Approach
All patients with overt primary hypothyroidism should be treated. The goal of treatment is reduction of symptoms and prevention of long-term complications.[1][8] Treatment is given upon establishing the diagnosis and is lifelong. Treatment is with levothyroxine. There is no evidence that 'natural' or pig thyroid extract provides clinically reliable therapy.[42]
Levothyroxine therapy
Indications:
Treatment is indicated in all symptomatic patients with overt primary hypothyroidism
Many experts also recommend treating sub-clinical hypothyroidism (asymptomatic with a normal serum free thyroxine [T4]) if thyroid-stimulating hormone (TSH) is >10 mIU/L, as the theoretical risk of progression to overt hypothyroidism is high.[2][8][43] 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.[44] Despite the lack of good evidence, some experts recommend treating the following groups of patients with sub-clinical hypothyroidism and TSH <10 mIU/L:
]
Dose:
Starting dose depends on age and presence of co-existing cardiac disease.[1][8] Adult patients who are healthy and aged 65 years or younger should be started on the full replacement dose of levothyroxine.[1][42][46]
Levothyroxine therapy may exacerbate angina in patients with coronary artery disease.[42] 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.[42]
Patients aged over 65 years without heart disease are less tolerant of full replacement initial doses.[42] 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.[1]
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.[29] 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.[29][47]
Nephrotic syndrome, which increases clearance of thyroid hormone, and malabsorption (e.g., coeliac disease), which impairs absorption of hormone, can increase levothyroxine requirements.[1][42]
Iron, cholestyramine, calcium, and sucralfate decrease levothyroxine absorption.[1][8] Anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine) increase its protein-binding capacity. Rifampin and sertraline increase its metabolism.[1][8] 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.[48]
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.[8]
Due to the long half-life of levothyroxine (1 week), TSH should be measured 4-6 weeks after initiation of therapy or dosage change.[8][42] Stable patients with normal serum TSH should have TSH measured every 12 months.[1]
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