Ch 120: Adrenal Glands Flashcards
List the endocrine functions of the adrenal cortex:
- Regulation of renal fluid and electrolyte balance (aldosterone)
- Chronic stress adaptation (steroids)
- Carbohydrate metabolism (steroids)
What does the adrenal medulla arise from?
What does it produce?
Neural crest ectoderm invades the cortical tissues
- Produces catecholamines (epinephrine and norepinephrine)
List the zones of the adrenal cortex and what does each produce:
- Zona glomerulosa - mineralocorticoids
- Zona fasciculata - glucocorticoids and sex steroids
- Zona reticularis - Sex steroids and some glucocorticoids
What are adrenal corticoids synthesized from?
Cholesterol
Describe the synthesis of adrenal corticoids
- Enzymatic cleavage of a carbon side-chain of cholesterol within mitochondria produces C-21 steroid pregnenolone
- In zona fasiculata and reticularis, pregnenolone is hydroxylated at C-17 to form glucocorticoids
- The zona flomerulosa lacks the 17alpha-hydroxylase enzyme, producing the mineralocorticoid aldosterone
Main difference between cortisol and aldosterone is last of hydroxyl group on C-17 of aldosterone
What is the main plasma protein which binds to cortisol?
Transcortin (75%)
- 15% bound to albumin
- 10% unbound
What is the main plasma protein which binds to aldosterone?
Albumin (50%)
- Unbound 40%
- Transcortin 10%
What physiologic conditions can affect transcortin levels?
Pregnancy - increases synthesis
Liver dysfunction - decreased synthesis
What is the clearance halflife of cortisol and aldosterone?
- Cortisol 60min
- Aldosterone 20min
What are the primary functions of glucocorticoids?
- Regulation of metabolism
- Inhibition of glucose uptake, protein synthesis, vasopressin release and inflammatory responses
- Stimulation of lipolysis, protein catabolism, gastric acid secretion, increases GFR
List the main functions of the mineralocorticoids
Aldosterone -> electrolyte balance and blood pressure homeostasis
RAAS and blood K concentration control
What is the RAAS?
Describe the pathway of the RAAS:
The renin-angiotensin-aldosterone system.
Renin is produced by juxtaglomerular apparatus of the kidney ->
Splits angiotensinogen (from liver) into angiotensin I -> In the lung endothelium, ACE converts angiotensin I into angiotensin II-> Stimulates peripheral vasoconstriction and secretion of aldosterone -> Aldosterone promotes Na, Cl and water reabsorption and K excretion in the kidney.
Where are catecholamines produced and from what substances?
What is the basic biosynthetic pathway of catecholamines?
Made by the chromaffin cells of the adrenal medulla from tyrosine and phenylalanine
Tyrosine -> dopa -> dopamine -> norepinephrine -> epinephrine
What are the receptors for catecholamines? What effects do they have?
Alpha-1 and 2:
Control catecholamine release from sympathetic nerve endings
Beta-1: Heart (increase rate and force of contraction)
Beta-2: Smooth muscle contraction, intermediary metabolism (gluconeogenesis/glycolysis)
Epinephrine is 10x more potent on Beta-2 receptors and so is more important in controlling metabolism
How does epinephrine effect metabolism?
Action on Beta-2 receptors:
- Promotes hepatic glycogenolysis and gluconeogenesis
- Stimulates glycogenolysis in skeletal muscle
- Inhibits insulin secretion (alpha-2)
- Stimulates pancreatic glucagon secretion
- Promotes lipolysis
How do norepinephrine and epinephrine effect the cardiovascular system?
Epinephrine:
- Increases contractility and HR (Beta-1)
- Vasodilation of skeletal mm. coronary arteries and all veins (Beta-2)
Norepinephrine:
- Generalized vasoconstriction (alpha)
What imaging characterisitics are suggestive of an adrenal mass?
Maximum length of adrenal exceeds >1.5 cm
Loss of kidney bean shape
Asymmetric from other adrenal
What is defined as positive suppression on a LDDST?
Any of these three are considered a positive:
4-hr post-dex serum cortisol below 1.5mcg/dL
4-hr post-dex serum cortisol that is less than 50% of baseline
8-hr post-dex serum cortisol that is less than 50% baseline
*Serum cortisol does not suppress for dogs with adrenal-dependent Cushing’s
*Failure to depress also does not rule out pituitary dependent (40% fail to suppress)
What diagnostic tests can be used to differentiate a cortisol-secreting tumor from a pheochromocytoma?
- Ultrasound (enlarged with no atrophy of contralateral gland) PLUS
- LDDST
- Urine creatinine : normetanephrine ratio
- Serum inhibin assay (dogs with adrenocorticism will have persistently elevated inhibin, pheo will have undetectable levels)
What percentage of adrenal tumors in cats are functional?
What is the most common substance that they produce?
- 76% functional
- Aldosterone most common / pheos rare
What is the prognosis for adrenalectomy in cats?
- 77% survive at least 2 weeks
- MST 50wk
Where are the right and left adrenal glands located?
They are retroperitoneal
Left is medial to the cranial pole of L kidney, adhered to the fascia of psoas minor and transverse process of L2 near aorta
Right is ventral to T13 and adhered to the vena cava, behind the caudate process of the liver
What is the blood supply and venous drainage of the adrenals?
Arterial supply from 20-30 small branches of phrenicoabdominal, renal and cranial abdominal arteries (plexus).
Venous drainage is a single adrenal vein for each.
Where do the adrenal veins empty into?
Right: Direct into cava
Left: Left renal vein
How is glucocorticoid production controlled?
By negative feedback -> glucocorticoids inhibit release of hypothalamic corticotropin-releasing hormone -> decreases corticotropin secretion -> decreases production of glucocorticoids
What percent of catecholamines produced are epinephrine and norepinephrine in dogs?
In cats?
Dog: 60% Epinephrine / 40% Norepinephrine
Cat: 70% Epinephrine / 30% Norepinephrine
What percentage of Cushing’s in dogs is pituitary dependent?
80-85%
An adrenal mass greater than what size is likely malignant?
20mm
What do you treat a cortisol-secreting adrenal tumor with for 3-4 weeks before surgery to reverse metabolic derangement and minimize complications?
Trilostane 2mg/kg q12
What is trilostane?
A competitive inhibitor of 3B-hydroxysteroid dehydrogenase.
It inhibits coversion of pregnenolone to17a-hydroxyprogesterone (cortisol precursor)
When should you do an ACTH stim and check electrolytes to see if your trilostane therapy is working?
10-14 days after starting and 4-6 hours after last dose.
What is an ideal post-ACTH stim cortisol prior to surgery for a cortisol-secreting tumor?
2-5ug/dL
How do you treat hypertension in dogs with cortisol-secreting tumors before surgery?
ACE inhibitors
Pulmonary thromboembolism is the most common complication associated with removal of cortisol secreting adrenal tumors. When does it most commonly occur?
What is the mortality?
What is the gold standard diagnostic?
How do you prevent it?
How do you treat it?
When: first 72hr
Mortality: High
Diagnostic: Selective pulmonary angiography
Prevention: Frequent walks, early ambulation post op (no studies on anticoagulants)
Therapy: O2 support, anticoagulants, +/- theophylline, sildenafil
Hypoadrenocorticism is also seen after cortisol-secreting tumor removal. How can you treat empirically for this after surgery?
Give 0.25-0.5mg/kg pred equivalent and taper to 0.1mg/kg/day by day 10. At 4 wk post op, discontinue steroids and stim.
Mild hyponatremia and hyperkalemia occurs within 72hr of functional adrenal tumor removal. When is mineralocorticoid therapy indicated?
If Na <135mEq/L or K> 6.4 mEq/L
Recheck at day 25, if normal, check again 7 days later and decide if need another dose.
Treatment with phenoxybenzamine for 2-3 weeks reduces mortality with pheochromocytomas from 48 % to what %?
What is phenoxybenzamine?
13%
It is an alpha receptor blocker.
How do you treat ventricular tachycardia intraoperatively for pheochromocytomas?
Lidocaine 2-4mg/kg IV
Caval invasion is more common with adrenal tumors on which side?
Right
