Adrenal Flashcards
1. When given a diagram of the adrenal gland, identify the layers of the cortex (glomerulosa, fasiculata, reticulate) and medulla, and identify and summarize the functions of the hormones synthesized in each anatomical region. 2. Compare and contrast the following diseases/disorders of the adrenal glands: • Addison’s disease and Cushing’s disease • Aldosteronism • Hirsutism & virilization • Pheochromocytoma 3. Discuss the difference between Cushing’s disease and Cushing’s syndrome. 4.
Where are the adrenal glands located?
Superior to the kidneys. Little hats on the kidneys
What the two regions of the Adrenal Gland?
- Cortex
- Medulla
What are the three components of the Cortex?
- Zona Glomerulosa
- Zona Fasciculata
- Zona Reticularis
The cortex takes up _____% of the adrenal gland?
80-90%
The Medulla takes up ______% of the adrenal gland?
10-20%
What molecules/hormones/etc come out of the Adrenal Gland?
- Aldosterone
- Cortisol
- Androgens
- Catecholamines
Aldosterone is a __________.
Mineralocorticoid
Cortisol is a __________.
Glucocorticoid
The Zona Glomerulosa is the most ______ layer of the cortex.
Superior
The Zona Fasciculata is the ______ layer of the cortex.
Middle/Intermediate
The Zona Reticularis is the most ______ layer of the cortex.
Inferior
The Zona Glomerulosa produces ________.
Mineralocorticoids (Aldosterone)
The Zona Fasciculata produces _________.
Glucocorticoids (Cortisol)
The Zona Reticularis produces __________.
Androgens (Androdtenedione, DHEA, and DHEA-S)
The Medulla produces ________.
- Catecholamines
- Metanephrines
- Normetanephrines
- Vanillylmandelic Acid
What are the two most common Catecholamines?
- Epinepherine
- Norepinephrine
If these products are overproduced, what effect will this have on the patient?
Make them sick!!!
Overproduction of Aldosterone will cause what disease/condition?
Hypertension
Aldosterone is secreted from the ________ and its site of action is on the ______________________.
Zona glomerulosa of the Adrenal Cortex;
Distal Nephrons of the Kidneys
What is the function of Aldosterone?
- Reabsorb Sodium and Chloride (which means water will follow)
- Secrete Potassium and Hydrogen
- Water Homeostasis
What initiates the Renin-Angiotensin-Aldosterone?
The system can be activated when there is a loss of blood volume or a drop in blood pressure (such as in hemorrhage or dehydration). This loss of pressure is interpreted by baroreceptors in the carotid sinus. In alternative fashion, a decrease in the filtrate NaCl concentration and/or decreased filtrate flow rate will stimulate the macula densa to signal the juxtaglomerular cells to release renin.
Release of cortisol from the ______ is stimulated by _______.
Zona Fasciculata; ACTH
Release of Androgens from the ______ is stimulated by _______.
Zona Reticularis; ACTH
T/F: The effect of ACTH is slow, taking hours to instigate an effect.
False, it is rapid and occurs within minutes.
The release of ACTH occurs _______ during the 24 hour cycle. Sometimes referred to as a ________ Pattern.
Episodically; Circadian
***Note: If ACTH is released episodically, then Androgens and Cortisol are also released episodically.
***Fun Fact: ACTH spikes in the morning. #MorningSex
When is ACTH secretion increased?
- Stress (Trauma, Sx, Anxiety, Emotional Disturbance)
- Low circulating levels of cortisol
When is ACTH inhibited?
- High circulating levels of cortisol
- Presence of synthetic glucocorticoids
Cortisol can inhibit ACTH secretion at two sites?
- Hypothalamus (Corticotropin Releasing Factor)
- Adenohypophysis (Corticotrophin)
When patients are taking exogenous Cortisol, this will inhibit the secretion of the endogenous pathway at the two ACTH secretion sites. Because of this, when the patient is being taken OFF of exogenous Cortisol, what should we do?
TAPER the exogenous cortisol off because the body needs to begin slowly making the glucocorticoids on its own again.
Physiologic Effects of Glucocorticoids
- Stimulate Gluconeogenesis
- Induce insulin resistance
- Increase release of AA and FA
- Elevate RBC and platelet levels
- Maintain normal vascular response to vasoconstrictors
- Stimulation of PMN leukocytosis
- Depletion of circulating eosinophils and lymphocytes
- Decrease macrophage adherence to endothelium
Elevated levels of aldosterone is a condition called _____________.
Hyperaldosteronism (Conn’s Syndrome)
Hyperaldosteronism can cause what conditions?
- Hypertension
- Hypokalemia
Causes of Hyperaldosteronism?
- Aldosterone producing Adenoma (60-70%)
- Bilateral Adrenal Hyperplasia (~34%)
- Unilateral Adrenal Hyperplasia (<1%)
- Familial Hyperaldosteronism
- Ectopic Hyperaldosteronism (very rare)
How do you screen for Hyperaldosteronism?
Measure 8 am plasma aldosterone (PA) and plasma renin activity (PRA) levels. Obtain PA/PRA ratio.
– Ratio of 4-10 is NORMAL
– Ratio of > 20 is Primary Aldosteronism
**Some drugs can alter hormone levels. i.e. Spironolactone will falsely increase PRA. ACE Inhibitors need to be stopped too.
How do you confirm a diagnosis of Hyperaldosteronism?
Saline or Salt loading test fails to suppress aldosterone levels.
Positive Diagnosis: Aldosterone > 10 ng/dL
Types of Adrenal Insufficiency?
- Primary (Addison’s Disease – autoimmune)
- Secondary: Pituitary Problem (ACTH inhibition)
- Tertiary: Hypothalamus Problem (CRH)
- Iatrogenic: Chronic exogenous steroids (caused by healthcare professionals because the axis is suppressed by these meds (asthma, arthritis, etc.))
Primary Adrenal Insufficiency
Addison’s Disease
Cause of Addison’s Disease
- Autoimmune (most common cause)
- Infiltration/Destruction of Adrenal Gland (TB, Amyloidosis, Hemochromotosis, Bilateral Adrenal Metastases)
- Fungal Infection
- Hemorrhage (Pts on Anticoags)
- Waterhouse-Friderichsen adrenal hemorrhage due to meningococcus septicemia
- Bilateral adrenalectomy (iatrogenic)
Symptoms of Addison’s/Primary Adrenal Insufficiency
- Vague/Gradual development
- Weakness
- Weight Loss
- Anorexia, Nausea
- Abdominal Pain
- Diarrhea or Constipation
- Postural Hypotension (dizziness, syncope)
- Salt craving
- Skin hyperpigmentation (ONLY IN PRIMARY)
How can primary adrenal insufficiency cause hyperpigmentation?
Primary adrenal failure
Low cortisol
Increased production of ACTH from POMC
Increased production/release of Melanocyte Stimulating Hormone (MSH)
Melanocyte stimulation
Hyperpigmentation
** We get more MSH because the precusor molecule for ACTH is the same as MSH, so more ACTH means more MSH **
Where is hyperpigmentation most noticeable in Primary Adrenal Insufficiency?
Dorsal surfaces, Creases of the Palm, Buccal Mucosa and Gums get dark spots
What is the cause of Iatrogenic Adrenal Insufficiency?
Chronic EXOGENOUS steroid Use
Iatrogenic adrenal insufficiency causes variable suppression on the person. This depends on what?
- Dosage
- Schedule
- Duration of Administration
At what dose does Hydrocortisol (HC) or its equivalents cause suppression?
15+ mg/day
Dividing the dosage of exogenous steroids are _______ more suppressive than taking steroids once per day or every other day. Why?
More
The axis is stimulated intermittently?
If treating a patient with steroids, you would want to give a safe dose for how many days to avoid adrenal insufficiency?
Less than 21 days!
What is an adrenal crisis?
Adrenal Insufficiency that becomes extreme. THIS IS A MEDICAL EMERGENCY!!
What can cause Adrenal Crisis to occur?
Lack of treatment
Previously undiagnosed
Acute adrenal failure (bilateral adrenal hemorrhage)
Acute exacerbation of existing chronic Adrenal Insufficiency
What can cause an acute exacerbation of existing Adrenal Insufficiency?
Inadequate steroid replacement
Stress
Illness
Surgery
Trauma
Non-compliance of treatment
(Not sure if this is an objective)
What are the signs and symptoms for an Adrenal Crisis?
Weakness
Malais
Abdominal Pain
Nausea
Vomiting
Hyponatremia
Hyperkalemia
Hypotension/Shock
NO HYPERPIGMENTATION in Acute failure
How do you treat an adrenal crisis?
IV Fluids
IV Steroids (HC 100 mg Q8 hours)
Evaluate and Treat underlying cause of crisis
How do you diagnose Adrenal Insufficiency?
- Check Cortisol levels in the morning (between 6 and 8 am):
– Greater than or equal to 19 = NORMAL
– 3-18 = Indeterminate
– Less than 3 = Definite Adrenal Insufficiency
*Clinical Symptoms are necessary especially in indeterminate studies.
**If adrenal crisis, it will be very easy to diagnose!
- Cosyntropin Stimulation Test
Peak levels of cortisol occur when?
In the morning between 6 and 8 am
What is Cosyntropin?
Synthetic bioactive portion of ACTH
What does the cosyntripin stimulation test do?
Inject IV/IM 250 mcg into the patient and check the serum cortisol levels at 0, 30, and 60 minutes.
If at any of these points, cortisol levels get greater than 19, you know the adrenal gland is being stimulated adequately.
If the diagnosis of secondary adrenal insufficiency, what is the likelihood of atrophy to the adrenal glands has been occurring?
Not very likely
If suspecting a patient is at high risk for AI, what should you do?
Repeat testing in a few weeks
What is the treatment for primary adrenal insufficiency?
- HC (or its equivalent) 20 mg q AM, 10 mg q PM.
- Florinef
- Double dose under stress
- HC 100 mg IM if unable to take orally (vomiting)
- Alert bracelet
What is the treatment for secondary adrenal insufficiency?
- HC (or its equivalent) 20 mg q AM, 10 mg q PM.
- Double dose under stress
- HC 100 mg IM if unable to take orally (vomiting)
- Alert bracelet
What causes Cushing’s Syndrome?
Adrenal source of high cortisol levels
What causes Cushing’s Disease?
Pituitary source of high ACTH
What is the normal daily secretion of glucocorticoids?
7.5 mg Prednisone
0.75 mg of Dexamethasone
30 mg of HC
Cushing’s Syndrome is…
The excessive production of glucocorticoids
Other causes of Cushing’s Syndrome includes
- ACTH or CRH production by tumors
- Exogenous Steroids (MOST COMMON)
Physical Findings of Cushing’s Syndrome
- Weight Gain
- Central Obesity
- Muscular Weakness
- Moon facies and facial plethora
- Supraclavicular fat pads
- Buffalo Hump
- Skin thinning, bruising
- Hirsutism
- Acne
- Skin Hyperpigmentation (+/-)
- Muscle wasting
- PURPLE STRIAE! Painful, wide!
Symptoms of Cushing’s Syndrome
- Oligomenorrhea or Amenorrhea
- Polyuria, Nocturia
- Decreased libido and impotence in males
- HTN because of salt and fluid retention
- DM, Impaired Glucose Tolerance
- Osteoporosis
- Avascular bone necrosis
- Depression or Psych problems (not psychosis so much)
- Malaise
- Headaches due to mass(es).
Ectopic ACTH Syndrome can
Also cause Cushing’s Syndrome (though not common)
What happens in Ectopic ACTH Syndrome relative to Exogenous Steroid overuse?
Levels of ACTH are way higher!!
Marked wasting and skin/nails pigmentation are more present in this cause of Cushing’s Syndrome
Ectopic ACTH Syndrome
How do you diagnose Cushing’s Syndrome?
- Rule out causes of pseudo-Cushing’s
- 24 hour urine free coritsol
- 1 mg overnight dexamethasone suppression test
Hard to diagnose
Things to keep in mind when diagnosing Cushing’s Syndrome
If patient is acutely ill, do not do a work up for this
What are the causes for Pseudo-Cushing’s Syndrome?
Psychological/Physical Stress
Alcoholism
Depression
What is the Urinary Free Cortisol Test?
- Urinary Free Cortisol is increased in more than 97% of patients with Cushing’s Syndrome
- These levels may also be increased in acute illness, trauma, surgery, alcoholism, depression and simple obesity.
> 300 mcg/24 hours = Cushing’s Syndrome
What is the Dexamethasone Suppression Test?
- 1 mg Dexamethasone is taken at midnight
- 8 am serum cortisol level is drawn the next morning
Plasma cortisol of < 5 mg/dL = Normal
>10 mg/dL = Cushing’s (commonly)
How do you tell if it is Cushing’s Disease or Cushing’s Syndrome?
Check ACTH levels in plasma
If patient has suppressed ACTH < 20, this is probably an adrenal source (Cushing’s Syndrome)
If patient has a “normal” (20-80) or modestly increased (80-200), this is probably Cushing’s Disease
If patient has a very high ACTCH of >200 then this suggests an ectopic source of ACTH (Cushing’s Syndrome)
If you diagnose Cushing’s, what is the next step needed to confirm!?
Imaging!
- Abdominal CT (suspected primary adrenal problem)
- MRI Pituitary (suspected pituitary disease)
- Chest and Abdominal CT Scan (suspected Ectopic ACTH)
If there is elevated ACTH and the MRI comes back normal, what can be happening?
Microadenomas or diffuse hyperplasia might be the cause.
Will want to do a inferior petrosal sinus sampling for further study
What is Pheochromocytoma?
Pheochromocytoma is a rare tumor of adrenal gland tissue. It results in the release of too much epinephrine and norepinephrine.
Sometimes the tumors are not on the gland itself, but can be in the sympathetic chain allowing for effects.
Pheochromocytoma can cause
HTN
Can mask as panic attacks
Occurs sporadically or familial
Symptoms of Pheochromocytoma
Headaches in 80% of the cases
Excessive Perspiration 70%
Palpitations 64%
Nausea 42%
Tremors 30%
Pallor due to vasoconstriction
How do you diagnose Pheochromocytoma?
- Urinary measurements of:
– free catecholamines
– urinary metabolites metanephrines, and VMA. - Drugs that can interfere with the assays
– catecholamine-containing drugs
– methyldopa
– Tricyclic antidepressants
– adrenergic blockers, etc - Diagnostic yield increased significantly if obtained after or during paroxysm
How do you treat Pheochromocytoma?
- Surgical excision of the tumor is curative
- Medical Management is used pre-operatively or in a failed surgery
– Alpha adrenergic blockade (Phenoxybenzamine)
– Beta blockade to control tachycardia/tachyarrhythmias (only after alpha is used)
What is Hirustism?
Cosmetically unacceptable terminal hair growth that appears in women in a male pattern.
Signs of Virilism
Increased muscularity, androgenic alopecia, deepening of the voice, clitoromegaly.
What is virilism?
The presence of male secondary sexual characteristics in a female.
