and 71.0%, respectively. No evidence of disease, stable disease, progressive disease and death was identified in 22.4%, 28.3%, 35.5%, and 13.8%, respectively, after 11 years of median follow-up (ranges, 2-41 years). Older diagnostic age (≥45 years), primary tumor size (≥2 cm), follicular thyroid cancer, metastasis diagnosed after initial evaluation or 131I remnant ablation (late metastasis), multiple metastases other than lung, 131I non-avidity, and macronodules (≥1 cm) were more frequent in poor prognoses. Cox proportional hazard ratio for progression free survival showed that ¹³¹I non-avidity was the only independent predictive factor for poor prognosis.

Conclusions:

Lung metastasis from DTC in Korea had higher overall and progression free survival rates than in other countries. ¹³¹I non-avidity, observed more frequently in late metastasis, was only independent factor predicting poor prognosis.

Background:

Recent studies have suggested that metformin (MF) may lower thyrotropin (TSH) concentration. This implies the need for a dose reduction of levothyroxine in hypothyroid patients taking MF. The contradictory results from heterogeneous study populations mean that the underlying causes have not been completely elucidated. Patients with postoperative hypothyroidism - a condition not influenced by endogenous thyroid hormone production - have not been evaluated in this way.

Aim:

To determine the impact of MF in total thyroidectomized patients receiving levothyroxine replacement. Patients and

Methods:

One hundred and ninety-two patients underwent total thyroidectomy during a period of 3 years and were receiving levothyroxine substitution. Patients were divided into two groups depending on MF use: non-MF group [159 patients: 134 women; 52 (15.7) years old, 70.2 (13.5) kg body weight; 56 with differentiated thyroid cancer (DTC)]; and the MF group [33 patients: 24 women; 63 (9.8) years old, 79.3 (13.9) kg body weight; nine with DTC]. Levothyroxine requirements were compared between the groups, and the DTC cases were also analyzed separately.

Results:

TSH levels did not differ significantly between the MF and non-MF groups. No differences in total levothyroxine dosage were found: 114 (100-150) g in the non-MF group versus 125 (100-142) g in the MF group (p=0.9). When calculating the weight-adjusted levothyroxine dose, significant differences were evident: 1.66 (1.38-2.08) g/kg in the non-MF group versus 1.53 (1.26-1.70) g/kg in the MF group (p=0.010). However, in a multivariate regression model with TSH levels, age, BMI, gender and type of thyroid disease, metformin treatment lost its significance.

Conclusions:

Thyroidectomized patients receiving MF treatment need a lower thyroxine dose than patients that do not receive the drug, probably related with a different profile of the subset of hypothyroid patients with type 2 diabetes mellitus.

Background:

As defined by the Dietary Supplement Health and Education Act (DSHEA) 1997 such substances as herbs and dietary supplements fall under general FDA supervision but have not been closely regulated to date. We examined the thyroid hormone content in readily available dietary health supplements marketed for "thyroid support".

Methods:

Ten commercially available thyroid dietary supplements were purchased. Thyroid supplements were dissolved in 10 ml of acetonitrile and water with 0.1% trifloroacetic acid and analyzed using HPLC for the presence of both thyroxine (T4) and triiodothyronine (T3) using levothyroxine and liothyronine as a positive controls and standards.

Results:

The amount of T4 and T3 was measured separately for each supplement sample. Nine out of ten supplements revealed a detectable amount of T3 (1.3- 25.4 mcg/tablet) and five of ten contained T4 (5.77-22.9 mcg/tablet). Taken at the recommended dose, five supplements delivered T3 quantities of greater than 10 mcg/day, and four delivered T4 quantities ranging from 8.57 to 91.6 mcg/day.

Conclusions:

The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products which hold potential danger to public health.

N/A.

Background.

Several of the currently used anticancer drugs may variably affect thyroid function, with impairment ranging from modified total but not free concentration of thyroid hormones to overt thyroid disease. Summary. Cytotoxic agents seem to alter thyroid function in a relatively small proportion of adult patients. Anticancer hormone drugs may mainly alter serum levels of thyroid hormone binding proteins without clinically relevant thyroid dysfunction. "Old" immunomodulating drugs, such as interferon-, interleukin-2 and others are known to induce variably high incidence of autoimmune thyroid dysfunction. Newer immune checkpoint inhibitors, such as anti-CTLA4 monoclonal antibodies, are responsible for relatively low incidence of thyroiditis and may induce secondary hypothyroidism resulting from hypophysitis. Bexarotene is the only example of an anticancer drug causing central hypothyroidism. Despite their inherent selectivity, tyrosine kinase inhibitors may cause high rates of thyroid dysfunction. Notably, thyroid toxicity seems to be restricted to tyrosine kinase inhibitors targeting key kinase-receptors in angiogenic pathways, but not other kinase-receptors (e.g., epidermal growth factor receptors family or c-KIT). In addition, a number of these agents may also worsen the levothyroxine requirement in thyroidectomized patients.

Conclusions.

The pathophysiology of thyroid toxicity induced by many anticancer agents is not fully clarified and for others remains speculative. Thyroid dysfunction induced by anticancer agents is generally manageable and dose reduction or discontinuation of these agents is not required. The prognostic relevance of thyroid autoimmunity, overt and subclinical hypothyroidism induced by anticancer drugs, the value of thyroid hormone replacement in individuals with abnormal TSH following anticancer systemic therapy, and the correct timing of replacement therapy in cancer patients need to be defined more accurately in well powered prospective clinical trials.

Aim:

To analyze the prognostic factors affecting disease-specific survival in patients with recurrent and/or metastatic differentiated thyroid carcinoma (DTC).

Methods:

77 patients with recurrent/metastatic DTC who were previously treated with total thyroidectomy followed by radioiodine therapy were enrolled. Recurrent/metastatic disease was detected by PET/CT. At the time of last follow-up (mean: 4.8±1.3 years), patients were grouped as having (a) clinical remission (n: 17), (b) stable disease (n: 22), or (c) progressive disease (n: 38). We retrospectively examined the prognostic impact of clinical factors (age, sex, TNM stage), histopathological factors of the primary tumor (tumor size, histology, the presence of vascular invasion, extrathyroidal spread and lymph node metastasis), serum thyroglobulin (Tg) levels, and metabolic parameters of recurrent/metastatic disease such as radioiodine avidity, F18-fluorodeoxyglucose (FDG) uptake (SUVmax) in metastatic deposits, number and location of FDG-avid lesions (locoregional vs. distant), and the impact of surgery on disease-specific survival.

Results:

Lack of vascular invasion (p= 0.04), presence of surgically amenable recurrence/metastasis (p=0.0001) and suppressible on-therapy serum Tg levels at the time of recurrent/metastatic disease (p=0.01) were strong predictors of clinical remission and good prognosis on multivariate analysis. Lesional SUVmax, number or location of FDG-avid lesions, and TNM stage did not correlate with clinical outcome. Clinical remission could only be achieved by curative surgery. Patients without curative surgery for recurrence/metastasis had a 43 times higher risk to develop progressive disease than patients with disease amenable to surgery.

Conclusions:

Curative surgery is an essential therapeutic modality to achieve clinical remission in metastatic/recurrent DTC. PET/CT is a powerful method to detect surgically resectable disease for the selection of patients who may benefit from curative surgery.

No abstract required.

<b>

Background:

</b>Hospital-based studies may be hampered by referral bias. We investigated how the phenomenon may influence studies of hyperthyroid patients. <b>

Methods:

</b> By means of a computer-based linkage to the laboratory database and subsequent detailed evaluation of subjects with abnormal test results, we prospectively identified all 1,148 patients diagnosed with overt hyperthyroidism in a four year period in and around Aalborg city, Denmark. Each patient was classified according to nosological type of hyperthyroidism. We studied referral pattern of patients to local hospital unit, and analyzed how referral depended on subtype of disease, sex, age, and degree of biochemical hyperthyroidism. <b>

Results:

</b> In a four year period, 1,032 hyperthyroid patients were diagnosed at primary care and 435 of these (42.2%) were referred to specialized unit, 92 patients had hyperthyroidism diagnosed in other hospital departments (referral: 43, 46.7%), and 24 patients had hyperthyroidism diagnosed at the specialized unit after referral for other diseases. Patients suffering from Graves´ disease (GD, n=474, median age=65.8 years) were referred more often (OR(95%-CI) : 1.7(1.3-2.2)) than those diagnosed with multinodular toxic goitre (MNTG, n=525, median age=74.6 years). Higher age was associated with less referral of patients suffering from MNTG (referred vs. non-referred patients, 64.0 vs. 77.4 years, p<0.001) and GD (43.9 vs. 56.4 years, p<0.001), whereas GD patients referred to hospital had more severe biochemical hyperthyroidism (serum total T3: 4.86 vs. 3.79 nmol/l, serum total T4: 204 vs. 180 nmol/l; both p<0.001). Findings were confirmed in multivariate models reporting age as a significant predictor for referral in both GD and MNTG (both p<0.001). Among referred hyperthyroid patients (all combined), those aged up to 40 years of age (referral rate: 66.8%) were represented 11.6(6.6-20.6) times more often than those aged 80 years and above (referral rate: 14.8%). <b>

Conclusions:

</b>Hyperthyroid patients referred to a specialized hospital unit were younger (GD + MNTG) and had more severe biochemical hyperthyroidism (GD) compared to non-referred patients. Thus, referral bias may influence hospital-based studies of hyperthyroid patients, and may hamper external generalization of such studies. <b>We don´t know if the referral bias of hyperthyroid patients in Denmark can be generalized to other countries or cultures.</b>

Background:

There continues to be controversy regarding what clinico-pathological features confer a higher risk of adverse outcome in papillary microcarcinomas (PMC). The aim of this study is to assess the prognostic values of a meticulous histologic examination in PMC.

Methods:

All papillary thyroid carcinoma (PTC) <1 cm in size without associated larger thyroid carcinomas (TC), identified between 1977 and 2002, were categorized as PMC and subjected to a meticulous histopathologic examination by 2 thyroid pathologists.

Results:

148 PMC fulfilled the inclusion criteria. Within PMC, young age, male sex, tumor multicentricity, extrathyroidal extension, infiltrative and larger tumor (> 0.5 cm) correlated with the presence of >1 cm metastatic node (MN) or >3 MN at presentation (p<0.05). With a median follow up (FU) of 9.9 years. only one (0.7%) of 134 PMC patients died of TC and 3 (2.2%) had recurrences in the neck. The patient who died harbored a poorly differentiated carcinoma (PDC) in his MN. The presence of MN and especially a large size MN (>1 cm) correlated with worse Recurrence free survival (RFS) (p=0.005, p<0.0001 respectively). Except for one, all individuals with clinically adverse outcomes had >1 cm MN. Patients whose MN were predominantly composed of PDC or tall cell variant PTC had a significant shorter RFS (p<0.0001). Only 1 of 80 radioactive iodine (RAI) naïve PMC patients with absent or small MN (<=1 cm) recurred with a median FU of 9.2 years.

Conclusions:

1) The size and histotype of the MN are predictors of outcome in PMC and should be recorded. 2) The very rare PMC who recur or even die of disease have usually aggressive histopathologic features at presentation. 3) PMC with nodal disease that is small or absent at presentation are at very low risk of recurrence and may be spared RAI therapy.