Increase in the tetrahydrocortisol/tetrahydrocortisone ratio from cortisol-4-¹⁴C: A nonspecific consequence of illness

The THF/THE ratio of the radioactive metabolites derived from iv cortisol-4-¹⁴C was compared in 20 normal subjects and 20 patients with miscellaneous diseases. None of the patients had elevated cortisol production, which is known to raise the THF/THE ratio. In normal subjects, the mean ratio was 0.65, with 95% confidence limits of 0.41 and 0.89. The patients showed a very wide range of values, from 0.34 to 2.08; the mean value was 1.03, 58% higher than normal (p < 0.001), and about (formula presented) of the patients had values higher than the upper 95% confidence limit of normal. The total excretion of THF + THE was the same in patients as in normals, so that the elevated THF/THE ratio in patients was due to increased THF precisely matched by decreased THE. This abnormality represents a second type of "nonspecific illness effect" on steroid metabolism. The previously described abnormality in androgen metabolism (decreased recovery of androsterone + etiocholanolone from tracers of androgens) was believed to be due to medication-induced microsomal hydroxylases; the present finding resembles the abnormality of cortisol metabolism we described in hypothyroidism, suggesting that patients with nonspecific illness may have physiological stigmata of hypothyroidism. This hypothesis is supported by our observations ot similar hypothyroidism- like abnormalities of androgen and estrogen metabolism in non-specific illness and by a recent report that plasma and tissue concentrations of triiodothyronine are greatly reduced in nonspecific illness. Thus the complex abnormalities of steroid metabolism seen in nonspecific illness may embrace metabolic factors such as hypothyroidism as well as enzyme-inducing effects of medications.