Adrenal Insufficiency Endocrinology.pptx

Adrenal Insufficiency Presentation

1. Adrenal insufficiency By : Dr. Busha K . IMR2 | Endocrine Team Moderator - Dr. Paulos Ephrem Consultant Internist and Endocrinologist Date : F eb 18/2025 2/18/2025 seminar on AI 1

2. Outline Introduction Anatomy and physiology Epidemiology Etiologies Clinical features Diagnosis Management 2 2/18/2025 seminar on AI

3. Adrenal insufficiency - Introduction serious pathologic condition - decreased production of Adrenocortical hormones - Glucocorticoids - Mineralocorticoids - Adrenal androgens Classified as primary & Central adrenal insufficiency 2/18/2025 seminar on AI 3

4. Anatomy: adrenal glands Retroperitoneal organs Each weigh around 4-6gm Rich arterial blood supply Each has a single draining vein with rare exceptions 2/18/2025 seminar on AI 4

5. Embryology: Adrenal glands Originate from the urogenital ridge Separate from the gonads and kidneys at about the 6 th week of gestation Adrenal cortex arise from mesodermal cells. Starts to produce cortisol and DHEA at the 7 th -9 th week of gestation Adrenal medulla arises from neuroectodermal cells, which migrate to cortex 2/18/2025 seminar on AI 5

6. Adrenal cortex Zona Glomerulosa 15% of the cortex mineralocorticoids (aldosterone) Zona Fasciculata 75% of the cortex glucocorticoids (e.g., cortisol) Zona Reticularis innermost Androgen precursors - DHEA 2/18/2025 seminar on AI 6

7. 7 Desmolase Synthesis and secretion of Adrenalocortical Hormones Dexoycorticosterone ACTH 2/18/2025 seminar on AI

8. 2/18/2025 seminar on AI Adrenal Steroidogenesis 8

9. Regulatory control of Steroidogenesis 2/18/2025 seminar on AI 9

10. Steroidogenesis ACTH stimulation Results in the up regulation of PKA signaling pathway increases the import of cholesterolesters; increases the activity of hormone-sensitive lipase increases the availability and phosphorylation of CREB that enhances transcription of enzymes required for glucocorticoid synthesis. Cholesterol import into the mitochondrion initiated by the action of the steroidogenic acute regulatory ( StAR ) protein 2/18/2025 seminar on AI 10

11. Cortisol effects 2/18/2025 seminar on AI 11

12. Typical diurnal variations in serum cortisol 2/18/2025 seminar on AI 12 Holt, R. IG. and Henley N. A. (2012) ‘The Adrenal Gland’, in: Essential Endocrinology and Diabetes, 6th edn, UK, Blackwell Publishing Ltd. Pp.99, ISBN-13: 978-1-4443-3004-5

13. Epidemiology Prevalence is 5 in 10,000 in the general population Primary adrenal insufficiency Accounts for 2 in 10,000 50% are acquired and the other half are of genetic causes Secondary adrenal insufficiency Accounts for 3 in 10,000 Exogenous glucocorticoid treatment is common occurring in 0.5–2% of the population in developed countries 2/18/2025 seminar on AI 13

14. Addison’s disease in Ethiopia, epidemiology, aetiology & clinical management Yeweyenhareg Feleke 1,2,4 , and Eystein Sverre Husebye 1,3 Division of Endocrinology, Institute of Medicine, Haukeland University Hospital Center for International Health, University of Bergen, Norway, 2005 A retrospective study of patients with Addison’s disease admitted to referral hospitals between 1996 and 2004 Sixty-two cases of primary adrenal insufficiency were identified. The period prevalence (1996 – 2004) in Addis Ababa was found to be 13 persons per million inhabitants. TB and HIV infection was the cause in 25/62 (40 %) autoimmunity in 3/62 (4.8 %) while a further 21 cases (33.9%) were probably autoimmune Nine cases (15%) were classified as idiopathic 14 2/18/2025 seminar on AI

15. International Journal of Endocrinology / 2022 / Results A wide range of etiology of PAI was encountered, but their true prevalence is unknown. Etiology varied with region and age of presentation as reflected by predominantly TB, HIV, and infective causes occurring in sub-Saharan Africa and more congenital forms described in North Africa associated with consanguinity. In Africa, the diagnostic criteria for PAI do not universally accord with conventional criteria, and there is a heavy reliance on clinical suspicion and biochemistry, including random cortisol of <400  nmol /L, rather than the tetracosactide test where stimulated cortisol <500–550  nmol /L confirms the diagnosis.  Conclusions A high index of suspicion is warranted to diagnose PAI in resource-limited settings, especially where tetracosactide tests are not universally available . 15 2/18/2025 seminar on AI

16. Adrenal insufficiency Failure of the adrenal glands to produce adequate amounts of adrenocortical hormones Primary hypoadrenalism (Addison Disease) Central hypoadrenalism Secondary AI Teritiary AI 2/18/2025 16 seminar on AI

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18. Primary Adrenal Insufficiency Addison Disease Addison disease is a rare condition incidence in - 0.8 cases per 100,000 prevalence of 4 to 11 cases per 100,000 significant morbidity and a twofold excess mortality rate Easily treated once diagnosed 2/18/2025 seminar on AI 18

19. Primary Adrenal Insufficiency-PAI Primary AI results from intrinsic pathology of both adrenal glands, leading to a deficiency in all adrenal hormones: cortisol, aldosterone, DHEAs due to abrupt destruction of the adrenal glands(acute AI) or Gradual progressive destruction or atrophy(chronic AI) of the adrenals 2/18/2025 seminar on AI 19

20. Etiology 2/18/2025 seminar on AI 20

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22. Autoimmune Adrenalitis Autoimmune process that destroy both cortices most common cause (80-90% ) in the western Age of onset=20-50 yrs age Isolated Autoimmune AI during first decades – male 71% 3 rd decades M=F after 3 rd decade F= 81% Adrenal autoantibodies (anti-21-hydroxylase antibodies); 75% of cases. 22 2/18/2025 seminar on AI

23. Con’t… Polyglandular autoimmune syndrome combination of AI with other autoimmune endocrine disorders type 1 and type 2 APSs type 1(monogenic) : a.k.a APECED AI, chronic mucocutaneous candidiasis, and hypoparathyroidism. APSs-type II(polygenic): AI, autoimmune thyroid disease, DM, hypogonadism. Treatment is lifelong steroid replacement 23 2/18/2025 seminar on AI

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26. Four stages in Development of Autoimmune in Primary AI Follow up of patients with adrenal antibodies for 3 years 1 - High plasma renin and normal to low serum aldosterone 2 - Impaired serum cortisol response to ACTH stimulation 3- Increased morning plasma ACTH with normal cortisol 4- Low morning serum cortisol and overt AI 2/18/2025 seminar on AI 26

27. Inherited causes Adrenal Hypoplasia congenita Mutations in SF1 Transcription factor Adrenoleukodystrophy - - Adrenomyeloneuropathy Familial Glucocorticoid Deficiency - Mutations in M2CR and MRAP gene Triple A syndrome 2/18/2025 seminar on AI 27

28. Tuberculosis adrenalitis Result from hematogenous spread Adrenal destruction is gradual with both cortex and medulla affected Enlarged adrenals by inflammatory cell infiltration of the cortex and granulomas early in the disease Caseous nodule and fibrosis then replaces the adrenal gland tissue Adrenal size becomes normal or smaller after successful treatment of the tuberculosis 2/18/2025 seminar on AI 28

29. Disseminated fungal infections Histoplasmosis and paracoccidioidomycosis (South American blastomycosis) are important causes of AI in endemic areas AI is rare in patients with cryptococcosis , coccidioidomycosis , and North American blastomycosis The adrenal glands are enlarged and may become calcified Recovery of adrenal function after prolonged anti-fungal treatment can occur 29 2/18/2025 seminar on AI

30. HIV/AIDS Decline in the incidence of endocrine complications Onset is insidious, causes are opportunistic infections, neoplasms, or concomitant systemic illness AI may be precipitated through the concomitant administration : ketoconazole or rifampicin 30 2/18/2025 seminar on AI

31. Hemorrhagic Infarction Acute AI may occur as a result of bilateral adrenal infarction caused by hemorrhage or adrenal vein thrombosis Associations - meningococcemia (Waterhouse-Friderichsen syndrome) , P .aeruginosa Risk factor - Anticoagulation with heparin (HIT), - Hypercoagulable state - Physical trauma - postop sepsis 2/18/2025 seminar on AI 31

32. Metastatic diseases Infiltration of adrenal gland - common due to rich blood supply - Lung and breast in( 40%% to 60%) - Melanoma (30%) gastric or colon ca(14% to 20%) Apparent low incidence - most of the adrenal cortex must be destroyed - symptoms of AI may mistakenly be attributed to cancer. 2/18/2025 seminar on AI 32

33. Drugs Inhibit cortisol biosynthesis :- Etomidate ,Ketoconazole/fluconazole Metyrapone , or Suramin , Mitotane Accelerate cortisol metabolism (inducing hepatic mixed-function oxygenase enzymes) :- Phenytoin , Rifampin, Checkpoint inhibitor immunotherapy - 33 2/18/2025 seminar on AI

34. Infiltration of the adrenal glands * Tumors (adrenocortical tumors, lymphomas, metastatic carcinoma) * Amyloidosis , hemochromatosis Adrenalectomy Impaired activity of enzymes that are responsible for cortisol synthesis * Drug-induced adrenal insufficiency Cortisol synthesis inhibitors - Ketoconazole , Fluconazole Accelerate cortisol metabolism - Rifampin , Phenytoin * Congenital adrenal hyperplasia - 21 β- Hydroxylase deficiency (90-95%) - 11 β- Hydroxylase deficiency - 17 α - Hydroxylase deficiency 34 2/18/2025 seminar on AI

35. Central adrenal insufficiency Secondary AI : interference with corticotropin ( ACTH ) secretion by the pituitary gland Tertiary AI : interference with corticotropin-releasing hormone ( CRH ) secretion by the hypothalamus. The hallmark laboratory finding is an inappropriately low ACTH value in the setting of diminished cortisol concentrations 2/18/2025 seminar on AI 35

36. Secondary AI 125 to 280 per million Large pituitary tumors or craniopharyngiomas , infectious diseases- TB or histoplasmosis, infiltrative diseases, lymphocytic hypophysitis , head trauma, and large intracranial artery aneurysms. Pituitary infarction (Sheehan syndrome), and hemorrhage may occur into a pituitary tumor (pituitary apoplexy) . 2/18/2025 seminar on AI 36

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40. Clinical manifestations Depends on : - Rate and extent of of loss of a drenal function - Whether MC function is preserved - Degree of physical stress Chronic adrenal insufficiency : Insidious onset, non specific signs and symptoms 2/18/2025 seminar on AI 40

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44. In areas exposed to light and chronic friction or pressure  The vermilion (outer) border of the lips may darken. Patchy pigmentation on the inner surface of lips and the buccal mucosa along the line of dental occlusion Generalized buccal, vaginal, and anal mucosal membrane hyperpigmentation Scars acquired during active PAI The hair and nails may become darker, the nails showing longitudinal bands of darkening Hyperpigmentation - Addison’s 2/18/2025 seminar on AI 44

45. Cont’d… Clues to differentiate between primary and secondary adrenal insufficiency Hyperpigmentation( ACTH --- MC1R, Melanogenesis ), Salt craving, hyperkalemia : Primary AI Involvement of other endocrine axes (thyroid, gonads, growth hormone, prolactin) visual impairment with bitemporal hemianopia caused by chiasmal compression: Secondary AI 2/18/2025 seminar on AI 45

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47. Acute Adrenal insufficiency (adrenal crisis) A medical emergency manifesting as hypotension and acute circulatory failure. Both MC and GC participate In 1 study incidence was similar b/n PAI(8%) and CAI (6%) 2/18/2025 seminar on AI 47

48. Adrenal crisis Clinical context adrenal crisis is suspected Patient with previously undiagnosed chronic primary adrenal insufficiency when they experience major stress An acute cause of adrenal gland destruction In patients with known primary or secondary adrenal insufficiency who are under-replaced due to several reasons An acute cause of secondary or tertiary adrenal insufficiency Patients who are abruptly withdrawn from supraphysiologic doses of glucocorticoid 48 2/18/2025 seminar on AI

49. Adrenal crisis 2/18/2025 seminar on AI 49

50. Precipitating factors for adrenal crisis Stress in patients with underlying AI GI illnesses other infections perioperative periods physical stress or pain psychological stress Sudden discontinuation of GC after prolonged use(>5mg prednisone equivalent for >4weeks regardless of indication or route) B/L adrenal hemorrhage(WFS) Pituitary apoplexy 2/18/2025 seminar on AI 50

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52. Confirming cortisol deficiency - Cortisol followed by ACTH stimulation test Determining the level of the defect As primary, secondary/tertiary is important :- Searching for specific etiology related Clinical manifestation and diagnostic investigation findings 52 Diagnostic approach - Adrenal Insuffciency 2/18/2025 seminar on AI

53. Endocrine testing for adrenal insufficiency Adrenal insufficiency Morning cortisol Morning ACTH ACTH Stimulation test Primary ↓ ↑ No increase in serum cortisol after stimulation Secondary/Tertiary ↓ Increase in serum cortisol after stimulation Long standing s econdary/Tertiary ↓ No (or very little) increase in serum cortisol after stimulation 53 2/18/2025 seminar on AI

54. Endocrine studies 1. Morning cortisol level - Levels ≥ 18 mcg/ dL have a high negative predictive value for ruling out adrenal insufficiency - Levels < 3 mcg/ dL strongly suggest hypocortisolism - Random cortisol levels are of limited value -Total serum cortisol is the preferred measurement - Cortisol levels are influenced by cortisol-binding globulin (CBG) & albumin levels Measurements of salivary cortisol may be useful in patients with abnormalities of CBG 54 2/18/2025 seminar on AI

55. 2. Morning ACTH level - Primary adrenal insufficiency: elevated ACTH levels > 100 pg/ mL - Secondary/tertiary adrenal insufficiency: ACTH levels low to normal - Exogenous glucocorticoids can suppress ACTH secretion through negative feedback 55 Endocrine studies 2/18/2025 seminar on AI

56. 3. Standard-dose ACTH stimulation test (cosyntropin test) Method - polyclonal immunoassays - Administration of 250 mcg exogenous ACTH to stimulate cortisol secretion - Measurement of cortisol levels before and 30 and/or 60 minutes after injection - Physiological response: exogenous ACTH → ↑ cortisol Interpretation - In primary adrenal insufficiency: Peak Cortisol level < 18–20 μg / dL (< 500–550 nmol /L) - In secondary/tertiary adrenal insufficiency: Cortisol > 18–20 μg/ dL (> 500–550 nmol /L) Variant: low-dose (1 mcg) ACTH stimulation test Uses a smaller dose of exogenous ACTH 56 Endocrine studies 2/18/2025 seminar on AI

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58. Con’t … SPECIAL SITUATIONS WHEN STANDARD TESTING MAY BE UNRELIABLE Abnormal CBG ( high/low) Salivary cortisol Serum free cortisol If no option, treat the patient with suspected adrenal insufficiency with GC In patients with CBG excess, cortisol <3 µg/ dL is diagnostic of adrenal insufficiency 58 2/18/2025 seminar on AI

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60. Salivary Tests Stimulated Salivary Cortisol AI - < 30ng/dl R/o AI - >470ng/dl Salivary Cortisone AI - <250ng/dl , R/O AI - >600ng/dl 2/18/2025 seminar on AI 60

61. Con’t … ACTH stimulation test is unreliable Recent ACTH deficiency After pituitary surgery, trauma, pituitary apoplexy and Long-term opioid use Partial ACTH deficiency pituitary surgery, hypothalamic-pituitary radiotherapy, trauma, or opioid use after discontinuation of glucocorticoids Instead, insulin-induced hypoglycemia test, the metyrapon test or trial of glucocorticoid replacement can be tried . 61 2/18/2025 seminar on AI

62. Dynamic endocrine studies 1. Insulin tolerance test (also insulin hypoglycemia test) - Physiological response - Insulin(0.1iu/kg) → hypoglycemia (strong stimulator for ACTH & cortisol secretion) . → stress-induced ↑ in plasma ACTH → ↑ in cortisol levels - Secondary adrenal insufficiency: No incremental rise in ACTH & cortisol levels - Unsafe in the elderly and in patients with known seizures & cardiac disease - Central AI is a peak serum cortisol <18 µg/dL (<500 nmol/L) at 60 to 90 minutes 62 2/18/2025 seminar on AI

63. 2. Overnight metyrapone stimulation test - HPA Axis - Physiological response Metyrapone inhibits 11 β hydroxylase → impaired conversion of 11-deoxycortisol to cortisol (last step of cortisol synthesis) → ↓ serum cortisol → ↑ in CRH and plasma ACTH (negative feedback) → ↑ in adrenal steroidogenesis → ↑ in 11-deoxycortisol level - In primary adrenal insufficiency Metyrapone → ↓ cortisol synthesis → ↑ in CRH/ACTH → no increase in adrenal steroid production → no increase in 11-deoxycortisol or cortisol levels ( <7 ug/dl) - In secondary/tertiary adrenal insufficiency Metyrapone → ↓ cortisol → no increase in CRH/ACTH → no increase in adrenal steroid production → no increase in 11-deoxycortisol or cortisol levels 63 2/18/2025 seminar on AI

64. - Used to distinguish between secondary and tertiary adrenal insufficiency - Physiological response CRH → ↑ ACTH → ↑ cortisol - Secondary adrenal insufficiency CRH → no increase in ACTH → no increase in cortisol - Tertiary adrenal insufficiency CRH → ↑ ACTH → ↑ cortisol 64 3. CRH stimulation test 2/18/2025 seminar on AI

65. Additional evaluation Primary adrenal insufficiency The most common cause of primary adrenal insufficiency in high-income countries is autoimmune adrenalitis Autoimmune screen * Antibodies against 21-hydroxylase * Consider further screening for autoimmune polyendocrine syndromes if antibodies against 21-hydroxylase are present: Hypoparathyroidism: calcium, PTH Diabetes: anti-GAD antibodies, islet cell antigen antibodies Pernicious anemia: antiparietal cell antibodies, anti-IF antibodies Thyroid disease: TSH-receptor antibodies, TPO antibodies Imaging * CXR: Screen for TB if an infective cause is suspected. * CT or MRI adrenal glands: Screen for adrenal hemorrhage and malignant or infiltrative disease 65 2/18/2025 seminar on AI

66. Screening for hypoaldosteronism and hypoandrogenism Hypoaldosteronism - ↑ Plasma renin activity (PRA) or ↑ plasma renin concentration (PRC) & - Inappropriately normal or ↓ serum aldosterone Hypoandrogenism - ↓ DHEA-S 66 2/18/2025 seminar on AI

67. Routine laboratory studies Primary adrenal insufficiency Na ↓, K ↑, Ca ↑ Normal anion gap Metabolic acidosis Hypoglycemia Creatinine ↑, BUN ↑ CBC: mild anemia, lymphocytosis, eosinophilia Thyroid function abnormalities - ↓ T4 to T3 Secondary adrenal insufficiency Hypoglycemia 67 2/18/2025 seminar on AI

68. Other tests Imaging CT of the adrenal glands To look for features of hemorrhage, infection, infiltration/metastases Pituitary protocol MRI I n patients with inappropriately low ACTH in the presence of cortisol deficiency If negative, ?pituitary apoplexy, ?sudden withdrawal of steroids 2/18/2025 seminar on AI 68

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71. Treatment: General principles Life long glucocorticoid(and often mineralocorticoid) replacement is required to treat primary adrenal insufficiency Treatment should be individualized -Hydrocortisone is the preferred glucocorticoid preparation Goal : - T o administer the lowest dose possible to relieve symptoms - Increased doses are required for stress situations and for adrenal crisis 2/18/2025 71 seminar on AI

72. Glucocorticoid regimens The ideal glucocorticoid replacement therapy would Mimic the endogenous cortisol rhythm Have little inter-individual variability in metabolism Be amenable to easy dose titration Be easily monitored Minimize the risk of overtreatment under investigation A once-daily dual-release hydrocortisone- approved in some European countries hydrocortisone ultradian pump- PULSES TRIAL 2/18/2025 seminar on AI 72

73. Glucocorticoid Replacement Hydrocortisone (15–25 mg ) or Cortisone acetate (20–35 mg) in two or three divided oral doses/day In BID /TID bases Prednisolone (3–5 mg/d), PO once or twice daily, especially in patients with reduced compliance Dexamethasone - Cushingoid side effects,long half life 2/18/2025 seminar on AI 73 Treatment of primary adrenal insufficiency in adults; An Endocrine Society, 2016

74. Monitor glucocorticoid replacement using clinical assessment; body wt , postural BP, energy levels, signs of frank glucocorticoid excess Undertreatment or over treatment - Increase/decrease by 2.5mg to 5mg and re- check in 1 week 2/18/2025 seminar on AI 74

75. Mineralocorticoid replacement in PAI Fludrocortisone - Starting dose, 50 – 100 g Morning time Not restrict their salt intake Monitor - clinical assessment (salt craving, postural hypotension, or edema), electrolytes Plasma renin below upper limit of Normal HTN while receiving fludrocortisone, reduce the dose of fludrocortisone 2/18/2025 seminar on AI 75

76. Special circumstances Temporary 50% to 100% increments of the usual fludrocortisone dose Hot climates Excessive sweating Vigorous , and Long-lasting exercise 2/18/2025 seminar on AI 76

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78. Dehydroepiandrosterone replacement (DHEA) Androgen replacement In women with features of androgen deficiency including loss of libido As an option in patients with lack of energy despite optimized GC and MC replacement DHEA 25- 50 mg po daily Monitoring of response : Clinical: sense of well being, improvement in libido Biochemical: DHEAS, androstenedione , testosterone, SHBG 24 hr after the last dose 78 2/18/2025 seminar on AI

79. Considerations in secondary adrenal insufficiency GC and Androgen replacement works here as well Should receive evaluation for other pituitary hormone deficiencies Before starting Growth and Thyroid hormone replacement, replace Glucocorticoids first - Thyroid hormone - accelerate Cortisol metabolism ( 11HSD2) - Growth hormone - inhibits conversion of Cortisone to cortisol ( 11HSD 1) 2/18/2025 seminar on AI 79

80. Special considerations Emergency precautions  patient should wear a medical alert (Medic Alert) bracelet or necklace and carry the EMIC Each patient should have injectable glucocorticoid An injury with substantial blood loss (more than a cup) or fracture Nausea and vomiting and inability to retain oral medications Symptoms of acute adrenal insufficiency The patient is found unresponsive 2/18/2025 seminar on AI 80

81. Surgery Recommendations take into account the severity of the operation and suggest lower daily doses For Minor procedures ( e,g herniorrhaphy ) a dose equivalent to (HC 25 mg), on the day of operation, with a return to the usual replacement dose on the second day For Moderate surgical stress ( eg , cholecystectomy, joint replacement) HC dose 50 to 75mg/daily, in divided iv doses, on the day of surgery and 1 st post op day. Return to usual after ward Major surgical procedures ( eg , cardiac bypass) HC dose 100-150mg/daily, in divided iv doses for 2-3 days. Return to usual after ward 2/18/2025 seminar on AI 81

82. PREGNANCY Increase HC dose by 20-40% in 3rd trimester MC dose adjustments generally not needed Monitor electrolyte, and volume status At onset of labor – GC therapy as for major surgical stress - give hydrocortisone 100mg IV at star of labor –then 50qid After delivery, the dose can be tapered rapidly to maintenance within three days 2/18/2025 seminar on AI 82

83. Glucocorticoid -Induced AI Glucocorticosteroids (GCs) used to manage various inflammatory conditions GCs can suppress hypothalamic-pituitary-adrenal axis and result in AI Central type of AI with preserved mineralocorticoid function Glucocorticoid-induced adrenal insufficiency – most frequent type of AI Clinicians must be aware of GI-AI during ongoing GC Rx during tapering & after withdrawal • AI – most dangerous side effects of GC treatment because of potentially fatal adrenal crisis 2/18/2025 seminar on AI 83

84. Risk factors for developing adrenal insufficiency Addtional - Night time use , Split doses ,long acting,Daily doses 2/18/2025 seminar on AI 84

85. Clinical Presentation at Diagnosis Signs and symptoms of GI-AI – overlap with those of the underlying disease for which glucocorticoids were prescribed Symptom onset of glucocorticoid-induced adrenal insufficiency may be insidious Degree of symptoms depends on the current level of stress Cause of stress may contribute to overlapping signs and symptoms 2/18/2025 seminar on AI 85

86. Clinical Presentation at Diagnosis 2/18/2025 seminar on AI 86

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88. On a physiologic daily dose equivalent, aiming to discontinue - HPA Axis recovery 1. Taper while monitoring symptoms 2. Cortisol test - Recovery of HPA Axis Cortisol is >10 μg / dL -stop Between 5 - 10 μg / dL - continue and re-test within weeks to months . < 5 μg / dL - Continue and repeat test in months 2/18/2025 seminar on AI 88

89. Treatment of GI-AI Taper slowly Continue physiologic dose - until recovery of adrenal function Use Hydrocortisone or prednisolone if on long acting initially Instruct patients on stress dosing and emergency dosing 2/18/2025 seminar on AI 89

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91. Critical illness AI Absolute AI rare Relative AI /CIRCI-may be common No agreement on diagnostic criteria Indications of steroids - specific disease that benefit from steroid - refractory septic shock 2/18/2025 seminar on AI 91

92. PROGNOSIS - Adrenal Insuffciency If not determined by underlying etiology, prognosis is good, as in autoimmune adrenal insufficiency .  risks of depression, poor quality of life and working diabilty In future, improved therapy that better mimics the normal diurnal cortisol rhythm or additional therapy with (DHEA) might ameliorate this problem 92 2/18/2025 seminar on AI

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