(M) Lec 4: Adrenal Glands (Aldosterone to Medulla) Flashcards
- The major electro-regulating hormone
- Most abundant/potent mineralocorticoid
- The main determinant of renal extraction of potassium
Aldosterone
- Aldosterone controls the ____ levels in the body
- It also facilitates the excretion of ____
- It promotes a ____ ratio exchange between sodium for potassium or hydrogen
- Sodium-Chloride
- Potassium and Hydrogen
- 1:1
What androgens are needed for the production of aldosterone?
18-Hydroxysteroid Androgens
What are the three stimulators of aldosterone?
- Angiotensin II
- ACTH
- Elevated plasma/serum potassium
What are the four suppressors of aldosterone?
- Progesterone and Dopamine
- ANP
- Intracellular Calcium
- Drugs (ketoconazole, ACE inhibitors, NSAIDs, and heparin)
Clinical Disorders of Aldosterone
- Caused by an aldosterone-secreting adrenal adenoma
- Is associated with elevated plasma aldosterone and low plasma renin
- Presents with hypertension, hypokalemia, mild hypernatremia, and metabolic alkalosis
Primary Hyperaldosteronism (Conn’s Disease)
Clinical Disorders of Aldosterone
What is the screening test for Primary Hyperaldosteronism (Conn’s Disease)?
Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)
Clinical Disorders of Aldosterone
In the Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA) for Primary Hyperaldosteronism, a PAC level and PAC/PRA ratio of what would be suggestive for the disease?
- PAC level > 15ng/dL
- PAC/PRA ratio of > 30
Clinical Disorders of Aldosterone
In the Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA) for Primary Hyperaldosteronism, a PAC/PRA ratio of what would be diagnostic for the disease?
PAC/PRA ratio of > 50
Clinical Disorders of Aldosterone
What are the 2 confirmatory tests for Primary Hyperaldosteronism (Conn’s Disease)?
- Saline Suppression Test
- Captopril Suppression Test
Clinical Disorders of Aldosterone
This test:
- Involves infusing 2L of 0.9% saline over 4 hours or administering 10-12 mg NaCl tablets daily for 3 days
- Negative result: aldosterone is suppressed
- Positive result: aldosterone level > 10ng/dL
Saline Suppression Test
Clinical Disorders of Aldosterone
A PAC level of 5 to 9 ng/dL is indicative of what disorder?
Idiopathic Hyperaldosteronism
Clinical Disorders of Aldosterone
This test:
- Is a substitute for the Oral Salt Tolerance Test
- Is a non-invasive procedure of measuring aldosterone levels
Captopril Suppression Test
Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)
This suggests a primary defect in aldosterone secretion (Addison’s disease, heparin therapy, and an aldosterone biosynthetic defect)
A. High PRA and high PAC
B. High PRA and low PAC
C. Low PRA and high PAC
D. Low PRA and low PAC
B. High PRA and low PAC
Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)
Suggests primary hyperaldosteronism (Conn’s disease due to an adrenal adenoma or bilateral hyperplasia)
A. High PRA and high PAC
B. High PRA and low PAC
C. Low PRA and high PAC
D. Low PRA and low PAC
C. Low PRA and high PAC
Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)
Presents with Liddle’s syndrome, hyporeninemic hypoaldosteronism, 11-hydroxylase deficiency, and drug-induced mineralocorticoid excess
A. High PRA and high PAC
B. High PRA and low PAC
C. Low PRA and high PAC
D. Low PRA and low PAC
D. Low PRA and low PAC
Clinical Disorders of Aldosterone
- Occurs as a result of excessive renin production
- Presents with elevated plasma levels of aldosterone and renin
Secondary Hyperaldosteronism
Clinical Disorders of Aldosterone
Renal artery stenosis, diuretic therapy, malignant hypertension, and congenital defects in renal salt transport such as Bartter’s syndrome and Gitelman’s syndrome are all diseases of secondary hyperaldosteronism that cause what symptom?
Hypokalemia
Clinical Disorders of Aldosterone
- A congenital disorder characteried by increased ENAC activity in the collecting ducts due to the absence of aldosterone
- It resembles primary aldosteronism clinically, but aldosterone level is low and with the absence of hypertension
Liddle’s Syndrome (Pseudohyperaldosteronism)
Clinical Disorders of Aldosterone
- A bumetanide-sensitive chloride channel mutation
- A rare potassium-losing autosomal recessive disorder caused by defective NaCl reabsorption in the thick ascending loop of Henle
- Presents with elevated aldosterone and renin
Bartter’s Syndrome
Clinical Disorders of Aldosterone
- A thiazide-sensitive transporter mutation
- Associated with a defect in NaCl reabsorption that occurs in the DCT
- Accompanied by elevated aldosterone
Gitelman’s Syndrome
Clinical Disorders of Aldosterone
- This is due to the destruction of the adrenal glands and deficiency of glucocorticoids
- Associated with a 21-Hydroxylase deficiency
- Presents with hyperkalemia and metabolic acidosis
Hypoaldosteronism
Clinical Disorders of Aldosterone
What 2 tests can be used for diagnosing hypoaldosteronism?
- Furosemide Stimulation/Upright Posture Test
- Saline Suppression Test
Clinical Disorders of Aldosterone
In the Furosemide Stimulation/Upright Posture Test for Hypoaldosteronism, what is the positive result?
Low plasma aldosterone level
Clinical Disorders of Aldosterone
In the Saline Suppression Test for Hypoaldosteronism, what is the positive result?
High aldosterone level
- These serve as precursors for the production of androgens and estrogens in tissue
- Are produced as byproducts of cortisol synthesis that are regulated by ACTH
Weak Androgens
What are the 2 precursors of androgens?
- Pregnenolone
- 17-Hydroxypregnenolone
What are 2 examples of androgens?
- Dehydroepiandrostenedione (DHEA)
- Androstenedione
- Excessive production of androgens results in ____ (3)
- Excessive production can be confirmed by measuring ____ and ____
- Virilization, Infertility, and Amenorrhea
- Total and Free Testosterone
This is composed primarily of chromaffin cells that secrete catecholamines
Adrenal Medulla
Adrenal Medulla
What is the precursor for catecholamines (e.g. dopamine and norepinephrine)?
L-Tyrosine
Adrenal Medulla
Norepinephrine and epinephrine are metabolized by what 2 enzymes to form metanephrines and VMA?
- Monoamine oxidase
- Cathecol-O-methyl transferase (COMT)
Adrenal Medulla
This enzyme catalyzes the conversion of norepinephrine to epinephrine especially in times of stress
Phenylethanolamine N-methyltransferase (PNMT)
Adrenal Medulla
What is the ratio of norepinephrine to epinephrine in serum?
9:1
Adrenal Medulla
The medullary hormones are ____% protein-bound
50%
Adrenal Medulla
What three hormones are produced by the adrenal medulla?
- Norepinephrine
- Epinephrine
- Dopamine
Hormones of the Medulla
- A primary amine
- Produced by the sympathetic ganglia or the adrenal medulla itself
- Highest concentrations are found in the brain
- Acts as neurotransmitters in both the CNS and sympathetic nervous system
Norepinephrine
Hormones of the Medulla
What is the major norepinephrine metabolite in the CSF and is also found in urine?
3-methoxy-4-hydroxyphenylglycol (MHPG)
Hormones of the Medulla
What is the major norepinephrine metabolite in the blood?
Vanillylmandelic acid (VMA)
Hormones of the Medulla
- Aka Adrenaline (Fight or Flight Hormone)
- The most abundant medullary hormone
- Produced from norepinephrine and comes only from the adrenal
Epinephrine
Hormones of the Medulla
- This increases glucose concentrations
- Best collected from an indwelling catheter
- Its major metabolites are VMA, metanephrines, normetanephrines, and HMA
Epinephrine
Hormones of the Medulla
- A primary amine which is the major intact hormone in urine
- A catecholamine produced in the body by the decarboxylation of 3,4-dihydroxyphenylalanine
- Highest concentrations are found in the brain
Dopamine
Hormones of the Medulla
What is the major metabolite of dopamine?
Homovanillic acid (HVA)
Clinical Disorders of the Medulla
- A medullary tumor abundant in adults
- A medullary tumor abundant in children
- Pheochromocytoma
- Neuroblastoma
Clinical Disorders of the Medulla
What 2 methods can diagnose pheochromocytomas and neuroblastomas?
- Chromatography
- Radioimmunoassays
Clinical Disorders of the Medulla
- Tumors of the adrenal medulla or sympathetic ganglia
- Commonly seen in the 3rd to 5th decade of life
- Due to the overproduction of catecholamines
- Presents with tachycardia, headaches, tightness of chest, sweating, and hypertension
Pheochromocytoma
Clinical Disorders of the Medulla
What is the screening test for Pheochromocytomas?
High Plasma Metanephrines and Normetanephrines by HPLC
Note: Stop intake of caffeine, nicotine, and anti-depressants for 5 days
Clinical Disorders of the Medulla
What is the confirmatory test for Pheochromocytomas?
High 24-hour Urinary Excretion of Metanephrines and Normetanephrines
Clinical Disorders of the Medulla
Pharmacological Tests for Pheochromocytomas:
- Differentiates pheochromocytomas (not suppressed) from neurogenic hypertension (50% decreased cathecolamines)
- Used only if the plasma catecholamines are greater than 1000pg/mL
Clonidine Suppression Test
Clinical Disorders of the Medulla
Pharmacological Tests for Pheochromocytomas:
- Used if it is highly suggestive of pheochromocytoma
- Only if the patient’s blood pressure is normal and cathecolamines are modestly elevated (3-fold increase)
Glucagon Stimulation Test
Clinical Disorders of the Medulla
- A fatal malignant condition in children resulting to excessive production of norepinephrine
- Positive result: high urinary excretion of HVA or VMA or both and dopamine
- Specimens for testing are 24H urine and plasma
Neuroblastoma
Patient Preparation for Medullary Tests
- The patient should undergo overnight ____
- Avoid smoking or caffeinated beverages at least ____ hours prior to collection
- The patient is placed in a ____ position in a quiet environment and a ____ lock is inserted intravenously
- Fasting
- 24 hours
- Reclining; heparin
Specimen Considerations for Medullary Tests
- The preferred method of blood collection to eliminate anxiety of venipuncture
- In urine preservation, what preservative is used?
- Catheterization
- 10mL of 6N HCl
Patient Preparation for Medullary Tests
- After 20 to 30 minutes, blood is collected in a ____ EDTA tube
- Plasma concentrations of cathecolamines are affected by body positioning and samples must be collected after ____ minutes in a stable position
- Pre-chilled EDTA
- 30 minutes
Specimen Considerations for Medullary Tests
- This is a test to assess the quality of urine collection (0.8 g/day of urine creatinine is needed to validate its completeness)
- Blood samples must be transported on ____
- 24H urine creatinine test
- Ice