Step 1 - Endocrine 1

denniskwinn's version from 2015-04-25 16:00


Question Answer
Glycogen regulation by Glucagon and epinepherine1)Increase cAMP
2)Which activates PKA (putting a P on Glycogen phosphorylase kinase making it active) and this lead to glycogenolysis.
Glycogen regulation by InsulinCauses Receptor tyrosine kinase to dimerize activating protein phosphatase which takes the phosphate off of glycogen phosphorylase inactivating it.
Glycogen branching-Branches have alpha 1,6 bonds
-Linkages have alpha 1,4 bonds
Glycogenolysis in muscleTo form glucose which is rapidly metabolized during exercise
Glycogenolysis in HepatocytesTo form glucose to maintain blood sugar at appropriate levels
Glucose to glycogen steps1)G6P to G1P
2)G1P to UDP Gluc (viaUDP gluc pyrophosphorylase)
3)UDP Gluc to Glycogen (via glycogen synthase)
4)Branches via branching enzyme
Glycogen to glucose stepsGlycogen broken down by glycogen phosphorylase and debranching enzyme
Glycogen storage diseases12 types all resulting in abnormal glycogen metabolism and accumulation of glycogen in cells - poor carbohydrate metabolism


Question Answer
Von Gierke’s diseaseGlycogen storage disease type 1
- severe fasting hypoglycemia
- ⇡⇡glycogen in liver, ⇡blood lactate, hepatomegaly
-Glucose-6-phosphatase deficiency(usually seen in the liver)
Pompe’s DiseaseGlycogen storage disease type II
- lysosomal alpha 1,4 glucosidase deficiency
- Cardiomegaly and systemic findings leading to early death - Pompe trashes the Pump(2 P's/type 2)
Cori’s diseaseGlycogen storage disease type III(Type 3/Cori)
- Deficiency in DeBranching enzyme (alpha 1,6 glucosidase)
- milder form of type I with normal blood lactate levels (gluconeogenesis is intact)
- severe fasting hypoglycemia, increased glycogen in liver, hepatomegaly
McArdle’s diseaseGlycogen storage disease type V
- skeletal muscle glycogen phosphorylase deficiency - increased glycogen in muscle but can’t break it down
- painful muscle cramps
- myoglobinuria w/strenuous exercise
RAAS Adrenal HormoneAldosterone
Aldosterone Adrenal locationZona Glomerulosa
GFR corresponds withSalt (Na+), Sugar (glucocorticoids), and Sex (androgens)
Pheochromocytomamost common tumor of the adrenal medulla in adults - causes episodic HTN
Neuroblastomamost common adrenal medulla tumor in children
- does not cause episodic HTN
ACTH, Hypothalmic CRH signalCortisol and sex hormones


Question Answer
Cortisol region of productionZona Fasciulata
Sex Hormone region of productionZona reticularis
Preganglionic SNS fibers stimulate ___ in the adrenal glandCatecholamines
Catecholamine region of productionMedulla (by chromaffin cells
Adrenal gland drainage1)Left adrenal to left adrenal vein to left renal vein to IVC
2)R adrenal to R adrenal vein to directly IVC (same as left and right gonadal vein)
Pituitary glandHypophysis(from below)
Posterior Pituitary akaNeurohypophysis(from up top)
Neurohypophysis productsADH, Oxytocin
AcidophilsGH, prolactin
Whole hypophysis products (FLAT PiG)FSH, LH, ACTH, TSH, Prolactin, GH
Alpha cell products [& location of cells]Glucagon (peripheral islet)
Beta cell productsInsulin (central islet)
Delta cell productsSomatostatin (interspersed in islet)


Question Answer
Glucagonoma-Hyperglycemia, necrolytic migratory erythema
-Treat with surgery, ocreotide (somatostatin analogue)
Insulinoma-Most common, 80% assoc w/MEN I
-Fasting hypoglycemia→mental status problems
- ↑ serum insulin and C peptide.
- Tx: surgery, streptozotocin
SomatostatinomaAchlorhydria, cholelithiasis, steatorrhea, DM, - Treat with surgery
VIPomaSecretory diarrhea, achlorhydria, Hypokalemia, Normal gap metabolic acidosis
-Tx: ocreotide, surgery
Z-EGastrin producing tumor, 20-30% MEN I, peptic ulceration, diarrhea, maldigestion, ↑↑ serum gastrin
-Tx: H+blockers, ocreotide, surgery


Question Answer
Body parts that don’t need insulin for glucose uptakeBRICK L (Brain, RBCs, Intestine, Cornea, Kidney, Liver)
GLUT-1 RBCs, brain
GLUT-2(bidirectional) beta islet cells, liver, kidney
GLUT-4(insulin responsive) adipose tissue, skeletal muscle
Insulin actions (7)⇡ glucose transport, ⇡glycogen synthesis and storage, ⇡triglycerde synthesis and storage, ⇡ Na retention in kidneys, ⇡Protein synthesis in kidney, ⇡cellular uptake of K+, inhibit glucagon release by alpha cells,
Insulin c-peptide marker that is present in endogenous insulin but not in exogenous
Sequence of Insulin secretion1) Glucose enters cell through GLUT2 and Aerobic respiration occurs
2)⇡ATP which closes K+ channel =depolarizing the cell leading to Ca++ influx and exocytosis of Insulin
Insulin independent organsBrain and RBCs - take up glucose independent of insulin levels
- brain depends on glucose for metabolism under normal circumstances and uses ketone bodies in starvation. -RBCs always depend on glucose.


Question Answer
TRH(+)⇢TSH, Prolactin
Dopamine(-)⇢Prolactin [feedback]
CRH(+)⇢ACTH [feedback]
Somatostatin (-)⇢ GH,TSH
Prolactin regulationinhibited by dopamine from hypothalamus and by prolactin (which increases dopamine synthesis).
Upregulated by TRH from hypothalamus
Prolactin actioninhibits GnRH syhtn and release


Question Answer
Dopamine agonists and prolactin inhibit (tx for prolactinoma)
Dopamine antagonists and prolactin stimulate (many antipsychotics are these)
Adrenal Glomerulosa makes Mineralcorticoids
Adrenal Fasiculata makesGlucocorticoids [made by]
Adrenal Reticularis makesAndrogens [made by]
Adrenal periphery [produces]Estrogens [Made where]
Testosterone Synthesis MAKE DIAGRAM THINGER


Question Answer
CAH A17 alpha hydroxylase deficiency - ⇣sex hormones, ⇣ Cortisol, ⇡ mineralocorticoids. Sx = HYPERtension.
hypokalemia. XY ⇣DHT ⇢pseudohermaphroditism (externally phenotypic female, no internal reproductive structures due to M1F). XX: externally phenotypic lemale with normal internal sex organs, but lacking secondary sexual characteristics ("sexual infantilism").
CAH B21 hydroxylase deficiency - most common form. ⇣ cortisol (increased ACTH), ⇣ mineralcorticoids, ⇡ sex hormones.
Sx: masculinization, female pseudohermaphroditism(Chick with clit-dick), HYPOtension, hyperkalemia, ⇡ plasma renin activity, and volume depletion.
Salt wasting can lead to hypovolemic shock in the newborn
CAH C11 beta hydroxylase deficiency -⇣cortisol, ⇣aldosterone and corticosterone, ⇡sex hormones.
Sx = masculinization, HYPERtension =The half-ass mineralcorticoid(11-deoxycorticosterone) is still a mineralcorticoid
Cortisol source Zona fasciculata
Cortisol Function (5)1.Maintain blood pressure (upregulate alpha1 receptors in arterioles)
2. ⇣ bone formation
3. Anti-inflammatory
4. ⇣ immune function
5. ⇡Gluconeogenesis= lipolysis, proetolysis.
Cortisol regulation CRH from hypothalamus stimulates ACTH release from pituitary causing cortisol production in adrenal zona fasciulata


Question Answer
PTH sourceChief cells of Parathyroid
PTH function (4)1.⇡ bone resorption of Ca and phosphate
2.⇡kidney rabsorption of calcium in DT
3.⇣ kidney reabsorption of phosphate
4. ⇡ 1,25 Vitamin D (calcitriol) production by stimulating 1 alpha hydroxylase
PTH regulation-1)⇣ free serum Ca= ⇡PTH secretion.
2) ⇣Free serum Mg ⇣= PTH secretion
-Low Mg caused by diarrhea, aminoglycosides, diuretics and alcohol abuse
PTH action in bonestimulates Ca release - directly stimulates osteoblastic cells to make RankL which binds to Rank on osteoclasts
PTH action in Kidneystimulates reabsorption of Ca and blocks reabsorption of Phosphates and stimulates production of dideoxy D=(1,25(OH)2
Vit D source-D3 from sun exposure in skin
-D2 ingested from plants
BOTH converted to 25 OH in liver and 1,25 (OH)2 in kidney (active form)
Lack of Vitamin D leads to Rickets (in kids) or Osteomalacia (adults)
Vit D function (3)1. ⇡absorption of dietary calcium
2. ⇡ absorption of dietary phosphate
3.⇡bone resorption of Ca and PO4
Vit D Regulation1)⇡ PTH causes ⇡ dihydroxyD
2)⇣[Ca] causes ⇡ dihydroxyD production
3) ⇣phosphate causes ⇡ dihydroxyD,
- DihydroxyD feedback ihibits its own production
24,25OH Vit Dan inactive form of Vitamin D
3 ways CRF can lead to Hypocalcemia1. Decre Ca2+ reabsorption
2. Decre Ca2+ GI absorption
3. Incre PHO4-= binds Ca2+ and Decre ionized Free Ca2+


Question Answer
Calcitonin sourceParafollicular cells (C cells) of thyroid
Calcitonin function- ⇣ bone resorption of Ca
-BUT not important in normal Ca homeostasis
Calcitonin regulation increased serum Ca causes calcitonin secretion
cAMP hormones (11)FSH, LH, ACTH, TSH, CRH, hCG, ADH(V2 receptor), MSH, PTH, calcitonin, glucagon, (C-FLAT G-CHAMP)
cGMP hormones (2)ANP, NO(both vasodilators)
Ip3 hormones (5)GnRH, GHRH, Oxytocin, ADH (V1 recepor), TRH - (GGOAT)
Steroid receptor hormones (7) Cytoplasmic vs nuclearCytoplasmic: Cortisol, Estrogen, Progesterone, Testosterone, Aldosterone, Vitamin D, (VET CAP)

Nuclear: T3/T4
Tyrosine Kinase Hormones (6) [specify type of pathway]Insulin, IGF-1, FGF, PDGF, Prolactin, GH [MAP Kinase Pathway](Think GF)
Steroid/Thyroid hormonesProgesterone, Estrogen, Testosterone, Cortisol, Aldosterone, Thyroxine/T3 (PETCAT)
SHBG-Sex hormone binding globulin - lowers free testosterone
- if too high in men you get gynecomastia
- if too low in women you get hirsutism


Question Answer
Steroid hormones mechanisms lipophilic and relatively insoluble in plasma - circulate bound to specific binding globulins which ⇡ solubility and allow for ⇡ delivery of steroid to the target organ. The need for gene transcription and protein synthesis delays the onset of action of these hormones.
Thyroid hormones sourceFollicles of thyroid
T3 functions (5)1. Bone growth
2. CNS maturation
3. ⇡beta1 receptors in heart = ⇡CO,HR,SV, contractility 4.⇡Basal metabolic rate via ⇡Na/K ATPase activity = ⇡ O2 consumption, RR, body temp.
5. ⇡glycogenolysis, gluconeogenesis, lipolysis
Thyroid hormone regulationTRH stimulates TSH which stimulates folicular cells.
Free T3 is negative feedback to TRH.
Major thyroid productT4 more than T3
Higher affinity for thyroid receptorT3 more than T4
PeroxidaseThe enzyme responsible for oxidation and organification of iodide as well as coupling on MIT and DIT



Question Answer
Cushing syndrome ⇡ cortisol
Causes of Cushing syndrome (4)1. Exogenous steroids (⇣ACTH level)
2. Cushing Disease (⇡ ACTH from pituitary adenoma)
3. Ectopic ACTH (15%)
4. Adrenal -adenoma, carcinoma, nodular adrenal hyperplasia (low ACTH)
Cushings findingsHTN, weight gain, moon faces, truncal obesity, buffalo hump, hyperglycemia (insulin resistance), skin thinning, striae, osteoperosis, amenorrhea and immune suppression, muscle weakness, hypokalemia, metabolic alkalosis
Cushing screening test24 hour urine free cortisol
Dexamethasone testsWill suppress ACTH - normal response is low cortisol after a dose.
1. ACTH pitu tumor will have high cortisol after a low dose and low cortisol after a high dose (but will have normal ACTH level when it should be low).
2. Ectopic ACTH tumor will have high cortisol after both tests and will have a high ACTH
3. Cortisol producing tumor will have high cortisol after both tests and will have low ACTH
Primary HyperaldosteronismConn’s syndrome
- benign aldosterone producing tumor
- HTN, hypokalemia, metabolic alkalosis and low plasma renin.
Primary hyperaldosteronism treatmentSpironolactone -K+ sparing diuretic that acts as aldosterone antagonist
Secondary hyperaldosteronism-Kidney perception of low intravascular volume results in overactive RAAS system
Secondary hyperaldosteronism causesRenal artery stenosis, chronic renal failure, CHF cirrhosis, nephrotic syndrome - assoc with high plasma renin.


Question Answer
Addison’s disease(primary vs secondary)Chronic adrenal insufficiency
- primary deficiency of cortisol and aldosterone
- primary causes is atrophy or destruction (autoimmun, Mets, or TB)
- secondary causes ⇣ pituitary ACTH and No hyperkalemia
Addison's tests-Zero increase in ACTH stimulation of cortisol or 17OH
-Increased ACTH in metyrapone test
-HypoNa, HyperK, acidosis
Addison's txGlucocorticoids, Mineralcorticoids
Addison’s sxhypotension (hyponatremic hypovolemia), skin hyperpigmentation (ACTH byproduct from POMC=MSH), Adrenal atrophy,
Waterhouse-Friederichsen syndromeAcute adrenocortical insufficiency due to adrenal hemorrhage assoc w. N.Meningitidis septicemia, DIC and endotoxic shock
PheochromocytomaMost common tumor of adrenal medulla - from chromaffin cells - most tumors secrete epinepherine, NE and dopamine
Pheochromacytoma sx-Episodic, Pressure (HTN), Pain (Headache), Perspiration, Palpitations, Pallor
Pheo rule of 10s 10% malignant, 10% bilateral, 10% extra-adrenal, 10% calcify, 10% kids, 10% familial
Pheo associationsNeurofibromatosis, MEN 2A and 2B
Pheo treatmentAlpha antagonists: Phenoxybenzamine - nonselective irreversible alpha blocker
NeuroblastomaMC tumor of adrenal medulla in children
- HVA in urine (break down product of dopamine)
- Less likely to develop hypertension
- N-myc oncogene= rapid tumor progression
- common mets to skin
- treat with surgery/rad/chemo
Neuroblastoma diagnosisAbd mass, diastolic HTN, in child, increased urine VMA and HVA, scan with I-MIBG [changed in 2011]