Adrenal/Pituitary Flashcards
What conditions results from hyperfunction of the adrenal glands?
Cushings syndrome
Hyeraldosteronism
What conditions result from hypofunction of the adrenal glands?
Primary adrenal insufficiency- addisons disease
Secondary adrenal insufficiency
What is the adrenal gland regulation and function?
- Hypothalamus releases corticotropin releasing hormone (CRH)
- Stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary
- ACTH stimulates the adrenal gland to release cortisol (also releases aldosterone and androgens)
- As cortisol levels rise it inhibits further release of CRH and ACTH through negative feedback
- Renin is released from the kidney (In response to ↓ blood pressure, salt depletion, CNS excitation)
- Conversion of angiotensinogen to angiotensin I then II stimulates aldosterone synthesis (Renal sodium and water retention and increased BP occur as a result of aldosterone secretion)
- Negative feedback to turn off renin release
What is involved with cushings syndrome?
↑adrenal function =↑cortisol production
Excess of cortisol in the plasma- hypercortisolism
What is the cause of Cushing’s Syndrome?
ACTH-dependent:
Pituitary tumor: excess ACTH secretion
Stimulates adrenal glands to secrete excess cortisol
Ectopic disease: ACTH secretion from another tumor
ACTH-independent: abnormal adrenocortical tissues (ACTH is functioning fine but you are still releasing too much cortisol)
Adrenal adenoma: benign
Adrenal carcinoma
Exogenous Steroids
What is the clinical presentation of Cushing’s Syndrome?
- Altered Fat Distribution- Central obesity
- Purple striae along the lower abdomen
- Facial rounding- “moon face”
- Supraclavicular fat pads
- Fat accumulation in the dorsocervical area- “buffalo hump”-Fat accumulation over chest & abdomen
- Hypertension
- Glucose intolerance
- Muscle weakeness
- Osteoporosis
- Psychiatric changes
- Gonadal dysfunction- Amenorrhea
How is Cushing’s syndrome diagnosed (confirmation)?
- Elevated urinary free cortisol- confirms hypercortisolism
- Plasma ACTH concentrations determine the etiology
Pituitary dependent
Ectopic ACTH
Adrenal Adenoma
Adrenal Carcinoma
What is the treatment of choice for Cushing’s syndrome?
Dependent on the etiology
Surgery is the treatment of choice
Transphenoidal removal of the pituitary tumor
Removal of the adrenal glands
Patient will require life-long treatment with glucocorticoids and mineralcorticoids
Steroidogenic inhibitors (Metyrapone (Metopirone®))- indications
Used for non-surgical candidates with cushings disease
Steroidogenic inhibitors (Metyrapone (Metopirone®)) - MOA
Steroidogenic inhibitors: inhibit synthesis and secretion of cortisol from the adrenal gland
Metyrapone (Metopirone®)- MOA
inhibits 11-hydroxylase activity in the adrenal cortex
Sudden drop in cortisol levels can result in an increase in plasma ACTH levels → increased androgenic and mineralcorticoid levels
Metyrapone (Metopirone®) (steroidogenic inhibitor)- indications
Used for Ectopic ACTH (something is causing the release of ACTH and it cant be reverse and these people are not candidates for surgery)
Metyrapone (Metopirone®) (steroidogenic inhibitor)- adverse effects
N/V
Hypertension
Alopecia
Hirsutism
Aminoglutethimide (Cytadren®) (steroidogenic inhibitor)- MOA
inhibits conversion of cholesterol to pregnenolone in adrenal glands
Blocks conversion of androstenedione to estrone and estradiol in the peripheral tissues
↓ production of cortisol, aldosterone, and estrogens
Aminoglutethimide (Cytadren®) (steroidogenic inhibitor)- Indications
Used for ectopic ACTH syndrome
Aminoglutethimide (Cytadren®) (steroidogenic inhibitor)- Adverse effects
N/V
Sedation
Hypothryoidism- blocks synthesis of thyroxine
Can cause problems with amenorrhea and fertility due to estrogen suppression
Ketoconazole (Nizoral) (Steroidogenic inhibitors)- MOA
imidazole antifungal agent
Also inhibits androstenedione synthesis
Ketoconazole (Nizoral) (Steroidogenic inhibitors)- Indications
Used for adrenal adenoma
Ketoconazole (Nizoral) (Steroidogenic inhibitors)- Adverse effects
Hepatotoxicity (need to monitor LFTs)
Gynecomastia (due to decreased testosterone levels)
Nausea
Ketoconazole (Nizoral) (Steroidogenic inhibitors)- drug interations
Inhibits CYP3A4, 1A2, 2C9, 2D6, 2A6
Ketoconazole (Nizoral) (Steroidogenic inhibitors)- absorption
Absorption requires an acidic pH
Administer 2 hours before antacids to reduce chance of decreased absorption
What are the adrenolytic agents?
Mitotane (Lysodren®)
Mitotane (Lysodren®) (adrenolytic agents)- MOA
cytotoxic drug that results in atrophy of the adrenal cells
Mitotane (Lysodren®) (adrenolytic agents)- indications
Used for adrenal carcinoma