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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 Endocrinology Apr 2022In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine.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In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine.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 -
Nature Reviews. Disease Primers May 2022Hypothyroidism is the common clinical condition of thyroid hormone deficiency and, if left untreated, can lead to serious adverse health effects on multiple organ... (Review)
Review
Hypothyroidism is the common clinical condition of thyroid hormone deficiency and, if left untreated, can lead to serious adverse health effects on multiple organ systems, with the cardiovascular system as the most robustly studied target. Overt primary hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) concentration in combination with free thyroxine (fT) concentration below the reference range. Subclinical hypothyroidism, commonly considered an early sign of thyroid failure, is defined by elevated TSH concentrations but fT concentrations within the reference range. Hypothyroidism is classified as primary, central or peripheral based on pathology in the thyroid, the pituitary or hypothalamus, or peripheral tissue, respectively. Acquired primary hypothyroidism is the most prevalent form and can be caused by severe iodine deficiency but is more frequently caused by chronic autoimmune thyroiditis in iodine-replete areas. The onset of hypothyroidism is insidious in most cases and symptoms may present relatively late in the disease process. There is a large variation in clinical presentation and the presence of hypothyroid symptoms, especially in pregnancy and in children. Levothyroxine (LT4) is the mainstay of treatment and is one of the most commonly prescribed drugs worldwide. After normalization of TSH and fT concentrations, a considerable proportion of patients treated with LT4 continue to have persistent complaints, compromising quality of life. Further research is needed regarding the appropriateness of currently applied reference ranges and treatment thresholds, particularly in pregnancy, and the potential benefit of LT4/liothyronine combination therapy for thyroid-related symptom relief, patient satisfaction and long-term adverse effects.
Topics: Child; Female; Humans; Hypothyroidism; Iodine; Pregnancy; Quality of Life; Thyrotropin; Thyroxine
PubMed: 35589725
DOI: 10.1038/s41572-022-00357-7 -
Annals of Internal Medicine Jul 2020Hypothyroidism is a common condition in which the thyroid gland provides insufficient amounts of thyroid hormone for the needs of peripheral tissues. The most common...
Hypothyroidism is a common condition in which the thyroid gland provides insufficient amounts of thyroid hormone for the needs of peripheral tissues. The most common cause in adults is chronic lymphocytic thyroiditis (Hashimoto thyroiditis), but there are many other causes. Because most of the clinical features of hypothyroidism are nonspecific, the diagnosis requires laboratory testing. Serum thyroid-stimulating hormone (TSH) measurement is the best diagnostic test; an elevated TSH level almost always signals primary hypothyroidism. Serum free thyroxine levels may be below the reference range (overt hypothyroidism) or within the reference range (subclinical hypothyroidism). All patients with overt hypothyroidism should be treated, but those with subclinical hypothyroidism do not always benefit from treatment, especially elderly patients and those with baseline TSH levels below 10 mU/L. Oral L-thyroxine is the treatment of choice because of its well-demonstrated efficacy, safety, and ease of use. Therapy goals are symptom relief and maintenance of serum TSH levels within the reference range. Myxedema coma is a life-threatening form of decompensated hypothyroidism that must be treated with aggressive L-thyroxine replacement and other supportive measures in the inpatient setting.
Topics: Diagnosis, Differential; Drug Therapy, Combination; Female; Hormone Replacement Therapy; Hospitalization; Humans; Hypothyroidism; Myxedema; Physical Examination; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Reference Values; Referral and Consultation; Thyrotropin; Thyroxine; Triiodothyronine
PubMed: 32628881
DOI: 10.7326/AITC202007070 -
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 -
Autoimmunity Reviews Oct 2020Hashimoto's thyroiditis, characterized by thyroid-specific autoantibodies, is one of the commonest autoimmune disorders. Although the exact etiology has not been fully... (Review)
Review
Hashimoto's thyroiditis, characterized by thyroid-specific autoantibodies, is one of the commonest autoimmune disorders. Although the exact etiology has not been fully elucidated, Hashimoto's thyroiditis is related to an interaction among genetic elements, environmental factors and epigenetic influences. Cellular and humoral immunity play a key role in the development of the disease; thus, a T and B cells inflammatory infiltration is frequently found. Histopathologic features of the disease include lymphoplasmacytic infiltration, lymphoid follicle formation with germinal centers, and parenchymal atrophy. Moreover, the occurrence of large follicular cells and oxyphilic or Askanazy cells is frequently associated to Hashimoto's thyroiditis. Clinically, Hashimoto's thyroiditis is characterized mainly by systemic manifestations due to the damage of the thyroid gland, developing a primary hypothyroidism. Diagnosis of Hashimoto's thyroiditis is clinical and based on clinical characteristics, positivity to serum antibodies against thyroid antigens (thyroid peroxidase and thyroglobulin), and lymphocytic infiltration on cytological examination. The mainstream of treatment is based on the management of the hypothyroidism with a substitution therapy. A relationship between Hashimoto's thyroiditis and a possible malignant transformation has been proposed in several studies and involves immunological/hormonal pathogenic links although specific correlation is still debated and needs to be further investigated with prospective studies.
Topics: Hashimoto Disease; Humans; Hypothyroidism; Prospective Studies; Thyroglobulin
PubMed: 32805423
DOI: 10.1016/j.autrev.2020.102649 -
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 -
Current Opinion in Endocrinology,... Feb 2020The present review summarizes recent advances in the diagnosis and management of patients with congenital hypothyroidism. (Review)
Review
PURPOSE OF REVIEW
The present review summarizes recent advances in the diagnosis and management of patients with congenital hypothyroidism.
RECENT FINDINGS
Although most newborn screening strategies are designed to detect severe primary hypothyroidism that presents shortly after birth, some infants display a pattern of delayed TSH rise despite normal initial newborn screening. Recent studies suggest that delayed TSH rise may be more common and more severe than previously recognized. Although much less common than primary hypothyroidism, central congenital hypothyroidism is as likely to be of moderate or severe degree, which has implications for its detection and treatment. The discovery of new genetic causes of central congenital hypothyroidism, including the X-linked genes IGSF1, TBL1X, and IRS4, has begun to expand our understanding of thyroid axis regulation. Recent long-term data indicate that current treatment recommendations for congenital hypothyroidism result in grossly normal neurocognitive outcomes even in severely affected patients, and that overtreatment may not be as harmful as previously suspected. Liquid levothyroxine is now commercially available in the United States, but more studies are needed to determine optimal dosing using this formulation.
SUMMARY
Prompt identification and adequate treatment of patients with congenital hypothyroidism is critical to optimize outcomes. New information continues to accumulate about how to improve detection of congenital hypothyroidism in specific subgroups of infants (particularly those with delayed TSH rise and central hypothyroidism) and about treatment of patients with this disorder.
Topics: Congenital Hypothyroidism; Genetic Testing; Humans; Infant; Infant, Newborn; Neonatal Screening; Thyrotropin; Thyroxine
PubMed: 31789720
DOI: 10.1097/MED.0000000000000520 -
Tierarztliche Praxis. Ausgabe K,... Jun 2021Hypothyroidism is one of the most common endocrinopathies in dogs. In rare cases, it may be associated with further endocrinopathies. The most common combination is the...
Hypothyroidism is one of the most common endocrinopathies in dogs. In rare cases, it may be associated with further endocrinopathies. The most common combination is the con-currence of hypothyroidism and hypoadrenocorticism. The diagnosis of hypothyroidism is based on the measurement of thyroid hormones (T4/fT4) and thyroid stimulating hormone (TSH). As thyroid hormone concentrations in the blood are influenced by various factors (e. g. systemic diseases or drugs), test results must be interpreted in conjunction with complaints demonstrated by the patient. In cases when diagnosis is not definite, stimulating tests or diagnostic imaging techniques (ultrasound, scintigraphy) are advisable. Dogs with hypothyroidism should be diagnosed and treated with thyroid hormones. When addiditional clinical signs are not consistent with hypothyroidism, co-existing additional endocrinopathies need to be considered. Furthermore, when treatment fails to result in the expected clinical response, the diagnosis of hypothyroidism must be subject to critical re-evaluation. This article provides an overview of the current diagnostic and treatment methods in canine hypothyroidism.
Topics: Animals; Dog Diseases; Dogs; Hypothyroidism; Radionuclide Imaging; Thyrotropin; Thyroxine
PubMed: 34157761
DOI: 10.1055/a-1367-3387 -
Hormones (Athens, Greece) Jun 2021Congenital primary hypothyroidism (CH) is a state of inadequate thyroid hormone production detected at birth, caused either by absent, underdeveloped or ectopic thyroid... (Review)
Review
PURPOSE
Congenital primary hypothyroidism (CH) is a state of inadequate thyroid hormone production detected at birth, caused either by absent, underdeveloped or ectopic thyroid gland (dysgenesis), or by defected thyroid hormone biosynthesis (dyshormonogenesis). A genetic component has been identified in many cases of CH. This review summarizes the clinical and biochemical features of the genetic causes of primary CH.
METHODS
A literature review was conducted of gene defects causing congenital hypothyroidism.
RESULTS
Mutations in five genes have predominantly been implicated in thyroid dysgenesis (TSHR, FOXE1, NKX2-1, PAX8, and NKX2-5), the primary cause of CH (85%), and mutations in seven genes in thyroid dyshormonogenesis (SLC5A5, TPO, DUOX2, DUOXA2, SLC6A4, Tg, and DEHAL1). These genes encode for proteins that regulate genes expressed during the differentiation of the thyroid, such as TPO and Tg genes, or genes that regulate iodide organification, thyroglobulin synthesis, iodide transport, and iodotyrosine deiodination. Besides thyroid dysgenesis and dyshormonogenesis, additional causes of congenital hypothyroidism, such as iodothyronine transporter defects and resistance to thyroid hormones, have also been associated with genetic mutations.
CONCLUSION
The identification of the underlying genetic defects of CH is important for genetic counseling of families with an affected member, for identifying additional clinical characteristics or the risk for thyroid neoplasia and for diagnostic and management purposes.
Topics: Congenital Hypothyroidism; Dual Oxidases; Forkhead Transcription Factors; Humans; Infant, Newborn; Iodides; Mutation; Serotonin Plasma Membrane Transport Proteins; Thyroid Dysgenesis; Thyroid Hormones
PubMed: 33400193
DOI: 10.1007/s42000-020-00267-x -
Endocrine Oct 2019The global population is aging with millions of people today living into their 90 s. Thyroid disease, particularly hypothyroidism, is widespread among all age groups,... (Review)
Review
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.
Topics: Aged; Hormone Replacement Therapy; Humans; Hypothalamo-Hypophyseal System; Hypothyroidism; Lipids; Longevity; Thyroid Hormones; Thyroxine
PubMed: 31482381
DOI: 10.1007/s12020-019-02067-9