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1.
Thyroid ; 23(6): 662-70, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23136932

ABSTRACT

BACKGROUND: When applying the recommended standard doses of recombinant human thyrotropin (rhTSH) in the diagnostic/therapeutic management of patients with differentiated thyroid cancer (DTC), the resulting peak TSH levels vary extensively. Previous studies applying multivariate statistics identified patient-inherent variables influencing the rhTSH/peak TSH relation. However, those results were inconclusive and partly conflicting. Notably, no independent role of renal function was substantiated, despite the fact that the kidneys are known to play a prominent role in TSH clearance from blood. Therefore, the study's aim was to investigate the impact of renal function on the peak TSH concentration after the standard administration of rhTSH used in the management of thyroid cancer. The second objective was to calculate a ranking regarding the effect sizes of the selected variables on the peak TSH. METHODS: There were 286 patients with DTC included in the study. Univariate and multivariate analyses were performed, testing the correlation of serum creatinine and glomerular filtration rate (GFR) as surrogate parameters of renal function, age, sex, weight, height, and body surface area (BSA) with the peak TSH level. In six additional patients, the subsequent TSH pharmacokinetics after the TSH peak were measured and qualitatively compared. RESULTS: By univariate analyses, TSH correlated negatively with BSA, GFR, weight, and height, and positively with age, female sex, and serum creatinine (p<0.001). On the multivariate analysis, the stepwise forward multiple linear regression revealed BSA and renal function as the two most influential independent variables, followed by age, sex, and height. The pharmacokinetic datasets indicated that these identified parameters also influence the TSH decline over time. CONCLUSION: Identifying those patients with a favorable combination of parameters predicting a high-peak TSH is the first step toward an individualization of rhTSH dosing. Additionally, the subsequent TSH decrease over time needs to be taken into account. A complete understanding of the interrelation of the identified key parameters and both the TSH peak and subsequent TSH pharmacokinetics might allow for a more personalized rhTSH dosage strategy to achieve sufficient TSH levels instead of the fixed dosing procedure used at present.


Subject(s)
Kidney/physiopathology , Renal Insufficiency/physiopathology , Thyrotropin/pharmacokinetics , Adolescent , Adult , Aged , Aged, 80 and over , Body Surface Area , Female , Humans , Hypothyroidism/diagnosis , Hypothyroidism/etiology , Kidney/drug effects , Male , Metabolic Clearance Rate , Middle Aged , Recombinant Proteins/blood , Recombinant Proteins/pharmacokinetics , Regression Analysis , Renal Insufficiency/blood , Renal Insufficiency/complications , Retrospective Studies , Thyroid Gland/drug effects , Thyroid Gland/physiopathology , Thyroid Neoplasms/complications , Thyroid Neoplasms/physiopathology , Thyroid Neoplasms/therapy , Thyrotropin/blood , Young Adult
2.
J Nucl Med ; 51(12): 1917-22, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21078788

ABSTRACT

UNLABELLED: This aim of this retrospective study was to determine the impact of glucocorticoid therapy on the effective (131)I half-life in radioiodine therapy for Graves disease. METHODS: Three hundred fifteen consecutive Graves disease patients undergoing radioiodine therapy at our institution between August 2004 and January 2009 were enrolled. We investigated the influences of thyroid state (hypothyroidism, euthyroidism, hyperthyroidism), antithyroid drug dose before (131)I therapy, thyroid-stimulating hormone receptor antibody (TRAb) level, and qualitative and quantitative factors of prednisolone therapy on the effective (131)I half-life, applying univariate (paired t test) and multivariate (multiple-regression) analyses. RESULTS: Multivariate analyses revealed independent significant effects of the thyroid metabolic state (P = 0.004), antithyroid drugs (P < 0.001), presence of TRAb (P = 0.004), and glucocorticoids (P = 0.046) on thyroidal radioiodine half-life. Compared with euthyroidism, thyrotoxicosis and hypothyroidism reduced the effective half-life; high doses of antithyroid drugs and high TRAb levels had the same effect. Also, glucocorticoid therapy shortened the effective thyroidal radioiodine half-life in a dose-dependent manner. Pharmacologically, this effect is attributable to the prednisolone-induced increase of renal plasma (131)I clearance and the resulting reduction of plasma (131)I available for reuptake into the thyroid during radioiodine therapy. CONCLUSION: Oral treatment with prednisolone results in a reduction of effective thyroidal (131)I half-life in Graves disease, especially at higher doses.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Glucocorticoids/therapeutic use , Graves Disease/drug therapy , Graves Disease/radiotherapy , Iodine Radioisotopes/pharmacokinetics , Iodine Radioisotopes/therapeutic use , Prednisolone/therapeutic use , Antibodies/analysis , Antithyroid Agents/therapeutic use , Drug Interactions , Female , Half-Life , Humans , Male , Middle Aged , Receptors, Thyrotropin/immunology , Regression Analysis , Thyroid Gland/metabolism , Treatment Outcome
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