Disorders and Treatment of the Adrenal Gland Exam 1 Flashcards
What are the layers of the adrenal gland?
- capsule
- cortex
- medulla
What are the zones of the cortex and what do they secrete?
- Zona glomerulosa -> mineralocorticoid secretion
- Zona fasciculate ->cortisol secretion
- Zona reticularis -> androgen secretion
What is the adrenal medulla responsible for secreting?
catecholamines
Explain the HPA axis
- CRH released from hypothalamus
- stimulates release of ACTH (aka corticotropin) from anterior pituitary
- stimulates adrenal cortex to release adrenal hormones
Cortisol
- Release is primarily controlled by HPA axis.
- main glucocorticoid in humans (AKA: hydrocortisone)
- Regulates physiologic stress response
- Increases when needed (e.g., illness)
- Secreted in diurnal circadian rhythm (Peaks in early morning, Nadir around mid-night)
Aldosterone
- Release is primarily controlled by renin-angiotensin-aldosterone system, not the HPA axis.
- Angiotensin II Receptors, Type 1 are present in adrenal gland.
- Regulates blood pressure control, electrolyte homeostasis
- Aldosterone promotes water retention, salt retention, and potassium excretion
Androgens
Androgen precursors are released and converted in target organs (e.g., gonads) to active sex steroids (progesterone, testosterone).
Clinical presentation of Cushing’s
- Central obesity
- Facial rounding (moon face)
- Abdominal striae (often red/purple colored)
- Thin skin
- Dorsocervical fat accumulation (“buffalo hump”)
- Supraclavicular fat pad
- Glucose intolerance/hyperglycemia
- Hypertension in 75-85%
- Gonadal dysfunction/amenorrhea
- Osteoporosis
- Myopathy/myalgia
- Hirsutism (in females)
Pathophysiology of Cushing’s
Excessive levels of glucocorticoids from: Endogenous overproduction by the adrenal glands OR Exogenous glucocorticoid administration
Endogenous Causes of Cushing’s
- ACTH-dependent
- ACTH-independent
Endogenous Causes of Cushing’s: ACTH-dependent
- Excess glucocorticoids are produced due to overproduction of ACTH
- Pituitary Adenoma: chronic ACTH stimulates adrenal glands -> bilateral adrenal hyperplasia (BAH)
- Ectopic (non-pituitary) ACTH-Secreting tumors: tumors that secrete CRH; often an endocrine tumor
Endogenous Causes of Cushing’s: ACTH-independent
- o overproduction of ACTH.
- Caused by direct adrenal stimulation (as with Adrenal Adenoma, Adrenal Carcinoma)
What are the different treatment options for Cushing’s?
- Surgery: Tumor resection, Adrenalectomy
- Pharmacologic therapy
Adrenalectomy
- Must replace glucocorticoids for 6-12 months post-op (if unilateral adrenalectomy) or lifelong if bilateral
- Hydrocortisone ± fludrocortisone
When can pharmacologic therapy be used in adjunct?
- Peri-operatively while preparing for surgery & waiting for clinical response to surgery.
- Incomplete surgery/incomplete resection
- Rarely used without surgery, but can be for those who aren’t surgical candidates.
Exogenous Causes of Cushing’s
- Induced by MEDS: glucocorticoids (oral, intravenous, topical, intranasal, etc…), progestins
- The most common type of Cushing’s Syndrome (med-induced).
- Treatment – wean off or dose reduce glucocorticoids if possible.
What are the classes of drugs that can be used to treat Cushing’s?
- Steroidogenesis inhibitors
- Adrenolytic agents
- Neuromodulators of ACTH release
- Glucocorticoid receptor blocking agents
Treatment for Cushing’s: Steroidogenesis inhibitors
- Metyrapone
- Ketoconazole
Treatment for Cushing’s: Adrenolytic agents
Mitotane
Treatment for Cushing’s: Neuromodulators of ACTH release
Cyproheptadine
Treatment for Cushing’s: Glucocorticoid receptor blocking agents
Mifepristone (RU-486)
Metyrapone
- Inhibits 11 β-hydroxylase (this is the enzyme that converts 11-deoxycortisol to cortisol)
- ADR: androgen side effects (hirsutism, acne), BP / electrolyte abnormalitites
Mitotane
- Inhibits 11-hydroxylation of 11-desoxycortisol and 11-desoxycorticosterone in the adrenal cortex, thereby inhibiting cortisol and corticosterone synthesis
- ADR: lethargy, somnolence, nausea, diarrhea,
hypercholesterolemia, prolonged bleeding time
Cyproheptadine
- Decreases ACTH secretion
- ADR: dizziness, blurred vision, anticholinergic ADR’s (sedation, weight gain)
Mifepristone (RU-486)
- Inhibits dexamethasone suppression; increases endogenous cortisol & ACTH
- ADR: hypokalemia, peripheral edema, headache, arthralgia, nausea, fatigue
- Contraindication: pregnancy (can abort baby)
What are the types of hyperaldosteronism?
- Primary
- Secondary
What are the causes of hyperaldosteronism: primary?
Caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma
What are the causes of hyperaldosteronism: seondary?
- ona Glomerulosa is stimulated by a non-adrenal factor.
- Most common – Renin-Angiotensin-Aldosterone System stimulation:
+ Heart failure, cirrhosis, 3rd trimester of pregnancy, menses, renal artery stenosis.
Clinical presentation of hyperaldosteronism
- Hypertension (more difficult to treat or resistant)
- Weakness, fatigue, paresthesias, headache
- Polydipsia / polyuria
- Hypokalemia
- Hypomagnesemia
- Hypernatremia
What are the treatment options for hyperaldosteronism
- Surgery
- Pharmacotherapy
Surgery option
for hyperaldosteronism
removal of aldosterone producing adenoma
Pharmacotherapy for hyperaldosteronism
- Eplerenone (Inspra®)
- Spironolactone (Aldactone®)
Eplerenone brand name and dose
- Inspra
- Starting dose: 25-50 mg QD
- Typical dose: 50mg BID
Eplerenone contraindications
- Renal insufficiency (SCr > 2.0 mg/dL in men
- > 1.8 mg/dL in women) Hyperkalemia
Eplerenone ADR’s
- Hyperkalemia
- Renal dysfunction
Eplerenone drug interactions
- CYP 3A4 substrate
- Caution with strong inhibitors/inducers
Spironolactone brand name and dose
- Aldactone
- Starting dose: 25 mg QD
- Typical dose: 50-400 mg QD
Spironolactone contraindications
- Renal insufficiency (SCr > 2.5 mg/dL)
- Hyperkalemia
Spironolactone ADR’s
- Hyperkalemia
- Renal dysfunction
- Gynecomastia
Clinical presentation of adrenal insufficiency
- Hyponatremia, hyperkalemia, elevated BUN
- Hyperpigmentation of areas where friction is more likely (Palms of hands, dorsal foot; More common in primary; secondary insufficiency will have pale pigment.)
- Weight loss/anorexia
- Depression
- Dehydration
- Salt craving
- Hypotension
- Nausea / vomiting
What are the two types of adrenal insufficiency?
- Primary
- Secondary
adrenal insufficiency: primary
- aka Addison’s disease
- destruction of all 3 zones of the adrenal cortex
- can be autoimmune
- Ketoconazole inhibit cortisol synthesis
- meds can accelerate cortisol metabolism
What are medications that can accelerate cortisol metabolism?
- Phenytoin
- rifampin
- phenobarbital
adrenal insufficiency: secondary
- Loss of glucocorticoid secretion
- Most common cause is extended or chronic exogenous steroid administration, which causes suppression of the HPA axis
- manifests when glucocorticoids are stopped / decreased or during times of increased physiologic stress
- HPA suppression occurs after approximately 2 weeks of supra-physiologic doses of corticosteroids
What are the different treatment options for adrenal insufficiency?
- replacement of cortisol
- replacement of mineralocorticoids
treatment of adrenal insufficiency: replacement of cortisol
- hydrocortisone, prednisone, cortisone
- needed in both primary and secondary
- corticosteroids given twice daily; goal: use lowest effective dose to mimic diurnal adrenal rhythm
- hydrocortisone: 15-25 mg orally; 67% in the AM, 33% 6-8 hours later
treatment of adrenal insufficiency: replacement of mineralocorticoids
- for primary only
- Fludrocortisone (Florinef) replacing aldosterone
- used in combination with cortisol replacement
- potent salt-retaining activity
- if hypertension develops, reduce to 0.05 mg daily
Fludrocortisone ADRs
- hypertension
- hypokalemia
- hyperglycemia
- edema
Acute Adrenal Insufficiency other names
- aka Adrenal Crisis, Addisonian Crisis
-
Acute Adrenal Insufficiency clinical presentation
- Nausea, vomiting
- Dehydration: Hyponatremia
- More severe – can lead to significant neurologic sequelae (seizures)
- Hypotension
- Hyperkalemia: Increased risk of ventricular arrhythmias
- Reduced cardiac function
What are the different treatment options for acute adrenal insufficiency?
- IV hydrocortisone
- 100 mg IV bolus, followed by 50-100 mg Q 8 hours
- Reduce to 25-50 mg Q6-8 hours until patient is stabilized
- treat same as chronic adrenal insufficiency once patient is stabilized
