Approach
All patients with overt primary hypothyroidism should be treated. The goal of treatment is reduction of symptoms and prevention of long-term complications.[2][62] Treatment is given upon establishing the diagnosis and is lifelong. Treatment is with levothyroxine (a synthetic form of thyroxine). There is no evidence that 'natural' or pig thyroid extract provides clinically reliable therapy.[55][76]
Levothyroxine therapy
Overt primary hypothyroidism
Treatment is indicated in all symptomatic patients
Sub-clinical hypothyroidism with thyroid-stimulating hormone (TSH) >10 mlU/L
Many experts recommend treating sub-clinical hypothyroidism (asymptomatic with a normal serum free thyroxine [T4]) if TSH is >10 mIU/L, as the theoretical risk of progression to overt hypothyroidism is high.[3][55][62][77][78] However, there is controversy and variable guidance in this area.[79][80][81]
Some observational data indicate that the risk of coronary heart disease and its resultant mortality is higher in individuals with sub-clinical hypothyroidism if TSH is >10 mIU/L.[82] However, low quality evidence from one randomised controlled trial in adults aged >65 years with sub-clinical hypothyroidism did not find that treatment with thyroid hormones had an effect on cardiovascular outcomes, although the trial was underpowered for this outcome.[81][83]
Sub-clinical hypothyroidism with TSH <10 mlU/L
There is controversy about whether patients with sub-clinical hypothyroidism and TSH <10 mlU/L should be treated.[84][85][86]
Despite the lack of good evidence, some experts recommend treating the following groups of patients:[56][62][87] [
]
Pregnant women with a TSH greater than pregnancy-specific reference range and positive antithyroid peroxidase antibody (anti-TPOAb). If women are anti-TPOAb negative, treatment is recommended if TSH is >10 mlU/L.
Women who are trying to conceive and have a history of infertility or ovulatory dysfunction.
Adults with evidence or risk factors for atherosclerotic cardiovascular disease or heart failure, anti-TPOAbs, or symptoms of hypothyroidism.
Practitioners often do not treat patients aged greater than 70 years due to the risk of treatment-related complications.[78][88]
Dose
Starting dose depends on age and presence of co-existing cardiac disease.[1][62]
Adult patients with overt primary hypothyroidism, who are healthy and aged 65 years or younger should be started on the full replacement dose of levothyroxine.[76][89]
If patients are treated for sub-clinical hypothyroidism, they should be started on a low dose of levothyroxine, with the dose adjusted in small increments to normalise TSH.[62]
Levothyroxine therapy may exacerbate angina in patients with coronary artery disease.[76] A lower starting dose of levothyroxine is recommended, with titration in small increments every 4-6 weeks to a full therapeutic dose and close attention to the development of ischaemic symptoms.[76]
Patients aged over 65 years without heart disease are less tolerant of full replacement initial doses.[76] A low starting dose is also recommended in these patients with titration in small increments every 4-6 weeks.
The main complication of treatment is over-replacement of thyroid hormone, which increases the risk of osteoporosis and atrial fibrillation.[2]
Special considerations
Pregnancy increases thyroid hormone requirements and the required dose of levothyroxine may increase accordingly. It may be necessary to increase the dose of levothyroxine by 25% to 30% in the first trimester.[56] 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]
Nephrotic syndrome, which increases clearance of thyroid hormone, and malabsorption (e.g., coeliac disease), which impairs absorption of hormone, can increase levothyroxine requirements.[76]
Iron, cholestyramine, calcium, and sucralfate decrease levothyroxine absorption.[2][62] Anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine) increase its protein-binding capacity. Rifampin and sertraline increase its metabolism.[62] Concomitant use of these drugs may cause an increase in dosage requirements.
Some patients achieve a normal TSH but still have symptoms. This should be acknowledged and alternative causes considered. Although there is no good evidence that combination therapy with levothyroxine and liothyronine is indicated, this is an area of ongoing research.[91]
Monitoring
The dose is increased or decreased in small increments to normalise TSH, which is the chemical goal of therapy. Some experts advocate consistently using one preparation of brand-name levothyroxine, arguing that it provides a more reliable dose than generic preparations.[62]
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][76] Stable patients with normal serum TSH should have TSH measured every 12 months.[51][55]
Use of this content is subject to our disclaimer