Cytokines and beta-cell destruction

Egypt J Pediatr Allergy Immunol 2004; 2(2): 77-8

Hypogonadism in the Prader-Willi syndrome from birth to adulthood: a 28-year experience in a single centre

Background. Hypogonadism is a key feature of Prader–Willi syndrome (PWS) but clear strategies for hormone replacement are lacking. Objective. To evaluate the gonadal status and outcome in patients attending a Scottish PWS clinic from 1991 to 2019. Methods. In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls. Results. Females:of 22 patients aged > 11, 9 had reached B4–5, while 5 were still at B2–3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8–21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular counts. Gonadotrophins were unremarkable, serum oestradiol 129 (70–520) pmol/L. Only 5 patients received oestrogen replacement. Males:fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections resulted in unilateral/bilateral descent in 2/1 of 25 patients. Of 37 boys aged > 11, 14 (9 with failed/untreated bilateral cryptorchidism) failed to progress beyond G1, 15 arrested at G2–3 (testes 3–10 mL), and 8 reached G4–5. Gonadotrophins were unremarkable except in boys at G2–5 in whom FSH was elevated: 12.3/27.3 vs 3.25/6.26 U/L in controls (P < 0.001). In males aged > 13, testosterone was 3.1 (0.5–8.4) nmol/L. Androgen therapy, given from 13.5 to 29.2 years, was stopped in 4/24 patients owing to behavioural problems. Conclusion. Despite invariable hypogonadism, few females and only half the males with PWS in this study received hormone replacement. Double-blind placebo-controlled crossover trials of sex steroids are required to address unproven behavioural concerns

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study

IMPORTANCE Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life

Congenital hypothyroidism: a case report of an Egyptian child with congenital heart disease, pelvic kidney and cavernous transformation of portal vein

Abstract Background A case of thyroid hormone deficiency which presented at birth. Thyroid hormones are essential for brain development and normal cognitive function. Common symptoms of congenital hypothyroidism (CH) include constipation, decreased activity, increased sleep and feeding difficulty. Common signs include dry skin, macroglossia and umbilical hernia. If congenital hypothyroidism is left untreated after birth, it can lead to permanent intellectual disability and growth failure. Case presentation. Here, we report a 10.5-year-old female with the typical features of CH. She is the sixth in order of birth of consanguineous Egyptian parents. No family history of similar condition. Our patient had primary CH caused by thyroid agenesis. She had congenital heart disease, pelvic kidney, cavernous transformation of portal vein and parenchymatous liver disease. Conclusions Congenital hypothyroidism is associated with an elevated risk of congenital anomalies. Clinical suspicion of symptoms and signs of congenital hypothyroidism are important for early diagnosis and prevention of serious problems that are related to congenital hypothyroidism

CLINICAL AND BIOCHEMICAL DATA OF ADULT THALASSEMIA MAJOR PATIENTS (TM) WITH MULTIPLE ENDOCRINE COMPLICATIONS (MEC) VERSUS TM PATIENTS WITH NORMAL ENDOCRINE FUNCTIONS: A RETROSPECTIVE LONG-TERM STUDY (40 YEARS) IN A TERTIARY CARE CENTER IN ITALY

Abstract. Introduction: It is well known that the older generation of adult TM patients has a higher incidence of morbidities and co-morbidities. At present, little information is available on adult TM patients with multiple endocrine complications (MEC). The main objectives of this longitudinal retrospective survey were: 1) to establish the incidence and progression of MEC (3 or more) in TM patients; 2) to compare the clinical, laboratory and imaging data to a sex and age-matched group of TM patients without MEC; 3) to assess the influence of iron overload represented by serum ferritin (peak and mean annual value at the last endocrine observation). Patients and Methods: The study was started in January 1974 and was completed by the same physician at the end of December 2015. The registry database of the regularly followed TM patients from diagnosis included 145 adults (> 18 years). All TM patients were of Italian ethnic origin. Eleven out of 145 patients (7.5 %) developed MEC. Twenty-four other patients (12 females and 12 males) had a normal endocrine function (16.5 %) and served as controls. Results: In our survey, four important, relevant aspects emerged in the MEC group. These included the late age at the start of chelation therapy with desferrioxamine mesylate (DFO); the higher serum ferritin peak (8521.8 ± 5958.9 vs 3575.2± 1801.4 ng/ml ); the higher percentage of splenectomized (81.8 % vs. 28.5%) patients and poor compliance registered mainly during the peripubertal and pubertal age (72.7 % vs.16.6 %) in TM patients developing MEC versus those without endocrine complications. Furthermore, a negative correlation was observed in all TM patients between LIC and final height (r: -0.424; p= 0.031). Conclusions: Our study supports the view that simultaneous involvement of more than one endocrine gland is not uncommon (7.5 %). It mainly occurred in TM patients who started chelation therapy with DFO late in life and who had irregular/poor compliance to treatment. Therefore, prevention of the endocrine complications through adopting early and regular chelation therapy appears mandatory for improving the quality of life and psychological outcome of these patients. When diagnosing and managing patients with MEC, it is of paramount importance that the multidisciplinary team have excellent knowledge relating to these complications. In ideal circumstances an endocrinologist with experience of TM will form part of the regular multidisciplinary team caring for such patients

The diagnostic approach to central adrenocortical insufficiency (CAI) in thalassemia

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Insulin resistance in obese pre-pubertal children: Relation to body composition

Background: Abdominal obesity is a strong determinant of obesity related metabolic complications. Data about pre-pubertal children are scarce. The aim of this study is to assess the presence of insulin resistance using different insulin sensitivity indices and investigate its relationship with abdominal fat distribution by Dual energy X-ray absorptiometry scan (DXA). Secondary outcome is to determine the frequency of the metabolic syndrome components. Subjects and methods: Twenty-three pre-pubertal obese children were recruited (14 females, 9 males). Height, weight, body mass index (BMI), waist and hip circumferences, waist to hip ratio, and blood pressure were measured. Fasting blood samples were withdrawn for glucose, insulin, lipid profile, thyroid and liver functions. Patients underwent oral glucose tolerance testing (OGTT) and DXA scan for body composition. Insulin sensitivity was determined using homeostasis model assessment for insulin resistance (HOMA-IR), fasting glucose to insulin ratio, Matsuda, and Cederholm indices. Results: All patients had BMI, waist circumference, and DXA trunk fat more than 2 SDS. Mean fasting glucose, insulin, fasting glucose to insulin ratio, 120 min glucose and HOMA-IR were within normal limits, but mean Matsuda and Cederholm indices exceeded cut off limits. Dyslipidaemia was detected in 13 patients (56.5%), disturbed glucose homeostasis in 8 patients (34.8%), and systolic hypertension in 1 patient (4.3%). Metabolic syndrome diagnosis was established in three patients (13%). More insulin resistant patients were detected by Matsuda index. Trunk fat SDS correlated with Matsuda and Cederholm indices only. Conclusion: Dysglycaemia and dyslipidaemia are common among pre-pubertal obese children. Insulin sensitivity indices based on OGTT are superior to fasting indices in identifying at risk children. OGTT should be included in assessing obese children with BMI > 2 SDS. DXA scanning has limited value for this purpose in clinical settings