Adrenal Disease Flashcards
(27 cards)
What is the HPA axis and hormones involved for adrenal function
Hypothalamus - corticotropin releasing hormone
Anterior pituitary - adrenocorticotropin hormone
Adrenal cortex - aldosterone, cortisol, androgens (salty, sweet, sex)
*medulla - catecholamine production
What is adrenal insufficiency
What are the most common primary and secondary causes of AI
Life-threatening deficiency of glucocorticoid +/- mineralocorticoid
Addison’s disease
Primary - CAH and autoimmune, other dysgenesis
Secondary - withdrawal of therapeutic glucocorticoids
What are causes of primary adrenal insufficiency (5)
Damage to gland - Hemorrhage (Friedrichson-Waterhouse), Autoimmune (Addison’s disease, AIRE mutation - autoimmune regulator gene), Infection (TB, fungal, HIV), Drugs (ketoconazole)
Abnormal development - X-linked adrenal hypoplasia congenital (DAX1), adrenal hypoplasia (SF-1 mutation)
Steroidogenesis disorders - CAH (21 hydroxylase deficiency, 11 beta hydroxylase deficiency)
Peroxisomal defects - adrenoleukodystrophy, Zellweger syndrome
Unresponsive to ACTH - Allgrove syndrome
What are causes of secondary (pituitary) or tertiary (hypothalamic) adrenal insufficiency (3 categories)
Congenital - midline defects (septo-optic dysplasia), idiopathic, mutations (PROP-1, PIT-1, T-Pit, POMC)
Acquired - tumor, hemorrhage, surgery, cranial radiation
Infiltrative - hemochromatosis, sarcoidosis, Langerhans histiocytosis
*tertiary hypothalamic suppression - after cessation of supraphysiologic glucocorticoids
What are supraphysiologic doses of glucocorticoids (in hydrocort, prednisone, dexamethasone dosing)?
Baseline production of glucocorticoid
Hydrocortisone - 6-8mg/m^2/day
Prednisone - 1-1.5 mg/m^2/day
Dexamethasone 0.2-0.3mg/m^2/day
*approximately factor of 5
How do you calculate body surface area
SQAURE ROOT OF: (ht x wt)/3600
What two labs do you want to do on an undervirilized male?
Karyotype
Testosterone
Two reasons for low testosterone in undervirilized male?
testosterone synthesis defect
Defective testicular differentiation
What are two lab tests you want in a hypervirilized female?
karyotype
17-OHP
Two diseases causing normal to high testosterone in undervirilized males?
androgen receptor defects
5 alpha reductase deficiency
Name 3 things on the differential for a hypervirilized female with normal 17-OHP but high testosterone?
Aromatase deficiency (can’t convert testo to estrogen)
maternal androgens
tumour
What is the inheritance pattern of CAH
Autosomal recessive
What is congenital adrenal hyperplasia, and what is the most common cause
Enzymatic defect in steroidogenic pathway to cortisol
90-95% 21-hydroxylase mutation (elevated 17-OHP)
75% are classic salt wasting
Why do you get virilization with CAH (aka what is the pathway to create cortisol)
Pathway from cholesterol –> pregnenolone –> progesterone –> 17-OHP
Without 21-hydroxylase, cannot get from to aldosterone or cortisol
Shunting from 17-OHP to production of testosterone
What are the androgen related clinical findings in CAH
- genital ambiguity in females (clitoromegaly, fusion of labioscrotal folds, penile urethra, normal internal organs)
- subtle virilization in males
- early axillary and pubic hair
- acne
- body odor
- accelerated growth, but compromised final height from early fusion of growth plates
What are the salt-wasting features of CAH
Aldosterone deficiency - presents in first few weeks as adrenal crisis
- hyperpigmentation of skin creases and genitalia
- initial demand of frequent feeding (dehydration vs. salt craving)
- nonspecific unwell infant findings, including dehydration, hypothermia, hypotension, vomiting
- HYPOnatremia, HYPOglycemia
- HYPERkalemia
- metabolic acidosis
What investigations (labs/imaging) do you do to test for CAH?
*same as ambiguous genitalia
lytes, glucose, CBG
cortisol
ACTH and stim test
17-OHP
androstenedione
renin activity
karyotype
pelvic ultrasound *remember females will have female internal organs
How do you do an ACTH stim test
Cosyntropin (synthetic ACTH) 0.25mg
Prior and 60 min after - 17-OHP, cortisol, DHEA, androstenedione, 11-deoxycortisol, deoxycorticosterone, 17-hydroxypregnenolone
How do you manage an adrenal crisis
Fluids
Stress dose hydrocortisone 100mg/m^2/day
Treat electrolyte abnormalities
Which two steroid formulations have mineralocorticoid effect?
hydrocortisone
prednisone
*dex does not have any mineralocorticoid
What is the long-term management of CAH
Cortisol replacement - hydrocortisone 10-20mg/m^2/day divided TID (short half life and minimal growth suppression)
Monitor for Cushing syndrome
Monitor for growth - bone age
Stress dose steroids during illness
Fludrocortisone replacement 0.1-0.2mg with NaCl supplements
Monitor renin activity levels
Plastic surgery
What is the long-term outcome for CAH (growth, fertility, cognitive)
Growth - tall in childhood but short in adulthood from premature fusion of growth plates - may be able to supplement growth hormone/block puberty for increased height
Fertility - reduced in both males and females
Cognition - normal
What is Addison’s disease
Primary adrenal insufficiency
What are the clinical manifestations of Addison’s disease
Adrenal crisis
Salt-wasting
Fatigue, weakness, loss of appetite, poor weight gain
Gastro-like illness
“muddy” hyperpigmentation
