Term
| Describe the basic anatomy of the adrenal gland. |
|
Definition
Cortex (mesoderm) and Medulla (Neural crest)
Capsule
1) Cortex
- Zona gomerulosa (aldosterone)
- Zona fasciculata (Cortisol and sex hormones)
- Zona reticulata (Androgens)
2) Medulla
- Chromaffin cells producing Catecholamines (Epi, NE) |
|
|
Term
What are the primary and secondary regulatory mechanisms of each of the following adrenal regions?
1) Zona fasciculata
2) Medullary chromaffin cells
3) Zona reticularis
4) Zona glomerulosa |
|
Definition
GFR corresponds with Salt (Na+), Sugar (glucocorticoids) and Sex (androgens)
1) ACTH (pituitary) and CRH (hypothalamic)
- Makes cortisol and sex hormones
2) Pre-ganglionic sympathetic fibers
- Makes Catecholamines (NE and Epi)
3) ACTH (pituitary) and CRH (hypothalamus)
- Androgens
4) RAAS
- Makes Aldosterone (ENaC insertion and occupancy in distal nephron) |
|
|
Term
| What tumors arise in the adrenal gland? |
|
Definition
1) Pheochromocytoma (most common tumor of medulla in kids)
- Episodic HTN
2) Neuroblastoma (kids)
- No episodic HTN |
|
|
Term
| Describe the basic development of the fetal adrenal gland. |
|
Definition
Outer adult zone and inner active fetal zone
- Adult zone dormant until late gestation, when it secrtes cortisol
- Adult zone cortisol release controlled by ACTH and CRH from fetal pituitary and placenta
**responsible for fetal lung maturation and surfactant production** |
|
|
Term
| Why might you give a pregnant woman glucocorticoids to prevent RDS? |
|
Definition
| Cortisol is critical for fetal lung maturation and surfactant production. |
|
|
Term
| What is the venous drainage of the adrenal glands? |
|
Definition
Same as left and right gonadal veins, where left vein drains through renal vein before IVC, but right does not.
1) Left drains to left adrenal vein.....left renal vein.....IVC
2) Right drains to right adrenal vein.....IVC |
|
|
Term
| What hormones are made in the anterior and posterior pituitary, respectively? |
|
Definition
Acidophils- GH, prolactin
Basophils: B-FLAT (FSH, LH, ACTH, TH)
1) Adenohypophysis (Oral ectoderm- Rathke's pouch)
- peptide (ACTH, GH, ProL)- common alpha subunit
- glycoprotein (TSH, LH, FSH)
2) Neurohypophysis (Neuro-ectoderm)
- ADH (PVN and SON)
- Oxytocin (SON) |
|
|
Term
| What are the functions of the major glycoprotein hormones produced by the anterior pituitary? |
|
Definition
Common alpha sub-unit, with beta sub-unit determining hormone specificity.
All are Basophils: B-FLAT (FSH, LH, ACTH, TH)
1) FSH- growth of reproductive system
2) LH- Sex hormone production
3) TSH- Thyroid hormone production |
|
|
Term
| What are the major peptide hormones of the anterior pituitary? |
|
Definition
Acidophils: GH and prolactin
Basophils: B-FLAT (FSH, LH, ACTH, TSH)
1) GH (stim by GRH)
2) Prolactin (stim by Dopamine)
3) ACTH (stim by CRH) |
|
|
Term
| What are the major cell types of the endocrine pancreas and what are their products? |
|
Definition
Islets of langerhans
1) Alpha- Glucagon (Peripheral)
2) Beta- Insulin (Central) INSulin INSide
3) Delta- Somatostatin (interspersed) |
|
|
Term
| What organs do NOT require Insulin for glucose uptake? |
|
Definition
BRICK L
Brain, RBCs, Intesine, Cornea, Kidney, Liver |
|
|
Term
| How is insulin secretion regulated and are its effects? |
|
Definition
1) Secretion
- Stimulated by hyperglycemia, GH, beta agonists
- Inhibited by Cortisol, Somatostatin (delta cells) and alpha-2 blockers
Released by B-cells in islets of langerhans in response to ATP from glucose metabolism closing K+ channels and depolarizing cells.
2) Effects
- Required for adipose and skeletal muscle uptake of glucose (EXCEPT BRICK-L)
- Inhibits glucagon release from alpha-cells |
|
|
Term
| What are the major effects of insulin? |
|
Definition
Anabolic
1) Increase glucose transport in skeletal MM and adipose (GLUT-4)
2) Increase glycogen synthesis and storage
3) Increase TG synthesis and storage
4) Increase Na+ retention (kidney)
5) Increase protein synthesis (muscle)
6) Increase cellular uptake of K+ and amino acids |
|
|
Term
Which of the following is NOT a major effect of insulin signaling?
1) K+ uptake
2) Amino acid uptake
3) Glucose uptake into skeletal muscle and adipose
4) Sodium excretion by kidneys
5) Increased triglyceride synthesis and storage
6) Increased glycogen synthesis |
|
Definition
4- Insulin causes Na+ retention by kidney (maintain water)
Released in response to hyperglycemia, beta agonists and GH, via ATP-mediated K+ channel closure and membrane depolarization. |
|
|
Term
Which of the following inhibits insulin release?
1) Growth hormone
2) Hyperglycemia
3) Beta agonists
4) Cortisol |
|
Definition
| 4- Cortisol, hypoglycemia, alpha 2 agonists and somatostatin inhibit insulin release from beta cells. |
|
|
Term
| How can you tell between a patient with an insulinoma and someone who is over-injecting insulin? |
|
Definition
Look at serum C-peptide levels. If it is high, you have an insulinoma
C-peptide is not present with exogenous insulin intake (proinsulin-----insulin + C-peptide) |
|
|
Term
What is the function of each of the following glucose transporters? What will a beta agonist do to each of their activity?
1) GLUT-1
2) GLUT-2
3) GLUT-4 |
|
Definition
Beta agonists increase insulin, so only insulin sensitive channels will be affected.
1) RBCs and brain
- Nothing
2) Bidirectional transport in Beta islet cells, liver, kidney and small intestine
- Nothing
3) Insulin responsive channels in adipose and skeletal muscle
- Increased uptake |
|
|
Term
| Describe how Insulin is released from pancreatic beta cells and how it causes glucose uptake in skeletal muscle and adipose cells. |
|
Definition
1) Glucose uptake
- Glucose is taken up by beta cells via GLUT-2 channels, where it undergoes glycolysis
2) Membrane depolarization (beta cell)
- Beta cell metabolism produces ATP, which causes K+ channels on cell membrane to close, resulting in membrane DEPOLARIZATION
- This also occurs with Epi or Glucagon stimulation, but via AC activaiton and increased cAMP and opens voltage gated Ca2+ channels
3) Insulin release
- Released from granules and enters circulation, traveling to muscle and fat, where it binds TK receptor
4) Insulin effect
- Tyrosine phosphorylation activates P13K and RAS/MAPK pathways
- P13K produces glycogen, lipid and protein synthesis and delivers GLUT-4 to membrane for glucose uptake
- RAS/MAPK causes cells growth and DNA synthesis |
|
|
Term
| What are the insulin dependent organs? |
|
Definition
Those that express GLUT-4- Skeletal muscle and adipose
Brain and RBCs have GLUT-1, which is independent of glucose.
Brain uses ketone bodies in starvation, but RBCs always need glucose, because they have no mitochondria. |
|
|
Term
| What is glucagon and what are its major effects? |
|
Definition
Peptide made by alpha islet cells and secreted in response to hypoglycemia (inhibited by insulin, hyperglycemia and somatostatin).
1) Glycogenolysis, gluconeogenesis
2) Lipolysis and ketone production
3) Stimulation of insulin release |
|
|
Term
What is the action of each of the following hormones in HPA axis regulation?
1) TRH
2) Dopamine
3) CRH
4) GHRH
5) Somatostatin
6) GnRH
7) Prolactin |
|
Definition
1) Stimulates TSH and prolactin production
2) Inhibits prolactin
3) Stimulates ACTH
4) Stimulates GH
5) Inhibits GH and TSH
6) Stimulates FSH and LH
7) Inhibits GnRH |
|
|
Term
| Describe the regulation and function of prolactin |
|
Definition
1) Regulation
- tonic dopamine inhibition from hypothalamus
- stimulated by TRH
- release increases dopamine synthesis (feedback)
2) Function
- stimulates milk production in breast
- inhibits ovulation (in females) and spermatogenesis (males) by inhibiting GnRH synthesis and release. |
|
|
Term
| Why might you use Bromocriptine in a patient with prolactinemia? |
|
Definition
Inhibits ovulation (females) and spermatogenesis (males)
- Dopamine agonist increases tonic inhibitory tone from hypothalamus to prevent release
- Anti-psychotic would have the opposite effect |
|
|
Term
| Why might a patient taking an anti-psychotic medication become impotent? |
|
Definition
| Anti-dopamine effects release hypothalamic inhibition of prolactin, causing prolactinemia, which inhibits spermatogenesis. |
|
|
Term
| How estrogens (OCPs, pregnancy) inhibit ovulation? |
|
Definition
| Stimulate prolactin secretion, which inhibits GnRH from hypothalamus and inhibits ovulation. |
|
|
Term
| Describe the regulation and function of growth hormone |
|
Definition
Acipophillic peptide hormone released by anterior pituitary in response to GHRH from hypothalamus
1) Regulation
- Secreted in pulses in response to GHRH, exercise and sleep
- Inhibited by glucose and somatostatin
2) Function
- Stimulates linear growth and muscle mass through somatomedin secretion
- Increased insulin resistance (diabetogenic) |
|
|
Term
| What is the most common cause of acromegaly? |
|
Definition
Pituitary adenoma producing growth hormone.
- Too much somatomedin with linear growth (unless epiphyses have already fused, then horizontal)
- Insulin-resistance (Type II DM) |
|
|
Term
What is the function of each of the following enzymes?
1) 17-alpha hydroxylase
2) 3-beta HSDH
3) 21-hydroxylase
4) 11-beta hydroxylase
5) Aldosterone synthase
6) Aromatase
7) 5-alpha reductase |
|
Definition
All involved in adrenal steroid synthesis (Stimulated by ACTH and inhibited by Ketoconazole)
Start from cholesterol, which (via Desmolase) becomes Pregnenolone.
1) Converts pregnenolone to 17-hydroxypregnenolone, which becomes either DHEA (testoterone and estrogen path) or 17-hydroxyprogesterone (cortisol path).
2) Converts Pregnenolone to Progesterone , 17-hydroxypregnenolone to 17 hydroxyprogesterone, and DHEA to Andostenedione
3) Converts progesterone to 11-deoxycorticosterone (aldosterone) and 17-hydroxyprogesterone to 11-deoxycortisol (Cortisol)
4) Converts 11-deoxycorticosterone to Corticosterone (aldosterone) and 11-deoxycortisol to Cortisol
5) Converts Corticosterone to Aldosterone in the zona glomerulosa
6) Converts Testosterone (from Androstenedione) to Estradiol in the periphery
7) Converts testosterone to DHT in the zona reticularis |
|
|
Term
What happens to the synthesis of mineralocorticoids, cortisol and sex hormones in response to each of the following?
1) 17-alpha hydroxylase deficiency
2) 21-hydroxylase deficiency
3) 11-beta hydroxylase deficiency |
|
Definition
Congenital bilateral adrenal hyperplasias (all have enlargement from ACTH because of low cortisol
1) Enzyme that converts Pregnenolone to 17-hydroxypregnenolone
- More pregnenolone will go Aldosterone route
- Less goes towards Cortisol and Sex hormones
- Get HYPERtension, hypokalemia form hyperaldosteronism
2) Enzyme that converts progesterone to 11-deoxycorticosterone (aldosterone) and 17-hydroxyprogesterone to 11-deoxycortisol (cortisol).
- Lose Aldosterone and Cortisol
- Gain sex hormones (more goes towards androstenedione)
- HYPOtension, hyperkalemia, increased renin and volume depletion.
3) Enzyme that converts 11-deoxycorticosterone to corticosterone (aldosterone) and 11-deoxycortisol to cortisol (cortisol)
- Low aldosterone and cortisol
- Elevated sex hormones and 11-deoxycorticosterone
- HYPERtension (11-deoxycorticosterone is mineralocorticoid) |
|
|
Term
| Which congenital bilateral adrenal hyperplasia present with masculinzation? |
|
Definition
Those that increase sex hormones
1) 21-hydroxylase deficiency
- Hypotension (low aldosterone)
2) 11-b hydroxylase deficiency
- Hypertension (low aldosterone but high 11-deoxycorticosterone |
|
|
Term
Describe how a female might present with 17-a hydroxylase deficiency.
How would this differ in a male? |
|
Definition
Increased Aldosterone, but low cortisol and sex hormones, producing hypertension, hypokalemia
1) Female- externally phenotypic female, with normal internal sex organs, but NO secondary sex characteristics
2) Male- Low DHT: Pseudohermaphroditism (phenotypic female, no internal reproductive structures due to MIF) |
|
|
Term
| What is the most common form of congenital bilateral adrenal hyperplasia and how does it present? |
|
Definition
21-hydroxylase deficiency: Low aldo, low cortisol, high sex hormones
Hypotension (aldo), Hyperkalemia (aldo), Increased renin (aldo), Volume depletion (aldo)
Masculinzation and female pseudohermaphroditism |
|
|
Term
| Why do patients with 11-beta hydroxylase deficiency get hypertension and those with 21-hydroxylase deficiency get hypotension, despite the fact that BOTH have low aldosterone levels? |
|
Definition
11-beta hydroxylase deficiency hits later in the pathway and causes a buildup of 11-deoxycorticosterone, which acts as a mineralocorticoid.
21-hydroxylase deficiency would build up progesterone, which would just go to the sex steroid pathway. |
|
|
Term
| Describe the regulation and function of Cortisol. |
|
Definition
1) Regulation
- Produced in adrenal zona fasciulata in response to ACTH (stimulated by CRH from hypothalamus) and travels in blood bound to CBG
2) Function- BBIIG
- Blood pressure (up-regulates alpha 1 receptors)
- decrease Bone formation
- anti-Inflammatory/immunosuppressive
- Insulin resistance (diabetogenic)
- Gluconeogenesis, lipolysis, proteolysis. |
|
|
Term
| What are the anti-inflammatory/immunosuppressive actions of cortisol? |
|
Definition
1) Inhibits production of LCT and PGE
2) Inhibits leukocyte adhesion (neutrophilia)
3) Blocks histamine release from mast cells
4) Reduces eosinophils
5) Blocks IL-2 production. |
|
|
Term
Which of the following is NOT caused by cortisol?
1) Decreased IL-2 production
2) Reduced histamine release from mast cells
3) Reduced eosinophils
4) Inhibition of LCT and PGE
5) Neutropenia
6) Decreased leukocyte adhesion |
|
Definition
5- Without leukocyte adhesion, neutrophils are left in blood causing neutroPHILIA
IL-2 (T cells), Eosinophils, Mast cells, LCT/PGE and Leukocyte adhesion are all disturbed |
|
|
Term
Which of the following is NOT caused by cortisol?
1) Bone growth
2) Increased BP
3) Anti-inflammatory effects
4) Insulin resistence
5) Gluconeogenesis |
|
Definition
1- Decreased bone growth
All others are true
BP through alpha-1 receptor synthesis
Anti-inflamation (IL-2 suppression, block PGE/LCT, ect.)
Insulin resistance (diabetogenic)
Gluconeogenesis, lipolysis and proteolysis |
|
|
Term
Which of the following is not a result of increased PTH?
1) Increased bone resorption of calcium and phosphate
2) Decreased kidney reabsorption of phosphate
3) Decreased kidney reabsorption of calcium
4) Increased 1,25 (OH)2 vitamin D (calcitriol) |
|
Definition
3- Kidney reabsorption of calcium in DCT increases
PTH, secreted from chief cells in parathyroid, increases serum Ca2+, decreases serum PO4 and increases urine PO4
1) Increases bone turnover
2) Increases PO4 excretion
4) PTH increases Calcitriol production by stimulating 1-alpha hydroxylase in kidney, which increases intestinal calcium reabsorption. |
|
|
Term
| How does PTH stimulate bone resorption? |
|
Definition
| Increases production of M-CSF and RANK-L in osteoBLASTS, stimulating osteoCLASTS |
|
|
Term
| How is PTH release regulated by calcium and magnesium? |
|
Definition
PTH= phosphate trashing hormone
1) Calcium
- low serum calcium causes secretion from parathyroid chief cells
2) Magnesium does the same.
- low Mg causes include diarrhea, aminoglycosides, diuretics and alcohol abuse. |
|
|
Term
| How does the body compensate for hypophosphatemia? |
|
Definition
| Kidney produces 1-alpha hydroxylase to convert 25-OH-vitamin D to Calcitrol, which increases intestinal phosphate reabsorption and releases phosphate from bone matrix. |
|
|
Term
| Why might a patient suffering from Giardiasis have poor bone strength? |
|
Definition
| Diarrhea causes Mg2+ losses, which stimulates PTH release and bone reabsorption to maintain Mg2+ and Ca2+ serum levels. |
|
|
Term
| Describe the basic pathway of vitamin D metabolism and how it functions. |
|
Definition
Activation stimulated by PTH, low Ca2+ and low phosphate
Inhibited by high Calcitrol levels
1) Metabolism
- Vitamin D3 from sun exposure and D2 from plants
- D3 ad D2 converted to 25-OH D in liver
- 25-OH D converted to Calcitrol in kidney (1-alpha hydroxylase)
2) Function
- Calcitrol increases dietary calcium and phosphate absorption in intestine.
- Increases bone resorption of Ca2+ and phosphate |
|
|
Term
| What is 24,25-OH2 vitamin D- inactive form of vitamin D |
|
Definition
|
|
Term
| How does the action of PTH differ from that of 1,25-OH2 vitamin D on bone? |
|
Definition
1) PTH increases Ca2+ reabsorption and PO4 excretion
2) Calcitrol increases absorption of BOTH in intestine |
|
|
Term
| Where is Calcitonin produced and what does it do? |
|
Definition
1) Parafollicular cells (C cells) of thyroid (vs. chief cells of parathyroid for PTH).
2) Opposes PTH action, but not normally relevant.
- Decreases bone resorption of calcium when Ca2+ is high |
|
|
Term
| Which endocrine hormones exert their action via cAMP? |
|
Definition
FLAT CHAMP
FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2), MSH, PTH
also, calcitonin, GHRH and glucagon. |
|
|
Term
| Which endocrine hormones act via cGMP? |
|
Definition
Vasodilators
ANP, NO (EDRF) |
|
|
Term
| Which endocrine hormones act via IP3? |
|
Definition
GOAT
GnRH, Oxytocin, ADH (V1), TRH
Also, histamine (H1), angiotensin II, gastrin |
|
|
Term
Which of the following hormones does NOT act via IP3?
1) GnRH
2) hCG
3) ADH
4) TRH
5) Oxytocin |
|
Definition
2- hCG works via cAMP
**ADH only utilizes IP3 when acting through the V1 receptor**
IP3= GOAT
GnRH, Ocytocin, ADH (V1), TRH
cAMP= FLAT CHAMP
FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2), MSH, PTH |
|
|
Term
| Which endocrine hormones act via cytosolic steroid receptors? |
|
Definition
VET CAP (adrenal hormones + vitamin D)
Vitamin D, Estrogen, Testosterone, Cortisol, Aldosterone, Progesterone
Only nuclear receptor-mediated action is T3/T4 |
|
|
Term
Which of the following hormones does NOT work through cytosolic steroid receptors?
1) T3/T4
2) Progesterone
3) Estrogen
4) Aldosterone
5) Vitamin D
6) Cortisol |
|
Definition
1- T3/T4 works via nuclear steroid receptors
Cytosolic steroid receptors= Adrenal hormones + vit D
VET CAP
Vitamin D, Estrogen, Testosterone, Cortisol, Aldosterone, Progesterone |
|
|
Term
Which of the following does NOT act through intrinsic tyrosine kinase/MAPK pathway?
1) IGF-1
2) T3/T4
3) FGF
4) PDGF
5) Insulin |
|
Definition
2- T3/T4 acts through nuclear steroid hormone receptor
- Receptor binding activates P13K or RAS/MAPK pathways
For TK/MAPK, think Growth Factors
- Insulin, IGF-1, FGF, PDGF |
|
|
Term
| Which endocrine hormones act via receptor-associated tryosine kinase (JAK/STAT) pathways? |
|
Definition
JAK-STAT Pathway
- Receptor-binding leads to auto-phosphorylation of JAK. - STAT binds pJAK and is phosphorylated.
- pSTAT binds a second pSTAT and dimer migrates to nucleus and binds genes
PiG
Prolactin, GH, cytokines (IL-2, IL-6, IL-8) |
|
|
Term
Name the signaling pathway through which each of the following hormones acts.
1) TSH
2) TRH
3) GnRH
4) IGF-1
5) Prolactin
6) ANP
7) Vitamin D |
|
Definition
1) cAMP (FLAT CHAMP)
2) IP3 (GOAT)
3) IP3 (GOAT)
4) Intrinsic TK (growth factors and insulin)
5) RTK (JAK/STAT)- PiG
6) cGMP (vasodilators)
7) Cytosolic steroid hormone receptor (D + adrenals) |
|
|
Term
| What effect might increased sex-hormone-binding globulin (SHBG) have on men and when might this happen? |
|
Definition
Hyperthyroidism, Anorexia, Drugs
Gynecomastia- decreased free testosterone
Steroid hormones are lipophilic and carried by binding globulins.
If you increase SHBG, then free hormone levels decrease. |
|
|
Term
| What effect might decreased sex-hormone-binding globulin (SHBG) have on women and when might this happen? |
|
Definition
SHGB increase during pregnancy
SHGB decrease from steroids, polycystic ovary syndrome, hypothyroidism, diabetes, obesity, cushing's syndrome, and acromegaly
Raises free testosterone= Hirsutism |
|
|
Term
| Why does a woman with hypothyroidism sometimes get hirsutism? |
|
Definition
Decreased synthesis of SHBG leads to increased free testosterone levels.
Also caused by anabolic steroids, polycystic ovarian syndrome, cushings (cortisol) and acromegaly (GH) |
|
|
Term
| Where is T3 produced and what are its major functions? (hint, 4 B's) |
|
Definition
1) Produced in cytoplasm of cells.
2) Functions
- Brain maturation
- Bone growth (synergism with GH)
- Beta-adrenergic effects (increase B1 in heart)
- BMR increases (Increase Na/K ATPase activity increasing O2 consumption, RR, and body temperature
Also increases glycogenolysis, gluconeogenesis and lipolsyis (opposite of Insulin) |
|
|
Term
Which of the following is NOT a major effect of T3?
1) Bone growth
2) Increased BMR
3) Decreased MAP
4) Increased Gluconeogenesis and Glycogenolysis
5) CNS maturation |
|
Definition
Binds nuclear steroid hormone receptor
3- T3 increases B1 receptors in heart, which increases HR, CO, SV and contractility. MAP= CO X HR, so it should increase.
1) Bone growth (synergistic with GH)
2) BMR (Increased Na/K ATPase with increased O2 consumption, RR and body temperature)
4) Opposes insulin effects
5) Critical |
|
|
Term
Why might you see each of the following?
1) Low Thyroxine-binding globulin
2) Increased Thyroxine-binding globulin |
|
Definition
1) Decreased in cirrhosis/hepatic failure
2) Increased in pregnancy and OCP use (estrogen increases TBG) |
|
|
Term
| How is T3/T4 release regulated? What is the Wolff-Chaikoff effect? |
|
Definition
Iodine-containing hormones released from follicular cells
- TRH (hypothalamus) stimulates TSH secretion (pituitary), which stimulates follicular cells (cAMP-mediated)- normal negative feedback
- Wolff-Chaikoff effects is transient decrease in T3/T4 with excess iodide ingestion, which inhibits thyroid peroxidase (oxidation/organification/coupling) |
|
|
Term
| How are T3/T4 synthesized and released from follicular cells of the thyroid? |
|
Definition
1) Synthesis
- Iodide is taken up from blood via basolateral Na+/I- symporter (secondary active transport) and enters colloid through apical membrane (Pentrad transporter)
- Oxidation and Organification: I is oxidized to I2 by thyroperoxidase and added to tyrosil groups on Thyroglobulin secreted from ER (forming MIT and DIT)
- Coupling/folding of MIT and DIT occurs
2) Release
- TSH binds Gs on follicular cell membrane leads to cAMP-mediated internalization of colloid vesicle containing MIT/DIT
- vesicles fuse with lysosomes, and lysozyme and protease cleaves i-TG to T4 (which becomes T3 via deiodinase)
- Released via exocytosis |
|
|
Term
| How do Propylthiouracil and Methimazole act on the thyroid? |
|
Definition
1) Propylthiouracil
- Inhibits thyroid peroxydase and 5' deiodinase, preventing oxidation/organification and T3 activation (from T4), respectively
2) Methimazole
- Inhibits thyroid peroxidase only, prevening oxidation/organification |
|
|
Term
| What are the major exogenous and endogenous causes of Cushing's Syndrome? |
|
Definition
Excess cortisol
1) Exogenous- #1 Steroids (see decreased ACTH)
2) Endogenous (Pituitary adenoma most common)
- Cushing's disease (70%)- ACTH-secreting pituitary adenoma (increased ACTH)
- Ectopic ACTH (15%) from small cell lung cancer or bronchial carcinoid) (increased ACTH)
- Adrenal (15%)- Adenoma, carcinoma, nodular adrenal hyperplasia (decreased ACTH) |
|
|
Term
| How can you distinguish between the various causes of Cushing's disease based upon ACTH and low/high dose dexamethasone suppression testing? |
|
Definition
Hypertension, weight gain (central), moon facies, hyperglycemia (insulin resistance), skin striae, osteoporosis, immune suppression, ect.
1) High ACTH= Secondary (pituitary) or Ectopic (small cell lung cancer or lung carcinoid
- Will look the same on low dose suppression, but pituitary can be suppressed at high doses.
2) Low ACTH= Primary or Exogenous/steroids
- Low/high dose will NOT be able to suppress adrenal tumor, but will suppress exogenous |
|
|
Term
| What are the classic findings of Cushing's? |
|
Definition
Hypertension, Truncal obesity with Striae, Moon facies and Diabetes/hyperglycemia,
Also, immunosuppression, osteoporosis and amenorrhea |
|
|
Term
| How can you distinguish between primary and secondary hyperaldosteronism and what is/are the treatments? |
|
Definition
Will see hypertension, hypokalemia, metabolic acidosis: Look at renin level.
1) Primary= adrenal hyperplasia or secreting adenoma (Conn's syndrome)
- Low renin by negative feedback (bilateral or unilateral)
- Surgery +/- spironolactone (aldosterone antagonist)
2) Secondary= Renal artery stenosis, chronic renal failure, CHF, cirrhosis, nephrotic syndrome
- kidney perceives and hits RAAS (high renin)
- treat condition |
|
|
Term
| Why might you get secondary hyperaldosteronism? |
|
Definition
Kidney perceives low volume status and revs up RAAS (high renin)
Hypertension, hypokalemia and metabolic acidosis.
1) Renal artery stenosis or chronic renal failure
2) CHF
3) Nephrotic syndrome
4) Cirrhosis |
|
|
Term
| What are the defining features of Addison's disease and how can it be distinguished from secondary adrenal insufficiency? |
|
Definition
1) Chronic primary insufficiency with deficient aldosterone and cortisol, causing
- Hypotension (hyponatremic volume contraction,
- Hyperkalemia
- Acidosis
- Skin hyper-pigmentation (MSH, byproduct of increased ACTH from POMC)
- ADDisons= -(Cushing's + Conn's)
2) Secondary (decreased pituitary ACTH), will have hypotension, but NO pigmentation or hyperkalemia |
|
|
Term
True or False:
True primary Addison's disease spared the zona reticularis. |
|
Definition
| False- spares the medulla (Catecholamine) |
|
|
Term
| What is Waterhouse-Friderichsen syndrome and how does it differ from Addison's disease? |
|
Definition
In WFS, there would be no time to develop hyper-pigmentation, like in the chronic course of Addison's
1) WFS is ACUTE primary adrenal insufficiency due to hemorrhage
- N. meningitidis septicemia, DIC and endotoxic shock
2) Addison's is CHRONIC primary failure |
|
|
Term
| What is the most common tumor of the adrenal medulla in adults and what are the associated complications? |
|
Definition
1) Pheochromocytoma- derived from chromaffin (neural crest) cells.
- Elevated VMA in urine (catecholamine breakdown) and plasma catecholamine levels
- Treat with alpha antagonists (phenoxybenzamine), followed by surgery to remove tumor.
2) Episodic hyper-adrenergic symptoms (5 P's)
- Pressure (BP)
- Pain (headache)
- Perspiration
- Palpitation (tachycardia)
- Pallor |
|
|
Term
Patient presents complaining of episodic headaches, palpitations and sweating.
Urine VMA is elevated and plasma catecholamines are elevated as well.
What conditions are associated with this and what is the appropriate treatment? |
|
Definition
1) Pheochromocytoma- most common tumor of adrenal medulla in adults (vs. Neuroblastoma in kids)
- Associated with Neurofibromatosis, MEN 2A and 2B
- VMA elevated b/c it is NE breakdown product (like HVA for dopamine and Metanephrine for Epi)
- Episodic Pain (headache), Perspiration and Palpitations (tachycardia) are 3 of 5 P's (Pressure and Pallor)
2) Treatment
- Alpha antagonist (Phenoxybenzamine- non-selective, irreversible alpha blocker), followed by Surgery. |
|
|
Term
| What is the "Rule of 10" for the most common adrenal medullary tumor of adults? |
|
Definition
Pheochromocytoma- associated with neurofibromatosis and MEN 2A/2B (relapsing and remitting "spells" of symptoms)
10% malignant
10% bilateral
10% extra-adrenal
10% calcify
10% kids
10% familial |
|
|
Term
| What are HVA, VMA and Metanephrine, respectively? |
|
Definition
Breakdown products of catecholamines
Phen...Tyr....L-DOPA...Dopamine (HVA)......NE (VMA)...EPi (Metanephrine) |
|
|
Term
| Why might you be worried for a kid with elevated HVA levels in his urine and a N-myc over-expression mutation? |
|
Definition
Neuroblastoma is most common cause of adrenal medullary tumor in kids, and is associated with Homovanillic acid elevation (breakdown of Dopamine)
Tumor can occur anywhere along sympathetic chain and N-myc oncogene is associated with RAPID progression. |
|
|
Term
Which of the following is NOT a symptom of Hypothyroidism?
1) Cold intolerance
2) Palpitations and chest pain
3) Decreased reflexes
4) Dry, cool skin and brittle hair
5) Weight gain and appetite suppression |
|
Definition
2- These are HYPER symptoms. HYPO is bradycardia and DOE
HYPO
- Cold intolerance, weight gain/appetite suppression, constipation, decreased reflexes, Myxedema (face/periorbital), hypo-activity,
HYPER
- Heat intolerance, weight loss/increased appetite, diarrhea, increased reflexes, Pre-tibial myxedema (Grave's), hyper-activity, chest pain/palpitations/beta-adrenergic |
|
|
Term
Which of the following is NOT characteristic of Hyperthyroidism?
1) Heat intolerance
2) Peri-orbital myxedema
3) Weight loss
4) Chest pain
5) Warm, moist skin
6) Diarrhea |
|
Definition
2- This is HYPO sign, HYPER gets pre-tibial myxedema
HYPO
- Cold intolerance, weight gain/appetite suppression, constipation, decreased reflexes, Myxedema (face/periorbital), hypo-activity,
HYPER
- Heat intolerance, weight loss/increased appetite, diarrhea, increased reflexes, Pre-tibial myxedema (Grave's), hyper-activity, chest pain/palpitations/beta-adrenergic |
|
|
Term
| What are the classic TSH, T4 (total and free) and T3 uptake measurements of hypo and hyperthyroidism? |
|
Definition
1) Hyperthyroidism
- Decreased TSH (only primary)
- Elevated T4 (total and free)
- Elevated T3 uptake
2) Hypothyroidism
- High TSH (only primary)
- Low T4/T3 |
|
|
Term
Describe the classic findings of each of the following causes of hypothyroidism.
1) Hashimoto's thyroiditis
2) Cretinism
3) Subacute thyroiditis
4) Riedel's thyroiditis |
|
Definition
Also can be caused by iodine deficiency, thyroglossal duct cyst, Goitrogens and Wolff-Chaikoff effect.
1) Most common/HLA-DR5 association and risk of NHL
- Anti-microsomal and anti-TG antibodies
- Moderately enlarged, non-tender thyroid with Hurthle cells, lymphocytic infiltrate and germinal centers
2) Severe fetal hypothyroidism
- Endemic where iodine deficiency
- Sporadic caused by T4 formation defect or development thyroid failure
- Pot-bellied, pale, puffy-faced child with protruding umbilicus and protuberant tongue
3) Self-limited/follows flu-like illness
- May have transient hyperthyroidism
- Granulomatous inflammation, elevated ESR, jaw pain, early inflammation and tender thyroid.
4) Thyroid replacement by fibrous tissue
- Fixed, hard (rock-like) and painless goiter |
|
|
Term
What form of hypothyroidism is associated with each of the following presentations?
1) Moderately enlarged, non-tender thyroid with Hurthle cells, lymphocytic infiltrate and germinal centers
2) Pot-bellied, pale, puffy-faced child with protruding umbilicus and protuberant tongue
3) Self-limited tender thyroid following flu-like illness
4) Fixed, hard (rock-like) and painless goiter |
|
Definition
1) Hashimoto's thyroiditis
- Most common/HLA-DR5 association and risk of NHL
- Anti-microsomal and anti-TG antibodies (IgG)
- Can be hyperthyroid early in course due to follicular rupture
2) Cretinism: Severe fetal hypothyroidism
- Endemic where iodine deficiency
- Sporadic caused by T4 formation defect or development thyroid failure
3) Subacute thyroiditis (de Quervain's)
- Granulomatous inflammation, elevated ESR, jaw pain, early inflammation.
4) Riedel's thyroiditis
- Thyroid replacement by fibrous tissue
- May have early hyperthyroid |
|
|
Term
| Why do some patients with Hashimoto's thyroiditis get hyperthyroidism early during the disease course? |
|
Definition
Most common cause: HLA-DR5 and risk of NHL
Moderately enlarged, non-tender goiter
Thyrotoxicosis during follicular rupture |
|
|
Term
| What are the 3 primary causes of Hyperthyroidism and how do they present? |
|
Definition
1) Grave's (Anti-TSH receptor IgG: stimulatory)
- Proptosis/Exophthalmos and Pre-tibial myxedema (glycosaminoglycan deposition)
- Diffuse goiter and presenting during stress (childbirth)
2) Thyroid storm: Complication of grave's and other hyperthyroid disorders
- Stress-induced catecholamine surge leading to death by arrhythmia
- Elevated ALP from elevated bone turnover
3) Toxic multi-nodular goiter
- Patches of hyper-functioning follicular cells working independently of TSH due to TSH-R mutation
- Hot nodules are rarely malignant
- Jod-Basedown phenomenon with thyrotoxicosis if iron deficiency goiter is made iodine replete |
|
|
Term
| Why should you be careful making a patient with hyperthyroidism and iodine deficiency, iodine replete? |
|
Definition
| Toxic multinodular goiter or Graves can exhibit Jod-Basedow phenomenon, with thyrotoxicosis! |
|
|
Term
|
Definition
Thyroid nodule that makes excess T3/T4 (multinodular goiter).
Unlike cold nodules, they rarely metastasize. |
|
|
Term
| What is the most common cause of death in elderly patients with Grave's disease? |
|
Definition
| They have "apathetic" graves and die from thyroid storm (Arrhythmia/A-fib) |
|
|
Term
Which form of thyroid cancer is described by each of the following?
1) "Ground glass" nuclei (Orphan Annie), Psammoma bodies and nuclear grooves
2) Uniform follicles
3) Calcitonin-producing tumor with sheets of cells in amyloid stroma
4) Older patients with poor prognosis
5) Associated with Hashimoto's |
|
Definition
1) Papillary carcinoma
- Most common with excellent prognosis
- Risk with childhood radiation
2) Follicular carcinoma
- Good prognosis
3) Medullary carcinoma
- From para-follicular C cells (calcitonin producing)
- Associated with MEN 2A and 2B
4) Anaplastic/undifferentiated
5) NH Lymphoma |
|
|
Term
| Which thyroid cancer has the poorest prognosis? |
|
Definition
Anaplastic/Undifferentiated- seen in elderly
Papillary and Follicular have good prognosis. |
|
|
Term
Patient presents with weakness and constipation.
Urinalysis reveals hypercalciuria and cAMP elevation.
Serum shows elevated Ca2+, PTH, ALP and low phosphate.
What is going on? |
|
Definition
Primary hyperthyroidism-most commonly adenoma (Stones, Bones and Groans)
- High PTH, despite high Ca2+ and low PO4 suggests a primary cause
- ALP suggests bone turnover
May cause osteitis fibrosa cystica, where cystic bone spaces are filled with brown fibrous tissue (bone pain)
Hypercalcemia |
|
|
Term
| How can you distinguish primary hyperparathyroidism from secondary and tertiary causes? |
|
Definition
Primary causes Osteitis fibrosa cystica
Secondary and Tertiary cause Renal Osteodystrophy
1) Primary- most commonly parathyroid adenoma
- High serum and urine Ca2+ with high PTH
2) Secondary- Poor GI Ca2+ absorption and high phosphorous (hypovitaminosis D) in chronic renal disease
- Hypocalcemia, hyperphosphatemia, high ALP and High PTH
3) Tertiary: refractory (autonomous) hyperparathyroidism from chronic renal disease (persistent stimulation)
- Very high PTH and high Ca2+ |
|
|
Term
True or False:
Chronic renal disease is a common cause of Osteitis fibrosa cystica. |
|
Definition
False! OFC is associated with primary hyperparathyroidism
- cystic bone spaces filled with brown fibrous tissue
Renal disease produces secondary (hypovitaminosis D) and tertiary (refractory/autonomous PTH) hyperparathyroidism and is associated with Renal osteodystrophy. |
|
|
Term
| What are Chvostek's and Trousseu's signs and what do they indicate? |
|
Definition
Signs of hypoparathyroidism (hypocalcemia with lowered threshold for firing and spasticity)
1) Chvostek- Tapping of facial nerve leading to contraction of facial muscles
2) Trousseu- Occlusion of brachial artery with BP cuff causing Carpal spasm. |
|
|
Term
| What are the major causes of Hypoparathyroidism and what are the classic findings? |
|
Definition
Hypocalcemia and Tetany, with + Chvostek (tap facial nerve and see contractions) and Trousseu (brachial artery occlusion and carpal spasm)
1) Accidental surgical excision (thyroid surgery)
2) Autoimmune
3) DiGeorge |
|
|
Term
Describe what each of the following lab values indicate.
1) Low PTH and Low Calcium
2) High PTH and Low Calcium
3) Low PTH and High Calcium
4) High PTH and High Calcium |
|
Definition
1) Primary hypoparathyroidism (autoimmune, Digeorge or surgery)
2) Secondary hyperparathyroidism (chronic renal failure)
3) PTH-independent hypercalcemia (excess calcium ingestion, cancer)
4) Primary hyperparathyroidism (hyperplasia, adenoma, carcinoma) |
|
|
Term
What are the classic PTH and Ca2+ levels associated with each of the following? (Low or High)
1) Autoimmune parathyroid destruction
2) Chronic renal failure
3) Excess calcium ingestion
4) Parathyroid hyperplasia |
|
Definition
Low calcium= tetany
High calcium= muscle weakness
1) Primary hypoparathyroidism (also surgery or DiGeorge)- Low PTH and Low Ca2+
2) Secondary hyperparathyroidism- High PTH and low Ca2+
3) PTH-independent hypercalcemia (also cancer)- Low PTH and high Ca2+
4) Primary hyperparathyroidism (also adenoma or carcinoma)
- High PTH and High Ca2+ |
|
|
Term
2 year old presents with tetany and shortened 4th/5th digits. You also notice he is too short for his age.
Labs come back and he is hypocalcemic, despite normal/high PTH levels.
What is going on? |
|
Definition
Pseudohypoparathyroidism (Albright's hereditary osteodystrophy)= short, short fingers and hypocalcemia
AD kidney unresponsive to PTH |
|
|
Term
What are the most common findings of a pituitary adenoma?
What is the treatment? |
|
Definition
1) Prolactinoma
- Amenorrhea, galactorrhea, low libido, infertility (decreased GnRH)
- Watch out for bitemporal hemianopsia (optic chiasm is right there!)
2) Bromocriptine/Cabergoline- dopamine agonist
- Increase hypothalamic inhibition of cause shrinkage |
|
|
Term
| How do you diagnose/treat Acromegaly? |
|
Definition
1) Diagnose
Findings: Large tongue with deep furrows, deep voice, large hands and feet, coarse facial features, insulin resistance.
Labs: Increased serum IGF-1 and failure of GH suppression with oral glucose load
2) Treat
- Pituitary adenoma resection followed by Octreotide (somatostatin analogue) |
|
|
Term
| Under what conditions is an increase in GH normal? |
|
Definition
1) Stress
2) Exercise
3) Hypoglycemia (inhibit insulin to prevent glucose uptake and stimulate gluconeogenesis) |
|
|
Term
| Why might a child with gigantism have fasting hyperglycemia? |
|
Definition
| GH-secreting pituitary adenoma causing insulin resistance. |
|
|
Term
| What is the difference between central and nephrogenic diabetes insipidus and how can you diagnose/treat them? |
|
Definition
Thirst and Polyuria together with inability to concentrate urine
Diagnose with water deprivation test (can't concentrate urine)
1) Central DI has low ADH and will respond to ddAVP
- Fluids and intranasal ddAVP
2) Nephrogenic has resistant receptors (V2-cAMP) and will not respond to ddAVP
- Fluids, hydrochlorothiazide (Ca+ sparing), indomethcin or amiloride (K+ sparing) |
|
|
Term
Which of the following is NOT a cause of secondary nephrogenic DI?
1) Lithium
2) Hypercalcemia
3) Demeclocycline
4) Thiazide diuretics |
|
Definition
4- Actually used to treat it (amiloride and indomethicin also)
nDI has urine specific gravity <1.006 and serum osmolality >290 mOsm/L, failed water dep test and no improvement with ddAVP administration.
Lithium, Hypercalcemia and Demeclocycline (ADH antagonist) can all cause it. |
|
|
Term
Which of the following is NOT a cause of central DI
1) Pituitary tumor
2) Trauma
3) Hypercalcemia
4) Surgery
5) Histiocytosis X |
|
Definition
| 3- This is cause of secondary nephrogenic DI, along with Demeclocycline and Lithium |
|
|
Term
| Why might you see SIADH in the context of central DI? |
|
Definition
2nd part of tri-phasic response following neurohypophysis stalk section.
As neurons are dying, they release a TON of ADH, which causes water retention, hyponatremia and increased urine osmolality.
Treat with Demeclocycline or H20 restriction (be careful if it is part of DI, because Demeclocycline will hurt you later). |
|
|
Term
Why do patients with SIADH have hyponatremia?
What are the major causes? |
|
Definition
Excess ADH causes excess water retention and urine osmolality, which decreases Adlosterone, preventing sodium reabsorption through ENaC.
SEIZURE problem, so replace (slowly). Restrict water or give Demeclocycline (ADH antagonist)
1) Ectopic ADH (small cell lung cancer)
2) CNS disorder/head trauma (central DI-related)
3) Pulmonary disease
4) Drugs (cyclophosphamide) |
|
|
Term
Which of the following is NOT a cause of SIADH?
1) Small cell lung cancer
2) Pulmonary disease
3) Head trauma
4) Cyclophosphamide
5) Lithium |
|
Definition
5- Cause of nephrogenic DI
Treat with demeclocycline or H20 restriction and replace sodium slowly to prevent seizures.
1) Ectopic ADH
3) Stalk section |
|
|
Term
Which of the following is NOT a major cause of hypopituitarism?
1) Hashimoto's thyroiditis
2) Non-secreting adenoma
3) Craniopharyngioma
4) Empty sella syndrome in obese women
5) Sheehan's syndrome |
|
Definition
1) This is related to lymphoma, not hypopituitarism
Non-secreting adenoma and Craniopharyngeoma (kids) are most common, followed by Sheehan's post-partum bleed and necrosis |
|
|
Term
| Why might a women who just delivered her baby be unable to lactate? |
|
Definition
| Sheehan's post-partum necrosis due to bleed, leading to Hypopituitarism (no prolactin). |
|
|
Term
Which of the following is NOT an acute presentation of DM type 1
1) DKA
2) Hyperosmolar coma
3) Weight loss
4) Polyphagia
5) Polyuria
6) Polydypsia |
|
Definition
2- Characteristic of Type 1
Both are thirsty, skinny, pee a lot and eat a lot.
Unopposed secretion of GH and epinephrine exacerbates hyperglycemia |
|
|
Term
| How do patients with Diabetes mellitus get dehydration and acidosis, which can proceed to coma and even death? |
|
Definition
Starts with insulin deficiency and glucagon excess.
Osmotic diuresis (dehydration) and ketone production from FFA (acidosis)
1) Decreased glucose uptake
- Hyperglycemia...glycosuria... osmotic diuresis and electrolyte depletion (DEHYDRATION)
2) Increased protein catabolism
- Increased plasma amino acids and nitrogen losses in urine.... osmotic diuresis (Dehydration)
3) Increased lipolysis
- Increased plasma FFAs, ketogenesis, ketonuria and ketonemia (ketoACIDOSIS) |
|
|
Term
| What are the chronic manifestations of Diabetes? |
|
Definition
Non-enzymatic glycosylation
1) Small vessel disease (Diffuse BM thickening)
- Retinopathy (hemorrhage, exudates, micro-aneurysm, vessel proliferation)
- Glaucoma
- Nephropathy (Nodular sclerosis, progressive proteinuria, CRF, arteriosclerosis leading to HTN, Kimmelstiel-Wilson nodules)
2) Large vessel atherosclerosis
- CAD, peripheral vascular occlusive disease and gangrene (limb loss and cerebrovascular disease)
Osmotic damage
1) Neuropathy (motor, sensory and autonomic degeneration)
2) Cataracts (sorbitol accumulation) |
|
|
Term
| How do patients with diabetes get cataracts and peripheral neuropathy? |
|
Definition
Osmotic damage from sorbitol accumulation
- Conversion of excess glucose to sorbitol (aldose reductase) with accumulation and damage in eyes and myelin sheaths (Schwann cells). |
|
|
Term
| How do you diagnose diabetes? |
|
Definition
1) Fasting serum glucose (elevated)
2) Glucose tolerance test (how quick is it cleared?)
3) HbA1c (measures long-term diabetic control)
- glycosylated Hgb- see how high your blood glucose has been on average over the last 8-12 weeks
- Diabetics are good at 6.5% and regular is good at 3.5-5.5% |
|
|
Term
| What distinguishes type 1 from type 2 diabetes? |
|
Definition
Type 1 (Juvenile onset, IDDM)
- Autoimmune destruction of b cells after infection
- Severe glucose intolerance with high sensitivity
- Young onset (<30) without obesity and weak genetic predisposition (polygenic)
- HLA pre-disposition (DR3 and 4)
2) Type 2 (adult onset, NIDDM)
- Resistance to insulin in patients >40
- Mild to moderate glucose intolerance with poor insulin sensitivity
- Associated with obesity and strong genetic predisposition (polygenic)
- NO HLA disposition |
|
|
Term
Which of the following is NOT associated with type 1 diabetes?
1) Onset <30
2) Autoimmune destruction of beta cells in pancreas
3) Islet amyloid deposits
4) Severe glucose intolerance
5) Weak genetic predisposition
6) HLA-DR3/4 association |
|
Definition
3- This is type 2
Type 1 has Islet leukocytic infiltrate (autoimmune) |
|
|
Term
Which of the following is NOT associated with type 2 diabetes?
1) Obesity
2) Onset >40
3) Islet amyloid deposits
4) Poor insulin sensitivity
5) strong genetic predisposition
6) HLA-DR3/4 association |
|
Definition
| 6- NO HLA in type 2- only type 1 |
|
|
Term
True or False:
DKA is rare in type 2 DM |
|
Definition
True. It is more common in type 1, where stress (infection) requires more insulin
Increased lipolysis and FFA production leading to production of ketone bodies (beta-hydroxybutyrate>acetoacetate) |
|
|
Term
Patient presents with rapid, deep respirations, nausea/vomiting, abdominal pain and a fruity breath odor.
His Hba1c is 9%. H+ is elevated and HCO3- is low. There is also evidence of hyperkalemia, but depleted intracellular potassium.
Why are you worried and what do you do? |
|
Definition
Fruity breath (acetone) and Kussmaul respirations are classic DKA (AG MA) and Hba1c suggests type 1 DM.
Intracellular K+ is low because insulin is not available to stimulate shift into cells.
1) Life-threatening mucormycosis, Rhizopus infection, crebral edema, arrythmias and HF.
2) Give IV fluids, IV insulin and K+ (intracellular stores). May give glucose also to prevent hypoglycemia. |
|
|
Term
| Why is intracellular K+ storage depleted in DKA? |
|
Definition
No insulin around to shift K+ into cells- type 1 DM
Give K+, IV fluids and IV insulin (perhaps with glucose to prevent hypoglycemia) |
|
|
Term
| What is the rule of 1/3s in relation to Carcinoid syndrome? |
|
Definition
Rare syndrome caused by carcinoid tumors (especially metastatic small bowel tumors), where 5-HT secretion causes recurrent Diarrhea, Cutaneous flushing, Asthmatic wheezing and Right-sided valvular disease.
**If tumors are restricted to bowel, 5-HT undergoes 1st pass in liver and never causes this problem**
1/3 metastasize
1/3 present with 2nd malignancy
1/3 multiple |
|
|
Term
| How do you treat the most common tumor of the appendix? |
|
Definition
| All Carcinoid tumors/syndrome are treated with Octreotide (Somatostatin analog) |
|
|
Term
| Why do metastatic small bowel carcinoid tumors cause cutaneous flushing, diarrhea, asthmatic wheezing and right-sided valve disease that does not occur in localized tumors? |
|
Definition
Neuroendocrine tumors that produce 5-HT and are treated with Octreotide.
Carcinoid syndrome doesn't occur in local tumors because 5-HT undergoes 1st pass in liver. |
|
|
Term
Which of the following symptoms is NOT associated with carcinoid syndrome?
1) Diarrhea
2) Cutaneous flushing
3) Left-sided valvular disease
4) Asthmatic wheezing
5) Elevated 5-HIAA in urine |
|
Definition
| 3- RIGHT-sided disease from 5-HT secretion, mostly from metastatic neuroendocrine tumors of small bowel. |
|
|
Term
| What is "Zollinger-Ellison syndrome" and how does it differ from Carcinoid tumors? |
|
Definition
Gastrin-secreting tumor of pancreas or duodenum associated with MEN 1 (Wermer's syndrome)
Stomach shows rugal thickening with acid hypersecretion, causing recurrent ulcers
Carcinoid tumors are neuroendocrine tumors (appendix and small bowel) that secrete 5-HT and cause carcinoid syndrome (flushing, diarrhea, right valve disease, wheezing) |
|
|
Term
| What characteristics define Multiple endocrine neoplasia syndrome 1 (MEN 1= Wermer's syndrome) |
|
Definition
MEN 1= 3 P's (cephalad to caudad): AD like all MEN
**present with kidney stones and stomach ulcers**
1) Pituitary (prolactin or GH)
2) Parathyroid
3) Pancreas (Zollinger-Ellison/gastrin-secreting, insulinoma, VIPoma, glucagonoma) |
|
|
Term
| What characteristics define Multiple endocrine neoplasia syndrome 2A (MEN 2A= Sipple's syndrome) |
|
Definition
AD like all MEN syndromes
MEN 2A and 2B with RET gene
2' Ps (Parathyroids and Pheochromocytoma)
- remember by drawing a square!
1) Parathyroid
2) Medullary thyroid carcinoma (secretes calcitonin)
3) Pheochromocytosma |
|
|
Term
| What characteristics define Multiple endocrine neoplasia syndrome 2B (MEN 2B) |
|
Definition
AD like all MEN syndromes
MEN 2A and 2B with RET gene
1 P (Pheochromocytoma): draw a triangle!
1) Pheochromocytoma
2) Medullary thyroid carcinoma (secretes calcitonin)
3) Oral/intestinal ganglioneuromatosis (associated with marfanoid habitus) |
|
|
Term
Which endocrine neoplasia is NOT associated with the RET gene?
1. Medullary thyroid carcinoma
2. Pheochromocytoma
3. GH-secreting Pituitary tumor
4. Oral ganglioneuromatosis
5. Parathyroid tumor |
|
Definition
3- Associated with MEN 1 (Wermer's)- Diamond (Pituitary, Parathyroid and Pancreatic endocrine)
RET is associated with MEN 2A and 2B
2A (square)= Parathyroid, Pheo, medullary thyroid carcinoma
2B (triangle)= Pheo, Oral/intestinal ganglioneuromatosis and Medullary thyroid carcinoma |
|
|
Term
True or False:
All multiple endocrine neoplasia syndromes are inherited in an autosomal dominant manner. |
|
Definition
True!
MEN 2A (Sipple's)/2B associated with RET
2A= Square (Parathyroid, Pheo, Medullary thyroid carcinoma)
2B= Triangle (Oral/intestinal ganglioneuromatosis, Pheo, Medullary thyroid carcinoma)
1= Diamond (Pituitary/GH or ProL, Parathyroid, Pancreatic endocrine/ZE |
|
|
Term
Which of the following is NOT associated with MEN 1 (Wermer's)
1. Insulinoma
2. Parathyroid tumor
3. Prolactin-producing pituitary tumor
4. ZE syndrome
5. Pheochromocytoma |
|
Definition
5- This is MEN 2A/2B (RET gene)
MEN 1 is pituitary (GH or ProL), Parathyroid or Pancreas (ZE, insulinoma, VIPoma, glucagonoma)
- See stomach ulcers and kidney stones. |
|
|
Term
| How do the treatment strategies for type 1 DM and type 2 DM differ? |
|
Definition
1) Type 1 DM
- Low-sugar diet, insulin replacement
2) Type 2 DM
- Dietary modification and exercise for weight loss
- Oral hypoglycemics and insulin replacement |
|
|
Term
| What are the available forms of Insulin to treat diabetes and how do they work? |
|
Definition
Bind Insulin receptor (intrinsic receptor tyrosine kinase) and
- Liver: increase glucose stored as glycogen
- Muscle: increase glycogen and protein synthesis, and K+ uptake
- Fat: aids TG storage
1) Rapid-acting: Lispro, Aspart
2) Short-acting: Regular
3) Intermediate: NPH
4) Long-acting: Glargine, Detemir |
|
|
Term
What is the most dangerous toxicity(s) of each of the following drugs?
1) Lispro
2) Tolbutamide
3) Glyburide
4) Metformin
5) Rosiglitazone |
|
Definition
1) Rapid-acting insulin: Hypoglycemia or hypersensitivity (rare)
2) Tolbutamde and Chlorpropamide are 1st generation Sulfonylurea compound (Type 2 DM) that closes K+ channel in B-cell membrane, depolarizes it and leads to Ca-mediated insulin release: Disulfiram-like effects (blurred vision, peripheral tingling, icteric sclera)
3) Glyburide, Glimepiride and Glipizide are 2nd generation Sulfonylurea compounds (Type 2 DM): Hypoglycemia
4) Biguanide compound that decreases Gluconeogenesis, increases glycolysis and increases peripheral glucose uptake (insulin sensitivity): First line in type 2 DM and can be used in patients without islet function.
- Lactic acidosis (don't give in renal failure)
5) Rosiglitazone and Pioglitazone are Glitazone/Thiazolidinediones that increase insulin sensitivity in peripheral tissues by binding PPAR-y nuclear transcription regulation (fatty acid storage and glucose metabolism)
- Monotherapy or combined with above for type 2 DM
- Weight gain, edema, hepatotoxicity, HF |
|
|
Term
| What are the major drug classes used in treating diabetes and what are their mechanisms? |
|
Definition
Type 1 DM needs insulin
Type 2 DM can use others as well
1) Insulin (rapid, short, intermediate and slow-acting)
- Bind insulin receptor (TK activity)
- Liver: increase glycogen storage
- Muscle: glycogen/protein synthesis and K+ uptake
- Fat: TG storage
2) Sulfonylureas
- Close K+ channel in Beta cell membrane for depolarization and ca-mediated insulin release
3) Biguanide
- Decrease gluconeogenesis, increase glycolysis, increase peripheral glucose uptake
4) Glitazone/thiazolidinediones
- Bind PPAR-y nuclear transcription regulator in peripheral tissue (insulin sensitivity and adiponectin levels)
5) Alpha-glucosidase inhibitors
- Inhibit intestinal brush-border alpha-glucosidase to delay sugar hydrolysis and glucose absorption-prevent post-prandial hyperglycemia
6) Mimetics (Pramlintide)
- Decrease glucagon
7) GLP-1 analogs (Exenatide)
- Increase insulin and decrease glucagon release |
|
|
Term
| Why might you use insulin replacement therapy? |
|
Definition
1) Type 1 DM
2) Type 2 DM
3) Threatening hyperkalemia (increases uptake into muscle)
4) Stress-induced hyperglycemia |
|
|
Term
Which class of diabetes drugs does each of the following?
1) Increase K+ uptake into muscle cells rapidly
2) K+ channel closure in pancreatic beta cell membrane and insulin release
3) Bind PPAR-y increasing fatty acid storage and glucose storage by increasing insulin sensitivity and adiponectin levels in peripheral tissues
4) Decrease gluconeogenesis and increase peripheral glucose uptake
5) Decrease glucagon
6) Increase insulin and decrease glucagon release
7) Inhibit intestinal brush-border alpha-glucosidases |
|
Definition
1) Lispro or Aspart (Insulin)
2) Sulfonylureas
- 1st gen (Tolbutamine, Chlorpropamide)
- 2nd gen (Glyburide, Glimepiride, Glipizide)
3) Glitazones/thiazolidinediones (Pioglitazone, Rosiglitazone)
- Weight gain, hepatotoxic, edema and HF
4) Biguanide (Metformin)
- FIRST LINE in type 2 DM
- Look out for lactic acidosis
5) Mimetics (Pramlintide)
6) GLP-1 analogs (Exenatide)
7) Alpha-glucosidase inhibitors (Acarbose, Miglitol)
- Delay sugar hydrolysis and glucose absorption to prevent post-prandial hyperglycemia |
|
|
Term
How does each of the following diabetes drugs work?
1) Pioglitazone
2) Tolbutamide
3) Pramlintide
4) Exenatide
5) Glyburide
6) Glargine
7) Miglitol
8) Metformin |
|
Definition
1) Glitazones bind PPAR-y in peripheral tissues and increase insulin sensitivity by regulating fatty acid storage and glucose metabolism (increase adiponectin).
2) 1st generation Sulfonylurea compound that closes K+ channels in beta cell membranes (insulin release via Ca2+)
3) Mimetic compound that decreases glucagon
4) GLP-1 analog that increases insulin and decreases glucagon release
5) 2nd generation sulfonylurea compound (hypoglycemia instead of eye/neuro SE)
6) Long-acting Insulin
7) a-glucosidase inhibitor that delays sugar hydrolysis and glucose uptake in SI to prevent post-prandial hyperglycemia
8) 1st line in type 2 DM- Biguanide compound that decreases gluconeogenesis, increases glycolysis and increases peripheral glucose uptake. |
|
|
Term
| What are Propylthiouracil and Methimazole used for? |
|
Definition
Anti-thyroid drugs for Hyperthyroidism
Look out for skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity (propylthiouracil) and teratogen (methimazole)
Both drugs inhibit thyroid peroxidase, preventing organification of iodine and coupling of thyroid hormone synthesisis
Propylthiouracil also inhibits 5'-deiodinase, which prevents peripheral conversion of T4 to T3. |
|
|
Term
| What are Levothyroxine and Trriodothyronine? |
|
Definition
Drugs used for thyroxine replacement in Hypothyroidism and Myxedema (per-orbital probably)
SE are thyroid hormone releated: Tachycardia, heat intolerance, tremors and arythmias |
|
|
Term
How is each of these drugs used to treat hypothalamic/pituitary issues?
1) GH
2) Somatostatin (Octreotide)
3) Oxytocin
4) ADH (ddAVP) |
|
Definition
1) GH deficiency, Turner syndrome
2) Acromegaly, carcinoid, gastrinoma, glucagonoma
3) Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage.
4) Pituitary (central DI) |
|
|
Term
| What is Demeclocycline and how is it used? WHat are its SE? |
|
Definition
1) ADH inhibitor (tetracycline family) used in SIADH
2) Nephrogenic DI, photosensitivity, abnormalities of bone and teeth. |
|
|
Term
| What is the therapeutic mechanism of action of glucocorticoids and how are they used? What are the side effects? |
|
Definition
Hydrocortisone, Beclomethasone, Dexmethasone, Prenisone, Triamcinolone.
1) Mechanism.
- Inhibit LCT and PGE production by inhibiting phospholipase A2 and expression of COX-2
2) Use
- Addison's disease, inflammation, immune suppression,a sthma (chronic)
3) SE
- Iatrogenic cushings- buffalo hump, moon facies, truncal obesity, muscle wasting, ect.
- Diabetes (chronic use)
- Adrenal insufficiency when dropped after long-term use (withdrawal). |
|
|
Term
| How are stimulation and suppression tests used, respectively? |
|
Definition
1) Stimulation: Organ hypo-function (autoimmune most common)
- ACTH stimulation to workup hypocortisolism
2) Depression: Organ hyper-function (most common benign adenoma)
- Dexamethasone suppression for hypercortisolism
- Only hyper-functional disorders that CAN be suppressed are Prolactinoma and Pituitary cushings |
|
|
Term
| What are the most common causes of endocrine gland hyper- and hypo-function, respectively? |
|
Definition
1) Hyper (suppression test)
- Benign adenoma (e.g. pituitary cushing's)
- Other cancer, inflammation and hyperplasia are also common
2) Hypo (stimulation test)
- Autoimmune most common (Hashimoto's, Addison's)
- Infarction (Sheehan's PPN and waterhouse-Friderichsen) and Decreased hormone stimulation (low TSH in hypopituitarism) are also common. |
|
|
Term
What conditions cause the following findings?
- Secondary hypopituitarism
- CDI
- Hyper-prolactinemia
- Precocious puberty
- Bi-temporal hemianopia |
|
Definition
Hypothalamic dysfunction (lack of dopamine inhibition of prolactin, absent ADH release).
- Visual field defect suggests a mass in the region of the optic chiasm (craniopharyngeoma?).
1) Tumors
- **Pituitary adenoma (most common)
- Craniopharygioma (supracella tumor)
- MIdline hamartoma (not neoplasm- most common cause of precocious puberty
- Langerhan's histiocytosis
2) Inflammatory disorders
- Sarcoid or Meningitis |
|
|
Term
65 year old patient presents with paralysis of upward gaze, specifically and evidence of obstructive hydrocephalus.
What could be going on? |
|
Definition
pg 476 GP
"Setting sun" sign with compression of aqueduct of Silvius in 3rd ventricle suggests Pineal gland tumor or Dystrophic calcification of the gland
Site of Melatonin production, which is important in sleep/mood and circadian rhythms (released at night) |
|
|
Term
| What are the most common causes of hypopituitarism in adults and kids? |
|
Definition
1) Adults- Non-functioning adenoma
- Part of MEN 1 (with pancreas/ZE syndrome and hyper-parathyroid)
- 2nd most common is Sheehan's post-partum necrosis (hypovolemic shark and infarction with sudden cessation of lactation)
2) Kids- Craniopharyngioma
- Benign tumor from Rathke's pouch remnants (ectodermal derivative of oral cavity that becomes adenohypophysis)
- May cause bi-temporal hemianopia and CDI
Other causes include apoplexy, lymphocytic hypophysitis, and empty sella syndrome (ESS) |
|
|
Term
What clinical findings are associated with deficits in each of the following pituitary tumors following Sheehan's post-partum necrosis?
1) Failed GnRH stimulation test
2) Failed arginine and sleep stimulation tests
3) Low T4 and TSH
4) Metyrapone test: no increase in ACTH or 11-deoxycortisol |
|
Definition
1) GH: Delayed puberty
- adult females have secondary amenhorea (estrogen)
- adult males are impotence (testosterone)
2) GH: Decreased synthesis/release of IGF-1
- Children have growth defect
- Adults have hypoglycemia, decreased gluconeogenesis, loss of muscle
3) TSH: Secondary hypothyroidism
- Cold intolerance, weakness and constipation
4) Inhibits 11-hydroxylase: ACTH loss in hypopituitarism vs. adrenal insufficiency |
|
|
Term
What is the most common pituitary tumor and how does it manifest clinically in men and women?
How do you treat? |
|
Definition
35% are Prolactinoma, which are benign and inhibit GnRH
Treat with dopamine agonists (Cabergolide) or surgery for macroadenomas.
1) Men- Impotence (Decreased testosterone), Headache
2) Women- Secondary amenorrhea and Galactorhea |
|
|
Term
| What pituitary hormones are produced by the neurohypophysis? |
|
Definition
1) ADH (PVN and SON)- water retention
2) Oxytocin (SON)- milk ejection and uterine contraction |
|
|
Term
| Why do GH adenomas produce hyperglycemia? |
|
Definition
In adults, acromegalic growth is lateral, with organomegaly and hyperglycemia.
Patients die from heart failure.
**Failed glucose suppression test**
1) GH increases gluconeogenesis (hyperglycemia); amino acid uptake in muscle and stimulates IGF-1 in liver
2) IF-1 stimulates bone, cartilage and soft tissue growth |
|
|
Term
| Describe the major steps of thyroid hormone synthesis |
|
Definition
1) TSH-mediateed iodide trapping in follicular cell via Na/I symporter
2) Iodide enters colloid through apical membrane as is oxidized (Peroxidase) to iodine and added to TG to form MIT and DIT (organification)
3) Coupling (MIT+DIT= T3 and DIT + DIT= T4) occurs and hormones are stored as colloid
4) TSH binding leads to pinocytosis of colloid vesicles and lysosomal fusion and proteolysis in cell releases T4
5) Released T4/T3 (T4 becomes T3 via 5' iodinase) mostly binds TBG and free T4 becomes free T3 (active) |
|
|
Term
Describe the physiological response to each of the following in terms of Total serum T4 and TSH
1) Oral contraceptives
2) Anabolic steroids
3) Grave's disease
4) Hashimoto's thyroiditis |
|
Definition
GP 481: TSH responds to FT4 level and is best screening tool for thyroid dysfunction.
1) TBG increases, so thyroid must produce more T4 to replace FT4 that is now bound to TBG
- TSH is normal, since FT4 is normal
- Also occurs in pregnancy and hormone replacement
2) TBG decreases, and so does Total T4
- TSH normal, since FT4 is normal
- Also occurs in nephrotic syndrome
3) FT4 increases but TBG remains the same (Total increases)
- Since FT4 increases, TSH decreases
4) FT4 decreases, but TBG remains the same (T4 increases)
- Since FT3 decreases, TSH increases |
|
|
Term
| How is I123 uptake useful in diagnosing thyroid pathology? |
|
Definition
Evaluates synthetic activity: GP 482
1) Increased when T4 synthesis is increased (HOT nodule)
- Grave's, Toxic nodular goiter
- Hot nodules don't metastasize
2) Decreased uptake (COLD nodule)
- Inactivity (taking thyroid hormone)
- inflammation (acute/subacute/chronic thyroiditis)
- Cold nodules are more likely cancer (or cysts or adenoma) |
|
|
Term
| What is the difference between a Lingual thyroid and a thyroglossal duct cyst and branchial cleft cyst? |
|
Definition
GP: 482
1) Lingual Thyroid
- Failed descent from base of tongue with dysphagia for solids
- Suppress with thyroxine, ablate with radioactive Iodine or remove
2) Thyroglossal duct cyst
- Midline mass close to hyoid bone- surgery
3) Branchial cleft cyst
- Anterolateral cyst. |
|
|
Term
| What is the pathogenesis of Hashimoto's thyroiditis? |
|
Definition
Most common cause of hypothyroid.
- HLA DR5 with increased incidence in older adults.
- Treat with IV levothyroxine and steroids
Type II (anti-microsomal, anti-TG, anti-TSH)
Type IV (CD8 and Th cytokines)
1) CD8 T cells destroy parenchyma (type IV)
2) anti-TSH antibodies (type II)
3) Th cytokines attract macrophages (type IV)
4) anti-microsomal and anti-TG antibodies (type II) |
|
|
Term
True or False:
Grave's disease produces transient hyperthyroidism in fetus. |
|
Definition
True!
IgG against TSH cross placenta |
|
|
Term
| What is Plummer's disease and why do you see "hot nodules"? |
|
Definition
Toxic mutli-nodular goiter, where one or more nodules become TSH-independent
- NO exophthalmos and pre-tibial myxedema (Graves)
- See systolic HTN (vs. diastolic for hypothyroid) |
|
|
Term
| How should you treat Grave's disease? |
|
Definition
1) Beta blocker- hits everything except for sweating
2) Thionamides decrease hormone synthesis
3) Ablative rI131 therapy if treatment-resistant. |
|
|
Term
| What is Euthroid sick syndrome and how do you treat it? |
|
Definition
1) T3/T4 abnormalities with normal gland function
- Outer ring deiodinase is blocked and inner ring deiodinase converts T4 to inactive reverse T3
- Malignancy, HF, CRF, sepsis and MI related
2) Usually goes away with illness, but can use Levothyroxine if needed. |
|
|
Term
What can you draw from the following laboratory findings?
1) Increased T4, FT4 and decreased TSH and I123 uptake
2) Increased T4, FT4 and I123 uptake, with decreased TSH
3) Increased serum T4 with normal FT4 and normal TSH
4) Decreased serum and free T4, as well as TSH |
|
Definition
1) Taking thyroid hormone
- normal feedback with increased hormone, but not synthesis marker
2) Primary hyperthyroidism (grave's or TNG)
- Normal feedback with increased hormone and synthesis marker
3) Estrogen therapy, pregnancy, OCP
- TBG is increased, but FT4 is normal
- Opposite of anabolic steroids
4) Secondary hypothyroidism (hypopituitarism) |
|
|
Term
| What is the difference between non-toxic goiter and toxic goiter? |
|
Definition
Treat with levotyroxine to reduce side or surgery for jugular vein compression/congestion (Pemberton's sign)
1) NTG
- Hyperplasia/hypertrophy followed by involution/nodular formation
- Absolute or relative hormone deficiency
2) TNG
- One or more nodules becomes TSH-independent and produces T4
- Hot nodule |
|
|
Term
| What is the first step in management of a patient with a solitary thyroid nodule? |
|
Definition
Get a fine need aspiration (FNA) biopsy to see if it is malignant (15%).
Remove if necessary, otherwise followup periodically
GP-490 |
|
|
Term
Patient presents with solitary "cold" thyroid nodule and you order a FNA biopsy.
What is the most common benign thyroid tumor and what are its associated pathological findings?
What is the most common malignant tumor and associated findings? |
|
Definition
1) Follicular adenoma- Most common benign
- Surrounded by complete capsule
- 10% progress to folicular carcinoma
2) Papillary carcinoma (TSH-dependent)
- Empty-appearing nuclei (Orphan Annie)
- Psammoma bodies
- Lymphatic invasion and metastasis to cervical nodes and lung |
|
|
Term
Which thyroid carcinoma is described by each of the following and how do you treat it?
1) Orphan Annie nuclei and Psamomma bodies with cervical lymphatic metastasis
2) Neoplastic follicles that invade blood vessels, lungs and bone, but not lymph nodes.
3) Calcitonin-producing tumors that are converted into amyloid and are associated with MEN IIa/IIb syndromes
4) Associated with Hashimoto's thyroiditis
5) Rapidly agressive/fatal tumor of elderly women who tend to have multi-nodular goiter or a h/x of follicular cancer |
|
Definition
1) Papillary carcinoma (most common)
- Thyroidectomy with node sampling, radiotherapy and suppressive therapy with T4 (TSH dependent)
- great prognosis
2) Follicular carcinoma (most common solitary cold nodule cancer)
- Same treatment as papillary cancer (good prognosis)
3) Medullary carcinoma
- 80% sporadic and 20% familial (better prognosis)
- Treat with total thyroidectomy and genetic screening (RET)
4) Primary B-cell malignant lymphoma
- Chemotherapy depending on sub-type
5) Anaplastic cacner
- Palliative (often compresses trachea)
- Irradiation or chemo |
|
|
Term
True or False:
The superior and inferior parathyroid glands are derived from the 3rd and 4th pharyngeal pouches, respectively. |
|
Definition
False.
Superior= 4th
Inferior= 3rd
GP 492 |
|
|
Term
Which of the following is NOT a primary action of PTH?
1) Increase calcium reabsorption in early DCT
2) Increase HCO3- reclamation in PCT
3) Decrease phosphorus reabsorption in PCT
4) Increase bone resorption
5) Increase synthesis of 1-a-hydroxylase in PCT |
|
Definition
2- Decreases reclamation producing acidosis
PTH is stimulated by hypocalcemia and hyperphosphatemia, as it increases and decreases reclamation of each, respectively.
1-a-hydroxylase converts 25-OH D from liver into 1,25-OH2 D in the kidney, which can stimulate calcium/phosphorus absorption in small intestine, as well as increasing bone turnover.
GP 492 |
|
|
Term
| How do serum calcium levels regulate Calcitrol levels? |
|
Definition
1) Low Calcium
- Increased PTH...increased 1-a-hydroxylase in PCT....increased Calcitrol production and inhibition of 24-hydroxylase....decreased synthesis of inactive 24,25 (OH)2 D
2) High calcium
- Decreased PTH, decreased 1-a-hydroxylase..decreased calcitrol via activation of 24-hydroxylase |
|
|
Term
| How does respiratory/metabolic alkalosis (hyperventilation at high altitudes) influence serum calcium handling? |
|
Definition
Increases negative charges on albumin bind more free (ionized calcium)
- Normal total calcium, but less free calcium (opposite of hypoalbunemia)
- Produces Tetany (Chvostek and Tousseu signs) and increased PTH |
|
|
Term
| Which is the most common cause of hypoparathyroidism and what are the clinical findings? |
|
Definition
1) Autoimmune
- Can also be thyroid surgery, DiGeorge (failed descent of 3rd and 4th pharyngeal pouches) and Hypomagnesemia (diarrhea, aminoglycosides, diuretics, alcohol)
2) Findings
- Tetany (hypocalcemia)
- Calcification of basal ganglia (increased phosphorus drives calcium into brain tissue)
- Cataracts and Candida infections |
|
|
Term
How does each of the following produce hypocalcemia?
1) Acute pancreatitis
2) Hypovitaminosis D
3) Vitamin D-dependent rickets
4) Pseudohypoparathyroidism |
|
Definition
MOST common is Chronic Renal Failure, via hypovitaminosis D (no 1-alpha-hydroxylase)
1) Calcium bound to fatty acids in enzymatic fat necrosis (poor prognosis)
2) Malabsorption of calcium
- Celiac, Cirrhosis, Drugs/phenytoin, CRF
3) type 1 AR (absent 1-a hydroxylase) or type 2 AR (absent calcitrol receptors)
4) Autosomal dominant end-organ resistance to PTH
- Short 4th and 5th digits with short stature and mental retardation |
|
|
Term
| What is the most common cause of primary hyperthyroidism and what are the classic clinical findings? |
|
Definition
Associated with MEN1 and MENIIa and see diastolic HTN (vs. hyper-cortisol)
Stones, Bones and psychic Groans
1) Adenoma (80%)
- asymptomatic (>50%) or producing stones
- usually singular, right inferior gland.
** can also be caused by primary hyperplasia, involving all 4 glands**
2) Findings
- Renal stones (most common) and/or nephrocalcinonsis
- GI (PUD, acute pancreatitis)
- Bone/joints (Osteitis fibrosa cystica, osteoporosis, pseudogout)
- CNS disturgances |
|
|
Term
Which of the following does NOT cause hypercalcemia and how do each of the others work?
1) Hypervitaminosis D
2) Familial hypocalciuric hypercacemia
3) Thiazides
4) Loop diuretics
5) Sarcoidosis |
|
Definition
4- They are calcium sinks! Used in treatment with IV fluids.
1) Increased intestinal reabsorption in jejunum, and in kidneys.
2) AD (100% penetrance)- elevated calcium baseline "set point"- none in urine and a bunch in serum
3) Increase early distal tubule reabsorption
5) Macrophages in granulomas synthesize 1-a-hydroxylase |
|
|
Term
| What are the classic findings associated with Hypophosphatemia? |
|
Definition
Caused by alkalosis (MOST COMMON), hypovitaminosis D, and primary HPTH
1) Muscle weakness (ATP deficit with rhabdomyolysis)
2) RBC hemolysis (ATP deficit disrupts membrane integrity)
3) Osteomalacia (soft bones)- poor mineralization |
|
|
Term
| What is the most common cause of hyperphosphatemia? |
|
Definition
Chronic Renal failure due to decreased excretion.
Also most common cause of HYPOcalcemia (due to hypovitaminosis D) |
|
|
Term
Diagnose each of the following laboratory study results.
1) Low serum calcium, high serum phosphorus, low PTH, low Calcitrol
2) High serum calcium, low serum phosphorus, low PTH, low Calcitrol
3) High serum calcium, low serum phosphorus high PTH and high Calcitrol
4) Low serum calcium, high serum phosphorus, high PTH, low Calcitrol |
|
Definition
1) Primary hypoparathyroidism
2) Squamous cell lung cancer or renal cell (PTHr producing)
- phosphorus is low because PTHr binds same receptor as PTH
3) Primary hyperparathyroidism
4) Chronic renal failure causing vitamin D deficiency (most common cause of hypocalcemia)
- PTH is unable to induce renal production of 1-a-hydroxylase, so calcitrol is low and calcium reclamation is low. Phosphorus is high because it cannot be excreted (vs. non-renal causes) |
|
|
Term
What region of the adrenal glands house each of the following hormones/enzymes
1) 18-hydroxylase
2) 17-Ketosteroids
3) 11-Hydroxycorticoids
4) Testosterone |
|
Definition
Zona granulosa (mineralocorticoids)/fasiculata (cortisol)/ reticularis (sex hormones)
1) Induced by AT-II to produce aldosterone from corticosterone in zona glomerulosa
2) Sex-hormone precursor in zona reticulata (becomes DHEA and androstenedione)
3) Zona fasciulata glucocorticoids including 11-Deoxycortisol and cortisol
4) Zona reticularis hormone that is converted to DHT in the periphery by 5-alpha reductase |
|
|
Term
| What cause of adrenal failure is associated with gram-negative diplococci that metabolize glucose and maltose? |
|
Definition
Waterhouse-Friderichsen syndrome (Hemorrhage due to DIC) associated with N. meningiditis Septicemia.
**N. meningiditis is most common cause of meningitis 1m- 18y of age**
- Endotoxic shock leads to release of factor 7 and causes DIC, which leads to bilateral adrenal hemorrhage (hemorrhagic infarction due to thrombosis) |
|
|
Term
| What is the most common cause of acute adrenocortical insufficiency? |
|
Definition
Corticosteroid withdrawal.
Also, Waterhouse-Friderichsen (N. meningiditis septicemia/DIC) and Anti-coagulation therapy |
|
|
Term
| What is the most common cause of chronic adrenal insufficiency in the US and in developing countries? |
|
Definition
Weakness and Hypotension, with diffuse hyper-pigmentation (increased ACTH stimulates melanocytes)
1) US
- Autoimmune Addison's
2) Abroad
- MIliary TB |
|
|
Term
What happens to 17-Ketosteroids, 17-Hydroxyprogesterone, 17-Hydroxycorticodis and Mineralocorticoids in each of the following Adrenogenital syndromes?
1) 17-OHase deficiency
2) 11-OHase deficiency
3) 21-OHase deficiency |
|
Definition
1) Get mineralocorticoids only- HTN low 17-OH progesterone
- Low 17-ketosteroids (sex hormones)
- Low 17-hydroxyprogesterone (sex hormones)
- Low 17-Hydroxycorticoids (cortisol)
2) Just lose cortisol (HTN)
- High 17-ketosteroids (sex hormones)
- High 17-hydroxyprogesterone (sex hormones)
- High 17-Hydroxycorticoids (cortisol precursor)
- High mineralocorticoids (11-deoxycorticosterone)
3) MOST COMMON: Salt losers with high androgens (Hypotension)
- High 17-ketosteroids (sex hormones)
- High 17-hydroxyprogesterone (sex hormones)
- Low 17-Hydroxycorticoids (cortisol)
- Low mineralocorticoids |
|
|
Term
| What is the first step in working up a suspected andreogenital syndrome? |
|
Definition
1) 17- hydroxyprogesterone screening
- Low is 17-OHase deficiency
- High in 21 and 11-OHase deficiencies
2) 21 is most common and will be hypotensive salt-loser, while 11 will be hypertensive salt-retainer |
|
|
Term
Which adrenogenital syndrome is described by each of the following clinical presentations?
1) Ambiguous genitalia in females and Precocious puberty in males with rapid early growth and fusion of epiphyses. Diffuse pigmentation and hypotension.
2) Delayed menarche in females and Pseudohermaphrotism in males. Diffuse pigmentation and hypertension.
3) Ambiguous genitalia in females and Precocious puberty in males with rapid early growth and fusion of epiphyses. Diffuse pigmentation and hypertension. |
|
Definition
All are AR conditions treated with steroids, mineralocorticoids, and/or estrogen/testosterone at puberty.
Screening with 17-OH progesterone
1) 21-OHase deficiency (most common).
- High androgens (17-KS, DHT and testosterone)
- High ACTH with low cortisol (pigmentation)
- Low mineralocorticoids (hypotension and salt loss)
2) 17-OHase deficiency
- Low androgens
- High ACTH, low cortisol (pigment)
- High mineralocorticoids (hypertension)
3) 11-OHase deficiency
- High androgens
- Low cortisol (pigment from ACTH)
- High 11-dexoycorticosterone (hypertension)
pg 501 GP |
|
|
Term
What are the major causes of Cushing's?
How can you differentiate based on ACTH and cortisol levels, and suppression tests? |
|
Definition
Diastolic HTN, truncal obesity, diabetes, muscle weakness, purple striae
1) Chronic corticosteroid use (most common)
2) Pituitary (adenoma)- most common pathalogical cause
- High ACTH and cortisol (no feedback)
- Suppressible with high dexa
3) Adrenal
- Low ACTH and high cortisol (feedback intact)
- Not suppressible
4) Ectopic
- Low ACTH and high Cortisol
- No dexa suppression
pg 502 GP |
|
|
Term
Why do you see each of the following in Cushing's syndrome?
1) Weight gain
2) Muscle weakness
3) Diastolic HTN
4) Hirsutism
5) Purple abdominal striae
6) Osteoporosis |
|
Definition
1) Hyper-insulinism from hyperglycemia
2) Cortisol uses up muscle AA to make glucose
3) Increase in weak mineralocorticoids and glucocorticoids
- NOT aldosterone
4) Increased androgens
5) Cortisol weakens collagen, causing rupture of vessels in stretch marks
6) Increased bone breakdown. |
|
|
Term
| What is Nelson's syndrome? |
|
Definition
Bilateral adrenalectomy causes enlargement of preexisting pituitary adenoma (sudden drop in cortisol causes increase in ACTH synthesis)
Headache and diffuse hyper-pigmentation (ACTH) |
|
|
Term
Why might a patient have diastolic hypertension and muscle weakness/tetany, with hypernatremia, hypokalemia and metabolic alkalosis?
(hint: low renin activity) |
|
Definition
Primary hyper-aldosteronism (If renin was high- think secondary)
1) Diastolic htn- water and salt retention (Hypernatremia)
2) Tetany and weakness from alkalosis (K+ and H+ loss) |
|
|
Term
| What organs are capable of producing Epinephrine and can this help localize a Pheochromocytoma? |
|
Definition
Most common tumor of adrenal medulla in adults.
Associated with NF type 1, MEN IIa and IIb (RET) and Von-hippel Linau disease
1) Only adrenal medullar and Organ of Zukerkandl (at aortic bifurcation) have N-methyltransferase (PNMT), the enzyme required to to produce Epi from NE
2) If the the tumor produces Epi, it must be at one of these locations. |
|
|
Term
| What are the clinical findings associated with the most common adrenal medullary tumor of adults? |
|
Definition
Pheochromocytoma- brown hemorrhagic/necrotic tumor
Associated with NF-1, MEN IIa/IIb and VHL disease
1) Diastolic HTN (sustained or paroxysmal)
2) Pounding headache (80%)
3) Palpitations (70%)
4) Drenching sweats (70%) with htn periods
5) Anxiety
6) Ileus (catecholamine inhibition of peristalsis) |
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Term
| How can you distinguish a patients with a pheochromocytoma from one with essential htn? |
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Definition
1) Symptoms
- Drenching sweats and palpitations that align with paroxysmal bursts of diastolic HTN, along with anxiety are NOT seen in Essential HTN
2) Labs
- Plasma free metanephrines is best screen
- 24h urine metanephrine (best test) and VMA
- No clonidine suppression
- Neutrophillic leukocytosis and hyperglycemia |
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Term
| What is the best screen and confirmation test for pheochromocytoma? |
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Definition
1) Screen with plasma metanephrine
2) Confirm with 24h urine metanephrine (100% sensitivity) |
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Term
Child presents with abdominal mass with hypertension.
What is the prognosis of the most common adrenal medullary tumor? |
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Definition
Neuroblastoma (malignant)- small cell tumor of neurosecretory granules in post-ganglionic cells: associated with N-MYC oncogene
- 70% have metastasized at diagnosis to skin and bone.
- Overall survival is 40%, but 90% if they are <1 |
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Term
What is the leading cause of each of the following in the US?
1) Legal blindness
2) Peripheral neuropathy
3) Chronic renal failure
4) Below-the-knee amputation |
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Definition
| Diabetes mellitus for all! |
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Term
| What is the basic pathogenesis of type 1 diabetes? |
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Definition
Autoimmune
Type II (antibody against beta islet cell and insulin)
Type IV (T-cell cytokine destruction of beta cells) |
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Term
What is the basis for each of the following pathological processes in diabetes?
1) Non-enzymatic glycosylation
2) Osmotic damage
3) Poor glycemic control
4) Diabetes microangiopathy |
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Definition
1) glucose combines with AA in protein and produces products that increases vessel permeability o protein, increasing atherogenesis
- HbA1C level and Hyaline arteriolosclerosis
2) Aldose reductase converts glucose to sorbitol, which draws water into eyes, schwan cells and optic pericytes, causing cataracts, peripheral neuropathy and retinopathic microaneurysms, respectively.
3) Key factor in organ damage
4) Increased synthesis of type IV collagen in basement branes and mesangium, as seen in nephrotic syndrome |
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Term
Why do you see each of the following in DKA associated with type 1 diabetes?
1) Muscle wasting
2) Hyperglycemia
3) Ketoacidosis
4) Hypertriglyceridemia |
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Definition
5-10% Mortality: GP 511
1) Gluconeogenesis in liver requires AA from protein in muscle
2) Increased gluconeogenesis (increased glucagon and Epi)
3) Excess lipolysis produces FA, which undergo beta oxidation to produce aCOA. Liver converts this to ketone bodies
4) Without LPL activity in peripheral blood, chylomicron and VLDL levels increase |
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Term
| What are the diagnostic requirements for diabetes? |
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Definition
1) Random plasma glucose >200
2) Fasting glucose >126 (set for sensitivity)
3) Glucose intolerance after 75-g load (>200 2h later)
- Confirmed with repeat of 1 of the previous 3
HbA1c for long-term monitoring (8-12 weeks) |
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Term
| What are the newborn risks of gestational diabetes? |
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Definition
All pregnant women screened 24-28 weeks gestation with 50-g glucose challenge (>140 at 1h is +)
1) Macrosomia
- Insulin increases fat storage and muscle mass (AA uptake in muscle)
2) RDS
- Insulin inhibits fetal surfactant
3) Neural tube defects
4) Neonatal hypoglycemia
- High insulin |
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Term
| What are the 2 major polyglandular deficiency syndromes? |
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Definition
1) Type 1= Autosomal recessive (mean age 12)
**NO HLA**
- Addison's
- Primary hypoparathyroidism
- Mucocutaneous candidiasis
2) Type 2= Autosomal dominant (mean age of 24)
**HLA DR3/DR4**
- Addison's
- Hashimoto's
- Type 1 DM |
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Term
What are the cause of "fed state" hypoglycemia?
What about "fasted state"? |
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Definition
1) Fed
- Reactive type, due to excess insulin (No C peptide elevation) with adrenergic symptoms
2) Fasting (if its a kid; it is an inborn error, like CAT deficiency)
- Alcohol (NADH converts pyruvate to lactate and uses it up!)
- Insulinoma
- Cirrhosis |
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