Tratamento do hipotireoidismo subclínico

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O tratamento de reposição do hipotireoidismo subclínico (hipoSC) com L-T4 pode ser benéfico para impedir a progressão da doença subclínica ao hipotireoidismo instalado em pacientes com concentrações séricas do TSH superior a 10 mIU/L e com anticorpos antitireoidianos positivos, especialmente em mulheres e naqueles com idade superior a 55 anos(B).

Há controvérsias no tratamento do hipotireoidismo subclínico em pacientes com níveis séricos do TSH entre 4,5 e 10 mIU/L.
Um painel de especialistas capitaneado por três sociedades científicas norte-americanas recomendou o seguimento sem tratamento farmacológico desses pacientes com reavaliações semestrais ou anuais (D). No entanto, o tratamento poderia ser considerado em pacientes com anticorpos tireoidianos positivos, uma vez que está associada com maior risco de progressão a doença clínica(A) e em pacientes com dislipidemia, pois a terapia com L-T4 em pacientes com hipotireoidismo subclínico associou-se com redução dos níveis séricos do colesterol total, do colesterol LDL e com melhora da função endotelial(A).

A presença de risco cardiovascular elevado deve ser ponderada no momento do julgamento clínico. O hipotireoidismo subclínico tem sido associado com maior risco de doença coronariana e mortalidade(A), mas este risco parece estar restrito a pacientes relativamente jovens, com menos de 65 anos(A). Em pacientes idosos, concentrações séricas do TSH < 10 mIU/L associaram-se com menor risco e eventos cardiovasculares e de mortalidade(A). Assim, pacientes com risco cardiovascular elevado e com menos de 65 anos poderiam se beneficiar do tratamento do hipotireoidismo subclínico, mas não há estudos aleatorizados e controlados sobre os efeitos da terapia de reposição com L-T4 na mortalidade ou morbidade cardiovascular em pacientes com
hipotireoidismo subclínico. Pacientes com mais de 65 anos e com TSH entre 4,5 e 10 mIU/L devem manter-se sem tratamento farmacológico, com reavaliações semestrais ou anuais(D).

O hipotireoidismo subclínico é duas a três vezes mais frequente nos portadores de hipercolesterolemia, além do nível de colesterol total ser ligeiramente elevado nestes pacientes.
A terapia de substituição do hormônio da tireoide nos pacientes com o hipotireoidismo subclínico, restaurando os níveis de TSH ao normal, diminuiu o colesterol total por 0,4 mmol/l (intervalo de confiança de 95% (IC) 0,2-0,6 mmol/l), independente do nível inicial do colesterol, sem mudança significativa no nível do HDL. Esta diminuição é pequena, o que faz com que o nível plasmático de colesterol permaneça elevado na maioria de pacientes, que
necessitarão de tratamento adicional e específico para a dislipidemia(A).

Compararam-se os efeitos da terapia de reposição com hormônios tireoidianos (LT4 e/ou T3) ao placebo ou a nenhum tratamento. Dados extraídos sobre a qualidade de vida e sintomas relacionados ao hipotireoidismo subclínico não demonstraram diferença significativa entre placebo e droga ativa(A).
Recomendação Recomenda-se tratamento para pacientes com hipotireoidismo subclínico persistente e com níveis séricos de TSH ≥ 10 mIU/L(B).

Em pacientes com níveis séricos do TSH < 10 mIU/L, o tratamento deve ser considerado na presença de anticorpos positivos(A), de dislipidemia(A), de risco cardiovascular elevado(A) ou quando há sintomas associados ao hipotireoidismo(A). Nestas condições, o hipotireoidismo subclínico deve ser tratado, pois é associado com maior risco de doença arterial coronariana e mortalidade, principalmente em pessoas com menos de 65 anos(A).
Recomenda-se para pacientes com níveis séricos do TSH < 10 mIU/L, mas sem comorbidades e em idosos maiores de 65 anos, seguimento sem tratamento farmacológico com reavaliações semestrais ou anuais(D).


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Candidates for T4 replacement — Although virtually all experts recommend treatment of patients with serum TSH concentrations >10 mU/L, the routine treatment of asymptomatic patients with TSH values between 4.5 and 10 mU/L remains controversial.

In view of data linking subclinical hypothyroidism with atherosclerosis and myocardial infarction, and the increased risk of progression to overt hypothyroidism, we suggest treatment of patients with subclinical hypothyroidism and TSH levels greater than 10 mU/L. This recommendation is consistent with that of a clinical consensus group (comprised of representatives from the Endocrine Society, American Thyroid Association, and the American Association of Clinical Endocrinologists).

There are few data to show benefit or harm of T4 treatment in patients with TSH values between 4.5 and 10 mU/L. The consensus group did not recommend routine treatment for such patients, but recommended monitoring TSH levels every 6 to 12 months . However, others have recommended treatment for patients with TSH values in this range because unrecognized symptoms may improve, correction of abnormal serum lipid concentrations may be cardioprotective, and there is little risk associated with monitored T4 replacement.

We suggest T4 therapy in non-elderly patients with serum TSH values of 4.5 to 10 mU/L who have symptoms suggestive of hypothyroidism. Patients with high titers of antithyroid peroxidase antibodies, who may rapidly progress to overt hypothyroidism, and patients with goiter may also benefit from early treatment. Some experts suggest that the presence of risk factors for cardiovascular disease is a reason for initiating treatment. Other experts caution that overtreatment with T4 is common, occurring in as many as 41 percent of individuals ≥65 years of age, and that overtreatment may result in adverse consequences, such as cardiac arrhythmias, especially in the elderly. Thus, we do not treat elderly patients (over age 70 years) with subclinical hypothyroidism and TSH between 4.5 and 8 mU/L.

We suggest initiating T4 replacement in pregnant women with subclinical hypothyroidism (TSH values above trimester-specific normal reference range with normal free T4) and in women with subclinical hypothyroidism who wish to become pregnant or have ovulatory dysfunction and infertility. Because of the changes in thyroid physiology during pregnancy, trimester-specific reference ranges for TSH should be used. During the first trimester of pregnancy, subclinical hypothyroidism is defined as a serum TSH above 2.5 (above 3 mU/L in the second or third trimester) with a normal free T4 concentration.
The treatment of pregnant women with normal serum TSH levels and positive antithyroid peroxidase antibodies is reviewed separately.

Anecdotal reports suggest that T4 therapy may be beneficial in patients with symptoms of hypothyroidism but normal thyroid function tests. However, in a randomized, crossover trial of 22 such patients, T4 was no more effective than placebo in increasing cognitive function and psychological well-being.

Thus, T4 should not be prescribed for patients with hypothyroid symptoms but normal thyroid function.

Arguments for treatment — Treatment will prevent progression to overt hypothyroidism, especially in those with serum TSH concentrations greater than 10 to 15 mU/L and high serum antithyroid peroxidase antibody concentrations. Treatment in patients with lesser elevations in serum TSH concentrations may possibly ameliorate nonspecific symptoms of hypothyroidism, such as fatigue, constipation or depression, and may decrease the size of goiter, if present. Treatment may also improve cardiac contractility and serum lipid concentrations in some patients and secondarily reduce the risk of atherosclerosis.

Arguments against treatment — Arguments against T4 treatment include its cost (for both the hormone and for monitoring its efficacy), the lifelong commitment to daily medication in asymptomatic patients, the potential risk of overtreatment and inducing symptoms from excess thyroid hormone, and the possible induction or exacerbation of angina pectoris or cardiac arrhythmia in susceptible patients, especially in view of data from a community survey showing that 41 percent of patients over age 65 taking thyroid hormone replacement had a subnormal serum TSH. Although these concerns are not usually sufficient to counterbalance the potential benefits of therapy in younger patients, we do recommend a higher TSH threshold for treating elderly patients, especially since the upper limit of normal for serum TSH may be higher in this age group. If the patient is not treated, regular follow-up is indicated.

Goals of treatment — The goal of therapy is to reduce the patient's serum TSH concentration into the normal reference range. Since the mean serum TSH for the general population is around 1.4 mU/L, with 90 percent having serum TSH levels <3.0 mU/L, many experts recommend a therapeutic TSH target of 0.5 to 2.5 mU/L in young and middle-aged patients. A TSH target of 3 to 5 mU/L may be appropriate in patients over age 70 years.

There are two approaches to initiating T4 therapy. One option is to start with the lowest dose necessary to normalize the serum TSH concentration, typically 25 to 50 mcg daily. This approach will avoid overtreatment and is most appropriate in the elderly or in patients with underlying cardiovascular disease.

For younger patients with Hashimoto's thyroiditis who do not have autonomy (eg, a prior history of toxic adenoma or Graves' disease treated with radioiodine) and who have normal negative feedback, an alternative approach is to initiate treatment at slightly below full replacement doses (1.6 mcg/kg/day). This approach obviates the need for periodic dose increases, should there be progressive autoimmune destruction of their gland. Alternatively, younger patients could be started on low dose therapy, as is recommended for older patients. Dose adjustments and long-term monitoring are the same as for the treatment of overt hypothyroidism.


Referencias: uptodate.com
http://www.projetodiretrizes.org.br/ans/diretrizes/hipotireoidismo-tratamento.pdf