1. REVIEW
CURRENT
OPINION Thyroid hormone and obesity
Elizabeth N. Pearce
Purpose of review
To review several of the most recent and most important clinical studies regarding the effects of thyroid
treatments on weight change, associations between thyroid status and weight, and the effects of obesity
and weight change on thyroid function.
Recent findings
Weight decreases following treatment for hypothyroidism. However, following levothyroxine treatment for
overt hypothyroidism, weight loss appears to be modest and mediated primarily by loss of water weight
rather than fat. There is conflicting evidence about the effects of thyroidectomy on weight. In large
population studies, even among euthyroid individuals, serum thyroid-stimulating hormone is typically
positively associated with body weight and BMI. Both serum thyroid-stimulating hormone and T3 are
typically increased in obese compared with lean individuals, an effect likely mediated, at least in part, by
leptin. Finally, there is no consistent evidence that thyroid hormone treatment induces weight loss in obese
euthyroid 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 modest weight loss following initiation of levothyr-
Both thyroid dysfunction and obesity are highly oxine (L-T4) therapy, but all had returned to their
prevalent in the general population. National data weights before treatment by 12–24 months. Eighty-
suggest that hypothyroidism is present in 4.6% of seven hyperthyroid patients had lost a mean of 16%
the US population, and hyperthyroidism in 1.3% of their body weights before hyperthyroidism at the
[1]. Obesity rates have climbed in the USA and time of presentation; 2 years following initiation of
worldwide over the last several decades; more than treatment, they had regained and slightly exceeded
30% of the US population is now classified as obese their baseline weight. A recent study of weight
[2]. This review focuses on recent clinical studies change following treatment of thyroid dysfunction
regarding the effects of thyroid treatments on in 57 hyperthyroid and 29 hypothyroid children
weight change, associations between thyroid status similarly found that weight loss was minimal
and body weight, and the effects of obesity and following treatment for hypothyroidism (mean
weight change on thyroid function. 0.3 kg by the first follow-up visit) [5]. However, there
was an average 7.1 kg gain in weight by the second
follow-up visit following initiation of treatment
WEIGHT CHANGE AFTER TREATMENT FOR for hyperthyroidism.
THYROID DYSFUNCTION Weight change was followed for 1 year in
Thyroid hormone increases the basal metabolic 12 overtly hypothyroid individuals [mean baseline
rate [3]. Patients with overt hypothyroidism often
present with a history of weight gain, and those with
Boston University School of Medicine, Boston, Massachusetts, USA
hyperthyroidism frequently present with weight
Correspondence to Elizabeth N. Pearce, MD, MSc, Boston University
loss. However, the degree of weight change with School of Medicine, Section of Endocrinology, Diabetes, and Nutrition,
thyroid dysfunction, and the effects of treatment 88 East Newton Street, Evans 201, Boston, MA 02118, USA. Tel: +1
on body weight are surprisingly poorly understood. 617 414 1348; fax: +1 617 638 7221; e-mail: elizabeth.pearce@bmc.
A 1984 study described weight change following org
initiation of treatment for thyroid dysfunction [4]. Curr Opin Endocrinol Diabetes Obes 2012, 19:408–413
Nine of 18 hypothyroid patients experienced a DOI:10.1097/MED.0b013e328355cd6c
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2. Thyroid hormone and obesity Pearce
(on average 1.8 kg), whereas L-T4 treatment was not
KEY POINTS associated with significant weight change. On the
Body weight increases following hyperthyroidism basis of DEXA scans, there was a nearly significant
treatment and modestly decreases following decrease in fat mass of 5.3% (P ¼ 0.052) with
hypothyroidism treatment. L-T3 treatment.
In population studies, serum TSH (within the normal
range) is positively associated with baseline BMI and OBESITY AND THYROID SURGERY
with weight change over time.
A large multicenter retrospective study of 18 825
Serum TSH and free triiodothyronone (FT3) are both patients who underwent total thyroidectomy
increased in obese individuals; levels normalize with recently demonstrated that the duration of surgery
weight loss.
is longer in obese and overweight patients than in
There is no clear effect of thyroid hormone treatment on lean patients, and surgical complications are more
weight loss in obese euthyroid individuals, however, frequent [10]. However, the authors concluded that
there may be a future role for thyroid hormone these differences did not seem to impact on duration
analogues as an obesity treatment. of hospital stay, and therefore might not be clin-
ically meaningful. A retrospective study compared
weight change in 102 thyroid cancer patients fol-
thyroid-stimulating hormone (TSH) 102 mIU/L] fol- lowing thyroidectomy with weight change in euthy-
lowing initiation of L-T4 treatment, and compared roid patients with benign nodules or goiter whose
with 10 euthyroid controls [6 ]. At 1 year (mean
thyroids were not resected [11 ]. There was no differ-
serum TSH 2.2 mIU/L), mean weight had decreased ence in weight or BMI change between the two
significantly, from 83.7 to 79.4 kg (P ¼ 0.002). Dual groups at a median 5.9 years of follow-up. In another
energy X-ray absorptiometry (DEXA) scans demon- retrospective study, 120 patients with achievement
strated that the weight loss following initiation of of euthyroidism on thyroid hormone therapy 1 year
L-T4 was due to decreases in lean mass, with no following total thyroidectomy were compared with
significant changes in either bone mass or fat mass; age, gender, height, menopausal status, and baseline
the authors concluded that weight loss after L-T4 weight-matched treated hypothyroid individuals
treatment for hypothyroidism is mediated primarily
who did not undergo thyroidectomy [12 ]. In con-
by loss of excess body water. trast to the previous study, at 1 year, the thyroidec-
Among hypothyroid patients, the degree of TSH tomized patients had experienced significantly
suppression achieved by L-T4 therapy does not more weight gain (3.1 vs. 2.2 kg, P ¼ 0.004) than
appear to strongly influence body weight. In a pro- the matched controls.
spective study examining the effects of treating
hypothyroid patients to a TSH goal of 0.4–2 mIU/L
compared with 2–4 mIU/L, the patients treated to ASSOCIATIONS BETWEEN THYROID
the lower TSH target had higher resting energy STATUS AND WEIGHT AND WEIGHT
expenditure, but there was no difference in lean CHANGE
or fat body mass or percentage body fat between the Recent population studies have examined the
groups at 1 year [7 ]. Polotsky et al. [8 ] retrospec- effects of thyroid status on weight and on weight
tively examined changes in body weight among change over time. In a cross-sectional study of 778
153 athyreotic thyroid cancer survivors treated euthyroid (serum TSH 0.4–5 mIU/L) Spanish adults,
with TSH-suppressive L-T4 doses (median serum serum TSH, and BMI were positively correlated, and
TSH 0.05 mIU/L) for up to 5 years. There was a individuals with serum TSH levels in the highest
median 3.2% weight gain at 3–5 years of follow- tertile had the highest BMI values [13]. However,
up, despite ongoing iatrogenic hyperthyroidism, when this cohort was restricted to a subgroup of 375
similar to or higher than previously published individuals without detectable serum thyroperoxi-
euthyroid population values. dase antibodies, these relationships were no longer
A blinded cross-over study examined the effects observed. Another Spanish study examined longi-
of liothyronine (L-T3) compared to L-T4 treatment tudinal weight change in relation to baseline TSH
in 14 adults with primary hypothyroidism who were levels in 784 euthyroid adults followed for 6 years
already on L-T4 therapy [9 ]. Patients were treated [14]. At baseline, TSH, FT3, and free thyroxine (FT4)
with L-T3 or L-T4 taken three times daily, in order to levels did not differ in obese and nonobese individ-
achieve a serum TSH 0.5–1.5 mIU/L at three con- uals. Increases in FT3 were positively correlated with
secutive biweekly visits. The L-T3 treatment (for a increases in weight over the follow-up period,
mean of 19 weeks) resulted in significant weight loss and the authors suggested that increases in thyroid
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3. Thyroid
hormone were a consequence, rather than a gastric bypass surgery. At baseline, TSH receptor
cause, of interval weight gain. In the Norwegian and thyroid hormone receptora1 expression were
Nord-Trøndelag health cohort study, associations decreased in both visceral and subcutaneous fat
between baseline thyroid status, weight, and BMI deposits in obese individuals, and did not differ
were investigated in 15 020 euthyroid (serum TSH by glucose tolerance. Following a 33% decrease in
0.5–3.5 mIU/L) individuals over a mean follow-up BMI at 1 year after bariatric surgery, the subcu-
of 10.5 years [15 ]. In women, for every 1 mIU/L taneous fat expression of TSH receptor increased
increase in baseline serum TSH, there was a 0.9 kg by 150% and the expression of thyroid hormone
increase in weight and a 0.3 kg/m2 increase in BMI receptora1 increased by 70%.
over the follow-up period, whereas in men, for each
1 mIU/L TSH increment, weight increased by 0.8 kg
and BMI by 0.2 kg/m2. EFFECTS OF OBESITY ON THYROID
STATUS
The relationship between thyroid status and obesity
EFFECTS OF THYROID STATUS ON FAT is likely to be bidirectional, with hypothyroidism
DISTRIBUTION affecting weight and BMI, but obesity also influenc-
Limited data suggest that thyroid status may influ- ing thyroid function. Thyroid function abnormal-
ence adipose tissue distribution as well as the overall ities are highly prevalent in obese individuals:
amount of adipose tissue present. Both thyroid hor- among 783 consecutive obese patients seen for bari-
mone and visceral fat (as quantified by abdominal atric surgery evaluation, 18.1% had elevated serum
ultrasound) were measured in 174 euthyroid prepu- TSH [21]. In 1976, Bray et al. [22] demonstrated a
bertal children [16]. In cross-sectional analyses positive correlation between T3, but not T4, and
adjusted for age, BMI, and total body fat, FT4 body weight. This observation has since been con-
was independently and inversely associated firmed in multiple studies [23,24 ]. Most recently, in
with visceral fat stores. In a cross-sectional study a cross-sectional analysis of data from the National
of euthyroid adults with known vascular disease, Health and Nutrition Examination Survey 2007–
higher serum TSH was associated with increased 2008, among 3114 euthyroid adults without a
visceral fat thickness, although only among indi- history of thyroid disease, BMI and waist circum-
viduals aged 67–80 years. Serum TSH was not ference were positively associated with serum TSH
associated with either weight or BMI. A previous and FT3, but not FT4 [25 ]. These relationships are
study in 303 healthy volunteers had demonstrated present in children as well as in adults. A recent
that the amount of subcutaneous fat and the review describes four studies in which childhood
subcutaneous-to-visceral fat ratio were inversely obesity was associated with moderate serum TSH
correlated with free T4 levels and that TSH elevations [26 ]. In two of those studies, weight loss
was positively correlated with subcutaneous fat led to normalization of serum TSH. Another recent
thickness [17]. review concluded that 7–23% of obese children
The effects of thyroid status on fat distribution exhibit serum TSH elevations with normal or
may be explained by differential TSH receptor and/ slightly elevated FT3 levels [24 ]. In obese patients
or thyroid hormone receptor expression in different with mild TSH elevations, it may be difficult to
fat depots, and receptor expression seems to differ in distinguish between true subclinical hypothyroid-
obese compared with lean individuals. TSH receptor ism and physiologic alterations in thyroid function;
expression was recently measured in subcutaneous however, individuals with undetectable thyroid
fat samples from 120 euthyroid patients [18]. Sub- antibodies and high-normal serum T3 levels are
cutaneous fat TSH receptor expression was found to unlikely to have true underlying thyroid failure
be increased in individuals with higher BMI. A [27,28 ].
previous study had demonstrated that thyroid hor- The reason for elevations in both TSH and T3 in
mone receptora and thyroid hormone receptora1 obese individuals is not entirely clear. However, it is
expression is increased in subcutaneous compared likely that leptin plays a role in regulating this
with visceral fat deposits in obese, but not normal- process. Leptin, secreted by adipose cells, serves as
weight patients [19]. Finally, Nannipieri et al. [20] a signal to the central nervous system regarding
measured TSH receptor and thyroid hormone recep- energy balance and the presence of energy stores.
tora1 expression in subcutaneous and visceral fat in Leptin promotes thyrotropin releasing hormone
obese and lean patients, and then prospectively gene expression directly in the paraventricular
measured TSH receptor and thyroid hormone recep- nucleus, ultimately stimulating TSH release [29–
tora1 expression in subcutaneous fat samples from a 31]. Leptin may also increase T4 to T3 conversion
subset of 27 obese patients before and 1 year after by deiodinases in a tissue-specific fashion [32,33]. In
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4. Thyroid hormone and obesity Pearce
addition to the effects of leptin, it has also been study, 24 obese and overweight adults were
postulated that thyroid function abnormalities treated with hypocaloric diets and randomized to
in obesity may be related to peripheral thyroid receive recombinant leptin therapy vs. placebo for
hormone resistance, altered TSH bioactivity, or 6 months [42 ]. Leptin treatment was not associated
may constitute an adaptive process designed to with differences in thyroid function as compared
increase resting energy expenditure [34,35]. with the placebo-treated controls, suggesting that
leptin alone may not mediate changes in thyroid
function in response to weight loss induced
THYROID FUNCTION CHANGES AFTER by dieting.
WEIGHT CHANGE
In 1979, Danforth et al. [36] demonstrated that
short-term and long-term overnutrition in human THYROID HORMONE AND THYROID
volunteers resulted in increased T3, but not T4, HORMONE ANALOGUES FOR WEIGHT
production, and that serum T3 decreased with LOSS IN EUTHYROID INDIVIDUALS
caloric restriction. More recent observational stud- A systematic review by Kaptein et al. [43] identified
ies have demonstrated alterations in thyroid func- 14 studies describing the effects of T3 or T3/T4
tion following weight loss in obese individuals, treatment on weight loss in euthyroid individuals
regardless of the way in which weight loss is during caloric deprivation. Sample sizes were small,
achieved. In a study comparing adolescent girls ranging from only five to 12 in treated groups.
with normal weight, obesity, or anorexia nervosa, Thyroid hormone treatment reduced serum TSH
TSH and FT3 were significantly lower in the ano- and T4 concentrations, resulting in subclinical
rexic girls and significantly higher in the obese hyperthyroidism, and there was no consistent effect
girls than the normal-weight girls [37]. Following on weight loss across studies.
weight gain of more than 5%, TSH and FT3 Despite the lack of clear efficacy of thyroid
increased in the anorexic girls, and following more hormone for weight loss in euthyroid individuals,
than 5% weight loss, TSH and FT3 decreased in the thyroid hormone has been used illegally in dietary
obese girls. In another pediatric study, 246 obese supplements marketed for weight loss in several
children attending a weight loss program were countries. A recent study from Hong Kong noted
followed for 1 year [38]. At baseline, serum TSH the presence of illicit thyroid hormone in 20 of 66
and FT3 were higher in the obese children than in cases of weight loss products resulting in poisoning
normal-weight controls, but FT4 did not differ. At between 2004 and 2009 [44]. Nine of these patients
1 year, there was a significant decrease in TSH and presented with overt thyrotoxicosis, and one had
FT3 in the 49 children who had achieved signifi- thyrotoxic periodic paralysis.
cant weight loss, whereas there was no change in Several thyroid hormone analogues are cur-
serum TSH in the 197 obese children who did not rently in development. Most of the thyroid
lose weight. hormone’s effect on bone and heart are mediated
In a prospective study of 11 obese premeno- by a isoforms of the thyroid hormone receptor,
pausal women, thyroid function was assessed before whereas effects on the liver, such as lipid lowering,
and after 50% excess weight loss was achieved by are mediated primarily by thyroid hormone recep-
diet [39]. At baseline, serum TSH was higher than in torb. Selective thyroid hormone receptorb agonists,
normal-weight controls, and weight loss was associ- therefore, are appealing as medications for hyper-
ated with reductions in serum TSH and FT3. The lipidemia or obesity that might selectively lower
decline of serum TSH correlated with decreases in lipids or weight without bone or cardiac toxicity
serum leptin. In a retrospective study of 258 euthy- [45]. Weight loss has been observed with some
roid morbidly obese patients who underwent gastric of these compounds in animal studies. However
banding, thyroid function was ascertained before weight loss with thyroid mimetic treatment has
and up to 24 months after the bariatric surgery not yet been reported in clinical trials [45,46],
[40]. Following weight loss, FT3 levels decreased despite improvements in lipid parameters in
and FT4 increased, without significant changes in patients treated with the thyroid hormone analogue
serum TSH. In a prospective study of 98 premeno- eprotirome [46], and knockout studies suggest that
pausal obese women, thyroid function was studied regulation of basal metabolic rate is more dependent
before and after 6 months of treatment with sibutr- on thyroid hormone receptora than thyroid
amine or orlistat [41]. At 6 months, although hormone receptorb [45]. One recent preliminary
BMI and leptin levels had decreased significantly, study of treatment with 3,5-diiodo-L-thyronine in
there were no significant changes in TSH, FT3, two euthyroid human volunteers did demonstrate a
or FT4 values. In another recent prospective significant 4% decrease in body weight without
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5. Thyroid
8. Polotsky HN, Brokhin M, Omry G, et al. Iatrogenic hyperthyroidism does not
changes in serum FT3, FT4, or TSH; changes in fat promote weight loss or prevent ageing-related increases in body mass in
mass were not evaluated [47 ]. thyroid cancer survivors. Clin Endocrinol (Oxf) 2012; 76:582–585.
In this retrospective study, iatrogenic hyperthyroidism in thyroid cancer survivors
over up to a 5-year follow-up period was associated with weight gain similar, or
even greater than that seen in euthyroid population controls.
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3474.
thyroid status are complex. Weight decreases fol- In this blinded cross-over clinical trial, carefully titrated L-T3 therapy was asso-
lowing treatment for hypothyroidism. However, ciated with weight loss, whereas L-T4 therapy was not.
10. Buerba R, Roman SA, Sosa JA. Thyroidectomy and parathyroidectomy in
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11. Weinreb JT, Yang Y, Braunstein GD. Do patients gain weight after thyroi-
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A single recent study suggests that carefully titrated This observational study found no difference in weight change in thyroid cancer
patients following total thyroidectomy compared with euthyroid controls.
L-T3 treatment in hypothyroid patients may cause 12. Jonklaas J, Nsouli-Maktabi H. Weight changes in euthyroid patients under-
greater weight loss than treatment with L-T4. There going thyroidectomy. Thyroid 2011; 21:1343–1351.
This observational study found that patient who had undergone a thyroidectomy in
is conflicting evidence about the effects of thyroid- the previous year gained more weight than matched hypothyroid controls who had
ectomy on weight. In large population studies, even not undergone thyroid surgery.
´
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No funding was received for this work. 18. Lu S, Guan Q, Liu Y, et al. Role of extrathyroidal TSHR expression in adipocyte
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Conflicts of interest 19. Ortega FJ, Moreno-Navarrete JM, Ribas V, et al. Subcutaneous fat shows
There are no conflicts of interest. higher 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 and
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iodine, leptin, and adiponectin in obese women before and after weight loss. volunteers. Body weight was reduced, whereas FT3, FT4, and TSH did not change
Med Princ Pract 2011; 20:43–46. significantly.
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