Hypothyroidism Treatment & Management

The treatment goals for hypothyroidism are the reversal of clinical progression and the corrections of metabolic derangements as evidenced by normal blood levels of TSH and free T4. Thyroid hormone is administered to supplement or replace endogenous production. In general, hypothyroidism can be adequately treated with a constant daily dose of levothyroxine (LT4).

Clinical benefits begin in 3-5 days and level off after 4-6 weeks. Anticipated full replacement doses may be initiated in individuals who are otherwise young and healthy. In elderly patients or those with known ischemic heart disease, treatment should begin with one fourth to one half the expected dose, and the dose should be adjusted in small increments no sooner than 4-6 weeks.

Achieving a TSH level within the reference range may be slowed because of delay of hypothalamic-pituitary axis readaptation and may take several months. After dose stabilization, patients can be monitored with annual clinical evaluations and TSH monitoring. Patients should be monitored for symptoms and signs of overtreatment, which include tachycardia, palpitations, nervousness, tiredness, headache, increased excitability, sleeplessness, tremors, and possible angina.

A meta-analysis of randomized controlled trials of thyroxine-triiodothyronine combination therapy (T4 + T3) versus thyroxine monotherapy (T4) for treatment of clinical hypothyroidism found no difference in the effectiveness of the combination vs monotherapy in bodily pain, depression, fatigue, body weight, anxiety, quality of life, total cholesterol, LDL-C, HDL-C and triglyceride levels. Hence, T4 monotherapy remains the treatment of choice.^[12]

Pregnancy

Hypothyroidism in pregnancy is associated with preeclampsia, anemia, postpartum hemorrhage, cardiac ventricular dysfunction, spontaneous abortion, low birth weight, impaired cognitive development, and fetal mortality. Even mild disease may be associated with adverse affects for offspring.

Increased dosage requirements should be anticipated during pregnancy, especially in the first and second trimesters. Studies have suggested that patients with hypothyroidism should augment the LT4 dose by 30% at the confirmation of pregnancy, followed by adjustments according to TSH levels. For previously diagnosed women, serum TSH should be measured every 3-4 weeks during the first half of pregnancy and every 6 weeks thereafter. LT4 dose should be adjusted to maintain a serum TSH less than 2.5 mIU/L. TSH and free T4 levels should be measured every 3-4 weeks after every dosage adjustment.^[13]

Autoimmune thyroid disease without overt hypothyroidism has been associated with a higher miscarriage rate. Negro et al showed that euthyroid Caucasian women with positive anti-TPO antibodies treated with levothyroxine during the first trimester had lower miscarriage rates when compared with those who were not treated. They also had lower incidence of premature delivery, comparable to women without thyroid antibodies.^[14] This will need to be confirmed by other studies, and, if confirmed, there will be an indication to treat euthyroid pregnant women who have thyroid antibodies.

LT4 should not be taken with prenatal vitamin preparations containing iron and calcium. After delivery, the LT4 dose can be reduced to the prepregnancy level and TSH should be checked in 6 weeks.

Subclinical hypothyroidism

Significant controversy persists regarding the treatment of patients with mild hypothyroidism. Some have argued that treatment of these patients improves symptoms, prevents progression to overt hypothyroidism, and may have cardioprotective benefits. Reviews by the US Preventive Services Task Force^[15] and an independent expert panel^[16] found inconclusive evidence to recommend aggressive treatment of patients with TSH levels of 4.5-10 mIU/L. The Endocrine Society recommends thyroxine replacement in pregnant women with subclinical hypothyroidism^[17] ; the American College of Obstetricians and Gynecologists does not recommend it as a routine measure.^[18]

Ultrasonography may have prognostic value in subclinical hypothyroidism. In an Italian study, progression to overt hypothyroidism occurred more often in patients whose ultrasonographic thyroid scan showed diffuse hypoechogenicity (an indication of chronic thyroiditis).^[19]

Following subclinical hypothyroidism and treating on a case-by-case basis is reasonable. Treatment of subclinical hypothyroidism has been shown to reduce total cholesterol, non-HDL cholesterol, and apolipoprotein B,^[20] and to decrease arterial stiffness and systolic blood pressure.^[21] In patients with concomitant subclinical hypothyroidism and iron deficiency anemia, iron supplementation may be ineffective if LT4 is not given.^[22]

The American Association of Clinical Endocrinologists (AACE) guidelines state that treatment is indicated in patients with TSH levels above 10 mIU/mL or in patients with TSH levels between 5 and 10 mIU/mL in conjunction with goiter and/or positive antithyroid peroxidase antibodies, as these patients have the highest rates of progression to overt hypothyroidism. An initial dose of 25-50 mcg/d of LT4 can be used and can be titrated every 6-8 weeks, to achieve a target TSH of between 0.3 and 3 mIU/mL.^[23]

Myxedema coma

An effective approach is to use intravenous LT4 at a dose of 4 mcg/kg of lean body weight, or approximately 200-250 mcg as a bolus in a single or divided dose, depending on the patient's risk of cardiac disease followed by 100 mcg 24 hours later and then 50 mcg daily IV or PO along with stress doses of intravenous glucocorticoids. Adjustment of the dose can then be made based on clinical and laboratory along with stress doses of intravenous glucocorticoids. Use of intravenous triiodothyronine is controversial and based on expert opinion. It has a higher frequency of adverse cardiac events and is generally reserved for patients who are not improving clinically on LT4. LT3 can be given initially as a 10 mcg IV bolus and repeated every 8-12 hours until the patient can take maintenance oral doses of T4. Advanced age, high dose T4 therapy, and cardiac complications had the highest associations with mortality.^[24]

Surgery is indicated for large goiters that compromise tracheoesophageal function; surgery is rarely needed in patients with hypothyroidism and is more common in the treatment of hyperthyroidism.

Patients with a nodular thyroid, suspicious thyroid nodules, or compressive symptoms such as dysphagia; pregnant women; patients with underlying cardiac disorders or other endocrine disorders; persons younger than 18 years; and those unresponsive to treatment should be referred to an endocrinologist.

Some patients with thyroiditis can develop hyperthyroidism (or symptoms consistent with hyperthyroidism) before developing hypothyroidism and may benefit from consultation with an endocrinologist.

Suspected myxedema coma is a medical emergency with a high risk of mortality that requires initiation of parenteral (intravenous) LT4 and glucocorticoids prior to laboratory confirmation. An urgent endocrinology consultation should be obtained.

Rarely an increase in size of a goiter in a patient with autoimmune thyroid disease could be a lymphoma and should be evaluated by an endocrinologist.

No specific diets are required for hypothyroidism.

Subclinical hypothyroidism has been seen in increased frequency in patients with greater iodine intake. The World Health Organization recommends a daily dietary iodine intake of 150 mcg for adults, 200 mcg for pregnant and lactating women, and 50-120 mcg for children.

Patients who have hypothyroidism have generalized hypotonia and may be at risk for ligamental injury, particularly from excessive force across joints. Thus, patients should exercise caution with certain activities, such as contact sports or heavy physical labor.

Patients with uncontrolled hypothyroidism may have difficulty maintaining concentration in low-stimulus activities and may have slowed reaction times. Patients should use caution if an activity has a risk of injury (eg, operating presses or heavy equipment, driving).