primary adrenal insufficiency

PRIMARY ADRENAL INSUFFICIENCY

ADRENAL GLAND

• FUNCTION :

The adrenal glands are composed of two functionally distinct endocrine units, the adrenal cortex and medulla, contained within a single capsule.

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).

ADRENAL GLAND

• Adrenal medulla function :

The adrenal medulla synthesizes and secretes catecholamines, which modulate the body's sympathetic response to stress.

ADRENAL GLAND

ADRENAL INSUFFICIENCY

• Primary.

• Secondary.

• Tertiary.

WHAT IS THE SIGN & SYMPTOMS OF ADRENAL

INSUFFICIENCY?

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).

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 .

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.

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.

PRIMARY ADRENAL INSUFFICIENCYAUTOIMMUNE ADRENALITIS

Primary hypogonadism occurs in 60% .

Malabsorbation 25%.

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

TYPE1 VS. 2

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

PRIMARY ADRENAL INSUFFICIENCY INFECTIOUS ADRENALITIS

Disseminated fungal infections :

• Histoplasmosis &paracoccidioidomycosis

HIV infection.

INFECTIOUS ADRENALITIS

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

PRIMARY ADRENAL INSUFFICIENCY

5.DRUGS

anesthetic-sedative drug etomidate.

Antimycotic ketoconazole & fluconazole.

RECOMMENDATIONS

Who should be tested and how?

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.

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.

RECOMMENDATIONS

diagnostic tests??

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 .

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.

RECOMMENDATIONS

Treatment of primary adrenal insufficiency in adults??

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)

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

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.

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.

RECOMMENDATIONS

Management and prevention of adrenal crisis in patients with PAI ?

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

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.

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 .

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

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.

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

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.

SPOT DIGNOSIS

• Bilateral adrenal enlargement & calcification. • INFECTIOUS ADRENALITIS most likely due active

TB infection.

THANK YOU

QUESTION

DONE BY :

DR.AMER HISHAM ALBOUSH

MEDICAL INTERN

UMM ALQURA UNIVERSTY