The Diagnosis and Management of Hypothyroidism

Bhuvana Guha, MD, Guha Krishnaswamy, MD, And Alan Peiris, MD, PhD, MRCP


South Med J. 2002;95(5):475-480. 

In This Article


Many different forms of thyroid replacement therapy have been used in the past. Currently, patients should be treated with levothyroxine.[1,16] The use of generic thyroxine, with its variable bioavailability, may result in the need for additional testing. Since the cost difference between brand-name and generic thyroxine preparations is not substantial, many endocrinologists prefer not to use generic thyroxine. In patients with primary hypothyroidism, the TSH level should be lowered to about the midpoint of the normal range. The average dose of levothyroxine required in adults is approximately 1.0 to 1.7 µg/kg. In young adults without associated illnesses, the starting dose can be estimated from this calculation. The etiology of hypothyroidism may influence the replacement dose of thyroxine needed. Patients who have had a total thyroidectomy or chronic autoimmune thyroiditis may need larger doses than those who have not. Kabadi et al[17] were able to predict the dose of thyroxine required based on the pretreatment TSH level. Following total thyroidectomy for differentiated thyroid cancer, a lower TSH value (eg, <0.1) may be desirable. In the treatment of central hypothyroidism, the goal is to achieve a normal free-T4 level, since the TSH level may be unreliable in this setting. Patient education regarding the adverse effects of thyroxine replacement should include advice against "doubling-up" following days in which the usual dose was not taken. Once thyroid function tests and clinical status are stable, thyroid function tests should be monitored approximately every 6 to 12 months.

Patients unable to take thyroxine for several days do not need additional intervention, given the long half-life of thyroxine. Patients unable to take oral thyroxine for more prolonged periods, however, may need daily intravenous supplementation with approximately 80% of the daily oral dose.

The persistence of symptoms while taking thyroxine replacement have raised questions about the role of T3 in therapy. Moreover, the increased interest in alternative medicine has resulted in patient inquiries regarding replacement therapy with "more natural" whole thyroid. While the administration of thyroxine leads to normal levels of T4 and T3, the question of tissue levels achieving normality has been raised by studies of thyroidectomized animals. Using T3 for chronic replacement is currently not recommended, due to its short half-life and the wide fluctuations in serum levels. Combined T4-T3 preparations are available as desiccated thyroid, with 10 µg of T3 and 40 µg of T4 in one grain (60 mg), and liotrix, which contains a 4:1 ratio of T4 to T3. Most endocrinologists favor levothyroxine therapy over these combined preparations or thyroid extract, due to its more predictable absorption leading to more stable serum levels, as well as better standardization of the medication. Bunevicius et al[18] reported improved mood and symptom relief when T4 was combined with T3, compared with thyroxine replacement alone. At the end of that study, patients preferred the combination form of treatment. Given the short duration of the study, additional investigations are needed to confirm these findings and evaluate possible adverse effects from combination therapy before widespread use is recommended. Multiple factors lead to persistent elevation of TSH values in patients treated for primary hypothyroidism ( Table 5 ).[19]