Addison’s disease Definition and symptoms
Adrenal insufficiency / failure to produce hormones
Weight loss-not for diagnosis
Fatigue
Weakness
Dizziness upon standing
Abdominal pain
Suspended menstrual cycles
Dehydration
Increased potassium in blood
Decreased sodium in blood
Low BP
Skin discoloration
Depression
Cushing’s syndrome Definition and symptoms
Hyperadrenocorticism
Weight gain
Lipodystrophy-buffalo hump
Moon face/temporal filling
Dial action of capillaries-telengiectasis- stretch marks
Excessive sweating-hyperhidrosis
Hirsutism
Low libido
Impotence
Amenorrhea/Infertile
Polyuria/dipsia
Hypokalemia
High BP
2 types of glucocorticoids
Cortisol
Corticosterone
1 type Mineralcorticoid and origin
Aldosterone From zona glomerulosa
1 type androgen
Androstenedione
Aldosterone description and what happens in absencence
Required for reabsorbtion of Na in exchange for K
In absence plasma K inc. (arrhythmia)
Plasma Na and Cl dec.
Dec. volume
Dec. CO
RESULTS IN SHOCK/ HYPOTENSION/ DEATH in 2 weeks
MOA Aldosterone
Diffused into tubular cells Bind to proteins Hormone-receptor complex enters nucleus to make mRNA of sodium channels and Na-k ATPase
How to increase aldosterone. 6 ways
High K in ECG
Dec BP
Dec. blood volume
RAAS
Low Na
ACTH-pituitary hormone
Glucocorticoids definition and MOA and origin
Hormones are responsible for RESPONDING TO STRESS
MOA: similar to aldosterone but results in metabolism
* cortisol produces faster effect
Decrease BG/ muscle weakness
Susceptible to stress-death
From zona fasciculata
Glucocorticoids in glucose metabolism
Increase: gluconeogenesis/ glycogen synthesis in liver
Decrease: Glycolysis/ glucose transport into cells Effect:increase blood glucose (adrenal DM)
Glucocorticoids in liver metabolism
Increase: movement of fat FROM adipose tissue / plasma FFA/oxidation of FA
increase hepatic glucose PRODUCTION by inc. substrate availability via proteolysis and lipolysis
****induce hyperinsulemia and insulin resistance, tx as DM2
Decrease: glucose used in adipocytes/TG synthesis
Glucocorticoids in protein metabolism
Increase: catabolism
Decrease: stores in all tissues EXCEPT liver/ synthesis/ AA transport into extra patio tissues/ formation of RNA in extraheoatic tissues In liver: increase AA transport/ synthesis/ plasma proteins/ gluconeogenesis
Effect: transfer of AA FROM MUSCLE TO LIVER
Inflammatory pathway
Increase cell damage
Histamine cause vasodilation Increase capillary permeability
Increase infiltration of leukocytes
Glucocorticoids and inflammation intervention
Increased stabilization of lysosomal membrane = decrease release of enzymes
Cortisol dec. vasodilation
Cortisol decrease capillary permeability
Cortisol dec. migration of leukocytes
Cortisol secretion
- CRH
- ACTH
- Cortisol
- inhibits
- Stimulate
- Promote
- Inhibit
ACTH function/ origin
Adrenocorticotrophic hormone Stimulated by CRH From hypothalamus Released from anterior pituitary
Causes: Cortisol secretion from adrenal cortex (zone fasciculata) Aldosterone secretion from adrenal cortex (zone glomerulosa) Bind to melanocytes to increase melanin
Androgens definition and origin
Weak androgens secreted then converted to testosterone by peripheral tissues. Stimulate pubic and axillary hair growth and sexual drive in females
From zona reticularis
Adrenal Medulla Hormones and function
Epinephrine: Increase blood glucose Increase fat breakdown in fat tissues Dilation of bv in skeletal muscle and cardiac muscle
Epi and NE: Inc. HR and force BV constriction in skin/ kidneys/ GI
Diagnosis of low aldosterone secretion
EKG: T wave is high from K Blood work for aldosterone
Diagnosis of low glucocorticoids
Blood cortisol levels
Increased ACTH
3 Addisons causes
Autoimmune response against cortical tissue
Bacterial infection
Cancer
Addison’s diagnosis and treatment
Dianosis: Measure ACTH will be high
Inject or with 250mcg corticotropin (ACTH) if no rise in cortisol positive diagnosis normal rise is >20mcg/dl
Treatment: Aldosterone injection AND Glucocorticoid injection or oral
Hydrocortisone 300mg IV daily & taper to LIFELONG maintenance dose of 15-20mg AM 5mg PM
2/3 dose in AM 1/3 dose PM (stimulate circadian G production)
Fludricortisone 0.1mg daily
3 causes of Cushing’s disease and effects
Hyperplasia of adrenal corticies (increased ACTH)
Increased cortisol from tumer
Hyperplasia of adrenal corticies in non- pituitary tissues
Brackett’s reasons
systemic inflammatory diseases
solid organ transplant
cancer
steroid administration
Effects: Increased androgens- hair and infertility in women Increased fat movement- buffalo hump Increased BP- b/c mineralcorticoid activity Increased glucose, Increased protein catabolism-muscle-weakness/ low immunity/ osteoporosis
Diagnosis of Cushing’s
Diagnosis:
- Measure plasma cortisol will be high
- normal serum cortisol
- 16-20 mcg/dl in AM
- 6-10 mcg/dl
- Dexamethasone suppression test
- increased ACTH
- normal <80
LDT: 1 mg dexamethasone/ no change in cortisol is abnormal = cushing’s
HDT: 8mg dexamethasone
- less cortisol cushing’s is from pituitaty ACTH producing tumor
- no change in cortisol cushing’s is from adrenal tumor or ectopic ACTH producing tumor
Primary aldosteronism definition and treatment
Small tumor in cells which produce aldosterone Low K ,HTN ,Glucocorticoids normal
Treatment: remove tumor
Adrenogenital syndrome defintion and treatment
Inherited disorder of adrenal gland due to lack of enzyme 21-hydeoxylase Tumor secretes androgens Intense masculinization Tumor hard to detect in men
Treatment: Dexamethasone/fludrocortisone/hydrocortisone
Treatment of Cushing’s
corrective intervention (surgery) if possible
manage signs and symptoms
What to Manage in G excess/Cushing’s s/s
decrease cortisol
glucose control
mood stabilizaiton
HTN control
Protect against osteoporosis
Ketaconazole in G
moa and dose
manages excess G (cushing’s)
inhibits 1st step in cortisol sysnthesis, and the conversion of 11-deoxycortisol to cortisol
potent inhibit of c17-20 desmolase (decrease androstenedione and testosterone)
Dose: 200mg 2-3qd
how much cortisol do the adrenal glands produce
15-30mg daily
G comparison of doses
hydrocortisone
prednisone
methylprednisolone
dexamethasone
Hydrocortisone
- 20mg
- no G high M
prednisone
- 5mg
- some G and M
Methylprednisolone
- 4mg
- some G and no M
Dexamethasone
- 0.75mg
- high G no M
Prevention or Minimization of Iatrogenic G excess
minimize dose and length of tx
use of steroid-sparing therapies
dose steroids in AM b/c cortisol highest in AM from GH overnight
use lowest dose
QOD if possible
Purpose of FRAX tool
assessment of fracure risk
NNT
numer needed to treat
average number of patients who need to be treated to prevent one additional bad outcome
1/ARR (absolute risk reduction)
Primary Adrenal insufficiency
failure of adrenal gland itself
destruction of adrenal cortex either rapidly or slowly, and loss of BOTH G and M
Acute: sepsis/adrenal hemorrhage
- ab. pain/fever/chills/HA/hypotension/death
Chronic: Addison’s/HIV/TB
- weak/weight loss/ hypotension/ hypoglycemia/ hyperpigmentation
secondary adrenal insufficiency
failure of hormone production
failure of piuitary/hypothalamus
suppression of adrenal function by steroids
G overtreatment
weight gain
adnormal fat distribution
osteopenia
hyperglycemia
G undertreatment
myalgias
Flu-like
anorexia
GI upset
fever
hypoglycemia
M overtreatment
HTN
low plasma renin
low K (great way to measure it)
possibly high NA
M undertreatment
orthstatsis(SBP drop 20, DBP drop 10, HR inc. 20)
Fatigue
inc. plasma renin
inc. K
possibly low Na
M and G in physiologic stress
minor: DOUBLE G daily until better
major: 150-300mg HC
HPA axis
G dose <10-14 days will not change it
use cosyntropin stimulation test for HPA axis suppression
HPA will recover after 1 month for ACTH, and 2-3 months for cortisol, 1 year for stress response
do steroids suppress fever?
YAS
Pneumocystis jeroveci pneumonia prophylaxis
cause: prednisone >10mg/day
Tx: bactrim 1qdx21d