Adrenal Insufficency

Question 1

Adrenocortical insufficiency definition

Answer 1

Hypofunction of adrenal cortex that can be either:

• primary adrenal issues = primary hypoadrenalism
• deficiency of ACTH = secondary hypoadrenalism

Question 2

Common causes of primary hypoadrenalism

Answer 2

Loss of cortical cells

Congenital adrenal hypoplasia

Adrenoleukodystrophy

Autoimmune adrenal insufficiency (#1)

TB infections (use to be most common but anti-Tb therapy has made this 2nd now)

Steroid induced ACTH inhibition

Metastatic cancer

Amyloidosis/sarcoidosis/hemochromatosis

TB or fundal infections

Question 3

What are the two versions of primary adrenocortical insufficiency

Answer 3

Primary acute = adrenal crisis

Primary chronic = Addison disease

Question 4

Primary acute adrenocortical insufficiency

Answer 4

A crisis that occurs with acute exacerbation of chronic adrenocortical insufficiency
- usually due to stress or rapid withdrawal of corticosteroids or massive adrenal hemorrhages

Question 5

Causes of massive adrenal hemorrhage

Answer 5

Commonly occurs in newborns following prolonged difficult delivery and with considerable trauma and/or hypoxia

Can also occur with patients on anticoagulation therapy, patients who develop DIC and infections or disseminated bacterial infection (Waterhouse-Friderichsen syndrome)

Question 6

Waterhouse-Friderichsen syndrome

Answer 6

Uncommon syndrome that occurs in overwhelming bacterial disseminated infections

Can occur at any age but most common in children

Most commonly seen in neisseria meningitids infections
- can be pseudomonas, pneumococcus, haemophilus or staph species

Leads to rapid progressive hypotension, shock and DIC with systemic purpura
- the DIC causes rapidly developing adrenocortical insufficiency due to massive bilateral adrenal hemorrhages

Will kill within a day if not caught and dealt with

Question 7

Primary chronic adrenocortical insufficiency (Addison disease)

Answer 7

Uncommon disorder that results from progressive detection of the adrenal cortex
- symptoms really only arise once 90% of the cortex is destroyed

All races and both sexes may be affected but autoimmune adrenalitis is most common in white women

Autoimmune adrenalitis is the most common cause also (60-70%)

if you give a ACTH shot, nothing happens

Question 8

Autoimmune adrenalitis

Answer 8

Can occur with multiple autoimmune polyendocrine syndromes
- the most characterized one is APS1 = mutations in the AIRE gene on chromosome 21

Always shows mucocutaneous candidiasis and abnormalities of the skin/dental enamel and nails
- also dependent on other organs hit, will show symptoms based on that

Histology = loss of subcapsular rim with extensive mononuclear cell infiltrate
- also shrunken glands all around

Question 9

APS1 and mutated AIRE proteins

Answer 9

Is involved in expression of tissue antigens in the thymus

APS1 subtype develops autoantibodies against IL-17 and IL-22
- antibodies against these IL’s results in decreased TH-17 T-cell production

*Because TH-17 derived cytokines aren’t working, fungal infections are very difficult for patients of this to fight fungal infections. Patients always have chronic mucocutaneous candidiasis

Question 10

What fungi infections can induce chronic adrenocortical insufficiency

Answer 10

Histoplasma capsulatum and coccidioides

Question 11

What additional pathogens can cause Addison disease (primary insufficiency)

Answer 11

Mycobacterium Avium complex

CMV

Kaposi sarcoma/HHV-8

Question 12

What primary sites of metastatic cancer often go to the adrenal glands and cause addisons

Answer 12

Lung and breast carcinomas

Question 13

Secondary adrenocortical insufficiency

Answer 13

Any disorder of the hypothalamus or pituitary that reduces the output of ACTH

Induces:

• meatastatic cancers
• infections
• infarction
• irradiation

Almost always presents with multiple endocrine abnormalities

**DOESNT present with hyperpigmentation and has normal aldosterone synthesis so NO hyperkalemia and hyponatremia and low BP **
(All of these help differ between primary )

if you give an ACTH shot the cortisol will rise

Question 14

What does the gross morphology of secondary adrenocortical insufficiency?

Answer 14

Adrenals are reduced to small flattened structures that retain their yellow color

They have an intact medulla and reveals atrophy of the zona fasciculata/reticularis layers of the cortex

Question 15

Clinical features of adrenocortical insufficiency

Answer 15

Progressive weakness

Fatigue

Anorexia/weight loss

Nausea/vomiting

Diarrhea