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Lancet (London, England) Sep 2017Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. The... (Review)
Review
Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. The definition of hypothyroidism is based on statistical reference ranges of the relevant biochemical parameters and is increasingly a matter of debate. Clinical manifestations of hypothyroidism range from life threatening to no signs or symptoms. The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors. The standard treatment is thyroid hormone replacement therapy with levothyroxine. However, a substantial proportion of patients who reach biochemical treatment targets have persistent complaints. In this Seminar, we discuss the epidemiology, causes, and symptoms of hypothyroidism; summarise evidence on diagnosis, long-term risk, treatment, and management; and highlight future directions for research.
Topics: Disease Management; Hormone Replacement Therapy; Hypothyroidism; Thyroxine
PubMed: 28336049
DOI: 10.1016/S0140-6736(17)30703-1 -
Nature Reviews. Endocrinology Apr 2022In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine. Since then, no major innovation has emerged for... (Review)
Review
In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine. Since then, no major innovation has emerged for the treatment of hypothyroidism. The biochemical definition of subclinical hypothyroidism is a matter of debate. Indiscriminate screening for hypothyroidism has led to overdiagnosis and treatment initiation at lower serum levels of thyroid-stimulating hormone (TSH) than previously. Adverse health effects have been documented in individuals with hypothyroidism or hyperthyroidism, and these adverse effects can affect health-related quality of life (QOL). Levothyroxine substitution improves, but does not always normalize, QOL, especially for individuals with mild hypothyroidism. However, neither studies combining levothyroxine and liothyronine (the synthetic form of tri-iodothyronine) nor the use of desiccated thyroid extract have shown robust improvements in patient satisfaction. Future studies should focus not only on a better understanding of an individual's TSH set point (the innate narrow physiological range of serum concentration of TSH in an individual, before the onset of hypothyroidism) and alternative thyroid hormone combinations and formulations, but also on autoimmunity and comorbidities unrelated to hypothyroidism as drivers of patient dissatisfaction. Attention to the long-term health consequences of hypothyroidism, beyond QOL, and the risks of overtreatment is imperative.
Topics: Hormone Replacement Therapy; Humans; Hypothyroidism; Quality of Life; Thyrotropin; Thyroxine; Triiodothyronine
PubMed: 35042968
DOI: 10.1038/s41574-021-00625-8 -
Methodist DeBakey Cardiovascular Journal 2017Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility,... (Review)
Review
Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart. Additionally, we attempt to briefly describe how hypothyroid treatment affects cardiovascular parameters.
Topics: Heart; Heart Diseases; Humans; Hypothyroidism; Prognosis; Risk Assessment; Risk Factors; Thyroid Gland
PubMed: 28740582
DOI: 10.14797/mdcj-13-2-55 -
Advances in Therapy Sep 2019Hypothyroidism affects up to 5% of the general population, with a further estimated 5% being undiagnosed. Over 99% of affected patients suffer from primary... (Review)
Review
Hypothyroidism affects up to 5% of the general population, with a further estimated 5% being undiagnosed. Over 99% of affected patients suffer from primary hypothyroidism. Worldwide, environmental iodine deficiency is the most common cause of all thyroid disorders, including hypothyroidism, but in areas of iodine sufficiency, Hashimoto's disease (chronic autoimmune thyroiditis) is the most common cause of thyroid failure. Hypothyroidism is diagnosed biochemically, being overt primary hypothyroidism defined as serum thyroid-stimulating hormone (TSH) concentrations above and thyroxine concentrations below the normal reference range. Symptoms of hypothyroidism are non-specific and include mild to moderate weight gain, fatigue, poor concentration, depression, and menstrual irregularities, while the consequences of untreated or under-treated hypothyroidism include cardiovascular disease and increased mortality. Levothyroxine has long been the main tool for treating hypothyroidism and is one of the world's most widely prescribed medicines. In adults with overt hypothyroidism, levothyroxine is usually prescribed at a starting dose of 1.6 µg/kg/day, which is then titrated to achieve optimal TSH levels (0.4-4.0 mIU/L), according to the therapeutic target. We here summarise the history of levothyroxine and discuss future issues regarding the optimal treatment of hypothyroidism. Because nearly one-third of patients with treated hypothyroidism still exhibit symptoms, it is important that levothyroxine is used more appropriately to achieve maximum benefit for patients. In order to ensure this, further research should include more accurate assessments of the true prevalence of hypothyroidism in the community, optimisation of the levothyroxine substitution dose, proper duration of treatment, and identification of patients who may benefit from combination therapy with levothyroxine plus levotriiodothyronine.Funding: Merck.Plain Language Summary: Plain language summary available for this article.
Topics: Adult; Cardiovascular Diseases; Depression; Female; Humans; Hypothyroidism; Thyrotropin; Thyroxine
PubMed: 31485975
DOI: 10.1007/s12325-019-01080-8 -
Frontiers in Endocrinology 2020Subclinical hypothyroidism is a biochemical condition defined by elevated serum thyroid-stimulating hormone levels in the setting of normal levels of the peripheral... (Review)
Review
Subclinical hypothyroidism is a biochemical condition defined by elevated serum thyroid-stimulating hormone levels in the setting of normal levels of the peripheral thyroid hormones, thyroxine and triiodothyronine. Thyroid hormones act on the heart through various mechanisms and subclinical hypothyroidism has been associated with risk factors for cardiovascular disease, such as hypertension and dyslipidemia. In addition, evidence from multiple studies supports an association between subclinical hypothyroidism and cardiovascular disease. However, the use of levothyroxine in subclinical hypothyroidism to reduce cardiovascular disease risk is not clearly beneficial. Treatment with levothyroxine may only provide benefit in certain subgroups, such as patients who are younger or at higher risk of cardiovascular disease. At present, most of the international societal guidelines advise that treatment decisions should be individualized based on patient age, degree of serum thyroid-stimulating hormone (TSH) elevation, symptoms, cardiovascular disease (CVD) risk, and other co-morbidities. Further study in this area is recommended.
Topics: Animals; Cardiovascular Diseases; Humans; Hypothyroidism; Thyroxine
PubMed: 33193104
DOI: 10.3389/fendo.2020.591588 -
Acta Bio-medica : Atenei Parmensis Apr 2017Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic... (Review)
Review
Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) impairs thyroid metabolism in animals and human and may negatively affect growth and develpment of children. On the other hand both overt and subclinical hypothyroidism are associated with anemia and adding iron to thyroxine therapy improves both conditions compared to thyroxine therapy alone. In addition patients with chronic hemolytic anemia requiring repeated blood transfusion have high prevalence of hypothalamic-pituitary thyroid axis. Both primary hypothyroidism and central hypothyroidism occur in these patients with increasing prevalence with age, severity of the anemia and higher ferritin concentration denoting poor chelation. Proper blood transfusion and intensive chelation appears to prevent deterioration of thyroid function and in many cases can reverse thyroid pathology. Physicians treating these forms of anemia should be aware of thyroid disorders in these patients for early screening, prevention and proper management of any thyroid dysfunction.
Topics: Anemia, Iron-Deficiency; Anemia, Sickle Cell; Animals; Blood Transfusion; Chelation Therapy; Dietary Supplements; Humans; Hypothyroidism; Iron; beta-Thalassemia
PubMed: 28467346
DOI: 10.23750/abm.v88i1.6048 -
Medicina 2017The thyroid axis is particularly prone to interactions with a wide variety of drugs, whose list increases year by year. Hypothyroidism is the most frequent consequence... (Review)
Review
The thyroid axis is particularly prone to interactions with a wide variety of drugs, whose list increases year by year. Hypothyroidism is the most frequent consequence of drug-induced thyroid dysfunction. The main mechanisms involved in the development of primary hypothyroidism are: inhibition of the synthesis and/or release of thyroid hormones, immune mechanisms related to the use of interferon and other cytokines, and the induction of thyroiditis associated with the use of tyrosine kinase inhibitors and drugs blocking the receptors for vascular endothelial growth factor. Central hypothyroidism may be induced by inhibition of thyroid-stimulating hormone (bexarotene or corticosteroids) or by immunological mechanisms (anti-CTLA4 or anti-PD-1 antibody drugs). It is also important to recognize those drugs that generate hypothyroidism by interaction in its treatment, either by reducing the absorption or by altering the transport and metabolism of levothyroxine. Thus, it is strongly recommended to evaluate thyroid function prior to the prescription of medications such as amiodarone, lithium, or interferon, and the new biological therapies that show important interaction with thyroid and endocrine function in general.
Topics: Humans; Hypothyroidism; Thyroid Function Tests
PubMed: 29044016
DOI: No ID Found -
The Journal of Clinical Endocrinology... Oct 2021Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients.
METHODOLOGY
Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect.
RESULTS
Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component).
CONCLUSIONS
As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
Topics: Adult; Aged; Cross-Over Studies; Desiccation; Double-Blind Method; Female; Hormone Replacement Therapy; Humans; Hypothyroidism; Male; Middle Aged; Placebos; Prospective Studies; Quality of Life; Surveys and Questionnaires; Thyroid Gland; Thyroxine; Tissue Extracts; Treatment Outcome; Triiodothyronine
PubMed: 34185829
DOI: 10.1210/clinem/dgab478 -
The Journal of Clinical Endocrinology... Sep 2020It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist,... (Review)
Review
CONTEXT
It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist, and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure.
EVIDENCE ACQUISITION
This review is based on a collection of primary and review literature gathered from a PubMed search of "hypothyroidism," "levothyroxine," "liothyronine," and "desiccated thyroid extract," among other keywords. PubMed searches were supplemented by Google Scholar and the authors' prior knowledge of the subject.
EVIDENCE SYNTHESIS
In most LT4-treated patients, normalization of serum thyrotropin levels results in decreased serum T3/T4 ratio, with relatively lower serum T3 levels; in at least 15% of the cases, serum T3 levels are below normal. These changes can lead to a reduction in TH action, which would explain the slower rate of metabolism and elevated serum cholesterol levels. A small percentage of patients might also experience persistent symptoms of hypothyroidism, with impaired cognition and tiredness. We propose that such patients carry a key clinical factor, for example, specific genetic and/or immunologic makeup, that is well compensated while the thyroid function is normal but might become apparent when compounded with relatively lower serum T3 levels.
CONCLUSIONS
After excluding other explanations, physicians should openly discuss and consider therapy with LT4 and LT3 with those hypothyroid patients who have persistent symptoms or metabolic abnormalities despite normalization of serum thyrotropin level. New clinical trials focused on symptomatic patients, genetic makeup, and comorbidities, with the statistical power to identify differences between monotherapy and combination therapy, are needed.
Topics: Drug Resistance; Drug Therapy, Combination; Hormone Replacement Therapy; Humans; Hypothyroidism; Practice Patterns, Physicians'; Precision Medicine; Thyroid Function Tests; Thyrotropin; Thyroxine; Treatment Failure; Triiodothyronine
PubMed: 32614450
DOI: 10.1210/clinem/dgaa430 -
Frontiers in Endocrinology 2022Preterm newborns are forced to adapt to harsh extrauterine conditions and endure numerous adversities despite their incomplete growth and maturity. The inadequate... (Review)
Review
Preterm newborns are forced to adapt to harsh extrauterine conditions and endure numerous adversities despite their incomplete growth and maturity. The inadequate thyroid hormones secretion as well as the impaired regulation of hypothalamus-pituitary-thyroid axis may lead to hypothyroxinemia. Two first weeks after birth are pivotal for brain neurons development, synaptogenesis and gliogenesis. The decreased level of thyroxine regardless of cause may lead to delayed mental development. Congenital hypothyroidism (CH) is a disorder highly prevalent in premature neonates and it originates from maternal factors, perinatal and labor complications, genetic abnormalities, thyroid malformations as well as side effects of medications and therapeutic actions. Because of that, the prevention is not fully attainable. CH manifests clinically in a few distinctive forms: primary, permanent or transient, and secondary. Their etiologies and implications bear little resemblance. Therefore, the exact diagnosis and differentiation between the subtypes of CH are crucial in order to plan an effective treatment. Hypothyroxinemia of prematurity indicates dynamic changes in thyroid hormone levels dependent on neonatal postmenstrual age, which directly affects patient's maintenance and wellbeing. The basis of a successful treatment relies on an early and accurate diagnosis. Neonatal screening is a recommended method of detecting CH in preterm newborns. The preferred approach involves testing serum TSH and fT4 concentrations and assessing their levels according to the cut-off values. The possible benefits also include the evaluation of CH subtype. Nevertheless, the reference range of thyroid hormones varies all around the world and impedes the introduction of universal testing recommendations. Unification of the methodology in neonatal screening would be advantageous for prevention and management of CH. Current guidelines recommend levothyroxine treatment of CH in preterm infants only when the diagnose is confirmed. Moreover, they underline the importance of the re-evaluation among preterm born infants due to the frequency of transient forms of hypothyroidism. However, results from multiple clinical trials are mixed and depend on the newborn's gestational age at birth. Some benefits of treatment are seen especially in the preterm infants born <29 weeks' gestation. The discrepancies among trials and guidelines create an urgent need to conduct more large sample size studies that could provide further analyses and consensus. This review summarizes the current state of knowledge on congenital hypothyroidism in preterm infants. We discuss screening and treatment options and demonstrate present challenges and controversies.
Topics: Congenital Hypothyroidism; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Neonatal Screening; Pregnancy; Thyroid Dysgenesis; Thyroxine
PubMed: 35370986
DOI: 10.3389/fendo.2022.860862