Heba Elsedfy

Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I‑CET) position statement and guidelines

The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patients care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.

Unexpected Phenotype in a Boy with Trisomy of the SHOX Gene

The assessment that heterozygous SHOX mutations leading to SHOX haploinsufficiency play a role in patients with idiopathic short stature (ISS) is already documented in the literature as well as the suggestion that additional copies of SHOX are strongly implicated in a condition of tall stature. However, we report the first case of short stature in a male associated with the presence of three copies of the SHOX gene. Through chromosomal analysis, using Multiplex Ligation-dependent Probe Amplification method of SHOX salsa P018B kit and microsatellite analysis, we identify a new interstitial isolated duplication of the SHOX gene and its enhancer caused by a larger duplication of the PAR1 region in a boy with ISS. Consequently, we propose the hypothesis that this chromosome re-arrangement disrupts the regular interaction between the enhancer and promoter, resulting in a transcription block, thus producing a lack of gene activation, causing the clinical feature of short stature.

Penile length and genital anomalies in Egyptian male newborns: epidemiology and influence of endocrine disruptors.

Abstract This is an attempt to establish the normal stretched penile length and prevalence of male genital anomalies in full-term neonates and whether they are influenced by prenatal parental exposure to endocrine-disrupting chemicals. A thousand newborns were included; their mothers were subjected to the following questionnaire: parents’ age, residence, occupation, contact with insecticides and pesticides, antenatal exposure to cigarette smoke or drugs, family history of genital anomalies, phytoestrogens intake and history of in vitro fertilization or infertility. Free testosterone was measured in 150 neonates in the first day of life. Mean penile length was 3.4±0.37 cm. A penile length <2.5 cm was considered micropenis. Prevalence of genital anomalies was 1.8% (hypospadias 83.33%). There was a higher rate of anomalies in those exposed to endocrine disruptors (EDs; 7.4%) than in the non-exposed (1.2%; p<0.0001; odds ratio 6, 95% confidence interval 2–16). Mean penile length showed a linear relationship with free testosterone and was lower in neonates exposed to EDs.

Prevalence of minor musculoskeletal anomalies in children with congenital hypothyroidism

In the last decade a high frequency of extrathyroidal congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in a cohort of children with confirmed primary CH due to thyroid dysgenesis was investigated. A high prevalence of extrathyroidal major congenital anomalies (15.9%), more than 5-fold higher than that reported in the Egyptian population (2.7%), was found. The cardiac and musculoskeletal systems were the most commonly involved, comprising 9.09 and 47.72% of all anomalies, respectively. The high prevalence of musculoskeletal anomalies in this study was mostly due to minor anomalies as brachydactyly and digitalization of thumbs. The type of dysgenesis (i.e. aplastic, ectopic or hypoplastic) as well as the severity of hypothyroidism, as assessed by TSH and T4 levels at diagnosis, had no relation with the occurrence of extrathyroidal abnormalities.

Uterine development in patients with Turner syndrome: relation to hormone replacement therapy and karyotype.

Abstract Our study aimed to assess uterine development in Turner syndrome patients and its relation to dose and type of estrogen therapy; and karyotype. Pelvic ultrasound was used to assess uterine size and shape, and ovarian volume in 40 Turner syndrome patients. Information on hormone replacement therapy was collected from patients’ notes. Among the 40 patients studied, 57.5% started estrogen therapy and 30% were taking progestins. Sixty-five per cent had immature uterus, 17.5% had fully mature uterus and 17.5% had transitional uterus. Uterine volume was associated with age (p<0.001), height (p=0.002), weight (p=0.001), years of estrogen use (p<0.001), estrogen dose (p=0.016), current estrogen use (p=0.001) and Tanner breast stage (p<0.001). Uterine volume was not affected by the type of estrogen used (p=0.40) and karyotype (p=0.40). Patients with Turner syndrome treated with estrogen (of adequate dose and duration) may attain a normal, mature uterine size and configuration, even at a late start of hormone replacement therapy and regardless of karyotype.

Growth Hormone/IGF-I Axis and Growth Hormone Receptor Mutations in Idiopathic Short Stature

Background/Aims: It was hypothesized that some children with idiopathic short stature (ISS) may have partial insensitivity to growth hormone (GH). In this study analysis of the GH/IGF-I axis as well as GH receptor (GHR) gene was done in children with ISS to determine the possible underlying factor(s) to their short stature. Methods: Forty-eight patients with a diagnosis of ISS were studied; 33 boys and 15 girls aged 13.6 ± 3.7 years. Molecular analysis of the GHR was performed and GH sensitivity was tested by the IGF-I generation test. Results: Basal IGF-I levels were <–2 SD in 22.9%, and 53.5% showed an IGF-I response below 40% (0–38%) to GH stimulation. GH-binding protein (GHBP) levels were below the normative mean in almost all patients. Mutations in the region of the GHR gene that codes for the extracellular domain of the receptor were found in 15.5%; one newly described mutation was recorded. Conclusion: With the possible exception of the novel G62V mutation, functional studies of the other 2 heterozygous mutations found in 6 of our patients are needed in order to prove their impact on short stature.

Diabetes and Glucose Metabolism in Thalassemia Major: An Update

ABSTRACT In patients with TM, uncontrolled iron overload has serious clinical consequences with considerable morbidity and mortality. Complications include liver damage, cardiac disease and endocrine dysfunction. Diabetes is an important complication of TM. The mechanisms of abnormal glucose homeostasis are complex and multifactorial. This review updates the current knowledge about glycemic abnormalities in TM patients and directs the attention to an early diagnosis and proper management

Pegvisomant‐primed GH stimulation test

Objective  Provocative stimulation tests for GH assessment have poor reproducibility and can often elicit false positive results in normal children. The aim of our study was to evaluate the capability of pegvisomant, as an enhancer of GH secretion, in unmasking false‐positive results in short children undergoing GH testing.

Gonadal dysfunction in adult male patients with thalassemia major: an update for clinicians caring for thalassemia

ABSTRACT Introduction: Hypogonadism is the most frequently reported endocrine complication, affecting 40%–80% of thalassemia major (TM) patients. The prevalence and severity of hypogonadism in TM varies among studies, depending on patients’ age, genotype, transfusion frequency and starting age and efficiency of iron chelation. Areas covered: The diagnosis requires careful clinical assessment and appropriate laboratory testing. Its management is more complex compared to other ‘classical’ causes of hypogonadism because of multiple associated disorders (cardiac, hepatic and endocrine) and other contributing factors basically iron overload and iron toxicity. Expert commentary: Early recognition and treatment of hypogonadism in TM patients is most important to prevent late complications and to enhance the chances of parenthood. The goal of management is to restore deficient glandular function. If fertility is the issue and the testis is under-stimulated because of gonadotropin deficiency, it is possible to induce or restore spermatogenesis with exogenous gonadotropins in some patients. Assisted reproductive techniques may supplementary help to overcome previously untreatable causes of male infertility. These positive achievements should encourage health care providers to pay closer attention to the reproductive health of TM patients. This would involve the collaboration of clinicians caring for thalassemia with endocrinologists and specialists in assisted reproductive technologies.

Endocrine check-up in adolescents and indications for referral: A guide for health care providers

The American Academy of Pediatrics recommends that young people between the ages of 11 and 21 years should be seen annually by their pediatricians, since annual checkups can be an important opportunity for health evaluation and anticipatory guidance. Parents of infants and young children are accustomed to regularly visiting a pediatrician for their childs checkups. Unfortunately, when children reach the teen years, these annual checkups may decrease in frequency. In routine check-ups and medical office visits, particular attention should be paid to the possibility of a developmental or endocrine disorder. Early diagnosis and treatment may prevent medical complications in adulthood and foster age-appropriate development. Our purpose is to acquaint readers with the concept, based on current scientific understanding, that some endocrine disorders may be associated with a wide range of deleterious health consequences including an increased risk of hypertension and hyperlipidemia, increased risk of coronary artery disease, type 2 diabetes, significant anxiety and lack of self-esteem. Understanding the milestones and developmental stages of adolescence is essential for pediatricians and all other health providers who care for adolescents. Treating adolescents involves knowledge of a variety of medical, social and legal information; in addition, close working relationships must be established within the adolescents network to create an effective care system. In summary, we underline the importance of a periodic endocrine checkup in adolescents in order to identify endocrine problems early and develop an approach to treatment for those patients who need help during this time. Indications for endocrine referral for professional and other healthcare providers are also included. These lists are clearly not intended to be comprehensive, but will hopefully serve as a guide for specific clinical circumstances.