Abstract Introduction In the patient with acromegaly, pituitary surgery is the therapeutic standard. Despite undergoing surgery, a significant number of patients with acromegaly continue to have uncontrolled growth hormone secretion. These patients require other treatments such as external irradiation and/or drug therapy. Case presentation We present the clinical and laboratory responses to six months of treatment with rosiglitazone in four cases. In all four cases, the patients had persistent growth hormone overproduction despite previous surgical treatment and other conventional therapy. Case 1 is a 57-year-old Caucasian woman, case 2 is a 51-year-old Hispanic man, case 3 is a 32-year-old Hispanic woman, and case 4 is a 36-year-old Hispanic man. In three of these patients, basal and nadir growth hormone and insulin-like growth factor 1 levels were significantly decreased (<it>P </it>< 0.05 and <it>P </it>< 0.01, respectively). Conclusion Rosiglitazone could be a treatment option in select patients with acromegaly.</p

Alejandra L Tamez-Peña

Ana Bahena-García

AP Heaney

BL Wajchenberg

F Castinetti

G Magenta

GM Besser

Hugo Gutiérrez-Hermosillo

Héctor E Tamez-Pérez

K Winczyk

M Bastemir

M Grardišer

M Morcos

María D Gómez de Ossio

MN Emery

S Melmed

English

PubMed

Abstract Introduction In the patient with acromegaly, pituitary surgery is the therapeutic standard. Despite undergoing surgery, a significant number of patients with acromegaly continue to have uncontrolled growth hormone secretion. These patients require other treatments such as external irradiation and/or drug therapy. Case presentation We present the clinical and laboratory responses to six months of treatment with rosiglitazone in four cases. In all four cases, the patients had persistent growth hormone overproduction despite previous surgical treatment and other conventional therapy. Case 1 is a 57-year-old Caucasian woman, case 2 is a 51-year-old Hispanic man, case 3 is a 32-year-old Hispanic woman, and case 4 is a 36-year-old Hispanic man. In three of these patients, basal and nadir growth hormone and insulin-like growth factor 1 levels were significantly decreased (P P Conclusion Rosiglitazone could be a treatment option in select patients with acromegaly.</p

Bahena-García Ana

Tamez-Pérez Héctor E

Gómez de Ossio María D

Gutiérrez-Hermosillo Hugo

Tamez-Peña Alejandra L

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Journal of Medical Case Reports

Rosiglitazone as an option for patients with acromegaly: a case series

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CASE REPORT Open Access
Rosiglitazone as an option for patients with
acromegaly: a case series
Héctor E Tamez-Pérez1,2,3,4*, Ana Bahena-García3,4, María D Gómez de Ossio3,4, Hugo Gutiérrez-Hermosillo3,4 and
Alejandra L Tamez-Peña1,2
Abstract
Introduction: In the patient with acromegaly, pituitary surgery is the therapeutic standard. Despite undergoing
surgery, a significant number of patients with acromegaly continue to have uncontrolled growth hormone
secretion. These patients require other treatments such as external irradiation and/or drug therapy.
Case presentation: We present the clinical and laboratory responses to six months of treatment with rosiglitazone
in four cases. In all four cases, the patients had persistent growth hormone overproduction despite previous
surgical treatment and other conventional therapy. Case 1 is a 57-year-old Caucasian woman, case 2 is a 51-year-
old Hispanic man, case 3 is a 32-year-old Hispanic woman, and case 4 is a 36-year-old Hispanic man. In three of
these patients, basal and nadir growth hormone and insulin-like growth factor 1 levels were significantly decreased
(P < 0.05 and P < 0.01, respectively).
Conclusion: Rosiglitazone could be a treatment option in select patients with acromegaly.
Introduction
Pituitary tumors represent 10% to 15% of brain tumors,
and their presentation is characterized by clinical data
that can be summarized in three aspects: endocrine,
with hypopituitarism or excessive secretion of pituitary
hormone; a mass effect; and diverse neurological altera-
tions [1].
The standard treatment of small and non-functional
tumors is surveillance, but in the patient with acrome-
galy, pituitary surgery is the therapeutic standard. With
surgery, cure and/or remission depend on several fac-
tors, such as tumor size and extension, degree of infil-
tration, and the surgical team’s experience. Recently
published guidelines for the goals of treatment as well
as the appropriate imaging, biochemical, and clinical
monitoring of patients with acromegaly have been enun-
ciated, based on the available published evidence [2].
Despite undergoing surgery, a significant number of
patients with acromegaly continue to have uncontrolled
growth hormone (GH) secretion. These patients require
other treatments, such as external irradiation and/or
drug therapy [2,3].
Even multimodal therapy fails to control tumor pro-
gression in some patients, which is why other treatment
methods have been explored. There are two previous
reports of patients with acromegaly treated with rosigli-
tazone, a peroxisome proliferator-activated receptor g
(PPAR-g) agonist [4,5], as well as two recent in vitro stu-
dies [6,7].
The aim of the present case series is to present our
experience with rosiglitazone as rescue therapy in four
patients with acromegaly who had active disease. This
case series was approved by the local ethics committee.
Case presentation
Case 1 is a 57-year-old Caucasian woman diagnosed
twelve years ago with acromegaly on the basis of clini-
cal, radiological, and laboratory tests. Her first treatment
was transcranial surgery. Because of biochemical data
showing disease activity, she underwent additional treat-
ment with radiotherapy and octreotide for more than
two years. An evaluation of blood samples based on
assays for glucose, insulin-like growth factor 1 (IGF-1),
and growth hormone (GH) performed 0, 30, 60, 90, and
120 minutes after a 75 g oral glucose load showed an
* Correspondence: hectoreloytamez@aol.com
1Subdirección de Investigación, Facultad de Medicina, Universidad
Autónoma de Nuevo León, Monterrey, N.L., México
Full list of author information is available at the end of the article
Tamez-Pérez et al. Journal of Medical Case Reports 2011, 5:200
http://www.jmedicalcasereports.com/content/5/1/200 JOURNAL OF MEDICAL
CASE REPORTS
© 2011 Tamez-Pérez et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
absence of normalization of hormone levels in clinical
evaluation and led to the initiation of treatment with
rosiglitazone 4 mg orally as a single morning dose for a
period of six months. Clinical and biochemical evalua-
tions performed at three and six months showed statisti-
cally significant differences with regard to GH and IGF-
1 levels (P < 0.05 and P < 0.001, respectively). Treat-
ment with rosiglitazone was well-tolerated, and there
were no changes in standard biochemical profiles.
Case 2 is a 51-year-old Hispanic man with a diagnosis
of acromegaly since 2002. His initial treatment was tran-
scranial surgery, and because he had laboratory abnorm-
alities without radiological evidence of a tumor, he
received octreotide therapy for two years. An evaluation
of blood samples based on assays for glucose, IGF-1,
and GH performed 0, 30, 60, 90, and 120 minutes after
a 75 g oral glucose load showed an absence of normali-
zation of hormone levels in clinical evaluation, which
led us to initiate treatment with rosiglitazone 4 mg
orally as a single morning dose for a period of six
months. This treatment failed to achieve normalization
of GH and IGF-1 levels (P > 0.05). Treatment with rosi-
glitazone was well-tolerated, and there were no changes
in standard biochemical profiles.
Case 3 is a 32-year-old Hispanic woman diagnosed
with acromegaly ten years ago on the basis of clinical,
radiological, and laboratory results. Her first treatment
was transsphenoidal surgery, without improvement in
clinical or laboratory values. She received radiotherapy
and octreotide treatment three years ago. An evaluation
of blood samples based on assays for glucose, IGF-1,
and GH performed 0, 30, 60, 90, and 120 minutes after
a 75 g oral glucose load showed an absence of normali-
zation of hormone levels based on clinical evaluation,
and she was treated with rosiglitazone 4 mg orally in a
single morning dose for a period of six months. Her
clinical and biochemical evaluations at three and six
months showed statistically significant differences in GH
and IGF-1 levels (P < 0.05 and P < 0.001, respectively).
Treatment with rosiglitazone was well-tolerated, and
there were no changes in standard biochemical profiles.
Case 4 is a 36-year-old Hispanic man who was diag-
nosed with acromegaly seven years ago on the basis of
clinical, radiological, and biochemical laboratory results.
His initial treatment was transesphenoidal surgery.
Because of active disease without tumor as determined
by imaging tests, he received octreotide for more than
three years. An evaluation of based on blood samples
for glucose, IGF-1, and GH assays performed at 0, 30,
60, 90, and 120 minutes after a 75 gram oral glucose
load showed an absence of normalization of hormone
levels based on clinical evaluation, and we initiated
treatment with rosiglitazone 4 mg orally as a single
morning dose for a period of six months. Post-treatment
evaluation showed significantly decreased levels of GH
and IGF-1 (P < 0.05 and P < 0.001, respectively). Treat-
ment with rosiglitazone was well-tolerated, and there
were no changes in standard biochemical profiles.
Discussion
The demographic information and treatment results of
our four patients are shown in Table 1. In at least 95%
of cases, acromegaly is caused by a GH-secreting pitui-
tary adenoma. In view of the increased mortality asso-
ciated with acromegaly, successful management is of the
utmost importance, especially because reduction of GH
concentration produces a decrease in mortality [1-3].
Transsphenoidal surgery is currently the first-line treat-
ment for acromegaly. Remission is observed in 80% to
90% of patients with microadenomas, in 50% to 60% of
patients with non-invasive macroadenomas, and in fewer
than 20% of patients with invasive macroadenomas [8].
The low success rate of surgical treatment has led to
an increased interest in medical therapies for patients
with acromegaly. Three types of drugs are available:
somatostatin analogues for primary or adjunctive ther-
apy, which adequately control GH and IGF-1 in 60% to
75% of patients; dopamine agonists, which are associated
with a control rate that is unacceptably low; and pegvi-
somant, which normalizes IGF-1 levels in more than
90% of patients. Despite the use of combined therapy
(surgery and other treatments, including drugs and
radiotherapy), a significant number of patients with
acromegaly continue to have active disease. The factors
associated with tumor activity are patient characteristics,
tumor morphology, and genetic markers [1-3,8].
Table 1 Patient demographics and laboratory findingsa
3 months 6 months
Patient Sex Age,
years
Previous
treatment
GH normal
range,
ng/ml
Basal GH
level,
ng/ml
Nadir GH
level,
ng/ml
IGF-1 level,
ng/ml (normal
value for age)
GH
level,
ng/ml
IGF-1
level,
ng/ml
GH
level,
ng/ml
IGF-1
level,
ng/ml
1 Woman 57 S, R, O 0.003 to 0.97 10.0 4.32 990 (80 to 197) 3.26 400 1.24 284
2 Man 51 S, O 0.010 to 3.60 12 4.01 1016 (80 to 157) 20.73 1700 9.39 540
3 Woman 32 S, R, O 0.003 to 0.97 47 29.9 1640 (98 to 226) 11.1 715 4.29 635
4 Man 36 S, O 0.010 to 3.60 84 71 2400 (98 to 226) 51 2850 11 375
aS: surgery, R: radiotherapy, O: octreotide lar.
Tamez-Pérez et al. Journal of Medical Case Reports 2011, 5:200
http://www.jmedicalcasereports.com/content/5/1/200
Page 2 of 4
The molecular biology of these tumors has been inves-
tigated recently, with findings of over-expression of
PPAR-g in pituitary tissue as in other types of neoplasia,
such as breast, colon, or prostate cancer [6-11].
The activation of PPAR-g receptors inhibits tumor
growth in rodents and induces the oncostatic effect in
human cancer cell lines. In one study [6], there was no
correlation between PPAR-g expression and the efficacy
of rosiglitazone, suggesting that the action of this com-
pound is independent of PPAR-g expression and thus
may be useful in the treatment of non-functioning pitui-
tary adenomas. However, its efficacy in patients with
Cushing’s disease and acromegaly requires further study.
A beneficial effect of rosiglitazone has recently been
demonstrated in in vitro studies, animal models, and
short- and long-term clinical studies in patients with
central Cushing’s syndrome [12]. Rosiglitazone has been
a widely accepted drug for the treatment of type 2 dia-
betes mellitus since 1999 [13].
A previous report described one case of active acro-
megaly and type 2 diabetes mellitus in which a tumor
was not completely removed and octreotide, a somatos-
tatin analogue, was introduced but rapidly discontinued
one week afterward because of intolerance. Rosiglitazone
was introduced as an alternative treatment for hypergly-
cemia, and after 90 days of therapy with the drug, GH
and IGF-1 levels decreased and caused amelioration of
acromegaly features [4].
In another report, four patients did not demonstrate a
significant response with regard to GH and IGF-1 levels
before and after treatment with an 8 mg oral dose of
rosiglitazone [5].
Three of our four patients presented decreased GH
and IGF-1 levels after being treated with only 4 mg rosi-
glitazone (the usual dose for hyperglycemia in México)
for six months. Despite other reports describing the use
of higher doses, we suggest that dose variation, treat-
ment time, and maybe genetic factors are the causes of
the different results described previously.
It is also important to consider that treatment of acro-
megaly is effective in reducing morbidity and mortality
when biochemical profiles are below “safe” hormone
levels, which were not reached in any of the cases [1,2].
Conclusion
In selected patients with acromegaly, rosiglitazone ther-
apy may decrease GH and IGF-1 levels. Further research
with rosiglitazone, alone or in combination with other
treatment modalities, is required to define its possible
role in long-term medical therapy.
Consent
Written informed consent was obtained from the
patients for publication of this case series and any
accompanying images. A copy of the written consent is
available for review by the Editor-in-Chief of this
journal.
Abbreviations
GH: growth hormone; IGF-1: insulin-like growth factor 1; PPAR-γ: peroxisome
proliferator-activated receptor γ.
Author details
1Subdirección de Investigación, Facultad de Medicina, Universidad
Autónoma de Nuevo León, Monterrey, N.L., México. 2Av. Francisco I. Madero
Pte. s/n y Dr. Aguirre Pequeño, Mitras Centro, C.P. 64460 Monterrey, N.L.,
México. 3Hospital de Especialidades #25 IMSS, Monterrey, N.L., México.
4Lincoln y Gonzalitos s/n. Col. Nueva Morelos. Monterrey, N.L., México.
Authors’ contributions
TH analyzed and interpreted the patient data and was a major contributor
in writing the manuscript. Both BA and GM analyzed and interpreted the
patient data. GH analyzed and interpreted laboratory studies. TA analyzed
and interpreted the laboratory studies and the statistical reporting. All
authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 5 November 2009 Accepted: 21 May 2011
Published: 21 May 2011
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Cite this article as: Tamez-Pérez et al.: Rosiglitazone as an option for
patients with acromegaly: a case series. Journal of Medical Case Reports
2011 5:200.
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Effects of rosiglitazone-peroxisome proliferator-activated receptor γ (PPARγ) agonist on cell viability of human pituitary adenomas in vitro. Neuro Endocrinol Lett

Medical progress: acromegaly.

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Nawroth PP: Long-term treatment of central Cushing’s syndrome with rosiglitazone. Exp Clin Endocrinol Diabetes

Novel pituitary ligands: peroxisome proliferator activating receptor-γ. Pituitary

Rosiglitazone inhibits metastasis development of a murine mammary tumor cell line LMM3. BMC Cancer

T: Does first-line surgery still have its place in the treatment of acromegaly? Ann Endocrinol (Paris)

Yaylali GF: The PPAR-γ activator rosiglitazone fails to lower plasma growth hormone and insulin-like growth factor-1 levels in patients with acromegaly. Neuroendocrinology

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