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Item does not contain fulltext Introduction. Women with the classical form of congenital adrenal hyperplasia (CAH) are born with different degrees of virilization of the external genitalia. Feminizing surgery is often performed in childhood to change the appearance of the genitalia and to enable penile-vaginal intercourse later in life. There are suggestions that this affects sexual functioning. Aims. The aim is to study the anatomical, surgical, cosmetic, and psychosexual outcomes in women with CAH. Methods. Forty women with CAH, aged over 15 years, from two referral centers for management of Disorders of Sex Development in the Netherlands were included. Physical and functional status were assessed by a gynecological interview and examination. Sexual functioning was assessed with the Female Sexual Function Index and Female Sexual Distress Scale-Revised scales and compared with a reference group. Mean Outcome Measures. Surgery performed, anatomy, cosmetic score, sexual function and distress. Results. Thirty-six of the 40 women had undergone feminizing surgery; 25 women (69%) underwent more than one operation. Resurgery was performed in seven of the 13 (54%) women who had had a single-stage procedure. Anatomical assessment showed reasonable outcomes. Multiple linear regression showed that only level of confluence had a significant effect on cosmetic outcome, the impact depending on the number of surgeries performed. Cosmetic evaluations did not differ between the women and the gynecologists. Only 20 women had experience of intercourse. Eight women reported dyspareunia; seven women reported urinary incontinence. The women's perceived sexual functioning was less satisfactory than in the reference group, and they reported more sexual distress. Conclusion. The level of confluence was the major determinant for cosmetic outcome; the impact depended on the number of surgeries performed. Fifty-four percent of the women required resurgery after a single-stage procedure in childhood. Anatomical assessment showed reasonable outcomes. The women evaluated their sexual functioning and functional outcome less favorable than the reference group, and they experienced less often sexual intercourse. van der Zwan YG, Janssen EHCC, Callens N, Wolffenbuttel KP, Cohen-Kettenis PT, van den Berg M, Drop SLS, Dessens AB, Beerendonk C. Severity of virilization is associated with cosmetic appearance and sexual function in women with congenital adrenal hyperplasia: A cross-sectional study. J Sex Med 2013;10:866-875.

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Item does not contain fulltext BACKGROUND: There are only a few reports analyzing the long term outcome of feminizing surgery in females with congenital adrenal hyperplasia (CAH). Such analysis is crucial to evaluate the treatment and to make necessary adjustments. STUDY OBJECTIVES: To evaluate the adult outcome after feminizing surgery in adult females with salt wasting CAH. DESIGN: Retrospective observational followup investigation. SETTING: Outpatient clinic of a University Medical Center, in 2002. PARTICIPANTS: Eight patients (born 1973-1983) who underwent feminizing surgery in infancy by the same procedure and the same pediatric surgeon in our center, and 19 healthy female controls (for visual analog scales). METHODS: (a) Study of patients' records (n=8); (b) Systematic evaluation of the current situation (n=6): uroflowmetry, a written questionnaire to screen for psychopathology (Youth Adult Self Report, YASR), structured gynecologic examination and a structured psychosexual interview, including scoring on visual analog scales. RESULTS:(a) The first surgery (age 0.1-3.7 yr) consisted of clitoris reduction and vaginoplasty (single-stage) in 7 patients and clitoris reduction only in one patient. The latter patient had vaginoplasty in puberty. In puberty, 6 of the 7 patients with an initial single-stage procedure required re-vaginoplasty. All 6 patients who participated in this systematic evaluation had undergone (re-) vaginoplasty in puberty; (b) 2 of the 6 patients experienced some urinary incontinence, and in one of them, the uroflowmetry result was abnormal. The YASR showed no psychopathology, except for 1 patient with a slightly elevated externalizing score. Gynecologic examination (n=5) revealed vaginal strictures in 3 patients (1 severe, 2 mild). The 2 patients without vaginal strictures had coitus regularly. In the interview, 2 patients called themselves bisexual, the other 4 heterosexual. None of the patients had homosexual contacts. Sexual developmental milestones (romantic interest, falling in love, kissing and petting, coitus) had been reached by all, except for 1 patient who did not have coitus yet. In the patient group, satisfaction with height, body hair, and external genitalia and sexual fantasies and interest, measured with visual analog scales, was not different compared to the control group, except for satisfaction with total body appearance, which was significantly lower in the patients. CONCLUSION: Despite the poor outcome of the initial single-stage surgery in infancy and the inevitable re-operation in puberty, the adult outcome in our study population seems more positive than the findings in the few previous reports, especially with respect to sexual development and activity.

Item does not contain fulltext Fertility in women with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency appears to be reduced. The purpose of this review is to summarize the reported evidence about subfertility in women with CAH and to review the causes of reduced fertility. Compared with a non-CAH female population, pregnancy and live-birth rates are severely reduced in salt-wasting patients, mildly reduced in simple virilizing patients, and normal in nonclassical patients. Several factors have been suggested to contribute to the impaired fertility in CAH females: adrenal overproduction of androgens and progestins (17-hydroxyprogesterone and progesterone), ovarian hyperandrogenism, polycystic ovary syndrome, ovarian adrenal rest tumors, neuroendocrine factors, genital surgery, and psychological factors such as delayed psychosexual development, reduced sexual activity and low maternal feelings. It is obvious that these factors are interrelated. Improving endocrine, surgical, and psychological management could contribute to improving fertility chances in these patients. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to define the various types of CAH, to describe the fertility issues in the CAH patients, to outline the various other causes of hyperandrogenism, and to list the treatment options for the patient with CAH.

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Item does not contain fulltext BACKGROUND: Congenital isolated growth hormone deficiency (IGHD) is a rare endocrine disorder that presents with severe proportionate growth failure. Dominant (type II) IGHD is usually caused by heterozygous mutations of GH1. The presentation of newly affected family members in 3 families with dominant IGHD in whom previous genetic testing had not demonstrated a GH1 mutation or had not been performed, prompted us to identify the underlying genetic cause. METHODS: GH1 was sequenced in 3 Caucasian families with a clinical autosomal dominant IGHD. RESULTS: All affected family members had severe growth hormone (GH) deficiency that became apparent in the first 2 years of life. GH treatment led to a marked increase in height SDS. So far, no other pituitary dysfunctions have become apparent. In the first family a novel splice site mutation in GH1 was identified (c.172-1G>C, IVS2-1G>C). In two other families a previously reported splice site mutation (c.291+1G>A, IVS3+1G>A) was found. CONCLUSION: These data show that several years after negative genetic testing it was now possible to make a genetic diagnosis in these families with a well-defined, clearly heritable, autosomal dominant IGHD. This underscores the importance of clinical and genetic follow-up in a multidisciplinary setting. It also shows that even without a positive family history, genetic testing should be considered if the phenotype is strongly suggestive for a genetic syndrome. Identification of pathogenic mutations, like these GH1 mutations, has important clinical implications for the surveillance and genetic counseling of patients and expands our knowledge on the genotype-phenotype correlation.

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Item does not contain fulltext AIM: To assess cardiac anatomy and myocardial systolic function in children with Prader-Willi syndrome (PWS). METHODS: Physical examination, electrocardiographic (ECG) recordings and transthoracic echocardiograms including two-dimensional speckle tracking echocardiography (2DSTE) were performed and evaluated in the Radboud University Hospital Nijmegen, the Netherlands. In total, 19 children diagnosed with PWS and 38 age-matched control subjects underwent cardiac evaluation. RESULTS: Abnormal ECG findings were detected in nine PWS patients. Echocardiography revealed mild structural cardiac abnormalities in two patients. Conventional echocardiographic findings did not indicate systolic left ventricular dysfunction, in contrast to 2DSTE examination. Global peak systolic strain (rate) measurements, in all three directions of contraction, were significantly lower in children with PWS (p < 0.001) compared with healthy age-matched children. In two-thirds of the patients, 2DSTE revealed abnormal systolic deformation (peak systolic strain as well as strain rate). T2P values in PWS patients were similar to control subject. Systolic myocardial function appears more affected in case of maternal uniparental disomy. CONCLUSION: Cardiac evaluation, including 2DSTE, detects frequent alterations in myocardial systolic function in children diagnosed with PWS, whose conventional echocardiographic findings did not indicate ventricular systolic dysfunction. Because cardiovascular morbidity and mortality is substantial in PWS, especially adults, we emphasize the need for cardiac assessment in PWS. 01 mei 2012

Contains fulltext : 109060.pdf (Publisher’s version ) (Open Access) ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Contains fulltext : 98186.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To investigate the parental perspectives of being confronted with an unforeseen fetal sex chromosomal aneuploidy (SCA), in light of the fact that this accidental finding is avoidable by rapid aneuploidy detection (RAD). METHODS: Exploratory qualitative interview study. We conducted 16 semi-structured interviews with parents who decided to continue pregnancy after the unforeseen finding of a fetal SCA. RESULTS: The communication of the unforeseen finding of SCA; the informed decision-making process concerning the pregnancy follow-up and the child and its future were the extracted themes. Parents were not prepared to accidental findings in routine prenatal diagnostics. All started an unguided search on the Internet. It is not at all clear whether parents have preference for an RAD test with X and Y probes Parents were satisfied with the post-test professional information they received to make an informed decision, whereas after birth questions still remained to be answered. CONCLUSION: Parents' perspectives may serve as major contributors to research on the question whether or not the X and Y probes should be standard included for purposes of RAD. The fact that RAD has the possibility to avoid accidental findings of SCAs, brings up the question whether any benefits outweigh the potential harms.

Item does not contain fulltext A 3-year-old boy was treated for asthmatic symptoms with fluticasone inhalations. Due to a flattening growth curve Cushing's syndrome was suspected and the dosage of fluticasone was gradually decreased after which the boy became less active and his appetite decreased. Another patient, a 7-year-old boy with asthma was also treated with fluticasone inhalations. For 6 months he felt tired, nauseous and had abdominal pain. A third patient, an 8-year-old boy with asthma being treated with fluticasone inhalations was presented at the emergency department because he could not be roused; for the preceding few days he had been nauseous and pyrexic. Further laboratory tests showed that all three patients had adrenal cortex insufficiency (addisonism) due to exogenic glucocorticoids in the form of inhaled corticosteroids. This condition is difficult to recognize as its symptoms are aspecific and may resemble those that accompany inadequately treated asthma; furthermore, inhaled corticosteroids may mask the symptoms. On long-term use of inhaled corticosteroids accompanied by aspecific symptoms, the possibility of adrenal cortex insufficiency should be considered. In addition, it is important to prescribe the lowest possible dosage of inhaled corticosteroids.

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Item does not contain fulltext BACKGROUND: 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.

Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear.Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m(2) . d) from baseline, combined with placebo(Pl) or Oxin low (0.03 mg/kg . d) or conventional (0.06 mg/kg . d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed.Results: Compared with GH + Pl, GH + Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean +/- SD, 9.5 +/- 4.7 vs. 7.2 +/- 4.0 cm, P Conclusions: In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg . d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development. (J Clin Endocrinol Metab 95: 1151-1160, 2010)

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Item does not contain fulltext Growth failure in Noonan syndrome is mainly postnatal of character and is dominated by slow maturation and late puberty. The postnatal early decline seems to be an intrinsic part of the syndrome. Reported adult heights are about -2 SD and are indicative of a secular trend.

Contains fulltext : 79732.pdf (Publisher’s version ) (Closed access) Patient A, a 3-year-old boy with short stature, in whom a partial growth hormone deficiency had been diagnosed, was treated with growth hormone. Further evaluation, however, showed that there was evidence of psychosocial deprivation as a result of an unstable family situation. After psychosocial circumstances improved, growth hormone therapy was discontinued, following which no further growth retardation was observed. In the case of patient B, a 10-year-old girl with short stature, reconstruction of the growth curve showed that growth stagnation had occurred around the age of 6 years. The cause was psychosocial deprivation during a severe illness in one of her triplet sisters. Following stagnation, there was insufficient compensatory growth, resulting in short stature. These cases emphasize the importance of reconstruction of the growth curve and of taking a thorough psychosocial case history in all children with growth retardation or small stature. The clinical picture of psychosocial growth retardation can be similar to the picture of idiopathic, isolated growth hormone deficiency. Prompt and accurate diagnosis prevents unnecessary, extensive investigations and enables adequate treatment and support.

Item does not contain fulltext Persistent Mullerian Duct Syndrome (PMDS) is a rare disorder of the anti-mullerian hormone (AMH) synthesis or receptor, which due to the visual contrast of normal masculine external genitalia and female internal genitalia can raise confusion, sometimes during surgery for cryptorchidism or hernia inguinalis. For an acute and accurate analysis of such a situation a thorough knowledge of gonadal embryology is mandatory. The diagnosis is made on finding Mullerian structures in an individual with complete virilization without signs of hypocortisolism or exposition to maternal androgens during foetal life. Karyotyping and gonadal biopsy provide additional information to confirm the diagnosis. As the risk of malignant transformation is not clear, orchidopexy is advised in patients with cryptorchidism, with lifelong palpatory follow-up. In case of urologic symptoms, surgical removal of the Mullerian remnants can be considered, with careful attention for the vulnerable ductus deferens. Despite optimal treatment the prognosis regarding fertility remain uncertain.

Contains fulltext : 51562.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To report repeated successful induction of fertility in an adult male patient with congenital adrenal hyperplasia (CAH) and testicular adrenal rest tumors (TART). DESIGN: Case report. SETTING: Radboud University Nijmegen Medical Centre. PATIENT(S): A 23-year-old male CAH patient with bilateral TART and azoospermia. INTERVENTION(S): Changing glucocorticoid medication from 30 mg of hydrocortisone to 0.75 mg of dexamethasone (DXM) daily. MAIN OUTCOME MEASURE(S): Improved semen analysis. RESULT(S): With the use of ultrasound screening, TART were detected in the 23-year-old patient. The semen analysis showed azoospermia. In an attempt to decrease tumor size and improve testicular function, his glucocorticoid medication was changed from hydrocortisone to an equivalent dosage of DXM. The azoospermia was quickly reversed, and his partner conceived within 7 months of stopping oral contraceptives. Due to his progressive weight gain and striae, his medication was changed back to hydrocortisone, and he again developed again azoospermia. Two years later, the patient started again with DXM at the same dosage. His sperm concentration increased with progressive weight gain. Seven months later his partner became pregnant for the second time; afterward, the DXM treatment was changed back to hydrocortisone. CONCLUSION(S): In male CAH patients with testicular adrenal rest tumors, infertility may be reversible by replacing hydrocortisone with short courses of an equivalent dosage of DXM.

Objective: In newborn screening programs for congenital adrenal hyperplasia, 17-α-hydroxyprogesterone (17OHP) cutoff levels are based on birth weight (BW) or on gestational age (GA). We investigated which approach would result in the greatest specificity and sensitivity. Study design: For the determination of 17OHP, a neonatal 17OHP assay was used in filter paper blood of 9492 newborns. The relationships between 17OHP and BW and between 17OHP and GA were studied by regression analysis. Reference curves with a specificity of 99.95% were constructed with the method that summarizes the distribution by three smoothed curves representing the skewness (L curve), the median (M curve), and the coefficient of variation (S curve). Median cutoff levels for BW and for GA according to the 99.95% reference curves were calculated. Results: Regression analysis showed that GA is a better predictor of 17OHP than BW (R2 was 50.6 vs. 35.8%, respectively). At a specificity of 99.95%, the calculated median 17OHP cutoff level was lower for GA [12.6 μg/liter (38 nmol/liter)] than for BW [17.6 μg/liter (54 nmol/liter)], thus leading to a greater sensitivity. Conclusion: This study demonstrates that GA is a better predictor of 17OHP in newborns and will result in greater specificity than BW despite the fact that the determination of GA might be less reliable than BW. Copyright © 2005 by The Endocrine Society.

Item does not contain fulltext Congenital adrenal hyperplasia (CAH) is a disorder of adrenal steroid synthesis. The symptoms and signs of CAH depend on the degree of enzyme deficiency; severe salt-wasting (SW) form, less severe simple virilizing (SV) form and mild nonclassic (NC) form. In this paper, puberty and fertility in CAH are discussed. The time of onset of puberty and progress of pubertal development is quite normal, except in NC patients (earlier). Also the age of menarche in CAH girls is normal, but it can depend on the level of therapeutic control. In prepuberty, bone age is advanced. In puberty, peak height velocity is normal but occurs at a younger age and can therefore be considered to be low (compared to healthy early maturers). In puberty there seems to be an increased sensitivity for glucocorticoids leading to growth inhibition. All three above factors can play a role in reducing adult height. Subfertility is frequently found in both female and male CAH patients. In females, the pregnancy rate depends on the severity of 21-hydroxylase deficiency (SW

Item does not contain fulltext During operation for a right inguinal hernia, a baby boy aged 3 months was discovered to have internal female genitalia. Biopsies were taken from the gonads and blood was sent for karyotyping. The biopsies showed normal testicular tissue and the karyotyping result was 46XY, so the diagnosis of persistent Mullerian duct syndrome (PMDS) was made. Recovery was uneventful. At the age of 2 he underwent bilateral orchidopexy. PMDS is a rare disorder of the MIF synthesis or receptor. Patients present with cryptorchism, inguinal herniation of Mullerian structures, or problems related to the abnormal urinary tract, such as infection or stone formation. In cryptorchism, orchidopexy and life-long palpatory follow-up are advised. If urological symptoms occur, surgical removal of the Mullerian remnants may be considered. The prognosis for fertility is poor.

Contains fulltext : 58608.pdf (Publisher’s version ) (Open Access) AIM: To study the course of asymptomatic testicular adrenal rest tumours in patients with congenital adrenal hyperplasia (CAH) and the association between tumour changes and glucocorticoid therapy adjustments. PATIENTS AND METHODS: Fifteen male patients with CAH (21-hydroxylase deficiency), in whom asymptomatic testicular adrenal rest tumours had been found at a baseline investigation, underwent scrotal ultrasonography and venous blood sampling (for LH, FSH and testosterone) on average 2.6 years later. The level of hormonal control was assessed by measurement of androstenedione in three diurnal saliva samples. Data on changes in glucocorticoid therapy since baseline were obtained from the patients' records. RESULTS: Tumour decrease, defined as > or =30% decrease in the sum of the longest diameter(s) of the lesion(s), was found in six patients; tumour increase, defined as > or =20% increase, in six and stable tumours in three patients. All three patients with overtreatment showed tumour decrease and of the six patients with undertreatment only one showed tumour decrease. Tumour increase was not only observed in undertreated patients but also in patients with adequate treatment. Changing the night dose of hydrocortisone into dexamethasone, to obtain prolonged ACTH suppression, had resulted in better adrenal suppression in only one patient. CONCLUSIONS: Tumour decrease could be achieved by aiming at adrenal oversuppression, but the required high glucocorticoid doses may induce side effects. In asymptomatic tumours in young male patients with CAH, a practical guideline could be to optimise adrenal suppression to a maximal tolerable glucocorticoid dose and to offer analysis and cryopreservation of semen as soon as the patient can be motivated.

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