Adrenal Flashcards
What gene is associated with congenital adrenal hypoplasia?
DAX1
Name the 3 zones of the adrenal cortex and what they produce
- Zona glomerulosa: mineralocorticoid (aldosteron)
- Zona fasciculata: glucocorticoid (cortisol) and androgens, thickest layer (75%)
- Zona reticularis: glucocorticoid (cortisol) and androgens (possibly basal glucocorticoid production only rather than ACTH-dependent)
Draw a picture of the adrenal gland and its layers
Draw steroidogenesis
When do ACTH and glucocorticoid production peak?
In the morning just before awakening (6th-8th hourse of sleep)
List 5 things that may impact the timing and height of 8:00 am cortisol test
- Physical stress (major illness, surgery, trauma or starvation)
- Psychological stress (anxiety, depression, mania or psychosis)
- CNS and pituitary disorders
- Cushing syndrome
- Liver disease
- Chronic renal failure
- Alcoholism
What is the advantage of measuring salivary cortisol?
No binding proteins in saliva, so it reflects free cortisol
What percentage of cortisol in circulation is bound?
- 10% free
- 75% bound to CBG
- 15% bound to albumin
What is the difference between low dose and high dose dexamethasone suppression tests?
- Low dose (1 mg): screening test for Cushing syndrome, negative if <50 nmol/L
- False positives in hospitalized/chronically ill patients, acute illness, depression/anxiety, alcoholism, high estrogen states, uremia
- High dose (8 mg): historically used to differentiate Cushing disease vs ectopic ACTH and adrenal tumors as Cushing disease was thought to be suppressible to <50% of baseline (HOWEVER it is not a great test and excptions are common)
List 1 advantage and 2 disadvantages of low-dose ACTH stimulation test over high-dose
- Advantage: more sensitive/specific in secondary adrenal insufficiency
- Disadvantage:
- Logistics (must be done in AM, with IV ACTH)
- Technical limitations (ACTH is only available in 250 mcg vials, unstable in solution, adheres to glas and tubing)
What is the metyrapone test used for?
- To diagnose suspected pituitary ACTH deficiency
- Metyrapone inhibits 11-beta hydroxylase (11-deoxycortisol –> cortisol), which should stimulate ACTH secretion
Describe the insulin induced hypoglycemia test
- Hypoglycemia –> CNS stress response
- CRH –> ACTH –> cortisol
List 4 causes of hypoglycemia and low cortisol in a 4 week old female
- Congenital adrenal hyperplasia (StAR mutation, 3-beta-hydroxysteroid dehydrogenase, 21-hydroxylase)
- Adrenal hypoplasia congenita (DAX1 mutation)
- Hypopituitarism (PROP1, POU1F1, POMC mutation, SOD)
- ACTH resistance syndromes/hypoplasia (familial glucocorticoid deficiencies, triple A/Algrove syndrome)
- Peroxisome biogenesis disorders (ex. Zellweger syndrome, neonatal adrenaleukodystrophy)
- Birth trauma
- Infection/sepsis
List 5 causes of primary adrenal insufficiency
- Autoimmune (Addisions)
- Metastatic malignancy or lymphoma
- Adrenal hemorrhage
- Coagulopathy
- Antiphospholipid antibody syndrome
- Infectious (sepsis, TB, CMV, fungi, HIV)
- Adrenaleukodystrophy
- Peroxisome disorders (Zellweger)
- Infiltrative (amyloidosis, hemochromatosis)
- Congenital adrenal hyperplasia/hypoplasia
- Familial glucocorticoid deficiency and hypoplasia
- Triple A (Algrove) syndrome
- Drugs (ketoconazole, metyrapone)
What conditions are seen in APS type 1?
What is the gene associated?
- AIRE (autoimmune regulator) gene
- Addisons
- Hypoparathyroidism
- Mucocutaneous candidiasis
- Less common: autoimmune hepatitis, dystrophy of dental enamel and nails, alopecia, vitiligo, keratopathy, dysfunction of gonads, thyroid, pancreatic beta cells, gastric parietal cells)
What conditions are seen in APS type 2?
- HLA-related disorders
- Type 1 diabetes
- Autoimmune thyroid disease
- Alopecia areata
- vitiligo
- Primary hypogonadism
- Pernicious anemia
- Celiac disease
Describe familial glucocorticoid deficiency
- Hereditary adrenocortical unresponsiveness to ACTH (high ACTH, low cortisol)
- Aldosterone secretion is preserved
- 2 subtypes:
- ACTH receptor mutation
- Allgrove/ Triple A syndrome with achalasia and alacrima
*
List 3 drugs that can cause primary adrenal insufficiency
- Antifungals (ketoconazole)
- Etomidate
- Antiparasitic agent suramin
- Metyrapone
Differential diagnosis for hypoglycemia and low cortisol in a 4 week old female infant
- Hypopituitarism
- PROP1, PIT1, POMC, POU1F1
- ACTH resistance syndrome & hypoplasia
- Familial glucocorticoid deficiencies
- Triple A (Algrove) syndrome
- Congenital adrenal hypoplasia (DAX1)
- CAH
- StAR mutation, 3 beta hydroxysteroid dehydrogenase, 21 hydroxylase (but expect virilization)
- Sepsis, infection
- Peroxisome disorders (Zellweger)
- Birth trauma
Where should you look for hyperpigmentation in a patient with Addisons?
- Buccal mucosa
- Palmar creases
- Nipples/areolae
- Perivaginal and perianal mucosa
- Sun-exposed areas
- Scars (will be hyperpigmented)
- Pressure areas (knuckles, toes, elbows, knees)
What is the differential diagnosis for Cushing syndrome?
- ACTH dependent: Cushing disease, nonpituitary neoplasm (ectopic ACTH)
- ACTH independent
- Iatrogenic (glucocorticoids)
- Adrenal carcinoma
- Adrenal neoplasm/adenoma
- Macronodular adrenal hyperplasia
- McCune albright syndrome
- Primary pigmented nodular adrenal disease
- Isolated micronodular adrenocortical disease
What tumors are associated with ectopic ACTH secretion?
Mostly thoracic origin
- Bronchial carcinoid
- Small and non-small cell lung cancer
What tests can you do to diagnose Cushing syndrome
- 24 hour urinary free cortisol
- Overnight 1 mg Dex suppression test
- Late night salivary cortisol
