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Therapeutics II > Block 4: Adrenal Disorders > Flashcards

Block 4: Adrenal Disorders Flashcards

1
Q

What is secreted in the adrenal cortex?

A

Glucocorticoids: cortisol, anti-inflammatory, can be replaced by any steroid
Mineralocorticoids: aldosterone, cortisol, regulated RAAS to maintain water and electrolyte balance, replaced by fludrocortisone
Androgens: androgen release is regulated by a negative feedback loop

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2
Q

What are the prohormones?

A
  1. Prednisone -> prednisolone
  2. Cortisone -> cortisol
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3
Q

What is Cushing’s syndrome?

A

Endogenous overproduction: the adrenal glands produce too much cortisol
Exogenous administration: steroids are taken in high doses AND the amount of cortisol is higher than what would have been produced naturally

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4
Q

What are the sx of cushings?

A
  1. Obesity
  2. Buffalo hump
  3. Moon face
  4. Red to purple striae usually on the lower abdomen
  5. HTN
  6. Glucose intolerance

Central obesity, HTN and glucose intolerance are components of metabolic syndrome and can ↑ risk of CHD and stroke 3 X

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5
Q

What are the steps of diagnosing Cushings?

A

Establishing presence of hypercortisolism:
* 24-hour urine free cortisol
* midnight plasma cortisol
* late-night salivary cortisol
* low-dose dexamethasone suppression test (DST)

Differenctiating between etiologies

Can’t determine cause so additional tests and procedures must be done

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6
Q
A
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6
Q

What are the tx goal of cushings?

A
  1. Limit morbidity and mortality
  2. Return the patient to a normal functional state
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7
Q

Tx of cushings?

A
  1. surgical resection
  2. Pharmacologic agents are available as secondary treatment options, if needed
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8
Q

How do you monitor Cushings?

A

Urinary free cortisol and steroid production

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9
Q

What are the steroidogenesis inhibitors?

A

Inhibits cortisol synthesis:
1. Metyrapone (Metopirone)
2. Ketoconazole
3. Levoketoconazole (Recorlev)
4. Osilodrostat (Isturisa)
5. Mitotane
6. Etomidate

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10
Q

Metyrapone

Brand, ADR, PiT, Admin

A

Meropirone
ADR: HTN, N/V, vertigo, headache, dizziness, abdominal discomfort, allergic rash
PiT: Second line choice in women due to hirsutism, Has been used in pregnancy
Admin: Take with food /milk to minimize GI upset

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11
Q

Ketoconazole

ADR, PiT, Admin

A

ADR: reversible elevation of hepatic transaminases, gynecomastia, low testosterone levels , GI upset
PiT:
* Highly effective in lowering cortisol in Cushing’s Disease
* Second line choice in men due to gynecomastia and hypogonadism
* Avoid in pregnant women due to risk of fetal harm

Admin: Take 2 hours before antacids; may take with sodas if have achlorhydria

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12
Q

Levoketoconazole

Brand, ADR, PiT, Admin

A

Recorlev
ADR: increased hepatic enzymes, GI upset, HYPOkalemia, cardiac arrhythmias
PiT:
* Avoid in patients with significant hepatic impairment
* Avoid in patients with QT prolongation
* NOT approved for treatment of fungal infections

Admin: Take with or without food

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13
Q

Osilodrostat

Brand, ADR, PiT, Admin

A

Isturisa
ADR: GI upset, HYPOkalemia, HTN, edema, cardiac arrhythmias, headache, cardiac arrhythmias, increased testosterone levels
PiT: Similar to all other steroidogenesis inhibitors
Admin: Take with or without food

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14
Q

Mitotane

ADR, PiT, Admin

A

ADR: N/V/diarrhea, lethargy, and somnolence
* Serious: Adrenal crisis, CNS toxicity, ovarian macrocysts

PiT: Rarely used and must be avoided in women who want to become pregnant in the next 5 years
Admin: Gradually increase dose and/or take with food to help with N/V/diarrhea

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15
Q

Etomidate

ADR, PiT, Admin

A

ADR: Sedation
PiT: Severe hypercortisolism in crit patients
Admin: IV in a monitoried ICU setting

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16
Q

Cabergoline

MOA, ADR, PiT, Admin

A

MOA: Dopamine agonist
ADR: CNS and GI
PiT:
* Avoid in lactating women due to suppression of prolactin
* Avoid in patients with uncontrolled HTN

Admin: Take with food/milk to minimize GI upset

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17
Q

Pasireotide

Brand, MOA, ADR, PiT, Admin

A

Signifor
MOA: Somatostatin analog
ADR: GI, malabsorption of fat, fart
PiT: Usually used in patients who have failed other therapies
Admin: SQ

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18
Q

Mifepristone

Brand, MOA, PiT, Admin

A

Korlym, Mifeprex
MOA: Cortisol receptor blocker
PiT:
* For hyperglycemic patients with cushings and T2DM glucose intolerance
* Should NOT be used for the management of HYPERglycemia in patients with T2DM
* Avoid in pregnant women — ABORTIFACIENT

Admin: Take with food. Swallow whole. Do NOT crush, split, or chew.

19
Q

What is addison’s?

A

Primary adrenal insufficiency: usually due to the destruction of the adrenal cortex (deficiencies in cortisol, aldosterone, adrogens)

20
Q

How do you diagnose addisons?

A

Short cosyntropin-stimulation test to check for hypocortisolism

21
Q

What is the tx for addisons?

A

Hydrocortisone, cortisone, and prednisone to establish lowest effective dose while mimicking normal diurnal adrenal rhythm and cortisol production

22
Q

How do you monitor addisons tx?

A
  1. Symptoms of Cushing’s syndrome indicates excessive replacement
  2. Reduction in hyperpigmentation is a clinical marker for effective treatment
23
Q

Agent of Choice to replace mineralocorticoid loss

A

Fludrocortisone Acetate (Minimizes development of HYPERkalemia)

24
Q

What are the ADR of fludrocortisone?

A
  1. Hypokalemia
  2. GI
  3. Edema
  4. HTN
  5. Insomnia
25
Q

What do you monitor with fludrocortisone?

A
  1. Weight
  2. BP
  3. EKG
26
Q

What is the cause of secondary adrenal hypofunction?

A

Exogenous steroid use by reduced glucocorticoid production secondary to decreased ACTH levels and results in impaired androgen and cortisol production

Secondary disease presents with normal concentrations of mineralocorticoids

27
Q

Tx of Secondary Adrenal Gland HYPOfunction?

A

Identical to primary with the exception that mineralocorticoid replacement is not usually necessary

28
Q

What are the differences between Addison’s and secondary insufficiency?

A
  1. Hyperpigmentation is seen in primary
  2. Aldosterone secretion is preserved in secondary
  3. Weight loss, dehydration, hyponatremia, hyperkalemia, and elevated blood urea nitrogen are common in Addison’s disease
  4. Addison’s disease will have an abnormal response to rapid ACTH-stimulation test
29
Q

What is adrenal crisis?

A

acute adrenocortical insufficiency (endocrine emergency)

30
Q

What is the cause of addisonian crisis?

A

Chronic use of oxogenous glucocorticoids and abrupt withdrawal

31
Q

What is the tx for adrenal crisis?

A

Parenteral GCC:
1. Hydrocortisone (mineralocorticoid and glucocorticoid activity): IV administration X 24-48hrs -> When stable, PO X another 48hrs -> taper until maintenance dose is established
2. If hyperkalemia is present may require additional mineralocorticoid replacement: Fludrocortisone acetate PO daily
3. Fluid replacement often is required at a rate to support BP

32
Q

Precautions for adrenal insufficiency?

A
  1. Med-Alert item w/ info on condition
  2. Have easy access to injectable hydrocortisone or glucocorticoid supplementation
33
Q

Labs of hypoaldosteronism? Monitoring?

A

Low Na and high K

BP and electrolytes

34
Q

Tx for hypoaldosteronism?

A

Fludrocortisone (mineralocorticoid replacement)

35
Q

How to cousel patients on GCC therpay?

A
  1. Take with food to minimize GI discomfort
  2. Do NOT abruptly stop the medication; gradual dose reduction is usually necessary
  3. Potential adverse effects
36
Q

Counseling on missed dose GCC therpay?

A
  1. Every other day dosing: Take ASAP if remembered that morning. If not remembered later, skip that day. Take next morning, and skip the following day
  2. Every day dosing: Take ASAP, but skip if almost time for next dose.
  3. Never double doses
37
Q

GCC monitoring labs?

A
  1. Glucose
  2. Electrolytes
  3. Ophthalmologic examinations
  4. Stool tests for occult blood loss
  5. Growth and development
38
Q

Posterior pituitary hormones?

A
  1. Oxytocin
  2. Vasopressin
39
Q

Anterior pituitary hormones?

A
  1. GH
  2. ACTH
  3. TSH
  4. Prolactin
  5. FSH
  6. LH
40
Q

What is acromegaly?

Labs, Tx, Adjunctive

A

Excessive production of GH
Lab: elevated GH, elevated ICF-1, may also see increased glucose
Tx: Surgery
Adjunct:
* Dopamine agonists : Advantages of oral dosing and reduced cost
* Somatostatin analogs: More effective than dopamine agonists
* GH receptor antagonist: Highly effective in normalizing IGF-1

41
Q

What are the dopamine agonist?

ADR

A

Bromocriptine, Cabergoline: PO
ADR: CNS and GI (take with food)

42
Q

What are the Somatostatin analogs?

ADR

A

Octreotide, Lanreotide, Pasireotide: SQ
ADR: GI, malabsorption of fat, flatulence, injection site pain

43
Q

What are the GH receptor antagonist?

ADR

A

Pegvisomant: SQ
ADR: GI, injection site pain, flu-like symptoms, elevated hepatic enzymes

44
Q

Tx for GH deficiency?

A

Recombinant GH IM or SQ

45
Q

Tx of hyperprolactenemia?

A

Dopamine Agonist (Bromocriptine, Cabergoline)

Therapeutics II (30 decks)

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