Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
low-dose levothyroxine
In cases where the thyroid-stimulating hormone (TSH) is only mildly raised, the patient is not symptomatic and the serum free thyroxine (T4) is normal, the diagnosis is sub-clinical hypothyroidism.[3] Many experts recommend treating if TSH is >10 mIU/L, as the theoretical risk of progression to overt hypothyroidism is high.[3][62][77] There is evidence from observational studies that these patients have an increased risk of coronary heart disease, heart failure and cardiovascular mortality, although it is unclear if treatment with levothyroxine reduces these risks.[81][82]
In patients with sub-clinical hypothyroidism and TSH <10 mIU/L, some experts recommend treating patients with evidence or risk factors for atherosclerotic cardiovascular disease or heart failure, antithyroid peroxidase antibodies (anti-TPOAbs), or symptoms of hypothyroidism, despite the lack of good evidence.[62] Practitioners often do not treat patients aged >70 years due to the risk of treatment-related complications.[78][88]
Treatment is recommended for pregnant women if the TSH is greater than the pregnancy-specific reference range and they are anti-TPOAb positive. If they are anti-TPOAb negative, treatment is recommended if the TSH is >10 mlU/L.[56]
It is uncertain whether women with sub-clinical hypothyroidism and a history of infertility who are trying to conceive benefit from thyroid hormone replacement and guidance varies.[51][56][87]
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Patients should be started on a low dose of levothyroxine. The dose is adjusted in small increments to normalise TSH, which is the chemical goal of therapy. Due to the long half-life of levothyroxine (1 week), TSH should be measured 4-6 weeks after initiation of therapy or dosage change.[62]
The main complication of treatment is over-replacement of thyroid hormone, which increases the risk of osteoporosis and atrial fibrillation.[2]
Pregnancy increases thyroid hormone requirements and the required dose of levothyroxine may increase. TSH should be measured every 4-6 weeks in pregnant women on levothyroxine therapy until mid-gestation, then once in each of the second and third trimesters.[56][90] It may be necessary to increase the dose of levothyroxine by 25% to 30% in the first trimester of pregnancy.[56]
Nephrotic syndrome and malabsorption (e.g., coeliac disease) can increase levothyroxine requirements.[76] Concomitant use of iron, cholestyramine, calcium, sucralfate, anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine), rifampin, and sertraline may cause an increase in dosage requirements.[2][62]
Primary options
levothyroxine: 1.5 micrograms/kg (or 25-50 micrograms in patients who require a low starting dose) orally once daily initially, adjust dose in increments of 12.5 to 25 micrograms/day every 4-6 weeks based on thyroid function tests
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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