disorders of the adrenal glands Flashcards
List the 3 sections of the adrenal cortex and what each produces
- zona glomerulosa: mineralocorticoids: aldosterone
- zona fasciculata: glucocorticoids: cortisol
- zone reticularis: adrenal androgens: mostly DHEA
cortisol is excreted in the urine in what form
17 hydroxysteroid (17OHS)
androgen is excreted in the urine in what form
17 ketosteroids (17KS)
what is the sign and symptom complex resulting from prolonged expsore to glucocorticoid hormones
cushings syndrome
List the causes of ACTH-dependent cushing’s syndrome
- excessive ACTH production from pituitary (pituitary adenoma): most common cause
- ectopic ACTH producing tumor
- small cell lung CA is most common
- excessive CRH production from hypothalamus
List the causes of ACTH-independent cushing’s syndrome
- adrenal tumor
- neuroendocrine tumors
- pheochromocytoma
which type of cushing’s syndrome, ACTH dependent or independent, is more common? Is it more likely in males or females
- ACTH dependent: 70%
- 8-10x more likely in females
clinical presentation
- weight gain/obesity
- facial plethora “moon face”
- truncal obesity with extremity wasting
- buffalo hump
- fatigability and weakness
- mostly proximal muscles
- abdominal straie
- acne and abnormal hair growth
- edema
- HTN
- insulin resistance
- vertebral fx, hypercalcuria, kidney stones
- dysphora, depression, paranoia
cushing’s syndrome
What two hormone levels do you get to work up possible cushing’s syndrome
- plama cortisol level
- 8AM
- 4PM
- serum ACTH level
- 8AM
- 4PM
what is an abnormal result for plasma cortisol level
- > or = 25 ug/dl at 8 AM
- less than the anticipated drop of 1/3 to 2/3 at the 4PM reading
what is abnormal serum ACTH levels
- > 80 pg/ml at 8am; >50 pg/ml at 4pm
- < 20 pg/ml at any time
Are cortisol and ACTH levels expected to be high or low in ACTH independent
- cortisol: high
- ACTH: low
Are cortisol and ACTH levels expected to be high or low in ACTH dependent
- cortisol: high
- ACTH: high
Why is 11-deoxycortisol measured at 8am when working up for cushing’s syndrome
- 11-deoxycortisol is a cortisol precursor
- it should be converted to cortisol and be undetectable at 8am
What is the gold standard for screening for cushing’s syndrome? What is an abnormal result
- Dexamethasone suppression test (DST): given at night, expect ACTH and cortisol levels to be low the next morning
- abn result: cortisol > 5 ug/d is highly suspicious
What is the main stay for diagnosis for cushing’s syndrome? What is an abnormal result
- 24 hour urine free cortisol
- measures 17-OCHS
- abnormal: cortisol > 125 ug/d is indicative of cushings
describe salivary sampling used to work up cushing’s syndrome or adrenal insufficiency
- free cortisol diffuses freely into saliva
- sample saliva obtained after rinsing mouth but before brushing teeth at
- 9:00 am 3 mornings in a row when evaluating for adrenal insufficiency
- 11:00pm 3 nights in a row when evaluating for cushing’s syndrome
abnormal results for salivary sampling in cushing’s syndrome vs adrenal insufficiency
- cushing’s syndrome: late evening salivary cortisol elevated
- adrenal insufficiency: morning salivary cortisol low
MOA of Mitotane
- induces permanent destruction of the adrenocortical cells
- AKA medical adrenalectomy
MOA of Ketoconazole in cushing’s syndrome? major side effect?
- antifungal with cortisol-reducing effects in higher doses
- liver toxicity
MOA of Metyrapone in cushing’s syndrome?
- inhibits cortisol synthesis
What is the most common cause of cushing’s syndrome
ACTH producing pituitary adenoma
What is the most common cause of cushingoid symptoms
exogenous steroid use
what is the inadequate production of mineralocorticoids, glucocorticoids, and or sex androgens
- adrenal insufficiency
- when all three are present -> addison’s disease
what is the most common cause of primary adrenal insufficiency
addison’s disease: autoimmune destruction of adrenal gland
what are some infectious agents that can cause adrenal insufficiency
- histoplasmosis
- TB
- coccidiodomycosis
What is the most common cause of secondary adrenal insufficiency
- suppression of HPA axis through abrupt cessation of exogenous steroid
list drugs that reduce corticosteroids and can cause secondary adrenal insufficiency
- phenytoin
- opiates
- ketoconazole
- rifampin
list the hallmark tetrad of adrenal insufficiency
- weakness/fatigue
- weight loss/anorexia
- hyperpigmentation
- hypotension (orthostatic)
clinical presentation suggest deficiency in which hormone
- weakness
- fatigue
- hypoglycemia
- weight loss
- anorexia
- nausea
- vomiting
- abd pain
glucocorticoid deficiency
clinical presentation suggest deficiency in which hormone
- Na++ wasting
- hyponatremia, salt craving
- hypovolemia
- orthostatic hypotension
- hyperkalemia
- mild metabolic acidosis
Mineralocorticoid deficiency
clinical presentation suggest deficiency in which hormone
- loss of axillary and pubic hair in females
- amenorrhea
adrenal androgen deficiency
What is an abnormal result in the plasma cortisol level in the work up for adrenal insufficiency
- < 5 ug/dl in the AM
What is an abnormal result in the serum ACTH level in the work up for adrenal insufficiency
- > 80 at 8am; > 50 at 4 pm
- < 20 at any time
what do you expect cortisol and ACTH levels to be in primary and secondary adrenal insufficiency
- primary (addison’s disease: cortisol low, ACTH high
- secondary: corticol low, ACTH low
explain the Cosyntropin stimulation test
- evaluates the ability of the adrenal gland to respond to ACTH administration: gold standard for diagnosis
- procedure
- obtain baseline cortisol level
- administer bolus of ACTH
- measure cortisol at 30 min and 60 min
- abormal result: cortisol level fails to increase > 18 mcg/dl
What is the benefit of the Metyrapone stimulation test
- can be completed while on glucocorticoid supplementation
what is an abnormal response on the Metyrapone stimulation test in regards to 24 hour 17-OCHs excretion, serum cortisol, plasma ACTH, and serum 11-deoxycortisol
- 24 hour 17-OCHs excretion: less than doubling from baseline
- serum cortisol: > 5
- plasma ACTH: < 75
- serum 11-deoxycortisol: < 7
Management of glucocorticoid deficiency
- hydrocortisone
- prednisone
- dexamethasone
Management of mineralcorticoid deficiency
fludrocortisone
Management of adrenal androgen deficiency
- DHEA
What should be done to the dose of glucocorticoids in the face of highly stressful events
increase dose
Two causes of primary hyperaldosteronism (Conn’s syndrome)
- adrenalcorticol adenoma
- cortical hyperplasia
elevated plasma and urine aldosterone, low plasma renin levels are indicative of
primary hyperaldosteronism (Conn’s syndrome)
management of primary hyperaldosteronism (Conn’s syndrome)
- surgical removal of adenoma
- medical = spironolactone and antihypertensive agents
clinical presentation
- HTN
- hypokalemia
- muscle weakness
- paresthesias
- HA
- polyuria and polydipsia
primary hyperaldosteronism (Conn’s syndrome)
What is a pheochromocytoma
- rare, catecholamine-producing tumor of neurochromaffin cells
- 10-15% malignant
- fatal if undiagnosed and untreated
extra-adrenal pheochromocytomas are called
paragangliomas
majority of pheochromocytomas arise from
adrenal medulla
pheochromocytomas can also occur in what autosomal dominant hereditary syndromes
- MEN2
- von hippel-lindau syndrome
- neurofibromatosis type 1
pheochromocytomas is characterized by classic paroxysm attacks of
- HA
- sweating
- palpitations
-
profound acute HTN at the time of episode
- usually last 30-40 min
- may be precipitated by displacement of abdominal contents
- tend to increase in frequency and severity over time
what test is used to definitively diagnose pheochromocytomas
- clonidine suppression test
clonidine suppression test procedure
- stop hypotensive meds x 24 hours, fast overnight
- baseline BP, pulse and labs taken
- administer clonidine
- continue to monitor BP, pulse, and labs
- results:
- expect suppression of NE and epi
tx for pheochromocytoma
- IV nitroprusside for crisis
- chemical sympathectomy: pure alpha blocker, then beta blocker
- surgical excision is definitive tx
what is the rule of 10s in Pheochromocytoma
- 10% w/o HTN
- 10% extraadrenal
- 10% extraabdominal
- 10% children
- 10% familial
- 10% bilateral
- 10% metastatic disease at diagnosis
after the initial workup for pheochromocytomas, what should be done
- anatomic localization
- CT, MRI, PET, MIBG scan, OctreoScan
what is a adrenal incidentaloma
- mass lesion greater than 1 cm discovered incidentally by radiologic exam
- prevalence higher in obese, HTN, and DM patients
- 85-90% are non-functional
an adrenal incidentaloma that is lipid rich is more indicative of a
benign lesion
evaluation of hormonal secretion after finding a adrenal incidentaloma
- plasma cortisol, serum ATCH, serum DHEA, plasma aldosterone
- sxs of cushing?
- yes: 24 hr urinary free cortisol
- no: 1 mg overnight dexamethasone suppression
- suspicion for pheo?
- 24 hr urine metanephrines, catecholamines
when is a fine needle aspiration indicated in adrenal incidentaloma
- if primary malignancy elsewhere
- dont use if
- evidence of pheo
- known widespread metastatic dz
when is resection indicated for adrenal incidentaloma
- > 2 cm
