Hormona tiroidea y obesidad

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REVIEW

CURRENTOPINION Thyroid hormone and obesity

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Elizabeth N. Pearce

Purpose of review

To review several of the most recent and most important clinical studies regarding the effects of thyroidtreatments on weight change, associations between thyroid status and weight, and the effects of obesityand weight change on thyroid function.

Recent findings

Weight decreases following treatment for hypothyroidism. However, following levothyroxine treatment forovert hypothyroidism, weight loss appears to be modest and mediated primarily by loss of water weightrather than fat. There is conflicting evidence about the effects of thyroidectomy on weight. In largepopulation studies, even among euthyroid individuals, serum thyroid-stimulating hormone is typicallypositively associated with body weight and BMI. Both serum thyroid-stimulating hormone and T3 aretypically increased in obese compared with lean individuals, an effect likely mediated, at least in part, byleptin. Finally, there is no consistent evidence that thyroid hormone treatment induces weight loss in obeseeuthyroid individuals, but thyroid hormone analogues may eventually be useful for weight loss.

Summary

The interrelationships between body weight and thyroid status are complex.

Keywords

body weight, obesity, thyroid

INTRODUCTION

Both thyroid dysfunction and obesity are highlyprevalent in the general population. National datasuggest that hypothyroidism is present in 4.6% ofthe US population, and hyperthyroidism in 1.3%[1]. Obesity rates have climbed in the USA andworldwide over the last several decades; more than30% of the US population is now classified as obese[2]. This review focuses on recent clinical studiesregarding the effects of thyroid treatments onweight change, associations between thyroid statusand body weight, and the effects of obesity andweight change on thyroid function.

Boston University School of Medicine, Boston, Massachusetts, USA

Correspondence to Elizabeth N. Pearce, MD, MSc, Boston UniversitySchool of Medicine, Section of Endocrinology, Diabetes, and Nutrition,88 East Newton Street, Evans 201, Boston, MA 02118, USA. Tel: +1617 414 1348; fax: +1 617 638 7221; e-mail: [email protected]

Curr Opin Endocrinol Diabetes Obes 2012, 19:408–413

DOI:10.1097/MED.0b013e328355cd6c

WEIGHT CHANGE AFTER TREATMENT FORTHYROID DYSFUNCTION

Thyroid hormone increases the basal metabolicrate [3]. Patients with overt hypothyroidism oftenpresent with a history of weight gain, and those withhyperthyroidism frequently present with weightloss. However, the degree of weight change withthyroid dysfunction, and the effects of treatmenton body weight are surprisingly poorly understood.A 1984 study described weight change followinginitiation of treatment for thyroid dysfunction [4].Nine of 18 hypothyroid patients experienced a

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modest weight loss following initiation of levothyr-oxine (L-T4) therapy, but all had returned to theirweights before treatment by 12–24 months. Eighty-seven hyperthyroid patients had lost a mean of 16%of their body weights before hyperthyroidism at thetime of presentation; 2 years following initiation oftreatment, they had regained and slightly exceededtheir baseline weight. A recent study of weightchange following treatment of thyroid dysfunctionin 57 hyperthyroid and 29 hypothyroid childrensimilarly found that weight loss was minimalfollowing treatment for hypothyroidism (mean0.3 kg by the first follow-up visit) [5]. However, therewas an average 7.1 kg gain in weight by the secondfollow-up visit following initiation of treatmentfor hyperthyroidism.

Weight change was followed for 1 year in12 overtly hypothyroid individuals [mean baseline

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KEY POINTS

� Body weight increases following hyperthyroidismtreatment and modestly decreases followinghypothyroidism treatment.

� In population studies, serum TSH (within the normalrange) is positively associated with baseline BMI andwith weight change over time.

� Serum TSH and free triiodothyronone (FT3) are bothincreased in obese individuals; levels normalize withweight loss.

� There is no clear effect of thyroid hormone treatment onweight loss in obese euthyroid individuals, however,there may be a future role for thyroid hormoneanalogues as an obesity treatment.

Thyroid hormone and obesity Pearce

thyroid-stimulating hormone (TSH) 102 mIU/L] fol-lowing initiation of L-T4 treatment, and comparedwith 10 euthyroid controls [6

&&

]. At 1 year (meanserum TSH 2.2 mIU/L), mean weight had decreasedsignificantly, from 83.7 to 79.4 kg (P¼0.002). Dualenergy X-ray absorptiometry (DEXA) scans demon-strated that the weight loss following initiation ofL-T4 was due to decreases in lean mass, with nosignificant changes in either bone mass or fat mass;the authors concluded that weight loss after L-T4treatment for hypothyroidism is mediated primarilyby loss of excess body water.

Among hypothyroid patients, the degree of TSHsuppression achieved by L-T4 therapy does notappear to strongly influence body weight. In a pro-spective study examining the effects of treatinghypothyroid patients to a TSH goal of 0.4–2 mIU/Lcompared with 2–4 mIU/L, the patients treated tothe lower TSH target had higher resting energyexpenditure, but there was no difference in leanor fat body mass or percentage body fat between thegroups at 1 year [7

&

]. Polotsky et al. [8&

] retrospec-tively examined changes in body weight among153 athyreotic thyroid cancer survivors treatedwith TSH-suppressive L-T4 doses (median serumTSH 0.05 mIU/L) for up to 5 years. There was amedian 3.2% weight gain at 3–5 years of follow-up, despite ongoing iatrogenic hyperthyroidism,similar to or higher than previously publishedeuthyroid population values.

A blinded cross-over study examined the effectsof liothyronine (L-T3) compared to L-T4 treatmentin 14 adults with primary hypothyroidism who werealready on L-T4 therapy [9

&&

]. Patients were treatedwith L-T3 or L-T4 taken three times daily, in order toachieve a serum TSH 0.5–1.5 mIU/L at three con-secutive biweekly visits. The L-T3 treatment (for amean of 19 weeks) resulted in significant weight loss

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(on average 1.8 kg), whereas L-T4 treatment was notassociated with significant weight change. On thebasis of DEXA scans, there was a nearly significantdecrease in fat mass of 5.3% (P¼0.052) withL-T3 treatment.

OBESITY AND THYROID SURGERY

A large multicenter retrospective study of 18 825patients who underwent total thyroidectomyrecently demonstrated that the duration of surgeryis longer in obese and overweight patients than inlean patients, and surgical complications are morefrequent [10]. However, the authors concluded thatthese differences did not seem to impact on durationof hospital stay, and therefore might not be clin-ically meaningful. A retrospective study comparedweight change in 102 thyroid cancer patients fol-lowing thyroidectomy with weight change in euthy-roid patients with benign nodules or goiter whosethyroids were not resected [11

&

]. There was no differ-ence in weight or BMI change between the twogroups at a median 5.9 years of follow-up. In anotherretrospective study, 120 patients with achievementof euthyroidism on thyroid hormone therapy 1 yearfollowing total thyroidectomy were compared withage, gender, height, menopausal status, and baselineweight-matched treated hypothyroid individualswho did not undergo thyroidectomy [12

&

]. In con-trast to the previous study, at 1 year, the thyroidec-tomized patients had experienced significantlymore weight gain (3.1 vs. 2.2 kg, P¼0.004) thanthe matched controls.

ASSOCIATIONS BETWEEN THYROIDSTATUS AND WEIGHT AND WEIGHTCHANGE

Recent population studies have examined theeffects of thyroid status on weight and on weightchange over time. In a cross-sectional study of 778euthyroid (serum TSH 0.4–5 mIU/L) Spanish adults,serum TSH, and BMI were positively correlated, andindividuals with serum TSH levels in the highesttertile had the highest BMI values [13]. However,when this cohort was restricted to a subgroup of 375individuals without detectable serum thyroperoxi-dase antibodies, these relationships were no longerobserved. Another Spanish study examined longi-tudinal weight change in relation to baseline TSHlevels in 784 euthyroid adults followed for 6 years[14]. At baseline, TSH, FT3, and free thyroxine (FT4)levels did not differ in obese and nonobese individ-uals. Increases in FT3 were positively correlated withincreases in weight over the follow-up period,and the authors suggested that increases in thyroid

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hormone were a consequence, rather than acause, of interval weight gain. In the NorwegianNord-Trøndelag health cohort study, associationsbetween baseline thyroid status, weight, and BMIwere investigated in 15 020 euthyroid (serum TSH0.5–3.5 mIU/L) individuals over a mean follow-upof 10.5 years [15

&&

]. In women, for every 1 mIU/Lincrease in baseline serum TSH, there was a 0.9 kgincrease in weight and a 0.3 kg/m2 increase in BMIover the follow-up period, whereas in men, for each1 mIU/L TSH increment, weight increased by 0.8 kgand BMI by 0.2 kg/m2.

EFFECTS OF THYROID STATUS ON FATDISTRIBUTION

Limited data suggest that thyroid status may influ-ence adipose tissue distribution as well as the overallamount of adipose tissue present. Both thyroid hor-mone and visceral fat (as quantified by abdominalultrasound) were measured in 174 euthyroid prepu-bertal children [16]. In cross-sectional analysesadjusted for age, BMI, and total body fat, FT4was independently and inversely associatedwith visceral fat stores. In a cross-sectional studyof euthyroid adults with known vascular disease,higher serum TSH was associated with increasedvisceral fat thickness, although only among indi-viduals aged 67–80 years. Serum TSH was notassociated with either weight or BMI. A previousstudy in 303 healthy volunteers had demonstratedthat the amount of subcutaneous fat and thesubcutaneous-to-visceral fat ratio were inverselycorrelated with free T4 levels and that TSHwas positively correlated with subcutaneous fatthickness [17].

The effects of thyroid status on fat distributionmay be explained by differential TSH receptor and/or thyroid hormone receptor expression in differentfat depots, and receptor expression seems to differ inobese compared with lean individuals. TSH receptorexpression was recently measured in subcutaneousfat samples from 120 euthyroid patients [18]. Sub-cutaneous fat TSH receptor expression was found tobe increased in individuals with higher BMI. Aprevious study had demonstrated that thyroid hor-mone receptora and thyroid hormone receptora1expression is increased in subcutaneous comparedwith visceral fat deposits in obese, but not normal-weight patients [19]. Finally, Nannipieri et al. [20]measured TSH receptor and thyroid hormone recep-tora1 expression in subcutaneous and visceral fat inobese and lean patients, and then prospectivelymeasured TSH receptor and thyroid hormone recep-tora1 expression in subcutaneous fat samples from asubset of 27 obese patients before and 1 year after

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gastric bypass surgery. At baseline, TSH receptorand thyroid hormone receptora1 expression weredecreased in both visceral and subcutaneous fatdeposits in obese individuals, and did not differby glucose tolerance. Following a 33% decrease inBMI at 1 year after bariatric surgery, the subcu-taneous fat expression of TSH receptor increasedby 150% and the expression of thyroid hormonereceptora1 increased by 70%.

EFFECTS OF OBESITY ON THYROIDSTATUS

The relationship between thyroid status and obesityis likely to be bidirectional, with hypothyroidismaffecting weight and BMI, but obesity also influenc-ing thyroid function. Thyroid function abnormal-ities are highly prevalent in obese individuals:among 783 consecutive obese patients seen for bari-atric surgery evaluation, 18.1% had elevated serumTSH [21]. In 1976, Bray et al. [22] demonstrated apositive correlation between T3, but not T4, andbody weight. This observation has since been con-firmed in multiple studies [23,24

&

]. Most recently, ina cross-sectional analysis of data from the NationalHealth and Nutrition Examination Survey 2007–2008, among 3114 euthyroid adults without ahistory of thyroid disease, BMI and waist circum-ference were positively associated with serum TSHand FT3, but not FT4 [25

&

]. These relationships arepresent in children as well as in adults. A recentreview describes four studies in which childhoodobesity was associated with moderate serum TSHelevations [26

&

]. In two of those studies, weight lossled to normalization of serum TSH. Another recentreview concluded that 7–23% of obese childrenexhibit serum TSH elevations with normal orslightly elevated FT3 levels [24

&

]. In obese patientswith mild TSH elevations, it may be difficult todistinguish between true subclinical hypothyroid-ism and physiologic alterations in thyroid function;however, individuals with undetectable thyroidantibodies and high-normal serum T3 levels areunlikely to have true underlying thyroid failure[27,28

&&

].The reason for elevations in both TSH and T3 in

obese individuals is not entirely clear. However, it islikely that leptin plays a role in regulating thisprocess. Leptin, secreted by adipose cells, serves asa signal to the central nervous system regardingenergy balance and the presence of energy stores.Leptin promotes thyrotropin releasing hormonegene expression directly in the paraventricularnucleus, ultimately stimulating TSH release [29–31]. Leptin may also increase T4 to T3 conversionby deiodinases in a tissue-specific fashion [32,33]. In




addition to the effects of leptin, it has also beenpostulated that thyroid function abnormalitiesin obesity may be related to peripheral thyroidhormone resistance, altered TSH bioactivity, ormay constitute an adaptive process designed toincrease resting energy expenditure [34,35].

THYROID FUNCTION CHANGES AFTERWEIGHT CHANGE

In 1979, Danforth et al. [36] demonstrated thatshort-term and long-term overnutrition in humanvolunteers resulted in increased T3, but not T4,production, and that serum T3 decreased withcaloric restriction. More recent observational stud-ies have demonstrated alterations in thyroid func-tion following weight loss in obese individuals,regardless of the way in which weight loss isachieved. In a study comparing adolescent girlswith normal weight, obesity, or anorexia nervosa,TSH and FT3 were significantly lower in the ano-rexic girls and significantly higher in the obesegirls than the normal-weight girls [37]. Followingweight gain of more than 5%, TSH and FT3increased in the anorexic girls, and following morethan 5% weight loss, TSH and FT3 decreased in theobese girls. In another pediatric study, 246 obesechildren attending a weight loss program werefollowed for 1 year [38]. At baseline, serum TSHand FT3 were higher in the obese children than innormal-weight controls, but FT4 did not differ. At1 year, there was a significant decrease in TSH andFT3 in the 49 children who had achieved signifi-cant weight loss, whereas there was no change inserum TSH in the 197 obese children who did notlose weight.

In a prospective study of 11 obese premeno-pausal women, thyroid function was assessed beforeand after 50% excess weight loss was achieved bydiet [39]. At baseline, serum TSH was higher than innormal-weight controls, and weight loss was associ-ated with reductions in serum TSH and FT3. Thedecline of serum TSH correlated with decreases inserum leptin. In a retrospective study of 258 euthy-roid morbidly obese patients who underwent gastricbanding, thyroid function was ascertained beforeand up to 24 months after the bariatric surgery[40]. Following weight loss, FT3 levels decreasedand FT4 increased, without significant changes inserum TSH. In a prospective study of 98 premeno-pausal obese women, thyroid function was studiedbefore and after 6 months of treatment with sibutr-amine or orlistat [41]. At 6 months, althoughBMI and leptin levels had decreased significantly,there were no significant changes in TSH, FT3,or FT4 values. In another recent prospective



study, 24 obese and overweight adults weretreated with hypocaloric diets and randomized toreceive recombinant leptin therapy vs. placebo for6 months [42

&

]. Leptin treatment was not associatedwith differences in thyroid function as comparedwith the placebo-treated controls, suggesting thatleptin alone may not mediate changes in thyroidfunction in response to weight loss inducedby dieting.

THYROID HORMONE AND THYROIDHORMONE ANALOGUES FOR WEIGHTLOSS IN EUTHYROID INDIVIDUALS

A systematic review by Kaptein et al. [43] identified14 studies describing the effects of T3 or T3/T4treatment on weight loss in euthyroid individualsduring caloric deprivation. Sample sizes were small,ranging from only five to 12 in treated groups.Thyroid hormone treatment reduced serum TSHand T4 concentrations, resulting in subclinicalhyperthyroidism, and there was no consistent effecton weight loss across studies.

Despite the lack of clear efficacy of thyroidhormone for weight loss in euthyroid individuals,thyroid hormone has been used illegally in dietarysupplements marketed for weight loss in severalcountries. A recent study from Hong Kong notedthe presence of illicit thyroid hormone in 20 of 66cases of weight loss products resulting in poisoningbetween 2004 and 2009 [44]. Nine of these patientspresented with overt thyrotoxicosis, and one hadthyrotoxic periodic paralysis.

Several thyroid hormone analogues are cur-rently in development. Most of the thyroidhormone’s effect on bone and heart are mediatedby a isoforms of the thyroid hormone receptor,whereas effects on the liver, such as lipid lowering,are mediated primarily by thyroid hormone recep-torb. Selective thyroid hormone receptorb agonists,therefore, are appealing as medications for hyper-lipidemia or obesity that might selectively lowerlipids or weight without bone or cardiac toxicity[45]. Weight loss has been observed with someof these compounds in animal studies. Howeverweight loss with thyroid mimetic treatment hasnot yet been reported in clinical trials [45,46],despite improvements in lipid parameters inpatients treated with the thyroid hormone analogueeprotirome [46], and knockout studies suggest thatregulation of basal metabolic rate is more dependenton thyroid hormone receptora than thyroidhormone receptorb [45]. One recent preliminarystudy of treatment with 3,5-diiodo-L-thyronine intwo euthyroid human volunteers did demonstrate asignificant 4% decrease in body weight without



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changes in serum FT3, FT4, or TSH; changes in fatmass were not evaluated [47

&

].

CONCLUSION

The interrelationships between body weight andthyroid status are complex. Weight decreases fol-lowing treatment for hypothyroidism. However,following L-T4 treatment for overt hypothyroidism,weight loss appears to be modest and mediatedprimarily by loss of water weight rather than fat.A single recent study suggests that carefully titratedL-T3 treatment in hypothyroid patients may causegreater weight loss than treatment with L-T4. Thereis conflicting evidence about the effects of thyroid-ectomy on weight. In large population studies, evenamong euthyroid individuals TSH is typically posi-tively associated with body weight and BMI. Bothserum TSH and T3 are typically increased in obesecompared with lean individuals, an effect likelymediated, at least in part, by leptin. Finally, thereis no consistent evidence that thyroid hormonetreatment induces weight loss in obese euthyroidindividuals, but thyroid hormone analogues mayeventually be useful for weight loss.

Acknowledgements

No funding was received for this work.

Conflicts of interest

There are no conflicts of interest.

REFERENCES AND RECOMMENDEDREADINGPapers of particular interest, published within the annual period of review, havebeen highlighted as:
& of special interest&& of outstanding interest Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (p. 433).
1. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroidantibodies in the United States population (1988 to 1994): National Healthand Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab2002; 87:489–499.

2. Centers for Disease Control and Prevention. Adult Obesity Facts. http://www.cdc.gov/obesity/data/adult.html. [Accessed 24 May 2012]

3. Kim B. Thyroid hormone as a determinant of energy expenditure and the basalmetabolic rate. Thyroid 2008; 18:141–144.

4. Hoogwerf BJ, Nuttall FQ. Long-term weight regulation in treated hyperthyroidand hypothyroid subjects. Am J Med 1984; 76:963–970.

5. Crocker MK, Kaplowitz P. Treatment of paediatric hyperthyroidism but nothypothyroidism has a significant effect on weight. Clin Endocrinol (Oxf) 2010;73:752–759.

6.&&

Karmisholt J, Andersen S, Laurberg P. Weight loss after therapy of hypothyr-oidism is mainly caused by excretion of excess body water associated withmyxoedema. J Clin Endocrinol Metab 2011; 96:E99–E103.

In this prospective observational study, body mass and body composition weremeasured in overtly hypothyroid patients at diagnosis and after 1 year of L-T4treatment; treatment was associated with a modest loss of lean mass and nochange in fat mass.7.&

Boeving A, Paz-Filho G, Radominski RB, et al. Low-normal or high-normalthyrotropin target levels during treatment of hypothyroidism: a prospective,comparative study. Thyroid 2011; 21:355–360.

This prospective study found no difference in weight change at 1 year inhypothyroid patients treated with L-T4 to a target TSH of 0.2–2 mIU/L comparedwith 2–4 mIU/L.

opyright © Lippincott Williams & Wilkins. Unautho

412 www.co-endocrinology.com

8.&

Polotsky HN, Brokhin M, Omry G, et al. Iatrogenic hyperthyroidism does notpromote weight loss or prevent ageing-related increases in body mass inthyroid cancer survivors. Clin Endocrinol (Oxf) 2012; 76:582–585.

In this retrospective study, iatrogenic hyperthyroidism in thyroid cancer survivorsover up to a 5-year follow-up period was associated with weight gain similar, oreven greater than that seen in euthyroid population controls.9.

&&

Celi FS, Zemskova M, Linderman JD, et al. Metabolic effects of liothyroninetherapy in hypothyroidism: a randomized, double-blind, crossover trial ofliothyronine versus levothyroxine. J Clin Endocrinol Metab 2011; 96:3466–3474.

In this blinded cross-over clinical trial, carefully titrated L-T3 therapy was asso-ciated with weight loss, whereas L-T4 therapy was not.10. Buerba R, Roman SA, Sosa JA. Thyroidectomy and parathyroidectomy in

patients with high body mass index are safe overall: analysis of 26 864patients. Surgery 2011; 150:950–958.

11.&

Weinreb JT, Yang Y, Braunstein GD. Do patients gain weight after thyroi-dectomy for thyroid cancer? Thyroid 2011; 21:1339–1342.

This observational study found no difference in weight change in thyroid cancerpatients following total thyroidectomy compared with euthyroid controls.12.&

Jonklaas J, Nsouli-Maktabi H. Weight changes in euthyroid patients under-going thyroidectomy. Thyroid 2011; 21:1343–1351.

This observational study found that patient who had undergone a thyroidectomy inthe previous year gained more weight than matched hypothyroid controls who hadnot undergone thyroid surgery.13. Dı́ez JJ, Iglesias P. Relationship between thyrotropin and body mass index in

euthyroid subjects. Exp Clin Endocrinol Diabetes 2011; 119:144–150.14. Soriguer F, Valdes S, Morcillo S, et al. Thyroid hormone levels predict the

change in body weight: a prospective study. Eur J Clin Invest 2011;41:1202–1209.

15.&&

Svare A, Nilsen TI, Bjøro T, et al. Serum TSH related to measures of bodymass: longitudinal data from the HUNT Study, Norway. Clin Endocrinol (Oxf)2011; 74:769–775.

In this prospective cohort study, weight gain over 10.5 years of follow-up wasassociated with increases in serum TSH.16. Prats-Puig A, Sitjar C, Ribot R, et al. Relative hypoadiponectinemia, insulin

resistance, and increased visceral fat in euthyroid prepubertal girls with low-normal serum free thyroxine. Obesity (Silver Spring) 2011. [Epub ahead ofprint]

17. Alevizaki M, Saltiki K, Voidonikola P, et al. Free thyroxine is an independentpredictor of subcutaneous fat in euthyroid individuals. Eur J Endocrinol 2009;16:459–465.

18. Lu S, Guan Q, Liu Y, et al. Role of extrathyroidal TSHR expression in adipocytedifferentiation and its association with obesity. Lipids Health Dis 2012;11:17.

19. Ortega FJ, Moreno-Navarrete JM, Ribas V, et al. Subcutaneous fat showshigher thyroid hormone receptor-alpha1 gene expression than omental fat.Obesity (Silver Spring) 2009; 17:2134–2141.

20. Nannipieri M, Cecchetti F, Anselmino M, et al. Expression of thyrotropin andthyroid hormone receptors in adipose tissue of patients with morbid obesityand/or type 2 diabetes: effects of weight loss. Int J Obes (Lond) 2009;33:1001–1006.

21. Fierabracci P, Pinchera A, Martinelli S, et al. Prevalence of endocrine diseasesin morbidly obese patients scheduled for bariatric surgery: beyond diabetes.Obes Surg 2011; 21:54–60.

22. Bray GA, Fisher DA, Chopra IJ. Relation of thyroid hormones to body-weight.Lancet 1976; 1:1206–1208.

23. Michalaki MA, Vagenakis AG, Leonardou AS, et al. Thyroid function in humanswith morbid obesity. Thyroid 2006; 16:73–78.

24.&

Pacifico L, Anania C, Ferraro F, et al. Thyroid function in childhood obesity andmetabolic comorbidity. Clin Chim Acta 2012; 413:396–405.

This review article describes possible mechanisms linking thyroid dysfunction andobesity in children.25.&

Kitahara CM, Platz EA, Ladenson PW, et al. Body Fatness and Markersof Thyroid Function among U.S. Men and Women. PLoS One 2012; 7:e34979.

These cross-sectional data from the 2007–2008 National Health and NutritionExamination Survey demonstrate that BMI is positively correlated with serum TSHand FT3, but not FT4, among euthyroid US adults.26.&

Reinehr T. Thyroid function in the nutritionally obese child and adolescent.Curr Opin Pediatr 2011; 23:415–420.

This review article describes four recent studies demonstrating thyroid functionabnormalities in obese children, and concludes that serum TSH elevations arelikely the consequence, rather than the cause of obesity.27. Biondi B. Thyroid and obesity: an intriguing relationship. J Clin Endocrinol

Metab 2010; 95:3614–3617.28.&&

Rotondi M, Magri F, Chiovato L. Thyroid and obesity: not a one-way interac-tion. J Clin Endocrinol Metab 2011; 96:344–346.

This commentary is a concise review of the literature regarding relationshipsbetween obesity and thyroid function, and describes several hypotheses regardingmechanisms for these relationships.29. Feldt-Rasmussen U. Thyroid and leptin. Thyroid 2007; 17:413–419.30. Ghamari-Langroudi M, Srisai D, Cone RD. Multinodal regulation of the

arcuate/paraventricular nucleus circuit by leptin. Proc Natl Acad Sci U S A2011; 108:355–360.



http://www.cdc.gov/obesity/data/adult.html

http://www.cdc.gov/obesity/data/adult.html


31. Vella KR, Ramadoss P, Lam FS, et al. NPY and MC4R signaling regulatethyroid hormone levels during fasting through both central and peripheralpathways. Cell Metab 2011; 14:780–790.

32. Araujo RL, Carvalho DP. Bioenergetic impact of tissue-specific regulation ofiodothyronine deiodinases during nutritional imbalance. J Bioenerg Biomembr2011; 43:59–65.

33. Amin A, Dhillo WS, Murphy KG. The central effects of thyroid hormones onappetite. J Thyroid Res 2011; 2011:306510.

34. Emerson CH. Anthropomorphic thyroidopathies? Thyroid 2010; 20:1195–1197.

35. Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol 2010; 316:165–171.

36. Danforth E Jr, Horton ES, O’Connell M, et al. Dietary-induced alterations inthyroid hormone metabolism during overnutrition. J Clin Invest 1979; 64:1336–1347.

37. Reinehr T, Isa A, de Sousa G, et al. Thyroid hormones and their relation toweight status. Horm Res 2008; 70:51–57.

38. Reinehr T, de Sousa G, Andler W. Hyperthyrotropinemia in obese children isreversible after weight loss and is not related to lipids. J Clin Endocrinol Metab2006; 9:3088–3091.

39. Kok P, Roelfsema F, Langendonk JG, et al. High circulating thyrotropin levelsin obese women are reduced after body weight loss induced by caloricrestriction. J Clin Endocrinol Metab 2005; 90:4659–4663.

40. Dall’Asta C, Paganelli M, Morabito A, et al. Weight loss through gastricbanding: effects on TSH and thyroid hormones in obese subjects with normalthyroid function. Obesity (Silver Spring) 2010; 18:854–857.

41. Eray E, Sari F, Ozdem S, Sari R. Relationship between thyroid volume andiodine, leptin, and adiponectin in obese women before and after weight loss.Med Princ Pract 2011; 20:43–46.



42.&

Shetty GK, Matarese G, Magkos F, et al. Leptin administration to overweightand obese subjects for 6 months increases free leptin concentrations butdoes not alter circulating hormones of the thyroid and IGF axes duringweight loss induced by a mild hypocaloric diet. Eur J Endocrinol 2011;165:249–254.

In this study, overweight and obese patients were given hypocaloric diets andrandomized to 6 months of treatment with recombinant leptin vs. placebo. Therewas no difference in thyroid function at 3 and 6 months between the leptin-treatedand placebo-treated groups.

43. Kaptein EM, Beale E, Chan LS. Thyroid hormone therapy for obesity andnonthyroidal illnesses: a systematic review. J Clin Endocrinol Metab 2009;94:3663–3675.

44. Tang MH, Chen SP, Ng SW, et al. Case series on a diversity of illicit weight-reducing agents: from the well known to the unexpected. Br J Clin Pharmacol2011; 71:250–253.

45. Baxter JD, Webb P. Thyroid hormone mimetics: potential applications inatherosclerosis, obesity and type 2 diabetes. Nat Rev Drug Discov 2009;8:308–320.

46. Ladenson PW, Kristensen JD, Ridgway EC, et al. Use of the thyroid hormoneanalogue eprotirome in statin-treated dyslipidemia. N Engl J Med 2010;362:906–916.

47.&

Antonelli A, Fallahi P, Ferrari SM, et al. 3,5-diiodo-L-thyronine increasesresting metabolic rate and reduces body weight without undesirable sideeffects. J Biol Regul Homeost Agents 2011; 25:655–660.

This is a study of a preliminary study of L-T2 administration in two healthyvolunteers. Body weight was reduced, whereas FT3, FT4, and TSH did not changesignificantly.



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Hormona tiroidea y obesidad