Addison Disease Year 4 Paediatrics Notes OmpathStudy

Addison Disease Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / ENDOCRINOLOGY -- Slide 1 Addison Disease Dr Rose Munge Slide 2 Addison disease (or Addison's disease) is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex.\n It affects glucocorticoid and mineralocorticoid function.\n The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional or destroyed. Slide 3 anatomy Slide 4 Regulation of adrenal gland secretion ACTH Cortisol Cortisol Slide 5 Patients usually present with features of both glucocorticoid and mineralocorticoid deficiency.\n The predominant symptoms vary depending on the duration of disease. Patients may present with clinical features of chronic Addison disease or in acute addisonian crisis precipitated by stress factors such as infection, trauma, surgery, vomiting, diarrhea, or noncompliance with replacement steroids. Slide 6 Primary Adrenal Insufficiency Primary adrenal insufficiency in children is most frequently caused by genetic conditions that are often but not always manifested in infancy and less often by acquired problems such as autoimmune conditions. Susceptibility to autoimmune conditions often has a genetic basis, and so these distinctions are not absolute. Slide 7 Inherited Etiologies Inborn Defects of Steroid synthesis\nThe most common causes of adrenocortical insufficiency in infancy are the salt losing forms of congenital adrenal hyperplasia. Approximately 75% of infants with 21-hydroxylase deficiency, almost all infants with lipoid adrenal hyperplasia, and most infants with a deficiency of 3β- hydroxysteroid dehydrogenase manifest salt-losing symptoms in the newborn period because they are unable to synthesize either cortisol or aldosterone. Slide 8 Adrenal Hypoplasia Congenita Adrenal hypoplasia congenita (AHC) is a relatively frequent cause of adrenal failure in males, along with congenital adrenal hyperplasia, autoimmune disease, and adrenoleukodystrophy (ALD).\nAHC is predominantly a failure of development of the definitive zone of the adrenal cortex; the fetal zone may be relatively normal.\nAdrenal insufficiency generally becomes evident as the fetal zone involutes postnatally with onset in infancy or in the first 2 yr of life but occasionally in later childhood or even adulthood.\nIn some cases, aldosterone deficiency becomes evident before cortisol deficiency. The disorder is caused by mutation of the DAX1 (NR0B1) gene, a member of the nuclear hormone receptor family, located on Xp21. Males with AHC often do not undergo puberty, owing to hypogonadotropic hypogonadism caused by the same mutated DAX1 gene. Slide 9 Cryptorchidism, sometimes noted in these males, is probably an early manifestation of hypogonadotropic hypogonadism, but often testicular function in infants is normal, with a typical or even an unusually prolonged testosterone surge in the 1st mo of life. AHC occasionally occurs as part of a contiguous gene deletion syndrome together with Duchenne muscular dystrophy, glycerol kinase deficiency, cognitive impairment, or a combination of these conditions. Slide 10 Other Genetic Causes of Adrenal Hypoplasia The transcription factor SF-1 is required for adrenal and gonadal development\nMales with a heterozygous mutation in SF-1 (NR5A1) have impaired development of the testes despite the presence of a normal copy of the gene on the other chromosome and can appear to be female, similar to patients with lipoid adrenal hyperplasia.\nRarely, such patients also have adrenal insufficiency. Adrenal hypoplasia is also occasionally seen in patients with Pallister-Hall syndrome caused by mutations in the GLI3 oncogene. Slide 11 Adrenoleukodystrophy In ALD, adrenocortical deficiency is associated with demyelination in the central nervous system.\n High levels of very long- chain fatty acids are found in tissues and body fluids, resulting from their impaired β-oxidation in the peroxisomes. The most common form of ALD is an X-linked disorder with various presentations.\n The most common clinical picture is of a degenerative neurologic disorder appearing in childhood or adolescence and progressing to severe dementia and deterioration of vision, hearing, speech, and gait, with death occurring within a few years. Slide 12 Neurologic symptoms may be subtle at onset, sometimes consisting only of behavioral changes or deteriorating academic performance.\n Generalized but incomplete alopecia, resembling that of chemotherapy, is a characteristic but inconsistent finding.\n A milder form of Xlinked ALD is adrenomyeloneuropathy, which begins in later adolescence or early adulthood. Slide 13 Patients may have evidence of adrenal insufficiency before, at the time of, or after neurologic symptoms develop, often with years separating their presentation.\nX-linked ALD is caused by mutations in the ABCD1 gene located on Xq28.\nThe gene encodes a transmembrane transporter invol