Endocrine Abstracts

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 only become apparent in later life.

Here, I will highlight three key areas we have been working on in recent years, which have potential implications for long-term endocrine practice. First, I will describe the wide spectrum of phenotypes associated with variations in the transcription factor, steroidogenic factor-1 (SF-1, NR5A1). Although SF-1 is widely regarded as a “master-regulator” of adrenal and gonad development and function, most pathogenic variants in humans cause a reproductive phenotype, ranging from complete gonadal dysgenesis to male factor infertility and primary ovarian insufficiency. The natural life-course of these conditions is still not well understood, and long-term follow up of individuals at risk of developing additional endocrine features is needed. Secondly, I will describe how milder or non-classic conditions can occur due to disruption of key enzymes and transcription factors such as steroidogenic acute regulatory protein (STAR), CYP11A1 and DAX-1 (NR0B1). Patients with these changes may present with adrenal insufficiency but develop reproductive dysfunction with time. Finally, a fascinating new multisystem growth disorder associated with gain-of-function of the growth repressor SAMD9 will be described. In this condition, somatic genomic changes can occur that modify the disease phenotype in different tissues.

Given the long-term and dynamic nature of these disorders, close liaison between paediatric and adult endocrinologists is needed to better understand the life-course of these conditions and to monitor and manage subsequent endocrine events.