Thyroidal and peripheral production of 3,5,3'-triiodothyronine in humans by multicompartmental analysis

Pilo, A.; Iervasi, Giorgio; Vítek, F.; Ferdeghini, M; Cazzuola, F.; Bianchi, R.

doi:10.1152/ajpendo.1990.258.4.e715

Cited by 127 publications

(141 citation statements)

References 21 publications

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“…It is well known that thyroxine production rates in individuals with endogenous thyroid function are under tight control, are affected by a variety of situations, and can be studied using multicompartment models (32)(33)(34). If gender was one of the factors that affected thyroxine production, it would be possible that the different dose requirements seen in this study are a reflection of gender-specific physiological needs.…”

Section: Discussionmentioning

confidence: 99%

Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age

Devdhar

Drooger

Pehlivanova

et al. 2011

Thyroid

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Background: Body weight (BW) and age have been shown to affect the dose of levothyroxine (LT 4 ) that results in normalization of serum thyroid-stimulating hormone (TSH) in hypothyroid patients. Our objective was to determine whether gender, menstrual status, and ideal BW (IBW) also affect the LT 4 dose required to achieve a serum TSH within the normal range. Methods: We retrospectively reviewed the charts of patients being treated for primary hypothyroidism who had TSH values within a normal range. We selected patients aged 18-85 years who were taking LT 4 without any confounding medications, and who had no serious chronic conditions. Their LT 4 doses, referred to here as LT 4 dose requirements, based on both BW and IBW were documented. The relationship between gender, menstrual status, age, serum TSH concentrations, and the degree of overweight on LT 4 dose requirements were determined using multivariate analyses. Results: Women were significantly more overweight than men (ratio of BW/IBW was 1.35 for women vs. 1.17 for men, p < 0.0001). LT 4 requirements based on BW did not differ by gender when age was included in the model. However, when degree of overweight was also included, men required lower LT 4 doses than both premenopausal women (1.34 mg/kg vs. 1.51 mg/kg, p ¼ 0.038) and menopausal women (1.34 mg/kg vs. 1.49 mg/ kg, p ¼ 0.023). When examining IBW using a model incorporating age, men also required lower LT 4 doses than both premenopausal women (1.64 mg/kg vs. 1.92 mg/kg, p ¼ 0.0033) and menopausal women (1.64 mg/kg vs. 1.90 mg/kg, p ¼ 0.0024). Serum TSH concentrations were not significantly different in any of the gender groups. There was no relationship between serum TSH and either age or BW. The initial serum TSH concentration was by design with the normal range, but the concentration within that range was not a significant predictor of the LT 4 replacement dose in any of the models. Conclusion: In contrast to previous studies suggesting that age affects LT 4 replacement requirements, we found that age-based differences in doses are secondary to differences in BW and gender. In addition, in contrast to prior studies showing that lean body mass, but not gender, affected LT 4 dose, we instead found a significant impact of gender. Gender-based differences in dose requirement only became apparent either when IBW was used to correct for the dose or when degree of overweight was included in the model. Gender differences in LT 4 dose requirement exist, but are masked unless gender-based differences in degree of overweight are also considered.

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Section: Discussionmentioning

confidence: 99%

Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age

Devdhar

Drooger

Pehlivanova

et al. 2011

Thyroid

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“…FT 3 and FT 4 were determined by non-analogue, twostep immunoassays from the same manufacturer, reference ranges being 2.23-5.36 and 9.5-25 pmol/l respectively. TPO Abs were determined by RIA (reference range !60 IU/ml) and TSH-R Abs by the secondgeneration TRAK assay (reference range !2 U/l; BRAHMS, Berlin, Germany).…”

Section: Laboratory Methodsmentioning

confidence: 99%

“…Cellular access to triiodothyronine (T 3 ) is tightly controlled by two mechanisms, an active transport into the cell and an enzymatic conversion of thyroxine (T 4 ) to T 3 by deiodinases, which exist in different subtypes (2,3). Conversion is also the main source of T 3 in humans, making up about 80% of its production, the rest being directly supplied by the thyroid gland (4). Failure of the thyroid gland or any change in hormone production is sensitively reflected at the pituitary level via a negative feedback within the hypothalamuspituitary-thyroid regulatory loop.…”

Section: Introductionmentioning

confidence: 99%

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Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Hoermann

Midgley²,

Larisch

et al. 2013

European Journal of Endocrinology

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Objective: In recognition of its primary role in pituitary-thyroid feedback, TSH determination has become a key parameter for clinical decision-making. This study examines the value of TSH as a measure of thyroid hormone homoeostasis under thyroxine (T 4 ) therapy. Design and methods: We have examined the interrelationships between free triiodothyronine (FT 3 ), free T 4 (FT 4 ) and pituitary TSH by means of i) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of L-T 4 and ii) independent mathematical simulation applying a model of thyroid homoeostasis, together with a sensitivity analysis. Results: Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH vs FT 3 and FT 4 between untreated patients and L-T 4 groups. Total deiodinase activity (G D ) was positively correlated with TSH in untreated subjects. However, G D was significantly altered and the correlation was lost under increasing L-T 4 doses. Ninety-five per cent confidence intervals for FT 3 and FT 4 , when assessed in defined TSH concentration bands, differed significantly for L-T 4 -treated compared with untreated patients. Higher doses were often needed to restore FT 3 levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including an important role of pituitary deiodinase type 2. Conclusion: The data reveal disjoints between FT 4 -TSH feedback and T 3 production that persist even when sufficient T 4 apparently restores euthyroidism. T 4 treatment displays a compensatory adaptation but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.

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“…The bulk of T3 production is a consequence of peripheral 5'-deiodination due to D1 and D2 as suggested by the observation of nearly normal T3 levels in athyreotic patients receiving L-thyroxine therapy in physiological amounts (4). The relative contribution of the two enzymes is still a matter of debate, as suggested by multicompartimental analysis (21). In patients with hypothyroidism receiving fixed replacement doses of L-thyroxine, PTU administration (which blocks D1) resulted in a 20-30% decrease in serum T3, suggesting D1-catalyzed T3 production is not the only contributor to extrathyroidal T3 production (22).…”

Section: The Deiodinases In T3 Homeostasis Including Hypothyroidism mentioning

confidence: 99%

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Marsili

Zavacki

Harney

et al. 2011

J Endocrinol Invest

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Thyroxine (T4) is a prohormone secreted by the thyroid. T4 has a long half life in circulation and it is tightly regulated to remain constant in a variety of circumstances. However, the availability of iodothyronine selenodeiodinases allow both the initiation or the cessation of thyroid hormone action and can result in surprisingly acute changes in the intracellular concentration of the active hormone T3, in a tissue-specific and chronologically-determined fashion, in spite of the constant circulating levels of the prohormone. This fine-tuning of thyroid hormone signaling is becoming widely appreciated in the context of situations where the rapid modifications in intracellular T3 concentrations are necessary for developmental changes or tissue repair. Given the increasing availability of genetic models of deiodinase deficiency, new insights into the role of these important enzymes are being recognized. In this review, we have incorporated new information regarding the special role played by these enzymes into our current knowledge of thyroid physiology, emphasizing the clinical significance of these new insights.

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Thyroidal and peripheral production of 3,5,3'-triiodothyronine in humans by multicompartmental analysis

Cited by 127 publications

References 21 publications

Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age

Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

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