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Thyroid function tests and hypothyroidism

BMJ 2003; 326 doi: (Published 08 February 2003) Cite this as: BMJ 2003;326:295

The pooped-out syndrome, ATP stores and hypothyroidism

William Silen, formerly Johnson and Johnson Professor of Surgery at
Harvard and Chief of the Surgical Services at the Beth Israel in Boston,
used to speak of the pooped-out syndrome that developed in patients after
major surgery. Depression is a common feature in these patients. He
ascribed the syndrome to hypothyroidism.

It is now appreciated that many patients develop haemodynamically
compensated shock, or an inadequacy of mitochondrial oxidative
phosphorylation, during or immediately after major surgery. Organ
dysfunctions and failures tend to occur almost exclusively in these
patients. If persistent this might lead to a depletion in adenine
nucleotide stores and hence in the capacity to replenish ATP stores after
the demand for energy release by ATP hydrolysis. ATP depletion is a
serious biochemical abnormality for I may take as long as 300 days to
replenish (1). It may take much longer and might not even be possible if a
significant degree of impairment of mitochondrial oxidative
phosphorylation persists.

Any impairment of ATP resynthesis is likely to compromise the
replenishment of endocrine pools and the electrohemical gradients needed
to release them in a timely and appropriate manner (2). Thyroid hormones
open the permeability transition pores on mitochondrial membranes and
thereby decrease the magnitude of the protonmotive force driving ATP
resynthesis. Oxidative phosphorylation is thus uncoupled and the
generation of heat increased. An increase in metabolic rate is required to
accommodate these changes. This effect appears to be beneficial for in
hypothyroidism it is deficient. If increased to to excessive degrees,
however, opening the permeability transition pores may induce apoptosis
and even cellular necrosis (3,4).

ATP turnover would seem to be a far more sensitive measure of the
adequacy of ATP resynthesis than measures of ATP, ADP, adenine nucleotide
energy charge, or phosphorylation potential (1). I suspect the same
applies to the assessment of thyroid function, hormonal turnover rates
being likely to be far more sensitive than the conventional measurements.
But what of the ATP pools upon which thyroid hormonal function would
appear to depend? Should ATP turnover rates be included in the assessment
of thyroid function (5)?

1. Ingwall JS. ATP synthesis in the normal and failing heart. In:
Heart failure, Poole-Wilson PA, Colucci WS, Massie BM, Eds, Churchill
Livingston, New York, 1997

2.Treating dementia with light and near infrared waves
Richard G Fiddian-Green, 12 Feb

3. Madness, hyperhomocysteinemia, metabolic rate and body temperature
Richard G Fiddian-Green, 6 Jan 2003

4. Coronary revascularisation: treatment or prevention? Richard G Fiddian-
Green, 22 Jan 2003

5. Thyroid function tests and hypothyroidism Anthony D Toft and Geoffrey J
BMJ 2003; 326: 295-296

Competing interests:  
None declared

Competing interests: No competing interests

05 March 2003
Richard G Fiddian-Green