Cortisol Disorders Flashcards
primary function of the adrenal gland
Make mineracorticoids and glucocorticoids
How does stress trigger cortisol release?
Stress triggers hypothalamus to secrete CRH -> CRH triggers anterior pituitary to secrete ACTH -> ACTH triggers adrenal gland to secrete cortisol
What does cortisol stimulate?
what does it stimulate?
- Immune system -> produce cytokines, inflammatory cascade and additional WBC
- Liver -> gluconeogenesis to incr gluc and lipid metab
- Kidneys -> retain salt to maintain volume
- Vasoconstriction -> incr BP
- Heart -> incr HR
- Hypothalamus -> STOP releasing CRH (negative feedback loop)
at sufficient cortisol levels, negative feedback loop. Cortisol will stim hypothalamus to stop releasing CRH
What layer of the adrenal gland secretes glucocorticoids?
Zona fasculata of the adrenal cortex
Glucocorticoids role in the body?
- steroid hormones produced from adrenal cortex
- major role in the metabolism of glucose, protein, and fat
Connect the dots between cortisol and cholesterol synthesis
ACTH triggers cortisol secretion. ACTH also activates HMG CoA (rate limiting enzyme in cholesterol synthesis). Cortisol levels and cholesterol synthesis are highest at 8AM and lowest b/w 12AM and 4AM
What is the HPA Axis?
Hypothalamic-Pituitary-Adrenal Axis Feedback Loop
(ACTH -> Adrenal Gland -> Cortisol)
does cortisol cause hyper or hypo - glycemia?
Hyperglycemia
- upregulates or activates or induces enzymes involved in gluconeogenesis and glycogenolysis.
- Inhibitsinsulin and decreases the cellular uptake of glucose to increase the availability of glucose for the brain, red blood cells, and skeletal muscles.
- Stimulates skeletal muscle breakdown to mobilize amino acids for liver to perform gluconeogenesis. (glucose from amino acids)
is cortisol inflammatory or anti-inflammatory?
anti-inflammatory
- Promote WBC maturation and release from bone marrow
- Decrease the cell death of neutrophils (first responder)
- Increase cell death of eosinophils (allergy histamine)
neuro effects of cortisol
hard to sleep
depression
hyperstimulation
- Hyperstimulation which results in difficulty falling asleep, a decrease in REM sleep latency, and often presents as depression.
Adrenal Excess of Cortisol is referred to as ____
Cushing’s Syndrome
2 main ways you get Cushing’s Syndrome
bigger picture
too many glucocrticoids (too much cortisol) via
1. Endogenous - pituitary or adrenals fault
2. Exogenous - taking steroids
Cushing’s Disease vs Cushing’s Syndrome
Endogenous pituitary tumor = Disease
collection of symptoms (any tumor NOT pituitary or exogenous) = Syndrome
Pt presents with H/A, Polyuria, Nocturia, Visual provlems, and galactorrhea. Dx?
Cushing’s Syndrome
what does glucocorticoid excess do to your hair?
Women -> hirsuitism (facial hair)
Men -> balding on head and excess hair other places
How does Cushing’s cause Galactorrhea?
Anterior pituitary tumors compress the pituitary stalk -> HIGH prolactin levels
pt with suspected cushing’s shows HGIH ACTH and Cortisol. What is the likely cause?
primary tumor in pituitary
Norm ACTH and HIGH cortisol.
Is this primary tumor Cushing’s Disease or Cushing’s Syndrome due to steroid use?
Steroid use (Cushing’s Syndrome)
Norm ACTH and HIGH Cortisol.
Cushing’s Disease or Syndrome?
Syndrome
Cushing’s WU
- 24 hour urinary free cortisol level
- low-dose dexamethasone suppression test
- evening serum and salivary cortisol level
- dexamethasone–corticotropin-releasing hormone test.
what time of day is best to do a cushing’s serum and salivary cortisol level
at night when it should be highest ONLY in those with cushing’s
Test to differentiate Cushing’s Syndrome vs Disease
Dexamethasone Suppression Test
Cushings
Dexamethasone Suppression Test
- Steroids inhibit secretion of CRH and ACTH
- Give dexamethasone and then check plasma cortisol level & dexamethasone levels
- Cortisol levels should be low after giving dexamethasone (“suppression is present”)
Low Dose Test
Suppression is absent in Cushing Syndrome bc the issue is a tumor on the adrenal gland (downstream)
High Dose Test
- Suppression is present in Cushing Disease bc the high dose is enough to suppress pituitary tumor secreting ACTH (upstream)
- Suppression is Absent in Cushing Syndrome due to ectopic ACTH secretion or adrenal abnormalities
Imaging orders for cushings?
Adrenal -> Abd CT
Pituitary -> Brain MRI W/Contrast
Ectopic -> chest/Abd CT
Cushings Trmnt
Adrenocortical insufficiency is referred to as _______ Disease
Addison
80% of Addison Dz is due to ______
10% of Addison Dz is due to ____
80% idiopathic
10% TB (granuloma deposition)
AIDS pts with low CD4 cell count are more susceptible for opportunistic infx such as _____, which may lead to Addison Disease
cytomegalovirus
Mycobacterium avium intracellulare
cryptococci
Drugs that can cause Addison Disease
Ketaconazole
Methadone (depletes pituitary ACTH)
Abd radiation
Addison Disease
Effects of Cortisol
Aldosterone’s Effects
promotes reabsorption of sodium and secretion of potassium and hydrogen to increase intravascular volume.
What factors can trigger an Adisonian crisis?
Stress factors:
stress
infx
trauma
Sx
Vomiting
Diarrhea
Replacement steroids noncompliance
SS of CHRONIC Adison Disease
- Skin Hyperpigmentation
- Vitiligo (autoimmune melanocyte destruction)
- N/V/D, Steatorrhea
- Weakness, fatigue, poor appetite, wt loss
- Dizzy, Orthostatin HypoTN
- Myalgias
- SALT CRAVING, heightened sense of smell, taste, hearing
- impotense, decr libido
- Amenorrhea
- Pt with DM may suddenly req LESS insulin and have more hypoglycemic episodes due to this incr in insulin sensitivity
These skin changes are signs of which cortisol disease?
Addison Disease
Hyperpigmentation
Excess ACTH causes melanocytes to produce melanin
Most prominent on sun-exposed areas (extensor surfaces, knuckles, elbows, knees, scars formed after onset of disease). Scars formed before onset of disease usu are not affected
Vitiligo
autoimmune destruction of melanocytes
Addison Disease Test
Rapid ACTH Stimulation Test
- Inject ACTH
- see if plasma cortisol and aldosterone levels are higher or lower than basal levels
rapid ACTH stimulation test interpretation
Increase in plasma cortisol and aldosterone levels (above basal level) after injecting ACTH
(-) Test
Normal adrenal cortex function
rapid ACTH stimulation test interpretation
aldosterone baseline is low and fails to double
Abnormal Mineralcorticoid Fn
rapid ACTH stimulation test interpretation
In times of stress, there may be a normal appearing amount of cortisol at baseline, however, it will not significantly increase in response to ACTH (+7) because production is already maxed out.
Abnormal Glucocorticoid Fn
Expected CMP for Addison Disease?
Na+
K+
Ca+
Gluc
BUN/Creat
GFR
High or low?
LOW Na+ (hyponatremia)
High K+ (Hyperkalemia)
High Ca+ (hypercalcemia)
Low Gluc (Hypoglycemia)
High BUN/Creat
Low GFR
Imaging order for Addison Disease
Abdominal CT
* Due to TB or Histoplasmosis -> Calcified adrenal glands
* Autoimmune Addison Dz -> Atrophied adrenal glands
Addison Disease Trmnt
- Refer to Endo
- Glucocorticoid replacement -> Prednisone
- Mineralcorticoid replacement ->** Fludrocortisone / Florinef**
- Prednisone -> 5-60 mg/day PO in single daily dose or divided q6-12hr
- Fludrocortisone/Florinef -> On average: 0.1 mg/day PO, range: as low as 0.1 mg 3 times a week to .2mg/day
Pt with Addison Disease reports morning headaches, weakness, dizziness, and ss of hypothyroidism. Endocrinologist has them on Prednisone and Fludrocortisone. Concern for what?
inadequate replacement of glucocorticoids and mineralcorticoids. They might need their meds increased
Pt with Addison Disease reports with moon face, buffalo hump, sudden wt gain, and other cushings features. Endocrinologist has them on Prednisone and Fludrocortisone. Concern for what?
signs of over-replacement
They may need their meds decreased
Aside from an Abdominal CT scan, what other imaging scan may you order for a pt with Addison Disease?
DEXA scan to detect early osteoporosis
Pt with Addison Disease is about to have surgery. They are on replacement Prednisone (Glucocorticoid) and Fldrocortisone (Mineralcorticoid). What medication changes will you make?
Glucocorticoid must be replaced during surgery. Give Hydrocortisone 100mg IM -> continous IV infusion -> rapid taper within 24-36hrs to usual replacement dose
mineralcorticoid replacement is usu NOT needed
What do you expect to see in a history of a pt with Addisonian/Adrenal Crisis?
- Prior steroid use (>20mg daily prednisone for >5 days within past year)
- Infx: H. flu, S. aureus, S. pneumonia, fungi
- Physio Stress (sepsis, trauma, burns, sx)
- Rapid withdrawal of long-term steroid therapy (>10mg prednisone daily)
Pt with Addison Disease presents with N/V, Vascular collapse (hypovolemic shock), confusion, hyperpyrexia, and HIGH fever (105F). Concern for?
Addisonian/Adrenal Crisis
Addisonian Crisis Causes
- **Stress
- Failure to incr daily replacement steroid doses in times of stress/illness**
- failure to incr steroids
- failure to adjust replacement in pts taking CYP450 drugs (rifampin, Dilantin)
- Bil adrenal hemorrhage due to Meningococcus or Pseudomonas Infx, Pregnancy, Heparin/warfarin, SLE)
The surgeon forgot to give hydrocortisone (replacement glucocorticoid) during trauma surgery. Now, you have to closely monitor for signs of ______
Addisonian Crisis
Signs of hypovolemic shock: N/V, vascular collapse, acute abd like ss, hyperpyrexia, high fever (105F), coma
Pt presents with hypovolemic shock ss. Parents say pt sees an endo for “something with her cortisol.” Labs show plasma cortisol >25mcg/dL. Is this adrenal insufficiency?
No, their adrenals are working well if they are producing cortisol >25mcg/dL. This EXCLUDES Addison Disease
Addisonian Crisis trmnt
- IVF 0.9% NS or D5NS if glucose is needed
- Hydrocortisone infusion
