primary adrenal insufficiency
TRANSCRIPT
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PRIMARY ADRENAL INSUFFICIENCY
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ADRENAL GLAND
• FUNCTION :
The adrenal glands are composed of two functionally distinct endocrine units, the adrenal cortex and medulla, contained within a single capsule.
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ADRENAL GLAND
• Adrenal cortex functionthree functional zones
• Zona glomerulosasecretes mineralocorticoids(aldosterone) which regulate sodium and potassium homeostasis.
• Zona fasciculata secretes glucocorticoids (most importantly, cortisol).
• Zona reticularis secretes sex steroids (primarily androgens).
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ADRENAL GLAND
• Adrenal medulla function :
The adrenal medulla synthesizes and secretes catecholamines, which modulate the body's sympathetic response to stress.
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ADRENAL GLAND
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ADRENAL INSUFFICIENCY
• Primary.
• Secondary.
• Tertiary.
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WHAT IS THE SIGN & SYMPTOMS OF ADRENAL
INSUFFICIENCY?
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SIGN & SYMPTOMS OF PAI
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SIGN & SYMPTOMS OF PAI
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PRIMARY ADRENAL INSUFFICIENCYAUTOIMMUNE ADRENALITIS
1. AUTOIMMUNE ADRENALITIS
• Autoimmune process that destroys the adrenal cortex .
• Associated with autoimmune destruction of other endocrine glands.
• Antibodies that react with several steroidogenicenzymes (most often 21-hydroxylase).
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PRIMARY ADRENAL INSUFFICIENCYAUTOIMMUNE ADRENALITIS
• Early findings The first evidence is increase in plasma renin activity .
• Normal or low serum aldosterone? If low suggesting zona glomerulosa is involved.
• Months to years later, zona fasciculata dysfunction becomes evident, by:
1. Decreasing serum cortisol in response to (ACTH).2. Increased basal serum ACTH concentrations. 3. Finally by decreasing basal serum cortisol
concentrations and symptoms .
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PRIMARY ADRENAL INSUFFICIENCYAUTOIMMUNE ADRENALITIS
• Approximately 65 % of patients with autoimmune adrenal insufficiency have one or more other autoimmune endocrine disorders such as type 1 DM, chronic autoimmune thyroiditis ,Graves' disease.
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PRIMARY ADRENAL INSUFFICIENCYAUTOIMMUNE ADRENALITIS
1. Polyglandular autoimmune syndrome type 1.
Polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome.
Hypoparathyroidism or chronic mucocutaneouscandidiasis is first manifestation (candidiasis mouth).
Adrenal insufficiency usually develops later, at age 10 to 15 years.
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PRIMARY ADRENAL INSUFFICIENCYAUTOIMMUNE ADRENALITIS
Primary hypogonadism occurs in 60% .
Malabsorbation 25%.
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PRIMARY ADRENAL INSUFFICIENCY
2. Polyglandular autoimmune syndrome type 2
Much more common than type 1 and primary adrenal insufficiency is its principal manifestation .
Chronic autoimmune thyroiditis & type 1 DM is common
with most cases occurring between age 20 and 40 years
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TYPE1 VS. 2
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PRIMARY ADRENAL INSUFFICIENCY INFECTIOUS ADRENALITIS
2. INFECTIOUS ADRENALITIS
Tuberculosis :
• Tuberculous adrenalitis results from hematogenous spread from active infection.
• No Antiadrenal autoantibodies
• Adrenal calcifications 50 % .
• Recovery of normal adrenal function ?? Usually not
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PRIMARY ADRENAL INSUFFICIENCY INFECTIOUS ADRENALITIS
Disseminated fungal infections :
• Histoplasmosis ¶coccidioidomycosis
HIV infection.
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INFECTIOUS ADRENALITIS
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PRIMARY ADRENAL INSUFFICIENCY
3. HEMORRHAGIC INFARCTION :
Hemorrhage or adrenal vein thrombosis.
Adrenal hemorrhage associated with meningococcemia (Waterhouse-Friderichsen syndrome) .
4. METASTATIC DISEASE
60% lung or breast cancer.
30 %melanoma.
20 % stomach or colon cancer.
but clinically evident adrenal insufficiency is uncommon
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PRIMARY ADRENAL INSUFFICIENCY
5.DRUGS
anesthetic-sedative drug etomidate.
Antimycotic ketoconazole & fluconazole.
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RECOMMENDATIONS
Who should be tested and how?
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RECOMMENDATIONS
1. Acutely ill patients with S & S suggestive of PAI volume depletion, , BP, NA, k ,
fever, abdominal pain, hyperpigmentation.
2. (Recommend) confirmatory testing with the corticotropin stimulation test in patients with clinical S & S of PAI when patient’s circumstance allow.
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RECOMMENDATIONS
3. Patients with severe adrenal insufficiency or adrenal crisis, we recommend immediate therapy with iv hydrocortisone with stress dose prior results of diagnostic tests.
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RECOMMENDATIONS
diagnostic tests??
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RECOMMENDATIONS
1. (Recommend) standard dose 250ug for adults iv corticotropin stimulation (30 or 60min), Peak cortisol levels below 500 nmol/L (18 g/dL) at 30 or 60 minutes indicate adrenal insufficiency.
2. If a corticotropin stimulation test is not available we suggest using a morning cortisol, 140 nmol/L (5 g/dL) in combination with ACTH as a initial test suggestive of adrenal insufficiency .
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RECOMMENDATIONS
3. (Recommend) measurement of plasma ACTH to establish PAI. In patients with confirmed cortisol deficiency.
Plasma ACTH 2 fold the upper limit of the reference range is consistent with PAI.
4. (Recommend) Measurement of plasma renin and aldosterone in PAI to determine the presence of mineralocorticoid deficiency.
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RECOMMENDATIONS
Treatment of primary adrenal insufficiency in adults??
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RECOMMENDATIONS
1. Glucocorticoid replacement regimen
• (Recommend) glucocorticoid therapy in all patients with confirmed PAI.
• (Suggest) using hydrocortisone (15–25 mg) or cortisone acetate (20 –35 mg) in two or three divided oral
• Alternative to hydrocortisone, we (suggest) using prednisolone (3–5 mg/d)
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RECOMMENDATIONS
• (Suggest) against using dexamethasone for the treatment of PAI because of risk of Cushingoid side effects & due to difficulties in dose titration
• (Suggest) against hormonal monitoring of glucocorticoid replacement and to adjust treatment only based on clinical response
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RECOMMENDATIONS
2. Mineralocorticoid replacement in PAI
• (Recommend) that all patients with confirmed aldosterone deficiency receive mineralocorticoid replacement fludrocortisone (starting dose, 50 –100 ug in adults).
• Monitoring mineralocorticoid replacement primarily based on clinical assessment ( postural hypotension, or edema), & blood electrolyte measurements.
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RECOMMENDATIONS
3. Dehydroepiandrosterone replacement.
• (Suggest) a trial of Dehydroepiandrosterone (DHEA) replacement in women with PAI and low libido, depressive symptoms or low energy levels despite otherwise optimized glucocorticoid and mineralocorticoid replacement.
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RECOMMENDATIONS
Management and prevention of adrenal crisis in patients with PAI ?
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RECOMMENDATION
1. (Recommend) that patient with adrenal crisis should be treated with an immediate parenteral injection of 100 mg hydrocortisone followed by appropriate fluid resuscitation & 200 mg of hydrocortisone /24 hours (continuous iv or every 6 hours injection)
2. If hydrocortisone is unavailable, we (suggest) pred-nisolone as an alternative. Dexamethasone is the least- preferred alternative and should only be given if no other glucocorticoid is available
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RECOMMENDATION
3. For the prevention of adrenal crisis, we (suggest) ad-justing glucocorticoid dose according to severity of illness or magnitude of the stressor.
4. Home management of illness with fever if 38 > double the dose , if 39> triple the dose.
5. Minor to moderate surgical stress we will give hydrocortisone 25-75mg/24h (1-2 days).
6. Major surgery like adrenal crisis. 7. We (recommend) that every patient should be equipped
with a glucocorticoid injection kit for emergency use and be educated on how to use it.
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CASE SCENARIO
• A 32 – years old man comes to the office after a year of weakness, fatigue , and weight loss. He has experienced reduced appetite and intermittent diarrhea. The patient hand no improvement after several sessions of clinical psychologist, who suggested evaluation for a physiological cause of his symptoms . His medical history unremarkable and he takes no medications , the patient does not use tobacco , alcohol or illicit drugs . Family history is notable for hypothyroidism (his sister).
• Temp is 37.2 ,blood pressure is 106/66 mm hg , pulse 94/min , & respirations are 14/min .
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CASE SCENARIO
On physical examination the patient does not appear to be in acute distress . His neck show no thyromegaly or lymphadenopathy. Cardiopulmonary examination is normal , abdomen is soft with normal bowel sound . Motor strength and deep tendon reflexes are normal and symmetrical
• LABS :
- Hemoglobin 12.3 g/dl
- WBC 3000
- serum sodium 130 mEq/L
-serum potassium 5.5 mEq/l
- 8 AM cortisol 7.2 ug/dl(normal 5-23)
- TSH 2.5 mLU/L
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CASE SCENARIO
Q - Which of the following is the most appropriate next step in management of this patient ?
A- 24-hours urine free cortisol.
B-ACTH stimulation test.
C- Insulin induced hypoglycemia test .
D-Intravenous hydrocortisone .
E – Low-dose overnight dexamethasone suppression test.
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CASE SCENARIO
• Answer is • B- ACTH stimulation test.
Explanation : The initial test evaluation should include
1- 8 AM cortisol level 2- Plasma ACTH level
However , the ACTH assay can take several days so ACTH stimulation test is usually preformed to rapidly confirm the dignosis
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SPOT DIAGNOSIS
• 44 years old female from India comes with fever , hemoptysis, weight loss 10 kg , for 3 weeks. Recently she started to complain of increasing weakness, fatigue.
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SPOT DIGNOSIS
• Bilateral adrenal enlargement & calcification. • INFECTIOUS ADRENALITIS most likely due active
TB infection.
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THANK YOU
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QUESTION
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DONE BY :
DR.AMER HISHAM ALBOUSH
MEDICAL INTERN
UMM ALQURA UNIVERSTY