Physical, social and societal functioning of children with congenital adrenal hyperplasia (CAH) and their parents, in a Dutch population

<p>Abstract</p> <p>Background</p> <p>Most research concerning congenital adrenal hyperplasia (CAH) and related conditions caused by primary adrenal insufficiency, such as Addison's or Cushing's disease, has focused on medical aspects rather than on patients' quality of life. Therefore, our objective was to investigate the physical, social and societal functioning of children with CAH and their parents in a Dutch population.</p> <p>Methods</p> <p>The study is descriptive and cross-sectional. Self-designed questionnaires, based on questionnaires developed in the Netherlands for different patient groups, were sent to parents of children with CAH between 0 and 18 years old. Participants were recruited through the Dutch patient group for Adrenal Disease (NVACP) and six hospitals in the Netherlands. Three different questionnaires were designed for parents: for children aged 0 - 4, aged 4 - 12 and aged 12 - 18. Additionally, a fourth questionnaire was sent to adolescents with CAH aged 12 - 18. Main outcome measures were experienced burden of the condition, self-management and participation in several areas, such as school and leisure time.</p> <p>Results</p> <p>A total of 106 parents returned the questionnaire, 12 regarding pre-school children (0-4 years), 63 regarding primary school children (4-12 years), and 32 regarding secondary school children (12-18 years), combined response rate 69.7%. Also, 24 adolescents returned the questionnaire. Children and adolescents with CAH appear to be capable of self-management at a young age. Experienced burden of the condition is low, although children experience several health related problems on a daily basis. Children participate well in school and leisure time. Few children carry a crisis card or emergency injection with them.</p> <p>Conclusions</p> <p>Overall, our research shows that, according to their parents, children with CAH experience few negative effects of the condition and that they participate well in several areas such as school and leisure time. However, improvements can be made concerning the measures parents and children must take to prevent an adrenal crisis.</p

Environmental aspects of tensile membrane enclosed spaces

Buildings enclosed by fabric membranes are very sensitive to changes in environmental conditions as a result of their low mass and low thermal insulation values. Development in material technology and the understanding of the structural behaviour of tensile membrane structures along with the vast progress in computer formfinding software, has made it possible for structural design of tensile membrane structures to be approached with almost total confidence. On the contrary, understanding of the environmental behaviour in the spaces enclosed by fabric membrane and their thermal performance is still in its infancy, which to some extent has hindered their wide acceptance by the building industry. The environmental behaviour of tensile membrane structures is outlined and the possible use of the fabric’s topology and geometry particularly to enhance ventilation rates and airflow velocities within the enclosed space is discussed. A need for further research in this area is identified in order to fully realise the potential benefits offered by these structures

Agricultural Microcredit and Household Vulnerability in Rural Malawi

textabstractSixteen girls with Turner syndrome (TS) were treated for 4 years with biosynthetic growth hormone (GH). The dosage was 4IU/m2 body surface s.c. per day over the first 3 years. In the 4th year the dosage was increased to 61 U/m2 per day in the 6 girls with a poor height increment and in 1 girl oxandrolone was added. Ethinyl oestradiol was added after the age of 13. Mean (SD) growth velocities were 3.4 (0.9), 7.2 (1.7), 5.3 (1.3), 4.3 (2.0) and 3.6 (1.5) cm/year before and in the 1st, 2nd, 3rd and 4th year of treatment. Skeletal maturation advanced faster than usual in Turner patients especially in the youger children. Although the mean height prediction increased by 5.6 cm and 11 of the 16 girls have now exceeded their predicted height, the height of the 4 girls who stopped GH treatment exceeded the predicted adult height by only 0 to 3.4 cm

Uniparental disomy 7 in Silver—Russell syndrome and primordial growth retardation

Maternal uniparental disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russell syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental disomy 7. Four of 35 patients were found to have maternal disomy, including three with isodisomy and one with heterodisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardatio

Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency

The microsomal enzyme cytochrome P450c17 is an important regulator of steroidogenesis. The enzyme has two functions: 17alpha-hydroxylase and 17,20-lyase activities. These functions determine the ability of adrenal glands and gonads to synthesize 17alpha-hydroxylated glucocorticoids (17alpha-hydroxylase activity) and/or sex steroids (17,20-lyase activity). Both enzyme functions depend on correct steroid binding, but it was recently shown that isolated lyase deficiency can also be caused by mutations located in the redox partner interaction domain. In this article we present the clinical history and molecular analysis of two patients with combined 17alpha-hydroxylase/17,20-lyase deficiency and four patients with isolated 17,20-lyase deficiency. In these six patients, four missense CYP17 mutations were identified. Two mutations were located in the steroid-binding domain (F114V and D116V), and the other two mutations were found in the redox partner interaction domain (R347C and R347H). We investigated the activity of these mutated proteins by transfection experiments in COS-1 cells using pregnenolone, progesterone, or their hydroxylated products as a substrate and measuring 17alpha-hydroxylase- and 17,20-lyase-dependent metabolites in the medium. The mutations in the steroid-binding domain (F114V and D116V) of P450c17 caused combined, complete (F114V), or partial (D116V) 17alpha-hydroxylase and 17,20-lyase deficiencies, whereas mutations in the redox partner interaction domain (R347C and R347H) displayed less severe 17alpha-hydroxylase deficiency, but complete 17,20-lyase deficiency. These findings are consistent with the clinical data and support the observation that the redox partner interaction domain is essential for normal 17,20-lyase function of P450c17

Prepubertal unilateral gynecomastia: a report of two cases

Item does not contain fulltextBACKGROUND: Gynecomastia is defined as the presence of excessive breast tissue in males, which can appear unilateral or bilateral. Bilateral gynecomastia is frequently found in the neonatal period, early in puberty, and with increasing age. Prepubertal unilateral gynecomastia in the absence of endocrine abnormalities is extremely rare, with only a few cases in literature. METHODS: We report the cases of two otherwise healthy boys of 8 and 11 years old with unilateral breast masses. No abnormalities were found on ultrasonography and all endocrine parameters were within normal limits. Treatment consisted of peripheral liposuction followed by subcutaneous partial resection of the gland, conducted through an infra-areolar incision. Results : Microscopy of the subcutaneous mastectomy specimen revealed gynecomastia without signs of malignancy. Postoperative course of both patients was uncomplicated, with no signs of recurrence of breast tissue. CONCLUSIONS: Atypical presentations of gynecomastia are often not recognized, with little attention to breast development in prepubertal non-obese children. Since prepubertal gynecomastia could be a sign of possible underlying diseases, a thorough examination and further research is recommended. If there is no causal treatment, surgical resection is the therapy of first choice. Peripheral liposuction and surgical resection of the gland tissue are the mainstay of treatment. In summary, we describe two cases of prepubertal unilateral gynecomastia with a normal endocrine workup. Further research is needed to establish the pathophysiologic mechanisms of prepubertal gynecomastia, since underlying etiology in most cases remains unclear

Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m(2).d; approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter 6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6 IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized 17beta-estradiol was given orally. After a mean duration of GH treatment of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV

De pasgeborene met een gestoorde geslachtelijke ontwikkeling

Een stoornis van de geslachtelijke ontwikkeling met onduidelijk geslacht na de geboorte is een ingrijpende situatie en eist multidisciplinaire behandeling door een gespecialiseerd team. Aan de hand van de karyotypering kan een eerste onderscheid gemaakt worden tussen virilisatie van een genotypisch meisje en ondervirilisatie van een genotypische jongen. Belangrijk in het diagnostische traject is de hormonale evaluatie op het juiste tijdstip. Echografisch onderzoek van de genitalia interna helpt bij verdere evaluatie van de genitalia interna en de positie van de gonaden. Geslachtstoewijzing wordt uitgesteld totdat een definitieve diagnose is gesteld. Naast snelle diagnostiek naar de onderliggende oorzaak is psychologische begeleiding van de ouders een belangrijk doel.A disorder in the sexual development with ambiguous genitalia in the neonatal period is a stressful situation for parents and requires early diagnostic procedures by a multidisciplinary team. The first step in the evaluation of a newborn child with ambiguous genitalia is karyotyping which gives a first difference between virilised 46,XX girls and 46,XY undervirilised males. Ultrasonography of the internal genitalia gives additional information about the presence and location of the gonads as well as the presence of Müllerian structures. It is important to perform hormonal evaluation at the right time. Gender assignment has to be made only after the diagnostic path is completed. Beside laboratory and radiological evaluation psychological support of the parents by experienced psychologists is important