Adrenal Glands

What are steroid hormones synthesized from?

Cholesterol

What are three types of steroid hormones?

1. Mineralocorticoids

2. Glucocorticoids

3. Androgens

What hormones does the adrenal cortex produce?

1. Mineralocorticoids

2. Glucocorticoids

3. Androgens

What do mineralocorticoids do, and what is an example?

1. Salt and water balance

2. Aldosterone

What do glucocorticoids do, and what is an example?

1. Glucose regulation, anti-inflammatory

2. Cortisol

What do androgens do, and what is an example?

1. Adrenal sex hormones, precursor to estrogen

2. Testosterone

What hormones does the adrenal medulla produce?

1. Epinephrine

2. Norepinephrine

3. Dopamine

What kind of hormones does the adrenal medulla produce, and what is needed to synthesize them?

1. Amine

2. Tyrosine

How would you describe the activity of steroid hormones?

Slow to respond but long lasting

Why are steroid hormones slow to respond but long lasting?

1. They cross plasma membranes

2. Steroid-receptor complex impacts transcription

3. Synthesized on demand and not stored

What does aldosterone do?

1. Na+ and water reabsorption

2. K+ and H+ secretion

3. Increases BP and blood volume

How is aldosterone transported?

1. Binds poorly to Cortisol-binding protein

2. Binds to albumin

3. 30-50% free

How is aldosterone regulated?

Renin-angiotensin system

What stimulates the release of aldosterone?

1. AG-II

2. Increased serum K+

Three functions of cortisol

1. Overall increases blood glucose

2. Immunosuppression

3. Anti-inflammatory

How is cortisol regulated?

1. Hypothalamus releases CRH

2. Pituitary releases ACTH

3. Adrenal gland releases cortisol

What signals prompt the release of cortisol?

1. Low glucose

2. Stress

How is cortisol transported?

High degree of binding to Cortisol-binding globulin

When is cortisol highest and what level does it reach?

1. Highest in AM

2. 5-20 ug/dL

When is cortisol lowest and what level does it reach?

1. Lowest in PM

2. 2-14 ug/dL

What is a sensitive test of overproduction?

24-hour urinary free cortisol test.

What are two disorders of the adrenal cortex?

1. Hyperfunction

2. Hypofunction

What are two disorders that cause cortex hyperfunction?

1. Hyperaldosteronism

2. Cushing’s syndrome (increased cortisol)

What disease causes cortex hypofunction?

Addison’s disease

What are three conditions caused by Hyperaldosteronism?

1. Resistant hypertension

2. Unexplained hypokalemia

3. Metabolic alkalosis

How common is hypokalemia in patients with hyperaldosteronism?

< 50% of patients have this

What are two types of hyperaldosteronism, and which is most common?

1. Primary (uncommon)

2. Secondary (most common)

Causes of primary hyperaldosteronism and how frequent are they?

1. Aldosterone-producing adrenal tumor (Conn’s syndrome) (75%)

2. Primary adrenal hyperplasia (25%)

What are three causes of secondary hyperaldosteronism?

1. Renal artery stenosis

2. Chronic renal failure

3. Renin-secreting tumor

What level of urine production and hypokalemia is consistent with hyperaldosteronism?

1. > 30 mmol/day urine

2. Hypokalemia in serum or increased urinary K

What levels of renin, aldosterone, and aldo/renin ratio does primary hyperaldosterone have?

1. Low renin

2. High aldosterone

3. High aldo/renin ratio

What levels of renin, aldosterone, and aldo/renin ratio does secondary hyperaldosterone have?

1. High renin

2. High aldosterone

3. < 15 aldo/renin ratio

How should you confirm abnormal values?

Suppression test measuring aldosterone and plasma renin and measure salt load

What are four symptoms of hypercortisolemia?

1. Cushinoid appearance

2. Poor wound healing

3. Hyperglycemia

4. Muscle weakness

What are five features of someone with a cushinoid appearance?

1. Moon face

2. Truncal obesity

3. Buffalo hump

4. Excessive bruising

5. Thin skin with striae

What are two causes of hypercortisolemia? How is ACTH affected in each?

1. ACTH-dependent (increased ACTH)

2. ACTH-independent (decreased ACTH)

What are two causes of ACTH-dependent hypercortisolemia? How common is each?

1. Pituitary adenoma (70%)

2. Ectopic ACTH (20%)

What are two causes of ACTH independent hypercortisolemia, and how common is each?

1. Adrenal cortical adenoma (95%)

2. Exogenous cortisol (<1%)

What is a screening test for cortisol, and what is a pro/con?

1. 24 hr urinary free cortisol

2. Sensitive but not specific

What is the normal cortisol level in urine?

< 50 ug/day

What happens to cortisol levels in Cushing’s disease?

Loss of diurnal variation

What is a confirmatory test, and what would you expect to see in Cushing’s disease?

1. Dexamethasone Suppression Test

2. Cortisol levels resist suppression

How does the Dexamethasone work in someone without cushing’s syndrome?

1. Dexamethasone suppresses ACTH

2. 1 mg DMT at 11 PM then measure cortisol at 8 AM

3. Normal is suppression < 5 ug/dL

When will DMT not work?

1. If pituitary tumor is present

What do you do if the 24 hr test is positive?

Confirm with formal test which is 48 hours with low and high dose protocol

What are two causes of cortex hypofunction? Which one causes Addison’s disease

1. Primary (Addison’s disease)

2. Secondary

What are two causes of Addison’s disease, and how common are they?

1. Autoimmunity (0-90%)

2. Infectious (TB, HIV, etc) (7-20%)

What are causes of secondary cortex hypofunction?

1. ACTH deficiency due to exogenous suppression, trauma, or infection

What kind of adrenal cortex deficiencies are most common? Which is rare?

1. Cortisol alone or Cortisol & aldosterone are common

2. Deficiency of aldosterone alone is rare

Symptoms of Cortisol deficiency

1. Weakness

2. Weight loss

3. Fatigue

4. Hypoglycemia

5. Nausea

Symptoms of Aldosterone deficiency

1. Hyponatremia

2. Hyperkalemia

3. Dehydration

4. Non-anion gap metabolic acidosis (bicarb loss)

5. Low BP

Symptom of ACTH excess due to decreased cortisol

1. Hyperpigmentation of skin and mucous membranes

Where are ACTH and Melanocyte stimulating hormone (MSH) derived?

From the same precursor

What lab result strongly suggests adrenal insufficiency?

Low serum AM cortisol < 5 ug/dL

What is the confirmation test for low serum cortisol?

ACTH stimulation test

How does the ACTH stimulation test work?

1. Give synthetic ACTH (cortrosyn)

2. Measure cortisol 30, 60, & 120 minutes later

3. Assesses the adrenal gland’s ability to increase cortisol secretion

What is the normal cortisol response to ACTH stimulation test?

>/= 20 ug/dL

What are catecholamines?

Biogenic amine hormones produced from tyrosine

What is a precursor to norepinephrine?

Dopamine

Where is the majority of dopamine produced?

In the brain, but some is produced in the adrenal medulla

What does dopamine do?

Regulate mood, reward, motor control

How does dopamine affect the pituitary?

It inhibits the release of prolactin

What is epinephrine and norepinephrine released in response to?

1. Emotional disturbances (stress, pain, fear)

2. Hypotension

3. Muscular exertion

What does epinephrine and norepinephrine do?

Increases HR, BP, O2 consumption, glucose

How do catecholamines work?

Effects are rapidly induced and dissipate quickly (labile)

What is responsible for reuptaking catecholamines, and what is it used to make?

1. Nerves

2. Metabolites

Where are catecholamines sometimes excreted?

Urine

What are two kinds of tumors that secrete catecholamines?

1. Pheochromocytoma

2. Neuroblastoma

What are symptoms of a Pheochromocytoma?

1. Hypertension

2. Spells of sweating, palpitations, flushing, headache

What are symptoms of Neuroblastoma?

1. Hypertension

2. Bone pain

3. Weight loss

What is the most common solid organ tumor in children?

Neuroblastoma

Where is a neuroblastoma located?

1. Adrenal Medulla

2. Paraspinal sympathetic nervous system

Which tumor often presents with an abdominal mass?

Neuroblastoma

What test is used to detect a Pheochromocytoma?

Fractionated plasma metanephrines

What test do you perform if the fractionated plasma metanephrines is borderline?

Perform 24 hr urine metanephrines via HPLC

How do you detect a neuroblastoma?

Urinary VMA and HVA with HPLC

What is the least useful test and why?

1. Plasma catecholamines

2. Easily induced, labile, poor specificity

Three causes of catecholamine deficiency?

1. Genetic disorder

2. Damage to adrenal gland

3. Neurogenerative disorder

What are two genetic disorders that cause catecholamine deficiency?

1. Phenylketonuria

2. Dopa-responsive dystonia

What cause Phenylketonuria?

Impaired conversion of phenylalanine to tyrosine

What causes Dopa-responsive dystonia?

Impaired dopamine production

What are three tests used to detect catecholamine deficiency?

1. Genetic testing

2. Urinary VMA and HVA

3. Plasma catecholamine levels