Hyper Adrenalism

Question 1

Where specifically in the adrenal cortex are glucocorticoids (cortisol), Mineralcorticoids (aldosterone) and sex steroids

Answer 1

Glucocorticoids = zona fasciculata

Mineralcorticoids = zona glomerulosa

Sex steroids = Zona reticularis

Question 2

What is the name of cells that generate catecholamines and epinephrine?

Answer 2

Chromaffin cells found in the adrenal medulla

Question 3

What are the 3 hyper-adrenal syndromes c

Answer 3

Cushing syndrome = excess cortisol

Hyperaldosteronism = excess aldosterone

Adrenogential/viririzing syndrome = excess androgens

Question 4

Cushing syndrome

Answer 4

Elevated glucocorticoid levels

Most common cause = iatrogenic (giving too much exogenous glucocorticoids)

Can also be:

• pituitary Cushing syndrome (Cushing disease) (#1 cause of endogenous Cushing)
• tumors in the adrenal cortex (primary)
• paraneoplastic cushings (usually lung cancer)

Question 5

Cushing disease (ACTH-dependent Cushing disease)

Answer 5

Primary hypothalamic-pituitary disease caused by a tumor in one of these two organs (usually a cause of pituitary)

• accounts for approximately 70% of cases of endogenous cushings
• these tumors usually DONT produce a mass effect

Hyper-secretion of ACTH leads to excess cortisol release due to cortical hyperplasia

Prevalence is 4x higher among women and occurs most frequently during young adulthood

Question 6

ACTH-independent cushing syndrome

Answer 6

Caused by primary adrenal neoplasms which secrete a lot or cortisol
- almost always unilateral adrenocortical neoplasms that can be adenoma or carcinomas

ALWAYS shows LOW ACTH and HIGH CORTISOL

Question 7

Primary cortical hyperplasia

Answer 7

A very rare cause of cushing syndrome

Two variants

1) macronodules (around 3 cm)
2) micronodules (1-3 mm)

Question 8

Morphological changes in adrenal glands and hypercortisolism

Answer 8

There are 4 different changes

1) cortical atrophy
- seen in exogenous glucocorticoid overuse since it turns off the adrenal cortex and lack of stimulation to zona fasciculata and reticularis

2) diffuse hyperplasia
- found in patients with ACTH-dependent Cushing syndrome
- shows very lipid-rich cells in the hyperplastic cells

3) macronodular/micro nodular hyperplasia
- seen in primary cortical hyperplasia

4) adenoma or carcinoma
- more common 30-50s
- looks identical to adrenal medulla

Question 9

How does hyper adrenalism cause hyperglycemia and secondary diabetes?

Answer 9

Glucocorticoids induce gluconeogenesis and inhibits uptake of glucose by cells

Results in

• hyperglycemia
• glucosuria
• polydipsia
• insulin resistance

Catabolic effects of insulin resistance results in loss of collagen
- skin thinning, fragile, easy brushing and cutaneous striae

Question 10

What psychiatric symptoms are tied to hyperadrenalism?

Answer 10

Mood swings

Depression

Frank psychosis

Question 11

How to diagnosis cushing syndrome with lab values

Answer 11

1) 24 hr urine free-cortisol of concentration is increased
2) loss of normal diurnal pattern of cortisol secretion

The CAUSE of cushing syndrome is determined based on the dexamethasone test (inject dexamethasone and wait)

• if pituitary cause = ACTH levels stay the same unless high dose
• if adrenal cause = ACTH levels will be decreased
• if ectopic cause (SCC of lung) ACTH levels dont decrease

Question 12

Primary hyperaldosteronism

Answer 12

Autonomous overproduction of aldosterone that results in suppression of the RAAS system and DECREASED plasma renin activity

Most common causes:

• bilateral idiopathic hyperaldosteronism
• adrenocortical neoplasm

Bilateral idiopathic = bilateral nodular hyperplasia of the adrenal glands and is the most common cause of hyperaldosteronism (60%)

Adrenocortical neoplasms = solitary alodsterone secreting adenomas (Conn syndrome) or carcinomas

Question 13

What is the genetic cause of bilateral idiopathic hyperaldosteronism and conn syndrome?

Answer 13

Germ line mutations in KCNJ5 gene which encodes a potassium channel protein that is expressed in the adrenal gland

Question 14

How to tell primary hyperaldosteronism from secondary aldosteronism apart with lab values

Answer 14

Primary = LOW renin levels

Secondary = HIGH renin levels
- common in conditions that include: decreased renal perfusion, arterial hypovolemia and edema and pregnancy

Question 15

How to differentiate adrenal cortical adenomas that produce excess cortisol vs hyperaldosteronism?

Answer 15

If the adrenal cortex of the contralateral gland is atrophy or not

• hyperaldosteronism = doesnt suppress ACTH so NO ATROPHY
• hyper cortisol = DOES suppress ACTH so YES ATROPHY

Nothing are solitary masses that are small and well circumcised

Question 16

What is the most importaint clincial consequence of hyperaldosteronism?

Answer 16

HTN

5-10% of HTN patients have primary hyperaldosteronism

Aldosterone induced HTN leads to quicker cardiovascular compromise (LVH and reduced diastolic volumes) as well as increased risks for stroke and MI

Question 17

What electrolyte abnormalities are seen in hyperaldosteronism?

Answer 17

Hypernatremia

Hypokalemia

• results in renal potassium wasting
• NMJ manifestations (weakness, paresthesia, visual disturbances PMNs frank tetany)

Question 18

Treatment for primary and secondary hyperaldosteronism

Answer 18

Primary

• adenomas = surgical excision
• bilateral hyperplasia = aldosterone antagonists (spironolactone)

Secondary
- correct underlying cause of RAAS hyper stimulation (renal stenosis, CHF/heart failure, pregnancy edema)

Question 19

Andreogential syndromes

Answer 19

A group of disorders caused by androgen excess that have multiple etiologies. All are AUTSOMAL RECESSIVE
- causes excess dehydroepiandroesterone and androstenedione release which gets converted into testosterone in peripheral tissues

Pretty much all cause virilizing activity

In the adrenal gland = congenital adrenal hyperplasia (CAH)
- all result in adrenal hyperplasia

Neoplasms that cause this condition are more likely to be carcinomas than adenomas

**Need to screen all CAH subtypes in any neonate with ambiguous genitalia

Question 20

Most common CAH

Answer 20

21-hydroxylase enzymatic defect
- 90%

This enzyme is required for cortisol and aldosterone production however NOT sex steroids
- there for there is no cortisol and aldosterone but excess sex steroids

Shows adrenal insufficiency symptoms

Produces masculinization of female external genitalia, hirsutism and acne

Produces precious puberty and enlargement of external genitalia in males

33% of cases show extreme salt wasting and hyperkalemia

Question 21

Treatment of CAH’s

Answer 21

Exogenous glucocorticoids always (hydrocortisone or prednisone)

May also need Mineralcorticoids if aldosterone insufficiency is present