Endocrine Function III: Adrenal Cortex and Adrenal Medulla Hormones Flashcards
Basic anatomy of the adrenal cortex
- Capsule (outer)
- Adrenal cortex
- Adrenal medulla (inner)
Three layers of the adrenal cortex
- Zona glomerulosa (outermost)
- Zona fasciculata (middle)
- Zona reticularis (innermost)
Three major hormone classes of the adrenal cortex
- Estrane
- Andosane
- Pregnane
Major hormone(s) produced by the zona glomerulosa layer
Mineralocorticoids
Major hormone(s) produced by the zona fasciculata layer
Glucocorticoids
Major hormone(s) produced by the zona reticularis layer
Sex hormones
Number of carbons on estrogens, androgens, and adrenal steroids
- Estrogens: 18
- Androgens: 19
- Adrenal steroids: 21
First biosynthetic pathway for adrenocorticosteroid formation
Acetate → Cholesterol → Pregnenolone → Adrenocorticoids
Second biosynthetic pathway for adrenocorticosteroid formation (not preferred)
Pregnenolone → DHEA → Androstenedione → Testosterone → (Estradiol)
Causes of adrenocorticosteroids utilizing alternate pathway instead of the preferred pathway
Enzyme deficiencies
Importance of enzymes in steroid biogenesis
Takes enzymes to make conversions to final product
Major site of steroid metabolism
Liver
Form of adrenocorticosteroids excreted in the urine
- Liver is the site of catabolism
- Water-insoluble hormones must be conjugated w/ sulfates or glucuronic acid to be excreted in urine
Which steroid has a negative feedback effect on adrenocorticotrophic hormone (ACTH)
Cortisol
Name of the principle cortisol-binding protein
CBG
Mineralocorticoids
- Metabolic effects
- Maintain sodium and potassium balance
- Aldosterone
Four regulatory factors for aldosterone secretion (order of importance)
- Potassium concentration
- RAAS
- Total body sodium concentration
- ACTH (has minor effect unless ACTH is pathologically in excess or is deficient)
Glucorticoids
- Metabolic effects
- Promotion of gluconeogenesis and lipolysis
- Promotion of liver glycogenesis
- Promotion of liver glycogenolysis
- Inhibition of protein synthesis and promotion of protein catabolism
- ↑ anti-inflammatory and immunosuppressive action
- ↓ intestinal absorption of Ca2+; ↑ loss of Ca2+ from bone matrix
- Miscellaneous: enzyme production, appetite promotion, regulation of blood pressure
Most potent glucocorticoid
Cortisol
Most potent mineralocorticoid
Aldosterone
Most potent adrenocortical androgen
Testosterone
What is the role of RAAS on the regulation of aldosterone?
Releases aldosterone and reabsorbs Na+ and releases K+
Three regulatory factors for the release of glucocorticoids
- ACTH stimulation of hormone
- Normal diurnal variation
- Stress
Feedback mechanism utilized in glucocorticoid hormonal regulation
Cortisol causes negative feedback on hypothalamus and anterior pituitary
Normal diurnal variation in cortisol
- While sleeping, cortisol is very low so negative feedback is removed
- ACTH is released and there is a sharp ↑ while waking up (BP and sugar ↑ so you don’t pass out)
The cortisol levels ↓ over the day - By 4pm it should be 1/3 the level it was at 8am
What androgen is produced in the greatest quantity by the adrenal cortex?
Testosterone
Six conditions associated w/ a hypofunctioning adrenal cortex
- Primary hypoaldosteronism
- Secondary hypoaldosteronism
- Addison’s disease
- Acute adrenal insufficiency
- Secondary and tertiary adrenal insufficiency
Differentiate causes of primary hypoaldosteronism
Inability to adjust to stress, low Na+, high K+, high renin, low aldosterone
Differentiate causes of secondary hypoaldosteronism
Occurs in patient w/ renal disease,
- Kidney is unable to produce and release renin and therefore cause low aldosterone
List the typical sodium, potassium, and renin levels observed in hypoaldosteronism
- Low Na+
- High K+
- High renin
Addison’s disease
- Clinical symptoms due to glucocorticoids deficiency
- Fatigue
- Weakness
- Weight loss
- GI disturbances
- Post-parandial hypoglycemia
Addison’s disease
- Clinical symptoms due to mineralacorticoid deficiency
- Dehydration
- Hypotension
- Hyperkalemia
- Metabolic acidosis (↓H+ secretion)
- Hyponatremia (↓Na+ reabsorption into blood)
Addison’s disease
- Reason for hyperpigmentation and infertility
No negative feedback on anterior pituitary (e.g., hyperpigmentation present b/c excess ACTH stimulates MSH production)
Addison’s disease
- Na
- K
- Blood sugar
- Cortisol
- ACTH
- ↓ Na+
- ↑ K+
- ↓ Blood sugar
- ↓ Cortisol
- ↑ ACTH
What is the cause of the Addisonian crisis?
During infection or acute stress, Addison’s patient cannot respond with ↑ aldosterone and cortisol and can go into shock with hypotension, fever, hypovolemia, and hyperkalemia (life threatening)
What is the cause of Waterhouse-Friderichsen?
Caused by meningococcal meningitis and septicemia; this causes acute adrenal insufficiency
What is the most common cause of tertiary adrenal insufficiency?
Chronic pharmacological administration of glucocorticoids
Four conditions associated w/ a hyperfunctioning adrenal cortex
- Primary aldosteronism (Conn’s syndrome)
- Secondary aldosteronism
- Cushing’s syndrome
- Congenital adrenal hyperplasia
Primary aldosteronism (Conn's syndrome) - Cause
Adenoma in outermost layer (tumors)
Primary aldosteronism (Conn's syndrome) - Outstanding clinical symptom
Hypertension
Primary aldosteronism (Conn’s syndrome)
- Na+ (blood)
- K+ (blood and urine)
- Aldosterone
- Renin
- ↑ Aldosterone
- Hypernatremia (b/c of ↑ aldosterone)
- Hypokalemia
- Hypokaluria
- ↓ Renin
- Metabolic alkalosis (↑H+ secretion in urine caused by ↑ Na+ reabsorption)
Secondary aldosteronism
- Two causes
Characterized by elevated aldosterone in the absence of an adrenal tumor
- ↓ blood flow to kidney causing ↓ GFR
- Hyperactivity of RAAS causing ↑ renin production
Secondary aldosteronism
- Na+
- K+
- Aldosterone
- Renin
- Hypernatremia
- Hypokalemia
- Hypokaluria
- ↑ Aldosterone (b/c of ↑ Na+)
- ↑ Renin
- Metabolic alkalosis (↑H+ secretion in urine caused by ↑ Na+ reabsorption)
Why is renin increased in secondary aldosteronism?
RAAS is continuously being activated
Secondary aldosteronism
- Clinical symptoms
↓ blood flow to kidney:
- Nephrosis
- CHF
- Obstructive renal disease
- Cirrhosis w/ Na+ depletion
- Pregnancy
- Diuretic use
Cushing’s Syndrome
- Five clinical symptoms
- Moon face
- Buffalo hump
- Truncal obesity
- Purple striae
- Hypertenion
Cushing’s Syndrome
- Three general causes
- Exogenous glucocorticoid therapy (prednisone)
- ACTH-dependent syndrome
- ACTH-independent
Cushing’s Syndrome
- Two specific causes of ACTH-dependent Cushing’s
- Cushing’s disease (ACTH-producing tumors)
- Ectopic ACTH-secreting tumors
Cushing’s Syndrome
- Two specific causes of ACTH-independent Cushing’s
- Adrenal adenoma (all 3 layers)
- Nodular adrenal hyperplasia (out of control)
Cushing’s Syndrome
- Two recommended screening tests and typical results if patient has syndrome
- 24 hour free cortisol (>120 = Cushing’s)
- Overnight dexamethasone suppression test
- AM/PM cortisol levels
Cushing’s Syndrome
- Expected morning and afternoon cortisol levels
↑ in AM, ↓ over the day normally
- In Cushing’s, it’s increased all the time)
Cushing’s Syndrome
- Na+
- K+
- Blood sugar
- Cortisol
- ACTH
- ↑ Na+
- ↓ K+
- ↑ Blood sugar
- ↑ Cortisol
- ↑ ACTH (due to adrenal cortex being continuously stimulated in Cushing’s Disease, ectopic ACTH-secreting tumor, and Cushing’s Syndrome)
CAH
- Full name (as well as the name of the adult condition)
- Congenital adrenal hyperplasia
- Aka adrenogenital syndrome
CAH/adrenogenital syndrome
- Pathogenesis
- Caused by enzyme deficiencies in the pathways to produce the glucocorticoids and mineralocorticoids
- No negative feedback since cortisol is not produced and aldosterone is ↓
CAH/adrenogenital syndrome
- Two common enzyme deficiencies
- 21-hydroxylase
- 11-beta-hydroxylase
CAH/adrenogenital syndrome
- Cortisol
- ACTH
- Progesterone
- DHEA
- Sodium
- Potassium
- ↓ Cortisol
- ↑ ACTH
- ↑ Progesterone
- ↑ DHEA
- ↓ Sodium
- ↑Potassium
CAH/adrenogenital syndrome
- Typical symptoms in boys and girls
Females - Abnormalities of external genitalia at birth (cannot tell if male or female) - Hirsutism - Infertility - Breast atrophy Males - Appear normal at birth but have sexual precocity (too much testosterone) Both - Acne - Coarsening of voice - Scalp recession early in life
CAH/adrenal hyperplasia
- Lab test included in newborn screen to check for this condition
17-hydroxyprogesterone
This is an enzyme kinetic assay used to measure angiotensin I produced from angiotensinogen by renin
Plasma renin activity test (PRA)
Stimulation tests are used to assess ____ hormonal states (hypofunctioning vs. hyperfunctioning)
Hypofunctioning
Suppression tests are used to assess ____ hormonal states (hypofunctioning vs. hyperfunctioning)
Hyperfunctioning
ACTH stimulation test
- Diagnostic use
Differentiate primary adrenal insufficiency (Addison’s) from secondary (hypopituitarism)
ACTH stimulation test
- Analyte measured
Cortisol
ACTH stimulation test
- Expected normal response
Serum cortisol should double in 30 minutes
ACTH stimulation test
- Results in Addison’s disease
Little or no change in cortisol levels
ACTH stimulation test
- Results in hypopituitarism
Increased levels of cortisol on successive days (2-3) of ACTH stimulation (delayed or “staircase” response)
Metyrapone test
- Principle
Selectively inhibits 11-beta-hydroxylase, so the conversion of 11-deoxycortisol to cortisol is inhibited, allowing unrestricted release of ACTH
Metyrapone test
- Diagnostic use
Differentiation of normal patients from secondary adrenal insufficiency (hypopituitarism);
- Assesses pituitary ACTH reserve basically to see how much ACTH the patient can produce
Metyrapone test
- Expected normal response
- ↓ cortisol
- ↑ 11-deoxycortisol
- ↑ ACTH
Metyrapone test
- Results in hypopituitarism
Unchanged cortisol, 11-deoxycortisol, and ACTH levels
Clinical use of the corticotropin releasing hormone (CRH) test
Differentiates secondary (pituitary) and tertiary (hypothalamic) adrenal sufficiency
Overnight Dexamethasone Suppression Test (screening test)
- Principle
Feedback mechanism of hypersecretion can be tested by administering a potent glucocorticoid and judging suppression of ACTH secretion
Overnight Dexamethasone Suppression Test (screening test)
- Analytes measured
Serum or urine cortisol levels
Overnight Dexamethasone Suppression Test (screening test)
- Diagnostic use
Differentiate normal patient from Cushing’s syndrome (either due to Cushing’s disease, adrenal tumor, or ectopic ACTH syndrome)
Overnight Dexamethasone Suppression Test (screening test)
- Expected normal response
↓ cortisol (<3 ug/dL)
Overnight Dexamethasone Suppression Test (screening test)
- Cause of abnormal results
↑ cortisol (>10 ug/dL) = Cushing’s Syndrome
Which causes of Cushing’s syndrome may be differentiated using the high-dose test?
- Adrenal tumors
- Nonendocrine ACTH-secreting tumors
- Pituitary Cushing’s disease
What do normal results look like in high dose dexamethasone suppression test look like?
50% suppression of cortisol production
How do abnormal results differ in Cushing’s and adrenal/ectopic tumors during the high dose test?
- Cushing’s = mostly suppressed cortisol production
- Adrenal/ectopic tumors = no change in cortisol levels
Three principle hormones classified as catecholamines and their sites of synthesis.
- Epinephrine (80-90% medulla production)
- Norepinephrine (10-20% medulla production)
- Dopamine (small amt produced in adrenal medulla)
These catecholamines have a marked influence on the vascular system
Dopamine and norepinephrine
This catacholamine influences metabolic processes, especially carbohydrate metabolism
Epinephrine
This catecholamine inhibits phenylethanolamine-N-methyltransferase
Epinephrine
This catecholamine inhibits tyrosine hydroxylase
Norepinephrine
Pheochromocytomas
- Cause
- Tumor in adrenal medulla
- Too much catecholamines
Pheochromocytomas
- Principle clinical symptom
Hypertension
Pheochromocytomas
- Best specific urine screening test
Urinary metanephrines
Pheochromocytomas
- Best diagnostic test
Urinary VMA
Neuroblastomas
- Commonly affected age group
Pediatric
Neuroblastomas
- Clinical symptoms
Tumor in or near adrenal gland producing a lot of dopamine, causing transient hypertension and tachycardia
Neuroblastomas
- Best specific urine screening test
Urinary HVA (diagnostic0