Congenital Adrenal Hyperplasia Year 4 Paediatrics Notes

Congenital Adrenal Hyperplasia Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / ENDOCRINOLOGY -- Slide 1 Congenital Adrenal Hyperplasia Dr Rose Munge Slide 2 THE ADRENAL GLANDS Located at the superior pole of each kidney. Each gland weigh 8-10gms. Consists of 2 parts- adrenal cortex & medulla. These are 2 endocrine glands one surrounding the other. Inner gland- adrenal medulla, secretes catecholamine. Outer gland- adrenal cortex, secretes steroid hormones. 2 Slide 3 anatomy Slide 4 Adrenal cortex The adrenal gland cortex consist of three zones: The zona glomerulosa:15% Located immediately beneath the capsule.\nSynthesizes mineralcorticoids The zona fasciculata The largest of the zones and constituting abt ¾ of the cortex\nSynthesizes glucocorticoids The zona reticularis 10% Adrenal androgens is synthesized by the zona fasciculata and zona reticularis. Slide 5 cont Each layer of the cortex synthesizes and secretes predominantly one type of steroid: glucocorticoid, mineralocorticoid, or androgen;\nthe specialization is based on the presence or absence of the enzymes that catalyze modifications of the steroid nucleus.\nThe zona reticularis makes androgenic steroids because it has 17,20-lyase;\nzona glomerulosa makes aldosterone because it has aldosterone synthase.\nCholesterol is provided to the cortex through circulation Slide 6 Adrenal medulla The adrenal medulla consists mainly of neuroendocrine (chromaffin) cells and glial cells. It synthesizes catecholamines: Epinephrine\nNorepinephrine The principle hormones of the adrenal medulla are the physiologically active catecholamines: dopamine, norepinephrine, and epinephrine Slide 7 Function of the Adrenal Medulla an extension of the sympathetic nervous system \nacts as a peripheral amplifier \nactivated by same stimuli as the sympathetic nervous system (examples – exercise, cold, stress, hemorrhage, etc.) Slide 8 Regulation of adrenal gland secretion ACTH Cortisol Cortisol Slide 9 CAH Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders of cortisol biosynthesis.\n Cortisol deficiency increases secretion of corticotropin (adrenocorticotropic hormone [ACTH]), leading to adrenocortical hyperplasia and overproduction of intermediate metabolites. Slide 10 Depending on the enzymatic step that is deficient, there may be signs, symptoms, and laboratory findings of mineralocorticoid deficiency or excess: incomplete virilization or precocious puberty in affected males;\nand\n-virilization or sexual infantilism in affected females Slide 12 Congenital Adrenal Hyperplasia Caused by 21-Hydroxylase Deficiency More than 90% of CAH cases are caused by 21-hydroxylase deficiency, which hydroxylates progesterone and 17- hydroxyprogesterone to yield 11-deoxycorticosterone and 11-deoxycortisol respectively.\nThese conversions are required for synthesis of aldosterone and cortisol. Both hormones are deficient in the most-severe, salt-wasting form of the disease. Slide 13 Slightly less-severely affected patients are able to synthesize adequate amounts of aldosterone but have elevated levels of androgens of adrenal origin; this is termed simple virilizing disease.\n These 2 forms are collectively termed classic 21-hydroxylase deficiency.\n Patients with nonclassic disease have relatively mildly elevated levels of androgens and may be asymptomatic or have signs of androgen excess at any time after birth. Slide 14 Congenital Adrenal Hyperplasia Slide 15 Epidemiology Classic 21-hydroxylase deficiency occurs in approximately 1 in 15,000-20,000 births in most populations.\n~70% of affected infants have the salt losing form,30% have the simple virilizing form of the disorder.\nIn the US, CAH is less common in African Americans compared with white children (1: 42,000 vs 1: 15,500).\nNonclassic disease has a prevalence of approximately 1 in 1,000 in the general population but occurs more frequently in specific ethnic groups such as Ashkenazi Jews and Hispanics. Slide 16 Pathogenesis and Clinical Manifestations: Aldosterone and Cortisol Deficiency Both cortisol and aldosterone require 21-hydroxylation for their synthesis, both hormones are deficient in the most-severe, salt-wasting form of the disease.\nThe signs and symptoms of deficiency include progressive weight loss, anorexia, vomiting, dehydration, weakness, hypotension, hypoglycemia, hyponatremia, and hyperkalemia.\nTypically first develop in affected infants at approximately 10-14 days of age.\nWithout treatment, shock, cardiac arrhythmias, and death may occur within days or weeks. Slide 17 Because cortisol is not synthesized efficiently, ACTH levels are high, leading to hyperplasia of the adrenal cortex and levels of precursor steroids that may be hundreds of times normal.\n In the case of 21-hydroxylase deficiency, these precursors include 17-hydroxyprogesterone and progesterone.\n Progesterone and other metabolites act as antagonists of the mineralocorticoid receptor and