Leading Biochemist Dr Carole Spencer from University of Southern California aacc.org/resourcecenters/ar...
Question: What in your opinion, should be taken into account in a study designed to assess the TSH reference range in a population 60-80 years old? Does the NACB guideline approach for TSH reference intervals apply? Do we need 120 euthyroid volunteers for each decade if we also want to know the TSH reference intervals for each decade of life?
Carole A. Spencer, PhD : The NHANES population found a TSH upper limit of 7.5 mIU/L for 80+ year olds (Surks JCEM 92:4575, 2007 Atzmon JCEM 94:1251, 2009). I do not believe we need a TSH population reference range for every decade but we need to educate physicians to expect higher TSH in older patients. The question to treat or not to treat ultimately depends on symptoms, TPOAb, medications and other patient-specific factors. I think we need abandon the concept of a fixed reference range for TSH or tailoring a reference range for every condition. Furthermore, different assays detect different TSH isoforms. In any situation not all of the TSH that we are measuring is biologically active, and an increase in bioinactive TSH may be involved with aging.
Question: Should there be age- and gender-specific reference ranges for TSH? What is the best marker for monitoring hypothuroidims treatment and what is the target value?
Carole A. Spencer, PhD : The target for L-T4 replacement for hypothyroidism is a TSH between 0.5 and 2.0 mIU/L. With regard to the TSH reference range, all thyroid tests have a low index of individuality (IoI is the relationship between the within-person and between-person variability). When a test has a low IoI the population reference range of that test is a weak parameter for detecting disease in the individual. In view of this I see no advantage in fine-tuning TSH reference ranges. I am not aware of gender-specific TSH differences, although population studies show a trend for higher TSH with aging. However the mechanism for this is unclear. Physicians need to interpret TSH relative to patient-specific factors rather than a fixed population range.
Question: WHO indicated that 5 mIU/L was an appropriate cutoff for clinical hypothyroidism in adults. Should that be revised?
Carole A. Spencer, PhD : Organizations such as WHO tend to report conservative cut-offs. Note a cut off of 5.0 mIU/L would be inappropriate for 1st trimester pregnancy! The Endocrine Society recommends 3.0 mIu/L for 2nd and 3rd trimester pregnancy and 2.5 mIU/L for the 1st trimester this has been well accepted by our physicians (Abalovich et al JCEM 92: S1-S47, 2007). The diagnosis of hypothyroidism and treatment decisions should be based on patient-specific risk factors (slide 21, Biondi & Cooper Endoc Rev 29:76, 2008) not the upper population reference limit for TSH.