Italian guidelines for the management of adult individuals with primary hypothyroidism outside pregnancy

Recommendations and indications for good clinical practice

• 1The panel recommends monotherapy with LT4 in comparison to combined therapy with LT4 + LT3Quality of evidence: Very Low; Strength of recommendation: Strong, in favor of the intervention
• 2The panel suggests the administration of oral LT4 on an empty stomachQuality of evidence: Very Low; Strength of recommendation: Conditional, in favor of the intervention
• 3In patients whose hypothyroidism is due to previous total thyroidectomy, the panel suggests an initial dose of LT4 adequate to completely replace the loss of thyroid function. This generally ranges between 1.5 and 1.9 µg/kg of body weight/day. Age and gender influence the dosage that should be adjusted according to the patient's conditionsQuality of evidence: Very Low; Strength of recommendation: Conditional, in favor of the intervention
• 4The panel suggests the measurement of serum TSH 4–6 weeks after the start of replacement therapy, to assess its adequacyQuality of evidence: Very Low; Strength of recommendation: Conditional, in favor of the intervention
• The use of the different formulations of LT4 currently available (tablets, liquid or soft-gel capsules) should be considered based on patient's preference, lifestyle habits and presence of comorbidities. In general, they are equally effective for the purposes of replacement therapy [61, 62] (ungraded).
• LT4 therapy should be preferably taken in the morning, at least 30 min — ideally 60 min — before the intake of food or beverages to optimize hormone absorption [63–65] (ungraded).
• LT4 therapy should be taken at an adequate time interval from the drugs potentially interfering with its absorption [66–70] (ungraded). Among these it is worthwhile mentioning proton pump inhibitors and other gastro-protectors, calcium and iron salts, and bile acid sequestrants.
• In patients who are unable to take LT4 in the morning, administration at different times, particularly late in the evening, can be considered. A fasting period of at least three hours should be observed beforehand as the absorption of LT4 depends on the gastric content acidity and is impaired by the food content of the stomach [71–73] (ungraded).
• Serum TSH should be monitored 4–6 weeks after any change of the dosage or formulation of LT4. Once the adequate replacement dosage has been found, monitoring is recommended after 6 months and then at 12-month intervals or more frequently as clinically indicated. Dosage adjustments may be necessary in case of weight changes, in the elderly, if internal medicine comorbidities occur or if drugs interfering with absorption are introduced [62, 74, 75] (ungraded).
• If the replacement treatment is effective, both biochemically and clinically, it is advisable to maintain the patient with a constant dosage and formulation over time [74] (ungraded).
• In the replacement therapy of hypothyroidism it is not advisable the use of desiccated thyroid or the therapy with LT3 alone [48, 49, 54, 56, 59] (ungraded).
• In the elderly, frail patients, and subjects with cardiovascular disease or significant comorbidities, regardless of the etiology and severity of hypothyroidism, it is advisable to start the replacement therapy cautiously with low doses. Afterwards, the dose should be gradually modified based on serum TSH values, symptom control and absence of side effects. In elderly patients, it is advisable to maintain TSH levels at the upper limits of normal range [76, 77] (ungraded).
• Follow-up of hypothyroidism is based on serial evaluation of TSH and FT4, while it is not useful to routinely measure FT3 [78] (ungraded).
• In subjects with overt hypothyroidism induced by the therapy with amiodarone, the anti-arrhytmic drug can be continued in presence of a defined cardiological indication. Treatment with LT4 should be started cautiously with gradual dose, to avoid a therapeutic over-dosage and the worsening of the risk of arrhythmia [79, 80] (ungraded).
• In subjects starting lithium therapy, due to the high frequency of incident hypothyroidism (especially in females), thyroid function should be monitored at 6–12-month intervals. If hypothyroidism occurs, LT4 replacement treatment should be started without withdrawing lithium therapy [81] (ungraded).
• Pre-menopausal women on replacement therapy for hypothyroidism should be informed about the need for medical consultation in case of diagnosis or planning of pregnancy, for early dosage adjustment [82–84] (ungraded).
• In elderly subjects with TSH not yet at target but with values below 10 mIU/L, the patient's overall conditions should be carefully evaluated before increasing the dose of LT4. The available evidence demonstrate that the normalization of TSH to the target levels of general population benefits lipid profile but has limited impact on the major clinical outcomes [85, 86] (ungraded).
• There is no strong evidence that treatment of subclinical hypothyroidism (elevated TSH associated with normal FT4 values) provides significant clinical benefits [87, 88]. However, in case of persistent subclinical hypothyroidism on LT4 replacement therapy, normalization of serum TSH is advisable (ungraded).
• After the diagnostic phase and the achievement of stable target hormonal values, routine management of the patient with hypothyroidism can be safely performed by the general practitioner (GP) (ungraded).
• Therapy with drugs that modulate the immune system and/or influence thyroid function (e.g., interferon, alemtuzumab, amiodarone).