Adrenals Flashcards
Describe the HPA (hypothalamic pituitary axis)
Primary organ: target organ
Secondary: Pituitary
Tertiary: hypothalamus
What are the hormones of the adrenals
zona Glomerulosa: Mineralocorticoids (Aldosterone)
zona Fasciculata: Glucocorticoids (cortisol)
zona Reticularis: Adrenal androgens (DHEA)
Medulla: catecholamines (epi/NE)
What does aldosterone do
controls body fluid volume!
Increase reabsorption of Na and H2O
Increase excretion of K+ and H+
Describe cortisol secretion
Pulsatile, diurnal under control of ACTH
Secreted mainly in the morning, around 8-9AM
What stimulates the hypothalamus to release CRH (then ACTH then cortisol)
Stress!
trauma, pain, hypoglycemia, hemorrhage
Mineralocorticoids mediate the long-term stress response
What can long term high dose glucocorticoid therapy cause
adrenal atrophy
What does primary overproduction of cortisol by the adrenals cause
ACTH secretion inhibition (negative feedback)
What are the functions of cortisol
Protect against hypoglycemia Decrease insulin sensitivity Anti-inflammatory Suppress immune system Maintain vascular responsiveness to NE/Epi Inhibit bone formation Promote increase in GFR
How does cortisol protect against hypoglycemia
Gluconeogenesis in liver
Proteolysis
Lipolysis
How is cortisol anti-inflammatory
Inhibits production of inflammatory mediators; histamine, leukotrienes, prostaglandins
What is DHEA
Little significance in men
Women: major source of androgens! causes early development of pubic and axillary hair, and masculinization
What are the physiologic effects of the catecholamines
Epi/NE Increase rate and force of heart contraction Vasoconstriction Dilate Bronchioles Stimulate lipolysis in fat cells Increase metabolic rate Pupil dilation Inhibit "non-essential" processes (GI secretions)
In other words, Epi/NE mediate
Short term stress response
What are the principles of endocrine testing
Hypofunction: do a stimulation test
Hyperfunction: do a suppression test
What are the possible results of a serum total cortisol
> 10: unlikely to have adrenal insufficiency
3-10: inconclusive
<3: very likely to have adrenal insufficiency
How do you preform a 24 hour urinary free cortisol test
Discard first morning void
Collect for next 24 hours (including void at end of 24 hours)
record last voiding time
Keep urine cool during collection (high temp alters results)
If urine is lost, start over the next day
What does a 24 hour urinary free cortisol test measure
quantity of free cortisol collected
Ideal for suspected hypercortisolism
What is the purpose of a Plasma ACTH test
Differentiate primary, secondary, and tertiary source of cortisol imbalance
-You collect it with a serum cortisol, as it has the same diurnal variation
What does the ACTH stimulation test assess
The source of adrenal insufficiency (cortisol deficiency)
How do you preform an ACTH stimulation test
Get baseline plasma cortisol level
Give 250 mg IV short acting Cosyntropin (synthetic ACTH)
Measure plasma cortisol at 30 and 60 min
What are the possible results of an ACTH stimulation test
Cortisol level doubles: normal adrenal fxn
Cortisol level subnormal: Adrenal Insufficiency
What is the Dexamethasone suppression test
Get baseline plasma cortisol
Give 1mg DXM (synthetic steroid) PO at 11PM
Measure plasma cortisol at 8AM
What are the possible results of the dexamethasone suppression test
Cortisol level no change: excess cortisol production (steroid can’t even suppress it)
Cortisol level suppressed: normal adrenal fxn
Prolonged exposure to elevated cortisol results in
Cushing’s Syndrome!
What are the MCC of Cushing’s syndrome
Exogenous: chronic excess corticosteroids
Endo: Pituitary adenoma (cushing’s disease)- W:M 10:1
(endo can also be 2/2 adrenal hyperplasia, sdrenocortical tumor, neuroendocrine tumor, small cell lung cancer, and ovarian cancer)
What are the physical manifestations of Cushing’s Syndrome
HTN
central obesity (moon face, buffalo hump)
Insulin resistance (overt DM)
Purple striae >1cm wide
easy bruising
androgen excess (hirsutism, acne, irreg menses)
severe fatigue and proximal muscle weakness
osteoporosis
impaired wound healing
infections
psych- depression, paranoia
If you have clinical suspicion for Cushing’s syndrome, how can you test for it and what will your results be
24 hour free urine cortisol: high
midnight salivary cortisol level: high on 2 separate nights
DXM suppression: no change in cortisol level
Plasma ACTH: <20 is an adrenal tumor- >80 at 8am is a pituitary adenoma (ACTH dependent)
How do you manage Cushing’s syndrome
If 2/2 pituitary tumor: get an MRI
If 2/2 ectopic ACTH secreting tumor: get CXR to r/o lung mass, and pelvic u/s to r/o ovarian mass
If 2/2 pituitary tumor: is there a palpable abd mass? get CT abdomen
If 2/2 exog steroids: taper to lowest possible therapeutic dose
What are treatments for Cushing’s syndrome
Pituitary adenoma: Transspheniodal resection
Adrenal tumor: adrenalectomy
Adrenal hyperplasia: meds
Ectopic ACTH syndrome: target source of ectopic production
Medical management of Cushing’s Syndrome includes
Adrenolytic agents (Mitotane): permanently destroys adrenocortical cells! medical adrenalectomy Adrenal enzyme inhibitors
What are the adrenal enzyme inhibitors used in Cushing’s syndrome
Ketoconazole: antifungal, cortisol reduction in higher doses (ADE liver toxic!!)
Metyrapone: inhibits cortisol synthesis, mostly a combo drug
What can cause Primary adrenal insufficiency
MC in USA: Addison’s disease (AI cortical destruction) causing mineral/glucocorticoid deficiency
MC in world: Tuberculosis
-Also: congenital enzyme deficiencies, infection, surgery (adrenalectomy)
What can cause Secondary adrenal insufficiency
Insufficient ACTH secretion
Long term exogenous steroid= HPA suppression= abrupt med withdrawal= Addison’s crisis
What causes tertiary adrenal insufficiency
insufficient CRH secretion
Clinical manifestations of adrenal insufficiency are
Insidious onset, non-specific Sx: weakness, fatigue, anorexia, weight loss
*Hyperpigmentation (creases, pressure areas, and nipples)
Hypotension
Hypoglycemia
Salt cravings
GI complaints
What drives hyperpigmentation
ACTH
Clinical manifestations of Addison’s Crisis (2ndry insuff) are
Extremely low cortisol Sudden onset Hypotension acute abd/back pain vomiting diarrhea dehydration AMS electrolyte abnormalities
What initial diagnostic studies should you get for adrenal insufficiency, and what are results
CMP: hyperkalemia, hypercalcemia, hyponatremia
CBC: Eosinophilia
If initial CBC and CMP are suspicious, what other labs can you get
Anti-adrenal antibodies, indicating AI if primary insufficiency (Addison’s)
AM plasma cortisol: abn low
Plasma ACTH: if high, primary. if low, second/tertiary
ACTH stimulation test: cortisol level does not change
Review of what to do if you suspect Addison’s disease
Get a CBC, CMP
Get a plasma ACTH, plasma cortisol, and ACTH stimulation test
When would you need a radiograph of the adrenals
CT: For secondary causes, to eval possible infection or malignancy; Not needed for primary adrenal insufficiency
MRI: pituitary if secondary insufficiency (hypothalamus or pituitary)
How do you treat Adrenal insufficiency
Primary: Glucocorticoids (hydrocortisone) AND mineralocorticoids (fludrocortisone) replacement
1/3: Glucocorticoids only (hydrocortisone)
What changes can be made to adrenal insufficiency meds
Increase dose in stressful times
Give DHEA to women
Taper long term steroids to prevent 2/3 adrenal insuff
How do you treat an adrenal crisis
IV steroics
Correct electrolytes (Volume resuscitation)
50% dextrose to correct hypoglycemia
when stable, look for the underlying cause
What is Conn’s syndrome
Primary hyperaldosteronism
MCC adrenocortical adenoma
also 2/2 cortical hyperplasia
How does primary hyperaldosteronism present
HTN Hypokalemia Muscular weakness Paresthesias Paresthesias HA Polyuria and Polydipsia
What should the work up for primary hyperaldosteronism include
Elevated plasma and urine aldosterone
low plasma renin (RAAS)
CT scan of adrenals to eval adrenal adenoma
How do you manage primary hyperaldosteronism
Surgically remove adenoma
Spironalactone, anti-HTN
What is a pheochromocytoma
Tumor arising from chromaffin cells in adrenals, MC in medulla;
Secretes catecholamines (epi/NE)
10% are malignant
What are the clinical manifestations of a pheochromocytoma
Paroxysmal Palpitations (tachycardia)
HA
Episodic sweating
Paroxysmal/sustained HTN (very high, 200/100 levels)
When I say “refractory hypertension” you say…
PHEOCHROMOCYTOMA!
What is a Pheochromocytoma attack
+/- displacement of abd contents (lift, bend)
Lasts 30-40 min
Increases in frequency and severity over time
Other Sx of pheochromocytoma include
pallor nausea tremor fatigue anxiety epigastric pain hypertensive retinopathy (from prolonged HTN)
When should you suspect a pheochromocytoma
Classic paroxsymal attacks Refractory HTN, HTN <20 y/o Idiopathic DCM Abdominal mass Fhx Adrenal mass MEN2 Neurofibromatosis
How do you diagnose a pheochromocytoma
1st*Metanephrine 24 hour urine screen (catecholamine metabolite)
Clonidine suppression
MRI abdomen and pelvis
MIBG (radio-isotope) to ID extra-renal tumors
What does Clonidine usually do to catecholamines
It causes them to decrease
If you have a pheochromocytoma, they do not decrease
How do you treat pheochromocytomas
Give alpha blocker (phenoxybenzamine) to control BP
Give beta blocker (propanolol) to control HR
Surgical resection
What is an adrenal incidentaloma
Mass >1cm discovered incidentally by radiographs (abd CT)
MC in obese, hypertensive, diabetic patients
Most are non-functional
What must you ask yourself when you find an adrenal mass
Is it malignant (<4cm, lipid rich, rapid contrast wash out)
Is it functioning
How do you work up an adrenal incidenteloma
Get a plasma cortisol, serum ACTH, serum DHEA, and plasma aldosterone
- Do they have Sx of cushing’s? (if yes, get 24 hr urine free cortisol) (if no, do DXM suppression)
- Are you susp of pheo? (24 hr metanephrine, catecholamines)
When would you order a fine needle aspiration/biopsy
If you have a known primary malignancy elsewhere and are evaluating an adrenal incidenteloma
When DON’T you need a FNA
If you have evidence of a pheo (dont want to release the contents)
Known widespread mets
How do you treat an adrenal incidenteloma
If pheo/carcinoma: Surgery
If underlying dz: pharm intervention
If benign in imaging:>2cm resect, <2cm repeat imaging at 6, 12, and 24 mo; test DXM suppression q4 years
