Adrenal Disorders & Endocrinology PDF

hypothalamus and pituitary endocrinology –part 2 Pharmacy -5th stage Clinical biochemistry Dr. rasha khalaf 2024-2025...

hypothalamus and pituitary endocrinology –part 2 Pharmacy -5th stage Clinical biochemistry Dr. rasha khalaf 2024-2025 Lec 7 Adrenal gland ▪ The adrenal glands play a major role in the response to stress, a state of threatened homeostasis. ▪ Located atop the kidneys (the renal organs), each adrenal gland is actually made up of two glands with different cell types, functions, and embryonic origins: ▪ the adrenal cortex, the outer portion, and the adrenal medulla, the central portion  Hypthalamus-pituitary –adrenal axis :(Hypothalamus) ‫الوطاء‬ ‫ أو الدورة اليومية‬،‫ املرض‬،‫يتأثر بعوامل مثل اإلجهاد‬.(Circadian Cycle) (‫” )الهرمون املطلق للكورتيكوتروبني‬CRH“ ‫يفرز هرمون‬ ‫استجابةً للتوتر‬ :(Hypophysis) ‫الغدة النخامية‬ ‫يتم تحفيزها بواسطة‬ (‫” )هرمون قشر الكظر‬ACTH“ ‫ لتفرز‬CRH :(Adrenal Glands) ‫الغدد الكظرية‬ ‫يتم تحفيزها بواسطة‬ ‫ إلفراز هرمون الكورتيزول‬ACTH :‫الكورتيزول‬ :‫ من خالل‬،‫يلعب دورًا أساسيًا في االستجابة للتوتر‬.‫زيادة مستويات الجلوكوز في الدم‬.‫تثبيط االلتهابات‬.‫تعزيز استجابة الجسم اإلجهادية‬ ‫( لتقليل إفراز كل من‬Negative Feedback) ‫يعمل أيضًا كآلية تغذية راجعة سلبية‬ ‫ مما يحافظ على التوازن الهرموني‬،ACTH‫ و‬CRH Adrenal gland dysfunctions 1) Adrenal insufficiency (Addison’s): - It is a rare condition that if unrecognized is potentially fatal. It is relatively simple to treat once it is diagnosed. - It is characterized by decrease in glucocorticoids, mineralocorticoids and androgens leading to : hypoglycaemia, hyperkalaemia, hyponatremia, postural hypotension, decreased androgen and hyper-pigmentation (due to Increase in ACTH). Causes of Addison's disease Diagnosis of Addison’s) 1) Hyponatraemia: low in aldosterone → increased Na and H2O loss → hypovolaemia and hypotension → stimulation of ADH → H2O retention 2) Hyperkalaemia 3) Hyperpigmentation: In primary hypofunction, ACTH increased due to feed-back stimulation of anterior pituitary. ACTH has melanocyte- stimulating activity  ◤ Serum cortisol and ACTH levels Plasma cortisol Plasma ACTH Disorder Affected gland low high Primary Addison Adrenal gland low low Secondary Pituitary gland Addison 2) Adrenal Hyperfunction: - Cortisol excess (Cushing’s Syndrome): Prolonged exposure of the body tissues to cortisol or other glucocorticoids leads to clinical feature known as Cushing’s Syndrome  ◤ ▪ Lab. diagnosis: ▪ 1. Urinary free cortisol: The excess amounts of cortisol will exceed the available capacity of plasma binding protein and the free cortisol is filtered readily into the urine. Free cortisol is measured in 24-hrs urine sample or assessed as cortisol:cratinine ratio in an early morning urine sample. Cortisol:cratinine ratio can be made on a small aliquot of urine, if the test is negative on three occasions, Cushing’s syndrome may be excluded. ▪ 2. Serum cortisol level: Cortisol is measured at 8:00 and 22:00 (morning sample having higher value than the evening). This difference is not apparent in Cushing's syndrome. ‫هذا الفرق ال يظهر في حالة‬ ‫متالزمة كوشينغ‬ ▪ 3. Dexamethasone suppression test ▪ Low dose DST: (1 mg Dexamethason orally at 23:00 and cortisol measured at 9:00, if < 50 nmol/L ® normal ▪ High dose DST: (8 mg of Dexamethason is used if failure to response to Low dose DST due to overproduction of ACTH (Cushing or ectopic malignant or adrenal production of cortisol) ▪ 4. Insulin-induced hypoglycaemia: In normal, a hypoglycaemia (< 2.2 mmol/L) leads to rise in serum cortisol more than 200 mmol/L. Failure of the serum cortisol to rise after insulin-induced hypoglycaemia is diagnostic for Cushing’s syndrome  ◤ ▪ 5. Differential diagnosis: Cortisol ACTH Disorder Affected gland High low Primary Cushing Adrenal gland high High or normal Secondary Pituitary gland Cushing high High Ectopic ACTH Ectopic foci production