Cortisol Disorders

Question 1

primary function of the adrenal gland

Answer 1

Make mineracorticoids and glucocorticoids

Question 2

How does stress trigger cortisol release?

Answer 2

Stress triggers hypothalamus to secrete CRH -> CRH triggers anterior pituitary to secrete ACTH -> ACTH triggers adrenal gland to secrete cortisol

Question 3

What does cortisol stimulate?

what does it stimulate?

Answer 3

• 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

Question 4

What layer of the adrenal gland secretes glucocorticoids?

Answer 4

Zona fasculata of the adrenal cortex

Question 5

Glucocorticoids role in the body?

Answer 5

• steroid hormones produced from adrenal cortex
• major role in the metabolism of glucose, protein, and fat

Question 6

Connect the dots between cortisol and cholesterol synthesis

Answer 6

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

Question 7

What is the HPA Axis?

Answer 7

Hypothalamic-Pituitary-Adrenal Axis Feedback Loop
(ACTH -> Adrenal Gland -> Cortisol)

Question 8

does cortisol cause hyper or hypo - glycemia?

Answer 8

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)

Question 9

is cortisol inflammatory or anti-inflammatory?

Answer 9

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)

Question 10

neuro effects of cortisol

Answer 10

hard to sleep
depression
hyperstimulation

• Hyperstimulation which results in difficulty falling asleep, a decrease in REM sleep latency, and often presents as depression.

Question 11

Adrenal Excess of Cortisol is referred to as ____

Answer 11

Cushing’s Syndrome

Question 12

2 main ways you get Cushing’s Syndrome

bigger picture

Answer 12

too many glucocrticoids (too much cortisol) via
1. Endogenous - pituitary or adrenals fault
2. Exogenous - taking steroids

Question 13

Cushing’s Disease vs Cushing’s Syndrome

Answer 13

Endogenous pituitary tumor = Disease
collection of symptoms (any tumor NOT pituitary or exogenous) = Syndrome

Question 14

Pt presents with H/A, Polyuria, Nocturia, Visual provlems, and galactorrhea. Dx?

Answer 14

Cushing’s Syndrome

Question 15

what does glucocorticoid excess do to your hair?

Answer 15

Women -> hirsuitism (facial hair)
Men -> balding on head and excess hair other places

Question 16

How does Cushing’s cause Galactorrhea?

Answer 16

Anterior pituitary tumors compress the pituitary stalk -> HIGH prolactin levels

Question 17

pt with suspected cushing’s shows HGIH ACTH and Cortisol. What is the likely cause?

Answer 17

primary tumor in pituitary

Question 18

Norm ACTH and HIGH cortisol.
Is this primary tumor Cushing’s Disease or Cushing’s Syndrome due to steroid use?

Answer 18

Steroid use (Cushing’s Syndrome)

Question 19

Norm ACTH and HIGH Cortisol.
Cushing’s Disease or Syndrome?

Answer 19

Syndrome

Question 20

Cushing’s WU

Answer 20

• 24 hour urinary free cortisol level
• low-dose dexamethasone suppression test
• evening serum and salivary cortisol level
• dexamethasone–corticotropin-releasing hormone test.

Question 21

what time of day is best to do a cushing’s serum and salivary cortisol level

Answer 21

at night when it should be highest ONLY in those with cushing’s

Question 22

Test to differentiate Cushing’s Syndrome vs Disease

Answer 22

Dexamethasone Suppression Test

Question 23

Cushings

Dexamethasone Suppression Test

Answer 23

• 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

Question 24

Imaging orders for cushings?

Answer 24

Adrenal -> Abd CT
Pituitary -> Brain MRI W/Contrast
Ectopic -> chest/Abd CT

Question 25

Cushings Trmnt

Answer 25

Question 26

Adrenocortical insufficiency is referred to as _______ Disease

Answer 26

Addison

Question 27

80% of Addison Dz is due to ______ 10% of Addison Dz is due to ____

Answer 27

80% idiopathic 10% TB (granuloma deposition)

Question 28

AIDS pts with low CD4 cell count are more susceptible for opportunistic infx such as _____, which may lead to Addison Disease

Answer 28

cytomegalovirus **Mycobacterium avium intracellulare** cryptococci

Question 29

Drugs that can cause Addison Disease

Answer 29

Ketaconazole Methadone (depletes pituitary ACTH) Abd radiation

Question 30

Addison Disease

Question 31

Effects of Cortisol

Question 32

Aldosterone's Effects

Answer 32

promotes reabsorption of sodium and secretion of potassium and hydrogen to increase intravascular volume.

Question 33

What factors can trigger an Adisonian crisis?

Answer 33

Stress factors: stress infx trauma Sx Vomiting Diarrhea Replacement steroids noncompliance

Question 34

SS of CHRONIC Adison Disease

Answer 34

* 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

Question 35

These skin changes are signs of which cortisol disease?

Answer 35

Addison Disease ## Footnote _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

Question 36

Addison Disease Test

Answer 36

**Rapid ACTH Stimulation Test** ## Footnote 1. Inject ACTH 2. see if plasma cortisol and aldosterone levels are higher or lower than basal levels

Question 37

# rapid ACTH stimulation test interpretation Increase in plasma cortisol and aldosterone levels (above basal level) after injecting ACTH

Answer 37

(-) Test Normal adrenal cortex function

Question 38

# rapid ACTH stimulation test interpretation aldosterone baseline is low and fails to double

Answer 38

Abnormal Mineralcorticoid Fn

Question 39

# 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.

Answer 39

Abnormal Glucocorticoid Fn

Question 40

Expected CMP for Addison Disease? Na+ K+ Ca+ Gluc BUN/Creat GFR | High or low?

Answer 40

LOW Na+ (hyponatremia) High K+ (Hyperkalemia) High Ca+ (hypercalcemia) Low Gluc (Hypoglycemia) High BUN/Creat Low GFR

Question 41

Imaging order for Addison Disease

Answer 41

Abdominal CT * Due to TB or Histoplasmosis -> **Calcified** adrenal glands * Autoimmune Addison Dz -> **Atrophied** adrenal glands

Question 42

Addison Disease Trmnt

Answer 42

* Refer to Endo * Glucocorticoid replacement -> **Prednisone** * Mineralcorticoid replacement ->** Fludrocortisone / Florinef** ## Footnote - 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

Question 43

Pt with Addison Disease reports morning headaches, weakness, dizziness, and ss of hypothyroidism. Endocrinologist has them on Prednisone and Fludrocortisone. Concern for what?

Answer 43

inadequate replacement of glucocorticoids and mineralcorticoids. They might need their meds **increased**

Question 44

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?

Answer 44

signs of over-replacement They may need their meds **decreased**

Question 45

Aside from an Abdominal CT scan, what other imaging scan may you order for a pt with Addison Disease?

Answer 45

DEXA scan to detect early osteoporosis

Question 46

Pt with Addison Disease is about to have surgery. They are on replacement Prednisone (Glucocorticoid) and Fldrocortisone (Mineralcorticoid). What medication changes will you make?

Answer 46

Glucocorticoid must be replaced during surgery. Give **Hydrocortisone** 100mg IM -> continous IV infusion -> rapid taper within 24-36hrs to usual replacement dose ## Footnote mineralcorticoid replacement is usu NOT needed

Question 47

What do you expect to see in a history of a pt with Addisonian/Adrenal Crisis?

Answer 47

* 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)

Question 48

Pt with Addison Disease presents with N/V, Vascular collapse (hypovolemic shock), confusion, hyperpyrexia, and HIGH fever (105F). Concern for?

Answer 48

Addisonian/Adrenal Crisis

Question 49

Addisonian Crisis Causes

Answer 49

* **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)

Question 50

The surgeon forgot to give hydrocortisone (replacement glucocorticoid) during trauma surgery. Now, you have to closely monitor for signs of ______

Answer 50

Addisonian Crisis ## Footnote Signs of hypovolemic shock: N/V, vascular collapse, acute abd like ss, hyperpyrexia, high fever (105F), coma

Question 51

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?

Answer 51

No, their adrenals are working well if they are producing cortisol >25mcg/dL. This EXCLUDES Addison Disease

Question 52

Addisonian Crisis trmnt

Answer 52

* IVF 0.9% NS or D5NS if glucose is needed * Hydrocortisone infusion