Growth and Endocrine Function in Tunisian Thalassemia Major Patients

Abstract

β-thalassemia major (β–TM) is among the most common hereditary disorders imposing high expenses on health-care system worldwide. The patient’s survival is dependent on lifetime blood transfusion which leads to iron overload and its toxicity in various organs including endocrine glands. This article provides an overview of endocrine disorders in beta-TM patients. This single center investigation enrolled 28 β-TM patients (16 males, 12 females) regularly transfused with packed red cell since early years of life. For each patient were determined: age, sex, number of transfusions received, history of splenectomy and anthropometric parameters. All patients underwent an evaluation of hormonal status including growth, gonadal, thyroid, adrenal cortex, and parathyroid glands. Dual-energy X-ray absorptiometry was used to diagnose low bone mass. Assessment of iron overload status was performed by measuring the serum ferritin concentration and the results of magnetic resonance imaging T2*. Growth retardation was found in 16 of the 28 studied patients (57 %). Thirteen among them had delayed puberty. Spontaneous puberty was achieved in 16 cases. Growth hormone (GH) deficiency was found in 10 cases (35 %). Seventeen among the studied patients (60 %) developed disorders of glucose homeostasis. Subclinical hypothyroidism was found in six patients (21 %). Intensive chelation therapy had allowed the reversibility of this complication in five cases. Adrenal Insufficiency was observed in 9 cases (32%). Hypoparathyroidism has occurred in one case. Ten of the 28 studied patients had low bone mass (35%). Twenty-three of the 28 studied patients (82%) had at least one endocrine complication.

A Systematic Review and Meta-Analysis of Stature Growth Complications in β-thalassemia Major Patients

“…After that, 433 records were excluded, and 213 records entered full-text assessment for eligibility criteria. Finally, 74 studies included in the meta-analysis ( Figure 1 ) [ 6 7 11 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 ].…”

Endocrinopathies complicating transfusion-dependent hemoglobinopathy

“…One study reported a prevalence of 86.8% of their total sample size of transfusion-dependent thalassemics having at least one endocrinopathy, 14 which is close to the 87.4% found in our sample and in keeping with the previously published literature. 15 The most common endocrine complication encountered was low bone mineral density at a prevalence of 72.6% with a statistically significant bias towards the female gender. This was followed by hypogonadism at a prevalence of 44.5% with a statistical significance correlated to patients who underwent a splenectomy.…”

Iron overload disorders: Growth and gonadal dysfunction in childhood and adolescence

“…26 Moreover, excessive iron supplementation in infants and young children have been associated with reduced linear growth. [27][28][29] It is therefore not surprising that a high prevalence of short stature has been reported in HC, affecting over 50% of patients with BTM, 18,23,30,31 and up to 40% of all transfusion-dependent thalassemias (TDT). 32,33 As stated above, growth impairment may originate from endocrine factors such as growth hormone deficiency (GHD) linked to pituitary dysfunction and low IGF-1 levels resulting from liver dysfunction.…”

“…A significant proportion of patients with BTM (50%-72%) exhibit reduced IGF-1 levels, 30,34,35 while only 8%-30% 18,35,36 experience impaired growth hormone (GH) secretion (assessed through provocative tests). Notably, decreased IGF-1 levels were also observed in patients with normal GH secretion, possibly linked to liver GH-receptor and/or in post-receptor signaling impairment 34,35 or a decline in liver protidosynthetic activity.…”

“…Iron infiltration can impair the function of different organs, among others, pituitary gland, gonads, and liver, responsible for insulin‐like growth factor 1 (IGF‐1) synthesis, 13–16 leading to delayed growth and pubertal development. Concurrent endocrine factors may include diabetes and primary hypothyroidism, limiting linear growth and pubertal spurt 17,18 . Additionally, HC exhibits lower leptin and ghrelin levels, independent from body mass index, 19,20 possibly due to iron accumulation in adipose tissue affecting adipose cell metabolism 21,22 …”