Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Thyroid gland: a rare site of metastasis.

PURPOSE: Despite its rich vascularity, metastasis (MTS) to the thyroid tissue is unusual, ranging from 1 to 3%. This entity is not usually considered as differential diagnosis and is not included in the upfront approach in patients with thyroid nodules. Once diagnosed, treatment is controversial. The aim of this study was to evaluate diagnosis, treatment, and outcome at the end of follow-up in patients with a diagnosis of MTS to the thyroid. METHODS: A retrospective multicenter study was designed from 1985 to 2022; 29 patients with MTS to the thyroid gland were included in the analysis. RESULTS: Clinical presentation included the presence of a nodular goiter (65.5%), compression symptoms (17.2%), diffuse goiter (10.3%), and suspicious lymph nodes in the neck (7%). Primary tumor sites were: kidney (44.8%), breast (24.1%), lung (13.8%), neuroendocrine system (6.9%), colon (3.4%), cervix (3.4%), and ovary (3.4%). In 18/23 patients, suspicious ultrasound criteria for malignancy were described. Preoperative diagnosis was made in 23/27 patients by FNA and confirmed in 18 cases by immunohistochemistry. Seventeen patients underwent surgery. At the end of the follow-up, 19 patients had died of oncological disease, and six were alive (2/6 disease-free with isolated intrathyroidal MTS). CONCLUSION: Renal carcinoma was the tumor that most frequently metastasized to the thyroid gland. Immunodiagnosis was a very useful tool for etiological confirmation. Patients with MTS to the thyroid gland as a unique site had a more favorable course compared to patients with multiple metastatic sites. Finally, outcomes and prognosis essentially depended on the biology of the primary tumor.

Thyroid cancer and insulin resistance.

Thyroid cancer has shown a parallel increase with diabetes in the last few years. This narrative review aims to explain the association between these two entities, focusing on insulin resistance as the mediator and exploring the effects of antidiabetic agents on thyroid cancer incidence and progression.We searched Pubmed for English-written articles on insulin resistance, diabetes, antidiabetic treatments, and thyroid cancer reported from January 2019 to April 2023. Exclusion criteria were preclinical and clinical studies involving a population with thyroid dysfunction, benign nodular goiter, or those that only analyzed thyroid cancer's association with obesity.The results of the narrative literature review revealed 96 articles. Additionally, four studies from a manual search were retrieved. After the exclusion criteria were applied, we included 20 studies. Out of 8 studies on insulin-resistant or Metabolic Syndrome patients, all suggest a positive association with thyroid cancer. At the same time, for diabetes, four out of five publications support a link with thyroid cancer. The seven remaining studies on antidiabetics suggest that metformin might benefit thyroid cancer. In contrast, the evidence for an association between Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and increased thyroid cancer findings is limited.In conclusion, the association between thyroid cancer and diabetes may be explained by insulin resistance, as shown in observational studies. However, the causal role is yet to be defined. Although the wide use of different antidiabetic agents has been related to thyroid cancer prevalence and progression, future research with drugs such as metformin or GLP-1 RA is still needed.

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Background: Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Methods: Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Results: Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. Conclusion: In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids.

Benefits of the omega-3 polyunsaturated fatty acids (PUFA) on a number of clinical disorders, including autoimmune diseases, are widely reported in the literature. One major dietary source of PUFA are fish, particularly the small oily fish, like anchovy, sardine, mackerel and others. Unfortunately, fish (particularly the large, top-predator fish like swordfish) are also a source of pollutants, including the heavy metals. One relevant heavy metal is mercury, a known environmental trigger of autoimmunity that is measurable inside the thyroid. There are a number of interactions between the omega-3 PUFA and thyroid hormones, even at the level of the thyroid hormone transport proteins. Concerning the mechanisms behind the protection from/amelioration of autoimmune diseases, including thyroiditis, that are caused by the omega-3 PUFA, one can be the decreased production of chemokines, a decrease that was reported in the literature for other nutraceuticals. Recent studies point also to the involvement of resolvins. The intracellular increase in resolvins is associated with the tissue protection from inflammation that was observed in experimental animals after coadministration of omega-3 PUFA and thyroid hormone. After having presented data on fish consumption at the beginning, we conclude our review by presenting data on the market of the dietary supplements/nutraceuticals. The global omega-3 products market was valued at USD 2.10 billion in 2020, and was projected to go up at a compound annual growth rate of 7.8% from 2020 to 2028. Among supplements, fish oils, which are derived mainly from anchovies, are considered the best and generally safest source of omega-3. Taking into account (i) the anti-autoimmunity and anti-cancer properties of the omega-3 PUFA, (ii) the increasing incidence of both autoimmune thyroiditis and thyroid cancer worldwide, (iii) the predisposing role for thyroid cancer exerted by autoimmune thyroiditis, and (iv) the risk for developing metabolic and cardiovascular disorders conferred by both elevated/trendwise elevated serum TSH levels and thyroid autoimmunity, then there is enough rationale for the omega-3 PUFA as measures to contrast the appearance and/or duration of Hashimoto's thyroiditis as well as to correct the slightly elevated serum TSH levels of subclinical hypothyroidism.

Development of Histologically Verified Thyroid Diseases in Women Operated for Breast Cancer: A Review of the Literature and a Case Series.

BACKGROUND: The possible relationships between breast and thyroid diseases have been reported in the literature. The purpose of our study was to evaluate the occurrence of histologically verified thyroid pathologies in women who were diagnosed with breast cancer and, after mastectomy/quadrantectomy complemented by oncological treatment, were thyroidectomized based on their periodic thyroid evaluation. PATIENTS AND METHODS: Our series consist of 31 women with a mean age of 62.9 ± 10.9 years (range, 45-81) treated for breast cancer (18 right-sided, 11 left-sided, and 2 bilateral), of whom 29 were thyroidectomized, since two women who developed Graves' disease refused thyroidectomy. These 31 women belong to a cohort of 889 women who referred to the Breast Surgery Unit of our university hospital during the period January 2010 through December 2020. RESULTS: The mean time interval between breast cancer and thyroid pathologies was 48.1 ± 23.4 months (range, 12-95). The final diagnosis at histopathology was infiltrating ductal breast carcinoma in 26 women (with 2/26 patients having bilateral carcinoma) and infiltrating lobular breast carcinoma in the other 5 women. Ten of the twenty-nine thyroidectomized women (34.5%) had a thyroid malignancy on histology: five papillary carcinomas, three papillary micro-carcinomas and two follicular carcinomas. Two of the five women with papillary carcinoma also had histological evidence of chronic lymphocytic thyroiditis/Hashimoto's thyroiditis, which was also detected in another five women with benign thyroid diseases. CONCLUSIONS: We suggest that breast cancer survivors should be made aware of the possible increased risk of thyroid pathologies (including thyroid malignancy) so that they can undergo screening and follow-up.

Incidence and predictive factors of postoperative hypocalcaemia according to type of thyroid surgery in older adults.

PURPOSE: Transient hypocalcaemia after thyroid surgery and its possible predictors have not been extensively described in the elderly. This study aimed to establish the frequency of postsurgical transient hypocalcaemia according to the extent of thyroid surgery in older adults and to assess mineral metabolism biochemical parameters as its predictors. METHODS: All patients ≥60 years undergoing thyroid surgery were prospectively included. Type of surgery (hemithyroidectomy(HT) or total thyroidectomy(TT)); and preoperative 25OH Vitamin D (25OHD) and pre and 6 (only TT), 24 h and 6 months postsurgical serum levels of calcium, magnesium, phosphate and parathormone (PTH) were considered. Postsurgical hypoparathyroidism (hPTpost) was defined at PTH levels ≤11 pg/mL. RESULTS: Out of 46 patients (87% female), age (mean ± SD) 70.1 ± 6.2 years, 24 h postsurgical hypocalcaemia was found in ten patients (22%). In 25 (54%) TT patients, 36% and 16% had postsurgical hypocalcaemia at 6 and 24 h respectively; 28% hPTpost but no definitive hPT was recorded and 44% had 25OHD deficiency. Lower 24 h magnesium levels were found in those TT patients with 24 h hypocalcaemia (1.6 ± 0.1 vs 1.9 ± 0.1 mg/dL (p = 0.005)). Among 21 (46%) HT patients, 28.6% had 24 h postsurgical hypocalcaemia; 9.5% had hPTpost. A positive correlation was observed between preoperative 25OHD and 24 h calcaemia (r:0.51,p = 0.02). 43% of the patients were 25OHD deficient, in whom 55% had 24 h hypocalcaemia vs only 9% in the 25OHD sufficient group (p = 0.049). CONCLUSION: Postsurgical hypocalcaemia was common in elderly thyroidectomized patients. After TT, lower magnesium levels were found in those patients with 24 h hypocalcaemia. In the HT group, preoperative 25OHD deficiency predicted lower postsurgical calcium levels.

Frequent neck US in papillary thyroid cancer likely detects non-actionable findings.

BACKGROUND: American Thyroid Association (ATA) low-intermediate-risk papillary thyroid cancer (PTC) patients without structural and biochemical evidence of disease on initial post-treatment evaluation have a low risk of recurrence. Studies have shown that with current ultrasound scans (US) and thyroglobulin assays, recurrences mostly occurred 2-8 years after initial therapy. The ATA recommends that neck US be done 6-12 months after surgery to establish patient's response to therapy, then periodically depending on risk of recurrence. The lack of clarity in recommendations on timing of follow-up US and fear of recurrence leads to frequent tests. OBJECTIVES: To evaluate the utility of routine neck US in ATA low-intermediate-risk PTC patients with no structural disease on neck US and non-stimulated thyroglobulin <1.0 ng/mL after initial therapy. METHODS: A retrospective study of 93 patients from Singapore, Saudi Arabia and Argentina with ATA low (n = 49) to intermediate (n = 44) risk PTC was conducted between 1998 and 2017. The outcome was to measure the frequency of identifying structural disease recurrence and non-actionable US abnormalities. RESULTS: Over a median follow-up of 5 years, five of the 93 patients (5.4%) developed structural neck recurrence on US at a median of 2.5 years after initial treatment. Indeterminate US abnormalities were detected in 19 of the 93 patients (20.4%) leading to additional tests, which did not detect significant disease. CONCLUSION: In ATA low-intermediate-risk PTC with no suspicious findings on neck US and a non-stimulated thyroglobulin of <1.0 ng/mL after initial therapy, frequent US is more likely to identify non-actionable abnormalities than clinically significant disease.

Sonographic Risk Stratification Systems for Thyroid Nodules as Rule-Out Tests in Older Adults.

Ultrasonographic risk-stratification systems (RSS), including various Thyroid Imaging Reporting and Data Systems (TIRADS), were proposed to improve reporting and reduce the number of fine-needle aspiration biopsies. However, age might be a confounder since some suspicious ultrasonographic features lack specificity in elderly patients. We aimed to investigate whether the diagnostic performance of the RSS varied between age groups. All patients consecutively referred for thyroid biopsy between November 1, 2015, and March 10, 2020, were included. The malignancy risk of each nodule was estimated according to five RSS: the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi guidelines, the American College of Radiology (ACR) TIRADS, the American Thyroid Association guidelines, the European TIRADS, and the Korean TIRADS. Overall, 818 nodules (57 malignant) were evaluated. The malignancy rate was higher in patients ≤ 65 years (8.1%) than in patients > 65 years (3.8%; p = 0.02). All RSS confirmed a significant discriminative performance in both age groups, with a negative predictive value of 100% in patients > 65 years, although specificity was lower in older patients. The ACR TIRADS was the best performing in both age groups. RSS could avoid a sizable number of biopsies when applied as rule-out tests in elderly patients.

Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity.

BACKGROUND AND AIMS: Glomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown. METHODS AND RESULTS: Cross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m2. Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (-12%), NEFA (-26%) and uric acid (-22%) than those without GH (all p < 0.05). Similarly to high sensitivity C-reactive protein (hsCRP), there were no differences in serum chemokines between children with GH or not (all p > 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = -0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05). CONCLUSION: GH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings.

Comparison of different systems of ultrasound (US) risk stratification for malignancy in elderly patients with thyroid nodules. Real world experience.

PURPOSE: To comparatively assess the performance of three sonographic classification systems, American Thyroid Association (ATA), the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), and American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE)/Associazione Medici Endocrinologi (AME) in identifying malignant nodules in an elderly population. METHODS: Cross-sectional study of patients referred for fine needle aspiration biopsy in an academic center for the elderly. One nodule/patient was considered. Nodules classified Bethesda V/VI were considered malignant. Receiver operating characteristics (ROC) curves were established and compared to evaluate diagnostic performance. Malignancy among biopsies below the size cutoff for each ultrasound classification was also compared. RESULTS: One thousand, eight hundred sixty-seven patients (92% females); median (Q1-Q3), age 71 (67-76) years, were studied showing 82.8% benign (Bethesda II) and 2.6% malignant cytology. The three classifications correctly identified malignancy (P < 0.01). Nonetheless, in the ATA and AACE/ACE/AME 16 and 2 malignant nodules, respectively, were unclassifiable. Including unclassified malignant nodules (n = 1234, malignant = 50), comparison of the ROC curves showed lower performance of ATA [area under the curve (AUC) = ATA (0.49) vs. ACR TI-RADS (0.62), p = 0.008 and ATA vs. AACE/ACE/AME (0.59), p = 0.022]. Proportion of below size cutoff biopsies for ATA, ACR TI-RADS, and AACE/ACE/AME was different [16, 42, and 29% (all p < 0.001)], but no differences in malignancy rate were observed in these nodules. CONCLUSION: The present study is the first to validate in elderly patients these classifications showing that AACE/ACE/AME and ACR TI-RADS can predict thyroid malignancy more accurately than the ATA when unclassifiable malignant nodules are considered. Moreover, in this aged segment of the population, the use of ACR TI-RADS avoided more invasive procedures.

CASE FINDING FOR HYPOTHYROIDISM SHOULD INCLUDE TYPE 2 DIABETES AND METABOLIC SYNDROME PATIENTS: A LATIN AMERICAN THYROID SOCIETY (LATS) POSITION STATEMENT.

OBJECTIVE: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients. METHODS: A search was made in PubMed using the following terms: "hypothyroidism" AND "diabetes" OR "metabolic syndrome." The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected. RESULTS: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60). CONCLUSION: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients. ABBREVIATIONS: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism.

Thyroid dysfunction, manifesting as either overt or subclinical hypothyroidism, negatively affects lipid metabolism: this leads to hypercholesterolemia which progressively increases the risk for cardiovascular disease and, potentially, mortality. Hypercholesterolemia in hypothyroidism is mainly due to a reduction in low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant diminishing control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate-limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity. Recently, 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, was found to repress the transcription factor carbohydrate-response element-binding protein (ChREBP) and also to be involved in lipid catabolism and lipogenesis, though via a different pathway than that of T3. While thyroid hormone could therapeutically reverse the dyslipidemic profile commonly occurring in hypothyroidism, it should be borne in mind that the potency of the effects may be age-and sex-dependent. Thyroid hormone administration possibly also sustains and enhances the efficacy of hypolipidemic drugs, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9), in patients with dyslipidemia and hypothyroidism.

Should Age at Diagnosis Be Included as an Additional Variable in the Risk of Recurrence Classification System in Patients with Differentiated Thyroid Cancer.

OBJECTIVE: To evaluate the influence of age at diagnosis on the frequency of structural incomplete response (SIR) according to the modified risk of recurrence (RR) staging system from the American Thyroid Association guidelines. PATIENTS AND METHODS: We performed a retrospective analysis of 268 patients with differentiated thyroid cancer (DTC) followed up for at least 3 years after initial treatment (total thyroidectomy and remnant ablation). The median follow-up in the whole cohort was 74.3 months (range: 36.1-317.9) and the median age at diagnosis was 45.9 years (range: 18-87). The association between age at diagnosis and the initial and final response to treatment was assessed with analysis of variance (ANOVA). Patients were also divided into several groups considering age younger and older than 40, 50, and 60 years. RESULTS: Age at diagnosis was not associated with either an initial or final statistically significant different SIR to treatment (p = 0.14 and p = 0.58, respectively). Additionally, we did not find any statistically significant differences when the percentages of SIR considering the classification of RR were compared between different groups of patients by using several age cutoffs. CONCLUSIONS: When patients are correctly risk stratified, it seems that age at diagnosis is not involved in the frequency of having a SIR at the initial evaluation or at the final follow-up, so it should not be included as an additional variable to be considered in the RR classifications.

Enfermedad no tiroidea / Non-thyroidal illness

La enfermedad no tiroidea es una entidad que se presenta frecuentemente en los pacientes que se encuentran cursando algún tipo de enfermedad, ya sea crítica o no; y puede manifestarse aun en ausencia de enfermedad tiroidea subyacente, condicionando cambios en el eje tiroideo. Es importante poder reconocer la enfermedad no tiroidea para hacer diagnóstico diferencial con la patología tiroidea verdadera y evaluar si merece ser tratada. Aún no existe consenso acerca de si la enfermedad no tiroidea representa una respuesta fisiológica a una enfermedad sistémica para que disminuyan los requerimientos de energía o si se trata de una condición adaptativa que induce un estado hipotiroideo que finalmente resulta perjudicial a nivel tisular.

Non-thyroidal illness is a disorder that occurs frequently in patients that are experiencing some kind of illness, whether critical or not. It can manifest even in the absence of thyroid dysfunction, leading to changes in the thyroid axis. It is important to detect Non-Thyroidal Illness in order to establish a differential diagnosis with the true thyroid disease and to determine whether treatment is required. Currently, there is still no consensus on whether Non-Thyroidal Illness is a physiological response to a systemic disease to reduce energy requirements or whether it is an adaptive condition that induces a hypothyroid state that ultimately is harmful at the tissue level.