Case studies: perplexing thyroid function test results

• Main Author: Shahar, Mohammad Arif
• Format: Article
• Language: English
• Published: Malaysian Endocrine & Metabolic Society (MEMS) 2016
• Subjects: RC Internal medicine
• Online Access: http://irep.iium.edu.my/52035/1/case%20studies%20perplexing%20thyroid%20function%20test%20results.pdf; http://irep.iium.edu.my/52035/; http://www.jmems.org
• Institution: Universiti Islam Antarabangsa Malaysia

Thyroid function test plays an important role in diagnosis and management of various thyroid disorders. Although the interpretation of thyroid function test is often straightforward, it is not uncommon to have situations where the process can be challenging. Take for an example of a real case where a 36 year old lady with history of Graves' disease presented in the 7th week of her 3rd pregnancy with a free T4 of 9.01 pmol/L and TSH 1.65 mIU/L. She had underwent a radio-ablative iodine therapy 2 years prior and had been euthyroid since without needing L-thyroxine replacement. Clinically, she was euthyroid. How would you interpret her thyroid function and what is the explanation behind it? How would this affect your management? The key to solving clinical dilemmas related to thyroid function requires thorough understanding of the assays being used, their principles and limitations, the hormones being evaluated and recognizing patterns of less common thyroid disorders and discrepancies between blood results and clinical features. The evolution of assays used to evaluate thyroid hormone (T4 and T3) and thyroid stimulating hormone (TSH) has made it more cost effective and less time consuming. However in certain conditions, newer assays have their own pitfalls. The fact that 99.97% of T4 and 99.7% of T3 are protein bound makes measuring total circulating hormones much easier compared to measuring the free moieties. In the 1950s, total thyroid hormones are measured using protein binding iodine methods. In the 1960s and 70s, competitive binding assays and radioimmunoassays (RIA) are developed. Methods using liquid chromatography tandem mass spectrometry (LC-MS) in recent decade are much more robust. Despite these advances, the total thyroid hormones at times do not reflect the clinical status of the patient since the biologically active T4 and T3 are in the free forms. In the 1950s, two step index methods such as the thyroid hormone binding ratio (“uptake” test) or the isotopic index methods were develop, which are cumbersome and time consuming. Later, immunoassays were introduced to ‘measure’ the free thyroid hormones. The assays which we now call free thyroid hormone assays (FT4 and FT3) are actually estimates of the unbound hormones. These assays to some extent are influence by the level of patients’ albumin and thyroid binding globulin. The gold standard remains direct measurements of the free thyroid hormones molecules via dialysis equilibrium and mass spectrometry. Unlike the T4 and T3 assays, the developments of TSH assays are less hurdled. The third generation TSH immunoassay which has the functional sensitivity of 0.01 mIU/L has become a necessity to meet the current standard of care. However, the debate on what constitute the normal TSH range for the population deserves a mention. The relationship between FT4, FT3 and TSH is strictly regulated. In hyperthyroxinemic conditions where the TSH is inappropriately elevated, a central thyroid resistant syndrome, familial dysalbuminemic thyrodxinemia or a TSHoma should be considered. In pregnancy and other conditions where there are elevated thyroid binding globulin or albumin, current free thyroid hormones immunoassays may underestimate their actual levels. In these conditions, it is reasonable to resort to older two-step index method estimation of the free hormone or direct measurements of the free hormone using mass spectrometry. A patient who recently complaint to L-thyroxine might have elevated TSH with normal levels of FT4 and FT3.