Adrenal insufficiency 25/09/57

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1 Adrenal insufficiency นายแพทย อ ดมศ กด เล ศส ทธ พร โรงพยาบาลมหาราชนครราชส มา 25/09/57

2 Adrenal insufficiency Cause Primary VS secondary Acute VS Chronic Diagnosis Critically ill VS non-critically ill Treatment Critically ill VS non-critically ill Adrenal incidentaloma

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5 CAUSE PRIMARY VSSECONDARY

6 Glucocorticoid Deficiency Primary Hypoadrenalism adrenal disease Secondary Hypoadrenalism deficiency of ACTH Distinction : mineralocorticoid deficiency in primary hypoadrenalism Williams textbook endocrinology 12th edition

7 primary Williams textbook endocrinology 12th edition

8 secondary Williams textbook endocrinology 12th edition

9 Infections most common cause Tuberculosis fungal infections histoplasmosis, cryptococcosis Except candida cytomegalovirus Adrenal failure may also occur in the acquired immunodeficiency syndrome (AIDS) Piedrola G, Casado JL, Lopez E,et al: Clinical features of adrenal insufficiency in patients with acquired immunodeficiency syndrome. Clin Endocrinol (Oxf) 1996; 45: 97

10 Tuberculous Addison's disease hematogenous spread Adrenals initially enlarged extensive epithelioid granulomas and caseation, and both the cortex and the medulla Fibrosis ensues : adrenals become normal or smaller in size calcification evident in 50% Williams textbook endocrinology 12th edition

11 ACUTE VSCHRONIC

12 Acute adrenal insufficiency adrenal crisis or Addisonian crisis medical emergency : hypotension acute circulatory failure Anorexia may be : early feature progresses to nausea, vomiting, diarrhea, and, sometimes, abdominal pain fever may be hypoglycemia may be Williams textbook endocrinology 12th edition

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14 chronic adrenal insufficiency weakness, tiredness, weight loss, nausea, intermittent vomiting, abdominal pain, diarrhea or constipation, general malaise, muscle cramps, arthralgia, and symptoms suggestive of postural hypotension Williams textbook endocrinology 12th edition

15 Salt craving may be low-grade fever may be Supine blood pressure is usually normal, but almost invariably there is a fall in blood pressure on standing Adrenal androgen secretion is lost; more in women loss of axillary and pubic hair dry and itchy skin Psychiatric symptoms memory impairment, depression, and psychosis Hahner S, Loeffler M, Fassnacht M,et al : Impaired subjective health status in 256 patients with adrenalinsufficiency on standard therapy based on cross-sectional analysis. J Clin Endocrinol Metab 2007; 92:

16 ACTH deficiency Malaise weight loss other features of chronic adrenal insufficiency Rarely, the presentation is more acute in patients with pituitary apoplexy Williams textbook endocrinology 12th edition

17 CLINICAL FEATURES OF ADRENAL INSUFFICIENCY

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19 primary adrenal failure glucocorticoid and mineralocorticoid deficiency differentiates primary from secondary hypoadrenalism is skin pigmentation Williams textbook endocrinology 12th edition

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22 Pigmentation : increased stimulation of the MC1R by ACTH sun-exposed areas old scars Axillar Nipples palmar creases pressure points mucous membranes (buccal, vaginal, vulval, anal) Williams textbook endocrinology 12th edition

23 DIAGNOSIS

24 Investigation of Hypoadrenalism Routine Biochemical Profile Mineralocorticoid Status Assessing HPA Axis Other Tests Williams textbook endocrinology 12th edition

25 Biochemical Profile hyponatremia 90% increased free water retention : vasopressin levels increase hyperkalemia in 65% aldosterone deficiency : absent in secondary BUN elevated secondary adrenal insufficiency may be a dilutional hyponatremia normal or low blood urea Laczi F, Janaky T, Ivanyi T,et al : Osmoregulation of arginine-8-vasopressin secretion in primary hypothyroidism and in Addison'sdisease. Acta Endocrinol (Copenh) 1987; 114:

26 Mineralocorticoid Status Primary hypoadrenalism Usually mineralocorticoid deficiency Elevated plasma renin activity and either low or low-normal plasma aldosterone Secondary adrenal insufficiency, the reninaldosterone system is intact Williams textbook endocrinology 12th edition

27 Assessing Function of HPA Axis Serum morning cortisol insulin-induced hypoglycemia test ACTH stimulation test Williams textbook endocrinology 12th edition

28 Assessing Function of HPA Axis Serum morning cortisol > 14.5 µg/dl intact HPA axis ACTH stimulation test Hagg E, Asplund K, Lithner F,et al : Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency. Clin Endocrinol (Oxf) 1987; 26: Williams textbook endocrinology 12th edition

29 insulin-induced hypoglycemia test insulin tolerance test (ITT) gold standard in this regard 1 IV insulin dose of 0.1 to 0.15 U/kg plasma cortisol at 0, 30, 45, 60, 90, and 120 minutes Adequate hypoglycemia blood glucose < 40mg signs of neuroglycopenia sweating and tachycardia normal : peak plasma cortisol > 18µg/dL 1Erturk E, Jaffe CA, Barkan AL,et al : Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 1998; 83:

30 insulin-induced hypoglycemia test not be performed ischemic heart disease (always check an electrocardiogram before the test) Epilepsy severe hypopituitarism (i.e., 9 a.m. plasma cortisol < 6.5µg/dL) cortisol response to hypoglycemia can be reliably predicted by the SST a safer, cheaper, and quicker test 2Lindholm J, Kehlet H:Re-evaluation of the clinical value of the 30min ACTH test in assessing the hypothalamic-pituitary-adrenocortical function. Clin Endocrinol (Oxf) 1987; 26: 53-59

31 ACTH stimulation test 250µg synthetic ACTH(1-24) comprising the first 24 amino acids of normally secreted ACTH(1-39) 1 Plasma cortisol levels at 0 and 30 minutes after ACTH normal response peak plasma cortisol level >20µg/dL 2 1 Lindholm J, Kehlet H: Re-evaluation of the clinical value of the 30min ACTH test in assessing the hypothalamicpituitary-adrenocortical function. Clin Endocrinol (Oxf) 1987; 26: Clark PM, Neylon I, Raggatt PR,et al: Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders. Clin Endocrinol (Oxf) 1998; 49:

32 1µg ACTH 1µg ACTH : screen for adequacy of function of the HPA axis more sensitive than 250-µg test 1 Sensitivity secondary adrenal insufficiency Recent adrenal insufficiency Mild adrenal insufficiency 1Kazlauskaite R, Evans AT, Villabona CV,et al : Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008; 93:

33 1µg ACTH 1 µg ACTH IV then cc NSS IV push Serum cortisol 0, 20 and 40 min after Peak cortisol > µg/dl exclude adrenal insufficiency Kazlauskaite R, et al. consumtium for Evaluation of Corticotropin Test in Hypothalamic-Pituitary- Adrenal insufficiency: metaanalysis. Jclin Endocrinol Metab 2008; 93 [11]: Williams textbook endocrinology 12th edition

34 Testing during Critical Illness Cortisol Binding Globulin (CBG) levels decrease substantially Increases ratio free to bound serum cortisol Williams textbook endocrinology 12th edition

35 Random cortisol Testing during Critical Illness <15µg/dL Corticosteroid insufficiency >33µg/dL Unlikely to compromised HPA axis function intermediate cortisol levels SST cortisol increment <9µg/dL is an independent prognostic marker for death in critically ill patients Annane D, Sebille V, Troche G,et al : A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000; 283:

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37 multicenter randomized trial septic shock showed that those with an increment <10µg/dL hydrocortisone not improve overall survival in patients with septic shock SST was not useful in predicting benefit Annane D, Sebille V, Charpentier C,et al : Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: Sprung CL, Annane D, Keh D,et al : Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358:

38 Acute Adrenal Insufficiency life-threatening emergency electrolytes and blood glucose ACTH and cortisol before corticosteroid therapy not critically ill, ACTH stimulation test can be performed Williams textbook endocrinology 12th edition

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40 Hydrocortisone 100mg every 6 to 8 hours After the first 24 hours hydrocortisone can be reduced 50 mg intramuscularly every 6 hours then to oral hydrocortisone, 40mg in the morning and 20mg at 6 p.m. rapidly reduced to a more standard replacement dose of 20mg on wakening and 10mg at 6 p.m. Williams textbook endocrinology 12th edition

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