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1.
Diagnosis and treatment of hypothyroidism in the elderly.
Duntas, LH, Yen, PM
Endocrine. 2019;(1):63-69
Abstract
The global population is aging with millions of people today living into their 90 s. Thyroid disease, particularly hypothyroidism, is widespread among all age groups, and it is expected to steadily increase as the population gets older. Clinical diagnosis of hypothyroidism is challenging, as the TSH reference range needs to be evaluated according to age, while evaluation of TSH levels must also take into account body weight and other variants such as polypharmacy, comorbidities, and general health condition. Since thyroid hormone has a potent regulatory effect on cholesterol metabolism, the possibility of thyroid dysfunction should be considered in cases of unexplained dyslipidemia. Once hypothyroidism has been confirmed, treatment requires caution, frequent cardiovascular monitoring, and individualized (precision) medicine. Treatment of subclinical hypothyroidism (SCH) in the elderly should be undertaken with care, guided by age and the degree of SCH: a TSH higher than 10 mU/l seems a reasonable threshold, though it should be regularly re-evaluated, while the LT4 dose needs to be tailored, taking into account the patient's health condition and the potential presence of dyslipidemia as well as other metabolic derangements.
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2.
Evaluation and management of the child with hypothyroidism.
Leung, AKC, Leung, AAC
World journal of pediatrics : WJP. 2019;(2):124-134
Abstract
BACKGROUND Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes. DATA SOURCES A PubMed search was completed in Clinical Queries using the key terms "hypothyroidism". RESULTS Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. CONCLUSIONS To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2 weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.
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3.
Amiodarone induced myxedema coma: Two case reports and literature review.
Hawatmeh, A, Thawabi, M, Abuarqoub, A, Shamoon, F
Heart & lung : the journal of critical care. 2018;(4):429-431
Abstract
Amiodarone is a benzofuran derivative that contains 37% iodine by weight and is structurally similar to the thyroid hormones. Amiodarone has a complex effect on the thyroid gland, ranging from abnormalities of thyroid function tests to overt thyroid dysfunction, with either thyrotoxicosis or hypothyroidism. Myxedema coma secondary to amiodarone use has been rarely reported in the literature. Our two case reports are an add on to the literature, and illustrate that amiodarone is an important cause of thyroid dysfunction including hypothyroidism and myxedema coma. Hence, healthcare providers should have a high index of suspicion for these conditions while treating patients who are taking amiodarone therapy as early recognition and management are essential to optimize outcomes.
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4.
Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm.
Favresse, J, Burlacu, MC, Maiter, D, Gruson, D
Endocrine reviews. 2018;(5):830-850
Abstract
Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.
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5.
Treatment of refractory thyroid cancer.
Berdelou, A, Lamartina, L, Klain, M, Leboulleux, S, Schlumberger, M
Endocrine-related cancer. 2018;(4):R209-R223
Abstract
Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two-thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.
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6.
Preconception management of thyroid disorders.
Kalra, B, Gupta, Y, Kalra, S
JPMA. The Journal of the Pakistan Medical Association. 2017;(4):645-647
Abstract
Thyroid function is closely interlinked with pregnancy. Maternal and foetal outcomes can be improved if optimal thyroid function is achieved, and maintained prior to conception. This needs a systematic approach which includes rational screening, appropriate management, and pragmatic counseling. This review describes pre-conception management of thyroid disorders, and completes an earlier article on preconception management of other endocrine diseases.
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7.
Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review.
Skelin, M, Lucijanić, T, Amidžić Klarić, D, Rešić, A, Bakula, M, Liberati-Čizmek, AM, Gharib, H, Rahelić, D
Clinical therapeutics. 2017;(2):378-403
Abstract
PURPOSE Levothyroxine (LT4) is a drug with a narrow therapeutic index, applied in small amounts (micrograms), which makes interactions in the absorption phase clinically significant. The main aim of this article was to review and present the latest information on factors that affect the gastrointestinal absorption of this drug. METHODS Relevant data were collected by using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words levothyroxine and absorption. Searches were not limited to specific publication types, study designs, dates, or languages. The reports were highly variable in the amount of information provided regarding study design and methods. Because of the heterogeneity of studies, no statistical analysis was performed. FINDINGS Many gastrointestinal disorders, such as celiac disease, atrophic gastritis, lactose intolerance, and Helicobacter pylori infection, may impede the absorption of levothyroxine. During treatment of these disorders, it is necessary to monitor serum thyroid-stimulating hormone and free T4 values to reduce the risk of developing iatrogenic hyperthyroidism. Soybeans and coffee have the greatest impact on the reduction of absorption, whereas vitamin C has the ability to increase it. Conversely, the effect of dietary fiber on the absorption of LT4 is not yet fully understood; further research is needed on this topic. A decrease in the absorption of LT4 is established and clinically significant when administered concomitantly with cholestyramine, colesevelam, lanthanum, calcium carbonate, calcium citrate, calcium acetate, iron sulfate, ciprofloxacin, aluminum hydroxide, sevelamer, or proton pump inhibitors. This effect should be taken into consideration when prescribing these drugs concomitantly with LT4. The effects of Giardia lamblia infection and the influence of orlistat, polystyrene sulfonate, raloxifene, and simethicone on absorption of LT4 have been poorly documented. For bariatric surgery, sucralfate and H2-antagonist interactions are not well founded or contradictory evidence is available regarding their existence; additional research should be conducted. IMPLICATIONS The majority of the interactions are clinically significant. They are based on the LT4 adsorption on interfering substances in the digestive tract, as well as a consequently reduced amount of the drug available for absorption. These interactions can be avoided by separating the administration of LT4 and the interfering substance.
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8.
Effect of levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: a meta-analysis.
Zhao, T, Chen, B, Zhou, Y, Wang, X, Zhang, Y, Wang, H, Shan, Z
BMJ open. 2017;(10):e016053
Abstract
BACKGROUND Subclinical hypothyroidism (SCH) has been associated with increased carotid intima-media thickness (C-IMT) in recent studies, but the effects of levothyroxine (L-T4) therapy on C-IMT in SCH patients are still controversial. AIM: To evaluate the effect of L-T4 therapy on endothelial function as determined by C-IMT in patients with SCH. METHODS BeforeJuly 2016, we searched the PubMed, Embase, Cochrane Library and Google Scholar databases, selecting published randomised controlled trials (RCTs) and self-controlled trials for the meta-analysis. RESULTS Three RCTs with 117 patients were considered appropriate for the meta-analysis. The results of the meta-analysis indicated that L-T4 significantly decreased the development of C-IMT (weighted mean difference (WMD) -0.05 mm, 95% CI -0.08 to -0.01 mm; p=0.025). We also analysed nine studies (self-controlled trials) with 247 patients and extracted the IMT of SCH patients before and after L-T4 treatment. After L-T4 therapy, the pooled estimate of the WMD of decreased C-IMT was -0.04 mm (95% CI -0.07 to -0.02 mm; p=0.05). Subgroup analysis showed that L-T4 therapy was associated with a decrease in C-IMT among patients of mixed genders (WMD -0.03 mm, 95% CI -0.06 to -0.01 mm; p=0.145). L-T4 therapy was associated with a decrease in C-IMT among female patients (WMD -0.07 mm, 95% CI -0.14 to -0.01; p=0.186). Longer treatment (>6 months) also resulted in a significant decrease in C-IMT (WMD -0.05 mm, 95% CI -0.08 to -0.02; p=0.335). CONCLUSION This meta-analysis indicates that L-T4 treatment of SCH patients can reduce C-IMT, possibly as a result of the reduction of total cholesterol, triglyceride, low density lipoprotein, systolic blood pressure, diastolic blood pressure, lipoprotein(a), and flow-mediated dilatation. Decreased C-IMT was observed in SCH patients after long-term (>6 months) L-T4 treatment. RCTs with larger samples are needed to verify these observations.
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9.
Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update.
Fallahi, P, Ferrari, SM, Ruffilli, I, Ragusa, F, Biricotti, M, Materazzi, G, Miccoli, P, Antonelli, A
Expert opinion on drug delivery. 2017;(5):647-655
Abstract
The most recent advance concerning levothyroxine (L-T4) therapy is the development of novel oral formulations: the liquid preparation, and the soft gel capsule. Areas covered: This review evaluates the most recent clinical studies about these new formulations. The liquid formulation has been shown to overcome: the food and beverages intereference with L-T4 tablets absorption, caused by food or coffee at breakfast; malabsorption induced by the increased gastric pH, resulting from atrophic gastritis, or due to proton-pump inhibitors; and malabsorption after bariatric surgery. The use of liquid L-T4 has been studied also in pregnancy, newborns and infants, suggesting a better bioequivalence than tablets. Finally, liquid L-T4 is more active than tablets in the control of thyroid-stimulating hormone (TSH) in hypothyroid patients without malabsorption, drug interference, or gastric disorders, leading to a hypothesized higher absorption of liquid L-T4 also in these patients. Few studies have evaluated soft gel L-T4 with promising results in patients with malabsorption related to coffee or gastritis. Expert opinion: Liquid L-T4 (and soft gel capsules) are more active than the tablet L-T4 in the control of TSH in hypothyroid patients with gastric disorders, malabsorption, or drug interference, but also in patients without absorption disorders.
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10.
Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis.
Winther, KH, Wichman, JE, Bonnema, SJ, Hegedüs, L
Endocrine. 2017;(2):376-385
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Abstract
By a systematic review and meta-analysis to investigate clinically relevant effects of selenium supplementation in patients with chronic autoimmune thyroiditis. Controlled trials in adults (≥18 years) with autoimmune thyroiditis, comparing selenium with or without levothyroxine substitution, versus placebo and/or levothyroxine substitution, were eligible for inclusion. Identified outcomes were serum thyrotropin (thyroid stimulating hormone) levels in LT4-untreated patients, thyroid ultrasound and health-related quality of life. Eleven publications, covering nine controlled trials, were included in the systematic review. Random effects model meta-analyses were performed in weighted mean difference for thyroid stimulating hormone, ultrasound and health-related quality of life. Quality of evidence was assessed per outcome, using GRADE. Meta-analyses showed no change in thyroid stimulating hormone, or improvements in health-related quality of life or thyroid echogenicity (ultrasound), between levothyroxine substitution-untreated patients assigned to selenium supplementation or placebo. Three trials found some improvement in wellbeing in patients receiving levothyroxine substitution, but could not be synthesized in a meta-analysis. The quality of evidence ranged from very low to low for thyroid stimulating hormone as well as ultrasound outcomes, and low to moderate for health-related quality of life, and was generally downgraded due to small sample sizes. We found no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound, in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients. Future well-powered RCTs, evaluating e.g. disease progression or health-related quality of life, are warranted before determining the relevance of selenium supplementation in autoimmune thyroiditis.