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Letter to the Editor

Editor, – Some further points on testing thyroid function need to be added to the useful information in Associate Professor Tran's review, 'Biochemical tests in pregnancy' (Aust Prescr 2005;28:98-101). First, a small but significant decrease in the concentration of serum free T4, most marked in the third trimester, has been clearly documented.1,2 In addition, albumin-dependent methods of free T4 estimation show marked negative bias, relative to the non-pregnant reference interval; in the late third trimester, such methods may give subnormal free T4 estimates in up to 50% of samples.3

These methods are unsuitable for assessing thyroid status during pregnancy4, unless results are evaluated in relation to reference intervals that reflect method-specific bias at various stages of pregnancy. Clinical chemists need to be aware of this issue when choosing an appropriate free T4 method for obstetric practice and by indicating appropriate reference intervals.

Professor Tran's counsel that 'Graves' disease needs to be rigorously controlled' in pregnancy goes beyond interpretation of test results. This advice must be tempered by the fact that any degree of maternal hypothyroidism in the first trimester can have an adverse effect on fetal brain development5,6, and that over treatment in the third trimester can be associated with fetal goitre.6 As thyrotoxicosis of immune origin often becomes less severe during pregnancy, it is often advisable to decrease the dose of antithyroid drug to minimise the chance of these adverse effects.6 As pointed out by Professor Tran, the exact cause of newly-diagnosed thyrotoxicosis can be difficult to establish in early pregnancy. When the disorder is mild, as judged by clinical rather than laboratory criteria, it may be best followed without treatment for several months until there is a clear indication for active treatment.6

Jim R. Stockigt
Epworth and Alfred Hospitals
Professor of Medicine, Monash University

Author's comments

Associate Professor H.A. Tran, author of the article, comments:

Professor Stockigt's comments are appreciated. As usual, they are incisive and informative. The small but significant decrease in serum free tetra-iodothyronine (fT4) can, in part, be explained by the peak of thyroid binding globulin concentrations in the third trimester, although these remain within the reference range in most cases.7

Selecting a special method for the obstetric population serviced by the relevant laboratory would always be a challenging task given the large scope of services imposed upon large laboratories by the current practice of pathology. The nuances of such a task are probably best reserved within the realm of clinical biochemists' practice.

As emphasised, the management of thyrotoxicosis in pregnancy is not a simple task. It should not be simply a matter of medication adjustment according to biochemical results, which are never error proof. The literature is littered with, sometimes fatal, adverse reactions8where laboratory results as given, are acted upon, when instead a considered and competent clinical assessment is warranted. As inferred by Professor Stockigt, it is best to first do no harm; a caveat that is not applicable to pregnancy alone.


  1. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-33.
  2. McElduff A. Measurement of free thyroxine (T4) levels in pregnancy. Aust N Z J Obstet Gynaecol 1999;39:158-61.
  3. Roti E, Gardini E, Minelli R, Bianconi L, Flisi M. Thyroid function evaluation by different commercially available free thyroid hormone measurement kits in term pregnant women and their newborns. J Endocrinol Invest 1991;14:1-9.
  4. National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Free thyroxine (FT4) and free triiodothyronine (FT3) estimate tests, in pregnancy. Section 3B 3c(i).[cited 2006 Jan 13]
  5. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999;341:549-55.
  6. Mandel SJ, Cooper DS. The use of antithyroid drugs in pregnancy and lactation. J Clin Endocrinol Metab 2001;86:2354-9.
  7. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-33.
  8. Gutierrez-Macias A, Lizzaralde-Palacios E, Martinez-Odriozola P, Miguel-De la Villa F. Fatal allopurinol hypersensitivity syndrome after treatment of asymptomatic hyperuricaemia. Br Med J 2005;331:623-4.