Natural History of Mild Subclinical Hypothyroidism: Prognostic Value of Ultrasound

Thyroid. 2009 Jan;19(1):9-12. doi: 10.1089/thy.2008.0221.


Background: Clinical repercussions, progression to overt hypothyroidism, and treatment benefits have been well established in patients with subclinical hypothyroidism (SCH) and TSH >10 mIU/L. In contrast, these aspects of the disease are poorly understood in patients with even milder SCH as defined by TSH < or = 10 mIU/L and normal thyroid hormone levels. Therefore, we sought to evaluate the natural history of this milder form of SCH (TSH < or =10 mIU/L with normal thyroid hormone levels) in adult women patients.

Patients: One hundred seventeen patients with TSH levels ranging from 5 to 10 mIU/L and normal free T4, without a previously known history of thyroid disease, were followed for a period of 3 years and had two consecutive assessments.

Results: Sixty patients tested positive for antithyroperoxidase antibodies (TPOAb) and 36 were TPOAb negative but had diffuse hypoechogenicity on thyroid ultrasound (US). Twenty-one patients were TPOAb negative and had normal US. During follow-up, 20.5% of the patients had spontaneous normalization of their TSH, 27.3% required replacement therapy with levothyroxine (L-T4) because of progression to overt hypothyroidism or persistence of serum TSH >10 mIU/L, and 52.1% continued to meet the criteria for mild SCH (persistence of TSH < or =10 mIU/L). If the patients were classified into two groups, one with positive TPOAb and/or US alteration and the other with testing negative for TPOAb and not having US alteration, the first group had a greater progression toward overt hypothyroidism (31.2% vs. 9.5%, respectively) and a lower rate of normalization of TSH (15.6% vs. 43% respectively). These rates were similar in TPOAb-positive patients and patients with negative TPOAb but with positive US.

Conclusions: Most patients with SCH and TSH < or = 10 mIU/L do not progress to overt hypothyroidism. The presence of chronic thyroiditis as demonstrated by US increases the evolution of SH to overt hypothyroidism or more severe SCH and thus the need for L-T4 treatment. US findings are important in determining the prognosis of mild SCH.

MeSH terms

  • Adult
  • Antibodies, Anti-Idiotypic / blood
  • Autoantigens / immunology
  • Disease Progression
  • Female
  • Humans
  • Hypothyroidism / blood*
  • Hypothyroidism / diagnostic imaging*
  • Hypothyroidism / drug therapy
  • Iodide Peroxidase / immunology
  • Iron-Binding Proteins / immunology
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Thyrotropin / blood*
  • Thyroxine / therapeutic use
  • Ultrasonography


  • Antibodies, Anti-Idiotypic
  • Autoantigens
  • Iron-Binding Proteins
  • Thyrotropin
  • TPO protein, human
  • Iodide Peroxidase
  • Thyroxine