Endocrinology USMLE Step 1

what is the embryonal origin of the adrenal cortex?

mesoderm

what is the embryonal origin of the adrenal medulla? what are the cells of the adrenal medulla called?

neural crest; chromaffin cells

T/F the chromaffin cells of the adrenal cortex are are considered preganglionic

false- postganglionic and ganglionic sympathetic

what autonomic is the adrenal medulla innervated by? what are the NT? what are the receptors called? what kind of receptors are they?

sympathetic; Ach; nicotinic (N); Na+/K ligand gated channels

what are the three layers of the adrenal cortex? (in order from outside to inside) which is the biggest?

Zona Glomerulosa, Zona Fasciculata, Zona Reticularis; Zona Fasciulata

what is the regulatory control of zona glomerulosa? and what does it produce in response?

renin-angiontensin (Ang II); Aldosterone

what is the regulatory control of the zona fasciculata? and what does it produce in response?

ACTH from ant pit (CRH from Hypothalamus); corticosteroids

what is the regulatory control of the zona reticularis? and what does it produce in response?

ACTH (ant pit) and CRH (Hypothalamus); sex androgens

what is the regulatory control of the adrenal medulla? what is secreted in response?

preganglionic sympathetic fibers; catecholamines (epi, NE)

from what aa are catecholamines made?

tyrosine

what is the most common tumor of the adrenal medulla in adults?

phechromocytoma

what is the most common tumor of the adrenal medulla in children? of what kind of cells is this tumor?

neuroblastoma; post ganglionic sympathetic neurons

what oncogene is upregulated in neuroblastoma? what does the gene transcribe?

N myc; a transcription factor

what type of hypertension does a pheochromocytoma result in? neuroblastoma?

episodic hypertension; diastolic hypertension

what can you find in the urine with neuroblastoma?

HMA and VMA

what is the left adrenal gland vein drainage? right adrenal gland vein drainage? to what veins is this system similar to?

left adrenal vein--> left renal vein--> IVC;

right adrenal vein--> IVC; gonadal veins

what are the two components of the pituitary? what are there embryological derivatives? which makes the majority of the pituitary?

adenohypophysis and neurohypophysis; oral ectoderm (rathkes pouch) and neuroectoderm; adenohypophysis

what two neuropeptides do the neurohypophysis secrete? where are these neuropeptides made? where do the cells in the neurophyophysis come from?

vasopressin (ADH) and oxytocin; in the neurons in the supraoptic and paraventricular nuclei (NEUROpeptides); they are the cell bodies of neurons in the hypothalamus (one and the same!)

what are neurophysins?

carrier proteins in the posterior pituitary that carry the ADH and oxytocin hormones in circulation

what does the adenohypophysis secrete?

FSH, LH, prolactin, GH, ACTH, TSH, melanotropin

from what precursor is melanotropin made from? what else does this precursor make?

POMC; ACTH

what type of cells make up the majority of the adenohyophysis and where are they located?

somatotrophs; centrally

what hormones have a common alpha subunit? what differentiates them and how?

TSH, LH, FSH, hCG; a beta unit which determines the hormones specificity

what is the most common pituitary adenoma? what kind of cells are these?

prolactinoma; acidophils

which cells in the adenohypophysis are acidophils?

prolactin and Growth hormone producing cells

what cells in the adenohypohysis are basophils? all of these cells produce hormones with what common subunit? what is the exception?

B-FLAT: basophils- FSH, LH, ACTH, TSH; alpha; ACTH

T/F the neurohypophysis receives less blood from the hypophysial portal system than adenohypophysis

true

what are the endocrine pancreas cell types and what do they produce? how are they organized?

alpha (glucagon), beta (insulin), and somatostatin; into islets of langerhans which are collections of these cells- with beta central (INsulin INside) and alpha cells peripheral and somatostatin cells interspersed

from where do the islets arise from? and where in the pancreas are the islets most abundant?

pancreatic buds; in the tail of the pancreas

what would be the symptoms of a somatostatinoma? where would it most likely arise from?

gallbladder stones (inhibition of CCK!), achlorydia (inhibition of gastrin!) steatorrhea and constipation; from the pancreas

what would be the main symptom of an insulinoma?

hypoglycemia

what would be the main symptom of a VIPoma? where would it be located?

diarrhea, hypotension, metabolic acidosis, hypokalemia

what other cells hormones are secreted from the endocrine pancreas (other than insulin, glucagon, somatostatin)?

gastrin (gastrinoma!), VIP (vipoma!) from pancreatic polypeptide (pp) secreting cells

where is insulin made? and in response to what is it released?

beta cells; ATP from insulin independent glucose entrance into beta cells (GLUT 2) closes K+ channels and results in depolarization which opens Ca+ channels and increased intracellular Ca causes exocytosis of insulin

which tissues are insulin dependent on getting glucose? through what channel does the glucose enter?

adipose tissue and skeletal tissue; GLUT 4

what is the proinsulin hormone made of? what happens when proinsulin gets cut into insulin?

alpha and beta chain connected by disulfide bonds and a c peptide chain; c peptide gets cut off

how do you differentiate between exogenous and endogenous insulin?

exogenous wont have increased serum c peptide levels

is insulins effect an overall anabolic or catabolic effect? give examples.

anabolic; increased glycogen and protein and triglyceride synthesis and storage

what effect does insulin have on sodium in the kidneys?

causes Na+ retention

what effect does insulin have on potassium?

increases cellular uptake of potassium

are there increased or decreased amino acids in the circulation with increased insulin?

decreased (increased uptake)

which cells dont require insulin for uptake?

brain, RBCs, liver, kidney, cornea, intestine (pancreas)

what is the glucose uptake transporter in brain and RBCs?

GLUT 1

which tissues use the GLUT 2 receptor?

B islet cells, small intestine, kidney, liver

what effect does sympathetic activation have on beta cells? through what receptors?

both activate and inhibit insulin secretion; Beta and alpha respectively

what effect does insulin have on fructose 2,6 bisphosphate? how?

increases it by phosphorylating phosphofructokinase 2

what type of receptor is the insulin receptor?

a tyrosine kinase receptor that is tetrameric (2alpha and 2Beta)- with the intracellular 2 Beta part with tyrosine kinase activity

what effect does TNF alpha have on insulin? how? what is the result on insulin senstivity?

inhibits its secretion by inducing the serine kinase of beta receptor rather than the tyrosine; results in increased insulin resistance

T/F glucose is freely filtered through bowmans capsule

true

what effect do glucocorticoids and glucagon have on insulin secretion? how?

inhibit its secretion by inducing threonine phosphorylation instead of tyrosine; results in increased insulin resistance

what effect does insulin have on alpha cells?

inhibits glucagon release

what is the peroxisome proliferator activator receptor gamma? what is the result? what drugs activate this?

PPAR gamma is a nuclear receptor that is a transcription factor and alters gene transcription to iNCREASES insulin sensitivity; TZDs

T/F PPAR gamma decreases insulin sensitivity

false! increases

T/F like the brain, RBCs depend on glucose and use ketones during starvation

false only the brain does this, RBCs cant use ketones

what is IGF2? what is it important for? in what type of tumors is it produced in and what is the result?

insulin like growth factor 2; fetal development; mesenchymal tumors; hypoglycemia

from where is TRH released? what does it result in?

hypothalamus; TSH and prolactin release from adenohypophysis

from where is dopamine released? what does it result in? in what kind of receptors?

hypothalamus; prolactin release inhibition in adenohypophysis; D2

from where is CRH released? what does it result in?

hypothalamus; ACTH release from adenohypophysis

from where is GHRH released? what does it result in?

hypothalamus; Gh release from adenohypophysis

from where is somatostatin released? what does it result in?

hypothalamus; inhibition of Gh and TSH from adenohypophysis

what effect does somatostatin on TSH?

decreases its release

from where is GnRH released? and does it result in?

hypothalamus; FSH and LH release

what is the difference between GnRH and GHRH?

GnRH stimulates release of FSH and LH; GHRH stimulates release of GH

from where is prolactin released? what effect does it have on the hypothalamus?

adenohypophysis; increases dopamine synthesis and secretion from the hypothalamaus (negative feedback!) and decreased GnRH from hypothalamus

T/F dopamine is tonically inhibited by dopamine

true

when is prolactin increased?

pregnancy and brestfeeding

what is the function of prolactin?

stimulates milk production in the best, inhibits ovulation and spermatogenesis

T/F prolactin stimulates milk release from the breasts

false- oxytocin stimulates the contraction the myoepithelial cells, prolactin stimulates milk release

what is the effect of a prolactinoma on males?

not only galactorrhea but also infertility d/t decreased GnRH

other than TRH what else increases prolactin release?

estrogen (from OCPs and pregnancy)

what effect does hypothyroidism have on prolactin? gonadism?

increased prolactin and thus hypogonadism

what drugs can be used in a prolactinoma? give an example.

dopamine agonists; bromocriptine

what effect do antipsychotics and OCPs have on prolactin secretion?

dopamine antagonists and estrogens stimulate prolactin secretion

what is the first step in adrenal steroid synthesis? what enzyme is involved in this step? what activates this enzyme? deactivates it?

production of pregnelone from cholesterol via desmolase; ACTH and ketoconazole

where is aldosterone produced? beyond desmolase what enzymes are required to produce aldosterone?

in the zona glomerulosa; 21 hydroxylase and 11B hydroxylase

where are glucocorticoids produced? what enzymes beyond desmolase are required to produced them?

zona fasciculata; 17 alpha hydroxylase, 21 hydroxylase and 11beta hydroxylase

what is the direct precursor to the last step in cortisol synthesis and what enzyme is involved in this last step? what type of steroid is the precursor?

11 deoxycortisol; 11 beta hydroxylase; mineralcorticoid

what type of steroid is aldosterone? 11 deoxycortisol? testosterone and estrogen? cortisol?

mineralicorticoid; mineralicorticoid; androgen; androgen; glucocorticoid

what steroids are produces in the zona reticularis? what enzymes beyond desmolase are required to produce them? what is excreted in the urine with production of these?

androstenedione; 17 alpha hydroxylase; 17 ketosteroids

what are the fates of androstenedione and where do these changes occur?

in the adrenal cortex androstenedione is turned into testosterone and in the periphery androstenedione is turned into estrone

what are the fates of testosterone in the periphery?

via 5alpha reductase to DHT; via aromatase to estradiol

what are the three enzyme deficiencies that cause congenital bilateral adrenal hyperplasias? which is the most common? what product requires all three of these enzymes? what is two common symptoms among all three and what causes these two symptoms?

17 alpha hydroxylase, 21 hydroxylase, 11 beta hydroxylase; 21 hydroxylase deficiency; glucocorticoids; enlargement of adrenal glands due to an increase in ACTH because of low cortisol levels and hyperpigmentation because MSH (melatonin stimulating hormone) is made from the same precursor as ACTH is (POMC)

what happens to all three products of the adrenal cortex with 17 alpha hydroxylase deficiency?

decreased sex hormones, decreased cortisol, increased aldosterone

what is the main clinical presentation in 17 alpha hydroxylase deficiency?

hypertension, hypokalemia, metabolic alkalosis, decreased renin, hypoglycemia

in 17 alpha hydroxylase deficiency, how does an XY present? XX?

XY: pseduohermaphroditism (because no DHT there is female external genitalia and because of MIF presence there is no internal reprostructures); XX: "sexual infantilism": externally phenotypic female with normal internal sex organs but no secondary sexual characteristics

what happens to all three products of the adrenal cortex with deficiency of 11B hydroxylase?

decreased aldosterone, decreased cortisol, increased sex hormones

what is the main clinical presentation? how does an XY present? XX?

hypotension, metabolic acidosis, hyperkalemia, hypoglycemia, increased renin and volume depletion; XY: precocious puberty; XX: virilization (female pseudohermaphrotidism)

what happens to all three products of the adrenal cortex with deficiency of 11 beta hydroxylase?

decreased aldosterone, increased 11-deoxycortisol, decreased glucocorticoids, increased sex hormones

what is the main clinical presentation and why? how does an XY present? XX?

though decreased aldosterone there is increased 11deoxcortisol and results in hypertension, hypokalemia, metabolic alkalosis; XY: precocious puberty; XX: pseudohermaphrotidism

why do you see increased sex hormones in deficiencies of 21hydroxylase and 11B hydroxylase?

because intermediates in the zona glomerulosa and fasciculata that build up can get into reticularis via progesterone intermediates

what can happen to a newborn in 21 hydroxylase deficiency?

saltwasting can cause hypovolemic shock

in which congenital bilateral adrenal hyperplasia do you see male pseudohermaphrotidism? female pseudohermaphrotidism?

17 alpha hydroxylase deficiency; 21 hydroxylase and 11beta hydroxylase deficiencies

in which congenital bilateral adrenal hyperplasia do you see hypertension? hypotension?

17 alpha hydroxylase def and 11 beta hydroxylase deficiency; 21 hydroxylase def.

in which congenital bilateral adrenal hyperplasia do you see increased renin? decreased?

21 hydroxylase def; 17 alpha hydroxylase and 11 beta hydroxylase def

what regulates release of ACTH from the adenohypophysis? what controls this hormone?

CRH from the hypothalamus; increased cortisol levels decrease CRH release (and vice versa)

T/F in circulation cortisol is free

false- bound to corticosteroid binding globulin (CBG)

what induces secretion of corticosteroids?

chronic stress

what effect does cortisol have on blood pressure? how?

maintains blood pressure; upregulates alpha 1 receptors

what effect does cortisol on bone formation? how?

decreases bone formation by decreasing type I collagen formation

what effect does cortisol have on inflammation? how?

its antiinflammatory by inhibiting phospholipase A2