The impact of genotype on endocrine complications in thalassaemia major.
BACKGROUND
The clinical severity in thalassaemia major (TM) depends on the underlying mutations of the beta-globin gene and the degree of iron overload.


OBJECTIVE
The aim of the study was to investigate the impact of genotype on the development of endocrine complications in TM in our center.


METHODS
126 (62 males, 64 females) thalassaemic patients of Greek Cypriot origin with a mean age of 31.2 (17-68) yr were included in the study. All patients, who were on the standard treatment protocol, were subsequently divided into two groups according to their genotype, group A (92): TM with no mitigating factor and group B (34): TM carrying one or more mitigating factors in the beta- and/or alpha-globin genes. Iron overload calculation was based on the amount of red cell consumption and the mean ferritin level over a 12-year period. Statistical analysis was performed with the SPSS program.


RESULTS
Patients in group A, who were consuming larger amounts of blood on transfusions, were more likely to develop hypogonadism (P = 0.001) compared with patients in group B, despite their similar mean ferritin levels. The incidence of other endocrinopathies (short stature, hypothyroidism, and diabetes mellitus) was similar in the two groups. The prevalence of hypothyroidism in splenectomized patients was significantly higher (P = 0.005), whereas the presence of hypogonadism, impaired glucose homeostasis and insulin resistance, although more frequent, was not statistically significant. The clinical severity of TM had no impact on bone mineral density (BMD) in both men and women. BMD was only influenced by gonadal function.


CONCLUSIONS
This study demonstrates that the underlying genetic defect in TM is a contributing factor for gonadal dysfunction, because the patients with the more severe defects have a greater rate of iron loading through higher red cell consumption.
Skordis
Nicos
N
Pediatric Endocrine Unit, Makarios Hospital, Nicosia, Cyprus. nskordis@cytanet.com.cy
Michaelidou
Monica
M
Savva
Savvas C
SC
Ioannou
Yiannis
Y
Rousounides
Andreas
A
Kleanthous
Marina
M
Skordos
George
G
Christou
Soteroulla
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001803:Blood Transfusion / Q000706:statistics & numerical data; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000453:epidemiology / Q000209:etiology*; D015913:Chelation Therapy / Q000009:adverse effects; D003131:Combined Modality Therapy; D003535:Cyprus / Q000453:epidemiology; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology*; D004392:Dwarfism / Q000453:epidemiology / Q000209:etiology*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000453:epidemiology / Q000209:etiology*; D007037:Hypothyroidism / Q000453:epidemiology / Q000209:etiology*; D015994:Incidence; D007333:Insulin Resistance / Q000235:genetics; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use; D019190:Iron Overload / Q000209:etiology; D008297:Male; D008597:Menstrual Cycle; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013156:Splenectomy; D065227:Transfusion Reaction; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery / Q000628:therapy
D001786:Blood Glucose; D007502:Iron Chelating Agents; D005914:Globins; D005293:Ferritins; D007501:Iron