Adverse effects of subclinical hypothyroidism and the role for levothyroxine
| Adverse effect | Evidence of adverse effect | Role for treatment with levothyroxine |
|---|---|---|
| Metabolic syndrome, obesity, diabetes | Associations observed, but cause and effect are unclear23,24 | No evidence to support |
| Dyslipidemia | Relationships observed between thyroid-stimulating hormone (TSH) elevation and altered lipid profiles13,43 | Associated with improved lipid profiles2,34,44–46 |
| Cardiovascular endothelial dysfunction | Increased risk of myocardial infarction, atherosclerosis, aortic calcification,48 cardiovascular disease and mortality37; increased arterial stiffness and systemic vascular resistance45,53 | Lessens cardiovascular risk and mortality in patients < 65 years |
| Stroke | Conflicting data: no association in patients ≥ 65 years, but some association in those < 65 | Lessens cardiovascular risk and mortality in patients < 65 years |
| Psychiatric and cognitive dysfunction | Associated with worsened preexisting depression and bipolar disease; may affect cognition65 | May improve mood, anxiety, cognition in older patients35 |
| Neuromuscular dysfunction, exercise intolerance | Associated with skeletal muscle dysfunction, exercise intolerance71 | Limited data on treatment; role is unclear75 |
| Bone health | Associated with increased risk of hip fracture attributed to suppression of bone turnover by elevated TSH18,76,77 | Too few clinical studies to define a role |
| Thyroid cancer | Some data suggest elevated TSH is associated with higher risk79–82 | More studies needed to understand association |
| Infertility, recurrent miscarriage | Inconclusive evidence links subclinical hypothyroidism with infertility86; infertility rate is higher in women who also have positive thyroid peroxidase antibody than in women without autoimmunity87 | Some studies have shown lower rates of miscarriage with levothyroxine when TSH > 4.0 mlU/L86,91–92; insufficient data to support its use in patients with subclinical hypothyroidism and infertility; however, consider in euthyroid patients with positive peroxidase antibody and recurrent miscarriage90 |
| Pregnancy complications | Associated with several pregnancy-related complications including preeclampsia, hypertension, placental abruption, and postpartum hemorrhage in some studies,26,96 but not in others; if present, screen for autoimmunity | No recommendations; insufficient evidence to evaluate role of treatment |
| Preterm delivery, pregnancy loss | Associated with high risk of miscarriage, preterm delivery, pregnancy loss at even mildly elevated TSH levels (2.5-5 mIU/L)99;104–107; risk is as high as 60% with TSH levels > 6 mIU/L and higher with positive thyroid peroxidase antibody108–110 | Improves maternal and fetal outcomes, including risk of low birth weight and low Apgar score, in women with subclinical hypothyroidism and TSH 2.5-10 mIU/L93,106; evidence less clear with TSH 2.5-4 mIU/L86; not recommended for the subgroup of pregnant patients with negative thyroid peroxidase antibody and TSH within pregnancy-specific range or < 4 mIU/L |