What are the guidelines for managing hypothyroidism (underactive thyroid)?

From the Guidelines

The primary treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium) 1.

Key Considerations for Management

• The serum TSH test is the primary screening test for thyroid dysfunction, with multiple tests done over a 3- to 6-month interval to confirm or rule out abnormal findings 1.
• Treatment efficacy is monitored by measuring TSH levels, with the goal of normalizing TSH levels (typically 0.4-4.0 mIU/L) 1.
• Certain conditions require special consideration, such as pregnancy, which may necessitate dose increases of 25-50%, and absorption can be reduced by iron supplements, calcium, antacids, and some foods.
• Patients should maintain consistent timing of medication and avoid switching between different levothyroxine brands without medical supervision.

Treatment Approach

• The standard starting dose for most adults is 1.6 mcg/kg/day, typically 75-125 mcg daily, taken on an empty stomach 30-60 minutes before breakfast or at bedtime, at least 4 hours after medications that can interfere with absorption.
• Elderly patients or those with cardiac disease should start at lower doses (25-50 mcg daily) with gradual increases.
• Treatment is typically lifelong, with the goal of resolving symptoms like fatigue, cold intolerance, and weight gain while normalizing thyroid function tests and preventing long-term complications such as cardiovascular disease and dyslipidemia.

Special Populations

• Patients with previously normal TSH levels may be rechecked every 1–2 years or obtained at any time the growth rate is abnormal 1.
• The presence of thyroid autoantibodies (antithyroid peroxidase [TPO] and antithyroglobulin [TG]) identifies patients at increased risk for thyroid autoimmunity 1.
• Comprehensive evaluation and treatment of hyperthyroidism should be initiated in patients with suppressed TSH and elevated T4/T3 levels 1.

From the FDA Drug Label

TIROSINT® (levothyroxine sodium) capsules, for oral use Initial U. S. Approval: 2000 Thyroid hormones, including TIROSINT, should not be used for the treatment of obesity or for weight loss. Doses beyond the range of daily hormonal requirements may produce serious or even life threatening manifestations of toxicity Levothyroxine (T4) indicated for adults and pediatric patients 6 years and older with: Hypothyroidism - As replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism Administer once daily, on an empty stomach, one-half to one hour before breakfast Administer at least 4 hours before or after drugs that are known to interfere with absorption Evaluate the need for dose adjustments when regularly administering within an hour of certain foods that may affect TIROSINT absorption Swallow TIROSINT capsules whole, do not cut, crush, or chew Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food, and the specific nature of the condition being treated. Peak therapeutic effect may not be attained for 4-6 weeks Adequacy of therapy determined with periodic monitoring of TSH and/or T4 as well as clinical status

The guidelines for hypothyroidism management include:

• Replacement therapy: Levothyroxine (T4) is indicated for adults and pediatric patients 6 years and older with primary, secondary, or tertiary congenital or acquired hypothyroidism.
• Administration: Administer once daily, on an empty stomach, one-half to one hour before breakfast.
• Dose adjustments: Evaluate the need for dose adjustments when regularly administering within an hour of certain foods that may affect TIROSINT absorption.
• Monitoring: Adequacy of therapy determined with periodic monitoring of TSH and/or T4 as well as clinical status.
• Special considerations: Pregnancy may require the use of higher doses of TIROSINT, and TSH levels should be monitored and the TIROSINT dosage adjusted during pregnancy 2.
• Pediatric use: TIROSINT is indicated for use in pediatric patients 6 years and older, and the initial dose varies with age and body weight 2.

From the Research

Guidelines for Hypothyroidism Management

• The current guideline-based management of hypothyroidism recommends monotherapy with levothyroxine (LT4), titrated to maintain the level of thyrotropin within a euthyroid reference range 3.
• The goal of treatment is to normalize signs and symptoms, as well as to achieve thyroid-stimulating hormone (TSH) concentrations within the reference range, on an individual basis 4.
• Approximately 5-10% of hypothyroid patients remain symptomatic, despite achieving the target TSH levels, and may benefit from the use of liothyronine (LT3) added to LT4 4, 5.
• The American Thyroid Association recommends levothyroxine monotherapy for treating hypothyroidism, but up to 15% of patients may experience residual symptoms despite normalized TSH levels 6.

Combination Therapy

• Combination therapy with LT4 and LT3 has been evaluated in several clinical trials, but the results have been inconclusive 7, 5.
• Some studies suggest that combination therapy may have beneficial effects on mood, quality of life, and psychometric performance of patients, compared with levothyroxine alone 7.
• However, the pharmacokinetics of LT4 and LT3 differ, which is a barrier to their co-administration 3.
• The recommended LT4/LT3 ratio is 13:1-20:1, and the goals of combination therapy should be to achieve a physiological ratio of free triiodothyronine/free thyroxine (FT3/FT4) and non-suppression of TSH 4.

Future Directions

• Additional high-quality studies are needed to further evaluate patient preferences, as well as to investigate long-term outcomes of combination therapy 6.
• Future clinical trials using LT4 + LT3 tablets better suited for combination therapy will resolve the outstanding research questions relating to the place of LT4 + LT3 combination therapy in the management of hypothyroidism 3.
• Polymorphisms in deiodinase genes that encode the enzymes that convert T4 to T3 in the periphery may provide potential mechanisms underlying unsatisfactory treatment results with LT4 monotherapy 5.