Newman Clin Med 2 Flashcards
What is the HPA axis and what does it regulate?
NE system that controls reactions to stress and regulates
- 1. Digestion
- 2. Immune system
- 3. Moods and emotions
- 4. Sexuality
- 5. Energy storage and expenditure
Why is negative feedback in the HPA axis important?
Regulate the concentration of hormones in the blood to prevent over/under correction
- Identify the “zone” of the adrenal cortex responsible for the production of
- a. Mineralocorticoids
- b. Glucocorticoids
- c. Sex steroids
- Glomerulosa => mineralcorticoids
- Fasiculata => glucocorticoids
- Reticulata => sex steroids
Describe the difference between short-term and long-term stress response in terms of the HPA axis and the adrenal cortex.
Short-term stress response: stimulation of the adrenal medulla via preganglionic sympathetic fibers => release of catecholamines (EPI and NE)
Long-term stress response: release of CRH from the hypothalamus => AP => ACTH => adrenal cortex => release of mineralcorticoids and glucorticoids.
What physiological changes do we see in the short-term response to stress?
- ↑ HR
- ↑ BP
- ↑ metabolic rate
- ↑ blood glucose: Glycogen conversion to glucose in the liver
- Dilation of bronchioles
- Changes in blood flow patterns leading to ↓ digestive system activity and ↓ urine output
What physiological changes do we see in the long-term response to stress?
-
Mineralcorticoids
- => ↑ retention of Na+/water by kidneys => ↑ BV/BP
-
Glucocortoids (cortisol)
- Proteins/fats => converted to glucose or broken down for NRG = > ↑ blood glucose
- Suppresion of immune system
The renin-angiotensin-aldosterone system is important in the regulation of what?
renal
cardiac
vascular physiology
Describe the renin-angiotensin-aldosterone system (RAAS) and how angiotensin II stimulates
aldosterone secretion from the adrenal cortex.
- Renin is secreted from the kidney dt ↓ renal perfusion and/or ↑ sympathetic activity
- Angiotensinogen is converted to angiotensin I (by renin)
- Angiotensin I becomes Angiotensin II (via ACE)
- Angiotensin II stimulates aldosterone secretion from the adrenal cortex
What is something you ALWAYS examine in a BB?
Genitalia
The most common cause of ambiguous genitalia in a genetically female infant is what?
CAH: congenital adrenal hyperplasia (causing virilization of the genitalia)
When ambigous genitalia is ID’d, what must be thought of?
CAH => LIFETHREATENING
What is the most common form of CAH?
21-hydroxylase deficiency (results in deficiency of aldosterone and cortisol, increase in testosterone)
What metabolic precursor will be elevated in 21-hydroxylase deficiency>
17- OH progesterone
Signs and sx of 21-hydroxylase deficiency
- i. Failure-to-thrive
- ii. Recurrent vomiting
- iii. Dehydration
- iv. Hypotension
- v. Hyponatremia/ Hyperkalemia
- vi. Shock
What do the effects of [low ald/cortisol and high testosterone] in 21-hydrolase deficiency depend on
severity of 21-hydroxylase abnormality
Treatment of an infant in crisis due to CAH
- Hydrocortisone (IV/IM) = MUST
- Fluids/glucose IV
- Management of hyperkalemia
- Summarize the purpose of mandatory newborn screening.
detect potentially fatal or disabling conditions in newborns as early as possible, hopefully before they develop serious illness.
Identify the three categories of adrenal gland defect responsible for primary adrenal insufficiency (Addison disease).
- a. Adrenal dysfunction
- b. Adrenal dysgenesis
- c. Impaired steroidogenesis
MCC of adrenal dynsfunction => Addisons disease
Autoimmune
Cause of adrenal dysgenesis => Addisons disease
Congenital adrenal insufficiency
Cause of Impaired steroidgenesis => Addisons disease
CAH
Nearly all patients with [primary adrenal insufficiency] complain of…
- Fatigue/weakness
- Reduced stamina
- WL/anorexia
- Hyperpigmentation
Most patients with [primary adrenal insufficiency] compain of…
- Abdominal pain, N/V
- HA
- MSK pain
- Psychiatric sx (depression, anxiety, irritability)
- Salt-craving
- Low BP (orthostasis)
- Discuss the laboratory findings seen in patients with [primary adrenal insufficiency]
- [↓ 8AM plasma cortisol] + [signficant ↑ of ACTH]
- ↓ serum Na+ and ↑ serum K+ (due to ↓ aldosterone)
- Fasting hypoglycemia and moderate neutropenia (↓ WBC) (due to ↓ cortisol)
Clinical signs in a patient with [acute adrenal insufficiency]
- Dehydration
- Dizziness/ light headed (dt low BP)/ confusion/ HA
- Fever, N/V
- Rapid HR and RR
- Abdominal pain/flank pain
Lab signs in a patient with [acute adrenal insufficiency]
- ↓ cortisol & nadequate bump in cortisol with ACTH stimulation
- ↓ Na+ / ↑ K+
- ↓ BP
- Metabolic acidosis
List the main components of acute adrenal crisis treatment.
- Hydrocortisone
- Fluids/glucose
- Fludrocortisone (after hydrocortisone is given)
- Treat hyperkalemia if needed.
What treatment for [acture adrenal crisis] is critical and emergent if in crisis?
Hydrocortisone
Lower than NL serum cortisol would typically result in an _____________ if everything was working normally.
↑ ACTH
↓ cortisol AND ↓ ACTH indicates _______.
The the problem is “higher” than the adrenal gland: pituitary tumor/damage, causing SECONDARY adrenal insufficiency.
Clinical signs of Cushings Syndrome (increased cortisol)
- Obesity/assymetric weight gain (truncal obesity + skinny/arms legs)
- Moon facies
- Buffalo hump
- Hirtusism/acne
- Dark purple striae
- Thirst and polyuria
- HTN
- Mental symptoms (diff concentrating and labilityo mood)
- Impaired wound healing
- Susceptable to opportunistic infections
ABNL Lab Results for Cushings
- ↑ midnight cortisol levels
What is the best screening test for Cushing syndrome?
How is it performed?
Dexamethasone Suppresion Test
- Before dexamethasone is given, serum ACTH is checked.
- Low dose dexamethasone is given at night
- Check serum cortisol in the morning and use results with serum ACTH levels that were checked BEFORE dexamethasone was given.
- Cushing syndrome is excluded = If serum cortisol is below a certain level
- Primary hypercortisolism = undetectable/↓ ACTH; cortisol is not suppressed by ↑/↓ dexamethasone
- Ectopic ACTH syndrome = ↑↑↑ ACTH (in hundreds); cortisol not suppressed by ↑/↓ dexamethasone
- Cushings disease = NL/↑ ACTH; cortisol suppressed with ↑ dose, not ↓.
When is the dexamethasone suppresion test performed?
When Cushing syndrome is suspected and serum cortisol levels are ↑
Ectopic ACTH syndrome is often caused by what?
Small cell lung cancer
Explain why most patients with primary aldosteronism (hyperaldosteronism) are hypertensive.
↑↑↑ aldosterone = ↑↑↑ Na+ retention = ↑↑↑ water retention = ↑↑↑ BP
Signs and Sx of primary hyperaldosteronism
- HTN
- Hypokalemia
- Muscle weakness
- PAresthesias with tetany
- HA
- Polyuria and polydipsia
When should you consider the dianogis of primary aldosteronism
-
HTN that is
- Treatment resisitant (despite triple drug therapy)
- Severe
- Early onset
- adrenal mass
- Low rening HTN
- HTN with FHx of early onset HTN or CVA
- 1st degree relative with aldosteronism
Triad of primary hyperaldosteronism
- Low renin HTN
- Hypokalemia
- Metabolic acidosis
Historically, what was Conn syndrome?
- JW Conn, who first described in it 1955.
- Initially, used to describe the condition in which a unilateral aldosterone producing adrenal adenoma resulted in HTN
Now, what is Conn Syndrome?
Used interchangeably with primary hyperaldosteronism, whether the patient has an adenoma or not.
Pheochromacytoma
- Location
- Signs:
- Location: adrenal medulla
- Secretes catecholamines (EPI/NE)
Paraganglioma
- Location
- Signs:
- Location: outside adrenal gland
- Signs: secretes catecholamines or non-secreting
Symptoms of Pheochromacytoma and Paraganglioma
- Paroxysmal in timing
- High BP
- Pounding HA
- Persipiration
- Panic (impending doom)
- Palpitations
- Pallow (after spell has subsided)
Most sensitive test for diagnosing secretory pheochromocytomas and paragangliomas.
Plasma fractionated free metanephrines
von Hippel-Lindau disease type 2
- Inheritance:
- 20% will develop ________.
- Patients will get (3)
- AD
- Pheochromacytomas
- Pts will get
- Retinal capillary hemangiomas/hemangioblastomas (BV tumors)
- CNS hemangioblastiomas
- ↑ risk for renal cysts that become [renall cell carcinoma]/
Treatment of Pheochromacytomas
Alpha-blockers (phenoxybenzamine) THEN beta-blockers.
Why is it important to treat pheochromacytomas with [alpha blocker] first, then [beta blockers]?
Unopposed alpha-receptor stimulation => further ↑ in BP.
What are adrenal gland incidentalomas?
tumors found incidentally on abdominal CT/MRI
What are most adrenal gland incidentalomas and when should resected?
Most are benign adrenal adenomas. but can be malignant. Resect if:
- 1. > 4cm and not obviously a lesion, cyst, hemorrhage
- 2. Hx of malignancy
Patients with adrenal incidentalomas require what?
- Assessment for Cushing syndrome
- Assessment for hyperaldosteronism
- Assessment for pheochromocytoma (plasma fractioned free metanephrines)
MEN syndromes are caused by ________ and therefore tend to run in families.
gene mutations
