Cushings/adrenal insufficiency

Question 1

know the top two zones and their hormones.

Question 2

Hypothalamic-pituitary-adrenal (HPA)axis

Answer 2

Hypothalamussecretes CRH →releaseof ACTH from the anteriorpituitary gland

ACTH release:
Like CRH, therelease of ACTH follows the circadian rhythm
Increased in the early morning hours (before awakening), with peak levels in the morning (~8:00 a.m.) and ↓ in the evening

Adrenal gland (cortex):
ACTH mainly stimulates thezona fasciculata (cortisol) andzona reticularis (androgens)
Zona glomerulosa (aldosterone) is primarily regulated by the renin-angiotensin system andpotassium levels

peaks in the morning, peaks off during day

Question 3

Cushing Syndrome

general

Answer 3

umbrella term

Constellation of clinical abnormalities caused by chronic high blood levels of cortisol

Question 4

cushing syndrome

Primary hypercortisolism

Answer 4

↑Production of glucocorticoids by adrenal glands (tumor - adrenal adenoma or adrenal carcinoma)

Question 5

Cushing syndrome

Secondary hypercortisolism

Answer 5

Cushing’s disease – a subtype of Cushing Syndrome
↑Pituitary ACTH production leading to adrenal gland hyperplasia (most likely due to a pituitary adenoma)

Ectopic ACTH syndrome
↑ ACTH production outside the pituitary andadrenal glands (paraneoplastic syndromes – small cell lung cancer)

Question 6

Exogenous Cushing syndrome

general

Answer 6

Most common form of hypercortisolism

Medical use ofglucocorticoids
Exogenous cortisol causes negative feedback at the level of the hypothalamus and anterior pituitary → (decreased CRH and ACTH)

Long-term exogenous glucocorticoid use
Cortisol will not be released by the body
Atrophy of the zona fasciculata

Abrupt discontinuation of exogenous glucocorticoid use
Body cannot produce enough cortisol and adrenal insufficiency will occur → adrenal crisis

Question 7

Answer 7

ACTH-dependent means the body makes too much ACTH which in turn increases the production of cortisol
ACTH-independent means the adrenal glands produce cortisol without stimulation from ACTH

ACTH-dependent causes account for 80% of cases
ACTH-independent causes account for 20% of cases

Question 9

cushings syndrome

clin man

Answer 9

Moon face
Truncal (central) obesity
Prominent supraclavicular and dorsal cervical fat pads (buffalo hump)
Thin distal extremities and fingers
Proximal muscle wasting
Weakness
Osteopenia/osteoporosis
Glucose intolerance or diabetes mellitus
Hypertension
Recurrent opportunistic or bacterial infections
Cryptococcus neoformans, Candida species
Easy bruising
Thin and atrophic skin
Facial acne
Poor wound healing
Violaceous striae wider than 1 cm (abdomen)

Question 10

Answer 10

Question 11

cushings syndrome

24 hour urine

Answer 11

Exclude use of exogenous glucocorticoids
24-hour urine for free cortisol level (> 4 times the upper limit of normal)

Serum or saliva cortisol measurement at midnight to assess the normal fall

Question 12

cushings syndrom

Dexamethasone suppression test

Answer 12

1-2 mg of dexamethasone is given orally at 11 p.m. (normally should ↓ ACTH) and serum cortisol is measured at 8 a.m. the next morning (normally should ↓ serum cortisol)
↑ cortisol levels = positive test and further testing is needed

Question 13

cushings syndrome

Plasma ACTH levels
Primary vs secondary

Answer 13

Measured to determine the cause of Cushing syndrome
High levels → secondary pituitary (Cushing disease) or ectopic source
Low levels → primary adrenal cause (adenoma, carcinoma, exogenous glucocorticoids)

might need additinal imaging for tumors

Question 14

cushings syndrome

CRH Stimulation Test

Answer 14

For secondary

Patient is given synthetic CRH
No ↑ in ACTH and cortisol – ectopic ACTH secretion → order a CT scan of the chest, abdomen, and pelvis
↑ in ACTH and cortisol – Cushing disease → order an MRI of the brain with contrast

Question 15

cushings syndrome

Tx

Answer 15

Stop exogenous glucocorticoids – gradual withdrawal

Pituitary, adrenal, or ectopic ACTH-producing tumors
Surgical removal
Radiation therapy

Adrenalectomy
Patients will require glucocorticoid replacement therapy

Nonresectable tumors
Glucocorticoid-receptor antagonists
Mifepristone - blocks the effects of cortisol in tissues
Adrenal enzyme inhibitors
Ketoconazole and metopirone - decrease cortisol production
Dopamine agonists
Inhibit ACTH secretion

Question 16

Pheochromocytoma

general (location ) and Tx

Answer 16

Catecholamine-secreting tumor that mimics over-activity of the sympathetic nervous system
Majority of tumors originate in the adrenal medulla (90%)

Treatment:
Surgical resection

Question 17

Pheochromocytoma

Clin Man

Answer 17

Clinical Presentation:
Headache
Sweating
Tachycardia/Palpitations
Hypertension (sustained or paroxysmal) – most common symptom
Elevated metabolic rate
Hyperglycemia
Nervousness

Question 18

Question 19

Question 20

Adrenal Glands

general

Answer 20

Sit at the superior poles of the kidneys

Consists of:
Adrenal medulla and cortex

Question 21

adrenal medulla

Answer 21

inner portion
Responds to sympathetic stimulation by secreting catecholamines (epinephrine and norepinephrine)

Question 22

adrenal glands

Adrenal cortex

Answer 22

Thicker outer portion
Synthesizes 25 steroid hormones that are collectively known as corticosteroids
Consisting of 3 layers
Zona glomerulosa (outer)
Zona fasciculata (middle)
Zona reticularis (inner)

Question 23

adrenal glands

mineralcorticoids

Answer 23

Mineralocorticoids
Secreted by the zona glomerulosa
Control electrolyte balance by acting on the kidneys
Main mineralocorticoid is aldosterone

Question 24

adrenal glands

Glucocorticoids

Answer 24

Secreted by the zona fasciculata
Stimulate fat and protein catabolism
Gluconeogenesis (the synthesis of glucose from non-carbohydrate sources) in the liver
Release of fatty acids and glucose into the blood
Help the body adapt to stress
Main glucocorticoid is cortisol

Question 25

# adrenal glands sex hormones

Answer 25

Sex steroids Secreted by the zona reticularis Androgens and estrogens Main androgen is dehydroepiandrosterone (**DHEA)**

Question 26

Question 27

# adrenals aldosterone Wren is it secreted

Answer 27

Part of a hormone family with renin and angiotensin **Secreted directly in response to hyperkalemia and via the RAA system** in response to low blood volume/low blood pressure

Question 28

# Actions of Aldosterone

Answer 28

aldosterone acts on collecting ducts and DCTs

Question 29

# Adrenal Insufficiency (AI) general

Answer 29

Inadequate production of adrenocortical hormones: glucocorticoids (cortisol), mineralocorticoids (aldosterone), and adrenal androgens Types of adrenal insufficiency Primary Secondary Tertiary

Question 30

# AI Primary

Answer 30

(Addison’s disease) Dysfunction or destruction of the adrenal cortex

Question 31

# AI secondary

Answer 31

Conditions that cause deficiency in pituitary adrenocorticotropic hormone (ACTH) secretion **Most common form**

Question 32

# AI Tertiary

Answer 32

Conditions that cause deficiency in the hypothalamic  secretion of corticotropin-releasing hormone (CRH)

Question 33

# Primary disease – Addison’s Disease etiology

Answer 33

Autoimmune Most common cause – 70% of cases Adrenal cortex is gradually destroyed → loss of mineralocorticoids, glucocorticoids, and adrenal androgen hormone production Infection (**tuberculosis**) Hemorrhage (rupture of the adrenal cortex blood vessels due to ↑ BP leading to tissue ischemia) Metastatic cancer

Question 34

# secondary AI etiology

Answer 34

Hypopituitarism - ↓ ACTH Pituitary tumors and surgery

Question 35

# tertiary AI etiology

Answer 35

Prolonged high-dose glucocorticoid use suppresses the hypothalamus–pituitary–adrenal axis Effects of Cushing’s syndrome treatment

Question 36

Question 37

# AI hormonal regulation

Answer 37

Hypothalamic–pituitary–adrenal (HPA) axis:  Hypothalamus secretes CRH → release of ACTH from the anterior pituitary gland ACTH release: Like CRH, the release is pulsatile, following the circadian rhythm ↑ in the early morning hours (before awakening), with peak levels in the morning (approximately 8:30 a.m.) and ↓ in the evening Adrenal gland (cortex): ACTH mainly stimulates the zona fasciculata (cortisol) and zona reticularis (androgens) The zona glomerulosa (aldosterone) is primarily regulated by the renin–angiotensin system and potassium levels

Question 38

# Addison's Disease Clin man

Answer 38

Symptoms relate to the degree of hormonal deficiency – ≥ 90% destruction of adrenal tissue by the time symptoms appear Hyperpigmentation from ↑ ACTH Most characteristic symptom

Question 39

# addisons ↓ Glucocorticoids Sx

Answer 39

Fatigue Weakness Weight loss/anorexia Myalgia/joint pain Abdominal pain/diarrhea Hypoglycemia

Question 40

# addisons ↓ Mineralocorticoids Sx

Answer 40

Hypotension, dizziness Hyperkalemia, hyponatremia (salt craving) Metabolic acidosis

Question 41

# addisons ↓ Androgens:

Answer 41

↓ Axillary and pubic hair Loss of libido Amenorrhea in women 

Question 42

# AI Morning serum cortisol test value that suggests Adrenal Insufficiency

Answer 42

Morning serum cortisol Normal: 10–20 µg/dL  ↓ serum cortisol levels (≤ 3 µg/dL): strongly suggests AI

Question 43

# AI ACTH levels for primary, secondary, tertiary

Answer 43

Obtain baseline level simultaneously with morning cortisol ↑ ACTH: suggests primary AI ↓  or normal ACTH: suggests secondary/tertiary AI

Question 44

# Adrenal insufficiency High-dose ACTH stimulation test

Answer 44

Measure a baseline serum cortisol and plasma ACTH Administer 250 mcg of cosyntropin (synthetic ACTH) IV or IM Measure serum cortisol at 30 and 60 minutes ↓ cortisol level; ↑ ACTH = primary adrenal insufficiency ↓ cortisol level; ↓ or low normal ACTH = secondary adrenal insufficiency

Question 45

# Addisons Tx Glucocorticoid replacement

Answer 45

Use the lowest tolerated dose to control symptoms Oral **hydrocortisone** in 2-3 divided doses **Stress dosing** Used for illnesses and before surgery Dose is **3x the maintenance dose x 3 days**

Question 46

# Addisons Tx Mineralocorticoid replacement

Answer 46

Fludrocortisone (Florinef) Mineralocorticoid agonist, but also stimulates glucocorticoid receptors Increase sodium and water reabsorption Duration of action 8-12 hours Side effects: fluid retention, hypertension, edema, hypokalemia, hyperglycemia

Question 46

# Adrenal Crisis general

Answer 46

Medical emergency More likely to occur in primary disease than secondary disease Usually precipitated by severe stress (infection, trauma, surgery

Question 47

# Adrenal crisis Clin man

Answer 47

Profound weakness Abdominal pain – mimics an abdominal emergency Hypotension Orthostasis Shock Fever – when precipitated by infection

Question 48

# Adrenal crisis Tx with dosing

Answer 48

IV fluid resuscitation **Hydrocortisone phosphate or hydrocortisone sodium 100-300 mg IV over 30 seconds, then 50 mg every 6 hours** Treat any electrolyte imbalances and hypoglycemia Search for the underlying condition and treat accordingly