Age modifies the response to recombinant human thyrotropin.

BACKGROUND: A standardized protocol is used to administer recombinant human thyrotropin (rhTSH) in preparation for diagnostic studies and treatment in patients with thyroid cancer. The expectation is that serum TSH concentrations will peak on the day after the second injection and will be sufficiently elevated to stimulate uptake of radioiodine. We wished to test the hypothesis that TSH concentrations achieved after rhTSH injection are influenced by age. METHODS: Patients with thyroid cancer undergoing diagnostic radioiodine scanning were identified by chart review. Serum TSH concentrations were documented 24 and 72 hours after two rhTSH injections (days 3 and 5, respectively). Responses were subdivided into four ascending patient age groups: <35, 35-49, 50-64, and >64 years. TSH concentrations after rhTSH administration were documented according to patient age. RESULTS: There was a significant correlation between the serum TSH concentrations at both days 3 and 5 and patient age (p < 0.0001). None of the other factors examined (gender, menopausal status, weight, body mass index, baseline TSH, serum creatinine, and estimated glomerular filtration rate) were significant in multivariate analyses. The mean TSH concentration on day 3 increased significantly when patients were divided into the aforementioned groups of ascending age (96, 107, 142, and 196 mIU/L, p < 0.0001). Day 5 concentrations increased in a similar manner. CONCLUSIONS: 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.

Age and the thyrotropin response to hypothyroxinemia.

CONTEXT: Some studies suggest altered pituitary functioning and TSH production with aging. OBJECTIVE: Our objective was to test the hypothesis that less TSH production occurs despite comparable hypothyroxinemia with advancing age. DESIGN: We retrospectively studied adult outpatients of all ages with confirmed hypothyroidism and documented their TSH and free T4 concentrations. PARTICIPANTS: Two populations of 112 patients were subdivided into four age groups: 1) patients newly diagnosed with primary hypothyroidism and 2) thyroid cancer patients undergoing l-T4 withdrawal in preparation for diagnostic or therapeutic radioiodine. MAIN OUTCOME MEASURE: The relationship between paired free T-4 and TSH concentrations and patient age was studied. RESULTS: With spontaneous hypothyroidism, the mean TSH concentration decreased nonsignificantly in each ascending age group with comparable free T4 (FT4) concentrations (<35 yr, 69 mIU/liter; 35-49 yr, 49 mIU/liter; 50-64 yr, 43 mIU/liter; >64 yr, 29 mIU/liter). With iatrogenic hypothyroidism, the mean TSH concentration decreased significantly in each ascending age group (<35 yr, 156 mIU/liter; 35-49 yr, 115 mIU/liter; 50-64 yr, 74 mIU/liter; >64 yr, 46 mIU/liter; P<0.001) despite similar FT4 concentrations. The relationship between the log-transformed TSH and FT4 was significantly and inversely affected by age in multivariate analyses in both spontaneous hypothyroidism (P=0.0005) and in iatrogenic hypothyroidism (P<0.0001). CONCLUSIONS: 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.

Combination pharmacotherapy with incretins: what works best and when?

The incretin hormone glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors fill an unaddressed therapeutic gap in the treatment of type 2 diabetes mellitus (T2DM) by potentiating insulin secretion in pancreatic beta cells, suppressing glucagon secretion, delaying gastric emptying, and reducing appetite. The incretin therapies, alone or in combination with metformin and/or thiazolidinediones, yield improved glycemic control without risk of hypoglycemia and the potential for weight neutrality or even weight loss. New incretin-based approaches offer promising new strategies for treating T2DM by recruiting new, physiologically based mechanisms of action for glucoregulation in the context of a favorable safety profile.