Lean Body Mass Is a Major Determinant of Levothyroxine Dosage in the Treatment of Thyroid Diseases

Santini, Ferruccio; Pinchera, Aldo; Marsili, Alessandro; Ceccarini, Giovanni; Castagna, Maria Grazia; Valeriano, Rocco; Giannetti, Monica; Taddei, Donatella; Centoni, Roberta; Scartabelli, Giovanna; Rago, Teresa; Mammoli, Claudia; Elisei, Rossella; Vitti, Paolo

doi:10.1210/jc.2004-1306

Cited by 207 publications

(144 citation statements)

References 28 publications

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“…This is in contrast with most studies, showing low/normal levels of FT 4 in obese subjects. As an alternative explanation, it should be considered that the turnover rate of T 4 is proportional to body size (73) that is indeed a main determinant of the substitution dose of levothyroxine (L-T 4 ) in hypothyroid subjects (74,75). Thus, an increased rate of thyroid hormone disposal (resulting from a large body size) would be the causative event promoting an activation of the hypothalamus-pituitary-thyroid axis aimed at maintaining serum thyroid hormones within the euthyroid range.…”

Section: Thyroid Function and Structure In Obese Subjectsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

Santini

Marzullo

Rotondi

et al. 2014

European Journal of Endocrinology

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204

185

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Obesity and thyroid diseases are common disorders in the general population and they frequently occur in single individuals. Alongside a chance association, a direct relationship between 'thyroid and obesity' has been hypothesized. Thyroid hormone is an important determinant of energy expenditure and contributes to appetite regulation, while hormones and cytokines from the adipose tissue act on the CNS to inform on the quantity of energy stores. A continuous interaction between the thyroid hormone and regulatory mechanisms localized in adipose tissue and brain is important for human body weight control and maintenance of optimal energy balance. Whether obesity has a pathogenic role in thyroid disease remains largely a matter of investigation. This review highlights the complexity in the identification of thyroid hormone deficiency in obese patients. Regardless of the importance of treating subclinical and overt hypothyroidism, at present there is no evidence to recommend pharmacological correction of the isolated hyperthyrotropinemia often encountered in obese patients. While thyroid hormones are not indicated as anti-obesity drugs, preclinical studies suggest that thyromimetic drugs, by targeting selected receptors, might be useful in the treatment of obesity and dyslipidemia.

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Section: Thyroid Function and Structure In Obese Subjectsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

Santini

Marzullo

Rotondi

et al. 2014

European Journal of Endocrinology

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204

185

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“…These estimates include 1.6 mg (1-8), 1.7 mg (4,6), 1.8 mg (5,9), 2.0 mg (9), and 2.1 mg (5) LT 4 per kilogram actual BW. LT 4 replacement doses in thyroid cancer patients requiring TSH suppression are generally higher and on the order of 2.0-2.56 mg/kg (1,5,6). A study by Santini et al showed that ideal BW (IBW) is a better predictor of LT 4 dose than actual BW and that any gender differences in LT 4 dose requirement were accounted for by lean body mass (5).…”

Section: Introductionmentioning

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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“…More specifically, only two patients out of 23 showed FT 3 values below normal and none showed subnormal FT 4 . Since T 4 metabolism is slowed down in elderly patients (12) and the dose of T 4 should be accordingly reduced, age may represent a confounding factor. So far, patients were subdivided into two agerelated groups: under 50 years of age (nZ11) and 50 years of age or older (nZ12) and the pre-and post-surgical dose has been compared accordingly.…”

Section: Resultsmentioning

confidence: 99%

“…The individually tailored dose is the dose of T 4 which is administered following a standardized assumption procedure and titrated on the basis of patient's age, weight, BMI, the amount of residual thyroid tissue and the ability to absorb the hormone (12,14,15,21,22,23,24). All patients were treated with the same brand of oral and agreed to take T 4 under fasting conditions, abstaining from eating or drinking anything other than water for at least 1 h after treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Several studies dealing with T 4 requirement have been carried out on patients with primary hypothyroidism, with or without thyroid in situ (see (6,9) for a review). Some of these studies focused on factors affecting the therapeutic dose, such as body weight (6,12), BMI (13), amount of residual thyroid tissue, patients' age and drugs (14,15,16), and only a fraction of them examined T 4 requirement after total thyroidectomy (7,8,9,10,11). However, most of these latter reports were retrospective and/or compared results obtained in different groups of patients (15,16,17), and/or in heterogeneous therapeutic settings (7,16).…”

Section: Introductionmentioning

confidence: 99%

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Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study

Duca

Santaguida

Brusca

et al. 2015

European Journal of Endocrinology

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Objective: Thyroxine (T 4 ) requirement after total thyroidectomy for differentiated thyroid carcinoma (DTC) is a debated issue. As most of the studies in the area have been retrospective and/or performed with heterogeneous therapeutic approaches, we designed our study to determine T 4 requirement in the same patients and treatment settings, before and after total thyroidectomy. Design, patients and methods: This was a longitudinal study including 23 goitrous patients treated with T 4 in an individually tailored fashion. All patients exhibited a stable TSH (median TSHZ0.28 mU/l) at a stable T 4 dose for at least 1 year before surgery (median T 4 doseZ1.50 mg/kg per day). The patients underwent total thyroidectomy based on cancer suspicion or compressive symptoms. Eventually diagnosed as having DTC (pT1b-pT2N0) and following surgical and radiometabolic treatment, they were treated with the same pre-surgical doses of T 4 . Results: Three months after surgery,using the same pre-surgical dose, median TSH increased up to 5.38 mU/l (P!0.0001) and so the T 4 dose had to be increased (median T 4 doseZ1.95 mg/kg per day; C30%; P!0.0001). Once divided by patients' age, we observed that, after thyroidectomy and maintaining the same pre-surgical dose, serum TSH significantly increased both in younger and in older patients (median TSHZ4.57 and 6.11 mU/l respectively). Serum TSH was restored to the pre-surgical level by increasing the dose up to 1.95 and 1.77 mg/kg per day (C25 and C21%) respectively. Conclusions: Following the same treatment regimen, a thyroidectomized patient requires one-third higher therapeutic T 4 dose than before surgery. Despite this increase, the dose of T 4 needed in our patients remains significantly lower than that previously described in athyreotic patients.

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Lean Body Mass Is a Major Determinant of Levothyroxine Dosage in the Treatment of Thyroid Diseases

Cited by 207 publications

References 28 publications

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

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

Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study

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