Original Paper
HOR MON E Horm Res Paediatr 2010;73:193197
RE SE ARCH I N DOI: 10.1159/000284361
PDIATRIC S
Thyroid Function in Obese Children and
Adolescents
Valeria Marras Maria Rosaria Casini Sabrina Pilia Daniela Carta
Patrizia Civolani Manuela Porcu Anna Paola Uccheddu Sandro Loche
Servizio di Endocrinologia Pediatrica, Ospedale Regionale per le Microcitemie, Cagliari, Italy
Key Words
Children, body mass index Insulin Obesity, children and
adolescents Thyroid function abnormalities Thyroid
hormones
Abstract
Objective: Obesity is frequently associated with modifica-
tions of thyroid size and function. We evaluated the preva-
lence of thyroid function abnormalities and the effects of
puberty and weight loss in obese children and adolescents.
Methods: We examined 468 obese children (255 girls and
213 boys aged 3.717.9 years) and 52 normal-weight age-
matched children as controls. TSH, fT3, fT4, fasting serum
insulin and glucose were measured at baseline. fT3, fT4 and
TSH were also measured after 6 months of lifestyle interven-
tion in a subset of 43 patients. Results: 109 obese children
showed abnormal circulating thyroid hormone concentra-
tions (84 had elevated fT3 levels, 15 elevated TSH, 6 elevated
fT4, 3 elevated fT3 and TSH, and 1 elevated fT3, fT4 and TSH
levels). Serum TSH and fT3 concentrations were positively
correlated with BMI-SDS. The prevalence of patients with ab-
normal thyroid hormone concentrations was similar be-
tween sexes and between prepubertal and pubertal sub-
jects. After 6 months of lifestyle intervention, thyroid hor-
mone concentrations normalized in 27 of the patients with
decreased BMI-SDS, and in 2 patients in whom BMI-SDS in-
creased. Conclusions: In obese children, an increased fT3
2010 S. Karger AG, Basel
16632818/10/07330193$26.00/0
Fax +41 61 306 12 34
E-Mail karger@karger.ch Accessible online at:
www.karger.com www.karger.com/hrp
Received: February 11, 2009
Accepted: April 2, 2009
Published online: March 3, 2010
concentration is the most frequent thyroid function abnor-
mality. Serum fT3 and TSH correlate with BMI. Moderate
weight loss frequently restores these abnormalities.
Copyright 2010 S. Karger AG, Basel
Introduction
Several endocrine abnormalities are reported in obe-
sity. Some of these abnormalities are considered to be sec-
ondary effects of obesity and are usually restored after
weight loss [1]. Recent attention has focused on the poten-
tial relationship between minor abnormalities of thyroid
function and obesity. Alterations of thyroid size and
function have been reported in some studies [2, 3], while
others have provided no evidence for an association be-
tween thyroid status and body mass index (BMI) [4].
Thyroid volume was found to be correlated with body
weight and BMI [3], a finding that may be partly attrib-
uted to the fact that TSH, which increases thyroid vol-
ume, was higher in obese as compared to non-obese sub-
jects [3]. Moderately elevated TSH and T3 levels in obese
children are a frequent finding [25], and in the majority
of the obese children these increases cannot be explained
by autoimmune thyroiditis, iodine deficiency or hypo-
thyroidism [5]. Serum T4 concentrations are usually nor-
mal. TSH and T3 levels in the upper normal range fully
normalized after weight reduction in obese children [5].
129.215.17.188 - 7/1/2013 6:18:08 PM
Dr. Sandro Loche
University of Edinburgh
Servizio di Endocrinologia Pediatrica, Ospedale Regionale per le Microcitemie
Via Jenner, IT09121 Cagliari (Italy)
Downloaded by:
Tel. +39 070 609 5536, Fax +39 070 609 5657
E-Mail sloche @ mcweb.unica.it
 The aim of this study was to evaluate the prevalence of Table 1. Baseline anthropometric and clinical characteristics of
thyroid function abnormalities in a large number of obese the study group
children and adolescents as well as their correlation with
Variable Obese children Controls p
the degree of obesity and the effect of puberty and weight
loss. Age (range/median) 3.717.9/10.25 316/12.2 NS
Male/female 213/255 24/28 NS
Prepubertal/pubertal 255/213 24/28 NA
BMI-SDS 2.6480.03 0.3280.10 <0.0001
Subjects and Methods Glycemia, mg/dl 90.880.3 87.181.08 <0.0005
Insulin, pmol/l 173.284.8 88.385.3 <0.0001
We examined 468 obese children aged 3.717.9 years (median FT3, pmol/l 6.280.05 5.480.1 <0.0001
10.25), 255 girls (116 prepubertal and 139 Tanner pubertal stage B FT4, pmol/l 17.580.3 17.180.4 NS
IIIV) and 213 boys (139 prepubertal and 74 Tanner pubertal TSH, mU/l 2.480.05 2.1780.1 NS
stage G IIIV). Subjects were consecutively recruited from chil-
dren attending the Obesity Clinic of the Pediatric Endocrine Unit
of the Regional Hospital for Microcytemia, Cagliari, during the
years 20032006, and data were recorded in a follow-up database.
A group of 52 normal-weight children, without any endocrine,
cardiovascular, gastrointestinal, or renal disorders, aged 316 dren were assessed for changes in weight and height and reviewed
years (median 12.2), 24 boys (12 prepubertal and 12 Tanner pu- for compliance to the lifestyle recommendations.
bertal stage G IIIV) and 28 girls (12 prepubertal and 16 Tanner fT3 and fT4 were determined by immunochemiluminescent
pubertal stage B IIIV) served as controls. The control children assay (Immulite 2000), and TSH was determined by immunora-
came to our observation during the same period for evaluation of diometric assay. Sensitivity of the assays was 1.5 pmol/l (fT3), 4.0
short stature or for minor non-endocrine complaints. The study pmol/l (fT4), and 0.03 mU/l (TSH), and intra- and interassay co-
was approved by the Institutional Ethical Committee and in- efficients of variation were 3.2 and 5% (fT3), 3.3 and 4.1% (fT4),
formed consent was obtained from the patients and/or from their 2.1 and 3.1% (TSH), respectively. Autoantibodies against thyroid
legal guardians. Obesity was defined by a BMI 195th percentile peroxidase (TPOab) and against thyroglobulin (hTGab) were de-
according to Italian Reference BMI charts [6]. Children with syn- tected by radioimmunoassay. Blood glucose was measured using
dromic obesity, endocrine or metabolic disorders including dia- the glucose-oxidase method. Serum insulin concentrations were
betes were excluded from the study. All subjects were measured measured using a commercial radioimmunoassay (Aldatis, Italy).
for weight, height, BMI and pubertal stage was determined by Sensitivity was 2.15 pmol/l with intra- and interassay coefficients
Tanner staging. The main clinical characteristics of the obese of variation of 2.3 and 3.5%, respectively. All reagents were pro-
subjects and controls are summarized in table 1. vided by Medical Systems Corp. (Genoa, Italy).
TSH, fT3, fT4, fasting serum glucose and insulin concentra-
tions were determined in all obese children at baseline in the Statistical Analysis
morning between 08: 00 and 09: 00 h after fasting overnight. In Normality of the data was evaluated using the Kolmogorov-
addition, thyroid ultrasound was performed in 59 randomly se- Smirnov test. Group differences were calculated by unpaired t
lected obese children with or without abnormal concentrations of test. Correlation was performed by Pearson analysis. Differences
thyroid hormones. Thyroid ultrasound was performed by a single between categorical variables were evaluated using Fishers exact
examiner using a 7.5-MHz linear electronic transducer and thy- test. BMI-SDS was derived from the Italian reference data [6].
roid echogenicity was subjectively evaluated by a conventional Data are expressed as mean 8 SE.
gray scale (from to +++ on a subjective basis). Antibodies against
thyroid peroxidase (TPOab) and human thyroglobulin (hTGab)
were determined in all patients with increased TSH and/or abnor-
mal thyroid ultrasound results. Patients with thyroiditis were ex- Results
cluded from the study.
Thyroid hormone concentrations were re-evaluated in a sub- Baseline Studies
set of 43 children (23 boys and 20 girls) after 6 months of lifestyle The main clinical and laboratory data at baseline are
intervention consisting in an educational program that involved reported in table 1. Mean TSH and fT4 were similar be-
dietary and physical activity modifications. To the child and his/
her parents, dietary guidelines, considering also the dietary hab- tween obese and controls, while mean fT3 concentra-
its and age of children, were proposed, recommending the adop- tions and mean BMI-SDS were significantly higher in the
tion of a normocaloric Mediterranean diet based on a balanced obese children than in the control group. Abnormal con-
distribution of carbohydrates (55%), proteins (15%), and lipids centrations of thyroid hormones were found in 109 obese
(30% total, with !10% saturated fat). Modifications in physical children (23.3% of the total). In particular, 84 (17.9%; 38
activity consisted in the recommendation to perform aerobic ex-
ercise 35 times/week for at least 4560 min. Finally, children boys and 46 girls) had fT3 concentrations above the up-
were advised to reduce sedentary behavior (particularly television per normal limit of 7 pmol/l, 15 (3.2%; 6 boys and 9 girls)
and video games) to ! 2 h/day. At the 6-month evaluation, chil- had elevated TSH concentrations (15 mU/l), and 6 (1.28%;
129.215.17.188 - 7/1/2013 6:18:08 PM

194 Horm Res Paediatr 2010;73:193197 Marras/Casini/Pilia/Carta/Civolani/

University of Edinburgh

Porcu/Uccheddu/Loche
Downloaded by:
 Table 2. Number of obese patients with thyroid function abnormalities according to sex and puberty
Subjects TSH
0.35 mU/l
PREP M (n = 34) 4 (11.7%)
PREP F (n = 33) 5 (15.1%)
PUB M (n = 15) 2 (13.3%)
PUB F (n = 27) 4 (14.8%)
Ranges in parentheses represent the normal values (95% confidence limits) in our laboratory.
3 boys and 3 girls) had elevated fT4 (125.7 pmol/l) (ta-
ble 2). In addition, 3 obese children (2 boys and 1 girl) had
both increased fT3 and TSH, and 1 girl presented eleva-
tion of fT3, fT4 and TSH concentrations (table 2). The
prevalence of patients with abnormalities of thyroid hor-
mone concentrations was similar between sexes and be-
tween prepubertal and pubertal subjects (table 2). Serum
TSH and fT3 concentrations were positively correlated
with BMI-SDS (TSH, r = 0.0941, p ! 0.05; fT3, r = 0.2282,
p ! 0.0001). Ultrasound examination was abnormal
in 3 out of 20 patients with abnormal thyroid function
tests and in 7 out of 39 obese children with normal thy-
roid hormone concentrations. In particular, ultrasound
showed a thyroiditis-like picture characterized by a mild
clinically undetectable glandular enlargement and a hy-
poechoic pattern (++ to +++). The presence of small thy-
roid nodules (!2 mm) was observed in 2 subjects. In these
patients, serum TPOab and hTGab were absent.
Fasting serum insulin and glucose concentrations
were significantly higher in the obese than in the control
group (table 1), and were not correlated with TSH, fT3 or
fT4.
Follow-Up Studies
43 of the 109 obese children with abnormal thyroid
hormone concentrations at baseline returned at the 6-
month follow-up visit after lifestyle intervention. Among
these children, 41 showed a reduced BMI-SDS (from 0.006
to 1.77 SDS, median 0.92). Circulating thyroid hormone
concentrations normalized in 27 of the patients who
showed a decrease of BMI-SDS, and in the 2 patients in
whom BMI-SDS increased. Thyroid hormone concentra-
tions deteriorated in 5 patients, improved but not normal-
ized in 6, and did not change in 3. We found no correlation
between the degree of weight loss (reduction in BMI-SDS)
and reduction of serum fT3 or TSH concentrations.
Thyroid Function in Obesity
fT3 fT4 fT3 + TSH fT3 +
37 pmol/l 10.325.7 pmol/l fT4 + TSH
26 (76.4%) 2 (5.8%) 2 (5.8%)
27 (81.8%) 1 (3.0%)
12 (80.0%) 1 (6.6%)
19 (70.3%) 2 (7.4%) 1 (3.7%) 1 (3.7%)
Discussion
Abnormalities of thyroid function are a frequent find-
ing in obese children. Stichel et al. [5] reported an in-
creased prevalence of elevated TSH concentrations (7.5%
above the upper normal limit of 4 U/l) in 290 obese chil-
dren, with T3 concentrations significantly higher than
the control group (but within the normal range) and nor-
mal T4. In addition, they found that T3 and TSH were
correlated with BMI-SDS. Reinehr and Andler [7] found
that peripheral thyroid hormones (T3, T4) and TSH were
moderately increased in obese children. T3, T4, and TSH
correlated with the degree of overweight but not with
leptin or lipids. They also found that a reduction in over-
weight caused a significant decrease in T3, T4, and leptin
serum concentrations, with no significant changes in
TSH [7]. In a more recent study [8] they reported that
TSH and fT3, but not fT4, were significantly increased in
obese children, and both were correlated with BMI. A
correlation between TSH and/or thyroid hormones and
BMI has been reported in adult obese subjects by some
investigators [9, 10], but not by others [4].
In the present study, abnormal thyroid hormone con-
centrations were found in 23.3% of our obese children.
These abnormalities mostly include increased fT3 (17.9%)
and TSH (3.2%) concentrations, and only occasionally in-
creased fT4 (1.3%). Similar to previous findings [8], mean
fT3 concentrations were higher in the obese than in the
normal-weight subjects of our study, and both fT3 and
TSH correlated significantly to BMI-SDS. The distribu-
tion of patients with thyroid function abnormalities was
similar between sexes and between prepubertal and pu-
bertal subjects. Although a significant correlation was
observed between TSH and BMI, its clinical relevance ap-
pears very minor. The level of significance suggests, in
fact, that less than 1% of the BMI values is explained by
129.215.17.188 - 7/1/2013 6:18:08 PM
Horm Res Paediatr 2010;73:193197 195
University of Edinburgh
Downloaded by:
TSH. This observation is in line with the concept that
thyroid hormone abnormalities are very unlikely to be
the cause of obesity.
Normalization of thyroid function abnormalities was
observed in a number of our patients whose BMI-SDS de-
creased after 6-month lifestyle intervention as well as in 2
who gained further weight. These findings support the
view that endocrine-metabolic abnormalities in obesity
might indeed improve following lifestyle intervention in-
dependently of substantial changes in BMI [11, 12].
Alterations of thyroid size have been reported in obese
adults [3]. Recently, Radetti et al. [13] have shown that thy-
roid structure can also be affected in obese children. Sim-
ilar to their findings, we have observed the presence of a
thyroiditis-like ultrasound picture in some of our pa-
tients, with either normal or abnormal thyroid hormone
concentrations. The exact nature of these structural ab-
normalities in the absence of thyroid autoantibodies and
whether or not they will normalize with weight loss is still
not known, and needs further investigation.
Little is known about the significance of thyroid func-
tion abnormalities in obesity. However, since these ab-
normalities often normalize with weight loss, they seem
to be a reversible consequence of the weight status. Weight
or nutrition-related factors may affect the regulation of
the hypothalamic-pituitary-thyroid axis [9], and the ac-
tivity of the axis may adapt to changes in the state of en-
ergy balance [14]. Under physiological conditions, thy-
roid hormones increase caloric intake and thermogenesis
and stimulate all the anabolic and catabolic pathways of
carbohydrate, protein and lipid metabolism [1518]. In
states of overfeeding the high caloric intake, as well as the
amount and composition of the ingested food increase
thermogenesis, which, if not counteracted by increased
physical activity, results in weight gain and obesity [14].
Weight gain or loss is associated with compensatory
changes in energy expenditure which are mediated by
catecholamines and thyroid hormones [18, 19]. Since thy-
roid hormones regulate both the resting energy expendi-
ture and thermogenesis, changes in thyroid hormone
concentrations may represent an adaptation process in
weight change [20]. In this regard, it has been shown that
fT3 concentrations are reduced in subjects with anorexia,
and normalize after weight gain [8, 20]. In analogy, the
increased fT3 concentration found in obese subjects nor-
malizes after weight loss [2, 7, 8, and this study]. In this
vein, it is conceivable that the increased fT3 in obesity
may contribute to energy consumption by increasing
resting energy expenditure, while decreased fT3 in ado-
lescents with anorexia allows energy sparing. Finally, in-
196 Horm Res Paediatr 2010;73:193197
creased deiodinase activity might also explain the in-
creased fT3/fT4 ratio observed in our patients.
The mechanism/s underlying the thyroid hormonal
changes in obesity are unclear. In a previous study [5],
neither iodine deficiency nor autoimmune thyroiditis
could explain the increased TSH in a group of obese chil-
dren. A correlation between insulin and insulin resistance
and thyroid hormones has been suggested [21]. However,
we found no correlation between insulin and thyroid hor-
mones or TSH. A role of leptin on thyroid function has
also been proposed [9, 10], with leptin being the link be-
tween weight status and thyroid hormones. Human leptin
concentrations are proportional to body fat mass and are
increased in obesity, and there is a synchronicity between
the secretion of leptin and TSH in children and in adults
[22], although this putative relation is not supported by all
studies [23]. Some reports suggest that leptin may modify
the hypothalamic production of TSH [24]. Leptin action
would take place at the hypothalamic level, directly or in-
directly stimulating TRH release which, in turn, stimu-
lates TSH secretion. However, a consistent relationship
between serum concentrations of leptin and thyroid hor-
mones has not been established [25, 26].
One of the limitations of our study is represented by
the fact that the control group included children with
short stature or other minor complaints. Although none
of the control children had abnormal thyroid hormone or
TSH concentrations, they may well be at risk of having
minor thyroid hormone abnormalities.
In conclusion, we have shown that abnormalities of
thyroid function are a frequent finding in obese children
and are correlated with BMI. An increased fT3 concentra-
tion is the most frequent thyroid function abnormality.
Moderate weight loss frequently restores these abnormal-
ities, and normalization was also found in patients who
did not lose weight. The pathophysiological significance
of these findings needs further studies. In addition, mod-
erately elevated levels of thyroid hormones are a conse-
quence rather than cause of being overweight, and, there-
fore, any treatment must be avoided in obese children.
Acknowledgements
Supported in part by a grant from Regione Autonoma della
Sardegna, Assessorato Igiene Sanit ed Assistenza Sociale. We are
grateful to Dr. Luigi Minerba for the statistical analysis of the
data. We are also grateful to our nursing staff (Donatella Arghit-
tu, Valentina Bianco, Patrizia Sanna) and our laboratory techni-
cians (Maria Grazia Contini, Danilo Mosinu, Teresa Trogu) for
their invaluable contribution and support.
129.215.17.188 - 7/1/2013 6:18:08 PM
Marras/Casini/Pilia/Carta/Civolani/
University of Edinburgh
Porcu/Uccheddu/Loche
Downloaded by:
 References
1 Kokkoris P, Pi-Sunyer FX: Obesity and endo-
crine disease. Endocrinol Metab Clin North
Am 2003;32:895914.
2 Reinehr T, De Sousa G, Andler W: Hyperthy-
rotropinemia in obese children is reversible
after weight loss and is not related to lipids. J
Clin Endocrinol Metab 2006;91:30883091.
3 Sari R, Balci MK, Altunbas H, Karayalcin U:
The effect of body weight and weight loss on
thyroid volume and function in obese wom-
en. Clin Endocrinol 2003;59:258262.
4 Manji N, Boelaert K, Sheppard MC, Holdert
RL, Gough SC, Franklyn JA: Lack of associa-
tion between serum TSH or free T4 and body
mass index in euthyroid subjects. Clin Endo-
crinol 2006;64:125128.
5 Stichel H, lAllemand D, Grueters A: Thyroid
function and obesity in children and adoles-
cents. Horm Res 2000;54:1419.
6 Cacciari E, Milani S, Balsamo A, Spada E,
Bona G, Cavallo L, Cerutti F, Gargantini L,
Greggio N, Tonini G, Cicognani A: Italian
cross-sectional growth charts for height,
weight and BMI (220 years). J Endocrinol
Invest 2006;7:581593.
7 Reinehr T, Andler W: Thyroid hormones be-
fore and after weight loss in obesity. Arch Dis
Child 2002;87:320323.
8 Reinehr T, Isa A, De Sousa G, Dieffenbach R,
Andler W: Thyroid hormones and their rela-
tion to weight status. Horm Res 2008;70:51
57.
9 Nyrnes A, Jorde R, Sundsfjord J: Serum TSH
is positively associated with BMI. Int J Obes
2006;30:100105.
10 Iacobellis G, Ribaudo MC, Zappaterrano A,
Iannucci CV, Leonetti F: Relationship of thy-
roid function with body mass index, leptin,
insulin sensitivity and adiponectin in euthy-
roid obese women. Clin Endocrinol 2005;62:
487491.
Thyroid Function in Obesity
11 Cambuli VM, Musiu MC, Incani M, Paderi
M, Serpe R, Marras V, Cossu E, Cavallo MG,
Mariotti S, Loche S, Baroni MG: Assessment
of adiponectin and leptin as biomarkers of
positive metabolic outcomes after lifestyle
intervention in overweight and obese chil-
dren. J Clin Endocrinol Metab 2008; 93:
30513057.
12 Bell LM, Watts K, Siafarikas A, Thompson
A, Ratnam N, Bulsara M, Finn J, ODriscoll
G, Green DJ, Jones TW, Davis EA: Exercise
alone reduces insulin resistance in obese
children independently of changes in body
composition. J Clin Endocrinol Metab 2007;
92:42304235.
13 Radetti G, Kleon W, Buzi F, Crivellaro C,
Pappalardo L, di Iorgi N, Maghnie M: Thy-
roid function and structure are affected in
childhood obesity. J Clin Endocrinol Metab
2008;93:47494754.
14 Penny T, Alevizaki M: Obesity and thyroid.
Obe Metab 2007;3:116130.
15 Silva JE: Thermogenic mechanism and their
hormonal regulation. Physiol Rev 2006; 86:
435464.
16 Bianco AC, Maia AL, da Silva WS, Christof-
folete MA: Adaptive activation of thyroid
hormone and energy expenditure. Biosci
Rep 2005;25:191208.
17 Chidakel A, Mentuccia D, Celi FS: Periph-
eral metabolism of thyroid hormone and
glucose homeostasis. Thyroid 2005; 15: 899
903.
18 Rosenbaum M, Hirsch J, Murphy E, Leibel R:
Effects of changes in body weight on carbo-
hydrate metabolism, catecholamine excre-
tion, and thyroid function. Am J Clin Nutr
2007;71:14211432.
Horm Res Paediatr 2010;73:193197
19 Snitker S, Macdonald I, Ravussin E, Astrup
A: The sympathetic nervous system and obe-
sity: role in aetiology and treatment. Obes
Rev 2000;1:515.
20 Onur S, Haas V, Bosy-Westphal A, Hauer M,
Paul T, Nutzinger D, Klein H, Muller MJ: L-
Tri-iodothyronine is a major determinant of
resting energy expenditure in underweight
patients with anorexia nervosa and during
weight gain. Eur J Endocrinol 2005;152:179
184.
21 Chuub SAP, Davis WA, Davis TME: Interac-
tions between thyroid function, insulin sen-
sitivity and serum lipid concentrations: The
Fremantle Diabetes Study. J Clin Endocrinol
Metab 2005;88:27142718.
22 Ghizzoni L, Mastorakos G, Ziveri M, Furlini
M, Solazzi A, Vottero A, Bernasconi S: Inter-
actions of leptin and thyrotropin 24-h secre-
tory profiles in short normal children. J Clin
Endocrinol Metab 2001;86:20652072.
23 Sceenan S, Caro JF, Refetoff S: Thyroid dys-
function is not associated with alterations in
serum leptin levels. Thyroid 1997; 7: 407
409.
24 Costa da Veiga M, de Jesus Oliveira K, Curty
FH, Pazos de Moura CC: Thyroid hormones
modulate the endocrine and autocrine/para-
crine actions of leptin on thyrotropin secre-
tion. J Endocrinol 2004;183:243247.
25 Kok P, Roelfsema F, Langendonk JG, Frolich
M, Burggraaf J, Meinders AE, Pijl H: High
circulating thyrotropin levels in obese wom-
en are reduced after body weight loss in-
duced by caloric restriction. J Clin Endocri-
nol Metab 2005;90:46594663.
26 Ortiga-Carvalho TM, Oliveira KJ, Soares
BA, Pazos Moura CC: The role of leptin in
the regulation of TSH secretion in the fed
state: in vivo and in vitro studies. J Endocri-
nol 2002;174:121125.
129.215.17.188 - 7/1/2013 6:18:08 PM
197
University of Edinburgh
Downloaded by: