Researchers at the Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, and collaborators characterized serum FT4, T4, FT3, T3, TSH and FT3/FT4 ratios in 349 Chinese nonagenarians. They applied GAMLSS modeling and CLSI EP28 guidelines to derive age-specific reference intervals, revealing hormone shifts and links with BMI and WHtR to refine thyroid diagnostics in elderly care.
Key points
Established nonparametric RIs for serum FT4 (10.39–20.46 pmol/L), T4 (81–193 nmol/L), FT3 (3.56–6.43 pmol/L), T3 (0.94–2.05 nmol/L), TSH (0.29–5.28 μIU/mL) and FT3/FT4 ratio (0.197–0.496) in 90+ Chinese cohort.
Utilized GAMLSS centile curve modeling and CLSI EP28 guidelines to map hormone distributions and age-related shifts across 90–108 years.
Identified significant positive correlation between FT4 and age, and associations of BMI/WHtR with FT3, T3 and FT3/FT4, integrating anthropometric factors in thyroid assessment.
Why it matters:
Defining age-tailored thyroid hormone norms for nonagenarians ensures accurate diagnosis and management of thyroid disorders, reducing misdiagnosis and optimizing geriatric care.
Q&A
What are reference intervals?
Why is the FT3/FT4 ratio important?
What is GAMLSS modeling?
How does age affect thyroid hormone levels?
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Thyroid Hormones and Aging
Introduction: The thyroid gland produces hormones—thyroxine (T4) and triiodothyronine (T3)—that regulate metabolism, growth, and neurologic function. In blood, most T4 and T3 bind carrier proteins; only the unbound fractions, free T4 (FT4) and free T3 (FT3), are biologically active. Thyroid‐stimulating hormone (TSH) from the pituitary regulates hormone secretion via a feedback loop called the hypothalamic‐pituitary‐thyroid (HPT) axis.
As people age, physiologic changes in the HPT axis, peripheral hormone conversion, and metabolism alter serum thyroid levels. Reduced deiodinase enzyme activity limits T4‐to‐T3 conversion, resulting in lower FT3 and T3 concentrations. Feedback sensitivity to TSH may decline, affecting TSH thresholds. These shifts necessitate specialized reference intervals for elderly populations to distinguish normal age‐related changes from disease.
Free vs. Total Hormone Measurements
Total T4 and T3: Measurements include bound and unbound hormone. Binding proteins (e.g., thyroxine‐binding globulin and albumin) can vary with nutritional status, medications, and illness, causing variability that may not reflect true thyroid status.
Free T4 and Free T3: Represent biologically active hormone levels unaffected by binding‐protein fluctuations. FT4 is the main secretory product of the thyroid. FT3 arises partly from peripheral conversion, hence the FT3/FT4 ratio gauges deiodinase function and peripheral responsiveness.
FT3/FT4 Ratio
The FT3/FT4 ratio is calculated by dividing FT3 (pmol/L) by FT4 (pmol/L). A higher ratio suggests efficient conversion to active hormone, while a lower ratio—common in older adults—reflects decreased peripheral deiodination. Clinically, the ratio helps differentiate hyperthyroid conditions (e.g., Graves’ disease) from destructive thyroiditis and guides treatment of subclinical disorders.
Reference Intervals in Geriatric Endocrinology
Defining Reference Intervals (RIs): RIs denote the range in which 95% of healthy individuals’ lab values fall, typically between the 2.5th and 97.5th percentiles. They must account for age, sex, ethnicity, and assay methods to avoid misinterpretation.
Methodology: For the oldest‐old (aged ≥90), RIs are established via:
- Screening a healthy cohort to exclude thyroid disease and medications.
- Measuring hormone levels using standardized assays (e.g., Roche Cobas).
- Plotting hormone distributions and centile curves using Generalized Additive Models for Location, Scale and Shape (GAMLSS).
- Applying nonparametric methods following CLSI EP28 guidelines to derive percentile limits.
Implications for Clinical Practice
Using age‐specific RIs prevents overdiagnosis of subclinical hypothyroidism or hyperthyroidism in the oldest‐old. Clinicians should integrate hormone levels with anthropometric indices and blood pressure readings to form a comprehensive endocrine assessment. Ongoing research will refine these intervals for diverse populations and assay platforms.