Ashraf Soliman

Iron Overload and Glucose Metabolism in Subjects with β-thalassaemia Major : An Overview

Thalassaemia is one of the most common genetic disorders caused by a reduction of the globin chains leading to chronic haemolytic anaemia from birth. The mainstay of treatment is blood transfusion to maintain adequate levels of the haemoglobin. Iron overload in β-thalassaemia major patients is secondary to multiple blood transfusions and increased iron absorption. Excess iron potentially catalyzes free-radicals generation and impairment in cellular function and integrity. Extensive iron-induced injury develops in the heart, liver, pancreas and endocrine system. Pancreatic iron loading in thalassaemia major patients begins at early childhood, and the prevalence of diabetes mellitus (DM) ranges from 6.4% to 14.1% in cross-sectional studies. Both insulin resistance and decreased insulin secretion contribute to DM in thalassaemia major patients. This has been shown by oral glucose tolerance test, euglycemic insulin clamp, homeostatic model assessment, intravenous glucose tolerance test and continuous glucose monitoring system. The prevalence of DM in thalassaemia has been shown to correlate with serum ferritin concentration, hepatitis C infection, and pancreatic and cardiac iron measured by imaging techniques. Therefore the incidence of disturbed glucose homeostasis depends on adherence to chelation treatment, the adequacy of the dosage, the chemical properties of the chelating agent and the prevention of liver infections.

Linear growth and endocrine function in children with ataxia telangiectasia.

Introduction: Ataxia telangiectasia (AT) is a rare, genetic, primary immune deficiency disease characterized by immunodeficiency and neurological manifestations, with an increased tendency to infection, malignancy, and autoimmune diseases. Both growth delay and endocrine abnormalities are occasionally reported in these patients. Patients and Methods: We studied growth parameters height (Ht), weight, body mass index (BMI) and calculated the Ht standard deviation scores (HtSDS) of 13 patients (age 7.7 ± 3.5 years-age range: 3–14.5 years) with AT in relation to their mid-parental Ht SDS (MPHtSDS). We measured their serum calcium (Ca), phosphorus (PO4), alkaline phosphatase, alanine transferase (ALT), serum ferritin, creatinine and albumin concentrations. Endocrine investigations included the assessment of serum free thyroxine (FT4), thyrotropin (TSH), insulin-like growth factor-I (IGF-I) and morning cortisol. Complete blood count and serum immunoglobulins (IgG, IgM and IgA antibodies) were also measured. Growth data were correlated to hormonal and immune data. Results: About 31% of patients with AT had short stature (HtSDS <−2). However, their MPHtSDS denoted that their short stature was familial because four out of 13 had MPHtSDS <−2. They had low BMI, and two of them had low serum albumin and IGF-I, denoting malnutrition or disturbed growth hormone secretion. Elevated serum ALT and ferritin in some patients suggest immune-related inflammation in the liver. 30% of patients had high TSH, two of them had low FT4 diagnosing overt (15%) and sub-clinical (15%) hypothyroidism. Anti-thyroid peroxidase antibodies were high in two out of 13 patients denoting immune-related thyroid aggression. Eight out of 13 patients had Vitamin D deficiency (<20 ng/ml) however, their serum Ca and PO4 levels were in the normal range. One adolescent girl (14.5 years) had hyper-gonadotropic hypogonadism (low estradiol and high follicle stimulating hormone). All patients had normal 8 AM cortisol and renal function. None of the growth parameters were correlated with the IgG, IgM or IgA levels. In summary: Patients with AT had a high prevalence of growth retardation and endocrine dysfunction in the form of low IGF-I, overt and subclinical hypothyroidism and hypogonadism. Physicians should be aware of these possible endocrinopathies for an early diagnosis and proper treatment.

Intravenous iron replacement therapy in eugonadal males with iron-deficiency anemia: Effects on pituitary gonadal axis and sperm parameters; A pilot study

Aim of the study: To evaluate semen parameters and to assess serum FSH, LH, Testosterone (T) concentrations before and 12 weeks after intravenous iron therapy (800-1200 mg elemental iron therapy - IVI) in adults with iron-deficiency anemia (IDA). Materials and Methods: We studied 11 eugonadal adults with IDA, aged 40 ± 5 years, due to defective intake of iron. Anemia was diagnosed when hemoglobin (Hb) was equal or below 10 g/dl. Serum iron, total iron-binding capacity (TIBC) and ferritin concentrations confirmed the diagnosis of IDA. Basal serum concentrations of FSH, LH, and T were measured. Semen parameters were evaluated before and 6-7 weeks after IVI therapy. Results: After IVI therapy and correction of anemia, a significant increase of Hb from 8.1 ± 1.17 g/dL to 13.1 ± 0.7 g/dL was observed and was associated with an increase of T (from 12.22 ± 1.4 nmol/L to 15.9 ± 0.96 nmol/L; P < 0.001), FSH (from 2.82 ± 0.87 to 3.82 ± 1.08 IU/L; P = 0.007), and LH (from 2.27 ± 0.9 to 3.82 ± 1.5 IU/L; P = 0.0002). Total sperm count (TSC) increased significantly from 72 ± 17.5 million/ml to 158 ± 49 million/mL (P < 0.001), rapid progressive sperm motility (RPM) increased from 22 ± 9.4 to 69 ± 30 million/ml (P < 0.001), and sperms with normal morphology (NM) increased from 33 ± 5 to 56 ± 7 million/ml (P < 0.001). Increment in Hb concentration was correlated significantly with LH, FSH, and T concentrations after IVI (r = 0.69 and r = 0.44, r = 0.75, respectively; P < 0.01). The increment in serum T was correlated significantly with increments in the TSC and total sperm motility and RPM (r = 0.66, 0.43, and 0.55, respectively; P < 0.001) but not with gonadotrophin levels. Conclusion: Our study proved for the first time, to our knowledge, that correction of IDA with IVI is associated with significant enhancement of sperm parameters and increased concentrations of serum LH, FSH, and T. These effects on spermatogenesis are reached by an unknown mechanism and suggest a number of pathways that need further human and/or experimental studies.

Glycemic Abnormalities in Adolescents

Glycemic abnormalities including prediabetes and Type 2 diabetes mellitus (T2DM) are emerging clinical problems in children and adolescents. Increased insulin resistance during pubertal development appears to uncover glycemic abnormalities. Pediatricians and physicians should be knowledgeable and conscious about the prevalence and progression of prediabetes to T2DM, the frequent mild or asymptomatic manifestation of T2DM in children and adolescents and the high risk of complications in these patients. Screening for glycemic abnormalities seems useful in high risk groups such as children and adolescents with obesity, family history of T2DM, and with clinical features suggestive of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Modification of life style and reduction of obesity is still the prime target of prevention and early management of early glycemic abnormalities. However, use of hypoglycemic drugs is indicated when these measures fail to achieve adequate glycemic control.

Towards an optimization of the management of endocrine complications of thalassemia.

Abstract Children with thalassemia are living longer due to better care. Physicians dealing with this group of patients now have to contend with new challenges resulting from iron overload. Endocrine complications represent the most common morbidities encountered. To provide a better quality of life, these complications have to be addressed in a consistent way. For this purpose, we have compiled a set of recommendations to help physicians provide the best care possible to these patients.

Linear growth and endocrine function in patients with ataxia telangiectasia; a cohort of 13 patients in Qatar

We studied growth parameters ( height (Ht) , weight, body mass index (BMI) and measured the HtSDS) of 13 patients ( age 7.7 +/3.5 years) with AT in relation to their mid-parental HtSDS. We measured their biochemical (serum calcium (Ca), phosphorus (PO4), Alkaline phosphatase (ALP) , alanine transferase (ALT), ferritin, creatinine and albumin, endocrine ( Free thyroxine (FT4), thyrotropin (TSH) , insulin-like growth factor-I (IGF-I) , 8 AM cortisol) and immune functions ( IgG, IgM and IgA antibodies).

Delayed puberty in a girl with ataxia telangiectasia: Multiple endocrine dysfunctions

cranial MRI showed marked cerebellar and vermis atrophy with iron deposition in the pituitary Occurrence of primary hypothyroidism and hypergonadotrophic hypogonadism points out to an autoimmune aggression in cases of AT to thyroid and ovaries. Conclusion: In patients with AT endocrine manifestations may include hypothyroidism and hypogonadism and should be kept in mind when evaluating delayed puberty in this condition