Endocrine Abstracts

Since the discovery of SRY as the main testis-determining gene more than 25 years ago, at least 30 other single gene conditions have been identified that can result in differences/disorders in sex development (DSD). Some of these are associated with ‘classic’ steroidogenic blocks or related conditions such as CAH, whereas others are associated with alterations in gonad determination and development. Reaching a specific genetic diagnosis can have implications...

It is well established that certain endocrine disorders can progress over time, such as autoimmune endocrinopathies or the multiple pituitary hormone insufficiency following cranial irradiation. Although most developmental endocrine disorders are widely considered to be paediatric conditions, milder “non-classic” variants may first present to adult endocrinologists or long-term monitoring may be needed of established conditions as additional endocrine features may on...

In humans, the adrenal gland develops from the intermediate mesoderm at around 4 weeks gestation and undergoes a series of distinct morphological and functional changes throughout pre- and post-natal life. Two key transcriptional regulators of adrenal development are the nuclear receptors DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1, Ad4BP). Mutations or deletions of DAX-1 result in X-linked adrenal hypoplasia congenita (AHC). Boys with this condition ty...

It is now around 20 years since the identification of SRY as a primary testis-determining gene and the molecular characterisation of many of the key enzymes and receptors involved in androgen synthesis and action. Although significant progress has been made since then in identifying other components involved in sex development, we are still unable to find an underlying genetic cause in many individuals with these conditions. Efforts to identify specific genetic causes o...

DAX1 (NR0B1) and steroidogenic factor-1 (SF1, NR5A1) are two nuclear receptors that play a central role in adrenal development and disease. DAX1 was discovered as the cause of X-linked adrenal hypoplasia congenita in 1994 and, to date, more than 250 individuals and families with this condition have been reported. Boys tend to present with salt-losing adrenal failure in the neonatal period or with signs and symptoms of glucocorticoid insufficiency throughout childhood. Hypogona...

The human adrenal gland develops from around 4 weeks gestation and undergoes distinct changes throughout pre- and post-natal life. Defects in these processes can cause adrenal hypoplasia and result in adrenal insufficiency. Adrenal hypoplasia can be: i) secondary to abnormal pituitary function, ACTH synthesis or splicing; ii) the result of ACTH resistance (familial glucocorticoid deficiency; triple A syndrome); or iii) due to a primary defect in adrenal development itself (pri...

Introduction: Differences/Disorders in Sex Development (DSD) represent a diverse range of conditions that present at various stages of life. A multidisciplinary team (MDT) approach is required to reach a specific diagnosis and management plan, but few large single centre studies of the range and prevalence of diagnoses have been undertaken.Method: Medical records of all children with DSD discussed at a single MDT between 1-Jan-1996 and 31-Dec-2015 (n...

Background: Gaining a correct genetic diagnosis for patients with adrenal insufficiency is important not only to enable genetic counselling within their families, but also for correct treatment and long term management. Adrenal insufficiency is genetically heterogeneous and the long-term sequelae for many of the gene defects, including the progression of the disease and involvement of other tissues, is unknown. Next-generation sequencing (NGS) technologies allow parallel seque...

Introduction and Case report: Congenital adrenal hyperplasia (CAH) is a heterogenous group of conditions resulting from inborn errors of steroidogenesis, of which over 95% are due to 21-hydroxylase deficiency.We present a 15-year-old Nepalese female, who was referred to the endocrine clinic for management of CAH. This diagnosis had been at 11 months of age, whilst resident in Hong Kong, when she presented acutely with vomiting and seizures. She had since...

Introduction: Congenital lipoid adrenal hyperplasia (CLAH) is rare and caused by mutations in the steroidogenic acute regulatory (STAR) gene, which is involved in a key step in the synthesis of pregnenolone from cholesterol. Cases typically present in the first days of life with severe adrenal crisis, salt wasting and severely disrupted androgen secretion which may result in sex reversal in 46, XY individuals.Case report: We present a 21-month-o...