1. Secondary Hypertension: Adrenal and Nervous Systems Ανδρέας Πιτταράς Καρδιολόγος Καρδιολόγος Clinical Hypertension Specialist ESH Υπερτασικό ιατρείο Τζάνειο νοσοκομείο Υπερηχοκαρδιογραφικό εργαστήριο ΝΜΥΑ ΙΚΑ

2. Adrenocortical Causes of Hypertension

3. The adrenal cortex can cause hypertension

4. Pathways of adrenal steroidogenesis

5. Algorithmic approach to mineralocorticoid-induced hypertension

6. Hypertensive Syndromes Secondary to Hypersecretion of Deoxycorticosterone

7. Abnormalities of steroid production

8. Findings on physical examination

9. 17 -hydroxylase deficiency syndrome

10. Physical characteristics

11. Hypertensive Syndromes Secondary to Cortisol Excess

12. Causes of Cushing's syndrome

13. Abdominal striae caused by excess cortisol production

14. Ectopic adrenocorticotropic hormone excess

16. Inferior petrosal sinus sampling for ACTH

17. Inferior petrosal sinuses before and after oCRH

18. OHSD deficiency syndromes

19. Hypertensive Syndromes Secondary to Hypersecretion of Aldosterone

20. Primary aldosteronism

21. Clinical clues to the presence of primary aldosteronism Spontaneous hypokalemia Diuretic-induced hypokalemia Difficulty in maintaining a normal serum potassium while on diuretics despite concomitant use of potassium-sparing agents or KCl supplementation Refractory hypertension Family history of primary aldosteronism Primary aldosteronism can occur at all ages

22. Serum potassium concentrations in primary aldosteronism

23. Stimulated plasma renin activity in primary aldosteronism

24. Aldosterone excretion rate

25. Plasma aldosterone concentration

26. Sensitivity and specificity of screening tests

27. Biochemical confirmation of adenoma versus hyperplasia MEASUREMENTS ADENOMA BILATERAL HYPERPLASIA Serum potassium, mEq/L 3.0 3.0 Plasma 18-OHB, ng/dL 100 100 Plasma aldosterone response to ambulation Decrease Increase Urinary 18-hydroxycortisol Increase Normal

28. CT scan of normal adrenal glands

29. CT scan of a right adrenal tumor

31. Venography of a left adrenal tumor

32. Diagnostic accuracy of imaging techniques in adrenocortical disorders TRUE POSITIVES, % DISORDER PATIENTS, n NP-59 CT Cushing's syndrom 28 93 90 Primary aldosteronis 58 88 91 Nonfunctional tumors 13 100 89 Diagnostic accuracy of iodocholesterol NP-59 scanning

34. Hemodynamic features of primary aldosteronism

35. Diuretic therapy in patients with primary aldosteronism

36. Relationship between plasma volume and arterial BP

37. Calcium antagonists as alternatives to diuretics

38. Surgery is indicated in patients with solitary adenomas

39. Influence of the severity of hypertension on BP response after surgery

40. Efficacy of long-term medical management of aldosterone- producing adenomas ELECTROLYTE LEVELS AT DIAGNOSIS ELECTROLYTE LEVELS AT LAST FOLLOW-UP PATIENT AGE y SEX FOLLOW-UP, y BLOOD PRESSURE AT PRESENTATION *, mm Hg MOST RECENT BLOOD PRESSURE *, mm Hg SODIUM POTASSIUM CHLORIDE CARBON DIOXIDE SODIUM POTASSIUM CHLORIDE CARBON DIOXIDE 1 65 M 5 170/94 120/80 145 3.1 105 30 140 5.2 110 28 2 69 M 12 164/65 157/86 141 3.2 98 35 141 3.9 104 30 3 63 M 11 178/96 130/95 141 2.9 100 28 144 4.0 107 26 4 43 F 8 180/104 124/82 140 3.0 98 31 137 4.1 105 25 5 39 F 5 184/132 128/80 141 3.9 102 29 140 3.7 106 28 6 76 M 9 174/100 116/74 143 2.9 104 29 139 4.7 103 23 7 68 M 6 180/105 195/76 140 3.1 98 32 142 4.2 109 28 8 69 M 5 190/95 130/70 144 2.9 103 29 140 4.1 104 21 9 59 M 7 180/116 145/99 144 2.4 102 35 139 4.3 104 30 10 55 M 8 180/110 140/74 145 3.0 102 30 142 4.6 104 30 11 59 M 6 165/102 112/68 142 3.0 106 30 142 4.8 108 30 12 50 M 6 177/117 115/80 144 3.1 102 31 143 4.5 104 27 13 44 M 6 160/110 130/82 141 3.0 106 29 140 4.3 103 29 14 54 F 8 160/98 142/60 144 3.4 106 29 142 4.7 108 25 15 52 F 13 150/104 104/76 142 3.3 105 24 137 4.4 106 25 16 52 F 5 168/102 128/91 143 2.7 102 32 141 3.6 106 32 17 54 F 17 180/110 101/71 143 3.0 105 33 139 4.4 101 30 18 59 M 8 176/116 158/78 142 2.6 106 29 138 4.6 101 27 19 44 F 9 190/122 122/78 142 2.6 98 32 137 3.6 98 26 20 61 F 14 160/110 144/72 145 2.9 103 35 140 3.7 113 29 21 68 F 5 166/108 111/78 143 2.6 103 30 146 4.5 108 26 22 66 M 11 178/108 150/92 141 3.0 101 31 142 3.8 102 26 23 73 M 10 178/100 107/66 143 3.8 99 31 143 4.8 105 24 56 M 15 200/125 128/85 141 3.2 102 32 139 4.6 102 26 * Blood pressure values are the average of at least three measurements. Levels are measured in millimoles per liter.

41. Comparison of eplerenone and spironolactone

42. Glucocorticoid-remediable aldosteronism

43. Pheochromocytoma

44. Important facts about pheochromocytomas About 30% of pheochromocytomas reported in the literature are found either at autopsy or at surgery for an unrelated problem 35% to 76% of pheochromocytomas discovered at autopsy are clinically unsuspected during life The average age of diagnosis in those whose disease was discovered before death was 48.5 y, while the average in those diagnosed at autopsy was 65.8 y Death was usually attributed to cardiovascular complications

45. Pathologic features of pheochromocytoma

46. -Adrenergic hyperresponsiveness Acute state of anxiety Angina pectoris Acute infections Autonomic epilepsy Hyperthyroidism Idiopathic orthostatic hypotension Cerebellopontine angle tumors Acute hypoglycemia Acute drug withdrawal (Clonidine - Adrenergic blockade -Methyldopa Alcohol) Vasodilator therapy (Hydralazine, Minoxidil) Factitious administration of sympathomimetic agents Tyramine ingestion in patients on monoamine oxidase inhibitors Menopausal syndrome with migraine headaches Differential diagnosis of pheochromocytoma

47. Priorities for detection of pheochromocytoma Patients with the triad of episodic headaches, tachycardia, and diaphoresis (with or without associated hypertension) Family history of pheochromocytoma Incidental suprarenal masses Patients with a multiple endocrine adenomatosis syndrome, neurofibromatosis, or von Hippel-Lindau disease Adverse cardiovascular responses to anesthesia, to any surgical procedure, or to certain drugs (eg, guanethidine, tricyclics, thyrotropin-releasing hormone, naloxone, or antidopaminergic agents)

48. Supine resting plasma catecholamines

49. Relationship between BP and plasma catecholamines

50. Effect of clonidine on BP

51. Clonidine suppression test in pheochromocytoma

52. Glucagon stimulation test for pheochromocytoma

53. Urinary normetanephrine values

54. Comparison of indexes of catecholamine production

55. Sensitivity and specificity of tests for pheochromocytoma

56. Three modalities used to localize pheochromocytomas

60. Diagnostic strategies in pheochromocytoma

61. Medical management of pheochromocytoma

62. Perioperative hemodynamic variables OPEN, n=20 LAPAROSCOPIC, n=14 P VALUE Mean preoperative blood pressure *, mm Hg 140 18/78 10 144 13/74 14 0.50 Highest blood pressure *, mm Hg 191 33/98 25 194 19/106 19 0.50 Hypertension 0.5 (0 5) 1.0 (0 3) 0.41 SBP 200 mm Hg 0 (0 4) 0 (0 2) 0.70 Lowest blood pressure *, mm Hg 88 14/50 13 98 19/57 8 0.05 Hypotension 2.0 (0 6) 0 (0 2) 0.005 Highest heart rate, bpm 104 15 101 24 0.78 Heart rate 110 bpm 0 (0 3) 0 (0 3) 0.36 Lowest heart rate, bpm 61 11 60 9 0.81 Heart rate 50 bpm 0 (0 1) 0 (0 5) 0.81 Patients requiring treatment for hypertension ‡, n 17.0 13.0 0.63 Patients requiring treatment for hypotension, n 9.0 1.0 0.02 * Systolic and diastolic blood pressure presented as the standard deviation; P value based on the test. Median number of episodes for one patient, with the range in parentheses; P value based on the Jackson-Whitney U test. ‡ Includes patients who intraoperatively received at least one of the following treatments: nitroglycerin, sodium nitroprusside, -blocker, / -blocker, or a calcium channel antagonist. Includes patients who intraoperatively received at least one of the following treatments: phenylephrine, dopamine, or epinephrine.

63. Blood pressure response to calcium antagonists

64. References