Latent Hypothyroidism: Drug Therapy

Therapeutic targets

Euthyroid metabolic state with freedom from symptoms (depending on the patient’s age).

Important note!The transition from latent to manifest hypothyroidism depends mainly on the presence of autoantibodies against thyroid peroxidase (TPO-Ak) and the level of the antibody titer: the higher the antibody titer, the greater the probability of transition to manifest hypothyroidism (2.6%/year with a negative test vs. 4.3%/year with a positive test).Recent studies point to inadequate selenium supply as a risk factor for the manifestation of Hashimoto’s thyroiditis. It has also been shown that improving selenium intake can favorably influence the course of the disease. A daily intake of 200 µg selenium leads to a reduction of TPO antibodies (= marker of disease activity) by approximately 36% after 3 months.

Therapy recommendations

In patients with latent hypothyroidism and nonelevated or only mildly elevated TPO-Ak (thyroperoxidase antibodies), a wait-and-see approach and monitoring at quarterly intervals is warranted. Drug therapy for subclinical hypothyroidism (with L-thyroxine between 50 and 100 µg per day) is indicated in the following cases:

  • When the serum TSH level is <10 mU/l (European Thyroid Association (ETA),) and.
    • Patients < 70 years of age; patient shows symptoms of hypothyroidism – trial of L-thyroxine for three months.
    • Patients > 80 years – here a wait-and-see strategy should be considered
  • If the serum TSH level is > 10 mU/l and.
    • Patients < 70 years of age with or without symptoms – therapy recommended.
    • Patients > 70 years of age with significant hypothyroid symptoms or high risk of CHD – limited therapy is recommended in these cases
  • With a serum TSH level of > 5 mU/l and high titers of TPO-Ak – treatment with the aim of preventing manifest hypothyroidism.
  • Diffuse goiter
  • Infertility (prim. or sec. infertility) (ASRM);
    • TSH > 4 µIU/ml: therapy with L-thyroxine (levothyroxine) (goal: to maintain TSH < 2.5 µIU/ml) [Grade B].
    • TSH 2.5- 4 µIU/ml: wait; treat only once TSH > 4 µIU/ml (goal: to maintain TSH < 2.5 µIU/ml) [Grade B].
    • 1st trimester (pregnancy trimester) TSH > 2.5 µIU/ml treat [Grade B].

    No recommendation is made for routine screening for thyroid antibodies. It may be considered if TSH levels are repeatedly > 2.5 µIU/ml or other risk factors for thyroid disease are present. [Grade C]If thyroperoxidase antibodies are present, check TSH levels: TSH > 2.5 µIU/ml → consider therapy [Grade C].

  • Gravidity
  • After thyroidectomy
  • After radioiodine therapy
  • After radiotherapy (radiotherapy, radiatio) of the neck region.
  • Thyroid volume < 5 ml
  • Diabetes mellitus as a concomitant disease

Drug therapy for latent hypothyroidism may be indicated in the following cases:

  • Neonatal
  • Children
  • Teenagers
  • Cycle disorders (oligomenorrhea/regular tempo disorder: interval between bleeding is > 35 days and ≤ 90 days to amenorrhea/> 90 days) due to hyperprolactinemia (elevated prolactin serum levels): these lead in women to follicle maturation disorders (egg maturation disorders) to anovulation (failure to ovulate) with prolonged cycles (oligo-amenorrhea). This is usually accompanied by disturbance of the second cycle phase (corpus luteum insufficiency / yellow body weakness) – as a result, it comes to fertility disorders (disorders of fertility).
  • Male libido disorders due to hyperprolactinemia.
  • Hypercholesterolemia (excessive levels of cholesterol in the blood).
  • Depression

Other notes

  • In a larger randomized controlled trial (TRUST trial), L-thyroxine substitution did not improve symptoms in seniors (> 65 years) with subclinical hypothyroidism. Furthermore, no effect on blood pressure or body weight was detectable.In a new study, the group of patients with severe symptoms (about one fifth of the study participants in the TRUST study) was investigated: Neither the discomfort score was significantly improved, nor did hormone replacement have any benefit in terms of quality of life.
  • According to a study, women with thyroperoxidase antibodies in their blood are not more likely to be helped to successfully deliver a baby with treatment with L-thyroxine.

Instructions for taking L-thyroxine:

  • Tablets take in the morning on an empty stomach (at least 30 min before breakfast); if taken in the evening, it is recommended to take at least 2 hours after the last meal (taking in the evening is the better option for absorption).
  • Low starting dose (25-50 μg/d) and slow increase (25-50 μg/d); in elderly patients and cardiac-pregnant patients (“start low, go slow”), i.e., with 25% of the planned dose
  • Dose increase (at 2- to 4-week intervals); in elderly patients and cardiac-pregnant patients, gradual increase at 6- to 8-week intervals-until the optimal dose is reached clinically and by laboratory diagnosis

TSH control testing at the earliest 6 weeks after initial setting. If a TSH steady state is reached, the control intervals can be extended (every 6-12 months).The therapeutic goal is a reduction in TSH to 0.4-2.5 mU/l, in patients over 70 years to 1-5 mU/l.

Hypothyroidism/subclinical hypothyroidism and type 2 diabetes mellitus

According to a long-term study, type 2 diabetic patients treated with L-thyroxine for hypothyroidism more often had suppressed TSH levels. This association was not seen in patients with normal thyroid function.

Hypothyroidism/subclinical hypothyroidism and pregnancy

Therapy Recommendations

  • The TSH threshold for intervention, following the Endocrine Society International Guidelines, is 2.5 mIU/l in the first trimester and 3 mIU/l in the 2nd and 3rd trimesters
  • Clinical hypothyroidism is present with a TSH level > 10 mIU/l regardless of the concentration of free T4, and with elevated TSH levels associated with a T4 level < 9.7 pmol/l ( 7.5 μg/l).
  • Latent hypothyroidism during pregnancy (mean diagnosed after 16.7 weeks of gestation , i.e., elevated TSH (> 3mU/l) with normal T4, therapy with levothyroxine did not result in a significant IQ difference compared with the placebo group:This result may be due to the relatively late start of treatment. The main argument for early treatment is:Embryos are completely dependent on maternal thyroid hormones for the first few weeks (until the creation of their own thyroid gland).