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Aggressive “case finding” is warranted for subclinical hypothyroidism

Aggressive “case finding” is warranted for subclinical hypothyroidism

Most thyroid society guidelines strongly recommend active ‘case finding’ and aggressive testing of thyroid-stimulating hormone (TSH) levels to identify high-risk individuals.1 The case histories below illustrate why and who are worth testing for hypothyroidism

Case history 1

  • A 28-year old patient, with a family history of thyroid disease, presented to the gynaecologist when she was 8 weeks pregnant. A TSH test was ordered, which showed a level of 4.5 mU/L. As this patient’s TSH was between 2.5–10 mU/L, thyroid peroxidase antibody (TPOAb) levels were assessed, and were found to be elevated, confirming chronic thyroiditis. Therefore, levothyroxine was started right away.


During pregnancy, the thyroid gland increases 10% in size in iodine-replete countries and by 20–40% in areas of iodine deficiency. Production of thyroxine (T4) and triiodothyronine (T3) increases by 50%, in addition to a 50% increase in the daily iodine requirement. These physiological changes may result in hypothyroidism in the later stages of pregnancy in women who were euthyroid in the first trimester. Given that hypothyroidism has serious detrimental effects on the mother and the foetus, this patient, based on her family history of thyroid disease, was luckily identified. Universal screening of all pregnant women is not yet routine practice.

The woman in this case represents a woman at high risk for thyroid dysfunction during pregnancy according to the latest 2017 ATA Guidelines on pregnancy.2

According to these new guidelines, all patients planning to become pregnant or newly pregnant, with risk factors for thyroid dysfunction, such as in the patient above who had a family history of thyroid dysfunction, should undergo clinical evaluation.

Although the patient´s TSH levels of 4.5 mU/L can be observed in the general population, it may be too high for the first trimester of pregnancy. In fact, a downward shift in TSH reference ranges is seen in essentially all populations, but the extent of this reduction varies significantly between different racial and ethnic groups.

According to 2017 ATA Guidelines,2 the pregnancy-specific TSH reference range should be defined, when available, according to population and trimester-specific reference ranges. If internal or transferable pregnancy-specific TSH reference ranges are not available, an upper reference limit of ~4.0 mU/L may be used. For most assays, this represents a reduction in the non-pregnant TSH upper reference limit of ~0.5 mU/L. In the patient in the case history, TSH values were 4.5 mU/L, confirming subclinical hypothyroidism.

Since levothyroxine therapy is recommended for TPO antibody positive women with a TSH greater than the pregnancy-specific reference range2, the gynaecologist correctly initiated treatment.

Case history 2

  • A 14-year old girl with Down’s syndrome had her TSH level tested as part of her routine health screen. Her level was 14 mU/L, reducing to 10 mU/L when the measurement was repeated 3 months later. Her free T4 level was normal, and she had positive TPOAb, confirming the diagnosis of subclinical hypothyroidism. The patient had oligomenorrea, which improved on treatment.


This is another example showing that selective testing of thyroid function is worthwhile. After the neonatal period, TSH testing should be performed routinely in children with known autoimmune diseases, such as type 1 diabetes mellitus and coeliac disease, and in children with genetic syndromes (e.g. Turner syndrome, Down’s syndrome), all of whom are prone to develop Hashimoto thyroiditis.3

Case history 3

  • A 58-year old man with post-acute myocardial infarction was tested for TSH by the Cardiology Department. Subclinical hypothyroidism was diagnosed and confirmed after two consecutive TSH values of 8 and 6 mU/L, with normal free T4 levels. Levothyroxine was initiated after angioplasty and coronary stent insertion.


As subclinical hypothyroidism has been associated with an increase in cardiac mortality and overall death, patients with acute cardiac problems are a target for aggressive case finding of subclinical hypothyroidism.4

There are patient categories, as well as those with certain clinical conditions, who should be considered for thyroid testing,3 including:

  • Women from fertile age onwards, especially those >60 years
  • Pregnant women
  • Those who have received previous radiation treatment of the thyroid gland (radioactive iodine or therapeutic external beam radiation)
  • Previous thyroid surgery or thyroid dysfunction
  • Type 1 diabetes mellitus
  • Personal history of autoimmune disease (vitiligo, Sjögren’s syndrome, systemic lupus erythematosus, rheumatoid arthritis)
  • Down’s syndrome
  • Turner syndrome
  • Family history of thyroid disease
  • Presence of goiter and/or TPOAb positivity
  • Clinical symptoms of hypothyroidism
  • Taking drugs such as lithium, amiodarone, interferon alpha
  • Hyperprolactinaemia
  • Dyslipidaemia
  • Depression, mania
  • Addison’s disease
  • Infertility
  • Anaemia
  • Heart failure


  1. Hennessey JV, et al. Aggressive case finding: A clinical strategy for the documentation of thyroid dysfunction. Ann Intern Med 2015;163:311-2. 
  2. Alexander EK, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27(3):315-38.
  3. Brenta G, et al. Task force on hypothyroidism of the Latin American Thyroid Society (LATS). Clinical practice guidelines for the management of hypothyroidism. Arq Bras Endocrinol Metabol 2013;57:265-91.
  4. Jabbar A, et al. Thyroxine in acute myocardial infarction (ThyrAMI) - levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial. Trials 2015;16:115. 

Gabriela Brenta

Department of Endocrinology and Metabolism
Milstein Hospital
Buenos Aires University
Buenos Aires, Argentina
subclinical hypothyroidism
thyroid testing