What does a high TSH mean?

The ETA splits subclinical hypothyroidism into mildly increased TSH (4.0 to 10.0 mU/L) and more severely increased TSH (above 10 mU/L) [4]. Pooled cohort studies define it as TSH 4.5 to 19.9 mIU/L with normal thyroxine [7]. A high TSH with low free T4 indicates overt primary hypothyroidism [1].

Because TSH responds to free T4 on a log scale, TSH usually rises well before free T4 falls below its range [8]. Andersen and colleagues showed that the line between subclinical and overt disease is somewhat arbitrary, because it depends on where a person's own set point sits inside the lab range [9].

Free T4 appears in ng/dL or pmol/L; 1 ng/dL is about 12.9 pmol/L [10]. In one outpatient study, mean free T4 fell about 7% as TSH rose above 4.5 mIU/L [11].

• Hashimoto thyroiditis causes up to 85% of primary hypothyroidism in iodine-sufficient areas [1].
• Treatment of the thyroid or neck, including surgery and radiation, raises risk [1].
• Iodine: deficiency raises risk [1], and in iodine-rich Korea the whole TSH range ran higher, up to 6.84 mIU/L [12].
• Medicines: lithium raised the odds of clinical hypothyroidism 5.78-fold and TSH by about 4 units on average [13]; amiodarone and immune checkpoint inhibitors can also cause hypothyroidism [1].
• Recovery from illness: TSH can climb above normal for a time as T4 recovers [14].
• Age: TSH rises with age in people without thyroid disease, and 70% of older people with TSH above 4.5 mIU/L were inside their age-specific range [15].
• Timing: an early-morning or fasting sample reads higher than an afternoon or after-meal one [16][17].

In people with hypothyroidism, fatigue is reported by 68% to 83%, weight gain by 24% to 59%, cognitive problems by 45% to 48% and menstrual irregularity by about 23% [1].

These symptoms are common in people with normal thyroid function too. In TRUST, levothyroxine lowered TSH but did not improve hypothyroid symptom or tiredness scores compared with placebo in adults over 65 [6]. Fatigue has many causes, including low iron stores, so a broader check such as ferritin is often part of the same workup.

1. Free T4 in the same sample, which NICE recommends when TSH is above range [2].
2. Repeat after 2 to 3 months with TSH, free T4 and TPO antibodies [4]. In older adults, TSH normalized in 60.8% after one raised value and in 39.9% even after a confirming second test, so a third measurement may be sensible before treatment [5].
3. TPO antibodies once; NICE advises not repeating them [2]. Antibodies raise the chance of progression to overt hypothyroidism [3].
4. Cholesterol is often checked too, because hypothyroidism raises LDL cholesterol and ApoB [18]. See LDL cholesterol.

How guidelines approach treatment

• NICE: consider levothyroxine at TSH 10 mIU/L or higher on two tests 3 months apart; for adults under 65 with symptoms and TSH above range but below 10, consider a 6-month trial [2].
• ETA: treat younger patients (under 65 to 70) with TSH above 10; for people over 80 to 85 with TSH up to 10, generally wait and see [4].
• BMJ panel: recommends against thyroid hormones for most adults with subclinical hypothyroidism, excluding TSH above 20 and those trying to conceive [19].

Pregnancy and planning pregnancy follow separate, stricter guidance [20]. Diagnosis, starting treatment and any dose change are clinician decisions.

Untreated hypothyroidism may progress to severe decompensation called myxedema coma, with hypothermia, low blood pressure and altered mental status; it needs intensive care and has a mortality rate of up to 30% [1].

Also talk to a clinician promptly if you have a raised TSH and are pregnant or trying to conceive, since hypothyroidism is linked to disrupted ovulation, infertility and miscarriage [1]. A mildly raised TSH on a routine test with no symptoms is not urgent.