-
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 Endocrinology Apr 2022In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine.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In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine.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 -
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 -
Current Vascular Pharmacology 2017Hypothyroidism, characterised by low/normal free thyroxine (FT4) and free triiodothyronine (FT3) with elevated thyroid-stimulating hormone (TSH), is a well-known... (Review)
Review
BACKGROUND
Hypothyroidism, characterised by low/normal free thyroxine (FT4) and free triiodothyronine (FT3) with elevated thyroid-stimulating hormone (TSH), is a well-known complication of nephrotic syndrome (NS). This is a common feature of primary and secondary glomerular diseases and comprises loss of protein in the urine and increased urinary excretion of thyroid hormones and thyroxine- binding globulin. With a normal thyroid reserve, this scenario is associated with the development of subclinical hypothyroidism, with a slight increase in TSH and normal free fractions. However, with a low thyroid reserve the transition toward overt hypothyroidism is almost inevitable, affecting morbidity and mortality. As T4 replacement is a cheap and well-established treatment to achieve a stable hormone status in different types of thyroid deficiency, it is essential to recognise and appropriately treat this condition.
CONCLUSION
In this article we summarise the evidence on this nephro-endocrine disorder in humans and focus on diagnostic and therapeutic strategies.
Topics: Humans; Hypothyroidism; Nephrotic Syndrome; Thyroid Hormones; Thyrotropin; Thyroxine
PubMed: 28176633
DOI: 10.2174/1570161115999170207114706 -
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 -
JAMA Pediatrics Oct 2016Normal thyroid gland function is critical for early neurocognitive development, as well as for growth and development throughout childhood and adolescence. Thyroid... (Review)
Review
IMPORTANCE
Normal thyroid gland function is critical for early neurocognitive development, as well as for growth and development throughout childhood and adolescence. Thyroid disorders are common, and attention to physical examination findings, combined with selected laboratory and radiologic tools, aids in the early diagnosis and treatment.
OBJECTIVE
To provide a practical review of the presentation, evaluation, and treatment of thyroid disorders commonly encountered in a primary care practice.
EVIDENCE REVIEW
We performed a literature review using the PubMed database. Results focused on reviews and articles published from January 1, 2010, through December 31, 2015. Articles published earlier than 2010 were included when appropriate for historical perspective. Our review emphasized evidence-based management practices for the clinician, as well as consensus statements and guidelines. A total of 479 articles for critical review were selected based on their relevance to the incidence, pathophysiology, laboratory evaluation, radiological assessment, and treatment of hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid cancer in children and adolescents. Eighty-three publications were selected for inclusion in this article based on their relevance to these topics.
FINDINGS
The primary care physician is often the first health care professional responsible for initiating the evaluation of a thyroid disorder in children and adolescents. Patients may be referred secondary to an abnormal newborn screening, self-referred after a caregiver raises concern, or identified to be at risk of a thyroid disorder based on findings from a routine well-child visit. Irrespective of the path of referral, knowledge of the signs and symptoms of hypothyroidism, hyperthyroidism, and thyroid nodules, as well as the general approach to evaluation and management, will help the primary care physician complete an initial assessment and determine which patients would benefit from referral to a pediatric endocrinologist.
CONCLUSIONS AND RELEVANCE
Early identification and treatment of thyroid disease in children and adolescents is critical to optimize growth and development. The primary care physician plays a critical role in identifying patients at risk. An understanding of risk factors, clinical signs and symptoms, and interpretation of screening laboratories ensures an efficient and accurate diagnosis of these common disorders. Regular communication between the primary care physician and the subspecialist is critical to optimize outcome because the majority of patients with thyroid disorders will require long-term to lifelong medical therapy and/or surveillance.
Topics: Adolescent; Adolescent Health; Child; Child Health; Congenital Hypothyroidism; Female; Goiter, Endemic; Humans; Hyperthyroidism; Hypothyroidism; Male; Risk Factors; Thyroid Diseases; Thyroid Function Tests; Thyroid Neoplasms; Thyroiditis, Autoimmune
PubMed: 27571216
DOI: 10.1001/jamapediatrics.2016.0486 -
Thyroid : Official Journal of the... Feb 2021Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these... (Review)
Review
Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. The American Thyroid Association (ATA), British Thyroid Association (BTA), and European Thyroid Association (ETA) held a joint conference on November 3, 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from 12 content experts. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and after comments from ATA/BTA/ETA members. Of 34 Consensus Statements available for voting, 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 μg/kg of LT4 daily, use of twice daily LT3 or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized placebo-controlled adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. This article summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.
Topics: Consensus; Drug Combinations; Evidence-Based Medicine; Humans; Hypothyroidism; Thyroxine; Treatment Outcome; Triiodothyronine
PubMed: 33276704
DOI: 10.1089/thy.2020.0720