Original Paper

HOR MON E Horm Res Paediatr 2012;77:152–155 Received: July 1, 2011

RE SE ARCH I N DOI: 10.1159/000337215 Accepted: February 10, 2012
Published online: April 12, 2012
PÆDIATRIC S

© Free Author
Etiologies and Clinical Presentation
Copy – for per-of
sonal use only
Gigantism in Algeria ANY DISTRIBUTION OF THIS
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Farida Chentli Said Azzoug Mohammed El Amine Amani
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Ali El Mahdi Haddam Dalal Chaouki Djamila Meskine
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Key Words pathic cases. Only the first group had neurological, ophthal-
Gigantism ⴢ Hypersomatotropism ⴢ Pituitary tumor ⴢ Sotos © Free
mological, Author
metabolic Copy – forcomplications
and cardiovascular personal use andonly
syndrome ⴢ Constitutional overgrowth received
ANYtreatment.
DISTRIBUTION OFThe
THISresult was not
ARTICLE WITHOUT optimal
WRITTEN CONSENTasFROM
GH S.nor-
KARGER AG, BASEL
malization
Writtenwas not toobserved.
permission Reduction
distribute the PDF ofagainst
will be granted tumor sizeofand
payment a permission fee, wh
decreased GH plasma values were not observed. Conclu-
Abstract sion: Gigantism predominates in males. The main cause is
Background/Aims: True gigantism is an exceptional and fas- GH excess. The diagnosis was very late except for cerebral
cinating pediatric disease. Our aim in this study was to de- gigantism. Complications were observed in pituitary gigan-
scribe the different etiologies of a large group of children tism only. Copyright © 2012 S. Karger AG, Basel
with gigantism and the natural history of their growth. Meth-
ods: In this multicenter study, we considered as giant chil-
dren, adolescents and adults whose heights were 63 SD
compared to their target stature or to our population aver- Introduction
age lengths. Isolated hypogonadism and Klinefelter syn-
drome were excluded from this series. All underwent clinical True gigantism is an exceptional disease due to an
exam, and hormonal and neurological investigations. Re- oversecretion of growth hormone (GH) or genetic disor-
sults: From 1980 to 2010, we observed 30 giants: 26 males ders [1, 2]. Although gigantism has attracted a lot of at-
(86.6%) and 4 females (mean age 19.8 8 11 years). Among tention, there are very few publications on this syndrome
the 13 patients (40.3%) who consulted before the age of 16 because of the extreme rarity of the condition. Complica-
years, 9 had acromegaly and 6 had mental retardation and tions are frequent in those cases. They are observed espe-
body malformations. Based on growth hormone (GH) secre- cially in patients with pituitary tumors. Our objective is
tion evaluation, 2 groups were observed: pituitary gigantism to report a large group of giants observed in Algeria over
(n = 16): GH = 150 8 252 ng/ml (n ^ 5), and other causes with a long period of 30 years, and to describe clinical presen-
normal GH (0.7 8 0.6 ng/ml): 6 Sotos syndrome and 8 idio- tation and etiologies of this very rare affection.

© 2012 S. Karger AG, Basel Prof. Farida Chentli

1663–2818/12/0773–0152$38.00/0 Department of Endocrinology and Metabolism
Fax +41 61 306 12 34 Bab El Oued Hospital
E-Mail karger@karger.ch Accessible online at: Algiers (Algeria)
www.karger.com www.karger.com/hrp Tel. +213 21 96 00 40, E-Mail endofarida @ hotmail.fr
 Subjects and Methods
In this retrospective and prospective multicenter study, we
collected patients who were examined for gigantism from January
1, 1980 to December 31, 2010. These patients were observed in 6
different centers across the country.
Local body overgrowths and simple tallness between 2 and 3
SD observed in obesity, hyperthyroidism and in hypogonadism
such as Klinefelter syndrome were excluded.
We considered as giant children, adolescents and adults whose
heights were 63 SD compared to their target stature (TS) or to
our population average height: 158 cm for women and 170 cm for
men.
Clinical description of the patients was obtained as well as rou-
tine biological parameters. Endocrine evaluation was done at each
institution; it was based especially on plasma GH and IGF1 mea-
surement (when available) plus other hormones (prolactin,
ACTH, cortisol, TSH, FT4, FSH, LH, testosterone and estradiol).
When GH was elevated, oral glucose suppression test was per-
formed. All patients had cerebral CT scan, MRI or both. Genetic
study was not available.
Results
We have collected 30 patients with gigantism: 26 males
(86.6%) and 4 females, mean age: 19.8 8 11 years (1–55).
Thirteen (40.3%) were diagnosed before the age of 16
years. Pituitary gigantism was observed in 15 males and
1 female, Sotos syndrome in 6 boys, and in 8 (5 males, 3
females) no cause could be identified, so they were clas-
sified as idiopathic. The 30 cases were classified into 2
groups according to GH plasma values. In group 1 (G1),
GH was elevated above normal values, and in group 2
(G2) GH was normal.
G1 was composed of 16 patients in whom GH was
clearly elevated (150 8 252 ng/ml, range 7.2–840, n ^ 5),
and was not suppressed during oral glucose loading (na-
dir 83.9 8 132 ng/ml). Mean age at diagnosis was 25 8
10.5 years. The diagnosis was made before the age of 16
years in 4 patients. Their mean height was 186 8 6 cm for
children and 196 8 11 cm for men. The woman’s stature
was 186 cm. Five patients had a lack of pubertal develop-
ment, and 6 had experienced puberty, but they developed
an acquired hypogonadism. Among these giants, 9 had
signs of acromegaly (56%). A pituitary macroadenoma
(110 mm) was found in 15 cases, and an isoadenoma (10
mm) in the female patient. In 4 patients, an increased se-
cretion of GH and prolactin was observed. In 7 cases, a
giant or very large tumor (defined as 1 4 cm) was found
leading to intracranial hypertension in 5 patients. Com-
plications of the macroadenomas were: ophthalmological
troubles (7), psychiatric disorders (2) and pituitary defi-
Etiologies and Clinical Presentation of
Gigantism in Algeria
cits (13). GH excess complications were: glucose metabo-
lism disorders (3), dyslipidemia (6), cardiomyopathy (3),
arterioneuropathy (1) and vertebral abnormalities (4). In
2 patients, an associated tumor was observed: a pheo-
chromocytoma and a hot thyroid nodule.
Except for 2 patients who refused surgery, they were all
operated on (1–5 times). But, tumor resection was either
partial or impossible. The 16 patients received additional
conventional radiotherapy as somatostatin analogs were
not available and high doses of bromocriptine were inef-
ficient or not tolerated. The result of the combined treat-
ment was good for the tumoricidal action as pituitary pro-
cesses disappeared or were significantly reduced in all cas-
es, but GH remained slightly high (13.9 8 12 ng/ml, range
1–33). Metabolic and cardiovascular complications re-
mained stable, but our prepubescent subjects continued to
grow. Their final stature was 206 8 16 cm (190–244; fig. 1).
In G2, plasma GH was normal as well as pituitary area
on CT scan or MRI. Two types of patients were observed
in this group: G2a and G2b.
In G2a, 6 boys with Sotos syndrome were classified.
They were diagnosed during childhood at the age of 4.8
8 3.7 years (1–12). They had a history of tall stature and
mental retardation from birth. Several malformations
were observed such as facial or body deformities, ectopic
testis and/or cerebral asymmetry or atrophy.
Apart from psychological support, they did not receive
any medication. The follow-up did not show any tumor
development or metabolic disorders except for systemic
hypertension (n = 1). In 2 of them, the final heights were
1.80 and 1.86 m (respective TS 1.69–1.62; fig. 1).
In G2b, 8 cases were classified. Except for a family his-
tory of gigantism (4) and pituitary adenoma (1), clinical
exam was normal in all except one in whom prognathism
was observed. Mean age at diagnosis was 19.7 8 6.9 years
(11–31), and statures were 13 SD in 3 subjects aged 11, 12
and 16 years, respectively, and equal to 194 8 4.8 cm for
the others. This group was considered familial or idio-
pathic gigantism as other diagnoses were excluded. No
complications were observed either at diagnosis or during
the follow-up. They did not receive any medications. One
subject continued to grow until the age of 30 years (fig. 1).
Discussion
True gigantism is a very rare disease as only anecdotic
cases have been reported [3–7]. The affection is prevalent
in males. Although stature troubles were precocious, as
they occur in childhood before epiphyseal long bone clo-
Horm Res Paediatr 2012;77:152–155 153

a
Fig. 1. a Male growth chart. b Female
growth chart. b
sure, 60% were diagnosed very late. The diagnosis was
delayed especially in subjects suffering from excess GH.
For Sotos syndrome, the diagnosis was relatively preco-
cious because of evident tallness at birth, large cranial
perimeter and mental retardation.
Concerning the etiologies, similar to de Herder’s re-
view [8] and contrary to the first reports, we found that
154 Horm Res Paediatr 2012;77:152–155
Color version available online
the most important cause is pituitary gigantism. This dis-
ease caused the highest statures. In agreement with oth-
ers, we found that most pituitary gigantisms were due to
pure GH adenomas [9], sometimes to mixed adenomas
[10] secreting prolactin and GH, rarely to pituitary hyper-
plasia [11]. Although the studied population was relative-
ly young, one or more cardiovascular risk factors and
Chentli /Azzoug /Amani /Haddam /
Chaouki /Meskine /Chaouki
complications were present as reported in adults [12]. But,
after treatment they were stabilized. In 2 cases, pituitary
tumors were associated with a hot thyroid nodule and a
pheochromocytoma. Other complications related to gi-
ant or very large pituitary tumors (1 4 cm) were also ob-
served, especially hydrocephaly, optic atrophy and pitu-
itary insufficiency. In adult’s somatotroph adenomas,
surgery is still considered as the best solution for limited
tumors. But, for our patients, pituitary surgery was not
very efficient because of the tumor size and cavernous
system invasiveness. Radiotherapy was efficient as all the
tumors disappeared or were significantly reduced, but
GH normalization took many years. Of course, in this
retrospective study over a long period of time, new treat-
ments such as somatostatin analogues [6, 13] or GH re-
ceptor antagonists such as pegvisomant [5], which are
now very helpful for giant tumors, were not available.
Idiopathic gigantism, also named family gigantism
was the second etiology. But, if one considers simple tall-
ness [14, 15], family or idiopathic cause would be the first.
In idiopathic gigantism, there is not any dysmorphic syn-
drome, but some transitional cases with acromegaly fea-
tures may exist with normal pituitary MRI, normal or
even low GH and IGF1.
Sotos syndrome, also called cerebral gigantism [16–18]
is the third etiology. This heterogeneous genetic disease
is due to mutations and deletions of the NSD1 gene. Ex-
cessive stature may be present in the antenatal period [16].
The macrosomic newborns may also have psychomotor
disorders, a dysmorphic aspect, and many malforma-
tions. Increase in tumor risk has also been reported [18].
In adulthood or in prepuberty, Sotos syndrome is gener-
ally misdiagnosed because prepuberty and definitive
statures may be normal. In the follow-up, 2 boys had ex-
perienced puberty. Their final heights are superior to 3
SD compared to their TS.
Exceptional causes due to genetic disorders such as
multiple endocrine neoplasm syndromes, and very com-
plex syndromes, totally absent in our group, may also in-
duce gigantism.

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Gigantism in Algeria