Adrenal Disorders in Infants Flashcards
What are the cells of the adrenal medulla that produce hormones?
Chromaffin cells
What are the cells of the parathyroid gland that secreted PTH?
Chief cells
What is the MOA of ketoconazole?
Blocks 17-alpha-hydroxylase
What is the most common cause of congenital adrenal hyperplasia?
Deficiency/defect in 21-hydroxylase
What are the deficiencies associated with 21-hydroxylase deficiency?
Loss of mineralocorticoids and glucocorticoids, overproduction of androgens
What are the classic lab findings of 21-hydroxylase deficiency?
Hyponatremia
Hyperkalemia
Low BG
What are the two major forms of 21-hydroxylase deficiency?
Salt losing (“Classic”) vs non-salt losing (“non-classic”)
What are the clinical symptoms of CAH in females?
Ambiguous genitalia (clitoral enlargement, fusion and formation of urogenital sinus
What are the clinical symptoms of CAH in males?
Subtle hyperpigmentation of scrotum or enlarged phallus
What are the clinical symptoms with 21-hydroxylase deficiency?
FTT
Emesis
Dehydration
What is the non-classic form of CAH? What are the ssx of females vs males?
Non-salt losing form–
females = symptoms appear later in life as precocious puberty
Males = symptoms of early virilization at 2-4 yo
What is the enzymatic difference between classic and non-classic 21-hydroxylase deficiency?
Classic is full defect
non-classic is mild defect
What are the defects seen with 11-beta-hydroxylase deficiency? Why?
11-deoxycorticosterone still has some aldosterone-life effects, thus no salt wasting seen in 21-hydroxylase deficiency
What are the ssx of 11-beta-hydroxylase deficiency?
HTN
Virilization
No salt loss
What are the lab findings with 11-beta hydroxylase deficiency?
Hypokalemia
What is 17-alpha-hydroxylase deficiency?
Lack of androgen and cortisol production, causing excess aldosterone, HTN, ad hypokalemia
What is the best way to diagnose 21-hydroxylase deficiency?
Draw 17-hydroxyprogesterone levels (which will be supe high)
What are the ACTH and renin levels with 21-hydroxylase deficiency?
Both high
What is the gold standard for diagnosing 21-hydroxylase deficiency?
Cosyntropin (synthetic ACTH) stimulation test
What molecule is elevated with 11-beta-hydroxylase defect?
11-deoxycorticosterone and 11-deoxycortisol
What are the chemicals that are elevated with 17-hydroxylase deficiency?
Elevated aldosterone levels
How do you manage 21-hydroxylase deficiency?
Exogenous hydrocortisone and fludrocortisone
What is the treatment for the ambiguous genitalia that can occur with 21- or 11B hydroxylase deficiency?
Surgical correction
What is the synthetic aldosterone given to patients with 21 or 11B hydroxylase deficiency?
Fludrocortisone
Lack of pubic hair is classic for what type of pituitary pathology? Why?
Prolactinoma, since prolactin inhibits LH/FSH secretion, causing a loss of estrogen
What are the two hormones that act to induce and suppress prolactin secretion?
Dopamine inhibits
TRH stimulates
What is the natural course of addison’s disease?
Slow progression, with ssx appearing around age 10-14
What are the causes of Addison’s disease?
Autoimmune or TB
What is Waterhouse-Friderichsen syndrome?
Hemorrhage into the adrenal glands causing Primary adrenal insufficiency
What is the classical cause of Waterhouse-Friderichsen syndrome?
Neisseria meningitidis infection
What is autoimmune polyglandular syndrome type 1?
Hypoparathyroidism
Chronic mucocutaneous candidiasis
Adrenal insufficiency
What is autoimmune polyglandular syndrome type 2?
Adrenal insufficiency
Thyroiditis
DM I
Which is more common, APS type 1 or 2?
2
What are the ssx of APS type 1/ 2?
Muscular weakness
Dehydration
Weight loss
Hypotension
What are the electrolyte abnormalities that can occur with Addison’s disease?
Hyponatremia
Hyperkalemia
Hypoglycemia
How do you confirm adrenal insufficiency?
Low Morning cortisol levels
What is the confirmatory test for primary adrenal insufficiency?
Cosyntropin test (synthetic ACTH)–given and if there is no increase in cortisol, then primary
What is the most common cause of Cushing’s in Infants? Children?
Infants = Adrenal tumor Children = pituitary adenoma
What are the two most common malignancies that produce ACTH?
Small cell lung carcinoma
Renal cell cancer
What lung cancer typically leads to the development of gynecomastia?
Large cell carcinoma
What is Eaton-Lambert syndrome, and what type of lung cancer can cause this?
Autoimmune attack against Ca channels–gets better with more muscle movement
SCLC
What lung cancer leads to PTHrP secretion?
Squamous cell CA
What sign/symptom of cushing’s is specific to children?
Growth retardation
What will a growth pattern plot show with Cushing’s?
Slowed height, gain in weight
How do you diagnose Cushing’s?
24 hours urine cortisol
What is the low dose dexamethasone test used to differentiate? High dose?
Low dose = if primary or secondary
High dose = Pituitary or ectopic ACTH secretion
What is the treatment for Cushing’s?
Treat the underlying cause–stop exogenous steroids, excise a tumor etc
What are the cells that a pheochromocytoma arises from?
Chromaffin cells
What are the two major areas outside of the adrenal glands where pheochromocytomas usually arise from?
Superior and inferior para-aortic regions
What are the three hereditary disorders that pheochromocytoma are usually found in? What is the genetic defect in these?
MEN2A and MEN2B
RET protooncogene
VHL
VHL tumor suppressor gene on Chr 3
What are the diseases that are associated with MEN2A? Does this have marfanoid ssx?
-Medullary thyroid cancer
-Pheochromocytoma
-Parathyroid adenoma
No marfanoid
What are the diseases that are associated with MEN2B? Does this have marfanoid ssx?
Medullary thyroid cancer
Pheochromocytoma
Mucosal neuroma
Has marfanoid
What is the primary hormone secreted by pheochromocytomas?
NE
How do you differentiate between adrenal and extra-adrenal sites of pheochromocytomas?
Extra adrenal sites only produce NE, since adrenal gland has enzyme that converts NE to epi
What are the three classical signs of a pheochromocytoma?
Episodic HA
Sweating
Tachycardia
What are the eye findings of a pheochromocytoma?
Papilledema d/t elevated ICP
What is the heart condition caused by a pheochromocytoma?
Dilated cardiomyopathy 2/2 HTN
How do you diagnose a pheochromocytoma?
24 hour urinary fractionated metanephrines and catecholamines
What is the f/u test done if a 24 hour urine tests shows elevated levels of metanephrines and catecholamines?
CT or MRI of abdomen and pelvis
What is a MIBG scan?
Iodinated form of NE that pools to areas of NE secretion
What is the drug that is used to treat a pheochromocytoma?
Alpha blocker–Phenoxybenzamine
Why alpha blockers before beta blockers with a pheochromocytoma?
If beta blocks first, then alpha will cause super HTN
