Flashcards in Endocrinology Deck (312):
Most common ectopic thyroid tissue site
tongue (lingual thyroid). removal may result in hypothyroidism if it is the only thyroid tissue present.
branchial cleft cyst origin
persistent cervical sinus
Thyroid tissue origin
parafollicular cell origin
adrenal cortex and medulla origin
cortex from mesoderm, medulla from neural crest
chromaffin cell regulatory control
preganglionic sympathetic fibers
Melanotropin (MSH) origin
Intermediate lobe of pituitary.
Anterior pituitary other name
Anterior pituitary origin
oral ectodrm (Rathke pouch)
Hormones that share alpha subunit
TSH, LH, FSH, and hCG. Beta subunit determines specificity.
ACTH and MSH are derivates of proopiomelanocortin (POMC)
hormones of anterior pituitary
FLAT Pig: FSH, LH, ACTH, TSH, PRL, GH.
B-FLAT: basophils-FSH, LH, ACTH, TSH
posterior pituitary other name
Origin of ADH and oxytocin
supraoptic and paraventricular nuclei
ADH and oxytocin transport
carrier proteins called neurophysins.
posterior pituitary embryo origin
Islets of langerhans
collections of alpha, beta, and gamma endocrine cells in the pancreas.
Islets of langerhans origins
Arise from pancreatic buds.
Islets of langerhans organizations
alpha cells peripherally, beta cells centrally, delta cells interspersed
alpha cells secrete
delta cells secrete
preproinsulin synthesized in RER --> cleavage of "presignal" --> proinsulin (stored in secretory granules) --> cleavage of proinsulin --> exocytosis of insulin and C-peptide equally.
increased in insulinoma and sulfonylurea use, whereas exogenous insulin lacks C-peptide
activates gene transcription
anabolic effects of insulin
1) Increases glucose transport in skeletal muscle and adipose tissue.
2) increases glycogen synthesis and storage
3) increases TG synthesis
4) increases Na+ retention
5) increases protein synthesis
6) increases cellular uptake of K+ and amino acids
7) decreases glucagon release
8) decreases lipolysis in adipose tissue
insulin and placenta
doesn't cross it, unlike glucose
adipose tissue + striated muscle. exercise can also increase GLUT-4 expression
RBCs, brain, cornea, placenta
beta-islet cells, liver, kidney, small intestine
fructose, spermatocytes, GI tract
insulin-independent glucose uptake pneumonic
BRICK L, brain, RBCs, intestine, cornea, kidney, liver
Major regulator of insulin release
Why is there increased insulin sensitivity with oral vs. IV glucose?
Incretins such as glucagon-like peptide 1 (GLP-1), which are released after meals + increased beta cell sensitivity to glucose.
Insulin growth pathway
insulin binds to receptor --> tyrosine phosphorylation --> RAS/MAP kinase pathway --> cell growth, DNA synthesis
Insulin glucose uptake pathway
insulin binds to receptor --> tyrosine phosphorylation --> Phosphoinositide-3 kianse pathway --> vesicles containing GLUT-4 translocate to membrane --> glucose enters via GLUT-4 carriers
Insulin release pathway
Glucose enters beta cells through GLUT-2 transporters --> undergoes glycolysis --> increased ATP/ADP ratio--> ATP-sensitive K+ channels close --> membrane depolarized --> voltage-gated Ca2+ channels open --> Ca2+ influx --> exocytosis of insulin vesicles.
1) glycogenolysis, gluconeogenesis
2) lipolysis, ketone production
increases ACTH, MSH, beta-endorphin
CRH and steroids
chronic exogenous steroids decrease CRH
decrease prolactin, decrease TSH
GHRH analog used to treat HIV-associated lipodystrophy
prolactin endocrine effects
decreases GnRH (which explains amenorrhea/hypogonadism in pituitary prolactinoma)
somatostatin endocrine efects
decreases GH, TSH
increases TSH + *prolactin
homologous to GH
1) tonically inhibited by dopamine from hypothalamus. 2) Prolactin in turn inhibits its own secretion by increasing dopamine synthesis and secretion from hypothalamus. 3) TRH increases prolactin secretion.
4) renal failure increases prolactin release via reduced prolactin elimination
5) pregnancy --> estrogen --> increased prolactin
TRH and hypothyroidism and amenorrhea
TRH increases prolactin secretion in hypothyroidism --> hyperprolactinemia inhibits GnRH
cry of baby and prolactine mechanism
cry of baby activates higher cortical centers --> inhibit hypothalamus from secreting dopamine
1) stimulates linear growth and muscle mass through IGF-1 secretion
2) increased insulin resistance
GH regulation and secretion
- released in pulses in response to GHRH.
- secretion increases during exercise, deep sleep, puberty, hypoglycemia.
- secretion inhibited by glucose and somatostatin release via negative feedback by somatomedin.
means stimulates hunger
positive ghrelin regulation
sleep deprivation + Prader-Willi
stimulates hunger + GH release
endocannabinoids and munchies mechanism
act at cannabinoid receptors in hypothalamus and nucleus accumbens, two key brain areas for the homeostatic and hedonic control of food intake, thus increasing appetite.
source of ADH
V1 vs. V2 ADH receptors
V2 regulate serum osmolarity, V1 regulate BP
ADH level in Central and nephrogenic DI
down in central, normal or increased in nephrogenic
nephrogenic DI etiology
mutation in V2 receptor
desmopressin acetate 1) MOA, 2) clinical use
central DI + nocturnal enuresis
osmoreceptors in hypothalamus; hypovolemia
17alpha-hydroxylase lab profile
3) sex hormones
6) decreased andostenedione
21-hydroxylase lab profile
3) sex hormones
6) increased renin activity + increased 17-hydroxy-progesterone
11beta-hydroxylase lab profile
3) sex hormones
1) decreased aldosterone, but increased 11-deoxycorticosterone so increased Bp
6) decreased renin
Cortisol carrier protein
corticosteroid-binding globulin (CBG)
cortisol and immunology caveat
exogenous corticosteroids can cause reactivation of TB and candidiasis by blocking IL-2 production
cortisol and BP mechanism
1) Upregulates alpha1-receptors on arterioles, increasing sensitivity to NE and E.
2) At high concentrations, can bind to mineralocorticoid (aldosterone) receptors.
Increases Insulin resistance
Increases Gluconeogenesis, lipolysis, and proteolysis
Decreases Fibroblast activity (causes striae)
Decreases Inflammatory and Immune responses
Decreases Bone formation (by decreasing osteoblast activity)
Cortisol and immune modification mechanism
1) inhibits production of leukotrienes and PGs
2) inhibits WBC adhesions --> neutrophilia
3) blocks histamine release from mast cells.
4) reduces eosinophils
5) blocks IL-2 production
CRH --> ACTH --> cortisol production. Excess cortisol deceases CRh, ACTH, etc.
Plasma calcium forms
1) ionized (45%)
2) bound to albumin (40%)
3) bound to anions (15%)
calcium and pH mechanism
increased pH increases affinity (negative charge) of albumin for Ca --> hypocalcemia (cramps, pain, paresthesias, carpopedal spasm).
sun, fish, plants
Ingestion of plants, fungi, yeasts
Vitamin D negative regulation
1,25-(OH)2 feedback inhibits its own production
PTH and urine cAMP
PTH increases urine cAMP
- receptor activator of NH-kB ligand.
- secreted by osteoblasts and osteocytes.
- Binds RANK (receptor) on osteoclasts and their precursors to stimulate osteoclasts and increase calcium, leading to bone resportion.
other regulator of PTH
decreased serum Mg increases PTH, but severely decreased Mg decreases PTH secretion.
Common causes of hypomagnesemia
diarrhea, aminoglycosides, diuretics, alcohol abuse.
PTH and vitamin D mechanism
positive regulator of 1alpha-hydroxylase
parafollicular cells (C cells) of thyroid
Source of T3/T4
Follicles of thyroid. Most T3 formed in target tissues.
4 B's --> Brain maturation, Bone growth (synergistic with GH), Beta-adrenergic affects (increases beta1 receptor expression in heart), increases Basal metabolic rate.
*also increases glycogenolysis, gluconeogenesis, lipolysis.
How does T3 increase basal metabolic rate?
via increased Na+/K+-ATPase activity, leading to increased O2 consumption, RR, body temperature
thyroid-stimulating immunoglobulin. Graves disease.
Excess iodine temporarily inhibits thyroid peroxidase, leading to decreased iodine organification, and decreased T3/T4 production.
When is TBG (thyroxine-binding globuline) increased and decreased?
Decreased --> hepatic failure, steroids.
Increased --> pregnancy (via estrogen), OCP use.
what converts T4 to T3?
T3 vs. T4 potency
T3 binds nuclear receptor with greater affinity
Thyroid peroxidase functions
1) oxidation and organification of iodide
2) coupling of monoiodotyrosine (MIT) and di-iodotyrosine (DIT).
DIT + DIT
DIT + MIT
propylthiouracil and methimazole and thyroxine actions
Propylthiouracil inhibits both thyroid peroxidase and 5'deiodinase. Methimazole inhibits thyroid peroxidase only.
Thyroglobulin secreted into follicular lumen --> organification of I2 by thyroid peroxidase --> T4 endocytoses back into epithelial cell --> coupling reaction, T4, T3 to circulation
thyroglobulin derived from
Iodine uptake mechanism
cotransport with Na
hormones that act through cAMP pathway
FLAT ChAMP --> FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2), MSH, PTH.
ALSO --> calcitonin, GHRH, glucagon.
hormones that act through cGMP
Think vasodilators. BNP, ANP, EDRF (NO)
other name for NO
EDRF, endothelium-derived relaxation factor.
Hormones that act through IP3 pathway
GnRH, Oxytocin, ADH (V1), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin
hormones that act through an intracellular receptor
Progesterone, estrogen, testosterone, cortisol, aldosterone, T3/T4, vitamin D
hormones that act through receptor tyrosine kinase (MAP kinase pathway)
Insulin, IGF-1, FGF, PDGF, EGF
hormones that act through nonreceptor tyrosine kinase (JAK/STAT)
Prolactin, immunomodulators (eg, IL-2, IL-6, IFN), GH, G-CSF, Epo, thrombopoietin.
lipophilic. thus must be bound to specific binding globulins to increase their solubility
affect of SHBG in men
Sex hormone binding globulin. Lowers free testosterone causing gynecomastia.
Cause of hirsutism in women
Decreased SHBG raises free testosterone.
SHBG increased with...
steroid signaling pathway
Hormone binds to receptor in nucleus or cytoplasm --> transformation of receptor to expose DNA-binding domain --> bidns to enhancer-like element in DNA --> activates gene transcription.
Most common cause of cushings
exogenous corticosteroids (resulting in decreased ACTH and bilateral adrenal atrophy)
Causes of cushings
1) exogenous corticosteroids
2) primary adrenal adenoma, hyperplasia, or carcinoma -- result in decreased ACTH, atrophy of uninvolved adrenal gland. Can also present with pseudohyperaldosteronism.
3) ACTH-secreting pituitary adenoma (Cushing disease).
4) paraneoplastic ACTH secretion
what causes most endogenous Cushings?
ACTH-secreting pituitary adenoma.
ACTH-secreting pituitary adenoma
HTN, weight gain, moon facies, abdominal striae, truncal obesity, buffalo hump, skin changes, osteoporosis, hyperglycemia (insulin resistance), ammenorrhea, immunosuppression
Cushing's screening tests
1) increased free cortisol on 24-hr urinalysis
2) increased midnight salivary cortisol
3) NO suppression with overnight low-dose dexamethasone test.
4) measure serum ACTH
What is the use of a high-dose dexamethasone suppression test?
Suppression = Cushing disease
No suppression = ectopic ACTH secretion
What is the use of a CRH stimulation test?
Increased ACTH, cortisol = Cushing disease
No increased ACTH, cortisol = ectopic ACTH secretion
Lab findings for exogenous glucocorticoids or adrenal tumor
ACTH will be LOW
Adrenal insufficiency presentation
weakness + fatigue + orthostatic hypotension + muscle aches + weight loss + GI disturbances + sugar and/or salt cravings
Adrenal insufficiency diagnosis
1) measurement of serum electrolytes
2) morning/random serum cortisol and ACTH
3) ACTH/cosyntropin stimulation test
4) metyrapone stimulation test
difference in labs between primary and 2/3 adrenal insufficiency
low cortisol, high ACTH in primary adrenal insufficiency; low cortisol, low ACTH in secondary/tertiatry due to pituitary, hypothalamic disease
metyrapone stimulation test + analyzing results
Metyrapone blocks last step of cortisol synthesis (11-deoxycortisol to cortisol). Normal response is decreased cortisol and compensatory increased ACTH and 11-deoxycortisol. In primary adrenal insufficiency, ACTH is increased but 11-deoxycortisol remains low after test. In secondary/tertiary adrenal insufficiency, both ACTh and 11-deoxycortisol remain decreased after test.
primary adrenal insufficiency labs
hypotension (hyponatremic volume contraction) + hyperkalemia + metabolic acidosis.
Why do you have skin hyperpigmentation in primary adrenal insufficiency?
Increased MSH, byproduct of ACTH production from proopiomelanocortin (POMC).
primary adrenal insufficiency association
Autoimmune polyglandular syndromes.
Acute adrenal insufficiency cause and presentation
Massive hemorrhage. Shock.
Acute, primary adrenal insufficiency due to adrenal hemorrhage with septicemia (usually neisseria), DIC, endotoxic shock.
autoimmune in Western world, TB in developing.
Secondary adrenal insufficiency
Decreased pituitary ACTH production.
Difference in presentation with secondary adrenal insufficiency
No skin/mucosal hyperpigmentation, no hyperkalemia (aldosterone synthesis preservd). (secondary spares the skin/mucosa)
Cause of tertiary adrenal insufficiency
Chronic exogenous steroid use, precipitated by abrupt withdrawal. Aldosterone synthesis unaffected.
Why is there no edema in hyperaldosteronism?
causes of primary hyperaldosteronism
adrenal adenoma (Conn syndrome) or idiopathic adrenal hyerplasia.
Causes of secondary hyperaldosteronism
1) renovascular hypertension
2) juxtaglomerular cell tumor (due to independent activation of RAAS)
secondary hyperaldosteronism labs
Increased aldosterone + increased renin.
origin of neuroendocrine tumors
Kulchitsky and enterochromaffin-like cells.
examples of neuroendocrine tumors
1) medullary thyroid
2) small cell carcinoma
3) islet cell tumor in pancreas
hormones secreted by neuroendocrine tumors
5-HIAA, neuron-specific enolase (NSE), chromogranin A
What do neuroendocrine cells contain?
amine precursor uptake decarboxylase (APUD)
neural crest cells
can occur anywhere along the sympathetic chain.
Most common presentation of neuroblastoma
Firm, irregular mass that can cross the midline (vs. wilms, which is smooth and unilateral).
urine metabolites in neuroblastoma
increased HVA and VMA
neuroblastoma tumor markers
Bombesin + NSE positive.
Up to 25% associated with germline mutations (NF-1, VHL, RET [MEN 2A, 2B]0
pheochromocytoma rule of 10s
10% malignant, bilateral, extra-adrenal, calcify, kids
pheochromocytoma management and caveat
Irreversible alpha-antagonists (eg phenoxybenzamine) followed by beta-blockers prior to tumor resection. alpha-blockade must be achieved before giving beta-blockers to avoid a hypertensive crisis.
proximal muscle weakness, increased CK associated with hypothyroidism
hypothyroidism derm presentation
appetite in hypo/hyperthyroidism
decreased in hypo, increased in hyper
hyperthyroidism -- proximal muscle weakness, normal CK
hyperthyroidism derm presentation?
pretibial myxedema (Graves), periorbital edema
skin and hair findings in hyperthyroidism
warm, moist skin; fine hair
adrenergic response to hyperthyroidism
increased number and sensitivity of beta-adrenergic receptors
hyper/hypocholsterolemia in hyper and hypothyroidism
Hypercholesterolemia in hypothyroidism (decreased LDL receptor expression); hypocholesterolemia in hyper (increased LDL receptor expression).
Causes of smooth/diffuse goiter
1) Graves disease
2) Hashimoto thyroiditis
3) Iodine deficiency
4) TSH-secreting pituitary adenoma
Causes of nodular goiter
1) Toxic multinodular goiter
2) Thyroid adenoma
3) thyroid cancer
4) thyroid cyst
antibodies in hashimoto's
antithyroid peroxidase (antimicrosomal)
HLA hashimoto's association
hashimoto and cancer
Increased risk of non-Hodgkin lymphoma (typically of B-cell origin)
May be hyperthyroid early in course due to thyrotoxicosis during follicular rupture
Hurthle cells, lymphoid aggregates with germinal centers
moderately enlarged, NONTENDER thyroid.
Causes of cretenisism
1) maternal hypothyroidism
2) thyroid agenesis
3) thyroid dysgenesis
4) iodine deficiency
5) dyshormonogenetic goiter
most common cause of cretinism in US
subacute granulomatous thyroiditis progression
Can be hyper early in course, followed by hypo
subacute granulomatous thyroiditis findings
Elevated ESR + jaw pain + *****very tender thyroid.
Thyroid replaced by fibrous tissue with inflammatory infiltrate. Fibrosis may extend to local structures (eg, trachea, esophagus), mimicking anaplastic carcinoma.
1/3 are hypothyroid
IgG4-related systemic disease (eg, autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis).
fixed, hard (rock-like), PAINLESS.
other causes of hypothyroidism
1) iodine deficiency
2) goitrogens (amiodarone, lithium)
3) Wolff-Chaikoff effect
cause of pretibial myxedema in graves
thyroid-stimulating immunoglobulin stimulates dermal fibroblasts
common presentation of graves
during stress (eg, pregnancy)
Tall, crowded follicular epithelial cells; scalloped colloid.
Exophthalmos in Graves mechanism
Infiltration of retroorbital space by activated T-cells --> increased cytokines (TNF-alpha, IFN-gamma) --> increased fibroblast secretion by hydrophilic GAGs --> increased osmotic muscle swelling, muscle inflammation, and adipocyte count --> exophthalmos.
etiology of toxic multinodular goiter
Focal patches of hyperfunctioning follicular cells working independently of TSH usually due to TSH receptor mutations.
Hot vs. cold nodules
Hot nodules are rarely malignant.
uncommon but serious complication that occurs when hyperthyroidism is incompletely treated/untreated and then significantly worsens in the setting of acute stress such as infection, trauma, surgery.
thyroid storm presentation
agitation + delirium + fever + diarrhea + coma + tachyarrhythmia (cause of death).
thyroid storm labs
can see increased LFts
thyroid storm treatment
4 P's: propranolol, propylthiouracial, prednisolone, potassium iodide
thyrotoxicosis if a patient with iodine deficiency is made iodine replete. opposite of Wolff-Chaikoff.
cold thyroid adenoma
nonfunctional, becomes "hot" or "toxic" via autonomous thyroid hormone production (rare)
Most common histology of thyroid adenoma
*Differentiating thyroid adenoma from follicular carcinoma
Absence of capsular or vascular invasion in thyroid adenoma.
complication of ligating superior laryngeal artery
transection of superior laryngeal nerve
complication of ligating inferior thyroid artery
transection of recurrent laryngeal nerve
genetics associated with increased risk of papillary carcinoma
RET + BRAF mutations
histology of papillary carcinoma
Empty-appearing nuclei with central clearing (orphan annie eyes), psammoma bodies, nuclear grooves.
follicular carcinoma characteristics
Invades thyroid capsule and vasculature (unlike follicular adenoma), uniform follicles; hematogenous spread is common.
follicular carcinoma genetics
associated with RAS mutation
undifferentiated/anaplastic carcinoma and prognosis
older patients; invades local structures. very poor prognosis.
familial hypocalciuric hypercalcemia pathophys
Defective Ca2+-sensing receptor (CaSR) in multiple tissues (eg parathyroids, kidneys). Higher than normal Ca2+ levels required to suppress PTH.
familial hypocalciuric hypercalcemia labs
mild hypercalcemia + hypocalciuria + normal to elevated PTH
unresponsiveness of kidney to PTH --> hypocalcemia despite elevated PTH levels. Due to defective Gs protein alpha subunit causing end-organ resistance to PTH. Defect must be inherited from mother due to imprinting.
Pseudopseudohypoparathyroidism pathophys and presentatoin
physical exam features of Albright hereditary osteodystrophy but without end-organ PTH resistance. Occurs when defective Gs protein alpha-subunit is inherited from father.
Dwarfism, caused by a mutation in the GH receptor.
Labs in Laron syndrome
Increased GH, decreased IGF-1
Laron syndrome presentation
Short height + small head circumference + characteristic facies with saddle nose and prominent forehead + delayed skeletal maturation + small genitalia.
usually pituitary adenoma
large tongue with deep furrows + deep voice + large hands and feet + coarsening of facial features with aging + frontal bossing + diaphoresis (excessive sweating) + impaired glucose tolerance (insulin resistance) + increased risk of colorectal polyps and cancer.
Enlargement of existing ACTH-secreting pituitary adenoma after bilateral adrenalectomy of refractory Cushing disease (due to removal of cortisol feedback mechanism).
Nelson syndrome presentation
Hyperpigmentation+ headaches + bitemporal hemianopia.
Nelson syndrome treatment
pituitary irradiation or surgical resection.
prolactinoma arises from..
treatment for prolactinoma
dopamine agonists (ergot alkaloids such as bromocriptine, cabergoline), transsphenoidal resection.
consists of osteoclasts and deposited hemosiderin from hemorrhages. Causes bone pain.
refractory (autonomous) hyperparathyroidism resulting from chronic renal disease.
tertiary hyperparathyroidism labs
Very hight PTH + hypercalcemia
cause of primary hyperparathyroidism
usually parathyroid adenoma or hyperplasia.
Primary hyperaparathyroidism labs
hypercalcemia, hypercalciuria, hypophosphatemia, increased PTH, increased ALP, increased cAMP in urine.
17-hydroxypregnenolone --> dehydroepiandosterone (DHEA
17-hydroxyprogesterone --> adrostenedione
Pregnenolone --> 17-hydroxypregnenolone
Progesterone - 17-hydroxyprogesterone
Androstenedione --> Estrone
Testosterone --> Estradiol
How would you differentiate pituitary apoplexy from sheehan's?
apoplexy is hemorrhaging vs. sheehan's, which is ischemic infarct, so you get more of a mass effect presentation with apoplexy.
Lab findings in central DI
1) urine SG
2) serum osmolality
1) Less than 1.006
2) Greater than 290 mOsm/kg
3) Hyperosmotic volume contraction
Mechanism of gynecomastia in liver disease
Mechanism of hirsutism in PCOS
insulin resistance --> excess insulin lowers SHBG --> increased free testosterone levels.
Water deprivation test in central DI vs. nephrogenic DI
Central --> Greater than 50% increase in urine osmolality only after administration of ADH analog.
Nephrogenic --> Minimal change in urine osmolality, even after administration of ADH analog.
other causes of nephrogenic DI
Hypercalcemia, hypokalemia, lithium, demeclocycline (ADH antagonist)
Lab values in nephrogenic DI
1) urine SG
2) serum osmolality
1) less than 1.006
2) greater than 290 mOsm/kg
3) hyperosmotic volume contraction
nephrogenic DI treatment
HCTZ, indomethacin, amiloride. hydration, avoidance of offending agent.
when do you give desmopressin for DI?
1) serum osmolality greater than 295-300
3) urine osmolality doesn't rise despite a rising plasma osmolality.
Why is SIADH euvolemic?
Body responds with decreased aldosterone and increased ANP/BNP --> increased urinary sodium secretion --> this normalizes ECF fluid volume.
Causes of hypopituitarism
1) pituitary adenoma
4) Empty sella
5) pituitary apoplexy
6) brain injury
failure to lactate + absent menstruation + cold intolerance
empty sella syndrome and epidimiology
Atrophy or compression of pituitary gland, which lies in the sella turcica. Common in obese women.
Other causes of DM
1) unopposed secretion of GH and epinephrine.
2) glucocorticoid therapy (steroid diabetes).
vascular presentation of DM
arteriolosclerosis, leading to HTN + chronic renal failure. Also large vessel atherosclerosis, CAD, and peripheral vascular occlusive disease.
Most common cause of death in diabetes
motor, sensory (glove and stocking distribution) and autonomic degeneration.
Cause of cataracts in DM
sorbitol accumulation in organs with aldose reductase and decreased or absent sorbitol dehydrogenase.
1) HbA1c greater than 6.5
2) Fasting plasma glucose greater than 126 mg/dL
3) 2-hour oral glucose tolerance test, greater than 200 mg/dL
Fasting plasma glucose procedure
Need to fast for at least 8 hours
Test 2 hours after consumption of 75 g of glucose in water.
Why are diabetics thirsty?
hyperglycemia --> increased plasma osmolality --> stimulation of thirst
coma/death pathophys in DM
hyperglycemia --> osmotic diuresis --> sodium and potassium wasting --> hypovolemia --> circulation failure and decreased tissue perfusion --> coma/death
pathophys of ketogenesis in DM
increased lipolysis --> increased plasma free fatty acids --> ketogenesis, ketonemia, ketonuria --> vomiting.
Hyperosmolar hyperglycemia nonketotic syndrome
State of profound hyperglycemia-induced dehydration and increased serum osmolarity, classically seen in elderly type 2 diabetics with limited ability to drink.
Hyperosmolar hyperglycemia nonketotic syndrome pathophys
Hyperglycemia --> excessive osmotic diuresis --> dehydration.
Hyperosmolar hyperglycemia nonketotic syndrome pathophys
hyperglycemia + increased serum osmolarity + ***no acidosis (ketone production inibited by presence of insulin).
Hyperosmolar hyperglycemia nonketotic syndrome treatment
IV fluids, insulin therapy.
dermatitis (necrolytic migratory erythema) + diabetes + DVT + declining weight + depression.
octreotide + surgery
low blood glucose + symptoms of hypoglycemia (lethargy, syncope, diplopia) + resolution of symptoms after normalization of glucose levels.
How would you differentiate insulinoma from exogenous insulin use?
Increased C-peptie levels.
10% of cases associated with MEN 1
Decreased secretion of secretin + CCK + glucagon + insulin + gastrin.
diabetes/glucose intolerance + steatorrhea + gallstones
surgical resection; octreotide for symptom control
carcinoid syndrome rule of 1/3's
1/3 present with 2nd malignancy
1/3 are multiple
Most common malignancy in the small intestine
Menin and location
tumor suppressor gene on chromosome 11
parathyroid presentation of MEN 1 vs. MEN 2A
parathyroid adenomas in MEN 1, parathyroid hyperplasia in MEN 2A
Managing type 1 DM
low-carb diet + insulin
Managing type 2 DM
dietary modification and exercise for weight loss + oral agents, non-insulin injectables, insulin replacement.
Managing gestational DM (GDM)
dietary modifications, exercise, insulin replacement if lifestyle modification fails
Rapid acting insulin drugs
Lispro, Aspart, Glulisine (no LAG)
Rapid acting insulin drugs SE's
hypoglycemia + lipodystrophy + hypersensitivity reactions
Insulin type for DKA
Regular insulin (short acting)
Long acting insulins
detemir + glargine
biguanides, metformin metabolic actions
Increased peripheral glucose uptake
Renal insufficiency (causes metabolic acidosis)
weight loss or gain with biguanides?
modest weight loss
1st generation sulfonylureas
2nd generation sulfonylureas
glimepiride, glipizide, glyburide
SE's in first vs. 2nd generation sulfonylureas
1st generation: disulfiram-like effects
thiazolidinediones clinical use
monotherapy in type 2 DM or combined with other agents.
meglitinides clinical use
Monotherapy in type 2 DM or combined with metformin
Hypoglycemia (increased risk with renal failure) + weight gain
exenatide, liraglutide (sc injection)
GLP-1 analogs MOA
increase glucose-dependent insulin release, decrease glucagon release, decrease gastric emptying, increase satiety
GLP-1 analogs SE's
Nausea, vomiting, pancreatitis; modest weight loss
Lingaliptin, saxagliptin, sitagliptin
DPP-4 inhibitors MOA
Inhibit DPP-4 enzyme that deactivates GLP-1, thereby increasing glucose-dependent insulin release, decreasing glucagon release, decreasing gastric emptying, and increasing satiety.
DPP-4 inhibitors SE's
mild urinary or respiratory infections; weight neutral
pramlintide (sc injection)
Amylin analogs MOA
decrease gastric emptying = decrease glucagon
Amylin analogs SE's
Hypoglycemia in setting of mistimed prandial insulin + nausea
Amylin analogs clinical use
DM1 and DM2
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors
Canagliflozin, dapagliflozin, empagliflozin
Sodium-glucose co-transporter 2 (SGLT-2) mechanism
Block reabsorption of glucose in PCT
Sodium-glucose co-transporter 2 (SGLT-2) SE's
glucosuria + UTIs + vaginal yeast infections + hyperkalemia + dehydration (orthostatic hypotension)
Genes regulate fatty acid storage and glucose metabolism. Activation increases insulin sensitity + increases levels of adiponectin
acarbose + miglitol
alpha-glucosidase inhibitors MOA
Inhibit intestinal brush-border alpha-glucosidases. Delayed carbohydrate hydrolysis and glucose absorption, thus decreasing postprandial hyperglycemia.
alpha-glucosidase inhibitors SE's
PTU + methimazole
Ptu blocks Peripheral conversion
thionamide safe for pregnancy
Drug to use to control uterine hemorrhage
2) carcinoid syndrome
5) esophageal varices
1) Most effects mediated by interactions with GC response elements.
2) inhibite phospholipase A2
3) inhibite transcription factors, such as NF-kappaB
1) iatrogenic cushing syndrome
2) adrenocortical atrophy (when stopped abruptly after chronic use)
3) peptic ulcers
4) peptic ulcers
5) steroid diabetes
6) steroid psychosis
synthetic analog of aldosterone with little GC effects
fludrocortisone clinical use
Mineralocorticoid replacement in primary adrenal insufficiency
similar to GC's + edema, exacerbation of HF, hyperpigmentation
sensitizes Ca2+ sensing receptor (CaSR) in parathyroid gland to circulating Ca2+
cinacalcet clinical use
primary or secondary hyperparathyroidism