Check whether you are uptodate with current evidence about subclinical hypothyroidism (SCH)
TRUE / FALSE
1- TSH values are 50% higher at night and in the early morning than during the rest of the day.
2- Patients with TSH levels between 4.5 and 10 mIU/L If followed for 5 years, approximately only 30% of patients will normalize without intervention.
3- 1 in 3 patients with SCH do not have any symptoms attributed to the overt hypothyroidism
SCH has been associated with depressive symptoms
4- High doses of Vitamin C has been shown to cause spurious thyroid testing results
5- Risk for progression to overt hypothyroidism appears to be lower for thyroid peroxidase antibodies (TPOAbs)
6- Treatment of SCH in older adults appear to improve cardiovascular outcomes.
7- RCT failed to find benefits – pregnancy outcomes, neurodevelopmental outcomes in children) following treatment of SCH in pregnancy.
Read the text for answers
Subclinical hypothyroidism (SCH) is a biochemical state in which the thyroid-stimulating hormone (TSH) is elevated while the free thyroxine (T4) level is normal. Overt hypothyroidism is not diagnosed until the free T4 level is decreased, regardless of the degree of TSH elevation.
The overall prevalence of SCH in iodine-rich areas is 4% to 10%, with a risk for progression to overt hypothyroidism of between 2% and 6% annually. The prevalence range is likely to widen with increasing age.
SCH is most common among women, the elderly, and White individuals.2
The not-so-significant role of symptoms in subclinical hypothyroidism
Symptoms associated with overt hypothyroidism include constipation, dry skin, fatigue, slow thinking, poor memory, muscle cramps, weakness, and cold intolerance. In SCH, these symptoms are inconsistent, with around 1 in 3 patients having no symptoms at all. Hence there is a question of the validity of attributing symptoms to SCH.
Adverse health associations
Observational data suggest that SCH is associated with an increased risk for dyslipidemia, coronary heart disease, heart failure, and cardiovascular mortality, particularly in those with TSH levels ≥ 10 mIU/L. Such associations were not found for most adults with TSH levels between 5 and 10 mIU/L. There are also potential associations of SCH with obesity, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. Despite thyroid studies being commonly ordered as part of a mental health evaluation, SCH has not been statistically associated with depressive symptoms.
Caveats with laboratory testing
There are several issues to consider when performing a laboratory assessment of thy- roid function. TSH levels fluctuate considerably during the day, as TSH secretion has a circadian rhythm. TSH values are 50% higher at night and in the early morning than during the rest of the day. TSH values also may rise in response to current illness or stress. Due to this biological variability, repeat testing to confirm TSH levels is recommended if an initial test result is abnormal.14
An exact reference range for TSH is not widely agreed upon—although most laboratories regard 4.0 to 5.0 mIU/L as the high-end cut-off for normal. Also, “normal” TSH levels appear to differ by age. A TSH level of 6.0 mIU/L (or even higher) may be more appropriate for adults older than 65 years.1
Biotin supplementation has been shown to cause spurious thyroid testing results (TSH, T3, T4) depending on the type of assay used. Therefore, supplements containing biotin should be withheld for several days before as- assessing thyroid function.
Patients with SCH are often categorized as having TSH levels between 4.5 and 10 mIU/L (around 90% of patients) or levels ≥ 10 mIU/L.8,17 If followed for 5 years, approximately 60% of patients with SCH and TSH levels between 4 and 10 mIU/L will normalize without intervention. Normalization is less common in patients with a TSH level greater than 10 mIU/L.18
The risk for progression to overt hypothyroidism also appears to be higher for those with certain risk factors. These include higher baseline TSH levels, the presence of thyroid peroxidase antibodies (TPOAbs), or a history of neck irradiation or radioactive iodine uptake.1 Other risk factors for eventual thyroid dysfunction include female sex, older age, goiter, and high iodine intake.13
Evidence for treatment varies
Most guidelines prioritize treatment for individuals with a TSH level > 10 mIU/L and for those with TSH values < 10 mIU/L but still elevated and apparent symptoms of hypothyroidism. (The strength of evidence behind this guidance is challenged by a lack of data from prospective randomized controlled trials (RCTs) demonstrating the health benefits following the treatment of SCH.) The British Medical Journal (BMJ) Guideline cites this lack of evidence and recommends against treating SCH at any TSH level, regardless of symptoms.
RCT support also is lacking for a reduction in cardiovascular mortality following treatment for SCH.
A measured approach to treating subclinical hypothyroidism – consider several factors when deciding whether to treat SCH.
- RCT data suggest a lack of treatment benefits in relieving depression, improving cognition, or reducing general hypothyroid symptoms.
- Treatment of SCH in older adults does not appear to improve cardiovascular outcomes.
- The question of whether long-term treatment of SCH in younger patients reduces cardiovascular morbidity or mortality lacks answers from RCTs.
- Before diagnosing SCH or starting treatment, always confirm SCH with repeat testing in 2 to 3 months, as a high percentage of those with untreated SCH will have normal thyroid function on repeat testing.
- In the event you and your patient elect to treat SCH, guidelines and trials generally support a low initial daily dose of 25 to 50 mcg of levothyroxine (T4), followed by dose changes every 4 to 8 weeks and a goal of normalizing TSH to within the lower half of the reference range (0.4-2.5 mIU/L).
- Thyroid supplements are best absorbed when taken apart from food, calcium, or iron supplements. The ATA suggests taking thyroid medication 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal).33
Screening guidelines differ
Lacking population-level screening data from RCTs, most organizations do not recommend screening for thyroid dysfunction or they note insufficient evidence to make a screening recommendation
What about subclinical hypothyroidism in pregnancy?
Overt hypothyroidism is associated with adverse events during pregnancy and with subsequent neurodevelopmental complications in children, although the effects of SCH during pregnancy remain less certain.
Concerns have been raised over the potential association of SCH with pregnancy loss, placental abruption, premature rupture of membranes, and neonatal death. Historically, the prevalence of SCH during pregnancy has ranged from 2% to 2.5%
Guided by a large RCT that failed to find benefits (pregnancy outcomes, neurodevelopmental outcomes in children) following treatment of SCH in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) recommends against routine screening for thyroid disease in pregnancy.
Key recommendations on screening for thyroid dysfunction
US Preventive Services Task Force
There is insufficient evidence to recommend for or against thyroid dysfunction screening in nonpregnant, asymptomatic adults.
American Association of Clinical Endocrinology, and American Thyroid Association20
Screening for thyroid dysfunction should occur in adults starting at age 35 years, with repeat testing every 5 years in asymptomatic patients and more frequently in those with symptoms suggestive of hypothyroidism or with risk factors for thyroid disease such as history of autoimmune disease, neck irradiation, or medications affecting thyroid function.
National Institute for Health and Care Excellence19
Test for thyroid dysfunction in those in whom there is clinical suspicion for dysfunction or in patients with atrial fibrillation, depression, type 1 diabetes, or other autoimmune diseases.
American College of Obstetricians and Gynecologists (ACOG)34
ACOG recommends against universal screening for thyroid disease in pregnancy because identification and treatment of maternal SCH has not been shown to result in improved pregnancy outcomes and neurocognitive function in offspring.
Select professional society recommendations for treatment of persistent subclinical hypothyroidism
Guideline organization(s) Recommendations for treatment
American Thyroid Association and American Association of Clinical Endocrinology, 201220
TSH > 10 mIU/L: Consider treatment given risks for heart failure and cardiovascular disease.
TSH ≤ 10 mIU/L, but above reference range: Consider treatment based on individual factors.
National Institute for Health and Care Excellence, 201919
TSH ≥ 10 mIU/L: Consider levothyroxine for adults if this TSH level is measured on 2 occasions, 3 months apart.
TSH < 10 mIU/L, but above reference range: Consider levothyroxine for adults who are ≤ 65 years and have symptoms of hypothyroidism. If symptoms do not resolve with normalization of TSH, discontinue therapy.
European Thyroid Association Guideline on Management of Subclinical Hypothyroidism, 201314
≤ 70 years old
TSH ≥ 10 mIU/L: Treat with levothyroxine.
TSH < 10 mIU/L, but above reference range: Treat for 3 months with levothyroxine if hypothyroid symptoms are present. If symptoms are absent, repeat measurement in 6 months.
> 70 years old
TSH ≥ 10 mIU/L: Consider treatment if symptoms are present or if the patient’s vascular risk is high.
TSH < 10 mIU/L: Repeat measurement in 6 months.
British Medical Journal Guideline Panel, in collaboration with the Making Grade the Irresistible Choice project, 2019 (magic evidence.org)8
Do not treat subclinical hypothyroidism with thyroid hormones in nonpregnant adults. This recommendation may not apply to those with a TSH ≥ 20 mIU/L.