Adrenal Flashcards
The zona glomerulosa produces _____ but lacks 17a-hydroxylase so it cannot produce _____ or _______
aldosterone
cortisol or androgens
The production of cortisol and androgens is regulated by ______
ACTH from the pituitary
What regulates ACTH secretion?
CRH from hypothalamus as well as vasopressin
______ feed back and inhibit both the pituitary and hypothalamus
glucocorticoids
List the metabolic effects of glucocorticoids
catabolic increase blood glucose increase glycogen deposition stimulate GNG inhibit glucose uptake in muscle and fat increase lipolysis inhibit protein synthesis
List the effects of glucocorticoids on bone
decrease bone formation
inhibit GI calcium absorption/ increase renal calcium excretion
What inflammatory cell types are increased/ decreased in the presence of glucocorticoids
Decrease circulating lymphocytes and eosinophils; cause neutrophilia- demargination
What is the effect of glucocorticoids in the kidney?
Enhance water clearance by antagonizing the action of ADH at the kidney
What are the physiologic effects of adrenal androgens?
most significant in women; minimal significance in men
contribute to development of axillary and pubic hair
What is the most common cause of primary adrenal insufficiency?
Western: autoimmune adrenalitis (Addison’s)
worldwide- infectious esp TB
What is the most common cause of secondary adrenal insufficiency?
space occupying lesion in sella turcica
What is the most common cause of tertiary adrenal insufficiency
HPA suppression by exogenous glucocorticoids, get sx when medications are abruptly stopped
_______ adrenal insufficiency presents with symptoms related to glucocorticoid and mineralocorticoid deficiency
______ adrenal insufficiency has only glucocorticoid deficiency
primary; secondary (RAAS system intact)
List symptoms of primary adrenal insufficiency
cortisol deficiency: weight loss, weakness, fatigue, NV, myalgia
aldosterone deficiency: orthostatic hypotension, salt craving
excess ACTH: hyperpigmentation
List laboratory abnormalities seen in primary adrenal insufficiency
hyponatremia- due to low cortisol and aldosterone
hyperkalemia- due to aldosterone deficiency
- normochromic anemia
eosinophilia
A low early morning _____ suggests any cause of adrenal insufficiency
cortisol
Lack of response to _____ stimulation testing is diagnostic of adrenal insufficiency
ACTH
- lack of response in secondary/ tertiary is possible but not always seen due to adrenal atrophy from chronic lack of ACTH stimulation
- lack of response in primary is because of problem with adrenal itself
______ levels in the blood distinguish primary from secondary/ tertiary adrenal insufficiency
ACTH
- high in primary
- low or inappropriately normal in secondary/ tertiary
Describe the premise of the insulin tolerance test to assess HPA axis function
normally HPA axis responds to hypoglycemia by increasing CRH, ACTH, cortisol
dysfunctional HPA axis will not respond
List causes of ACTH dependent Cushing’s syndrome
ACTH secreting pituitary tumor
Ectopic ACTH production by a tumor
What specifically is meant by “Cushing’s disease”
ACTH secreting pituitary tumor
List causes of ACTH independent Cushing’s syndrome
cortisol secreting adrenal tumor- adrenal adenoma or carcinoma
List classic signs of excess glucocorticoids
- changes in fat distribution to central regions
- thinning of skin, facial plethora, easy bruising, abdominal striae
- immune suppression
- glucose intolerance, hypertension, CV disease
- osteoporosis, easy fracturing
- insomnia, depression, psychosis
- hypogonadism from GnRH/LH/ FSH suppression
List initial tests for Cushing syndrome
- low dose dexamethasone suppression test
- 24 hour free cortisol urine collection
- midnight salivary cortisol
How does high dose dexamethasone suppression test differentiate Cushing’s disease from ectopic ACTH secretion
some feedback suppression is still possible in ACTH secreting pituitary tumors, so there will be lower cortisol production
ectopic ACTH production is not suppressed even with high dose
What is the utility of bilateral simultaneous inferior petrosal sinus sampling?
determine if ACTH in the petrosal sinus is higher than in peripheral blood
if yes, pituitary tumor is the course
if no, look for ectopic source of ACTH
What is Nelson’s syndrome
Aggressive growth of pituitary ACTH-secreting pituitary tumor after bilateral adrenalectomy
thought to be due to complete loss of all feedback on the pituitary tumor
Glucocorticoids induce transcription of _______, which binds NF-kB and prevents it from becoming active
IkB
_________ is a pure glucocorticoid
dexamethasone
______ is a potent mineralocorticoid
fludrocortisone
The enzyme ______ is present on renal mineralocorticoid target cells, and prevents glucocorticoids from having mineralocorticoid effects by converting cortisol to cortisone
11B-hydroxysteroid dehydrogenase
What are side effects of mineralocorticoid antagonists like spironolactone and eplerenone
hyperkalemia, spironolactone is nonspecific and also has progestational effects
_________ is characterized by bilateral enlargement of the adrenal glands and diffusely thickened, nodular adrenal cortices.
adrenocortical hyperplasia
Most adrenocortical adenomas are clinically ______
silent
________ is characterized as a well circumscribed, encapsulated nodular lesion on one adrenal cortex
adrenocortical adenoma
________ presents with a large invasive lesion on the adrenal gland that may have areas of necrosis, hemorrhage, and cystic change.
adrenal carcinoma
List the rule of 10 of pheochromocytoma
10% are extra-adrenal (paragliomas) 10% sporadic 10% malignant 10% not associated with hypertension 10% (actually more) are associated with familial syndromes
Describe the histology of pheochromocytomas
clusters of cells in nests (zellballen), rich vascular network, supporting cells, highly granular cytoplasm, salt and pepper chromatin
List the diseases seen in MEN2a
pheochromocytoma, medullary thyroid carcinoma, parathyroid hyperplasia
List the diseases seen in MEN2b
pheochromocytoma, medullary thyroid carcinoma, mucocutaneous ganglioneuromas, marfanoid habitus
Describe the presentation of NF-1
pheochromocytoma, neurofibromatosis, café-au-lait spots, and optic nerve gliomas
Describe the diseases seen in VHL syndrome
pheochromocytoma (rarely paraganglioma), renal cell carcinoma, hemangioblastoma, and pancreatic endocrine neoplasms