Ashraf T Soliman

Defective growth hormone secretion in children with pycnodysostosis and improved linear growth after growth hormone treatment.

Short stature is a characteristic feature of pycnodysostosis. We report defective growth hormone secretion in response to provocation and low insulin-like growth factor-I (IGF-I) concentration in five out of six patients with pycnodysostosis. Physiological replacement with growth hormone increased IGF-I concentration and improved linear growth in these children.

Growth and endocrine function after near total pancreatectomy for hyperinsulinaemic hypoglycaemia.

Seven children, with a mean (SD) age of 4.6 (2.1) years, who as infants (21 (7.5) days) underwent near total (95-98%) pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) were studied. At birth all the infants were macrosomic. Four infants had been born after a difficult labour, of whom three had moderate birth asphyxia and respiratory distress. All had normal thyroid function. After surgery transient hyperglycaemia was manifest in six of the children and required insulin treatment for 5.8 (3.8) weeks, and transient hypoglycaemia was encountered in one child and responded well to increased carbohydrate intake and diazoxide for three weeks. Six of the children rapidly crossed down their length and weight centiles during the first year after surgery. At the end of the first year these children were at or below the 5th centile of height and weight for their age and gender. After a period of 4.6 (2.1) years, their mean (SD) height score was -2.57 (0.5), growth velocity 3.9 (0.75) cm/year, and growth velocity SD score -2.1 (0.55)l these were significantly low and denoted significant growth retardation. The growth hormone peak responses to provocation with clonidine were normal (13.5 (2.8) micrograms/l). However, the circulating insulin-like growth factor-I (IGF-I) concentrations were significantly decreased (79 (34) ng/ml). Three of the children developed diabetes at two and a half, five, and seven years after surgery, two others had impaired oral glucose tolerance and six out of the seven children had an impaired C peptide response to glucagon. Defective insulin secretion in these children might directly inhibit IGF-I synthesis in the liver. The body mass index of the pancreatectomised children was 14.9 (0.5) and was normal for age and gender; they had a normal 72 hour faecal fat content and normal serum albumin concentration. These data indicated grossly adequate exocrine pancreatic function. It appears that children requiring near total pancreatectomy for PHHI have normal developmental milestones but defective linear growth with impaired insulin secretion and low IGF-I production despite normal growth hormone response to provocation.

Continuous glucose monitoring system and new era of early diagnosis of diabetes in high risk groups.

Continuous glucose monitoring (CGM) systems are an emerging technology that allows frequent glucose measurements to monitor glucose trends in real time. Their use as a diagnostic tool is still developing and appears to be promising. Combining intermittent glucose self-monitoring (SGM) and CGM combines the benefits of both. Significant improvement in the treatment modalities that may prevent the progress of prediabetes to diabetes have been achieved recently and dictates screening of high risk patients for early diagnosis and management of glycemic abnormalities. The use of CGMS in the diagnosis of early dysglycemia (prediabetes) especially in high risk patients appears to be an attractive approach. In this review we searched the literature to investigate the value of using CGMS as a diagnostic tool compared to other known tools, namely oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin (HbA1C) in high risk groups. Those categories of patients include adolescents and adults with obesity especially those with family history of type 2 diabetes mellitus, polycystic ovary syndrome (PCO), gestational diabetes, cystic fibrosis, thalassemia major, acute coronary syndrome (ACS), and after renal transplantation. It appears that the ability of the CGMS for frequently monitoring (every 5 min) glucose changes during real-life settings for 3 to 5 days stretches the chance to detect more glycemic abnormalities during basal and postprandial conditions compared to other short-timed methods.

Growth hormone deficiency and empty sella in DIDMOAD syndrome: an endocrine study.

Two girls with DIDMOAD syndrome are presented. One also had severe megaloblastic-sideroblastic anaemia and the other several neurological manifestations. Both were short with defective growth hormone secretion. Computed tomography revealed empty sella in both girls; one had widespread atrophic cortical and cerebellar changes. High doses of thiamine improved the anaemia in the first case, increased C peptide secretion in both, but had no effect on the neurological abnormalities.

Permanent neonatal diabetes mellitus: Epidemiology, mode of presentation, pathogenesis and growth

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788±0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37±9 mmol/L, pH 7.12±0.1). Hypertriglyceridemia was a constant feature (19.4±4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.

Hand X-ray in pediatric endocrinology: Skeletal age assessment and beyond

Skeletal age assessment (SAA) is a clinical procedure which is used in determining the SA of children and adolescents. Bone development is influenced by a number of factors, including nutrition, hormonal secretions, and genetics. There are several factors to be borne in mind when using methods of assessing skeletal maturity. These include: Variability among methods, degree of variability in the estimation of skeletal maturation, sources of low accuracy, and dispersion of the values of skeletal maturation. Currently, the main clinical methods for SAA are the Greulich and Pyle (GP) and Tanner and Whitehouse (TW) methods. The GP method has the advantage of being quick and easy to use. A well-trained radiologist takes few minutes to determine the bone age (BA) from a single hand radiograph. The method of TW, however, seems to be more reliable than the GP method. In recent years, the increasing speed in computer sciences and reduction of their cost has given the opportunity to create and use computerized BA estimation system. Despite the fact that the number of automated systems for BAA have increased, most are still within the experimental phase. The use of automated BA determination system, cleared for clinical use in Europe (BoneXpert), has been validated for various ethnicities and children with endocrine disorders. Ultrasound imaging has some limitations that include operator dependence, lower intra-rater and inter-rater reliability of assessment and difficulties with standardization of documentation and imaging transfer. Magnetic resonance imaging (MRI) is noninvasive alternative tool for SA assessment in children. However, few studies have been reported on this topic, and further research is needed to evaluate the reliability and validity of MRI BAAs. In conclusion, at present radiographic methods for the assessment of BA remain the gold standards. Whatever method one adopts, it is essential to minimize the causes of imprecision by taking care to consider the quality of the X-ray. Moreover, it is imperative to assume a correct hand positioning because poor positioning can change the appearance of some bones. It is also preferable to employ scoring methods to these techniques and percentiles rather than BA in years and months. In addition, the possible differences in maturation among different population should be kept in mind.

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

Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center

Aim: Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40–50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and appearance of severe complications from the heart and endocrine glands that require special health care from well-informed specialists. Objectives: The aims of our study were to: (1) Imprint the clinical profile of long-lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients health needs. Design: A retrospective cross-sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic. Participants: Forty-three long-lived TM patients (mean age: 50.3 ± 10.8 years; range: 45.8–59.5 years; 23 females) were studied. Patients and Methods: An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained. Results: The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml). Conclusions: These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow-up. Physicians strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide-established long-term treatment protocols for hypogonadism and osteoporosis are needed.

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.

An adolescent with an asymptomatic adnexal cyst: To worry or not to worry? Medical versus surgical management options

Paraovarian cysts or paratubal cysts (PTCs) arise from either the mesothelium or from paramesonephric remnants. These present as either adnexal mass or as an incidental finding. Diagnosis is usually established on ultrasound and it is important to differentiate these from ovarian cysts. Typically PCTs appear as simple cysts by ultrasound and are indistinguishable from ovarian cysts if one does not recognize the extraovarian location. Occasionally, PTCs have internal echoes due to hemorrhage. PTCs are usually asymptomatic and benign. The differential diagnosis includes a simple ovarian cyst, peritoneal inclusion cyst and hydrosalpinx. Malignant changes have been reported in about 2% to 3%, and it should be suspected if papillary projections are present. PTCs management depend upon the presence and severity of the symptoms, the cyst size and US characteristics, CA 125 results, age of the patient and the risk of malignancy. Simple PTCs can be expected to regress and may be managed expectantly. When surgery is indicated, a joint multidisciplinary management by the paediatric surgeons and trained paediatric gynaecologists should be the gold standard. (www.actabiomedica.it)