Levothyroxine treatment of mild subclinical hypothyroidism: a review of potential risks and benefits

Abstract

Subclinical hypothyroidism (SCH) is defined as elevated thyroid stimulating hormone (TSH) with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4). SCH is further classified into a milder condition with TSH levels between 4.0 and 10.0 milli-international units (mIU)/l (mild-SCH) and a severe form with TSH >10.0 mIU/l (severe-SCH). SCH is a common problem (prevalence is greater in women than men), which increases further with increasing age and TSH levels. Even though the risk of progression to overt hypothyroidism is higher in patients with severe-SCH, the risk is also significant in patients having mild-SCH; it has been suggested that every twofold rise in serum TSH would increase the risk from 1 to 4%, which further increases to 38% if thyroid antibodies are positive. Current data have shown increased cardiovascular risk in patients with mild-SCH and have demonstrated some benefits of levothyroxine treatment in reducing these events. However, evidence on the association of mild-SCH and musculoskeletal system, cognitive dysfunction, mood disorders, dyslipidaemia, diabetes and goitre is conflicting. Similarly, the discussion regarding the exact upper limit of normal for serum TSH remains controversial. The data have also shown increased risk of adverse pregnancy outcomes in patient with mild-SCH, with some benefits of thyroxine treatment. The recent available guidelines related to management of patients with serum TSH <10 mIU/l have suggested decisions should be made taking into account the age of the patient, associated risk factors and comorbid conditions. This chronicle review assesses current evidence regarding the risks associated and the recommendations related to benefits of levothyroxine treatment in patients having mild-SCH.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

“…First, we chose to set a thyrotropin target of 0.40 to 4.60 mIU per liter with levothyroxine treatment, which is an approach that reflects recent guidelines, particularly for older persons. 7 However, some authorities have recommended a lower thyrotropin target (e.g., 0.40 to 2.50 mIU per liter). 29 We cannot exclude the possibility that this more aggressive treatment approach might be beneficial.…”

“…Antibody-positive patients are more likely than antibody-negative patients to have progressive hypothyroidism and therefore may be more likely to have a benefit from long-term levothyroxine treatment. 7 Finally, our trial was underpowered to detect any effect of levothyroxine on the incidence of cardiovascular events or mortality. Therefore, we cannot exclude the possibility that treatment with levothyroxine may provide cardiovascular protection or cause harm.…”

The Hypothyroid Brain

“…SCH is characterized by an increase in TSH levels that can range from 4.0 to 10.0 mIU/l in milder SCH and TSH >10.0 mIU/l in severe SCH [15,16] . Notwithstanding, SCH patients may present positive anti-thyroid peroxidase (TPO) antibodies, as well as a TSH level of between >2.0 mIU/l and <10.0 mIU/l [17] .…”

Dynamics of airway functions in untreated hypothyroidism

“…[6,7] In hypothyroidism, respiratory muscle weakness is present in both inspiratory and expiratory muscles both affects pulmonary functions accordingly. [7][8][9] Researchers reported that pulmonary functions may decrease in hypothyroid females and after thyroid hormone replacement these values may increase significantly, [10][11][12][13] but studies are limited to the expiratory respiratory functions only. Moreover, the effect of hormone deficiency on expiratory and inspiratory flow rates was not found place in literature.…”