Lecture 16: Adrenal Pathophysiology Flashcards
What is Cushing’s syndrome?
Defined as EXCESS cortisol secretion
Regardless of cause or source
What is the most common cause of Cushing’s syndrome?
Iatrogenic from exogenous glucocorticoid use
ACTH-INDEPENDENT
What are the pathophysiologic derangements of the HPA axis?
- loss of diurnal variation of cortisol secretion
- Autonomy from central ACTH control
- los of response to negative feedback
- excess cortisol secretion
What are the two types of Cushing’s Syndrome?
- ACTH-Dependent
2. ACTH-independent
What are the causes of ACTH-dependent Cushing’s?
- Cushing’s disease (pituitary adenoma) 68% of patients
- Ectopic ACTH syndrome
- Ectopic CRH syndrome
- Factitious ACTH administration
What are the causes ACTH-independent Cushings?
- Iatrogenic/factitious
- adrenal adenoma
- adrenal carcinoma
- micro/macronodular hyperplasia
What does dexamaethasone do to the ACTH?
It suppresses it
Normal pituitary tissue should not secrete ACTH
So you should have low cortisol after administration
What are the sign and symptoms of Cushings?
- Gluconeogensis stmulated so HYPERglycemia
- Increased lipogenesis from increased insulin
- INSULIN RESISTANCE
- Protein metabolism
- catabolism of gluconeogenesis
- Fat deposition in suprclavicular fossa
- Immunity is impaired
- Increased clotting factors
- Cataract formation
- OSTEOPOROSIS
- Wide variation of psychiatric disturbances
- depression, psychosis
- integument, acne, streaks in skin
- cardiomyopathy, hypertension
Where is fat deposition in Cushing’s?
Round face DEWLAP (in chin)
Fat pads (supraclavicular fat pads)
Buffalo humps
What are the mineralocorticoid and androgen effects in Cushings?
- HTN and HYPOkalemia
- testosterone increase in females
- menses is abnormal
- virilization
Onl in ACTH DEPENDENT because ACTH fucks
With androgens
Bilateral adrenal hyperplasia
If you suspect patient with Cushing’s, what would You need to do first?
You need to make sure they are not using exogenous cortisol
How do you measure Cushings?
- measure late night salivary cortisol
- 1 mg dexamethasone suppression test
- 24 urinary free cortisol
What is the 1 mg dexamethasone suppression test?
The DST indicates inappropriate cortisol secretion
Does not indicates source
Dex is taken by patient at 11pm and cortisol is measured at 8am
Normal test = <2 mcg/dl after Dex
Dexamethasone = cortisol in that it downregulates (or should downregulate) ACTH
What does it mean to have a positive dex test?
It means there is an autonomous adrenal tissue that is generating cortisol
ACTH adenoma will continue to stimulate adrnals
Loss of negative feedback control
Could be ACTH adenoma
You suspect Cushing’s in a patient. Their urine cortisol is elevated and cortisol is elevated after DST. ACTH levels are normal. What is source of Cushing’s?
Pituitary Adenoma (cushing’s disease)
If you have normal ACTH and high cortisol, you have?
Pituitary adenoma
If you have high ACTH and high cortisol, you have?
Ectopic ACTH excess
If you have low ACTH and high cortisol, you have?
Adrenal tumor
If iatrogenic glucocorticoids, what si ACTH level?
ACTH should be suppressed by iatrogenic cortisol
What is being burned when you have too much cortisol?
Glucose from gluconeogenesis (so that’s why you lose muscle)
How long does it take hypercortisolism to resolve?
12 months
Psychiatric complications can remain
What is primary adrenal failure?
Addison’s disease Typically 90% of cortex is destroyed Elevated ACTH concentrations Course can be acute or indolent depending on cause All adrenal hormones can be lost
What type of symptoms would you expect in primary adrenal failure?
Symptoms consistent with both mineralocorticoid and glucocorticoid deficiency
i. HYPOnatremi
ii. HYPERkalemia
iii. HYPOtension
iv. HYPERpigmentation
What are the clinical characteristics of primary adrenal failure?
- hyperpigmentation from increased ACTH, increasing melanin
- EXHAUSTED (real fatigue)
- Weight loss
- muscle or joint pains
- Fatigue
- Nausea, abdominal pain
- hypoglycemia can occur
What are the etiologies of primary adrenal insufficiency?
- Autoimmune destruction of adrenal cortex: 60%
- Infectious: TB, fungus, HIV (CMV, MAI, KS)
- Bilateral hemorrhage/Infarction: anticoagulants, trauma, embolic disease, meningococcemia (Waterhouse-Friderichsen syndrome)
- Metastatic cancer
- Drugs: aminoglutethimide, ketoconazole, etomidate; rifampin, phenytoin (increase cortisol metabolism)
Which of the following clinical/lab findings would you expect with Addison’s?
HYPOnatremmia and HYPERkalemia
That’s because glomerulosa and fasciculate is fucked
How do you diagnose adrenal insufficiency?
- early AM cortisol and ACTH concentration (when shit is supposed to be highest)
- if early am cortisol <5mcg/dl with an elevated ACTH very likely primary adrenal insufficiency
- Cosyntropin stimulation testing, IM injection of synthetic ACTH. Cortisol measured 30 to 60 min later
What is cosyntropin testing?
Cosyntropin is synthetic ACTH
Cortisol should be higher
If serum cortisol is >20 mcg/dl, then it cant be adrenal failure cuz ACTH worked
How do you treat Addisons?
Give dexamethasone first because it will NOT INTERFERE with cortisol assay
Initial treatment
What is an addisonian (adrenal) crisis)?
- Defined as acute deficiency in cortisol and mineralocorticoids
- Can be life threatening
- Often masquerades as other conditions i.e. sepsis, acute abdomen
- HYPOtension, shock
- Fatigue, weakness, malaise
- Fever, lethargy
- Abdominal pain, nausea, vomiting
- Anorexia
- Hypoglycemia
What is the short term treatment of addisonian crisis ?
- 1-3 liters of saline IV over 12-24 hours
- Dexamethasone 4mg IV
- Monitor electrolytes
- Monitor blood pressure
What is vitiligo?
A condition that causes depigmentation of sections of skin
-loss of brown color from areas of skin, resulting in irregular white patches
What is the association between Addison’s and autoimmune disorders?
Half of persons with autoimmune adrenalitis have at least one other autoimmune disorder
What are the symptoms of primary hyperaldosteronism?
- Hypertension
- Hypokalemia (muscle weakness)
- Mild hypernatremia
- Metabolic alkalosis
Can a patient have hyperaldosteronism AND normal serum potassium?
Yes
While potassium wasting is common in mineralocorticoid excess syndromes but is not absolute; and patients may have hyperaldosteronism and normal serum potassium
What are the characteristics of androgen excess?
- in women, hirsutism, male pattern baldness, menstrual irregularities
- gonadotropin secretion is disrupted in men
- adrenal adenomas rarely cause androgen excess, they are efficient at secreting cortisol
Cushing’s syndrome can cause elevations in testosterone and DHEA-S
What is a pheochromocytoma?
Tumor that secretes excess catecholamines (epinephrine)
-arises from chromaffin cells
Feeling of impending doom
Which of the following would you screen for primary hyperaldosteronism? EXAM QUESTION
- Persons under 30 with hypertension, no obesity or family history
- Persons with unexplained hypokalemia
- Persons with resistant hypertension
- Persons with an adrenal incidentaloma and hypertension
What are the causes of hyperaldosteronism?
- Adrenal adenoma producing aldosterone
- Bilateral adrenal hyperplasia
- elevated aldosterone:renin ratio
- needs to demonstrate it after salt lpad
If you have bilateral adrenal hyperplasia, how do you treat?
Mineralocorticoid antagonists
If you have unilateral adenoma, what do you do?
Surgical resection
What is the most common cause of addisons? EXAM QUESTION
Autoimmune destruction of adrenal cortex
In pituitary Cushing’s you might expect which of the following lab abnormalities? EXAM QUESTION
Normal ACTH, high cortisol
In a normal individual 1 mg of dexamathesone would result in which of the following? Exam question
ACTH and cortisol suppression after a night of sleep
Which of the following electrolytes imbalances would you expect with Cushing’s? EXAM QUESTION
HYPERnatremia
HYPOkalemia
