Subclinical Hypothyroidism: Not Every Patient Requires Treatment
Treatment of subclinical hypothyroidism is generally recommended with an initial level of thyroid stimulating hormone >10 mIU/L. Pregnant women and those attempting to get pregnant should definitely be treated, and treatment should be considered strongly in nonelderly patients who have positive thyroid peroxidase antibodies, said Douglas Paauw, MD.
Subclinical hypothyroidism is defined as an elevated level of thyroid stimulating hormone (TSH) with a normal free T4. One third to one half of patients with subclinical hypothyroidism will progress to overt hypothyroidism, with the risk of progression greater if the initial TSH level is >10 mIU/L.1 An initial TSH between 5.5 and 10 mIU/L normalizes without treatment in 62%.2 The presence of thyroid antibodies increases the risk of progression.
The recommendation to treat an initial TSH >10 mIU/L is controversial because of concerns over progression and potentially an increased cardiac risk with treatment, said Dr. Paauw, professor of medicine, Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle.
The appropriate TSH range for pregnancy is 0.4 to 2.5 mIU/L, and is up to 3.0 mIU/L during the second and third trimesters. “The developing fetus will be getting all of its thyroid hormone from mom up to about 12 weeks, so we do not want them to be deficient in any way,” he said. Complications of maternal hypothyroidism include preeclampsia and gestational hypertension, placental abruption, preterm delivery, low birth weight, and neuropsychologic and cognitive impairment in the child.
Increasing the TSH dose by two doses per week in early pregnancy prevents TSH elevation >5.0 mIU/L throughout the first trimester.
If patients with subclinical hypothyroidism, other than those defined above, insist on being treated, know that the risk of therapy is minimal in patients who are followed closely. Caution should be exercised in the elderly, in whom the risks of treatment are higher.
Levothyroxine replacement does not lead to improved survival or improved quality of life, nor does it lead to an improvement in symptoms in adults with subclinical hypothyroidism.3
The starting dosage of levothyroxine in the treatment of primary hypothyroidism in a young patient is the full replacement.4 “If you start with full replacement dose, you get to your target much quicker than if you start slow and ramp up,” he said. The average dosage needed is 1.6 µg/kg daily. With a body mass index (BMI) <25 g/m2, the required dosage is 1.76 µg/kg.5 With a BMI of 35 to 39 g/m2, the needed daily dosage drops to 1.27 µg/kg. For patients with known coronary artery disease or those >70 years, start at 12.5 to 25.0 µg/day. The target TSH in the elderly is 4 to 6 mIU/L.
No evidence supports the use of combination T4/T3 therapy over T4. Some patients may want to be treated with dessicated thyroid, which has a T4 to T3 ratio of 4:1, because they perceive it to be “natural,” whereas others want it because they get an energy burst from it, he said. “I prefer that they go on levothyroxine [the standard for treating hypothyroidism], but if my patient absolutely insists, I will relent and give them a trial of it. If they’ve been on it before, we’ll continue them on it,” he said.
How should a patient on previously adequate thyroid replacement who has a rising TSH be managed? Know that decreased absorption of levothyroxine can occur in patients on a proton pump inhibitor (PPI) as well as those with atrophic gastritis. In one study, the daily requirements for thyroxine was 22 to 34% higher for patients with Helicobacter pylori infection or atrophic gastritis.6 Omeprazole-treated patients needed their thyroxine dose increased by 37%. Besides increasing the dosage of levothyroxine, another option for patients on PPIs is gel cap or liquid formulations of levothyroxine.
Other considerations for patients with a rising TSH while on thyroxine are noncompliance; dosing on an empty stomach (it must taken with food); coadministration of iron or calcium, treatment with estrogen, raloxifene, or sucralfate/cholestyramine; the presence of a disease that causes achlorhydria; and the presence of celiac disease. In patients with adherence difficulties, levothyroxine can be given as a single weekly dose, he said.
Also note that high-dose biotin can make thyroid tests look like the patient is hyperthyroid, as high-dose biotin can interfere with the biotin-streptavidin chemistry of the thyroid immunoassay, he explained. The biotin washout period is 10 hours to 2 days.
Drugs that can induce hypothyroidism include amiodarone, lithium, and tyrosine kinase inhibitors.
Disclosure
Nothing to disclose.
References
- Huber G, Staub J-J, Meier C, et al. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002;87:3221-6.
- Meyerovitch J, Totman-Pikielny P, Sherf M, Battat E, Levy Y, Surks M. Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch Intern Med 2007;167:1533-8.
- Feller M, Snel M, Moutzouri E, et al. Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: a systematic review and meta-analysis. JAMA 2018;320:1349-59.
- Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP, Berghout A. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med 2005;165:1714-20.
- Papoian V, Yli D, Felger EA, Wartofsky L, Rosen JE. Evaluation of thyroid hormone replacement dosing in overweight and obese patients after a thyroidectomy. Thyroid 2019;1558-62.
- Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med 2006;354:1787-95.