مرحبـــــا بالســـــادة

1. مرحبـــــا بالســـــادة الحضــــور

2. بسم الله الرحمن الرحيم مَنْ عَمِلَ صَالِحًا مِّن ذَكَرٍ أَوْ أُنْثَى وَهُوَ مُؤْمِنٌ فَلَنُحْيِيَنَّهُ حَيَاةً طَيِّبَةً وَلَنَجْزِيَنَّهُمْ أَجْرَهُم بِأَحْسَنِ مَا كَانُوا يَعْمَلُونَ صدق الله العظيم سورة النحل آية 97

3. Ain-Shams university Faculty of Medicine Department of Anesthesiology, ICU, and Pain management CME Program – Endocrine course

4. Adrenocortical disordersByAbdAlAziz AbdAllah, MD

5. The adrenal gland is divided into two parts, adrenal cortex and medulla. The adrenal cortex secretes androgen, mineralocorticoids (eg, aldosteron) and glucocorticoids (eg, crtisol). The adrenal medulla secretes catecholamines (eg, epinephrine, norepinephrine, dopamine).

6. Aldosteron is primarily involved with fluid and electrolyte balance. • Aldosteron secretion causes sodium reabsorption in the distal renal tubule in exchange for potassium and hydrogen ions. • The net effects are, fluid retention, decrease in plasma potassium and metabolic alkalosis.

7. Aldosteron secretion is stimulated by; -Renin-angiotensin system. -ACTH. -Hyperkalemia. -Hypovolemia. -Hypotension. -congestive heart failure. -Surgery.

8. Glucocorticoids are essential for life and have mutiple pysiological effects. • Metabolic actions include enhanced gluconeogenesis and inhibition of peripheral glucose utilization. • Glucocorticoids are required for vascular and bronchial smooth muscle to be responsive to catecholamines. • Glucocorticoids are structurly related to aldosteron, so they have aldosteron like action.

9. ACTH is the principal regulator of Glucocorticoids secretion. • Secretion of ACTH and glucocorticoids exhibit a diurnal rhythm, stimulated by stress and inhibited by circulating glucocorticoids. • Endogenous production of cortisol averages 20 mg \ day.

10. Mineralocorticoid excess • I- 1ry hyper-aldosteronism (Conn syndrome): • Conn syndrome is characterized by increased aldosterone secretion from the adrenal glands, it was first described in 1955 by J. W. Conn in a patient who had an aldosterone-producing adenoma.

11. Pathophysiology • Primary hyperaldosteronism is caused by increased aldosterone excretion from the adrenals, which results primarily from 2 major subtypes: • (1) unilateral aldosterone-producing adenoma , Conn syndrome, (50-60% of cases) (2) idiopathic hyperaldosteronism (IHA) or bilateral adrenal hyperplasia (40-50% of cases). (3) Rarely, aldosterone can be secreted by adrenocortical carcinomas and ovarian tumors.

12. Aldosterone, by inducing renal distal tubular reabsorption of sodium, enhances secretion of potassium and hydrogen ions, causing hypernatremia, hypokalemia, and metabolic alkalosis.

13. Frequency: • Prevalence for Conn syndrome; 0.05-2% of the population. • Mortality/Morbidity: • The morbidity and mortality associated with Conn syndrome, are primarily related to; • 1- Hypertension, especially if left untreated for many years, can lead to many complications, including heart disease (eg, coronary artery disease, congestive heart failure), stroke, and intracerebral hemorrhage (with very high blood pressure).

14. 2-Hypokalemia, especially if severe, causes cardiac arrhythmias, which can be fatal • Age • Peak incidence occurs in the third to sixth decades of life. • Sex • Primary hyperaldosteronism is twice as common in women as in men.

15. II- 2ry hyperaldosteronism: • There is increased renin-angiotensin with increased aldosteron secretion; • -CHF • -Liver cirrhosis and ascitis • -Nephrotic syndrome • -Renal artery stenosis

16. Clinical manifestations • -Hypertension; • -Hypokalemia; • patients with severe hypokalemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalemia-induced nephrogenic diabetes insipidus.

17. -Metabolic alkalosis; • will lower ionized calcium levels and can cause tetany. • Investigations: • Laboratory Studies • -hypernatremia • -Hypokalemia; normokalemia does not exclude primary hyperaldosteronism. Several studies have shown that 7-38% of patients with primary hyperaldosteronism have normal baseline serum levels of potassium

18. -metabolic alkalosis • -Renin levels are suppressed to less than 1 ng/mL/h in patients with primary hyperaldosteronism. • -A 24-hour aldosterone excretion rate of greater than 14 ug is diagnostic of primary hyperaldosteronism

19. Imaging Studies • -CT scanning • -MRI

20. Treatment • Medical • medical therapy is used preoperatively to prevent the morbidity and mortality associated with hypertension and hypokalemia, thus decreasing surgical risk. • - Sodium-restricted diet (<80 mEq or <2 g of sodium per day. • -Potassium-sparing agent (first-step agent) such as spironolactone100 mg initially, increase to 400 mg/d for control of blood pressure.

21. -Potassium supplementation should not be routinely administered with spironolactone because of the potential for the development of hyperkalemia. • -Second-step agents include thiazides diuretics, ACE inhibitors, calcium channel antagonists, and angiotensin II blockers.

22. Surgical Care • Surgery is the main therapy for Conn syndrome. A laparoscopic adrenalectomy is favored, when possible

23. Anesthetic considerations • Preoperative correction of hypertension, CHF and volume and electrolytes imbalance specially potassium is mandatory.

24. Mineralocorticoid deficiency • -Hypo-aldosteronism • Atrophy or destruction of both adrenal glands results in a combined deficiency of Mineralocorticoid and glucocorticoid ( addison disease) . • -Isolated Mineralocorticoid deficiency; • -Unilateral adrenalectomy • -DM -Heparine therapy • -congenital

25. C\P • *Hypotension; due to hypovolemia • *Metabolic acidosis • *Hyperkalemia; any increase in s. potassium without renal impairment, hypoaldosteronism should be considered. • *hyponatremia

26. Anesthetic management • Preoperative preparation includes; • *correction of fluid and electrolyte imbalance • *exogenous mineralocorticoid, fludrocortison 0.1-0.3 mg\ day.

27. Glucocorticoid excess • Cushing syndrome • Cushing syndrome is caused by prolonged exposure to elevated levels of either endogenous glucocorticoids or exogenous glucocorticoids

28. Causes: • -Exogenous steroid administration • Symptoms of glucocorticoid excess generally occur with the administration of oral steroids; however, occasionally injections of steroids into joints and the use of steroid inhalers can cause Cushing syndrome.

29. Patients at risk to develop cushing syndrome includes: • -rheumatological, pulmonary, neurological, and nephrologic diseases that respond to steroid therapy. • -Patients who have undergone organ transplants due to exogenous steroids required as part of graft antirejection medication regimens.

30. Endogenous glucocorticoid administration • -ACTH-producing pituitary adenoma ( Cushing disease). • -Primary adrenal lesions; Overproduction of glucocorticoids may be due to an adrenal adenoma, adrenal carcinoma, or macronodular or micronodular adrenal hyperplasia.

31. -Ectopic ACTH is sometimes secreted by oat cell or small-cell lung tumors or by carcinoid tumors

32. Frequency • Most cases of Cushing syndrome are due to exogenous glucocorticoids. Endogenous Cushing syndrome has been estimated at 13 cases per million individuals. • Age • The peak incidence of Cushing syndrome due to either an adrenal or pituitary adenoma is in persons aged 25-40 years • Ectopic ACTH production due to lung cancer occurs later in life

33. Sex • The female-to-male incidence ratio is approximately 5:1 for Cushing syndrome due to an adrenal or pituitary tumor

34. Mortality/Morbidity • *Morbidity and mortality associated with Cushing syndrome are related primarily to the effects of excess glucocorticoids. However, a large primary pituitary tumor may cause panhypopituitarism and visual loss. • *adrenocortical carcinomas are associated with a 5-year survival rate of 30% or less.

35. * multiple medical problems, including hypertension, obesity, osteoporosis, fractures, impaired immune function, impaired wound healing, glucose intolerance, and psychosis. • * adrenal crisis

36. C\p • Obesity • -moon facies • -buffalo hump • -Central obesity, increased waist-to-hip ratio greater than 1 in men and 0.8 in women

37. Skin • Facial plethora • abdominal striae • lanugo facial hair • Hirsutism and Steroid acne

38. Cardiovascular and renal • Hypertension and possibly edema may be present due to cortisol activation of the mineralocorticoid receptor leading to sodium and water retention • Gastroenterologic • Peptic ulceration may occur with or without symptoms. 

39. endocrine • Galactorrhea and menstrual disturbances decreased libido and impotence in men. • Skeletal/muscular • Proximal muscle weakness • Osteoporosis and osteopenia • Avascular necrosis of the hip

40. Neuropsychological emotional liability, fatigue, and depression • Visual-field defects, often bitemporal, and blurred vision • Adrenal crisis

41. Investigations • Laboratory Studies • Hyperglycemia • Hypokalemic metabolic alkalosis Biochemical evaluation of Cushing syndrome: • 1-Urinary free cortisol excretion over 150 ug\ day.

42. 2- dexamethasone suppression test; glucocorticoids inhibit secretion of hypothalamic CRH and pituitary ACTH but do not directly affect adrenal cortisol production. The overnight 1-mg dexamethasone suppression test requires administration of 1 mg of dexamethasone at 11 PM with subsequent measurement of cortisol level at 8 am.4 In healthy individuals, the serum cortisol level should be less than 2-3 ug/dL.

43. 3-loss of circadian rhythm of cortisol secretion • Normal values, 10-25 ug\ml in the morning, 2-10 ug\ml in the evening, elevated serum cortisol at 11 PM can be an early finding. • Recently, measuring salivary cortisol level has gained interest, as it is a simple and convenient way of obtaining a nighttime sampl. levels less than 1.3-1.5 ng/mL exclude Cushing syndrome.

44. 4- A plasma ACTH of less than 5 pg/mL is suggestive of a primary adrenal tumor. An ACTH level greater than 10-20 pg/mL is consistent with ACTH-dependent Cushing syndrome.

45. Imaging studies • CT or MRI brain and abdomen

46. Treatment • *Hypopysectomy for pituitary tumors, or adrenalectomy for adrenal tumors. • *Pituitary irradiation is employed when transsphenoidal surgery is not successful or not possible • *Patients with endogenous Cushing syndrome who undergo resection of pituitary, adrenal, or ectopic tumors should receive stress doses of glucocorticoid in the intraoperative and immediate postoperative period

47. *lifelong glucocorticoid and mineralocorticoid replacement is necessary in those patients who undergo bilateral adrenalectomy.

48. Anesthetic considerations • Preoperative management • From the C\P those pt. Tend to be volume overloaded, hypertensive and hypokalemic, so Preoperative correction of these factors are essential by potassium and spironolactone.

49. Intaoperative • Patients with osteoprosis are at risk for fracture during positioning. • Preoperative weakness may indicate an increased sensitivity to muscle relaxants.

50. Supplemental steroids are indicated for; • -patients with Cushing syndrome due to exogenous glucocorticoids • -patients undergoing adrenalectomy • Dose; I.V. hydrocortisone succinate 100 mg every 8 h beginning the evening before surgery or on the morning of surgery. • Other complications of adrenalectomy include significant blood loss and unintentional pneumothorax.