| Coverage Policy Manual | |
| Policy #: | 2024026 |
| Category: | Laboratory |
| Initiated: | November 2024 |
| Last Review: | October 2024 |
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| RTM_Thyroid Disease Testing | |
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| Description: |
Thyroid hormones are necessary for both prenatal and postnatal development, as well as metabolic activity in adults (Brent, 2024).
Thyroid disease includes conditions which cause hypothyroidism, hyperthyroidism, goiter, thyroiditis (which can present as either hypo- or hyperthyroidism), and thyroid tumors (Rugge, 2015).
Thyroid function tests are used in a variety of clinical settings to assess thyroid function, monitor treatment, and screen asymptomatic populations for subclinical or otherwise undiagnosed thyroid dysfunction (Ross, 2023b).
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
This policy applies to health plans that utilize a routine laboratory management vendor, which include Arkansas Blue Cross and Blue Shield, Federal Employee Health Benefit Plan and Postal Service Health Benefit Plan, Health Advantage, and Octave Blue Cross and Blue Shield fully insured plans, including the Metallic and ARHOME plans and Complete/Complete Plus plans. Additionally, this policy will apply to the Farm Bureau and Level Funded plans.
Effective February 1, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Thyroid function testing meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the following situations:
A. For individuals with signs and symptoms consistent with hypothyroidism (see
Note 1 below):
B. TSH and fT4 testing (once every 4 weeks) for individuals who are pregnant or who are postpartum
and who have symptoms of thyroid dysfunction (see Note 1 and
Note 2 below);
C. Total T4 (TT4), antithyroglobulin antibody (Tg-Ab), thyrotropin receptor antibodies (TRAb), and anti-thyroid peroxidase antibody (TPOAb) for individuals who are pregnant or who are postpartum
and who have been diagnosed with hyperthyroidism (see Note 3 below);
D. Testing for thyroid antibodies (once every three years), for individuals with hypothyroidism or hyperthyroidism;
E. Testing for serum thyroglobulin and/or Tg-Ab levels for the detection of tumor recurrence, post-surgical evaluation, surveillance, and/or maintenance for differentiated thyroid carcinomas for individuals with thyroid cancer.
Note 1:
Signs and symptoms of hypothyroidism include:
Note 2:
Hyperthyroidism can mimic other health problems, which may make it difficult for doctors to diagnose. It can also cause a wide variety of signs and symptoms, including:
Note 3:
Due to significant changes in thyroid physiology during pregnancy, measurement of hormone levels should only be performed at labs that have trimester specific normal ranges for their assay(s). While fT4 is the preferred test, TT4 may be useful if the TSH and fT4 results are discordant or when trimester specific normal ranges for fT4 are unavailable.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Thyroid function testing for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes including but not limited to the following:
For members with contracts without primary coverage criteria, thyroid function testing, for any indication or circumstance not described above, including but not limited to the following, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
Due to the detail of the rationale, the complete document is not online. For a hardcopy print, please email:codespecificinquiry@arkbluecross.com
Metabolic homeostasis is regulated by the thyroid gland through production of thyroid hormones. Thyroid disease is estimated to occur in approximately 30 million Americans, much of which is undiagnosed (AACE, 2024). The thyroid gland is regulated by thyroid stimulating hormone (TSH or thyrotropin). TSH is secreted by the anterior pituitary and stimulates dthyroid gland to secrete two hormones, thyroxine (T4) and triiodothyronine (T3), and TSH secretion is stimulated by thyrotropin-releasing hormone (TRH), which is distributed throughout the hypothalamus with traces found in the central nervous system and in the pituitary gland, gastrointestinal tract, pancreatic islets, and reproductive tract. Both TSH and TRH levels are controlled through a negative feedback loop by T4 and T3. Thyroid hormone production is also regulated by the extrathyroidal conversion of T4 to T3, allowing for rapid changes in tissue thyroid hormone availability (Ross, 2023b; Ross, 2024).
More than 99.95 percent of T4 and 99.5 percent of T3 in serum are bound to several serum proteins, including thyroxine-binding globulin (TBG), transthyretin (TTR, formerly called thyroxine-binding prealbumin [TBPA]), albumin, and lipoproteins. Since nearly all the T4 and T3 found in serum is bound, changes in serum concentration of binding proteins, namely TBG, influence the total serum T4 and T3 concentrations and the fractional metabolism of T4 and T3 (Ross, 2024).
Thyroid function is best assessed by measuring TSH (assuming steady-state conditions and the absence of pituitary or hypothalamic disease). However, direct measurement of all TSH and all other serum thyroid hormone levels (serum total T3 and total T4, serum free T3 (fT3) and free T4 (fT4) is still important, as it may be difficult in some patients to be certain about the state of pituitary and hypothalamic function (Ross, 2023b)
Thyroid hormones must be maintained within a carefully regulated range, as levels outside this range (both hypo- or hyperthyroid) can result in adverse clinical consequences. Hypothyroidism diagnosis depends heavily on laboratory tests because of the lack of specificity of the typical clinical manifestations. Primary hypothyroidism is characterized by high TSH and low fT4 concentrations. Subclinical hypothyroidism is defined biochemically as a patient having elevated TSH but a normal fT4 concentration and secondary (central) hypothyroidism is characterized by a patient having low serum T4 concentration but a normal serum TSH concentration. Symptoms include fatigue and weakness, cold intolerance, weight gain, cognitive dysfunction, dyspnea on exertion, hair loss, hoarseness, dry skin, edema, decreased hearing, myalgia and paresthesia, depression, menorrhagia, arthralgia, or pubertal delay (Ross DS, 2024). Another well-documented consequence of hypothyroidism during childhood is that of short stature, serving as presenting feature and is linked to delayed bone age, as those treated for hypothyroidism often resume their normal growth potential (Richmond, 2024). Thus, newborns with undetected or untreated hypothyroidism will have both mental and physical developmental delay. Hypothyroidism during pregnancy increases the risk for miscarriage, preterm delivery, and pre-eclampsia (Alexander, 2017).
Overt hyperthyroidism refers to patients with elevated levels of fT4, fT3, or both, and subnormal TSH levels, while subclinical hyperthyroidism is defined as patients having normal T4 and T3 in the presence of subnormal TSH levels. Hyperthyroid symptoms are nonspecific, but can include tachycardia, heat intolerance, sweating, tremor, dyspnea on exertion, and weight loss. Because a number of these symptoms are so common and nonspecific, they may be subtle and unrecognized. Both hypothyroidism and hyperthyroidism conditions rely on laboratory testing to confirm diagnosis (Ross, 2023a, 2024).
Current assays for TSH are extremely sensitive at detecting changes in thyroid homeostasis prior to changes in T4 and T3 levels. Thus, TSH assessment is the most often used initial test for thyroid function. In general, if serum TSH is normal, no further testing is needed; however, if serum TSH is high, fT4 is used to determine the degree of hypothyroidism. In contrast, if serum TSH is low, fT4 and fT3 are used to determine the degree of hyperthyroidism. If a pituitary or hypothalamic condition is suspected, both serum TSH and fT4 may be measured, and serum fT4 may be measured if symptoms of hyper- or hypothyroidism are present in a patient with normal TSH levels (Ross, 2023b). Measurement of fT4 is regarded as a better indicator of thyroid function than total T4 measurement for most situations, as it reflects the amount of available hormone. Presently, there is considerable controversy as to the appropriate upper limit of normal for serum TSH, with most labs using upper limits of approximately 4.5 to 5.0 mU/L (current “normal” range 0.4-5 mU/L) and there are debates on the cost effectiveness of screening asymptomatic patients. In addition, research has shown an age-related shift toward higher TSH concentrations in older patients (Ross, 2023b).
While thyroid nodules (TNs) are prevalent and found in up to 50% of all individuals, with most being benign, some TNs can be malignant. Evaluation of these nodules is crucial to rule out malignancy and identify those individuals requiring surgical intervention. One important laboratory test for the differentiation between a benign or malignant TN is assessment of TSH levels. In individuals with a TN, serum TSH levels that either exceed the normal range or are near the upper limit of the range are concerning, as this corresponds to an increased risk of malignancy (AlSaedi, 2024; Haymart, 2008).
Thyroiditis may be caused by an autoimmune disorder, an infection, or exposure to certain drugs or toxic chemicals which can be either acute or chronic. The evaluation of possible autoimmune thyroid disorders includes testing for the presence of thyroid antibodies. Several antibodies against thyroid antigens have been described in chronic autoimmune thyroiditis. The antigens include thyroglobulin (Tg), thyroid peroxidase (TPO) and the thyrotropin receptor. However, different levels of antibodies correspond to different conditions—for example, nearly all patients with Hashimoto's thyroiditis (chronic autoimmune hypothyroidism) have high serum concentrations of antibodies to Tg and TPO (Ross, 2024). Thyrotropin receptor antibodies (TRAb) can be classified as stimulating, blocking, or neutral. Stimulating TRAb cause Graves' disease and thyroid receptor-blocking antibodies can cause hypothyroidism. Some patients will handrocytes and growth plate cartilage in bones. Mediation of the chondrogenesis—the formation of cartilage from condensed mesenchyme tissue—by the endocrine system takes place through the action of hormones, including growth hormone, insulin-like growth factor 1 (IGF-1), androgens, glucocorticoids, and thyroid hormone. It is believed that the balance between proliferation and senescence of chondrocytes at the growth plate of bones plays a crucial role in both normal and pathologic variations of linear growth, though the pathways are unclear as of date (Leung, 2016; Richmond, 2024).
Tests measuring levels of thyroid-related markers are widely available commercially, often as a panel. Many combinations of thyroid serum markers are available. For example, Testing.com offers thyroid tests which screen for individual thyroid hormones including TSH, fT4, and fT3 (Testing, 2024). EverlyWell offers a direct-to-consumer home-health panel testing for TSH, T3, T4, and thyroid peroxidase antibodies (EverlyWell, 2024). Other direct-to-consumer home-health panel tests include LetsGetChecked (LetsGetChecked, 2024), Paloma Health (Paloma Health, 2024), myLABBOX Thyroid Health Screening (myLABBOX, 2024), and TellmeGEN (TellmeGEN, 2023).
Common variable immunodeficiency is one of the more common antibody deficiency disorders. In one large series of primary immunodeficiency (PID) in children diagnosed over a 10-year period, CVID made up 17 of 189 total PID cases and 20 percent of the 87 cases of antibody deficiency. Most patients with CVID present after puberty, and the disorder is usually diagnosed in the second or third decade of life. However, about 25 percent of all CVID patients present in childhood or adolescence and there is an earlier peak of diagnosis occurring around eight years of age. A diagnosis of CVID before six years of age should be considered preliminary because of immunologic immaturity and the persistence of transient hypogammaglobulinemia of infancy in some children. In addition, the possible presence of a monogenic defect that causes a CVID-like disorder should be considered in children who present at a very young age. Children with failure-to-thrive should be evaluated for thyroid function and growth hormone deficiency. Growth hormone replacement therapy should be offered if deficiency is identified (Hogan, 2022).
Analytical Validity
The current generation of assays measuring serum TSH is a chemiluminometric assay, which have detection limits of about 0.01 mU/L. This amount is sufficiently low enough to distinguish between euthyroidism and hyperthyroidism as well as providing superior sensitivity to the prior generation of assays whose detection limits were approximately 0.1 mU/L (Ross, 2023b).
A study focusing on validating a new electrochemiluminescent assay for serum TSH, T4, and T3 found their intra-assay coefficient of variation to be under 8% for all three hormones and inter-assay coefficient of variation to be <2.9% for TSH, 2.3% for FT4, and 12.3% for T3. The correlation between this assay and the typical ELISA or RIA assays were all at least r = .8 with many correlations near or above .9 (Kazerouni, 2012).
Serum T4 and T3 are typically measured by automated competitive binding chemiluminometric assays. Older competitive binding radioimmunoassays are still available for serum total T4. Serum total T4 and total T3 measure both bound and unbound (free) T4 and T3, respectively. A large percentage o*f serum T4 is bound (99.97%) to thyroxine-binding globulin (TBG), transthyretin (also called TBPA [thyroxine0binding pre*albumin]), and albumin. Serum T3 is less tightly bound to TBG and TBPA but more tightly bound to albumin than T4. Normal reference ranges do vary among laboratories; however, a typical reference range for total T4 is 4.6-11.2 mcg/dL (60-145* nmol/L) and for total T3, while more variable across laboratories even than total T4, a typical reference range is ~75-195 ng/dL (~1.1-3 nmol/L) (Ross, 2023b).
The current immunoassays used to measure T3 do not always agree with other methods. For example, a study by Masika et al. (2016) compared immunoassay methods to LC/MS/MS and found that 45% of patients classified as “normal” by immunoassay were classified as “lower than 2.5th percentile” by LC/MS/MS. The authors also noted that in patients not receiving T4, 74% of their results were below the 2.5th percentile by LC/MS/MS whereas only 21% were under that mark by im*unoassay. The authors speculate that this discrepancy may be due to deiodinase polymorphisms, but overall conclude that because this is a significant method to diagnose thyroid issues, accuracy of T3 measurements should be paramount (Masika, 2016).
The measurement of reverse T3 may not be reliable. A study by Burmeister, focused on a total of 246 patients contributing 262 reverse T3 measurements, showed an inverse linear relationship between the log of TSH and reverse T3. However, Burmeister notes that hypothyroidism may cause reverse T3 to appear normal and euthyroidism may cause reverse T3 to appear low. Furthermore, it is possible that symptoms attributed to unusual reverse T3 levels are caused by hypothyroidism, despite normal TSH levels. Overall, Burmeister concludes that reverse T3 cannot differentiate between hypothyroidism and euthyroidism (Burmeister, 1995; Gomes-Lima, 2018).
Clinical Utility & Validity
Li and colleagues in 2017 conducted a preliminary study to investigate how certain dietary supplements could affect clinical assays. They examined 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassays and found that ingesting 10 mg/d of biotin for 1 week was associated with a potentially clinically important interference with some biotinylated assays. These immunoassays use a biotin-streptavidin binding system, so excess biotin may influence the results of assays using this system. The time at which the biotin was ingested was also a factor in the magnitude of the distortion (Li, 2017). Repeating a thyroid test at least two days after biotin discontinuation may be considered (Ross, 2023b).
Livingston and others assessed the impact of T3 testing and whether T3 testing provides clinically useful information to patients who are over-treated for hypothyroidism with levothyroxine. Out of 542 patients, 33 were placed in an over-treated group, 236 were placed in a control group, and the remaining 273 did not fulfill either group. None of the patients in the over-treated group had an increased T3 and the “most discriminant” T3 level was only at 58% sensitivity and 71% specificity. The authors concluded there is no reason to measure T3 in patients with hypothyroidism on levothyroxine therapy (Livingston, 2015).
In 2016, Yazici and colleagues assessed three predictors of thyroid cancer: thyrotropin (TSH), thyroglobulin (Tg), and their ratio. A study of 242 patients (134 with benign thyroid conditions, 68 with malignancy) was performed. The authors found that preoperative Tg levels were significantly lower in the malignant group (64 ng/mL vs 20 ng/mL) and that the TSH to Tg ratio was significantly higher in the malignant group, as there was no major difference in TSH between groups despite the Tg changes. However, the authors note that only fine-needle aspiration biopsy was a significant factor (Yazici, 2016).
Autoantibodies may also play a role in the diagnosis of cancer. A study by Gholve and others assessing 301 samples from differentiated thyroid cancer patients (compared to 37 euthyroid controls) found the prevalence of autoantibodies in the cancer patients to be significantly higher than the controls. The authors found the prevalence of the antibodies to be 17.3% by the Immunotech kit and 16.6% by the radioassay in patients with cancer, whereas the control group was found to be only 5.4% by both methods (Gholve, 2017).
Thyroid antibodies play a role in autoimmune thyroiditis. A 2016 study performed by Biktagirova and others found that 97% of patients with autoimmune thyroiditis had a high antibody-to-denatured DNA ratio compared to healthy controls. Most of these patients also had a thyroid condition (euthyroidism, hypothyroidism, hyperthyroidism) (Biktagirova, 2016). Another study performed by Diana investigated the prevalence of thyroid stimulating hormone receptor (TSHR) blocking antibodies (TBAb) in autoimmune thyroid disease. In total 1079 patients with autoimmune thyroid disease (AITD) were compared to 302 controls. The authors found that about 10% of patients with AITD were positive for TBAb (82/1079). TBAb also correlated positively with TSHR binding inhibiting immunoglobulins and negatively with TSHR stimulatory antibodies. The authors concluded that TBAb was a useful and important tool to identify hypothyroidism (Diana, 2017).
In 2018 Kluesner analyzed current thyroid function test ordering practices. The authors examined 38,214 tests (encompassing TSH, fT4, TSH + fT4, fT3, Total T4, and total T3). Overall, TSH alone comprised 52.14% of tests, TSH + fT4 26.72%, fT3 alone 10.63%, fT4 alone 4.26%, and TSH + fT4 + fT3 2.74%. Free thyroid hormone testing amounted to 36% of all tests. The authors estimated the annual cost of free thyroid hormone testing to be $107,720, with savings of up to $120,000 (Kluesner, 2018).
In 2018 Jin investigated the prevalence of subclinical hypothyroidism in obese children and its association with thyroid hormone. The study included 1,104 children and 27 of 111 (24.3%) obese children were found to have subclinical hypothyroidism, compared to 127 of 993 (12.8%) non-obese children. Body mass index was found to positively correlate with serum concentrations of TSH and negatively correlate with serum concentrations of fT4. Total cholesterol and triglyceride concentration were found to positively correlate with TSH concentrations, with fT4 negatively correlating with total cholesterol. Jin concluded that TSH is correlated with lipid profiles (Jin, 2018).
In a 2018 study, Muraresku reviewed mitochondrial disease and recent advances in clinical diagnosis, management, therapeutic development, and preventative strategies. They noted that routine screening of individuals with mitochondrial diseases is imperative. Screening should include examining the “multitude of symptoms known for diabetes mellitus, adrenal insufficiency, thyroid hormone insufficiency, hearing loss, cardiac arrhythmias, and other disease related symptoms, with appropriate multi-specialist management provided.” They also noted that “primary mitochondrial disease encompasses an impressive range of inherited energy deficiency disorders having highly variable molecular etiologies as well as clinical onset, severity, progression, and response to therapies of multi-system manifestations” (Muraresku, 2018).
Sarkar in 2012 examined literature surrounding recurrent pregnancy loss in patients with thyroid dysfunction. Disturbances in thyroid function and thyroid hormone levels are common in women during their reproductive years and that dysfunction can interfere with reproductive physiology, can reduce the likelihood of pregnancy, and can adversely affect pregnancy outcome. They note that “universal screening for thyroid hormone abnormalities should be conducted in females [individuals] with fetal loss or menstrual disturbances. Practitioners providing health care for women should be alert to thyroid disorders as an underlying etiology for recurrent pregnancy loss.” However, universal screening for thyroid hormone abnormalities is not routinely recommended at present. In individuals capable of pregnancy and of reproductive age, hypothyroidism can be reversed by thyroxine therapy and this can improve fertility and help individuals avoid needing to use assisted reproduction technologies (Sarkar, 2012).
Korevaar and colleagues performed a meta-analysis focusing on thyroid function test abnormalities and thyroid autoimmunity with preterm birth. They assessed 19 cohorts encompassing 47,045 pregnant individuals and found that 1,234 of these individuals had subclinical hypothyroidism, 904 had isolated hypothyroxinemia (“decreased fT4 concentration with normal thyrotropin concentration”), 3,043 were thyroid peroxidase (TPO) antibody positive, and 2,357 had preterm birth. Risk of preterm birth was found to be higher for individuals with subclinical hypothyroidism than with euthyroidism (odds ratio = 1.29), as well as higher for individuals with isolated hypothyroxinemia (odds ratio = 1.46). The authors also found that a one standard deviation increase in maternal serum thyrotropin concentration increased risk of preterm birth by an odds ratio of 1.04. Finally, TPO antibody positive individuals were found to have a higher risk of preterm birth compared to TPO antibody negative individuals by an odds ratio of 1.33 (Korevaar, 2019).
In a population-based study by Kiel in 2020, the use of thyroid hormone measurements in ambulatory care was assessed. Measurement of serum TSH, fT3, and fT4 within the 1-3 years prior to the study was reported. A total of 5,552 participants were included in the analysis, with 25% (1,409/5,552) having a diagnosed thyroid disorder or treatment. Of these, 30% (1626/5552) received at least one TSH measurement and 6.8% (378/5552) received at least one thyroid ultrasound. In the study, “TSH measurement rates were 1.7 times higher than the highest reported rate (438/1000), fT4 measurement rates were within the reported range (89/1000), and fT3 was measured at a 10- fold higher rate than the highest reported (89/1000).” The study results are in accordance with current guidelines, which recommend measuring TSH levels rather than fT4/fT3 both for patients with suspected hypo- and hyperthyroidism as well as for monitoring purposes. However, the data also suggests that fT4 and fT3 were tested at the same rate, even though fT4 is recommended as sufficient to distinguish between overt and subclinical hypothyroidism. Despite overuse of thyroid hormone testing, there is possible underuse in patients with diagnosed thyroid disorders who are taking thyroid medication. In the study, 40% did not receive a monitoring TSH test within 1 year, and 16% did not receive a TSH test within 3 years. The authors suggest that “Given the frequency of patients with thyroid disorders, diagnostic and monitoring tests should be used rationally with regard to costs. TSH levels should be monitored regularly in patients on thyroid medication” (Kiel, 2020).
In 2021, Degrandi and others examined the prevalence of thyroid autoimmunity in children with developmental dyslexia. Serum TSH, fT3, and fT4 were measured and thyroid autoimmunity was evaluated by measuring TPOAbs and antithyroglobulin antibodies (TG-Abs). The authors also performed thyroid ultrasonography in the subjects with developmental dyslexia. The study enrolled 51 subjects with developmental dyslexia (M : F = 39 : 12, mean age 12.4 ± 9 years) and 34 controls (M : F = 24 : 10, mean age 10.8 ± 4 years) and found a significant increase in TPOAb positivity in subjects as compared to controls (60.8% vs 2.9%, p<0.001) but no significant change in TG-Ab positivity (16% vs 5.8%). Additionally, in the subjects with developmental dyslexia who received ultrasonography (49 of 51 subjects), 60% of them had a thyroiditis pattern. Overall, this study showed a high prevalence of thyroid autoimmunity in children with developmental dyslexia and while further research is needed to confirm these initial findings, these results may change the approach to developmental dyslexia and eventually lead to a systematic determination of thyroid autoimmunity in affected children (Degrandi, 2021).
Wang and colleagues examined the association between thyroid function and serum lipid metabolism, utilizing a genetic analysis termed Mendelian randomization (MR). While thyroid dysfunction is known to be associated with cardiovascular disease, the role of thyroid function in lipid metabolism is still partly unknown. “The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial” and for this study, the authors performed a two-sample MR to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). TSH, fT3 and fT4 levels, the fT3:fT4 ratio, and the concentration of TPOAb were all used to get a clinical measurement of thyroid function. Serum lipid metabolism traits included total cholesterol (TC) and triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. To assess the association between thyroid function and serum lipid metabolism, the MR estimate, and MR inverse variance-weighted method were used. The authors found that increased TSH levels were significantly associated with higher TC and LDL levels, as was the fT3:fT4 ratio. However, they observed no significant differences between genetically predicted fT4 and TPOAb and serum lipids. They concluded that their results suggest an association between thyroid function and serum lipid metabolism, “highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility” (Wang, 2021).
In 2022 Toloza performed a systematic review and meta-analyses of data collected from pregnant patients (excluding pre-existing thyroid disease and multifetal pregnancies) to analyze the primary outcomes of gestational hypertension and pre-eclampsia; data was taken from cohort studies that included maternal concentrations of TSH, FT4, and TPO antibodies as well as data regarding maternal gestational hypertension, pre-eclampsia, or both. The study comprised 46,528 pregnant individuals, of which 39,826 individuals had enough data to be classified by thyroid function status. Individuals who had subclinical hypothyroidism made up 3.2% of the cohort (1,275 individuals). After analyses, a total of 933 individuals had isolated hypothyroxinemia, 619 had subclinical hyperthyroidism, and 337 had overt hyperthyroidism. The authors concluded that “compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia…In a continuous analysis, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia” (Toloza, 2022).
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| References: |
AACE(2023) All About the Thyroid. https://www.aace.com/disease-and-conditions/thyroid/all-about-thyroid AAFP(2012) Hypothyroidism An Update. https://www.aafp.org/afp/2012/0801/p244.html AAFP(2018) Thyroid Dysfunction Screening. https://www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/thyroid-dysfunction.html AAP(2017) Weblink http://www.choosingwisely.org/clinician-lists/aap-soen-avoid-measuring-thyroid-function-and-insulin-levels-in-obese-children ACOG(2020) Thyroid Disease in Pregnancy ACOG Practice Bulletin, Number 223. Obstet Gynecol, 135(6), e261-e274. https://doi.org/10.1097/aog.0000000000003893 Alexander, E.K., Pearce, E.N., Brent, G.A., Brown, R.S., Chen, H., Dosiou, C., Grobman, W.A., Laurberg, P., Lazarus, J.H., Mandel, S.J., Peeters, R.P., & Sullivan,S.(2017) Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum Thyroid, 27(3), 315-389. https://doi.org/10.1089/thy.2016.0457 ASCP. (2015). http://www.choosingwisely.org/clinician-lists/american-society-clinical-pathology-suspected-thyroid-disease-evaluation ASCP(2015) Weblink http://www.choosingwisely.org/clinician-lists/american-society-clinical-pathology-suspected-thyroid-disease-evaluation/ ASCP(2020) American Society for Clinical Pathology https://www.choosingwisely.org/clinician-lists/ascp32-avoid-thyroid-stimulating-hormone-tsh-screening-in-annual-well-visits-for-asymptomatic-adults-regardless-of-age Bernstein,J.A.,Lang,D.M.,Khan,D.A.,Craig,T.,Dreyfus,D.,Hsieh,F.,Sheikh,J.,Weldon,D.,Zuraw,B., Bernstein,D.I.,Blessing-Moore,J., Cox,L.,Nicklas,R.A., Oppenheimer,J., Portnoy,J.M., Randolph,C.R., Schuller,D.E., Spector,S.L.,Tilles,S.A.,& Wallace,D.(2014) The diagnosis and management of acute and chronic urticaria J Allergy Clin Immunol, 133(5), 1270-1277. https://doi.org/10.1016/j.jaci.2014.02.036 Biktagirova, E.M., Sattarova, L.I., Vagapova, G.R., Skibo, Y V., Chuhlovina, E N., Kravtsova, O.A., & Abramova, Z.I.(2016) Biochemical and immunological markers of autoimmune thyroiditis Biomed Khim, 62(4), 458-465. https://doi.org/10.18097/pbmc20166204458 (Biokhimicheskie i immunologicheskie markery khronicheskogo limfotsitarnogo tireoidita.) Brent, G.(2022) Thyroid hormone action https://www.uptodate.com/contents/thyroid-hormone-action Burmeister, L.A(1995) Reverse T3 Does Not Reliably Differentiate Hypothyroid Sick Syndrome from Euthyroid Sick Syndrome Thyroid, 5(6), 435-441. https://doi.org/10.1089/thy.1995.5.435 Degrandi, R., Prodam, F., Genoni, G., Bellomo, G., Bona, G., Giordano, M., Bellone, S., & Monzani, A(2021) The Prevalence of Thyroid Autoimmunity in Children with Developmental Dyslexia Biomed Res Int, 2021, 7656843. https://doi.org/10.1155/2021/7656843 Diana, T., Krause, J., Olivo, P. D., König, J., Kanitz, M., Decallonne, B., & Kahaly, G. J.(2017) Prevalence and clinical relevance of thyroid stimulating hormone receptor blocking antibodies in autoimmune thyroid disease Clin Exp Immunol, 189(3), 304-309. https://doi.org/10.1111/cei.12980 Donangelo, I., & Suh, S. Y.(2017) Subclinical Hyperthyroidism: When to Consider Treatment. 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