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169 Cards in this Set
- Front
- Back
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Physiology of vasopressin
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Receptors: V1 (vasoconstriction), V2 (AQP2 water channels in principal cells), V3 (increase ACTH release)
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Dx diabetes insipidus
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ADH deficiency = central DI
Polydipsia, polyuria (large volume) concentrated plasma dilute urine ddx: Congenital- AD vasopressin mutation (precipitates in posterior pituitary) Tumors Idiopathic |
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treat diabetes insipidus
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Central DI: DDAVP
Nephrogenic DI: treat underlying cause (K, Ca), thiazides |
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Somatostatin released from the hypothalamus inhibits which two hormones from the anterior pituitary
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GH
TSH |
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hypothalamic nuclei that produce oxytocin and vasopressin
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supraoptic
paraventricular - neurons pass from hypothalamus down the pituitary stalk to the posterior pituitary |
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where is the hormone produced, and what does it act on:
grehlin? leptin? |
both chemicals go to the arcuate nucleus, but lead to production of different peptides
grehlin: from stomach --> ARC --> NPY, AgRP --> lateral Hypothalamus = hunger leptin: from adipose --> ARC --> POMC, CART --> ventral medial Hypothalamus --> satiety/catabolism |
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two most common causes of neoplastic hypothalamic lesions
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craniopharyngiomas
pituitary adenomas |
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3 main signs of Hypothalamic lesion
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hypopituitism
hyperprolactinemia diabetes insipidus |
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Kallmann's Syndrome
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X-linked: KAL gene mutation - abnormal migration of GnRH and olfactory neurons
- no GnRH pulsatile secretions - no LH/FSH released - olfactory lobe hypoplasia = anosmia Rx: pulsatile GnRH therapy |
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disordered hypothalamus w/o primary hypothalamic defect
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anorexia nervosa
-amenorrhea -weight loss --> low Leptin --> negative feedback on GnRH and TRH release -behavioral changes |
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define and describe the triphasic response caused by pituitary stalk damage
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post surgery for pituitary adenoma, hypothalamic regions
1- acute/transient DI (neurons in shock, not releasing ADH) 2- interphase- dying neurons release all of their stored ADH- urine output temporarily returns to normal 3- neurons are dead- permanent DI (high urine output) |
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cause of nephrogenic DI (aka renal resistance to ADH)
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Hypokalemia, hypercalcemia, lithium, amphoB, Multiple Myeloma (often causes hypercalcemia)
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what test do you use to dx DI?
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Water deprivation test
- check to see if pt concentrates their urine - deprive of water for hours, then give DDAVP to see if urine Osm responds nml pt: will have increasing urine Osm, and no response to DDAVP DI pt: serum Osm increases, post DDAVP urine Osm fast and large increase |
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in the water deprivation test, which two pts do not respond to DDAVP?
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Nephrogenic DI
Primary polydipsia (because AGP2 channels are already maximally activated by functioning AVP) |
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which two pituitary hormones are inhibited by high levels of prolactin?
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LH, FSH
this leads to amenorrhea in women and decreased libido, impotence/hypogonadal symptoms in men w/ Hyperprolactinemia |
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why might a tumor in the somatotropes or lactotropes produce the same hormones?
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because they both derive from a very similar precursor cell
- so a somatotrope tumor may produce both GH (increase IGF-1) and prolactin |
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what is a non-functioning pituitary tumor?
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one that produces the alpha subunit shared by the glycoprotein hormones (TSH, LH, FSH, betaHCG)
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3Ps of Multiple Endocrine Neoplasia
- mt in menin, a tumor suppressor gene |
Pituitary adenomas (PRL, GH, ACTH)
Parathyroid hyperplasia (HPTH, hypercalcemia) Pancreatic neuroendocrine tumors |
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when, physiologically, are prolactin levels high?
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pregnancy (mid and last trimester), post partum breast stimulation
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which hormone increases release of prolactin, and in what disorder is prolactinemia a secondary symptom?
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TRH stimulates both TSH and PRL
Hypothyroidism (TRH increases, and T4 is low/absent) |
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causes of hyperprolactinemia?
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Prolactinoma
Pituitary masses--> stalk effect --> loss of dopaminergic inhibition Co-secretion w/ GH (common precursor cell)- Acromegaly Empty sella syndrome Neurogenic- herpes zoster Hypothyroidism, high estrogen states Hypothalamic disturbances Anti-dopamine drugs Chronic renal failure |
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diagnostic testing for hyperprolactinemia
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1. pregnancy (bHCG)
2. Thyroid function: (TSH, T4) 3. Other hormone levels (for panhypopituitarism) 4. MRI of pituitary w/ gadolinium contrast 5. Visual field testing |
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what is the hook effect?
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occurs when prolactinoma is so severe that the antigen (prolactin) clumps/aggregates out of solution in an immunoassay (w/ the testing antibody) and provides a falsely low value
- shoudl do a 1:100 dilution of serum |
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what is big prolactin?
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aggregate held together by autoimmune antibodies, not hormonally active, so elevated prolactin detected in lab assays, but there are no clinical symptoms
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Prolactinoma treatment
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Pharmacological first! then surgical
- dopamine agonists: bromocriptine (nausea, orthostasis), cabergoline caution with macros (>10mm)- more aggressive/invasive - follow up transphenoidal resection - this is the first treatment method in Acromegaly |
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growth hormone release cycle? when is GH at its highest?
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diurnal, levels rise during deep sleep
GH secretion stimulated by physical activity and emotional stress |
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main mediator of GH effects?
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IGF-1, somatomedin C
- skin, connective tissue, cartilage/bone, organs |
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biochemical confirmation of increased GH (acromegaly)
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Elevated IGF-1
- if it is high- suppress it: oral glucose tolerance test --> increase in insulin --> should decrease GH (nml pt). In acromegalic pt: GH will stay the same or even have paradoxical increase |
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Management of Acromegaly
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transphenoidal resection
- Somatostatin analogues- inhibits GH release from pituitary (octreotide, sandostatin/lanreotide- monthly injections) - Pegvisomant- GH receptor antagonist - dopamine agonist (bromocriptine/cabergoline) -possible radiation of GH remains >2ng/ml |
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what are the causes of increased mortality rate in acromegalics?
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cardiovascular and cerebrovascular!!
respiratory: enlarged tongue --> sleep apnea Malignancies Altered glucose metabolism --> DM |
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Release pattern for CRH (from hypothalamus) and ACTH (from anterior pituitary)
When is it highest? |
Pulsatile
Peaks in early morning, decreases throughout the day, then slowlys starts to rise after midnight Early morning |
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What is the only synthetic glucocorticoid that isn't detected in a cortisol assay?
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Dexamethasone
- best for pt w/ adrenal insufficiency - long acting |
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is cortisol catabolic or anabolic?
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catabolic, causes peripheral muscle wasting/weakness --> degradation of proteins
catabolism of subcutaneous connective tissue prtns causes fragility and easy bruising, and violacious colored striae (visible venous blood) |
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what are the two causes of elevated glucose in cushing's syndrome?
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insulin resistance --> decreased glucose uptake into tissues
muscle amino acid breakdown --> liver substrates --> increased hepatic glucose output |
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list the three things caused by long term glucocorticoid excess
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cataracts
glaucoma gastritis and peptic ulcer disease |
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cushing's disease
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ACTH dependent endogenous hypercortisolism
- pituitary lesion - or ectopic production of ACTH-neuroendocrine origin: small cell lung cancer and carcinoids |
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causes of ACTH independent Cushing's
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adrenal adenoma, adrenocortical carcinoma, macronodular hyperplasia
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in the diagnosis of cushing's syndrome, what do you do first: biochemical work up or imaging?
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Biochemical diagnosis
- Don't even think of imaging studies until after |
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biochemical diagnosis for cushing's syndrome (3)
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24h urine free cortisol (3X normal, repeat 3 times)
Dexamethasone suppression test (low dose)- check for feedback inhibition Midnight serum Cortisol (salivary)- check lack of diurnal rythm) Dexamethasone suppressed (48hrs), then CRH stimulation test - CS pt will respond to CRH (serum cortisol will increase) |
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in the diagnosis of cushing's syndrome, what do you do after confirming hypercortisolism?
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check ACTH levels
- undetectable: then the tumor is ACTH independent- CT adrenals - ACTH >20 pg/ml --> ACTH dependent- MRI pituitary |
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what is cushing's disease?
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pituitary adenoma >5mm secreting ACTH
60% sensitivity with Gad enhanced MRI |
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how do you differentiate a pituitary vs ectopic ACTH tumor?
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stimulate it: CRH
Suppress it: high dose Dexamethasone both tests are + = Cushing's disease both tests are - = ectopic cushing's syndrome --> small cell lung cancer, carcinoid |
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when is inferior petrosal sinus sampling useful?
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in proven hypercortisolism
checks petrosal sinus ACTH: peripheral ACTH ratios - >2, CRH stimulated |
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what is nelson's disease
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uncontrolled growth of residual ACTH producing pituitary tumor due to lack of feedback by cortisol --> hyperpigmentation
this occurs if you removal adrenal glands (adrenal hyperplasia, macronodular dysplasia in the adrenals) |
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what is the final treatment to try for cushing's syndrome?
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radiation
- EBRT - Gamma knife can take 5-10 years to take effect |
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how does ketoconazole work in the treatment of cushing's?
Mitotane? |
inhibits cortisol synthesis
atrophies the adrenal glands |
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etiologies of hypopituitarism
- single or multiple hormone deficiencies vascular, iatrogenic, infectious/infiltrative neoplastic, congenital, autoimmune, trauma/surgery |
Vascular:
- Sheehan's - low BP during birth (peripartum hypotentions --> infarction)- damages pituitary - Pituitary Apoplexy Iatrogenic: Brain radiation Infiltrative: Langerhan's cell histiocytosis, Hemachormatosis, Granulomatous diseases autoimmune- women, usually post partum- lymphocytes infiltrate pituitary/stalk neoplasms- pituitary adenoma, craniopharyngiomas, metastatic melanoma to pituitary congenital: deficiencies in transcription factors (Prop-1, Pit-1) trauma/surgery: leading to decreased vascular flow to pituitary |
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pituitary apolplexy = hemorrhage into the pituitary (often due to a lesion that is already present, such as an adenoma)
- which is more common, acute/catastrophic or silent/asymptomatic |
silent- spontaneous cures, empty sella, cysts
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major symptoms of acute catastrophic pituitary apoplexy
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headache, visual disturbance (field defects, cranial nerves II-VI), N/V, Blood in CSF, meningismus
symptoms can last hours to days |
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42 year old man
ER- double vision and headache left lateral rectus paralysis (CN VI) MRI shows acute hemorrhage into pituitary |
pituitary apoplexy
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what is the treatment for pituitary apoplexy?
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IV fluids, IV corticosteroids (assuming adrenal insufficiency), remove pressure on optic chiasm (craniotomy, decompression), eval for pituitary hormone deficiencies
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which hormone deficiencies are most often seen post pituitary apoplexy, and why?
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certain cells in pituitary are more sensitive to compression/lack of blood flow
- GH, HPAdrenal, Sex steroids, LH/FSH, HP-Tyoroid, ADH-DI (rare) |
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for which two hormones can you use the insulin tolerance test?
when do you use it and how does it work? |
ACTH/cortisol and GH
gold standard for assessment of pituitary hormone - based on counter-regulatory roles of insulin vs Cortisol and GH -insulin induced hypoglycemia- should see a rise in GH and cortisol/ACTH |
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how do you dose for adrenal hormone replacement?
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hydrocortisone given at largest dose in morning, then half that in afternoon
similar to diurnal rhythm none should be present at midnight |
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what is the metyrapone test? and when is it used?
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blocks the last step in cortisol synthesis (11-B-hyroxylase). Get build up of 11-deoxycortisol, and no/low cortisol. Hypothalamus/pituitary should see this lack of cortisol and pump out ACTH.
If there is no rise in ACTH, then there is pituitary deficiency |
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what do you see histologically in pituitary adenoma?
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effacement of acinar pattern, see sheets rather than nests of cells
then do IH staining to test for hormone overproduction |
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most dangerous of pituitary adenomas?
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Cushing's disease: hypersecreting pituitary adenoma--> ACTH secretor--> chronically driving adrenal glands
HTN, diabetes, poor wound healing, immune compromise, central fat redistribution |
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what is a sellar region meningioma?
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menigioma occuring at the portion of dura sheet at the base of the brain that separates pituitary from hypothalamus
field defects and cavernous sinus changes |
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second most common tumor in pituitary region after pituitary adenoma?
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sellar meningioma
- recurrence is frequent |
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what happens when migrating epithelial cells from rathke's pouch that normally form the adenohypophyseal migrate incorrectly?
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sellar region craniopharyngioma
- normally occurs above the sella - begins to invade the hypothalamus- see Rosenthal fibers as it is compressing adjacent brain = hard to treat - makes keratin - bimodal age occurence: childhool, then middle/late adult life |
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what is the difference b/t craniopharyngiomas in children vs adults?
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children: cystic, calcify
adults: solid |
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which cells are involved in an optic glioma?
Is the optic nerve being squashed? |
astrocytes and oligodendrocytes
nerve isn't being squashed, but rather there is invasion into the sub-arachnoid space |
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what are the symptoms of pinealoma?
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precocious puberty (early maturation of sexual features, growth factors)
compression of mid-brain: aqueduct of sylvia (hydrocephalus), vertical gaze palsy, pupillary control/convergence, CN 3 and 4 |
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what is a germinonma?
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germ cell tumors of pineal gland
see two different cell populations present most common pineal region mass very responsive to chemo and RT |
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when do you not want to perform an Insulin Tolerance Test?
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pt w/ angina or seizures
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32 year old female- fatigue, Nausea
Gets a UTI- progresses to FV, flank pain, Vom, shock Past history of: -Type I DM -hypothyroid (levothyroxine hasn't helped her fatigue) |
she has primary adrenal insufficiency (autoimmune process)
- infection caused an acute adrenal crisis- her body was unable to produce cortisol to the necessary stress levels treatment for adrenal crisis in chronic Adrenal Insufficient pt: 2-3X GC |
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60 yo male
suspected pulmonary embolism treated with heparin --> develops hypotension refractive to volume and vasopressors responds to IV Glucocorticoids what happened? |
heparin caused adrenal hemorrhage --> acute adrenal insufficiency - drop in cortisol --> low BP
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elderly pt
hyperkalemia, acidosis, mild-moderate renal impairment plasma renin - low aldosterone - low these levels don't respond to Na depletion or furosemide |
secondary selective hypoaldosteronism
pts have normal- elevated BP (unlike adrenal insufficient pts) |
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female pt comes in complaining of:
- fatigue - feeling cold all the time - having problems pooping - her menstrual cycle has been off, and she has noticed an occasional small amount of fluid from her breasts - having problems with her weight (she has been gaining) - she feels depressed she also thinks her hair is drier than normal and her skin is coarse |
hypothyroidism
- symptoms + lab test rx: -levothyroxine (T4) -Measure TSH after one mouth, alter T4 dose accordingly |
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what are the 3 somewhat specific Signs of hypothyroidism
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thinning of lateral third of eyebrows
delayed relaxation of deep tendon reflexes nonpitting edema (myxedema facial/periorbital) |
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what converts T4--> T3
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5'-deiodination
in target tissues, liver and kidney |
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what are the special patient populations that need to be considered when treating for hypothyroidism?
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Higher risk of cardiac arrhythmias (inducing or exacerbating angina) with sudden changes in thyroid levels (why? b/c TH stimulates B1 receptors in the heart)
- >50 yo (thyroxine clearance decreases with age) - Heart disease - Post-menopausal **Start low, go slow also caution in pregnant/postpartum women- effects mom and baby |
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in which situations do you need to increase the dose of thyroxine given (TSH is too high)?
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pregnancy- 50% more TH needed
malabsorption conditions- celiac drugs that reduce T4-->3 conversion drugs that alter absorption or clearance of T4: estrogens, rifampin |
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is the dose of the thyroid hormone what causes the arrhythmia in treating hypothyroid pts?
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NO
it is the thyroid functioning and blood test - so in pts with malabsorption problems/diseases (enteritis, pancreatic insufficiency, sprue, amyloid, whipple, sucralfate, aluminum, calcium carbonate) - don't need to worry about increasing dose causing cardiac problems |
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in mild thyroid failure is T4/3 higher than TSH?
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no
TSH is in the abnormal range, while T4/3 are still normal - the high levels of TSH are keeping TH normal, until pt reaches overt thyroid failure, and no level of TSH can keep the TH WNL treat with much smaller dose to prevent progression (in hypercholesterolemia, pts with symptoms, previous neck radiation, anti-TPO abs, goiter) |
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what are the problems associated with accidentally over-suppressing TSH levels?
especially in elderly |
Bone:
-decrease density Heart: - Increase HR, risk of atrial fibrillation, cardiac contractility, LV mass index, etc |
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butterfly shape of thyroid visible
white sclera visible under the top eyelid |
Grave's disease
thyrotoxicosis - Thyroid stimulating IgG (TSI)- competes fro TSH receptor on follicular cell |
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nonablative therapy for hyperthyroidism
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thionamides:
- PTU- additional benefit of blocking T4-->3 conversion. BUT- more dosing, immunosuppressive (agranulocytoisis) and hepatitis - methimazole |
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a pregnant woman with thyrotoxicosis, what do you treat her with?
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nonablative therapy:
- PTU- propylthiouracil- less transport across placenta and into milk basically the only time PTU is a superior treatment option to methimazole if she is thionamide resistant: surgery |
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what do you want to watch for when treated a hyperthyroid pt with thionamides (PTU or methimazole)?
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sore throat- agranulocytosis
hepatitis -PTU cholestasis-MTZ drug induced lupus, aplastic anemia |
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mechanism of action of thionamides
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stops iodination/organification and coupling
PTU also stops T4--> T3 conversioni n blood |
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nonablative agents lithium and iodine in hyperTH treatment
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stop export/endocytosis of T4/T3
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treatment for Grave's or toxic nodular goiter?
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radioiodine (RAI)- emits beta rays- local necrosis
Surgery: - RAI resistant Graves (or pregnant) - large toxic nodular goiter - thionamide resistant and pregnant risks: hypothyroid, hypoparathyroidism, laryngeal nerve injury |
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about 6 weeks after childbirth, woman comes in feeling tired, experiencing weight gain, and having her hair falling out
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postpartum thyroid dysfunction (form of silent lymphocytic thyroiditis)
autoimmune disease - risks: similar history, history of AI diseases, T1DM, goiter see small diffuse goiter triphasic course (like subacute and silent thyroiditis) some recover, others require hormones |
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female pt comes in complaining of severe neck pain, fever, malaise, tender goiter
she stats that she recently recovered from an Upper Respiratory VIRAL infection |
subacute (de Quervain's or granulomatous) thyroiditis
- high ESR, leukopenia (sign of infection/immune reaction) - neck pain in hyperthyroid phase (radiates to ear/jaw) triphasic disease (most recover in 6 months) rx: high doses of ASA, prednisone, Beta blocker for hyperthyroid phase, thyroid hormone |
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pt with tachyarrhythmia is on amiodarone, what are you concerns regarding this patient's thyroid?
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amiodarone-induced thyroid dysfunction
- amiodarone contains iodine need to screen before starting and periodic followup pt can be hypothyroid or rarely hyperthyroid |
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normal weight and size parameters of the thyroid, location?
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25 grams
2 lobes, isthmus, and pyramidal portion 2nd-3rd cartilage |
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what's the origin of C cells (parafollicular cells)
what do they produce and in what neoplasm are they increased |
neural crest
calcitonin medullary thyroid carcinoma thyroidesctomy- lose C cells- but do not see an effect on the body |
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most common cause of hypothyroidism in iodine sufficient regions
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hashimoto's thyroiditis
- autoimmune - lymphoid follicles (germinal centers- active B cell proliferation) - metaplasia of follicular cells (Hurthle cells) - possible asymmetric enlargement |
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female pt presents after recently recovering from an URI
her neck is tender/painful? what does she have? her clinical course? |
Subacute (DeQuervain, Granulomatous) Thyroiditis
- self-limited, 6-8 weeks - hyperthyroidism --> euthyroid --> hypothyroidism histo: multinucleated giant cells, acute inflammation, destruction of follicles acute + chronic = subacute, so see PMNs and giant cells colloid leaks out |
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simulates carcinoma clinically, extends into strap muscles/adjacent tissues
dense fibrosis replacing the thyroid gland |
reidel thyroiditis
scarring- may actually be an extension of Hashimoto's |
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what are you treatment options in Grave's disease?
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Radioablative therapy (over surgery)
surgery- in child bearing age, compressive symptoms |
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woman, thyrotoxicosis, moderate glandular involvement
what is the histology |
grave's
papillary hyperplasia- hypertrophy and hyperplasia of follicular epithelial cells gland is highly vascularized, but there is NO vasculature in the papillae diminished, pale colloid |
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extreme goiter
often mistaken for thyroid neoplasm F>M histology: multiple ill defined nodules with colloid lakes, huge follicles with papillary hyperplasia. degeneration- hemosiderin containing mphages Cystic, calcification diagnosis? prognosis? |
Multinodular goiter
- adenomatous or hyperplastic nodule - most are euthyroid possibility of developing into an individual toxic nodule (Plummer Syndrome)- hyperthyroidism - features of adenomatous nodules - suppresses the rest of the gland - RAU Scan- one dark nodule, the rest is very light |
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how can you differentiate between thyroid cancer and multinodular goiter?
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colloid
- lots present in MNG normal follicular cell cytology - MNG diffuse spread, highly aggressive - tumor |
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define follicular adenoma
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encapsulated, discrete nodules
cellular, slushy nodule no colloid nice fibrous capsule see microfollicles |
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define follicular carcinoma
treatment |
follicular cells invade capsule into surrounding thyroid
angioinvasion mostly benign rx: surgical excision then ablation |
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thyroid has waxy appearance due to production of amyloid (protein and calcitonin)
what is this a neoplasm of? prognosis? dx |
Neoplasms of C cells possibly virulent prognosis
dx: antibodies to calcitonin |
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what is the normal make up of the parathyroid glands?
what is altered in neoplasms? |
Chief cells (main type) --> Parathyroid hormone
oxyphil cells, clear cells 30-50% adipose tissue - this is displaced in neoplasm |
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older woman (>50yo)
hypercalcemia, renal stones (excess urinary excretion of calcium), hypophosphatemia, pancreatitis, neuromuscular weakness, cause, ddx? |
Primary Hyperparathyroidism (elevated serum PTH)
- Parathyroid adenoma (single gland, cured by removal) - Parathyroid hyperplasia - Parathyroid carcinoma (extremely high calcemia) |
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what is osteitis fibrosa cystica, causes?
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increased osteoclasts and fibroblasts
- cystic bone spaces filled with brown fibrous tissue (hemosiderin), bone pain (subperiosteal resorption) caused by: primary and secondary hyperparathyroidism |
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what are the main antibodies tested for in hashimoto's
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Anti-TPO, Anti-Tg
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is goiter present in hashimoto's thyroidits?
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yes, but only in the early stages of disease
late stages- atrophy |
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in what thyroid disease is it typical to hear a bruit with the stethoscope
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Grave's
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what is the pathogenic difference in iodine deficient vs iodine replete goiter?
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deficient
- heterogeneous response to TSH- chornic stimulation --> multiple nodules (euthyroid MNG or one large homogeneous gland) iodine replete- thyroid follicles are heterogeneous in growth and activity potential |
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what do you do with a pt who has non-toxic goiter (MNG) in regards to malignancy risk?
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longstanding risk due to hyperproliferation
-FNA - if negative- follow with annual US - inconclusive FNA or papillary cytology --> thyroidectomy |
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what are the treatment options in MNG w/o compressive symptoms
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US- q6-12 mo
?Thyroid suppression therapy- but goiter re-growth is rapid after therapy cessation Sx if: - suspicious neck lymphadenopathy - radiation to cervical region - rapid enlarged nodules |
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what are the treatment options in MNG w/ compressive symptoms
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RAI ablation
- reduces volume, improves dysphagia or dyspnea - disadvantage: hypothyroidism, need for additional ablation (always leaves some remnant tissue that can grow back) surgery: most commonly recommended for healthy pts |
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accumulation of glycoproteins retro-orbitally (edema and infiltration) causes what clinical manifestation
in which disease is this seen |
exophthalmos
Grave's Disease often acompanied by periorbital edema and ocular muscle paralysis (causing diplopia) |
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what is the pathology behind lid lag, in what disease is it seen?
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up-regulation of alpha and beta adrenergic receptors --> hyper-stimulation of sympathetic fibers of oculomotor nerve
Grave's Disease |
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what are the skin changes seen in Grave's disease?
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Nails- separate from nail bed (onycholysis- Plummer sign)
Pre-tibial myxedema (grave's dermopathy) |
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clinical manifestations of hyperthyroidism are often related to what?
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increased cellular metabolism and enhanced sympathetic adrenergic activity
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what are the treatment options for grave's disease?
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BetaBlockers for symptoms (anxiety, palpitations, tremors)
Thionamides (PTU, methimiazole) - high rate of remission - SE: allergies (rash, itching) - SE: fatal agranulocytosis (follow CBC, watch for severe sore throat, FV) Radioiodine ablation (I 131) - avoid in children and pregnant Surgery: large goiters not amenable to RAI, compressive symptoms |
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in a patient with toxic adenoma (single hyperfunctioning nodule leading to thyrotoxicosis), what are the treatment options, and what do you need to take into consideration when treating?
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Anti-thyroid meds
RAI (I 131) -risk of hypothyroidism - some require 2nd dose - **symptomatically toxic pts may need thionamides first before RAI to reduce risk of worsening toxicity (thyroid storm) surgery - children and adolescents - prefferred over RAI when nodules are very large Advantage: save rest of the gland (low risk of hypothyroidism) |
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A Grave's pt is admitted to the ICU with atrial fibrillation, on history it is noted that pt recently stopped taking their medications.
what is going on? How do you treat? |
thyroid storm
- extreme form of hyperthyroidism (tachycardia, GI symptoms, FV) - can also be caused by any of the hyperthyroid states, or stress - VERY high Mortality treat: - ICU, supportive measures, Betablockers, Anti-thyroid drugs (IV), steroids (need to replace rapidly metabolized GC and GCs necessary in high stress condition), then iodine ( MUST GIVE AFTER thionamides) |
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what is the wolff chaikoff effect?
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autoregulatory effect- increased levels of iodine inhibit further organification of iodide, inhibiting biosynthesis of TH
Do NOT give high dose iodine before giving thionamides (in treatment of thyroid storm) |
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what form of hyperthyroidism is seen in elderly patients with almost no symptoms or perhaps somewhat less of the typical full blown symptoms of hyperthyroidism?
what are the likely symptoms? |
Apathetic hyperthyroidism
less likely to have a goiter possible heart findings: tachycardia, atrial fibrillation weight loss, anorexia, fatigue constipation (despite thyrotoxic) cognitive dysfunction |
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when would you treat a pt with subclinical hyperthyroidism (low TSH, normal FT4 and FT3)?
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cardiac dz (CAD, AFib)
>60yo- risk of AFIB TMNG Osteoporosis |
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how does hyperthyroidism cause osteoporosis?
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increases bone metabolism (activates osteoblast to produce RANKL and to release MCSF- to activate osteoclasts)
stimulates osteoclasts |
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3months to 4 years after a pt begun taking amiodarone for arrhythmias, begins experiencing thyroid dysfunction.
what happened? |
amiodarone contains iodine
causes increase in iodine pool in body --> decrease in RAIU also, decreases peripheral deiodination of T4 to T3 (like what other drug? PTU) |
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in a pt with hypothyroidism
TSH: low FT4: Low what type of hypothyroidism is this, what tests should be done? |
Secondary or Tertiary hypothyroidism
- TRH stimulation test - MRI- (mass effect- CN involvement) |
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what causes hypothyroidism via inhibition of function?
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iodine deficiency, iodine administration excess, Anti-thyroid meds (PTU, methimazole, lithium, interferon), inherited defects
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what are the transient forms of hypothyroidism?
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postpartum thyroidits
silent/lymphocytic thyroiditis subacute thyroiditis (DeQuervain's, Granulomatous) |
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large tongue, periorbital edema, deep voice, dry skin
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hypothyroidism
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profound hypothyroidism leading to:
-depression of the respiratory center, hypothermia, hypoglycemia, hyponatremia what is the condition? |
Myxedema Coma
- very high mortality need early dx and ICU treatment |
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what are the most common forms of thyroid cancer?
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papillary then follicular
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cancer of the parafollicular cells
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Medullary thyroid cancer
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30-50yo female
presents with a slowly growing neck mass she is experiencing dysphagia and hoarseness and has a few enlarged cervical LN |
papillary thyroid cancer
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where does papillary thyroid cancer metastasize to?
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cervical and upper mediastinal lymph nodes
occasionally lungs unusual to see distant mets |
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how do you dx and treat papillary and follicular thyroid cancer
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Dx: FNA
- papillary: marginated chromatin to edge of nuclei, give clear looking nuclei appearance Rx: thyroidectomy +/- LN dissection and RAI therapy |
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40-60 yo woman
has a form of thyroid cancer that invades blood vessels early mets to lungs and bones |
follicular thyroid cancer
- 50% mortality at ten years |
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what is the difference between familial vs sporadic medullary thyroid cancer?
how do you diagnose |
familial- could be related to Multiple endocrine neoplasias types 2A/2B
- RET oncogene - perform genetic analysis for Dx and inquire about other endocrine tumors dx: calcitonin levels (very high) |
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65 yo +, majority in women
rapidly enlarging neck mass extensive local damage (trachea) |
anaplastic thyroid cancer
type of thyroid cancer that is extremely aggressive, therapy is only supportive (sx is not effective) from pre-existing goiter or pre-well differentiated cancer |
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what are the constituents of the Basic Multicellular Unit (BMU) or Bone Remodeling Units (BRU)
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osteoclasts and osteocytes
BRUs occur in multiple areas of bone at different times |
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what are the phases of bone turnover
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activation, reversal, formation, mineralization
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what intracellular processes are involved in osteoclast absorption of bone?
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CAII: creates HCO3 and H+
Cl/HCO3 exchanger Cl and H pumps located on membrane surface that faces bone --> dissolves mineral Secretes Cathepsin K --> dissolves matrix |
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what is Cbfa1? In which cell is it present?
What factors influence Cbfa1? |
transcription factor - causes differentiation and bone formation --> expression of RANKL
Osteoblasts IL-1, 6, 11, PTH, PTHrP, Calcitriol --> increase Cbfa1 |
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what effects do the hormones and cytokines (IL-1, 6, 11, PTH, PTHrP, Calcitriol) have on the Bone Remodeling Unit?
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increase Cbfa1 in osteoblasts
stimulate osteoblasts to produce MCSF --> stimulates osteoclasts |
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what does OPG do?
which cell produces it? |
made from ostoblasts- binds RANKL- stops it from binding to RANK on osteoclasts- blocks osteoclast activation
important to have sufficient OPG to inhibit diseases such as osteoporsis via HyperPTH, GC, osteolytic bone mets, etc |
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does osteoclast have feedback mechanism towards osteoblast?
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yes
releases TGFB1 (which is self inhibitory) and IGF1, FGF2 --> activate osteoblasts |
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systemic skeletal disease
low bone mass microarchitectural deterioration compromised bone strength (decreased bone mass and quality) |
osteoporosis
silent disease until fracture occurs |
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list causes of secondary osteoporosis
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endocrine (hyperTH, primary hyperPTH, Cushing's, Addison's, Hypogandism)
MM RA Post transplant Meds: GC |
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where are the common fracture sites of osteoporosis
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spine- see wedge shaped compression deformity on radiograph
hip- femural neck forearm- distal radius |
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what is the osteoporotic fracture syndrome
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compression of vertebral body puts other vertebral bodies at risk --> progressive curvature of spine and loss of height
pain, deformity, loss of height, disability |
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what age is peak bone mass achieved?
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build maximum peak bone mass occurs in adolescents to twenty's. 18-25
primary prevention key- increase in peak bone mass: Ca and VitD in kids/adolescents |
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Post-menopausal woman, with low body weight, who smokes, drinks, and has never been a big exerciser, comes in for a routine check up
she is no corticosteroids for an unknown reason she has + FHx of maternal hip fracture what is our concern? |
osteoporosis
-risk for fracture - low BMD (low peak bone mass + increased bone loss), high bone turnover (poor bone quality) - risk of falls |
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what happens to bone remodeling intensity after menopause?
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Remodeling intensity increases
- causes the bone to be porous - increased fracture risk multiple BRUs happening at a time = more bone loss. Post menopause BRU increases = lose lots of bone density |
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what hormonal factors increase the expression of OPG by osteoblasts?
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TGFB1 (released from old bone matrix during resorption)
- this is decreased in estrogen deficiency |
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what does Dual Energy Xray Absorptiometry (DXA) measure?
for what diagnosis is it useful? |
Bone marrow density (obtain T score- basis of definition of osteoporosis)
osteoporosis: BMD < 2.5 SD below T score osteopenia: BMD b/t -1- -2.5 SD below T score normal: win 1 SD of reference mean BMD |
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in measuring BMD, what is a T score, what is a Z score
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T score: compares BMD to young female (peak of bone mass density) reference
Z score: compares BMD to similar age, gender, race |
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what are serum measurements of N-telopeptide, A- telopeptide, and osteocalcin used for?
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Breakdown products of type I collagen- indicate bone resorption
pathogenesis of osteoporosis, risk of future fracture, monitor response to therapy NOT useful in osteoporosis diagnosis |
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when do you treat pts with osteoporosis?
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postmenopause, men >50yo
hip or vertebral fractures WHO FRAX algorithm |
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nonpharmacologic treatment of osteoporosis
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Calcium, Vit D
fall prevention, exercise, smoking and alcohol avoidance |
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mainstain pharmacologic treatment of osteoporosis:
anti-resorptives |
bisphosphonates (zoledronic acid can be given IV)- flattened ruffled border of osteocytes- stops acid release
Selective Estrogen Receptor modulators Calcitonin- nasal spray- vertebral fracture reduction, reduce acute fracture pain |
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what agent increases bone formation, used for osteoporosis treatment
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PTH- Teriparatide
- intermittent use - powerful bone forming agent - reduce vertebral and non-vertebral fractures |
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what agent cannot be used simultaneously with bisphosphonates?
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Teriparatide (PTH)
- use for two years, stop it, then initiate bisphosphonates |
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what is the treatment for GC induced osteoporosis?
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bisphosphonates
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pain, deformity, fracture (localized), high output cardiac failure, compression of neural tissue (CNs)
- structurally disorganized- susceptible to deformities and fractures what disease? typical radiographic findings? treatment? |
Paget's Disease
overactive osteoclasts leads to increase in osteoblastic bone formation radiographic: cortical thickening, lytic and sclerotic changes. Skull- cotton wool appearance Rx: bisphosphonates |
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marble bone disease, albers-shonberg
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osteopetrosis
- defective osteoclasts - normal osteoblasts |
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increase in bone formation leads to decreased bone marrow space
thickened cortical and trabecular bone |
Osteopetrosis
- osteoclast derived TRAP is elevated rx: bone marrow transplant |
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symptoms of DM
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polyuria, polydypsia, polyphagia, weight loss, blurred vision, numbness
OR pt presents with complications: - microvascular: renal, eye, nerve - macrovascular: cardiovascular, cerebrovascular, peripheral vasculature |
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what are the two diagnostic tests for diabetes?
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Fasting plasma glucose >= 126 mg/dl
- screening test 2h OGTT plasma glucose >200mg/dl - give a glucose load after a 10-16h fast. take blood at 2h. Do this test if pt is FPG - but with suspicious clinical syptoms |
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is the glucose threshold higher or lower for macrovascular complications in comparison to microvascular complications?
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lower. macrovascular complications can being in the pre-diabetic stages.
but microvascular complications are very specific for diabetes (renal, eye, nerve). so use glucose threshold for when micro complications begin to appear as the diagnostic point for diabetes |
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which type of diabetes has a strong family history?
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type 2DM
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what are women who develop gestational diabetes at risk of?
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type 2DM
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what is the "Metabolic Syndrome" and what does it put you at risk for?
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Precursor of diabetes- same macrovascular (CV) risks
5 categories of defects - Impaired Fasting glucose (>100,<126)/Impaired glucose tolerance (>140, <200) - body weight/abdominal obesity - high BP - low HDL - high TG cluster of risk factors that lead to CV disease risk for devo to type 2DM should initiate aggressive treatment -lifestyle interventions, drugs |
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what physical finding is a strong clue of insulin resistance?
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acanthosis nigricans
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describe the pathogenesis of autoimmunity in type1DM
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interaction b/t environment and genetics--> causing release of antigens (like GAD and insulin) --> activate Dendritic cells --> activate clonal T and B cells --> get T cell mediated and/or Humeral response
And cytokines released --> lead to Beta cell destruction There are some circulating antibody markers (GAD, Insulin, IA-2, ZnT8) |
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describe the progression of autoimmune type1DM
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genetic predisposition, then immunologic abnormality/markers kick in --> Beta cell destruction --> progressive impairment --> 80-90% destruction = overt diabetes.
at this point pt is begun on insulin. The insulin stops the toxic effects of hyperglycemia from killing remaining Beta cells for a while, causing the "honeymoon" period, but eventually these cells are killed off (humoral/cellular immunity) --> no Beta cells left |
