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EDITOR – I noted the letters (1, 2) in response to the Toft and
Beckett (3) with interest. Both letters (1, 2) raised concerns about over
treatment with thyroxine and the editorial recommendation to restore the
serum thyroid stimulating hormone to the low normal range (3). Would it
surprise the authors of the letters that the vast majority of normal
euthyroid subjects have a serum thyroid stimulating hormone between 0.3
and 2.0 mU/L when using an assay with a reference range of 0.5 – 3.5 mU/L?
This is because serum thyroid stimulating hormone does not have a Gaussian
distribution but has a skewed distribution with a median value of 1.35
mU/L and needs logarithmic transformation to give it a Gaussian
distribution. Accordingly, what Toft and Beckett (3) have advocated is in
keeping with normal physiological principles.
1 Crilly M. Reducing concentrations further would be harmful. BMJ
2003:326:1086. (17 May.)
2 Vanderpump MP, Franklyn JA. Restoring serum TSH to reference range
should be goal of replacement. BMJ 2003:326:1086-7. (17 May.)
3 Toft AD, Beckett GH. Thyroid function tests and hypothroidism. BMJ
2003;326:295-6. (8 February.)
Competing interests:
I work in the same department as GH Beckett and have worked with AD Toft.
Competing interests:
No competing interests
19 May 2003
Patrick J Twomey
Specialist Registrar
Department of Clinical Biochemistry, Royal Infirmary, Edinburgh EH16 4SA
It can be easily shown from convential control system theory that TSH
should not be the measure used to establish a "norm" in a hypothyroid
patient. It is well established that TSH level is set as a function of a
closed loop feedback system. When control system theory is applied to
model this activity, a variety of scenarios present themselves.
For example, an erroneous assumption usually made by the medical community
is that hypothyroidism is either primary OR secondary, when in fact it
could easily be a combination of both. In such instance, one can imagine
that the TSH level may well be limited by an underresponsive pituitary or
hypothalumus. The result would be that TSH could be driven to zero while
T3 and or T4 levels are still less than optimum for that patient. Thus
TSH can easily become a faulty measure of the desired result - patient
wellbeing.
Should we not look to physiology?
EDITOR – I noted the letters (1, 2) in response to the Toft and
Beckett (3) with interest. Both letters (1, 2) raised concerns about over
treatment with thyroxine and the editorial recommendation to restore the
serum thyroid stimulating hormone to the low normal range (3). Would it
surprise the authors of the letters that the vast majority of normal
euthyroid subjects have a serum thyroid stimulating hormone between 0.3
and 2.0 mU/L when using an assay with a reference range of 0.5 – 3.5 mU/L?
This is because serum thyroid stimulating hormone does not have a Gaussian
distribution but has a skewed distribution with a median value of 1.35
mU/L and needs logarithmic transformation to give it a Gaussian
distribution. Accordingly, what Toft and Beckett (3) have advocated is in
keeping with normal physiological principles.
1 Crilly M. Reducing concentrations further would be harmful. BMJ
2003:326:1086. (17 May.)
2 Vanderpump MP, Franklyn JA. Restoring serum TSH to reference range
should be goal of replacement. BMJ 2003:326:1086-7. (17 May.)
3 Toft AD, Beckett GH. Thyroid function tests and hypothroidism. BMJ
2003;326:295-6. (8 February.)
Competing interests:
I work in the same department as GH Beckett and have worked with AD Toft.
Competing interests: No competing interests