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Edited by: Peter PA Smyth, UCD, Dublin · Published by: Merck KGaA, Darmstadt, Germany
4 | 2010
The interaction between growth hormone
and the thyroid axis
Lucy Ann Behan, Amar Agha
Thyroid International 4 2010
The interaction between growth hormone
and the thyroid axis
Lucy Ann Behan, Amar Agha
Academic Department of Endocrinology
Beaumont Hospital and the Royal College
of Surgeons Medical School, Dublin, Ireland
Corresponding author:
Dr Amar Agha,
Academic Department of Endocrinology,
Beaumont Hospital, Beaumont,
Dublin 9, Ireland
[email protected]
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Thyroid International 4 2010
Dr Lucy-Ann Behan is a
Specialist
Registrar
in
Endocrinology and Diabetes
Metabolism. She graduated
from The Royal College of
Surgeons in Ireland in 2003.
She has just completed a clin­
ical research fellowship with
Dr Agha in Beaumont
Hospital and RCSI Medical School. Her research inter­
ests include corticosteroid metabolism, pituitary and
reproductive endocrinology.
Dr. Amar Agha MD FRCPI, is a
Consultant Pituitary Endo­
crinologist at Beaumont
Hospital and the RCS Medical
School in Dublin, Ireland. He
graduated
from
Trinity
College in 1995 and under­
went basic medical training
followed by specialist train­
ing in Endocrinology and Diabetes in Dublin. He sub­
sequently had research and clinical fellowship posts at
Queen Elizabeth Hospital in Birmingham and at Barts
hospital in London before returning to Dublin in 2006.
Dr. Agha’s research interests include the areas of pitu­
itary dysfunction after head trauma and radiotherapy
and glucocorticoids and he has published extensively
in the leading scientific journals on these topics. He is
a previous winner of the American Endocrine Society
research award, The American Endocrine Society/JCEM
outstanding reviewer’s award, the Irish Endocrine
Society Gold Medal and the IJMS Doctors awards in
Endocrinology and Diabetes.
Thy­roid Inter­na­tional
­Editor-in-Chief: Peter PA Smyth, UCD, Dublin
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­ hich the ­authors pos­sess
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­ ealing with
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The interaction between growth hormone and the thyroid axis
The interaction between growth hormone
and the thyroid axis
Lucy Ann Behan, Amar Agha
Abstract
Growth hormone (GH) administration to both adults
and children with and without GH deficiency (GHD)
may cause alterations to the hypothalamo-pituitarythyroid (HPT) axis; including reduced serum thyroxine
(T4), increased serum triiodothyronine (T3) with or
without a reduction in serum thyroid stimulating hor­
mone. There is considerable inconsistency in the litera­
ture regarding the nature of these alterations, and
indeed, their clinical significance. Some authors report
the perturbations in the HPT following GH administra­
tion to be transient, without significant clinical effect.
Others have shown reduced height velocity in children
who developed a low free T4 during GH therapy, which
resolved upon normalisation of the HPT with thyroxine
replacement. In adult hypopituitary patients GH has
been shown to unmask central hypothyroidism in
36-47 % of apparently euthyroid subjects, resulting in
an attenuation of the beneficial effects of GH replace­
ment on quality of life and necessitating thyroxine
replacement. Patients with organic pituitary disease and
multiple pituitary hormone deficits are at high risk of
developing clinical and biochemical features of postGH central hypothyroidism.
It is therefore necessary to monitor thyroid function
upon commencement of GH replacement therapy in
order to identify and manage those who will become
hypothyroid in a timely fashion.
Introduction
The widespread use of growth hormone (GH) to treat GH
deficiency (GHD) in adults has lead to the recognition of
the interaction between the GH-Insulin-Like Growth
Factor-I (IGF-I) system and other pituitary endocrine
systems including the thyroid, adrenal and gonadal axes.
The relationship between the GH-IGF-I system and the
hypothalamic-pituitary-thyroid (HPT) axis is complex
and a number of studies have attempted to characterise
alterations in the HPT axis following the administration
of GH in both GHD and non-GHD populations. Some
studies have demonstrated no change in free thyroxine
(T4) levels1-7 while others found decreased free T4 lev­
els following GH administration.8-21 The changes
reported in serum T3 are variable from decreased8­
to unchanged3,4,6,7,21 to increased.5,9,11,13,14,16,18,20,22
Discre­pancies evident in the published data may be
explained by the different size and type of population
studied; variation in the underlying cause of GHD, the
use of different assays and in some earlier studies in
children, the use of cadaveric GH that was occasionally
contaminated with TSH.
Here we will review the data available on the interaction
between GH and the thyroid axis in adults and children,
with particular reference to hypopituitary subjects and
we will discuss the potential clinical implications of
these interactions.
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Thyroid International 4 2010
The Hypothalamic Pituitary Thyroid axis
When considering the effect of GH on the hypothalamopituitary-thyroid (HPT) axis, it is important to be aware
of the complexity surrounding the diagnosis of central
hypothyroidism (CH). The challenge of making this
diagnosis is reflected in the reported frequency of CH in
non-functioning pituitary adenomas which varies from
18-43 % pre-operatively to 16-57 % post pituitary sur­
gery.23-29 The diagnosis of CH is challenging because
there is no reliable biological marker in adults and thus
the diagnosis is largely biochemical, based on the find­
ing of a low serum free T4 in conjunction with a low or
normal serum TSH.30,31 TSH is not a reliable marker of
CH in pituitary disease as it has been shown to be unde­
tectable in 35 %, normal in 41 % and above normal in
24 % of patients with known CH due to hypothalamicpituitary disease.32 Indeed studies have demonstrated
reduced bioactivity of circulating TSH in the setting of
hypothalamic-pituitary disease although immunoreac­
tivity is preserved.33,34
The diagnosis is further complicated by the fact that a
normal measurement of serum free T4 does not exclude
CH as the performance of the free T4 assay is variable,30
particularly at the lower end of the normal range.
Although T3 is the biologically active hormone, its mea­
surement is not recommended for the diagnosis of
hypothyroidism.35 Thus, the diagnosis of central hypo­
thyroidism is ultimately based on a combination of clin­
ical features, the presence of other pituitary hormone
abnormalities and biochemical measurements. It is rare
to have TSH deficiency in isolation and physicians must
consider the reciprocal effects of thyroid and GH
replacement therapy on the GH-IGF-I and the thyroid
axes respectively.
The relationship between the GH-IGF-I axis and the HPT
axis is complex and while the GH-IGF-I axis modulates
growth and metabolic function of the thyroid gland, thy­
roid hormones alter the secretion and action of GH.36-40
The effect of thyroid status
on the GH-IGF-I axis
Untreated primary hypothyroidism is associated with
decreased GH pulsatility, attenuation of GH response to
secretagogues41 and a reduction in IGF-I and IGF
Binding Protein-3 (IGFBP-3).40 Reduced levels of IGF-I,
that increase with L-thyroxine replacement therapy,
have also been demonstrated in the setting of subclini­
cal hypothyroidism.40
Conversely, hyperthyroidism is associated with an
increase in mean 24 hour GH concentration and secre­
tion rates,42,43 while serum IGF-I and IGFBP-3 levels
have been found to be normal in subclinical hyperthy­
roidism,40 with a normal44 or high39,44,45 IGF-I in overt
thyrotoxicosis.
Administration of T4 to hypophysectomised animals
has been shown to stimulate IGF-1 production in the
absence of GH, while IGF-BP3 was shown to be GH
dependent.46 Normalisation of thyroid function results
in decreased39,47 or unchanged40,44 serum IGF-1 and
decreased47 or unchanged39,40 IGFBP-3 concentrations.
While it is probable that these changes are due to direct
actions of thyroid hormones, no study has assessed the
indirect effect of changing body composition, in associ­
ation with return to euthyroidism, on the GH-IGF-I axis
and its binding proteins.
Growth Hormone effect on the Thyroid axis
There have been a number of studies examining the
effects of GH on the HPT axis in adults and children
both with and without GH deficiency.
In non GH deficient adults the administration of subcu­
taneous GH, 0.125 mg/day for 4 days, resulted in an 8 %
reduction in total T4, 5 % reduction free T4 and a 21 %
increase in total T3 with no effect on rT3 but a marked
decrease in serum TSH.11 In contrast, no changes in
­thyroid parameters were found in a placebo controlled
double-blind trial of GH therapy (0.222 mg/kg/week) in
non-GHD short children.6
The interaction between growth hormone and the thyroid axis
The available data in children with GH deficiency treat­
ed with high doses of GH show inconsistent findings
(Table 1). Some studies were unable to demonstrate any
changes in the HPT axis,3,6 while others found transient
alterations which resolved at 3–12 months of GH
replacement.15 However Giavoli et al demonstrated
­persistent, clinically relevant changes with 12 months
of GH replacement in children with multiple pituitary
hormone deficiencies (MPHD).18
The discrepancies noted in these studies are due to sev­
eral factors, including small population size ranging
from 5–57 children, different study protocols, differenc­
es in biochemical analytical methods and in the diag­
nostic cut offs used to define GHD and the difficulties in
making the diagnosis of central hypothyroidism, as TSH
can be in the normal reference range in over 50 % of
cases.32 The GH used in earlier studies was cadaveric
and was occasionally contaminated with TSH. In addi­
tion, the aetiology of GHD varied between studies with
some patients showing idiopathic isolated GHD and
others having organic pituitary disease and/or MPHD. It
is more likely that GH replacement will unmask subtle
hypothyroidism in subjects with multiple pituitary hor­
mone disease or organic pituitary disease.
There are similar inconsistencies in the data available in
the adult GHD population. Table 2 outlines the studies
that have examined the effects of GH on the HPT.
Monson et al demonstrated a decrease in free T4 in the
euthyroid subgroup of hypopituitary subjects and a
transient increase in T3 in the whole group, regardless
of thyroid status, following 0.2 U/Kg/week GH.14
However only one patient had a free T4 that fell below
the normal range and there were no clinical signs of
hypothyroidism.14 Amato studied 9 subjects with vary­
ing degrees of pituitary insufficiency, 7 of whom had
congenital GHD and no changes in thyroid parameters
were seen on 0.028 U/Kg/day GH replacement.7
These data are in contrast with recent larger studies
in subjects with organic pituitary disease and
MPHD.12,17,20,21,22
In a large prospective study we evaluated the biochem­
ical and clinical effect of standard clinical replacement
GH dose regimens on the HPT axis in 243 adult
patients.20 Of 84 subjects who were apparently euthy­
roid prior to GH replacement (untreated group), 36 %
demonstrated a reduction in serum thyroxine concen­
tration to below the normal range necessitating initia­
tion of T4 replacement at 3 or 6 months of GH therapy.
No further changes were seen at 9 and 12 months of GH
replacement and the main predictor for the develop­
ment of post-GH hypothyroidism in this group was the
presence of MPHD. 159 patients had previously diag­
Table 1 Alterations in HPT with GH replacement in children
Study
Porter et al 19732
Lippe et al 19758
Rubio et al 19763
Sato et al 19779
n=
5
6
12
8
GHD
yes
yes
yes
yes
CH*
2
no
no
3
T4
↔
↓
↔
↓
TSH
↓
↓
↔
↑
Cacciari et al 19794
Demura et al 198010
Rezvani et al 19815
Pirazzoli et al 199213
Rose et al 19956
Wyatt et al 199815
Portes et al 200016
Giavoli et al 200318
Seminara et al 200519
24
29
7
57
20
14
20
26
19
yes
yes
yes
yes
no
yes
yes
yes
yes
17
8
7
no
no
0
8
4
n
↔
↓
↔
↓
↔
↓
↓
↓
↓
↔
↔
↔
↔
↔
↔
↔
↔
↔
T3
n/a
↔
↔
↑ 5/8↔
3/8
↔
↔
↑
↑
↔
↑
↑
↑ ns
↑
rT3
n/a
n/a
n/a
n/a
New CH
no
6
no
no
n/a
n/a
↓
↓
↔
↓
↓
↓
n/a
no
7
no
no
no
no
1
2
no
5
Thyroid International 4 2010
Table 2 Alterations in HPT with GH replacement in adult subjects
Study
Oliner et al19681
Grunfeld et al198811
Jorgensen et al198912
Monson et al199414
n=
8
20
21
21
GHD
no
no
yes
yes
CH*
no
no
9
15
T4
↔
↓
↓
↓**
TSH
n/a
↓
↓ ns
n/a
Jorgensen et al199422
Amatoet al19967
Porretti et al200217
10
9
66
yes
yes
yes
8
9
49
↓ ns
↔
↓
↓
↔
↔
Agha et al200720
Losa et al 200821
243
49
yes
yes
159
37
↓
↓
↔
↔
nosed central hypothyroidism and were adequately
treated with T4 prior to GH commencement (treated
group), 16 % of whom had a reduction in serum thyrox­
ine level requiring an increase in thyroxine dose with no
further changes seen after 6 months of GH replacement.
(Figure 1)
T3
n/a
↑
↑
Transient
↑
↑
↔
Transient
↑
↑ ns
↔
rT3
n/a
↔
↓
n/a
New CH
no
no
no
1
↓
↔
↓
0
0
17
n/a
n/a
30
2
These findings are consistent with those of Porretti et
al17 and Losa et al,21 demonstrating that GH replace­
ment, at doses that achieve a serum IGF-I in the upper
reference range, as recommended by the GH Research
Society, unmasks underlying hypothyroidism in patients
with organic pituitary disease and MPHD.
Figure 1 Serum free T4 (left) and total T4 (right) concentrations at baseline in patients who subsequently became
­hypothyroid (Y) and those who remained euthyroid (N) after GH replacement. The horizontal line in the box indicates the
median. The lower and upper boundaries of the box indicate the 25th and 75th percentiles. Error bars above and below the
box indicate the 90th and 10th percentiles. Reproduced with permission, Blackwell Science, Oxford publishing20
140
Baseline total T4 (pmol/l)
24
Baseline free T4 (pmol/l)
6
21
18
15
12
130
120
110
100
90
80
70
60
N
Y
Post-GH hypothyroidism
50
N
Y
Post-GH hypothyroidism
The interaction between growth hormone and the thyroid axis
Mechanism of HPT changes with GH replacement
The mechanism of post GH hypothyroidism is unknown
and it is likely that alterations in serum thyroid hor­
mones during GH therapy do not have a unifying expla­
nation but are a result of a combination of factors.
It has been hypothesised that GH increases the periph­
eral deiodination of T4 to T3 and this is supported by the
findings from some studies that showed an increase in
T3 and/or a reduction in rT3 after GH thera­
py,5,9,11,13,15,16,19,22 which parallel the reduction in
serum T4 concentration. It has been postulated that this
effect is mediated by IGF-I rather than a direct effect of
GH as conditions such as malnutrition and critical ill­
ness, accompanied by impaired T4 to T3 conversion,
have high GH and low IGF-I,12 yet individuals with
Laron type GH resistance given exogenous IGF-I dem­
onstrate no changes in T3 levels.48 Hussain et al found
a greater magnitude of increase in serum T3 following
GH alone than after IGF-1 administration suggesting
that, although both contribute, GH has a more potent
effect on thyroid hormone metabolism.49
As the finding of increased T3 is not a consistent effect
throughout the literature,8,10,21 altered T4 to T3 conver­
sion is unlikely to be the only mechanism involved in
thyroid hormone alterations with GH therapy.
While random TSH concentration measured in many
studies did not appear to change, other studies have
shown altered TSH dynamics following GH therapy.
Jorgensen demonstrated a 10 fold decrease in mean
24 hour serum TSH profiles with GH therapy along with
a blunted nocturnal surge of TSH.22 In our study, the
reduction in serum T4 concentration was more pro­
nounced than the small increase in serum T3 concentra­
tion and the reduction in serum T4 concentration was
more marked in the euthyroid group who had measur­
able serum TSH concentration compared to the treated
hypothyroid group.20 Together these findings suggest a
dual role for GH in modulating thyroid hormone con­
centrations through both inhibition of peripheral con­
version of T4 to T3 and also a central inhibitory effect
on TSH secretion through pulse doses of GH8,22 possibly
through increased somatostatinergic tone.8,50 Untreated
acromegaly is associated with a diminished 24 hour TSH
output due to reduced basal and pulsatile secretion with
diminished pulse amplitude but with preserved pulse
frequency and TSH half-life.51
Although it was previously postulated by Oliner et al
that the changes seen in the thyroid axis with GH ther­
apy were related to altered binding proteins,1 the dose
of GH used in that study was supra physiological
(4–8 mg/day for 5–15 days) and there was also a decrease
in albumin and total protein suggesting these changes
were probably related to fluid retention. At lower GH
doses used in current clinical practice, Poretti et al dem­
onstrated no change in TBG,17 while Jorgensen showed
parallel changes in total and free thyroid hormones12
suggesting the alterations in binding proteins are
unlikely to be relevant with modern GH replacement
therapy using relatively low doses of GH.
Clinical Significance
It is imperative for the endocrinologist prescribing GH
replacement to be aware of the potential clinical impact
the therapy may have on patients.
In a study on 8 GHD children all subjects studied had a
reduction in serum thyroxine following treatment with GH,
3 of whom had been previously categorised as hypothyroid
based on an abnormal TSH response to thyrotropin releas­
ing hormone in the GHD state.9 Upon commencement of
GH therapy, growth accelerated in the euthyroid group.
However it was not until thyroxine was replaced in the
hypothyroid group that growth rates accelerated.
7
8
Thyroid International 4 2010
Of 6 GHD children who developed a reduction in serum
free T4 following GH replacement and had reduced lin­
ear growth and clinical symptoms of hypothyroidism, 3
returned to a euthyroid state clinically and biochemi­
cally upon cessation of GH therapy. Those that remained
hypothyroid after discontinuation of GH replacement
had MPHD while those who reverted to the euthyroid
state had isolated GHD.8
These findings are supported by those of Giavoli et al
who studied 26 GHD children. Of the children studied 20
had isolated idiopathic GHD, 6 had organic pituitary
disease with MPHD and 4 from this group had pre-exist­
ing CH and were on replacement T4. Reductions in
serum free T4 resulted in 2 new diagnoses of CH and all
four patients with pre-existing CH required increased
thyroxine replacement dose regimes while on growth
hormone. Height velocity did not normalise on GH ther­
apy until a euthyroid state was also achieved. None of
the patients with idiopathic isolated GHD developed
hypothyroidism supporting the theory that GH replace­
ment, rather than inducing hypothyroidism, unmasks
underlying pre-existing hypothyroidism in patients
with organic pituitary disease or MPHD.18
Recently, in a study on GHD children and adolescents,
Martins et al examined the effects of GH replacement on
biological markers of thyroid hormone action including
isovolumetric contraction time (ICT), a sensitive marker
of thyroid hormone action on the heart, and resting
energy expenditure (REE).52 Administration of GH to a
subgroup of 7 GHD subjects resulted in increased T3 and
decreased free T4 as expected, although free T4 did not
fall below the normal reference range. These changes
were associated with decreased ICT and increased REE
which suggest a more favourable biological effect.
However it is important to note that the changes in free
T4 occurred within the normal reference range and the
potential confounding direct effect of GH on REE and
possibly on ICT cannot be overlooked, making interpre­
tation of these results challenging, particularly in a
small sub-group of children studied.
Apparently euthyroid subjects who develop biochemical
hypothyroidism following GH replacement have reduced
quality of life (QoL) compared to those subjects who
remain euthyroid on GH.20 This occurs despite similar
QoL scores at the outset and the achievement of similar
serum IGF-I concentrations in both groups.20 This is
­particularly relevant for endocrinologists practicing under
the NICE guidelines53 in the United Kingdom where con­
tinuation of GH therapy is dependent upon an improve­
ment of QoL by 7 points on the QoL – adult growth hor­
mone deficiency assessment (AGHDA) questionnaire.54
Conclusions and Recommendations
Despite its clear benefits55 GH replacement is associat­
ed with a reduction in serum free T4 and unmasks clin­
ical and biochemical hypothyroidism in a significant
number of patients. Those most at risk include subjects
with a serum free T4 in the lower end of the normal ref­
erence range and those with organic pituitary disease
and/or multiple pituitary hormone deficiencies.
It has been suggested in the setting of pituitary disease
that physicians aim for thyroid hormone replacement
which results in a free T4 in the upper half of the nor­
mal reference range. However recent evidence suggests
the mid normal range may be adequate in GH replaced
subjects.52
We recommend that patients commencing GH replace­
ment should have their thyroid function measured regu­
larly, particularly those in the high risk group described
above. Patients who have serum free T4 near the lower
end of normal reference range prior to GH replacement
are most likely to manifest pre-existing hypothyroidism
and should be considered either for thyroxine therapy or
an increased dose of thyroxine as appropriate, in order to
optimise the potential beneficial effects of GH therapy.
10
Thyroid International 4 2010
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11
12
Thyroid International 4 2010
Former Editions of Thyroid International
No 3-2010 T ransient Hypothyroxinemia of Prematurity: Current
State of Knowledge (Nevena Simic, Joanne Rovet)
No 2-2010 3-Iodothyronamine (T1AM): A new thyroid
­hormone? (Barbara D Hettinger, Kathryn G Schuff,
Thomas S Scanlan)
No 1-2010 Report on the 34th Annual Meeting of the
European Thyroid Association
(Clara V Alvarez and Peter PA Smyth)
No 5-2009 Factors Affecting Thyroid Hormone Gastrointestinal
Absorption (Kenneth D. Burman, M.D.)
No 4-2009 Iodine Deficiency Disorders: Silent Pandemic
(Fereidoun Azizi)
No 3-2009 A
merican Thyroid Association:
Highlights of the 79th Annual Meeting
(Stephen W Spaulding, P.P.A. Smyth)
No 2-2009 E pidemiology of Thyroid Dysfunction –
Hypothyroidism and Hyperthyroidism
(M.P.J. Vanderpump)
No 1-2009 R
eport on the 33rd Annual Meeting
of the European Thyroid Association
(L.H. Duntas, P.P.A. Smyth)
No 4-2008 T hyroid autoimmunity and female infertility
(Kris Poppe, Daniel Glinoer, Brigitte Velkeniers)
No 3-2008 N
ew reference range for TSH?
(Georg Brabant)
No 2-2008 A
merican Thyroid Association: Highlights of the
78th Annual Meeting (Stephen W Spaulding, Peter
PA Smyth)
No 1-2008 R
eport of the 32th Annual Meeting of the European
Thyroid Association (GJ Kahaly, P.P.A. Smyth)
No 4-2007 T he Thyroid and Twins (Pia Skov Hansen, Thomas
Heiberg Brix, Laszlo Hegedüs)
Hypothyroxinaemia and
No 2-2005 Transient
Preterm Infant Brain Development
(Robert Hume, Fiona LR Williams, Theo J Visser)
No 1-2005 The
Spectrum of Autoimmunity in Thyroid Disease
(Anthony P. Weetman)
No 5-2004 Postpartum
Thyroiditis: An Update
(Kuvera E. Premawardhana, John H. Lazarus)
No 4-2004 Report
of the 29th Annual Meeting of the
European Thyroid Association (G. Hennemann)
utoimmune Thyroiditis And Pregnancy
No 3-2004 A
(Alex F. Muller, Arie Berghout)
No 2-2004 R
eport of the 75th Annual Meeting of the
American Thyroid Association (G. Hennemann)
No 1-2004 T hyroid and Lipids: a Reappraisal
(Leonidas H. Duntas)
No 5-2003 U
se of Recombinant TSH in Thyroid Disease:
An Evidence-Based Review (Sara Tolaney M.D.,
Paul W. Ladenson M.D.)
No 4-2003 New
Insights for Using Serum Thyroglobulin
(Tg) Measurement for Managing Patients with
Differentiated Thyroid Carcinomas (C.A. Spencer)
No 3-2003 The
Significance of Thyroid Antibody Measurement
in Clinical Practice (A. Pinchera, M. Marinò, E. Fiore)
diagnosis and treatment of Graves’ disease
No 2-2003 Etiology,
(A.P. Weetman)
No 1-2003 Report
of the 74th Annual Meeting of the
American Thyroid Association (G. Hennemann)
of the 28th Annual Meeting of the
No 6-2002 Report
European Thyroid Association (G. Hennemann)
No 5-2002 Iodine Deficiency in Europe anno 2002
(François M. Delange, MD, PhD)
No 3-2007 C
linical Aspects of Thyroid Disorders in the
Elderly (Valentin Fadeyev)
No 4-2002 Thyroid Imaging in Nuclear Medicine
(Dik J. Kwekkeboom, Eric P. Krenning)
No 2-2007 R
eport of the 31th Annual Meeting
of the European Thyroid Association
(John H Lazarus, Peter PA Smyth)
No 2-2002 T he Use of Fine Needle Aspiration Biopsy (FNAB) in
Thyroid Disease (Antonino Belfiore)
No 1-2007 T he story of the ThyroMobil (F. Delange,
C.J. Eastman, U. Hostalek, S. Butz, P.P.A. Smyth)
No 1-2002 R
eport of the 73rd Annual Meeting of the
American Thyroid Association (G. Hennemann)
No 3-2006 T hyroid Peroxidase – Enzyme and Antigen
(Barbara Czarnocka)
No 6-2001 R
eport of the 27th Annual Meeting of the
European Thyroid Association (G. Hennemann)
enetics of benign and malignant thyroid tumours
No 2-2006 G
(Dagmar Führer)
No 5-2001 S ubclinical Hyperthyroidism
(E.N. Pearce, L.E. Braverman)
No 1-2006 H
ighlights of the 13th ITC
(Sheue-yann Cheng, Peter PA Smyth)
No 4-2001 T hyroid hormone treatment – how and when?
(A.D. Toft)
No 4-2005 Thyroid
Eye Disease: Current Concepts and the EUGOGO Perspective
(Gerasimos E Krassas, Wilmar M Wiersinga)
No 3-2001 R
esistance to thyroid hormone
(O. Bakker, W.M. Wiersinga)
Expression of Mutations in the TSH
No 3-2005 Clinical
Receptor: TSH-R Disorders
(Davide Calebiro, Luca Persani, Paolo Beck-Peccoz)
No 3-2002 Congenital Hypothyroidism (Delbert A. Fisher)
No 1/2-2001 Report of the 12th International
Thyroid Congress (G. Hennemann)
No 5-2000 Percutaneous
­
ethanol injection therapy for t­ hyroid
diseases (Enio Martino)
Thyroid International is also published on the website ThyroLink: www.thyrolink.com (Literature)
When the thyroid
secretly steals life.
Taking the offensive against hypothyroidism. With Euthyrox.
Euthyrox®
Offensive against hypothyroidism.
• multiple dosage strengths for precise dose titration
• galenic formulation with reliable unit conformity
• first levothyroxine preparation with a European and FDA approval
Other registered tradenames: Eutirox, Supratirox, Lévothyrox
Active substance: Levothyroxine sodium. Prescription only medicine. Composition: Each tablet (round with cross score) of Euthyrox 25/50/75/88/100/112/125/137/150/175/200 µg contains 25/50/75/88/100/112/125/137/150/175/200 µg of levothyro­
xi­ne sodium. Other ingredients: Corn starch, croscarmellose sodium, gelatin, lactose monohydrate, magnesium stearate. Indications: Euthyrox 25 - 200 µg: Euthyroid goitre, prophylaxis of relapse goitre after goitre resection, hypothyroidism,
suppression therapy in thyroid cancer. Additional indication for Euthyrox 25 - 100 µg: Concomitant therapy in antithyroid drug therapy of hyperthyroidism after having achieved a euthyroid function. Additional indication for Euthyrox
100/150/200 µg: Thyroid suppression test. Contraindications: Intolerance to the active substance or any of the excipients. Untreated adrenocortical insufficiency, untreated pituitary insufficiency, untreated hyperthyroidism. Do not
initiate therapy in acute myocardial infarction, acute myocarditis, acute pancarditis. Adverse reactions: Adverse reactions are not to be expected under adequate therapy. In (individual) intolerance of the chosen dosage or overdosage
(particularly if the dose is increased too quickly at the start of treatment): tachycardia, palpitations, cardiac arrhythmias, angina pectoris, headache, muscle weakness and cramps, sensation of heat, fever, vomiting, menstrual disorders,
pseudotumor cerebri, tremor, restlessness, insomnia, hyperhidrosis, weight loss, and diarrhoea. In such cases reduce the daily dosage or interrupt treatment for several days. Allergic reactions may occur in the case of hypersensitivity. Other
notes: Treatment with thyroid hormones should be continued consistently during pregnancy in particular. The thyroid hormone quantity secreted into breast milk during lactation is not sufficient to cause development of hyperthyroid­ism
or suppression of TSH secretion in the infant. During pregnancy contraindicated as concomitant treatment to antithyroid drug therapy. Exclude or treat coronary insufficiency, angina pectoris, arteriosclerosis, hypertension, pi­tu­i­tary or
adrenocortical insufficiency, and thyroid autonomy before initiating therapy with thyroid hormones. Prevent drug-induced hyperthyroidism in coronary insufficiency, heart failure, and achycardiac arrhythmias. Clarify cause of secondary
hypothyroidism before initiating replacement therapy. In compensated adrenocortical insufficiency start adequate replacement therapy where necessary. When hypothyroid, postmenopausal women at increased risk of developing osteoporosis are treated, their thyroid function should be checked more frequently in order to prevent supraphysiologic levothyroxine blood levels. Do not use in: patients with galactose intolerance, lactase deficiency or glucose-galactosemalabsorption. Presentation and pack sizes: depending on the local registration state. For more detailed information please refer to the data sheet or package leaflet. Issued: August 2007. Merck KGaA, D-64271 Darmstadt, Germany.