Optimal - The Blog

May 6, 2024

T4 + T3 = Hypothyroidism Relief

A number of individuals receiving stand-along T4 thyroid hormone therapy report persistent symptoms... A combination of T4 + T3 therapy may help... 

Considerable research interest has focused on administration of combinations of T4 and T3 to a patient with symptoms of hypothyroidism that are apparently refractory to LT4 ().

An initial double-blind, randomized trial in patients with hypothyroidism demonstrated improvements in mood and neuropsychological function in patients for whom T3 was given in place of a proportion of their LT4 dose.

Further evidence from randomized or observational studies has supported the possibility of significant differences in quality of life (QoL) scores or psychological scores in favor of the combination vs LT4 monotherapy.

Typical symptoms of hypothyroidism.

Examples of medical conditions or treatments that produce symptoms resembling hypothyroidism

Typical symptoms resembling those of hypothyroidism

Chronic fatigue

GI diseases that affect LT4 absorption

Addison’s disease

Anemia

Stress

Changes in weight

Pregnancy

Medications that interfere with LT4 absorptiona

Constipation

Puffy eyes

Hoarse/deep voice

Muscle cramps

Hair loss or dry hair

Dry or scaly skin

Muscle weakness

Carpal tunnel syndrome

Feeling too cold

Slow thinking

Tired/lethargic

Weight gain

Depression

Loss of libido

Menstrual abnormalities

Poor memory

Overview of management of patients with hypothyroidism who continue to report symptoms of that condition despite receiving levothyroxine therapy.

Pragmatic approach to managing a patient with continued symptoms of hypothyroidism despite apparently adequate levothyroxine therapy.

  • Take a thorough medical history
  • Careful initial examination to identify potential other causes for hypothyroid-like symptoms
  • Check the diagnosis of hypothyroidism and lab results
  • Ensure TSH is well controlled first
    Check for patient factors and concomitant drug treatments that might have interfered with the TSH assay
  • Check for sub-optimal compliance
  • Is the patient taking all required doses?
  • Check for factors that could alter the metabolism of thyroid hormones
  • Potential for malabsorption of LT4
    Some treatments affect thyroid hormone metabolism
  • Check how the patient uses LT4
  • Does the patient take LT4 in the fasting state at the start of the day, as per label?
  • Does the patient adjust the timing of other therapies that could interfere with LT4 absorption?
  • Is the patient storing their LT4 correctly?
  • Does the patient have the correct LT4 tablets, as per prescription?

Personalized treatment with LT4 + LT3 may be of benefit for some patients with persistent symptoms of hypothyroidism such as those with polymorphisms in the deiodinase enzyme 2 (DIO2)

Reference

Razvi, Salman et al. “Managing symptoms in hypothyroid patients on adequate levothyroxine: a narrative review.” Endocrine Connections vol. 9,11 (2020): R241-R250. doi:10.1530/EC-20-0205. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Thyroid Function and Depression  

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