Investigating the Role of Ferritin in Determining Sexual Underdevelopment in Beta-Thalassemia Major Patients: A Cross-Sectional Analysis From Pakistan

Shahid, Zia; Hassan, Sarmad; Ghazanfar, Saqlain; Kaneez, Mehwish; Khan, Muhammad Sheharyar; Tariq, Hafiz Tanveer; Jawad, Arslan Tahir; Shuaib, Atifa; Bhatti, Assadullah Akram; Razzaq, Mustafa Tauseef

doi:10.7759/cureus.15572

Cited by 6 publications

(6 citation statements)

References 18 publications

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“…Patients in the pubescent (stage 3) or post-pubescent (stages 4 and 5) stages, on the other hand, were deemed sexually developed. 19 The gonadal function of the patient was evaluated by history, physical examination and laboratory tests, including the serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), serum testosterone for males and serum estradiol for females. The serum ferritin level was also measured to assess the iron overload status of the patients.…”

Section: Methodsmentioning

confidence: 99%

Prevalence of hypogonadism in transfusion-dependent β-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

Chowdhury

Iktidar

Ahmed

et al. 2023

Hematology, Transfusion and Cell Therapy

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Section: Methodsmentioning

confidence: 99%

Prevalence of hypogonadism in transfusion-dependent β-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

Chowdhury

Iktidar

Ahmed

et al. 2023

Hematology, Transfusion and Cell Therapy

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“…TED-related hypogonadism is due to IO, general health status, BTH complications, and potential side effects of different regimes. It manifests during puberty or adult life, either as primary or secondary amenorrhea in females [ 51 , 52 ]. Its prevalence varies among studies, related especially to whether or not the pubertal status is taken into consideration.…”

Section: Thalassemic Endocrine Diseasementioning

confidence: 99%

“…According to one study, the prevalence is 23.6% among patients at puberty age, and ferritin negatively correlates with pituitary volume [ 27 ]. Some suggested that puberty failure might be predicted by serum ferritin [ 22 , 52 ]. A transversal study from a single tertiary centre included 58 patients (33/58 males) with transfusion-dependent TH (aged between 17 and 19 y) and 72.4% of subjects experienced either normal puberty or delayed onset with spontaneous progression, but 26.7% of them experienced arrested puberty requiring hormonal intervention.…”

Section: Thalassemic Endocrine Diseasementioning

confidence: 99%

New Entity—Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement

et al. 2022

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Beta-thalassemia (BTH), a recessively inherited haemoglobin (Hb) disorder, causes iron overload (IO), extra-medullary haematopoiesis and bone marrow expansion with major clinical impact. The main objective of this review is to address endocrine components (including aspects of reproductive health as fertility potential and pregnancy outcome) in major beta-thalassemia patients, a complex panel known as thalassemic endocrine disease (TED). We included English, full-text articles based on PubMed research (January 2017–June 2022). TED includes hypogonadism (hypoGn), anomalies of GH/IGF1 axes with growth retardation, hypothyroidism (hypoT), hypoparathyroidism (hypoPT), glucose profile anomalies, adrenal insufficiency, reduced bone mineral density (BMD), and deterioration of microarchitecture with increased fracture risk (FR). The prevalence of each ED varies with population, criteria of definition, etc. At least one out of every three to four children below the age of 12 y have one ED. ED correlates with ferritin and poor compliance to therapy, but not all studies agree. Up to 86% of the adult population is affected by an ED. Age is a positive linear predictor for ED. Low IGF1 is found in 95% of the population with GH deficiency (GHD), but also in 93.6% of persons without GHD. HypoT is mostly pituitary-related; it is not clinically manifested in the majority of cases, hence the importance of TSH/FT4 screening. HypoT is found at any age, with the prevalence varying between 8.3% and 30%. Non-compliance to chelation increases the risk of hypoT, yet not all studies confirmed the correlation with chelation history (reversible hypoT under chelation is reported). The pitfalls of TSH interpretation due to hypophyseal IO should be taken into consideration. HypoPT prevalence varies from 6.66% (below the age of 12) to a maximum of 40% (depending on the study). Serum ferritin might act as a stimulator of FGF23. Associated hypocalcaemia transitions from asymptomatic to severe manifestations. HypoPT is mostly found in association with growth retardation and hypoGn. TED-associated adrenal dysfunction is typically mild; an index of suspicion should be considered due to potential life-threatening complications. Periodic check-up by ACTH stimulation test is advised. Adrenal insufficiency/hypocortisolism status is the rarest ED (but some reported a prevalence of up to one third of patients). Significantly, many studies did not routinely perform a dynamic test. Atypical EM sites might be found in adrenals, mimicking an incidentaloma. Between 7.5–10% of children with major BTH have DM; screening starts by the age of 10, and ferritin correlated with glycaemia. Larger studies found DM in up to 34%of cases. Many studies do not take into consideration IGF, IGT, or do not routinely include OGTT. Glucose anomalies are time dependent. Emerging new markers represent promising alternatives, such as insulin secretion-sensitivity index-2. The pitfalls of glucose profile interpretation include the levels of HbA1c and the particular risk of gestational DM. Thalassemia bone disease (TBD) is related to hypoGn-related osteoporosis, renal function anomalies, DM, GHD, malnutrition, chronic hypoxia-induced calcium malabsorption, and transplant-associated protocols. Low BMD was identified in both paediatric and adult population; the prevalence of osteoporosis/TBD in major BTH patients varies; the highest rate is 40–72% depending on age, studied parameters, DXA evaluation and corrections, and screening thoracic–lumbar spine X-ray. Lower TBS and abnormal dynamics of bone turnover markers are reported. The largest cohorts on transfusion-dependent BTH identified the prevalence of hypoGn to be between 44.5% and 82%. Ferritin positively correlates with pubertal delay, and negatively with pituitary volume. Some authors appreciate hypoGn as the most frequent ED below the age of 15. Long-term untreated hypoGn induces a high cardiovascular risk and increased FR. Hormonal replacement therapy is necessary in addition to specific BTH therapy. Infertility underlines TED-related hormonal elements (primary and secondary hypoGn) and IO-induced gonadal toxicity. Males with BTH are at risk of infertility due to germ cell loss. IO induces an excessive amount of free radicals which impair the quality of sperm, iron being a local catalyser of ROS. Adequate chelation might improve fertility issues. Due to the advances in current therapies, the reproductive health of females with major BTH is improving; a low level of statistical significance reflects the pregnancy status in major BTH (limited data on spontaneous pregnancies and growing evidence of the induction of ovulation/assisted reproductive techniques). Pregnancy outcome also depends on TED approach, including factors such as DM control, adequate replacement of hypoT and hypoPT, and vitamin D supplementation for bone health. Asymptomatic TED elements such as subclinical hypothyroidism or IFG/IGT might become overt during pregnancy. Endocrine glands are particularly sensitive to iron deposits, hence TED includes a complicated puzzle of EDs which massively impacts on the overall picture, including the quality of life in major BTH. The BTH prognostic has registered progress in the last decades due to modern therapy, but the medical and social burden remains elevated. Genetic counselling represents a major step in approaching TH individuals, including as part of the pre-conception assessment. A multidisciplinary surveillance team is mandatory.

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“…Transfusion-dependent beta-thalassemia (TDT) is a common hereditary disease caused by mutations in the gene encoding β-chains of hemoglobin (Hb) which leads to the reduced or absent synthesis of the β-globin chain in Hb tetramers. [1] These patients require continuous blood transfusions or bone marrow transplantation for their survival [2]. According to the World Health Organization (WHO), about 25,500 neonates globally are born with TDT each year [3].…”

Section: Introductionmentioning

confidence: 99%

“…Among these, hydroxyurea (HU) and thalidomide have emerged as notable HbF inducers, leading to a significant increase in HbF concentrations in TDT patients [1,15]. Studies have also shown an alarmingly high mortality rate in beta-thalassemic patients with increased ferritin levels [2]. ICT can decrease the morbidity associated with iron toxicity.…”

Section: Introductionmentioning

confidence: 99%

Unraveling Impact of Hemoglobin F and A2 Levels: Correlation With Disease Severity and Treatment Response in Transfusion-Dependent Beta-Thalassemia

Nawaz,

Khan,

Bashir

et al. 2024

Cureus

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Background: Fetal hemoglobin (HbF) has been reported to be associated with disease severity and treatment response to HbF-inducing therapies like Hydroxyurea and thalidomide in patients suffering from transfusion-dependent beta-thalassemia (TDT). However, the role of hemoglobin A2 (HbA2) remains less clear in TDT, therefore this study aims to determine the impact of both HbF and HbA2 levels on disease severity and treatment response.Methodology: A prospective observational study was conducted at the Peshawar Institute of Medical Sciences and Fatimid Foundation Peshawar from May 2023 to October 2023. A total of 232 TDT-diagnosed patients were enrolled using a convenient sampling technique, whereas coinheritance of beta-thalassemia with other hemoglobinopathies was excluded.Result: This study reveals a significant impact of HbF on disease severity (p<0.05) but finds no substantial correlation (p>0.05) between HbA2 levels and disease severity. Additionally, HbF and HbA2 levels exhibit no association with treatment response categories in patients receiving HbF induction therapy, and various mutations do not significantly alter HbF and HbA2 levels or disease severity parameters in TDT patients. Conclusion:The study established a significant association between HbF and disease severity. However, regarding treatment response, neither HbF nor HbA2 levels impact response categories. Combinatorial treatment with hydroxyurea and thalidomide showed superior efficacy compared to monotherapy. A larger sample size and extended follow-up are recommended to further explore the impact of HbF, HbA2, and various mutations on disease severity and treatment response.

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Investigating the Role of Ferritin in Determining Sexual Underdevelopment in Beta-Thalassemia Major Patients: A Cross-Sectional Analysis From Pakistan

Cited by 6 publications

References 18 publications

Prevalence of hypogonadism in transfusion-dependent β-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

Prevalence of hypogonadism in transfusion-dependent β-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

New Entity—Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement

Unraveling Impact of Hemoglobin F and A2 Levels: Correlation With Disease Severity and Treatment Response in Transfusion-Dependent Beta-Thalassemia

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