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Received: 5 July 2017    Revised: 18 September 2017    Accepted: 8 October 2017

DOI: 10.1111/cen.13493

ORIGINAL ARTICLE

Weight gain after treatment of Graves’ disease in children

Guy Todd Alonso | Shona Rabon | Perrin C. White

UT Southwestern Medical Center, Dallas, TX,

USA
Correspondence
Perrin C. White, Department of Pediatrics,
UT Southwestern Medical Center, Dallas, TX,
USA. Email: perrin.white@utsouthwestern.edu
Present addresses
Guy Todd Alonso, Barbara Davis
Center, University of Colorado, Denver, CO,
USA
Shona Rabon, Specially for Children, Austin,
TX, USA
Summary
Objective: The frequency of and risk factors for weight gain in children treated for
Graves’ disease have not been described. We evaluated change in BMI-­Z score and
predictors of weight gain in this population.
Design: Retrospective review of data from January 2000 to July 2011.
Patients: Two hundred and twenty two children and adolescents with Graves’ disease
(ages 2-­18 years) evaluated following radioactive iodine administration (RAI); (n = 101),
thyroidectomy (n = 9) and initiation of medical therapy (n = 112).
Measurements: Changes in body mass index Z score over 12 months (ΔBMI-­Z0-12).
Results: All treatment groups in each gender and race increased BMI-­Z (median
ΔBMI-­Z0-12 was positive). T3 levels following RAI (P = .04) and weight lost at the time
of administration (P = .02) in the RAI group and free T4 levels in the medical therapy
group (P = .03) were positively correlated with ΔBMI-­Z0-12. Race was a significant pre-
dictor only in the medical therapy group (P = .01). Age negatively correlated with
ΔBMI-­Z0-12 in both the RAI (P < .001) and medical therapy groups (P = .003). Gender,
maximum TSH in the 12 months after RAI and initial dose of LT4 replacement did not
correlate with ΔBMI-­Z0-12. The prevalence of overweight and obesity in our cohort
was similar to US children.
Conclusions: Weight gain during treatment for Graves’ disease is common in children,
and many children become overweight or obese during treatment. Risk factors include
greater degree of hyperthyroidism at presentation and time of RAI and younger age.
Weight lost upon presentation may also predict greater weight gain. Control of subse-
quent hypothyroidism does not appear to affect weight gain.

KEYWORDS
body mass index, levothyroxine, radioactive iodine ablation

1 | INTRODUCTION hyperthyroidism are likely to have lost more weight. Therefore, it

Weight gain in adults treated for hyperthyroidism is common.1-7
Weight eventually exceeds premorbid weight in up to 79%, although
2,3
studies relying on patients’ recall may be prone to bias.
6
Reports of weight loss upon presentation, pre-­existing obe-
sity6 and lower BMI at presentation8 positively correlate with
weight gain during treatment for hyperthyroidism. Additionally,
the degree of hyperthyroidism at diagnosis also predicts subse-
quent weight gain,7,9,10 perhaps because patients with more severe
appears that much of the weight gained is actually a return towards
premorbid weight.
The effect of gender on weight gain is unclear,6-8 and only one
study found race to be a factor,10 with African-­Americans and
Hispanics at risk of greater weight gain than Caucasians.
Information about weight gain during treatment of hyperthyroid-
ism in children and adolescents is limited,11-13 and no studies identify
predictors of weight gain in this population. In one study, patients pre-
dominantly receiving medical therapy had significant body mass index

66  |  wileyonlinelibrary.com/journal/cen
© 2017 John Wiley & Sons Ltd Clinical Endocrinology. 2018;88:66–70.
ALONSO et al.
Z score (BMI-­Z) increases evident by 3 months after presentation that
13
persisted throughout a 36-­month follow-­up period.
Therefore, we performed a cohort study of children and adoles-
cents with Graves’ hyperthyroidism to define weight gain risk fac-
tors and the magnitude of BMI-­Z change over the first 12 months
(ΔBMI-­Z0-12) after radioactive iodine treatment (RAI), thyroidectomy
or after initiation of medical therapy.
2 | MATERIALS AND METHODS
This study was approved by the Institutional Review Board at The
University of Texas Southwestern Medical Center and conducted in
accordance with the US Federal Policy for the Protection of Human
Subjects.
2.1 | Subjects
Charts of children ages 2-­18 years diagnosed with hyperthyroidism
at Children’s Medical Center Dallas between January 2000 and July
2011 were reviewed. The billing database was searched for ICD9
codes 242.xx (where x is any digit). Graves’ disease criteria included
elevated free T4 and/or total T3 and suppressed TSH along with posi-
tive thyroid stimulating immunoglobulin, thyrotropin receptor anti-
bodies or 2 clinical signs suggestive of Graves’ disease (exophthalmos,
tachycardia, hypertension, goitre and tremor). Patients with evidence
of autonomously functioning nodules, subacute thyroiditis, follow-­up
duration less than 1 year, obviously incomplete medical records or
other conditions expected to affect weight gain (3 simultaneously di-
agnosed with Graves’ disease and type 1 diabetes, 1 each with Seckel
and Cornelia de Lange syndromes) were excluded.
We identified 222 eligible patients and defined 3 groups by treat-
ment modality: eventual RAI (n = 101), eventual thyroidectomy (n = 9)
or medical therapy alone (n = 112). We collected data at diagnosis and
over the 12 months following either diagnosis (medical therapy group)
or the definitive procedure (RAI and thyroidectomy groups). Six pa-
tients who later received RAI and 2 who later underwent thyroidec-
tomy did not have adequate clinical data for the 12 months following
the procedure and were therefore included in the medical therapy
group. One in the thyroidectomy group had an inadequate response
to RAI 12 months prior to her thyroidectomy.
An analysis of success of antithyroid drug therapy in this popula-
tion has been previously published14.
2.2 | Data collection
We collected demographic data; report of weight lost or gained at
diagnosis; height, weight, body mass index, dose of methimazole, pro-
pylthiouracil (PTU) or levothyroxine at each clinic visit; TSH, free T4,
total T4, total T3 levels at each blood draw; the dates of cessation and
of starting methimazole, PTU or levothyroxine therapy.
To evaluate the timing of BMI-­Z change during the first year
­following definitive therapy (RAI and thyroidectomy groups), data
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were collected for 5 time points: date of definitive therapy, date of
maximum TSH and dates of thyroid function testing closest to 90
(median 91, interquartile range [IQR] 81-­103), 180 (182, 167-­205)
and 365 (375, 345-­405) days following RAI or thyroidectomy. When
weight and height were not available for the same date as laboratory
testing, weight and height were interpolated using the values from the
clinic visits directly before and after the date in question.
For the medical therapy group, data were collected at diagnosis
and the date of thyroid function testing closest to 365 days (375, 349-­
397) following diagnosis.
2.3 | Statistical analysis
We calculated BMI-­Z using the SAS program for the 2000 Centers for
Disease Control growth charts15, which are still the accepted stand-
ard for children aged 2-­19 years. Statistical analyses were performed
on Statview 5.0 (SAS Institute, Inc, Cary, NC, USA). Spearman rank
correlations were calculated between the change in BMI-­Z over the
12-­month period following RAI, thyroidectomy or initiation of medical
therapy for each group (ΔBMI-­Z0-12) and T3, free T4, TSH, age at the
beginning of the 12-­month period, amount of weight reported lost
or gained at initial presentation of Graves’ disease, the highest TSH
value during the first 12 months after RAI or thyroidectomy and start-
ing dose of levothyroxine (LT4). ΔBMI-­Z0-12 scores were not normally
distributed, and therefore, the associations between ΔBMI-­Z0-12 and
race and between ΔBMI-­Z0-12 and gender were tested with Kruskal-­
Wallis and Mann-­Whitney U tests, respectively.
3 | RESULTS
Median age was 14.7 years (IQR 12.8-­16.4) in the RAI group,
12.6 years (8.1-­15.3) in the thyroidectomy group and 12.3 years
(8.4-­14.4) in the medical treatment group, with a significant between-­
group difference in age by Kruskal-­Wallis testing (P < .001).
Median ΔBMI-­Z0-12 was 0.64 (0.28-­1.16) and was positive across
all treatment groups in each gender and race (Tables 1 and 2). There
were no differences in ΔBMI-­Z0-12 between groups. Differences be-
tween genders were not significant in any of the groups. In the RAI
group, BMI-­Z was greater at the time of RAI administration than at
diagnosis and greater 90, 180 and 365 days after than at RAI admin-
istration, although not significantly different between any of the fol-
low-­up times. Table 3 displays weight, BMI and BMI-­Z for the RAI
group at diagnosis, RAI administration and 1 year later; patients who
did or did not become hypothyroid after ablation are considered
separately.
The magnitude of reported weight change between the premorbid
state and at diagnosis was only recorded in 63% of patients’ charts
(Table 1) and was predictive of ΔBMI-­Z0-12 in the RAI group but not
the other groups or in all patients combined.
Median time from diagnosis to RAI was 202 (56-­681) days. Age
at diagnosis negatively correlated with longer time from diagnosis
to RAI (rho = −0.32, P < .001), whereas race and ethnicity were not
68       | ALONSO et al.

T A B L E   1   Correlation between ΔBMI-­Z0-12 and predictors

Group

All patients Medical therapy RAI recipients

Independent variable rho n P rho n P rho n P

T3 0.19 159 .02 0.20 74 NS 0.22 84 .04

fT4 0.18 181 .01 0.22 91 .03 0.15 89 NS
TSH −0.12 209 NS −0.12 109 NS −0.16 92 NS
Age −0.32 213 <.001 −0.28 112 .003 −0.37 92 <.001
Weight lost at dx 0.16 130 NS 0.07 69 NS 0.33 54 .02

ΔBMI-­Z0-12, change in BMI-­Z score over the defined 12-­month period; T3, triiodothyronine; fT4, free thyroxine; TSH, thyroid stimulating hormone; Weight
lost at dx, reported weight lost at diagnosis; rho, Spearman’s rho.

T A B L E   2   ΔBMI-­Z0-12 by racial group

Group (n) Caucasian Hispanic African-­American Other P

Median IQR (n) Median IQR (n) Median IQR (n) Median IQR (n)
All patients (213) 0.45 0.20-­0.90 (70) 0.66 0.26-­1.27 (87) .70 0.38-­1.16 (34) 0.27 0.13-­0.69 (21) NS
Medical (112) 0.38 0.19-­0.72 (40) 0.69 0.31-­1.22 (43) 1.00 0.78-­1.33 (16) 0.37 0.17-­0.99 (12) .01
RAI (101) 0.27 0.19-­0.99 (25) 0.61 0.21-­1.00 (40) .52 0.33-­0.67 (18) 0.24 0.10-­0.52 (9) NS

P values from Kruskal-­Wallis tests. A 1 SD change in BMI-­Z for boys and girls at the 50th percentile for height at 13 y, the median age in the study, is
8.29 kg and 8.12 kg, respectively. Seventeen patients were missing BMI data at the 12-­month time mark.

T A B L E   3   Interval changes in weight, BMI and BMI-­Z in the RAI group

2. At RAI
Group (N)a Median (IQR) 1. At diagnosis administration Change 2-­1 3. 1 y post-­RAI Change 3-­2

A (86) Weight, kg 48.7 (38.7-­60.8) 58.7 (46.2-­66.9) 3.8 (0.2-­11.3) 65.7 (52.9-­77.7) 10.0 (5.6-­14.1)*
BMI 19.7 (16.9-­23.8) 22.6 (19.0-­25.8) 1.2 (0-­2.7) 25.2 (21.0-­29.8) 3.3 (1.7-­5.2)**
BMIz 0.31 (-­0.61-­1.15) 0.64 (-­0.15-­1.41) 0.16 (-­0.04-­0.51) 1.25 (0.2-­1.80) 0.53 (0.21-­0.99)
B (15) Weight, kg 44.3 (37.9-­61.5) 57.8 (41.8-­63.9) 3.2 (1.2-­8.7) 62.2 (52.9-­70.8) 3.8 (2.5-­12.1)*
BMI 19.1 (16.1-­22.9) 19.2 (17.9-­24.8) 1.3 (0.1-­2.0) 23.6 (20.0-­25.3) 1.1 (0.2-­3.8)**
BMIz 0.37 (-­0.89-­0.93) 0.08 (-­0.77-­1.04) 0.17 (-­0.11-­0.36) 0.86 (-­0.34-­1.27) 0.22 (-­0.11-­0.83)
a
Group A, patients who became hypothyroid after RAI administration; B, patients who did not become hypothyroid.
*P = .03.
**P = .02 (Mann-­Whitney tests) for the difference between Groups A and B.

predictive. Patients receiving I-­131 treatment within the first tertile
of days from diagnosis (90 days) vs those who received I-­131 treat-
ment later tended to experience greater BMI-­Z increase (ΔBMI-­Z0-12
median 0.86 vs 0.24, IQR 0.54-­1.27 vs 0.11-­0.58, P = .01). In the RAI
group, maximum TSH value after RAI, age and weight adjusted starting
dose of levothyroxine (LT4), time after RAI to initiate LT4 and time from
LT4 initiation to maximum TSH were not significantly correlated with
ΔBMI-­Z0-12. At the time of maximum TSH, median TSH was 48 (24-­73)
μIU/mL, median free T4 was 0.57 (0.4-­0.8) ng/dL, and median T3 was
43 (40-­63) ng/dL.
In the 97 RAI patients followed at least until initiation of LT4 replace-
ment, the median time to start LT4 was 77 (60-­97) days. Median start-
ing LT4 replacement dose expressed as a fraction of the recommended
starting dose by age, gender and weight for acquired hypothyroidism
in our hospital formulary was 0.56 (0.40-­0.71)16. Maximum TSH values
during the first year of follow-­up occurred greater than 31 days after
starting LT4 replacement in 35 patients. Maximum TSH was >20 μIU/
mL in 29 of those 35 patients.
Median RAI dose was 26.8 (20.6-­28.8) mCi, equivalent to 992
(762-­1066) MBq. Fifteen of 132 patients receiving RAI did not
progress to hypothyroidism within the first 12 months after RAI. Of
these, 4 underwent a second RAI within 12 months, 1 received a
second dose of RAI 16 months after the first; 1 underwent thyroid-
ectomy 12 months after the RAI, and 9 had resumed thyroid func-
tion becoming euthyroid or hyperthyroid while off LT4 replacement
but did not undergo thyroidectomy or a second RAI. Of the 9 with
resumed thyroid function, at least 4 eventually became hypothyroid
again within 2 years of the RAI. The 15 patients who did not progress
ALONSO et al.
to hypothyroidism had significantly lower weight and BMI increases
during the year after RAI administration than the 86 patients who did
become hypothyroid (Table 3). Seventeen patients had lost contact
with our clinic <10 months after RAI, most of whom did not have doc-
umented plans for transition of care.
4 | DISCUSSION
As in adults, risk factors for weight gain in children treated for Graves’
disease include higher T3 and free T4 at diagnosis and before under-
going definitive therapy. Although Dallas children during the study
period likely had a higher frequency of overweight and obesity than
17,18
the ­cohorts used to generate the CDC 2000 growth charts , these
charts are nonetheless the gold standard, and change in BMI-­Z would
likely be negligibly different in a cohort from the background popu-
lation. Weight loss at diagnosis correlated with weight gain in those
undergoing definitive therapy with RAI, although the fact that many
patients did not have weight loss recorded at diagnosis limits the ro-
bustness of this conclusion. Together, these results are consistent with
data from adult patients and support the premise that greater degree of
hyperthyroidism leads to more weight loss and therefore more poten-
tial to rebound. Previous studies of children treated for Graves’ disease,
none larger than 45 patients, have been too small to show associations
11-13
between thyroid function testing, race and weight trends . Perrin C. White  http://orcid.org/0000-0001-6262-0289
At the end of the study period, 29.2% of patients were overweight
(85th to 95th percentile) and 10.8% were obese (>95th percentile),
representative of a predominantly teenage, multiracial cohort of US
children17. Unfortunately, because many of these patients were older
teens who graduated to adult care, we were unable to assess long-­
term weight trajectories.
Age negatively correlated with ΔBMI-­Z0-12 in the entire treatment
group. Younger patients with Graves’ disease may therefore be more
susceptible to weight loss or poorer weight gain prior to diagnosis.
Uncontrolled postablative hypothyroidism was frequent, with
half of RAI recipients having TSH levels >50 μIU/mL and a third with
maximum TSH values >20 μIU/mL even after starting LT4 replace-
ment. Initial LT4 replacement doses were often too modest but may
have been chosen to address the possibility of incomplete ablation of
thyroid function. Also, patients who were less adherent with medical
therapy may have been more likely to be selected for RAI. During the
study period, our group did not have a system for automatically track-
ing laboratory and clinic follow-­up and assuring compliance with mon-
itoring. Fortunately, postablative hypothyroidism was not correlated
with weight gain. Early and frequent thyroid function testing after RAI
administration and more aggressive thyroid hormone replacement,
balanced by monitoring for thyroid hormone excess, may improve
control of postablative hypothyroidism.
Preventing unhealthy weight gain in Graves’ disease is challeng-
ing. Strategies should include documentation of risk factors for rapid
weight gain and early nutrition counselling in selected cases. Fatigue
and weakness, common in untreated Graves’ disease and also as a side
effect of necessary beta-­adrenergic blocking medications, may lead to
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decreased energy expenditure and subsequent weight gain in some
patients. Therefore, in addition to weaning beta blocker use as quickly
as possible, there may also be a role for physical therapy in rebuilding
lost muscle mass and encouraging physical activity at a level safe for
patients’ current status.
The major limitation to this study is its retrospective nature,
which led to a lack of premorbid weight or BMI information in
37% of patients and an inability to monitor treatment adherence.
Additionally, longer follow-­up would have enabled us to assess the
long-­term effects of Graves’ disease and its treatment on BMI trajec-
tories. Some patients lacked complete data. Finally, there are world-
wide differences in the degree to which RAI is used to treat Graves’
disease, particularly in children (most likely to be used in the United
States, least in Europe)18-21, limiting the applicability of our findings.
Weight gain during treatment of Graves’ disease is common in
children and associated with greater degree of hyperthyroidism prior
to initiating treatment and younger age. Many patients become over-
weight and obese during the follow-­up period. Areas for improvement
include preventing unhealthy weight gain, more rigorously controlling
postablative hypothyroidism and more smoothly transitioning from
paediatric to adult care.
O RC I D
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How to cite this article: Alonso GT, Rabon S, White PC. Weight
gain after treatment of Graves’ disease in children. Clin
Endocrinol (Oxf). 2018;88:66–70. https://doi.org/10.1111/
cen.13493