Mohamed El Kholy

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.

24-Month Use of Once-Weekly GH, LB03002, in Prepubertal Children With GH Deficiency

BACKGROUND Sustained-release GH formulations may provide a strategy for improving treatment compliance and persistence in GH-deficient patients. OBJECTIVE The aim of the study was to examine efficacy and safety of LB03002, a sustained-release GH formulation for once-weekly administration. DESIGN We conducted a phase III, 12-month, multinational, randomized, open-label, comparator-controlled trial with a 12-month uncontrolled extension. PATIENTS Prepubertal GH treatment-naive GH-deficient children (mean age, 7.8 y) participated in the study. INTERVENTION We administered once-weekly LB03002 (n=91) or daily GH (n=87) for 1 year, followed by once-weekly LB03002 for all patients for another year (LB03002 throughout, n=87; switched to LB03002, n=80). OUTCOME MEASURES Height, height velocity (HV), IGF-1, GH antibodies, and adverse events were determined throughout. Primary analysis was noninferiority of LB03002 vs daily GH at 1 year by analysis of covariance. RESULTS Mean±SD HV during year 1 was 11.63±2.60 cm/y with LB03002, and 11.97±3.09 cm/y with daily GH, with increases from baseline of 8.94±2.91 and 9.04±3.19 cm/y, respectively. The least square mean HV difference for LB03002 - daily GH was -0.43 cm/y (99% confidence interval, -1.45 to 0.60 cm/y). Mean HV also remained above baseline in year 2 (8.33±1.92 cm/y in the LB03002 throughout group, and 7.28±2.34 cm/y in the switched to LB03002 group). Injection site reactions occurred more frequently in LB03002-treated patients but were considered mild to moderate in >90% of cases. CONCLUSIONS Growth response with once-weekly LB03002 in GH-deficient children is comparable to that with daily GH, achieving expected growth rates for 24 months. Once-weekly LB03002 is a strong candidate for long-term GH replacement in GH-deficient children.

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.

Latitudinal Clines of the Human Vitamin D Receptor and Skin Color Genes

The well-documented latitudinal clines of genes affecting human skin color presumably arise from the need for protection from intense ultraviolet radiation (UVR) vs. the need to use UVR for vitamin D synthesis. Sampling 751 subjects from a broad range of latitudes and skin colors, we investigated possible multilocus correlated adaptation of skin color genes with the vitamin D receptor gene (VDR), using a vector correlation metric and network method called BlocBuster. We discovered two multilocus networks involving VDR promoter and skin color genes that display strong latitudinal clines as multilocus networks, even though many of their single gene components do not. Considered one by one, the VDR components of these networks show diverse patterns: no cline, a weak declining latitudinal cline outside of Africa, and a strong in- vs. out-of-Africa frequency pattern. We confirmed these results with independent data from HapMap. Standard linkage disequilibrium analyses did not detect these networks. We applied BlocBuster across the entire genome, showing that our networks are significant outliers for interchromosomal disequilibrium that overlap with environmental variation relevant to the genes’ functions. These results suggest that these multilocus correlations most likely arose from a combination of parallel selective responses to a common environmental variable and coadaptation, given the known Mendelian epistasis among VDR and the skin color genes.

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.

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.

Further Observations on the Effects of Long-Term Treatment with Recombinant Human Insulin-Like Growth Factor 1 in Growth Hormone Insensitivity Syndrome

Background/Aim: Growth hormone insensitivity syndrome (GHIS) is a spectrum of disorders. Laron syndrome was the earliest discovered. Insulin-like growth factor 1 (IGF-1) therapy is used to improve growth. IGF-1 has diverse effects on the growth of body organs. We aim to assess the long-term effects of IGF-1 therapy in patients with GHIS particularly on adiposity and acral growth. Methods: Six patients (5 with Laron syndrome and 1 with type 1A growth hormone deficiency) were followed for a mean (±SD) of 8.2 ± 1.8 years. Mean age at start of therapy was 7.6 ± 4.1 years. Anthropometric evaluation including growth of hand, foot, ear, and skin folds, and assessment of internal organ growth were done. Results: Hand and foot sizes improved significantly, especially when treatment was initiated early. Prominent effects on adiposity were observed, reflected by increment in body mass index standard deviation score (SDS) and skin fold SDS. Mean height, height velocity, sitting height, and head circumference SDS improved with therapy. A significant increase in spleen and right kidney was appreciated. Conclusion: IGF-1 therapy improves growth in GHIS. The hand and foot sizes increase significantly with therapy, and can even normalize with early initiation of treatment. Ear length further improves with therapy. Other effects include increase in adiposity and internal organ growth.

Caffeinated energy drink consumption among adolescents and potential health consequences associated with their use: a significant public health hazard

Caffeinated energy drinks (EDs) are increasingly popular among adolescents despite growing evidence of their negative health effects. The consumption of EDs has seen a substantial increase during the past few decades, especially in the Western and Asian countries. EDs contain high levels of caffeine, sugar, and novel ingredients, and are often marketed through youth-oriented media and venues. The known and unknown pharmacology of the constituents of EDs poses a risk of caffeine toxicity and other ill effects when consumed by young people. Caffeine intoxication may result in tachycardia, vomiting, cardiac arrhythmias, seizures, and even death. Other health concerns related to consumption of EDs include obesity and dental enamel erosion resulting from the acidity of EDs. Coingestion of caffeine and ethanol has been associated with increased risk-taking behaviors in adolescent users, impaired driving, and increased use of other illicit substances. Several researchers have demonstrated that consuming alcohol mixed with energy drinks leads to altered subjective states including decreased perceived intoxication, enhanced stimulation, and increased desire to drink/increased drinking compared to consuming alcohol alone. Caffeine’s effect on intoxication may be most pronounced when mixers are artificially sweetened, that is, lack sucrose which slows the rate of gastric emptying of alcohol. In conclusion: 1) health care providers should educate youth and their parents about the risks of caffeinated drinks; 2) emergency department clinicians should consider asking patients about ED and traditional caffeine usage and substance use when assessing patient symptoms; 3) policy makers should increase their attention on introducing regulatory policies on television food advertising to which youth are exposed; 4) failure to comply with standards for efficacious product labelling, and absence of broader education regarding guidelines, need to be addressed and 5) further studies must be done to improve our understanding of potential negative consequences of caffeinated energy drinks on health. (www.actabiomedica.it)