Endocrine Flashcards
Which endocrine hormones are IP3 linked? T/F: Hormones from the posterior pituitary are IP3-linked.
GGOAT "butts" you: GnRH GHRH Oxytocin ADH TRH Oxytocin / ADH are from the posterior pituitary and are IP3-linked.
Which endocrine hormones are cAMP linked? (12)
FLAT ChAMP FSH LH ACTH TSH CRH hCG ADH MSH PTH calcitonin / GHRH / glucagon too!
Hormones in the anterior pitiutary tend to be linked to which signaling pathway? Can you name 4?
cAMP. These include FSH, LH, ACTH, TSH.
Endocrine hormones which signal through steroid receptors (6):
VET3 CAP
Vitamin D, Estrogen, Testosterone, T3/T4, Cortisol, Aldosterone, Progesterone
Effect of too much SHBG in men? Too little in women?
Men: Gynecomastia with high SHBG.
Women: Hirsutism with low SHBG.
What kind of signaling path does prolactin use?
Tyrosine kinase
What kind of signaling path does oxytocin use?
IP3
What signaling path does insulin use?
Tyrosine kinase
GH is secreted from:
Anterior pituitary
Glucocorticoids are secreted from:
The adrenal cortex, zona fasciculata
Progesterone is secreted from (2):
Ovaries, placenta
Prolactin comes from the:
Anterior pituitary
Oxytocin comes from the:
Posterior pituitary
Glucagon comes from the:
Insulin comes from:
Somatostatin comes from:
Glucagon from alpha cells of pancreas
Insulin from beta cells
Somatostatin from delta cells
FSH comes from the:
Anterior pituitary
Vasopressin (ADH) comes from:
The hypothalamus (supraoptic nucleus), is stored in the posterior pituitary
TSH comes from the:
Anterior pituitary
Estradiol comes from the:
Ovaries
Estriol comes from the:
Placenta
Estrone is made by:
Fat
Lutenizing hormone comes from the:
Anterior pituitary
Mineralocorticoids / aldosterone comes from the:
Zona glomerulosa of the adrenal cortex
ACTH is excreted by the:
Anterior pituitary
This molecule is the precursor to ACTH, lipotropins, MSH, and the beta-endorphins:
Pro-opiomelanocortin
Four main causes of hyperprolactinemia:
- Pregnancy / nipple stimulation
- Stress
- Prolactinoma
- Dopamine antagonists
Where is somatostatin made?
In the GI tract, mostly D cells in gut mucosa, pancreatic delta cells make it too.
What does somatostatin do?
Inhibits secretion of GI hormones, decreases endocrine / exocrine secretion, reduces GI motility and GB contraction.
Three somatostatin analogues that are used clinically:
Octreotide
Somatostatin LAR
Lanreotide-P
In the fetus, this hormone is secreted late in gestation and is responsible for lung maturation:
Cortisol
Most common tumor of adrenal medulla in adults:
Pheo
Most common tumor of adrenal medulla in chidren:
T/F this tumor causes episodic HTN.
Neuroblastoma. Does not cause episodic HTN.
The posterior pituitary is derived from this tissue layer:
Neuroectoderm
The anterior pituitary is derived from this tissue in embryonic development:
Surface ectoderm (Rathke’s pouch)
Hormones secreted by the anterior pituitary:
FSH, LH, ACTH, TSH, prolactin, GH, MSH
There are three cell types in the islets of the pancreas. What are they, where are they, and what do they make?
a on the outside make glucagon
b on the INSide make INSulin
d are throughout and they make somatostatin
The adrenal cortex is derived from this germ layer:
Mesoderm
The adrenal medulla derives from this cell lineage:
Neural crest
Is it the L or R adrenal vein that drains directly into the IVC?
The R. The left drains into the L renal vein then to the IVC.
What are the three zones of the adrenal cortex?
Glomerulosa
Fasciculata
Reticularis
This zone of the adrenal cortex is under control of the renin-angiotensin system.
The glomerulosa, this is where aldosterone is made.
Zone of the adrenal cortex that makes cortisol:
Zona fasciculata
Where does the thyroid gland come from?
Floor of the pharynx, it descends into the neck and leaves behind the foramen cecum = remnant of the thyroglossal duct.
The hypothalamus releases this hormone to stimulate prolactin release. What other hormone is stimulated by this substance?
TRH causes prolactin and TSH release from the anterior pituitary
This molecule released from the hypothalamus causes ACTH, MSH, and b-endorphin release from the anterior pituitary:
CRH
This hormone inhibits GH release from the anterior pituitary:
Somatostatin
Somatostatin inhibits these two hormones:
GH, TSH
What happens if you give someone a good whopping dose of GnRH?
GnRH in a steady dose will inhibit LH and FSH. It is PULSATILE secretion that drives FSH and LH production.
What effect does prolactin have on GnRH?
Inhibits its release
ACTH is released from the anterior pituitary in response to two major things:
- CRH from the hypothalamus
2. Stress
T/F: You would measure growth hormone levels to dx acromegaly.
F. Measure IGF-1.
T/F: GH increases insulin resistance.
T
Two things inhibit the secretion of growth hormone:
Somatostatin
Glucose
5 main effects of cortisol on the body:
- Maintains BP (increase in a1 receptors)
- Decreases bone formation
- Anti-inflammatory
- Insulin resistance
- Increases energy release (gluconeogenesis, lipolysis, proteolysis)
Primary adrenal insufficiency is defined as decrease in cortisol secondary to what kind of difficulty?
Secondary and tertiary, where are they?
Primary adrenal insufficiency = problem with the adrenal gland itself.
Secondary = problem with the pituitary.
Tertiary = problem with the hypothalamus.
How is iodine transported into cells?
Sodium gradient is used to drive it in.
This hormone binds most of the thyroid hormone in the blood:
Thyroxine-binding globulin
When would you see TBG decreased? Increased?
TBG is decreased in hepatic failure, increased in pregnancy and OCP use (estrogen upregulates it).
The enzyme that converts T4 -> T3:
5’ deiodonase
This drug works both to inhibit thyroid synthesis and to inhibit the conversion of T4 to T3:
Propylthiouracil
This anti-thyroid drug works only to inhibit the conversion of one thyroid hormone precursor to another. What is the enzyme this drug inhibits? The other drug that has the same effect?
Methimazole inhibits peroxidase, PTU works here too.
If you give someone a crazy excess of I2 you may see a paradoxical decrease in T4 production. What is this effect called?
Wolff-Chaikoff effect
This thyroid hormone feeds back to the anterior pituitary to cause a decrease in sensitivity to TRH:
T3
Thyroid hormone upregulates which adrenergic receptors?
b1, responsible for increase in cardiac contractility, HR, and stroke volume.
What hormone is elevated in Cushing syndrome?
Cortisol
What is Cushing disease?
Hypercortisol state 2/2 pituitary adenoma (ACTH-secreting pituitary tumor)
Second most common cause of Cushing syndrome:
Ha! Trick question!
Most common: Iatrogenic
Second: Pituitary adenoma
Third: Ectopic ACTH-producing tumor
Dexamethasone suppression test: In what case will a low dose of dex suppress cortisol? A high dose? When will there be no suppression?
Low dose suppresses a normal pituitary.
High dose suppresses a pituitary tumor.
Failure to suppress = the thing makes what it wants anyway without any input, ie it is an ectopic source of ACTH (lung CA) or an adrenal tumor making cortisol directly.
How do you tell an ectopic ACTH-producing tumor from an adrenal tumor making cortisol?
The ectopic tumor (usually small cell lung CA, bronchial carcinoid) will make ACTH. The adrenal tumor doesn’t.
What hormone is affected in Conn syndrome?
Conn syndrome = primary hyperaldosteronism
What is primary hyperaldosteronism caused by?
Secondary?
Primary hyperaldo = Conn syndrome = adrenal problem.
Secondary hyperaldo = overactivity of the RAA system (such as one kidney receiving low blood flow and flooding the system with renin)
T/F: Conn syndrome is associated with high plasma renin.
F. Renin is low, kidneys know they are getting enough blood and that there is HTN. Renin is high in secondary hyperaldosteronism.
Tx for Conn syndrome:
- Remove tumor
2. Spironolactone or epleronone (K+ sparing)
Hypertension / salt retention, low potassium, met. alkalosis… first thing that should come to mind:
Hyperaldosteronism
What effect should a rise in serum potassium have on aldosterone?
Should stimulate it, want to dump the K+
Hormone affected in Addison disease:
Aldosterone and cortisol
Most common cause of Addison disease:
Autoimmunity
T/F: The medulla of the adrenal gland is affected in Addison disease:
F. All three layers of the cortex get hit, but the medulla is untouched.
What is secondary adrenal insufficiency?
Secondary adrenal insufficiency occurs at the level of the pituitary.
In which case of adrenal insufficiency – primary or secondary – would you see skin hyperpigmentation and why?
Primary = problem with the gland = pituitary making loads of ACTH = POMC activation and MSH made = skin hyperpigmentation. Secondary = pitutary failure, no ACTH, no skin pigmentation.
What is tertiary adrenal insufficiency, and what usually causes it?
Tertiary adrenal insufficiency = HTH thinking there is still cortisol when there is not, ie in cases of steroid w/d that are too abrupt. HTH will make no CRH, so the pituitary will make no ACTH, so you get no cortisol / aldo. Need to taper.
Metabolic abnormalities in Addison disease:
Hyponatremic volume contraction, hyperkalemia, acidosis.
In secondary adrenal insufficency, do you see hyperkalemia?
No! There is no ACTH, but your adrenals still make aldosterone, so salt / H2O / K+ balance is normal.
With what three syndromes are pheochromocytomas associated?
NF-1
MEN-2A
MEN-2B
Medical treatment of a pheo prior to surgical removal?
a-block first: Phenoxybenzamine or phentolamine, then follow with b-block. Don’t want to b-block first, you leave Epi unopposed in the body to hit a1 receptors and cause through the roof HTN.
Pheochromocytomas can secrete epo. Three other tumors that do this:
Renal cell CA
Hemangioblastoma
Hepatocellular carcinoma
Most common tumor of adrenal medulla in adults? Kids?
Pheo in adults, adrenal neuroblastoma in kids.
Which oncogene is implcated in adrenal neuroblastoma?
N-myc
T/F: A pheo can calcify
T. Rule of 10’s:
10% calcified, malignant, bilateral, extra-adrenal, and 10% in kids.
HLA associated with Hashimoto thyroiditis (2):
HLA-DR5
HLA-B5
Endocrine disease that is a risk for B cell lymphoma:
Hashimoto
Severe fetal hypothyroidism, 5 Ps in addition to the mental retardation and FTT:
Pot-bellied Pale Protrubent tongue Puffy-faced Protruding umbilicus
HLA type associated with de Quervain’s thyroiditis:
HLA B35
What is Reidel’s thyroiditis? What do you see in there histologically?
Replacement of the thyroid with fibrous tissue. See macrophages and eosinophils in fibrous base.
Name for what happens when you give someone with a goiter or excess thyroid tissue who is iodine deficient a ton of iodine suddenly:
Jod-Basedow thyrotoxicosis
Three things that can cause Jod-Basedow:
Amiodarone
Contrast
Ppl w/ Graves who are iodine deficient getting iodine suddenly
Which anti-thyroid agent is preferred in pregnancy?
PTU. Methymazole causes fetal cutis aplasia.
Both PTU and methimazole cause this problem with WBCs:
Agranulocytosis
T/F: PTU, the preferred anti-thyroid drug in pregnancy, crosses the placenta:
T.
Tx for thyroid storm:
b-block aggressively, PTU
Autoimmune thyroid disease with thyroid stimulating Ab? With thyroid destruction?
Graves, Hashimoto
HLA subtypes associated with Graves disease:
HLA DR3
HLA B8
Most common thyroid cancer:
Papillary
Thyroid cancers with RET mutations:
Papillary, medullary
Thyroid cancer with Ras mutation:
Papillary
Thyroid cancer that likes to spread hematogenously:
Follicular
Sheets of cells in an amyloid base, hyperthyroidism:
Medullary thyroid CA
Disease in which you see an increased resin radioactive T3 uptake:
Graves. TBG is all occupied by endogenous thyroid hormone, give people a radiolabeled one and everything you give them will bind your test resin.
This teratoma has functional thyroid tissue:
Struma ovarii teratoma
Treatment for acromegaly:
Resect pituitary if you can
Octreotide or other somatostatin analogue
Three ways of diagnosing acromegaly:
- High serum IGF-1
- Fail to suppress GH with oral glucose
- Mass on MRI
What is Sheehan’s syndrome?
Postpartum bleeding drops BP so much that the pituitary gets damaged, can be any hormone affected. Most commonly presents with failure to lactate.
GH excess is called _____ in adults but is called _____ in children.
Acromegaly
Gigantism
Common presentation of MEN 1:
Renal stones (hyper PT) Ulcers in the stomach (ZE or another pancreatic endocrine tumor)
MEN 1 tumors:
Parathyroid
Pituitary
Pancreatic endocrine
MEN 2A and 2B tumors:
Medullary thyroid cancer & pheo in both.
2A = parathyroid
2B = mucosal neuromas, marfanoid habitus
MEN associated with 11q13
MEN 1
MEN syndromes associated with a problem on chromosome 10:
MEN 2 (RET)
What form of inheritance do all the MEN syndromes share?
Autosomal dominant
Glucocorticoid medication that is virtually the same molecule as cortisol:
Hydrocortisone
This drug is used in the treatment of aldosterone deficiency. Why?
Fludracortisone.
This drug has the highest mineralocorticoid effect of all the glucocorticoids.
How do the glucocorticoids work to decrease the production of leukotrienes and prostaglandins?
They block phospholipase A2 and inhibit COX-2.
T/F: Empty sella syndrome is most often sub-clinical.
T, usually there is some pituitary tissue glued to the sella somewhere. Can present with any deficiency.
These hormones share a common alpha sub-unit:
TSH, LH, FSH, b-HCG
Think pregnancy
This hormone increases blood glucose level and decreases protein synthesis:
Cortisol
These two cancers are associated with RET gene mutations:
MEN 2
Medullary thyroid cancer
Four clinical uses for somatostatin:
Inhibits GH, TSH, ACTH
Decreases sphlancnic circ. (can help control bleeding)
Tones down GI endocrine excess
Can be used for refractory diarrhea
Thyroid cancer associated with RAS or PAX8-PPAR gamma:
Follicular
Thyroid cancer associated with RET or NTRK1:
Papillary thyroid CA
Thyroid cancer associated with BRAF:
Papillary
Starting molecule for steroid synthesis:
Cholesterol
Cholesterol is converted to pregnolone, first step of steroid synthesis, by this enzyme. What drug inhibits this enzyme?
Desmolase
Ketoconazole inhibits desmolase
From pregnenolone, in order to make aldosterone, you need to first make this molecule. What is the enzyme?
To get to mineralocorticoids, you make progesterone with 3b-OH dehydrogenase.
What is the one arm of the steroid synthesis path that does not require 17a-hydroxylase?
Synthesis of mineralocorticoids, eg aldosterone.
What is the one arm of the steroid synthesis path that does not require 21-hydroxylase?
Synthesis of sex hormones.
Precursor molecule to the synthesis of sex hormones:
DHEA, which is made into androstenedione.
What is the main difference between 21-hydroxylase and 11b-hydroxylase deficiency?
The paths are really very close together. 11b-hydroxylase acts a little later in the path, so you get one extra product backing up. This product is 11-deoxycorticosterone, which causes HTN. Both syndromes = high sex hormones, 11b also has HTN.
Mnemonic involving 1’s for adrenal steroid synthesis:
1 in the first digit = HTN
1 in the second digit = masculinization
What would a male with 17a-hydroxylase deficiency look like? A female? Why?
17a-hydroxylase needed everywhere but the path that makes aldosterone, so you have no sex hormones. The little boy will have testes but ambiguous genitalia (no testosterone around). A little girl will look normal until puberty, at which point she will not develop secondary sex chars.
