Idiopathic hypogonadotropic hypogonadism: a rare cause of primary amenorrhoea in adolescence-a review and update on diagnosis, management and advances in genetic understanding.

Idiopathic hypogonadotropic hypogonadism (IHH) refers to a family of genetic disorders that affect the production and/or action of gonadotropic-releasing hormone, resulting in reduced serum levels of sex steroids. This condition has a prevalence of 1-10 cases/100 000 births and is characterised by the absence of spontaneous pubertal development. In women, the condition is characterised by the onset of normal adrenarche, with the absence of thelarche and menarche. Pubertal induction for breast development and uterine growth with oestradiol, and sequential maintenance of a normal menstrual cycle and adequate oestrogen for bone health, with an oestrogen and progesterone, is considered first-line treatment. Pregnancy can be achieved in patients who have received and responded to treatment with ovulation induction with exogenous gonadotrophins. Advances in genetic testing have led to increased research and understanding of the underlying genetics of IHH with gene mutations described in up to 50% of all IHH cases.

Hyperandrogenism, insulin resistance and acanthosis nigricans (HAIR-AN syndrome): an extreme subphenotype of polycystic ovary syndrome.

HAIR-AN-a syndrome of hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN)-is a specific subphenotype of polycystic ovary syndrome (PCOS), and it is seen in almost 5% of all women with hyperandrogenism. An adolescent girl aged 11 years old was referred with adrenarche, hyperandrogenism and obesity commencing at age 8. Clinical and biochemical investigations confirmed significant hyperandrogenism and insulin resistance, and a diagnosis of HAIR-AN syndrome was made after exclusion of other differential diagnoses. HAIR-AN syndrome is an important diagnosis for the adolescent gynaecologist to be aware of, and it requires a multidisciplinary approach, including endocrinology input, for optimal management. Weight loss, lifestyle modification and combined hormonal pill and metformin are considered first-line treatment.

Bleeding Disorders in Adolescents with Heavy Menstrual Bleeding: The Queensland Statewide Paediatric and Adolescent Gynaecology Service.

STUDY OBJECTIVE: Heavy menstrual bleeding (HMB) is a common gynecological complaint among young women with up to 40% having experienced HMB. Bleeding disorders are increasingly being recognized in adolescents and young adults with HMB. The aim of this study was to determine the prevalence of bleeding disorders in adolescents with HMB, among patients who presented to the Queensland Statewide Paediatric and Adolescent Gynaecology Service between July 2007 and July 2017. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: The study was a retrospective review of 124 female adolescents aged 8 to 18 years with HMB who presented to the Queensland Paediatric and Adolescent Gynaecology Service, Brisbane, Australia. The primary outcome measure was diagnosis of a bleeding disorder, with secondary outcomes including iron deficiency and/or anemia and treatment modalities. RESULTS: Screening for bleeding disorders was performed in 77/124 (62.1%) of patients with HMB. Twenty-seven adolescents were diagnosed with a bleeding disorder, giving a prevalence of 27/124 (21.7%) in those with HMB, and 27/77 (35%) with HMB who were screened. Of these 35%, von Willebrand disease was the most common bleeding disorder, found in 14/27 (51.6%), followed by inherited platelet function disorders diagnosed in 9/27 (33.3%), thrombocytopenia (inherited or acquired) in 3/27 (11.1%), and Factor IX deficiency in 1/27 (3.7%). Iron deficiency and/or anemia was diagnosed in 53/107 (49.5%) of patients with HMB who were screened for this, and 19/27 (70.3%) of those diagnosed with a bleeding disorder. CONCLUSION: Adolescents with HMB who present to a tertiary pediatric and adolescent gynecology service should be screened for bleeding disorders, because of the considerably high prevalence in this at-risk population.

Treatment of Primary Fetal Hydrothorax with OK-432 (Picibanil): Outcome in 14 Fetuses and a Review of the Literature.

BACKGROUND: Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include thoracocentesis, thoraco-amniotic shunting (TAS), and pleurodesis using OK-432. METHODS: A review of the literature was performed to identify all cases of PFHT treated with TAS and OK-432. All cases of PFHT referred to the Fetal Maternal Unit at Royal Prince Alfred Hospital between 2002 and 2012 were retrospectively reviewed. In the cohort of fetuses treated with OK-432, the main perinatal outcomes evaluated were termination of pregnancy, live birth, neonatal death, and fetal death in utero. Secondary outcomes included gestational age (GA) at diagnosis, GA at treatment, GA at resolution, birth weight, and GA at birth. The development of the children was screened using the Ages and Stages Questionnaires, Version 3 (ASQ-3, 2009). RESULTS: Primary hydrothorax was diagnosed in 31 fetuses, of which 14 had treatment with OK-432. One pregnancy terminated after treatment with OK-432. Survival was 85% (11/13): 100% in fetuses treated with OK-432 without hydrops, and 78% in those treated with hydrops. This compares well to the cases of TAS in the literature with an average survival of 63%: 85% in fetuses without hydrops and 55% with hydrops. The mean GA at birth was 36(+4) weeks and mean birth weight 3,007 g. Eight of the 9 children screened with ASQ-3 scored well within the normal range. CONCLUSION: OK-432 appears to be a valid treatment option in fetuses with PFHT, particularly in those diagnosed at early GAs.

Cervical varicosities and placenta praevia.

INTRODUCTION: Cervical varicosities (CVs) have been reported infrequently in pregnancy and have been associated with significant antepartum and postpartum haemorrhage. The most common association with CVs in pregnancy in the literature is placenta praevia. AIMS: To further investigate the association between placenta praevia and CVs. METHODS: A retrospective audit of all cases of placenta praevia that had an ultrasound in the Feto-Maternal Unit at Liverpool Hospital over the period January 2001 to January 2012. Patient outcomes were obtained from the hospital paper and electronic medical records, including mode of delivery and blood loss. RESULTS: Eighty-four cases of placenta praevia were identified, and 78 had saved images that were reviewed. 51 of these 78 cases had transvaginal ultrasound (TVUS) images, which identified nine further cases of cervical varicosities. All cases of CVs were complicated by APH and delivered by caesarean section. There was no significant difference in the blood loss at delivery between the placenta praevia with CVs and those without (925 vs 870 mLs P = 0.3877). CONCLUSIONS: Cervical varicosities are not as rare as the literature would suggest. The clinical relevance of the additional finding of CV on TVUS in cases of placenta praevia is questionable.

Genetic characterization of the carotenoid biosynthetic pathway in Methylobacterium extorquens AM1 and isolation of a colorless mutant.

Genomic searches were used to reconstruct the putative carotenoid biosynthesis pathway in the pink-pigmented facultative methylotroph Methylobacterium extorquens AM1. Four genes for putative phytoene desaturases were identified. A colorless mutant was obtained by transposon mutagenesis, and the insertion was shown to be in one of the putative phytoene desaturase genes. Mutations in the other three did not affect color. The tetracycline marker was removed from the original transposon mutant, resulting in a pigment-free strain with wild-type growth properties useful as a tool for future experiments.

Novel methylotrophy genes of Methylobacterium extorquens AM1 identified by using transposon mutagenesis including a putative dihydromethanopterin reductase.

Ten novel methylotrophy genes of the facultative methylotroph Methylobacterium extorquens AM1 were identified from a transposon mutagenesis screen. One of these genes encodes a product having identity with dihydrofolate reductase (DHFR). This mutant has a C(1)-defective and methanol-sensitive phenotype that has previously only been observed for strains defective in tetrahydromethanopterin (H(4)MPT)-dependent formaldehyde oxidation. These results suggest that this gene, dmrA, may encode dihydromethanopterin reductase, an activity analogous to that of DHFR that is required for the final step of H(4)MPT biosynthesis.