pituitary and adrenal Flashcards
hormones released by the anterior pituitary gland
ACTH, TSH, FSH, LH, GH, prolactin
ACTH
secretion of glucocorticoid, mineralocorticoids, and androgens
FSH
growth of the reproductive system
LH
sex hormone production
GH
promotes growth; lipid and cholesterol metabolism
prolactin
secretion of estrogens and progesterone; milk production; spermatogenesis; prostate hyperplasia
hormones secreted by the posterior pituitary gland
oxytocin and vasopressin
oxytocin
uterine contraction and lactation
vasopressin
stimulates water retention; raises blood pressure by contracting arterioles
common pituitary disorders
panhypopituitarianism, excess in growth hormone, growth hormone deficiency, hyperprolactinemia
panhypopituitarianism
deficiency in ACTH, Gn, GH, TSH; excess PRL
primary panhypopituitarianism
secretory issue in pituitary gland
secondary panhypopituitarianism
hypothalamus or other pituitary stimulus disorder
causes of panhypopituitarianism
surgery, trauma, radiation, ischemia, infection
treatment for panhypopituitarianism
replace deficient hormones; glucocorticoids, sex hormones, and levothyroxine (occasionally GH)
gigantism
excess in GH in children
acromegaly
excess in GH in adults
treatment for excessive growth hormone
DA agonists
Somatostatin analogues
GH antagonists
DA agonists
bromocriptine and cabergoline
somatostatin analogues
octreotide and lanreotide
GH antagonists
pegvisomant
GHD in adults
prior history of GHD as a child, GHD secondary to structural lesion or trauma, idiopathic GHD
GHD in children
congenital GHD, acquired GHD
GHD treatment
GH analogues and GHRH analogues
hyperprolactinemia etiology
prolactin-secreting tumors (prolactinomas), increased TRH, idiopathic, medication induced
medication induced
any medication that antagonizes dopamine or increases the release of prolactin
dopamine antagonists
phenothiazines, metoclopramide, haloperidol, atypical antipsychotics
prolactin stimulators
methyldopa, cimetidine, SSRIs, TCAs, estrogens, progestins, GRH analogues, benzos, MOAIs, opioids
adrenal gland is located
on the upper poles of each kidney
adrenal medulla
10% of the total gland, responsible for secretion of catecholamines
catecholamines
Epi, NE, dopamine
adrenal cortex
90% of the total gland, responsible for the secretion of 3 types of hormones, and 3 separate zones
3 zones of adrenal cortex
zona glomerulosa, zona fasciculate, zona reticularis
zona glomerulosa
15% of cortex, mineralocorticoid production
mineralocorticoid
aldosterone
zona fasciculate
60% of cortex, basal and stimulated glucocorticoid production
glucocorticoid
cortisol
zona reticularis
25% of cortex, adrenal androgen production
Cushing’s syndrome
excess cortisol in the plasma either by endogenous production or exogenous sources
etiology of Cushing’s
exogenous corticosteroids, overproduction of ACTH (70%), ACTH independent causes (18%), ectopic ACTH - secreting tumors and nonneoplastic corticotropin hypersecretion (12%)
is Cushing’s more common in men or women
women
90-100 prevalence of these symptoms in cushings
central obesity, moon face, facial plethora, decreased libido
tests that establish the presence of hypercortisolism
24 hour urine free cortisol, midnight plasma cortisol, low-dose dexamethasone suppression test (LDDST)
tests that differentiate between etiologies
high dose DST; plasma ACTH measured by radioimmunoassay (RIA) or immunoradiometric assay (IRMA); CT/MRI of adrenal, chest, of abdominal area; CRH stimulation test; inferior petrosal sinus sampling; MRI of pituitary gland
clinical suspicion for cushings
increased urinary free cortisol, lack of cortisol suppression after dexamethasone, increased late evening salivary cortisol
treatment of cushings
surgical resection if tumor is present, inhibitors of steroid production, neuromodulators of ACTH release, and spironolactone
advantages of surgical resection of tumor
preservation of pituitary function, low complication rate, and high clinical improvement rate
inhibitors of steroid production are used when
patients are not surgical candidates
inhibitors of steroid productions
metyrapone, aminoglutethimide, ketoconazole, mitotane, mifepristone
MOA metyrapone
inhibits 11-hydroxylase activity thereby interfering with cortisol and corticosterone synthesis
ADR of metyrapone
NV, vertigo, HA, GI discomfort, allergic rash, hypotonia
metyrapone
mostly used as a diagnostic agent, compensatory increase in endogenous ACTH occurs due to a sudden decrease in cortisol
aminoglutethimide
1) causes serum cortisol levels to decrease by 50%
2) as monotherapy - short term use in inoperable cases with ectopic ACTH syndrome as etiology
3) may decrease effect of warfarin
MOA aminoglutethimide
blocks the conversion of cholesterol to pregnenolone = reduction in all hormonally active steroids
ADR aminoglutethimide
sever sedation, nausea, ataxia, skin rash, myalgias
ketoconazole
high doses are need to inhibit steroid production
MOA ketoconazole
potent, non-selective inhibitor of adrenal and gonadal steroid synthesis
ADR ketoconazole
gynecomastia, GI upset, HA, increase in LFTs (reversible)
mitotane
hospitalization is required for administration due to the extreme reduction in cortisol production
MOA mitotane
cytotoxic to the adrenal gland thereby reducing the synthesis of cortisol and corticosterone
ADR mitotane
lethargy, somnolence, GI upset, change of taste, neuropsychiatric symptoms
mifepristone
1) binds to the glucocorticoid receptor 18x that of cortisol
2) effect is dose dependent
3) may block negative feedback of glucocorticoid on the HAP axis leading to increase in ACTH and cortisol
MOA mifepristone
glucocorticoid receptor antagonist
ADR mifepristone
uterine cramping, HA, dizziness, GI upset, fatigue
neuromodulators of ACTH release MOA
regulate neurotransmitters that control the HPA axis
neuromodulators of ACTH release
no agent has been shown to be very effective
cyproheptadine, valproic acid, bromocriptine, ritanserin, octreotide
spironolactone and cushings
provides symptomatic relief of HTN and hypokalemia
ectopic ACTH nondrug treatment
surgery, chemotherapy, irradiation
ectopic ACTH drug treatment
metyrapone, aminoglutethimide
pituitary dependent nondrug treatment
surgery, irradiation
pituitary dependent drug treatment
cyproheptadine, mitotane, metyrapone
adrenal adenoma non drug treatment
surgery, postoperative replacement
adrenal adenoma drug treatment
ketoconazole
adrenal carcinoma nondrug treatment
surgery
adrenal carcinoma drug treatment
mitotane
monitoring in cushings
24 hour urine free cortisol and serum cortisol level. steroid replacement as needed
primary aldosteronism
abnormality is within the adrenal cortex
causes of primary aldosteronism
adrenal adenoma (60%), idiopathic adrenocortical hyperplasia
other rare causes of primary aldosteronism
adrenal cortex carcinoma, primary adrenocortical hyperplasia, renin-responsive adrenocortical adenoma, and genetic mutations
clinical presentation of hyperaldosteronism
women age 30-50 yo
HTN, muscle weakness, fatigue, headache, metabolic alkalosis
tetany/paralysis, polydipsia, nocturnal polyuria
impaired glucose tolerance in 25% of patients
in hyperaldosteronism there is a decrease in
potassium, renin, magnesium
in hyperaldosteronism there is an increase in
aldosterone, sodium, bicarbonate
diagnosis for hyperaldosteronism
1) serum potassium < 3.5 with a urinary potassium > 30 per 24 hours
2) PA:PRA > 25
in hyperaldosteronism you have to differentiate between
aldosterone producing adenoma (APA) and bilateral adrenal hyperplasia (BAH)
APA
2/3 of cases
- more severe HTN
- profound hypokalemia
- higher plasma and urinary aldosterone levels
BAH
1/3 of cases
- similar to APA, but not as severe
- pts with this condition are able to maintain control of RAAS system with little effect following doses of ACTH
treatment of APA
surgical resection of adrenal adenoma and spironolactone as needed
treatment of BAH
spironolactone, amiloride, eplerenone
spironolactone and BAH
inhibits aldosterone binding to the MR, high doses are needed. low doses can be given to prevent ADR but may need additional agents for BP
amiloride and BAH
DOC in men. even at high doses not effective at achieving BP control
eplerenone and BAH
like spironolactone but has less progestational and antiandrogenic side effects
secondary aldosteronism
stimulation of the zona glomerulosa by a stimulus outside of the adrenal gland, such as RAAS
secondary aldosteronism causes
excessive potassium intake, oral contraceptives, pregnancy, menses, CHF, cirrhosis, renal artery stenosis, barter’s syndrome
lab changes in secondary aldosteronism
increase in serum renin
treatment of secondary aldosteronism
remove extra-adrenal sources and spironolactone should be used until etiology is known
addisons disease
primary adrenal insufficiency
addisons
destruction of all regions of the adrenal cortex, deficiencies seen with cortisol, aldosterone, and various androgens
______ of the adrenal cortex must be destroyed before symptoms occur
about 90%
______ of the cases are due to autoimmune disorders
about 70%
secondary adrenal insufficiency
exogenous steroid use leading to suppression of HPA axis, cushing’s, decrease release of ACTH = impairment of androgen and cortisol production BUT NOT aldosterone
prednisone can block
the release of CRH and ACTH, CRH level swill drop and the pituitary no longer is stimulated to release ACTH therefore adrenals fail to secrete sufficient amounts of cortisol
symptoms of addisons disease
hyperpigmentation, aldosterone secretion is lost, plasma ACTH levels after ACTH stimulation are elevated, weight loss, dehydration, hyponatremia, hyperkalemia, elevated BUN, salt craving
symptoms of secondary adrenal insufficiency
aldosterone secretion is preserved, plasma ACTH levels are stimulation are normal to low, hyponatremia not responsive to saline
symptoms of hypofunction of adrenal gland
depression, anxiety, fatigue, NVD, anorexia, orthostatic hypertension
treatment of hypoaldosteronism
prednisone, hydrocortisone, cortisone. doses are in the PM because replacement is trying to mimic bodys normal rhythm. fludrocortisone acetate in secondary aldosterone insufficiency
adverse effects of fludrocortisone acetate
GI upset, edema, HTN, hypokalemia, insomnia, excitability, DM
endpoint of therapy in hypoaldosteronism
reduction in excess pigmentation is a good clinical marker, stop therapy if cushings syndrome symptoms begin
treatment of secondary hypoaldosteronism vs. addisons
treatment is the same except fludrocortisone acetate is not necessary
patients with adrenal insufficiency
should wear a MedicAlert bracelet or necklace and they should have easy access to injectable hydrocortisone or glucocorticoids suppositories in case times of physical stress or illness
acute adrenal insufficiency
true endocrine emergency, adrenal crisis or Addisonian crisis
precipitating factors of adrenal crisis
chronic use of glucocorticoids with abrupt withdrawal, surgery, infection, stress, trauma
early symptoms of adrenal crisis
malaise, myalgia, anorexia, weakness
late symptoms of adrenal crisis
fever, hypotension, vomiting, hypoglycemia, hypercalcemia, hyponatremia
treatment in adrenal crisis
fluid replacement and IV glucocorticoids
fluid replacement
D5NS at a rate to support BP
IV glucocorticoids
hydrocortisone continue IV infusion for 24-48 hours then switch to oral
metabolism of glucocorticoids
stimulate gluconeogenesis, mobilize amino acids to serve as substrates for gluconeogenesis in the liver, stimulate fat breakdown in adipose tissue to glycerol and fatty acids, inhibits glucose intake in the muscle and fat
inflammation and glucocorticoids
potent anti-inflammatory and immunosuppressive properties that vary based on which glucocorticoid given
potency of glucocorticoids
least to most
cortisone, hydrocortisone, prednisone, prednisolone, triamcinolone, methylprednisolone, betamethasone, dexamethasone
complications of glucocorticoid administration
osteoporosis, Cushing’s syndrome, increased risk of infection, cataracts, hypokalemia, hypomagnesemia, seizures, edema, steroid myopathy, HPA pathway suppression
glucocorticoids and NSAIDs
peptic ulcer disease
major concern in steroid tapering
HPA suppression, much more concerning at high doses of steroid and/or long duration of therapy
how to test HPA function
ACTH test - if normal test results then daily steroid dose is not necessary
monitoring in glucocorticoid therapy
glucose concentrations, electrolytes, ophthalmologic exams, growth and development
counseling with glucocorticoid therapy
- take with food
- never DC medication on your own
- carry or wear ID
- dosage increase at times of stress
- take ASAP if missed dose
complications in early therapy of steroid use
insomnia, enhanced appetite, weight gain
common in patients with underlying risk factors and steroid use
HTN, DM, PUD
long-term intense treatment of steroids
cushingoid habitus, HPA suppression, impaired wound healing
delayed and insidious complications from steroid use
cataracts and atherosclerosis
rare and unpredictable complications from steroid use
psychosis, glaucoma, and pancreatitis
