A recent cross sectional study of apparently healthy young men and women has shown the accepted association between elevated thyroid-stimulating hormone (TSH) and adrenal dysfunction occurs at much lower TSH levels than previously thought - suggesting subclinical hypothyroidism is also more common than currently acknowledged.
The research published in the journal Thyroid Research found a positive association between TSH and elevated cortisol levels right down to 2.5 uIU/L. While TSH between 0.5 and 4.5 uIU/L is considered normal, a positive correlation with elevated cortisol is an accepted sign of hypothyroidism. The study results therefore raise the question of when subclinical hypothyroidism should be diagnosed.
Subclinical hypothyroidism is generally defined by serum TSH levels above 4.5 uIU/L when both thyroxine (T4) and triiodothyronine (T3) are within normal ranges. What the investigators on this study suggest based on their results is that even when TSH levels are within the accepted normal range below 4.5 uIU/L there may still be subclinical hypothyroidism present based on the persisting TSH-cortisol relationship.
The researchers conducting this study set out with the knowledge that there is a lot of controversy surrounding the diagnosis of subclinical hypothyroidism and the relationship between TSH levels, other biomarkers and a patient's health status. Their aim therefore was to provide some clarification by further investigation of the accepted TSH-cortisol relationship in overt hypothyroidsm.
Based on the hypothesis that excessive cortisol output seen in hypothyroidism would also be present in subclinical hypothyroidism the scientists set about testing the theory in 54 healthly young men (19) and women (35) with an average age of 21.
Blood samples were taken from all participants at the same time of day (1300 hrs) and serum levels of TSH, free T3, free T4, and cortisol levels were assessed.
Statistical analyses revealed that TSH levels in the 0.5-10 uIU/L range were significantly and positively correlated with cortisol levels. The positive TSH-cortisol relationship was maintained below the currently accepted 4.5 uIU/L subclinical hypothyroid cutoff.
After invidivual analyses conducted by systematically dropping the TSH cutoff by 0.50 uIU/L it was seen that the TSH-cortisol relationship was maintained for TSH levels down to 2.5 uIU/L, but not below.
The blood testing revealed free T4 levels for all participants were within the normal reference range, as was free T3 in all but one participant. Analysis did not reveal a relationship between free T3 or free T4 levels and cortisol levels.
The researchers conclude that: "In as much as this relationship (TSH-cortisol) may herald a pathologic disorder, these preliminary results suggest that TSH levels > 2.0 uIU/L may be abnormal. Future research should address this hypothesis further, for instance through an intervention study."
With large numbers of people suffering from persistent unexplained fatogue and other vague symptoms undiagnosed subclinical hypothyroidism may provide a treatable explanation in some cases. Further investigations as this study's authors suggest is therefore of great importance.
Source: Walter KN Corwin EJ Ulbrecht J Demers LM Bennett JM Whetzel CA Klein LC (2012) Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women Thyroid Research 5(1):13 [Epub ahead of print]