Journal of Advances in Medicine and Medical Research

33(6): 97-109, 2021; Article no.JAMMR.66412

ISSN: 2456-8899
(Past name: British Journal of Medicine and Medical Research, Past ISSN: 2231-0614,
NLM ID: 101570965)

Magnetic Resonance Imaging Versus Serum Iron

Status as Diagnostic Tools for Pituitary Iron
Overload in Children with Beta Thalassemia
Lamia M. Morad1*, Mohamed R. EL-Shanshory1, Nahed M. Hablas1,
Amal S. El-Bendary2, Rasha A. El-Shafey3 and Adel A. Hagag1
1
Departments of Pediatrics, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt.
2
Departments of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt.
3
Departments of Radiology, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt.

Authors’ contributions

This work was carried out in collaboration among all authors. Author LMM designed the study,
performed the statistical analysis, wrote the protocol and wrote the first draft of the manuscript.
Authors NMH, RAEl-S, ASEl-B and MREL-S managed the analyses of the study. Author AAH
managed the literature searches. All authors read and approved the final manuscript.

Article Information

DOI: 10.9734/JAMMR/2021/v33i630866
Editor(s):
(1) Dr. Kalpy Julien Coulibaly, Félix Houphouet-Boigny University, Côte d'Ivoire.
Reviewers:
(1) Daniela de Oliveira Werneck Rodrigues, Centro Universitario Presidente Antonio Carlos, Brazil.
(2) Muhammad Muizz Uddin, Dow University of Health Sciences, Pakistan.
Complete Peer review History: http://www.sdiarticle4.com/review-history/66412

Received 15 January 2021

Original Research Article Accepted 17 March 2021
Published 25 March 2021

ABSTRACT

Background: Thalassemia is a common genetic disorder associated with endocrine disorders. Iron
deposition may start in the anterior pituitary gland, but clinical signs are usually not evident until
puberty. Aim of the study was to evaluate pituitary iron overload in children with β thalassemia using
MRI T2* and correlate MRI T2* and biochemical markers of iron overload with pituitary hormones.
Patients and Methods: This study was carried out on 30 children with β-thalassemia major (19
females and 11 males ) with their age ranging from 10 - 18 years and mean age value of 12.8 ± 2.4
and 30 healthy children of matched age and sex as controls in the period from September 2018 to
September 2019. For all patients the following were done: complete clinical evaluation including
anthropometric data and Tanner staging, laboratory investigations including serum iron status,
thyroid function, basal and growth hormone provocation test by clonidine, Follicle stimulating
hormone (FSH) , Luteinizing hormone (LH) , and pituitary MRI T2*.
_____________________________________________________________________________________________________

*Corresponding author: E-mail: [email protected];

 Morad et al.; JAMMR, 33(6): 97-109, 2021; Article no.JAMMR.66412

Results: Weight, Z score of weight, height, Z score of height and Body mass index (BMI) were
found significantly lower in patients compared with controls. Patients had delayed puberty
compared with controls. Pituitary MRI T2* was found significantly lower in patients compared with
controls (P=0.001). FSH, LH, and provocative growth hormone levels were found significantly lower
in patients compared to controls (p <0.001). Serum ferritin & iron were found significantly higher in
patients than controls (P<0.001). Significant negative correlations were found between serum
ferritin and Weight, Height, Z score of Weight, Z score of Height, BMI and pituitary hormones.
Significant negative correlations were found between Pituitary MRI T2* and serum ferritin.
Significant positive correlations were found between Pituitary MRI T2* and Weight, Height, Z score
of Weight, Z score of Height and pituitary hormons. The pituitary T2* carried the sensitivity of 80%
,100% and 100% and specificity of 70% ,83.3% and 100% for predicting GH hormone abnormality,
LH and FSH respecetively.
Conclusions: There were a significant positive correlations between pituitary MRI T2*and
anthropometric measurement and pituitary hormones of studied patients. There was a significant
negative correlation between Pituitary T2* and serum ferritin. Pituitary iron overload can be detected
by MRI T2* which is a diagnostic tool in detecting pituitary iron overload with subsequent effect on
hormonal secretion especially growth hormone.
Recommendations: Children with thalassemia should undergo meticulous follow up regarding
regular blood transfusion, regular iron chelators in a proper manner and doses and routine use of
MRI T2* in the evaluation of pituitary iron overload before irreversible damage occur in the pituitary
gland.

Keywords: Thalassemia; iron overload; pituitary MRI T2*.

1. INTRODUCTION greater concern in large patients with

thalassemia. They are the second leading cause
Thalassemia is a category of genetic disorders of mortality in this population, after heart disorder
characterized by impairment of globin-chain [5].
synthesis [1].
There are three major clinical manifestations of
The human body lacks active mechanism to the hypothalamic–pituitary– gonadal axis
excrete excess iron, therefore repeated blood derangement (HPG) in TM, including delayed
transfusions lead to iron overload in these puberty, arrested puberty and hypogonadism [4].
patients. Excess iron can deposit in body organs
particularly in pancreas, liver, pituitary, and the Hypogonadotropic hypogonadism in thalassemia
heart. To avoid iron overload, thalassemia is associated not only with iron toxicity on
patients are treated with iron chelators gonadotropic cells, but also with adipose tissue
concomitantly with the blood transfusions [2]. and leptin resulting in impaired leptin synthesis
and decreased its physiological role in sexual
Labile plasma iron (LPI) or reactive plasma iron maturation and fertility as leptin significantly
(RPI) reflects the potentially harmful source of increases in early puberty and stimulates
circulating iron as it produces oxygen radical hypothalamic pituitary-gonadal axis [6].
species that can destroy cell membranes and
also intracellular organelles (including 1.2 Aim of the Work
mitochondria and nuclei) and DNA [3].
The aim of this work was to evaluate pituitary
Iron deposition may begin in the anterior pituitary iron overload in children with β thalassemia
gland in the first decade of life, but clinical using MRI T2* and correlate MRI T2* and
symptoms are usually not apparent before biochemical markers of iron overload with
puberty. Only reduced gonadotropin reserve was pituitary hormones.
observed at the earlier stage, with intact
gonadotropin pulse. Until hypogonadism occurs 2. PATIENTS AND METHODS
an asymptomatic process of pituitary siderosis
may occur [4]. This case control study was carried out after
approval from ethical committee of research
Disorders of endocrinopathy caused by frequent center of Tanta University permission number
blood transfusions and iron overload are of 32211/03/18 and obtaining written consents from

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the parents of all children included in this study serum was collected in three tubes. The 1st tube
and was conducted on 30 children with for assessment of serum growth hormone, GH
transfusion dependent β-thalassemia major provocation test by clonidine [9,10] , the 2 nd
including 19 females and 11 males with their age tube for measurement of liver and kidney
ranging from 10 - 18 years and mean age value functions [11] and The 3rd part for measurement
of 12.8 ± 2.4 who attended to Hematology Unit, of serum iron, total iron binding capacity [12],
Pediatric Department, Tanta University Hospital serum ferritin [13], Thyroid function (free T3, free
in the period from September 2018 to T4, TSH), FSH and LH [14].
September 2019 and 30 healthy children of
matched age and sex as a control group . 4. Radiological Investigations including:
Assessment of bone age by Greulich and
2.1 Inclusion Criteria Pyle method [15] and Pituitary MRI (MRI
T2*) [16].
Children with transfusion dependent β- 5. Chelation Therapy in studied patients:
Thalassemia major aged 10 - 18 years.
Deferasirox alone in a dose of 20-30 mg/kg/day
2.2 Exclusion Criteria once daily before meals [17], or Desferrioxamine
alone 20-40 mg/kg/day for 6 days /week but in
Children with thalassemia combined with other patients with persistently high serum ferritin
chronic hemolytic anemias as sickle levels above 3000 ng/ml, Deferasirox is
thalassemia. combined with Desferrioxamine in a dose of 20-
40 mg/kg/day for 10 days per month either by
Children with β- thalassemia with subcutaneous infusion using infusion pump in 8-
contraindication to MRI as prosthetic valve, and 12 hours/day or by continuous intravenous
dental prosthesis. infusion for 8-10 hours/day (combined chelation
therapy [18].
2.3 All Patients in this Study were
Subjected to the Following 2.4 Statistics
1. Complete history taking with special Statistical analysis of the present study was
account on: consanguinity between conducted, using mean, standard error, student
parents, family history of thalassemia, age t- test, Chi-square, Linear Correlation Coefficient
of diagnosis of thalassemia, frequency of tests by SPSS V17.
blood transfusion and iron chelation
therapy (types and regularity).
3. RESULTS
2. Thorough clinical examination with special
account on pallor, jaundice, mongoloid
facies, , hepatomegaly, splenomegaly or Weight, Z score of weight, height, Z score of
splenectomy, anthropometric height and body mass index was significantly
measurements including body weight , lower in patients compared with control group
height ,body mass index (BMI) and Tanner (Table 1).
staging for assessment of puberty.
3. Laboratory investigations; Delayed puberty was found in patients compared
with control group according to Tanner staging.
Specimen collection and preparation: Significantly higher prevalence of delayed
menstruation (primary amenorrhea) was found in
Ten ml of venous postprandial pre-transfusion female patients compared with control group
blood were collected using sterile needles (Table 1).
through gentle venipuncture after sterilization of
puncture site and were classified in to ; 2 ml on Pallor and jaundice were the most common
20 uL EDTA for CBC including differential WBCs presenting symptoms in thalassemic patients,
count which was done on Leishman stained while hepatomegaly and spleenectomy were the
blood smear with evaluation using ERMA PCE- most common signs (Table 2).
210 N cell – counter’ [7] and HPLC [8] and 3 ml
in a plain tube that was allowed for clotting in a Microcytic hypochromic anemia with
water bath at 37ºc. After clotting, centrifugation reticulocytosis was found in studied patients with
was done at 1500x for 10 minutes. Separated thalassemia. Total leucocytic count and platelet

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count were significantly higher in patients than Statistically significant positive correlation was
control group (Table 3). found between pituitary T2* with weight, height,
BMI, Z score of height and Z score of weight
Serum ferritin and serum iron were significantly (Table 5).
higher, while TIBC was significantly lower in
patients than control group (Table 3). Statistically significant positive correlation
was found between pituitary T2* with ferritin,
Serum growth hormone, FSH and LH were FSH, LH and growth hormone (Table 5 and Fig.
significantly lower in patients than controls (Table 3).
4).
No statistically significant correlation was found
Statistically significantly lower level of pituitary between pituitary T2* with bone age (Table 4).
T2* was found in patients compared to controls
(Table 4). Significant negative correlation was found
between serum ferritin and growth hormone of
Statistically significant negative correlation was thalassemic patients (Table 5).
found between serum ferritin with weight, height,
BMI, Z score of height and Z score of weight and Non-significant difference was found between
bone age (Table 5). patients and controls as regard TSH, free T3 ad
free T4 levels (Table 4).
Statistically significant negative correlation was
found between serum ferritin with FSH, LH and The pituitary T2* carried the sensitivity of 80%
GH (Table 5 and Fig. 1). ,100% and 100% and specificity of 70% ,83.3%
and 100% for predicting GH hormone
Statistically significant negative correlation was abnormality, LH and FSH respecetively (Table
found between pituitary T2* with serum ferritin 6).
(Fig. 2).

Table 1. Demographic data, anthropometric measurements and Tanner staging in studied

groups

parameters Patients (n=30) Controls (n=30) t or X2 P-value

Age(years)
Range 10 -18 10-18 - 0.494 0.623
Mean ±SD 12.8±2.4 13.1±2.3
Weight (kg)
Range 26 - 48 32.87 ± 5.26 -9.847 <0.001*
Mean ±SD 40 - 77 52.30 ± 9.44
Z score Weight
Range -3.5 - 0.6 -1.10 ± 1.14 -14.716 <0.001*
Mean ±SD 1-4 2.70 ± 0.84
Height (cm)
Range 125 – 155.5 136.95 ± 7.73 -12.203 <0.001*
Mean ±SD 145 - 169 158.60 ± 5.89
Z score Height
Range - 4 – 1.5 -1.60 ± 1.66 -12.592 <0.001*
Mean ±SD 1-4 2.67 ± 0.83
BMI (kg/m2)
Range 13.6 – 21.3 17.03 ± 1.97 -8.451 <0.001*
Mean ±SD 18.6 - 24 21.22 ± 1.88
Tanner Stage
Stage I Stage II Stage 9 (30%) 3 (10%) 28.932 <0.001*
III Stage IV Stage V 13 (43.3%) 5 (16.7%)
6 (20%) 5 (16.7%)
2 (6.7%) 7 (23.3%)
0 (0%) 10 (33.3%)
* Significant difference ( P < 0.05)

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Table 2. Clinical data, chelation therapy and frequency of blood transfusion in studied patients

Parameters Patients (n=30)

Clinical data
Pallor 30 (100%)
Jaundice 30 (100%)
Hepatomegaly 30 (100%)
Splenectomy 30 (100%)
Mongoloid Facies 30 (100%)
Types of iron chelators
SC Desferroxamine (Desferal) 7 (23 %)
Oral Deferasirox (Exjade) 9 (30 %)
Combined chelation therapy 14 (46.7 %)
Regularity of iron chelators
Regular 14 (46.7%)
Irregular 16 (53.3 %)
Frequency of blood transfusion
Every 2 Weeks 5 (16.7 %)
Every 3 Weeks 10 (33.3 %)
Every 4 Weeks 9 (30 %)
Every >4 Weeks 6 (20 %)
Table 3. Comparison between patients and controls as regard pre-transfusion complete blood
count and iron profile

Measure Patients (n=30) Controls (n=30) t or X2 P value

Hemoglobin Range 5-8 11 - 13.5
(gm/dl) Mean±SD 6.3 ± 1.1 11.8± 0.6 - 19.401 0.001*
RBCs Range 1.7 – 2.7 3.5 – 5
(million/mm3) Mean±SD 2.1 ± 0.4 4.3 ± 0.4 -17.115 0.001*
Range 15 – 24 33 – 39
Hematocrit (%) Mean±SD 18.9 ± 3.2 35 ± 1.7 -19.450 0.001*
Range 50 -70 79 – 93
MCV (fL) Mean±SD 52 ± 12.2 85.9 ± 4 -11.510 0.001*
Range 20 -26 28- 32
MCH (pg) Mean±SD 21.8 ± 2.5 30.6± 1.7 -12.807 0.001*
Range 30 -34 31 -36
MCHC (%) Mean±SD 32.2 ± 1 32.9 ± 1.3 -1.965 0. 737
Retics (%) Range 3–7 0.7 – 2
Mean±SD 5.3 ± 1.2 1.3 ± 0.5 13.108 0.001*
Platelets Range 178 -555 150 -453
(thousands/mm3) Mean±SD 336 ± 108.6 253.9± 95.8 3.129 0.003*
WBCs Range 4 – 12 4 – 9.876
(thousands/m m3) Mean±SD 7.36± 24.53 5.89± 16.21 2.724 0.009*
Serum Ferritin Range 2000 - 9876 40 – 321
(ng/ml) Mean±SD 4907.6±2288.9 150.2±88.2 11.376 < 0.001*
Serum Iron Range 155 – 543 66 – 176
(μg/dl) Mean±SD 315.5±117.2 119.3±32.4 8.839 < 0.001*
Total iron binding Range 122 – 333 250 – 345
capacity (μg/dl) Mean±SD 207.4± 49.2 281.8± 19.7 -7.692 < 0.001*
MCV= mean corpuscular volume, MCH= mean corpuscular hemoglobin MCHC= mean corpuscular hemoglobin
concentration. WBCs= White blood cells

4. DISCUSSION various organs non-invasively and without

contrast [19].
MRI is a crucial instrument in the current
management of thalassemia patients owing to The aim of this work was to evaluate pituitary
its ability to measure iron overload in iron overload in children with β thalassemia

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using MRI T2* and correlate MRI T2* and In the current study, there was delayed
biochemical markers of iron overload with puberty according to tanner staging in
pituitary hormones. patients with thalassemia compared with control
group.
In the current study, significantly lower
anthropometric measurements including weight, This is in agreement with Al-Naama et al. [20]
Z score of weight, height, Z score of height and who reported that 63% of male patients with
body mass index (BMI) were found in patients beta thalassemia major ≥ 14 years of age and
compared with control group. 54.5% of female patients with beta thalassemia
major ≥ 13 years of age showed signs of
This comes in agreement with Al-Naama et al. delayed puberty. In contrast, all individuals in
[20] and Alsharnoubi et al. [1], they found the control group exhibited normal pubertal
significantly lower BMI, BMI -score, height, development and Dhouib et al. [23] who
and weight in patients of both sexes with -TM reported that 42% of studied patients had a
than in controls. Short stature was observed in delayed puberty.
52% of patients with –TM and as regard to
BMI, our results are in agreement with Eissa There was significantly higher prevalence of
and El-Gamal [21] and Hagag et al. [19] who amenorrhea in female patients with thalassemia
found significantly lower BMI in patients compared to control group. Also Sutay et al.
compared with controls which was explained by [24] studied 56 females with βTM and 50
chronic nature of the disease. healthy girls. The cases and controls were
further divided into 2 groups based on age from
Growth retardation in thalassemic children could 8-12 years and > 12 up to 16 years. They found
be attributed to chronic anemia caused by no cases and 26.3% of controls had attained
inadequate transfusion, hypoxia, and other menarche in the age group of 8-12 years
endocrine disorders which occur due to iron whereas 11.4% of cases and 93.3% of controls
overload causing failure of puberty and in the age group of >12 years had attained
consequent growth retardation [22]. menarche.

Table 4. Comprison between patients and controls as regard thyroid hormones, basal GH,
provocative GH, FSH, LH , bone age and Pituitary MRI T2*

Measure Patients (n=30) Controls (n=30) t or X2 P value

TSH (IU/mL) Range 0.7 - 5 1.8 – 5
Mean±SD 2.9 ± 1.7 2.9 ± 0.8 -0.211 0.833
Free T3 (pg/ml) Range 2.7 - 6 1.0 – 4
Mean±SD 3.8 ± 1 3.5 ± 0.8 1.551 0.126
Free T4 (ng/dl) Range 12 – 21.3 11 -20
Mean±SD 16 ± 2.3 15.2± 2.5 1.333 0.188
Basal GH Range 0.2 – 4 7- 13
Mean±SD 1.2± 1 8.7± 1.4 -16.078 0.001*
GH after 30 minute Range 0.2 – 11.9 6 – 12 0.001*
Mean±SD 4.0 ± 2.8 8.2 ± 1.3 -3.917
GH after 60 minutes Range 0.9 – 10 4.0 – 3.4
Mean±SD 4.0 ± 2.8 7.9 ± 1.3 -2.409 0.001*
GH after 90 minutes Range 0.4 – 8.6 7.0 – 13
Mean±SD 2.5± 2.3 8.8± 1.3 -13.229 0.001*
GH after 120 Range 0.2 – 4.3 6 – 12
minutes Mean±SD 1.4± 1 8.1± 1.3 -22.109 0.001*
Range 0.1 – 3.8 2.5- 11.5
FSH (mIU/ml) Mean±SD 1.44± 1.15 5.72± 2.349 -11.67 <0.001*
LH (mIU/ml ) Range 0.1 – 5.2 2.5 – 12.5
Mean±SD 1.286±1.319 6.470±2.55 -12.74 <0.001*
Range 10 -14 10 -18
Bone age Mean±SD 11.5± 1.4 12.8±2.5 -2.409 0.001*
Pituitary T2* Range 5.83-16.34 10.24-54.37
ms Mean±SD 6.5 ± 29.9 40.0± 75.0 -17.681 0.001*

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Fig. 1. Correlation between serum ferritin and FSH (Lt) and LH (Rt) in studied patients

Fig. 2. Correlation between pituitary T2* and serum ferritin in studied patients

Fig. 3. Correlation between pituitary T2* and FSH (Lt) and LH (Rt) in studied patients

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Table 5. Correlations between serum ferritin, pituitary T2* and anthropometric measurements
and pituitary hormones of studied patients

Correlations
Serum ferritin (ng/ml) Pituitary T2*(ms)
r P-value r p-value
Wt (kg) -0.620 0.001* 0.732 0.001*
HT (cm) -0.659 0.001* 0.776 0.001*
BMI (Kg/m2) -0.609 0.001* 0.556 0.001*
FSH (mIU/ml) -0.772 0.001* 0.792 0.001*
LH (mIU/ml) -0.383 0.003* 0.453 0.007
Pituitary T2* (ms) 0.401 0.001*
Serum ferritin (ng/ml) ------- ------ - 0.866 0.001*
Basal GH (ng/ml) - 0.774 0.871 0.001*
After 30 min -0.562 0.453 0.001*
After 60 min -0.612 0.596 0.001*
After 90 min -0.678 0.798 0.001*
After 120 min -0.743 0.001* 0.835 0.001*

Table 6. ROC curve of Pituitary T2* for detection of growth hormone , FSH, LH abnormality and
comparison between pituitary T2* and serum ferritin as diagnostic tool for hormonal
abnormality

ROC curve Cutoff AUC P sensitivity specificity

Pituitary T2* GH 20.0 0.855 <0.001 80% 70%
LH 35.0 0.958 <0.001 100% 83.3%
FSH 35.5 1.000 <0.001 100% 100%
Serum ferritin GH LH - - - 68.2% 100%
FSH - - - 100% 83.3%
- - - 100% 100%

Hypogonadotropic hypogonadism is the most In the current study no significant differences

frequent endocrinopathy in patients with were found between patients and control group
transfusion-dependent thalassemia affecting 70- as regard TSH, free T3 and free T4.
80% of all thalassemia patients [25]. This
complication is largely explained by toxic effect This is in agreement with Al-Hakeim et al. [27]
of iron overload secondary to chronic blood who found no significant differences between
transfusions because the human body lacks a thalassemic patients and healthy control as
mechanism to excrete excess iron [26]. regard free T3, free T4, and TSH.

In our study, there were significantly higher Sharma et al. [28] found hypothyroidism in only
serum ferritin and serum iron and significantly 4.7 % of patients with thalassemia.
lower serum total iron binding capacity in studied
The thyroid pituitary axis seems to be less
patients compared with controls which could be
sensitive to iron deposition damage than
explained by frequent packed RBCs transfusion
gonadal and GH axis. Hence, secondary
and irregular iron chelators intake which was
hypothyroidism is rare in patients with
found in most of studied patients .
thalassemia, which was not observed in our
study.
This comes in agreement with Eissa and El-
Gamal [21] and Hagag et al. [19] who found the In contrast to our study Drema et al. [29] found
same results . subclinical hypothyroidism in 24% of patients
and in 2% overt hypothyroidism and explained
Iron overload in beta thalassemia could be the high prevalence of hypothyroidism in Indian
explained by two main mechanisms, increased patients with thalassemia by suboptimal
iron absorption due to ineffective erythropoiesis chelation due to high cost of iron chelation
and repeated blood transfusion [19]. therapy and poor compliance.

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Thyroid dysfunction in thalassemia (primary and Imtiaz et al. [32] found significantly lower
hypothyroidism) is mostly due to iron deposition mean growth hormone level among children with
in the thyroids with varying frequency depending thalassemia compared with control group.
on the region, quality of management and
treatment protocols [29]. Moreover, Ziari and Rahmani [34] found that
54.74% of patients with thalassemia major had
In the current study there were significantly lower growth hormone secretion disorder and Dhouib
levels of FSH and LH in patients compared to et al. [23] found GH deficiency in 35% of studied
control group. patients.

Our results come in agreement with Sutay et al. In contrast to our study Dhale et al. [35] found
[24] who found the same results. that the mean level of Growth Hormone among
thalassemia major patients was in the normal
Iron deposition may begin in the anterior pituitary range and insignificantly different from their
gland in the first decade of life, but clinical controls.This could be explained by regular
symptoms are usually not apparent before blood transfusion, effective chelation therapy
puberty. Only reduced gonadotropin reserve was and aggressive nutritional supplements.
observed at the earlier stage, with intact
gonadotropin pulse. Until hypogonadism occurs In the current study, there is statistically
an asymptomatic process of pituitary siderosis significantly lower level of pituitary T2* in
may occur [4]. patients compared to control group.

Hypogonadotropic hypogonadism is not only due This comes in agreement with Çetinçakmak etal.
to iron toxicity on gonadotropic cells, but also [36], Bozdag et al. [37] and Karadag et al. [16]
adipose tissue and leptin affection resulting in who found the same results .
decreasing leptin synthesis and impairement of
its role in sexual maturation and fertility as level In the current study, there is a statistically
of leptin increases dramatically in early puberty significant negative strong correlation between
and has positive effect on hypothalamic pituitary- ferritin with weight, height, BMI, Z score of height
gonadal axis [6]. and Z score of weight and bone age in studied
groups .
In contrast to our results Siripunthana et al. [30]
found that the basal levels of serum LH and FSH This comes in accordance with Moiz et al. [38]
were not significantly different between pubertal who found significant negative correlation
patients and controls suggesting that the between height for age z-score and serum
hypothalamic– pituitary–gonadal axis is intact. ferritin levels and Rathaur et al. [39] who found
They attributed their results to adequate (65.71%) of studied patients had short stature,
treatment with blood transfusion at an 77% were underweight and rest had normal BMI
appropriate time, effective iron chelation and and they found also statistically significant
relatively younger patients in their study. negative correlation between serum ferritin and
short stature .
In the current study there was significantly lower
bone age in patients compared to control group. In the present study, there was a statistically
This is in agreement with Shah et al. [31] who significant negative correlation between serum
found bone age deficit in 86% of patients with ferritin with FSH and LH.
thalassemia Dhouib et al. [23] who reported that
bone age delay was over one year in all patients This comes in agreement with Hagag et al. [6],
with thalassemia and Imtiaz et al. [32] who found AL TN and Zuhairy [40] who found significant
significant lower bone age in patients with negative correlations between serum ferritin ,
thalassemia compared with control group. FSH and LH. This could be explained by
progressive damage of pituitary gland with
In the present study there was significantly lower subsequent decrease of gonadal hormones with
serum growth hormone level in patients progressive increase in iron load.
compared to control group .This is in agreement
with Azeez et al. [33] who found significant However Abo-Elwafa et al. [41] found
decrease in serum GH in male patients with insignificant correlation between serum ferritin
thalassemia compared with that of control group and FSH, LH, estradiol and testosterone which

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could be explained as there are other etiological accumulation may develop around 4 years of
factors responsible for hypogonadism in these age, pubertal delay is apparent 10 years later
patients, the most important one is chronic when tissue changes often become irreversible.
persistent anemia, hepatic affection and Beside iron-induced damage and chronic
synchronous association of other endocrine hypoxia (low pre- transfusion hemoglobin) other
dysfunction as hypothyroidism. factors contributing to final adult height include
ethnicity, genetic composition, hormonal status,
In the current study, there was statistically nutritional deficiencies, degree of chelating
significant negative correlation between serum agents utilization, emotional factors,
ferritin with basal GH and provocative Growth endocrinopathies and chronic liver disease.
hormone level after 30 minutes, after 60
minutes, after 90 minutes, and after 120 In this study, the Receiver Operating
minutes. Characteristics (ROC) analysis was performed to
examine the ability of pituitary T2* for predicting
This is in agreement with Azeez et al. [33], GH, LH and FSH abnormality.
Fadlyana et al. [42] and Jahargirdar et al. [43]
who found significant negative correlation The pituitary T2* carried the sensitivity of
between serum ferritin level and Growth 80%,100% and 100% and specificity of
hormone. 70%,83.3% and 100% for predicting GH
In this study, there was statistically significant hormone abnormality, LH and FSH respecetively.
positive correlation between pituitary T2* with
weight, height, BMI, Z score of height and Z This comes in agreement with Mousa et al. [44]
score of weight, while no statistically significant who reported that pituitary T2* had sensitivity
correlation was present with bone age . and specificity of 100% and 88%, respectively in
patient with short stature and hypogonadism.
This could be explained by Moiz et al. [38] who
found that growth failure in thalassemia major is 5. CONCLUSION
multifactorial, iron overload is one of the main
factors, frequent blood transfusions can control There was a significant negative correlation
pretransfusion hemoglobin levels, but if serum between Pituitary T2* and serum ferritin. There
ferritin levels are greater than the desired levels, were a significant positive correlations between
patients’physical growth can be affected. pituitary MRI T2*and anthropometric
measurement and pituitary hormones of studied
In the present study, there was a statistically patients.
significant negative correlation between pituitary
T2* with serum ferritin. Pituitary iron overload can be detected by MRI
T2* which is a diagnostic tool in detecting
This is in agreement with Bozdag et al. [37] who pituitary iron overload with subsequent effect on
found significantly higher pituitary iron hormonal secretion
accumulation in β -TM with hypogonadism than especially growth hormone.
both healthy subjects and β -TM patients without
hypogonadism and Karadag et al. [16] who 6. RECOMMENDATIONS
found negative correlation between serum ferritin
level and pituitary T2* value in patient with Children with thalassemia should undergo
hypogonadism . meticulous follow up regarding regular blood
transfusion, regular iron chelators in a proper
In contrast to our results, Çetinçakmak et al. [36] manner and doses and routine use
found positive correlation between Pituitary T2* of MRI T2* in the evaluation of pituitary iron
values and serum ferritin. overload before irreversible damage occur in the
pituitary gland.
In the present study, there was statistically
significant positive correlation between pituitary CONSENT AND ETHICAL APPROVAL
T2* with FSH and LH.
This case control study was carried out after
This comes in agreement with Moiz et al. [38] approval from ethical committee of research
who reported that Pituitary MRI studies center of Tanta University permission number
demonstrated that severe pituitary iron 32211/03/18 and obtaining written consents from

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the parents of all children included in this study ARKRAY ADAMS A1c HA-8180T analyzer
and was conducted on 30 children with for diagnosis of thalassemia and
transfusion dependent β-thalassemia major hemoglobinopathies common in Southeast
including 19 females and 11 males with their age Asia. Laboratory Medicine.
ranging from 10 - 18 years and mean age value 2014;45(3):e112–e121.
of 12.8 ± 2.4 who attended to Hematology Unit, 9. Nicol L, Allen D Czernichow P, Zeitler P.
Pediatric Department, Tanta University Hospital Normal growth and growth disorders. In;
in the period from September 2018 to Kappy MSP, Allen DB ad Geffner ME
September 2019 and 30 healthy children of (Eds). Pediatric Practice: Endocrinology.
matched age and sex as a control group 2nd edition. McGraw-Hill Education /
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hormone deficiency in the paediatric and
Authors have declared that no competing transitional age. Best Pract Res Clin
interests exist. Endocrinol Metab. 2016;30(6):737-74.
11. Osman KS, Aly LH, Abd El-Hamid WM,
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