Hyper Adrenalism Flashcards
Where specifically in the adrenal cortex are glucocorticoids (cortisol), Mineralcorticoids (aldosterone) and sex steroids
Glucocorticoids = zona fasciculata
Mineralcorticoids = zona glomerulosa
Sex steroids = Zona reticularis
What is the name of cells that generate catecholamines and epinephrine?
Chromaffin cells found in the adrenal medulla
What are the 3 hyper-adrenal syndromes c
Cushing syndrome = excess cortisol
Hyperaldosteronism = excess aldosterone
Adrenogential/viririzing syndrome = excess androgens
Cushing syndrome
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)
Cushing disease (ACTH-dependent Cushing disease)
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
ACTH-independent cushing syndrome
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
Primary cortical hyperplasia
A very rare cause of cushing syndrome
Two variants
1) macronodules (around 3 cm)
2) micronodules (1-3 mm)
Morphological changes in adrenal glands and hypercortisolism
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
How does hyper adrenalism cause hyperglycemia and secondary diabetes?
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
What psychiatric symptoms are tied to hyperadrenalism?
Mood swings
Depression
Frank psychosis
How to diagnosis cushing syndrome with lab values
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
Primary hyperaldosteronism
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
What is the genetic cause of bilateral idiopathic hyperaldosteronism and conn syndrome?
Germ line mutations in KCNJ5 gene which encodes a potassium channel protein that is expressed in the adrenal gland
How to tell primary hyperaldosteronism from secondary aldosteronism apart with lab values
Primary = LOW renin levels
Secondary = HIGH renin levels
- common in conditions that include: decreased renal perfusion, arterial hypovolemia and edema and pregnancy
How to differentiate adrenal cortical adenomas that produce excess cortisol vs hyperaldosteronism?
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
What is the most importaint clincial consequence of hyperaldosteronism?
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
What electrolyte abnormalities are seen in hyperaldosteronism?
Hypernatremia
Hypokalemia
- results in renal potassium wasting
- NMJ manifestations (weakness, paresthesia, visual disturbances PMNs frank tetany)
Treatment for primary and secondary hyperaldosteronism
Primary
- adenomas = surgical excision
- bilateral hyperplasia = aldosterone antagonists (spironolactone)
Secondary
- correct underlying cause of RAAS hyper stimulation (renal stenosis, CHF/heart failure, pregnancy edema)
Andreogential syndromes
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
Most common CAH
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
Treatment of CAH’s
Exogenous glucocorticoids always (hydrocortisone or prednisone)
May also need Mineralcorticoids if aldosterone insufficiency is present
