Subclinical Hypothyroidism (SCH): Dealing with Diagnostic and Treatment Dilemmas
M3 India Newsdesk Aug 27, 2022
Subclinical hypothyroidism (SCH) is not very uncommon in clinical practice, many clinicians face dilemmas regarding indications for treating the same. This article gives physicians insight into how to manage SCH as per guidelines as well as covers the common co-morbidities and conditions where one needs to consider treatment.
Key takeaways
- SCH is quite common and good number progress to overt hypothyroidism.
- SCH is possibly associated with cardiovascular dysfunction, dyslipidemia, and poor outcomes in pregnancy if not treated.
- It normalises in the majority of children with time, one has to be careful in treating SCH in elderly patients keeping in mind the mild rise in TSH is physiological.
- SCH treatment is indicated for symptomatic patients, pregnancy, infertility and TSH> 10mU/L irrespective of the Anti-TPO antibodies.
What is subclinical hypothyroidism (SCH)?
It is a serum TSH concentration above the statistically defined upper limit of the reference range when serum free thyroxine (FT4) concentration is within the reference range(Ross ds et al.). TSH reference range: a consensus panel of ATA, AACE and endocrine society has defined the normal range of TSH as 0.45-4.5 mIU/L(Martin et al.).
Prevalence
The prevalence of SCH varies as depends on what criteria are used for diagnosis.
- Colorado study- A prevalence of 9.5 % was noted and in this 74% had TSH between 5.1-10 mIU/l and 26% had TSH greater than 10 mIU/l ( Canaris et al., 2000). A higher prevalence is noted in women than in men in most of the studies.
- Whickham study- It was 3 times more in women than in men ( Garber et al, 2012). Prevalence as well increases with age ( Surks et al.,2007). Increased prevalence as well seen in chronic kidney disease and prevalence increase from 7% ( GFR >90 ml/ min per 1.73m ) to 17.9% ( GFR <60 ml/min per 1.73 m) ( Choncol et al.,2008).
Criteria for diagnosis of subclinical hypothyroidism
SCH is an elevated TSH value with normal T4 levels on at least 2 occasions which should be at least 3 months apart.
There are 2 variants of SCH:
- Milder form in which the TSH is between 5-10 mIu/l
- The second type in which TSH is more than 10 mIu/l
Anti-TPO antibodies must be done for patients with SCH, as the chances for overt hypothyroidism in the such patient is high in future.
ETA ( European Thyroid Association) guidelines advise a normal reference range of 0.4-4.0 mIU/l and mild elevation in serum TSH (4.0-7.0 mIU/l )in the elderly ( over 80 years of age) is considered a physiological adaptation to ageing ( Simon, et al.,2013). This reference range is derived from major studies on the age-specific distribution of TSH and anti-thyroid antibodies in the US population ( Surks et al.,2007).
Management of SCH in different medical conditions
There are different guidelines for different conditions regarding how and when to treat subclinical hypothyroidism.
1. Dyslipidemia
- Studies consistently demonstrate elevated levels of serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, lipoprotein(a), and possibly triglycerides in individuals with overt hypothyroidism.
- The prevalence of SCH among patients with dyslipidemia range from 1.4 to 11.2% ( Ineck BA, Ng TM), and the effects of SCH on serum lipid values are less clear.
- Clinical trials to date have not consistently shown a beneficial effect of LT4 treatment on serum lipid levels in SCH patients.
- Evaluation for hypothyroidism is recommended as part of the initial workup in all patients with hyperlipidemia (2002 3rd report of NCEP).
2. Diabetes
- Prevalence of SCH, (10.7%).of thyroid dysfunction associated with type 2 DM. SCH in DM increases diabetic complications, so diabetes patients with SCH need early treatment to avoid complications and reduce mortality and morbidity.
- Type 1 Diabetes patients are more susceptible to hypothyroidism. According to ADA autoimmune thyroid disease occurs in 17 to 30 per cent of patients diagnosed with Type 1 DM.
3. Hypertension and increased incidence of Cardiovascular disease in SCH
- Diastolic BP increases in both rest and effort with SCH, it affects lipid and glucose metabolism, it is very important to check and control hypertension in SCH and screen TSH, T4, and T3 in hypertension cases, it is more common in females, obese and strong family history.
- Increased CVD risk is particularly seen in individuals <50 years old (Biondi B et al.), however large-scale RCT of treatment for SCH with regards to clinical CV endpoints is lacking. It has been observed that treatment of SCH patients with LT4 helps in decreasing arterial stiffness, and endothelial dysfunction.
4. Coronary heart disease
- A meta-analysis of ten pooled studies enrolling 14,449 participants found a pattern of moderately increased risk for CHD and mortality in SCH patients together with evidence for statistical heterogeneity.
- Indeed, the relationship between SCH and CHD depends on both the mean age of enrolled individuals (>65 or <65 years)and the degree of serum TSH elevation (>10 or <10 mU/l) [105,107].
5. Depression
- The patients diagnosed with depression are screened for thyroid disease, the overt hypothyroidism has been associated with depression as thyroid hormone has a major effect on the brain.
- Depressive symptoms in mild raise TSH with normal T4 patients are attributed to the SCH effect, and these patients are started on LT4 therapy with no drastic change in their symptoms resulting in overtreatment.
6. Pregnancy
- TPO Ab status should be checked in all pregnant women with TSH concentration >2.5mU/L.
- Pregnant women with SCH and positive TPO Ab status with TSH more than the reference range for pregnancy should be treated with LT4.
- Even if the pregnant women are TPOAb negative but TSH more than 10.0mU/L should be treated with levothyroxine.
- Levothyroxine should not be given to women with negative TPOAb status and having normal TSH value i.e. less than 4 mU/L, if the specific value for each trimester is not known or the TSH value within the reference range for pregnancy.
- SCH in pregnancy can be effectively treated with LT4 of 50 µg/day.
7. SCH in an infertile female patient
- It is to be noted that management decisions for an infertile or non-pregnant population are based on little scientific evidence.
- Among infertile women, especially those with unexplained infertility, ovulatory dysfunction, recurrent miscarriage or adverse obstetric outcome, thyroid dysfunction could be detected.
- Women diagnosed with SCH and having TSH >4muI/L when treated with LT4 have improved pregnancy rates and perinatal outcomes.
8. SCH in childhood and infancy
- Usually, mild elevation of TSH occurs in 10-23%of obese children mostly due to the leptin effect that increased transcription of thyrotropin-releasing hormone TRH.
- Children with positive antibodies mostly autoimmune thyroiditis and those with negative antibodies with persistent high TSH levels may have a mutation in the TSH receptor gene. Almost one-third of patients with Down and William syndrome have SCH and the antibody screening is usually negative in this group. The patient may present with stunted growth, weakness, sleepiness, high cholesterol level and anaemia.
- Treatment is required for those TSH levels>10mU/L, if less then exclude other causes like the presence of goitre, antibodies TPO and other autoimmune signs if present close follow up within 3-6 months if TSH decreased regular follow up needed if increasing then start treatment.
9. SCH in elderly patients
- In moderately old patients (e.g. 60-70 years) the decision whether to treat or not to treat should be preceded by a specific evaluation of the patient including history or evidence of the pre-existent CV risk, degree of TSH elevation, co-morbidity and frailty.
- The use of age-specific reference ranges for serum TSH is important before labelling somebody as having SCH.
- It is well documented that there is a ‘physiological’ age-dependent impairment of endothelial and cardiac function as well as lipid profile and the effective burden of mild thyroid failure on the CV system of older people, particularly in the ‘oldest old (85 years & above), is still to be firmly established.
Guidelines for management
- If TSH is > 10mU/L, consider anti TPO antibodies.If they are positive, treatment has to be started with LT4, Levothyroid and Synthroid. If anti-TPO is negative and symptoms related to hypothyroidism are present, therapy can be considered.
- If TSH is < 10mU/L, and anti-TPO, as well as symptoms, are absent, keep the patient under observation and repeat tests after 6 months. If antibodies are positive or symptoms are present, therapy can be considered.
T4 replacement therapy is indicated in the following,
- TSH>10 mU/L because of its high risk to be complicated by ischemic heart disease and frank hypothyroidism.
- The patient has positive antibodies ANTI TPO.
- History of treated Graves’ disease
- For patients with TSH 7.0 -9.9 mU/L consider the age and symptoms of the patient if less than 65 years start treatment if age 65-70 years with symptoms consider treatment.
If TSH from the upper limit to 6.9 mU/L,
- Age <65-70 years with symptoms start treatment
- Age >65-70 years don’t start treatment.
- Positive Anti Tpo antibodies should be started on LT4 treatment.
- For women seeking pregnancy with cycle disturbance.
Follow-up of SCH patients
- The aim of treatment is to normalise the TSH level recommended target (0.5-2.5mU/L), in young and middle age but higher in the elderly >65-70 (initial serum TSH>7.0 mU/L) the target TSH 3 up to 6 mU/L.
- Follow up of TSH level after 6 weeks from the initiation of therapy and then titrate the dose according to the TSH reading with recheck every 6 weeks till the target is achieved.
- For those without treatment repeat thyroid function after six months and if normal then annually.
Glossary
- AACE: American Association of Clinical Endocrinology
- TPO: Thyroperoxidase
- DM: Diabetes Mellitus
- ATA: American Thyroid Association
- ADA: American Diabetic Association
- LT4: Levothyroxine
- TSH: Thyroid stimulating hormone
- SCH: Subclinical hypothyroidism
- RCT: Randomised controlled trial
- CHD: Coronary heart disease
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Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.
About the author of this article: Dr Hitesh Saraogi is a diabetologist and physician at Dhanvantari Hospital, Raj Nagar Extension, Ghaziabad.
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