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Age modifies the pituitary set point or response to comparably reduced free T4 concentrations, resulting in lesser serum TSH elevation in older individuals. This phenomenon occurs with both spontaneous and iatrogenic hypothyroidism. This may be an adaptive response in normal aging or a pathological alteration of pituitary function with age.

Both days 3 and 5 TSH concentrations were higher in older individuals after rhTSH administration. This finding did not appear to be related to body weight, body mass index, or glomerular filtration rate in a simple manner. The TSH concentration achieved may be a result of complex interactions between distribution within fat and muscle body compartments, hepatic function, and renal function. Prospective studies could examine whether the magnitude of the TSH elevation after rhTSH administration affects diagnostic or therapeutic efficacy.