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Endocrine
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57
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Graduate
12/14/2012

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Term

What's the pathophysiology behind the exophthalmos in Graves disease?

How might this be treated?

Definition

Result of autoimmune attack on extraoccular mm, where lymphocytes infiltrate EOM and orbital fat causing edema and proliferation of local interstitial fibroblasts, and deposition of GAGs

This is pronounced b/c of SNS mediated lid retraction


Treat this by giving corticosteroids

Term

How can you differentiate Grave's from Plummer's disease in terms testing?

What's the difference in pathophys?

Definition

-Graves (diffuse toxic goiter) - autoimmune; production of thyroid stimulating antibodies -> diffuse stimulation of thyroid

  -Thus a radioiodide scan will show diffuse uptake b/c every cell is hyperfunctioning

-Plummers (multinodular toxic goiter) - caused by hyperfunctioning areas of thyroid gland (2/2 mutation in TSH-R); body responds by decreasing TSH -> atrophy of rest of thyroid

  -Radioiodide scan will show patchy uptake on thyroid scan

Term
What are the 4 carcinomas of the thyroid, and what is there prognosis?
Definition

1) Papillary - has psamomma bodies, often presents as a solitary cold nodule of thyroid,good prognosis

2) Follicular - capsular and vascular invasion, int. progn.

3) Anaplastic - large pleomorphic cells w/ large multinucleated osteoclast-like cells. Poor prognosis

4) Medullary - arise from parafollicular (C-cells), associated 20% of time with MEN2A/2B

 

Term

How does resin T3 uptake work?

What's the value of this test?

 

Definition

-The resin works by binding to free T3 in serum, then resin is removed, and amount of T3 bound to the resin is quantified. Recall, T4/T3 can either bind to TBG or the resin

-The test disinguished between increased TBG vs increased T4 production as the cause of increased throid hormones

  -True hyperthryoidism - excess T4 will use up all the binding sites on TBG -> radioactive T3 uptake will increase

  -Elevated TBG - more binding sites for T4 and T3, so resin T3 uptake decreases

Term

Pt being treated for Grave's disease is being given I^131. After 1 year of therapy, she still has hyperthyroidism.

NSIM?

 

Definition

Administer another dose of I^131

SU pg 159

 

Recall, you can't give this to pregnant women, or women who are breastfeeding!

Term

What is the treatment of choice of immediate control of adrenergic Sx of hyperthyroidism? How long do you treat pt wih this?

 

When do you start other therapies? How long do you keep these therapies?

Definition

-beta-blockers (propranolol) for immediate control

 

-you can start methimazole in add'n to beta-blockers, then pater beta-blocker afte 4-8 wks (once methimazole) starts to take effect.

  -continue methimazole for 1-2 yrs, check thyroid-stimulating IgG at 1 yr: if absent -> discontinue, if present -> then continue methimazole for 1 more year or consider radioiodide therapy

Term
When should you seriously consider radioactive iodide therapy as opposed to other medical therapies for hyperthyroidism (3 instances)?
Definition

1) Elderly pts with Grave's

2) Pts with solitery toxic nodule

3) Pts with Grave's disease in whom therapy w/ anti-thyroid drugs fail (e.g. relapse, agranulocytosis)

Term
What is the Wolf-Chaikoff Effect?
Definition

When high levels of iodine inhibit organification (and therefore synthesis) of thyroid hormone. This is the basis of Amioderone induced hypothyroidism

 

WCE can be followed by an "escape phenomenon," where follicular cells resume nml thyroxine synthesis b/c of normalization of iodine levels w/in cell 2/2 down-regulation of iodine symporter

Term

76 y/o female is brought in b/c of decreased mental status. Her vitals are: BP 90/60, HR 48, T 95. Exam shows an obtunded woman, cool pale skin, and marked non-erethematous swelling of hands, face, and tongue. Clinical chemistry shows Na 128 and glucose 68. Her daughter says she was recently Dx'd with pneumonia, and is being treated with AbX.

Dx?        Tx?

NSIM?    Prognosis?

Definition

Dx - myxedema coma (severe hypothyroidism), likely precipitated by pneumonia

  -other causes include: severe untreated hypothyroidism, trauma, cold exposure, and narcotics

NSIM - get TSH +/- cortisol BEFORE thyroid replacement

Tx - Thyroxine!!! You should also give glucocorticoids in stress doses until andrenal insufficiency is ruled out

Prognosis - very poor, 50-75% of pts die even w/ Tx

 

Term
Is the edema of hypothyroidism pitting or non-pitting? Why?
Definition
Non-pitting b/c edema is 2/2 GAG in interstitial tissues, NOT water and salt
Term

What is "subclinical hypothyroidism?"

What are the 4 indications for treating it?

Definition

It's when thyroid function is inadequate, but increased TSH production maintains T4 level w/in reference range of normalcy. So TSH is high, and T4 is nml

 

Treat with thyroxine if pts develop:

1) Goiter                         3) Sx of hypothyroidism

2) hypercholesterolemia   4) Highly elevated TSH (>20)

Term

For subacute (de Quervain's) thyroiditis (aka subacute granulomatous thyroiditis), fill in the following:

 

1) Phases of illness?

2) Tender or Non-tender thyroid?

3) Radioiodine uptake level?

4) TSH level?

5) Tx?

Definition

1) Prodromal phase first for a few weeks (fever, flu-like illness), f/b transient hyperthyroidism (2/2 leakage of hormone from colloid), f/b transient euthyroid state, f/b hypothyroidism

2) Painful and tender thyroid

3) Low radioiodine uptake b/c follicular cells damaged

4) Low TSH 2/2 suppression by increased T4 and T3; high ESR

5) Tx - NSAIDs and aspirin for mild Sx; steroids for severe pain

Term

For subacute lymphocytic thyroiditis, fill in the following:

1) Phases of disease?

2) Radioiodide uptake level?

3) Tender or nontender thyroid?

Definition

1) Phases:

  -Thyroitoxic phase for 2-5 months, f/b...

  -Hypothyroid phase  - usually self limited

2) Low radioactive iodine uptake - differentiates this from Grave's!!!

3) Painful and tendner - differentiates this from Subacute (viral) thyroiditis (de Quervains)

Term

Does a pt need to have hyperthyroidism to have Thyroid-associated ophthamopathy (proptosis, eye lid edema, exophthalmos)?

 

Tx?

Definition

No!!!

Pts may be hypo/eu/hyper-thyroid when TAO presents

 

Tx - oral steroids

Term

For Fibrous thyroiditis (aka Riedel's Thyroiditis), fill in the following:

1) What is occuring here?

2) How does thyroid feel on palpation?

Definition

1) Fibrous tissue replaces thyroid tissue

2) Thyroid is firm to palpation

 

Extension of fibrosis can extend posteriorily and cause tracheal obstruction -> difficulty breathing!!!

Term

What physical exam findings may suggest that a thyroid nodule is malignant (one of these is a lab value)?

 

What things history might suggest malignancy?

Definition

1) Fixed in place, doesn't move with swallowing

2) Unusually firm consistency or irregularity

3) Nodule is solitary

4) Vocal cord paralysis (recurrent laryngeal n paralysis)

5) Cervical adenopathy

6) Elevated serum calcitonin

 

1) Hx of radiation therapy (papillary carcinoma)

2) Hx of rapid development

Term
Fine needle aspiration is reliable for all thyroid cancers except which one?
Definition
Follicular carcinoma
Term

What 2 syndromes are a/w with papillary carcinoma?

What syndrome is a/w medullary carcinoma?

Definition

Papillary - Gardner's syndrome, Cowden's syndrome

Medullary - MEN type II

Term

What are the tumors are associated with:

1) MEN 1 (Wermer's syndrome)

2) MEN 2A (Sipple's syndrome)

3) MEN 2B

Definition

MEN 1 - Pituitary (GH, prolactin), Parathyroid, Pancreatic

MEN 2A - Medullary carcinoma (calcitonin), Pheo, Parathyroid

MEN 2B - Medullary carcinoma, Pheo, mucosal neuromas + marfanoid habitus

 

Recall, homocystinuria is also a/w marfanoid habitus

Term

Pt comes in with a thyroid nodule, and you do an FNA. What do you do if the FNA results are:

 

1) Benign

2) Intermediate

3) Malignant

 

Definition

1) Benign - observe; unless it persists, then you do U/S

2) Intermediate - thyroid scan (see iodine uptake)

  -Cold -> surgery!

  -Hot -> close observation, periodic thyroid studies

3) Malignant -> surgery!

Term

27 y/o male is brought in by his girlfriend b/c of recent headaches. On further questioning, he admits to recent onset arthralgias, excessive sweating, and the fact that he's outgrown all of his clothes and shoes. Clin chem is significant only for elevated glucose levels.

Most likely Dx?

How do you Dx?

Tx?

Definition

Dx - acromegally

How to Dx - measure IGF-1 levels (aka Somatomedin C), should be high

Tx - Transphenoidal resection is Tx of choice

  -Octreotide can also be used (growth hormone inhibiting hormone, aka somatostatin)

Term
Name 5 causes of nephrogenic diabetes insipidous.
Definition

-Severe hypokalemia

-Hypercalcemia

-Lithium

-Demeclocycline

-Pyelonephritis

 

Term

What is the normal plasma osmolality?

What is the plasma osmolality in primary polydipsia?

What is the plasma osmolality in diabetes insipidous?

Definition

NML - 250-290 mOsm/kg

PPD - 255-280 mOsm/kg

DI - 280-310 mOsm/kg

Term

What test is required for making Dx of Diabetes Insipidous?

 

Definition

Water deprivation test (dehydration test), w/ injection of desmopressin once urine osmolality has stabilized

  -the latter differentiated btwn nephrogenic or central DI

 

Note: Obtaining ADH level is not test of choice, b/c it takes too long to get results

Term
What's the main treatments for Central and Nephrogenic DI (the treatments are different for the 2)?
Definition

Central - desmopressin (DDAVP) is firstline; chlorpropamide can also be used, which increases ADH secretion and enhances effect of ADH

 

Nephrogenic - thiazide diuretics!

  -Thise depeletes the body of sodium -> increased reabsorption of sodium and water in PCT -> less sodium and water reaches distal tubules -> decreased urine vol

Term
Is volume expasion seen in SIADH? Why or why not?
Definition

Not seen b/c natiuresis occurs despite the hyponatremia

  -Increased blood volume is sensed by stretch receptors in atria -> increased atrial natiuretic peptide -> vasodilation of efferent arterioles -> increased GFR & RPF

  -Renin-angiotensin-aldosterone system is inhibited as well by the volume expansion

Term

List the 6 neoplasms that can cause SIADH.

 

What are 5 other types of causes of SIADH?

Definition

Neoplasms - lung [small cell], pancreas, prostate, bladder, leukemia, lymphoma

Other causes:

1) CNS disorders - trauma, stroke, infection

2) Drugs - carbamazepine, vincritine, SSRIs, oxytocin, NSAIDs, cyclophosphamide

3) Pulmonary disorders (pneumonia, TB)

4) Positive Pressure Ventilation (wierd!)

5) Post-Operative State (as result of anesthesia, pain)

Term

What's the sodium level and total body water in Conn's syndrome?

What's the sodium level and total body water in SIADH?

Definition

Conn's:

  -Sodium level is normal b/c of aldosterone escape 2/2 increased ANP release due to increased blood volume

  -Total body water is high

SIADH:

  -Sodium level is low b/c of increases water reabsorption w/o concomittant sodium reabsorption, and b/c of increased natiuresis 2/2 increased ANP release

  -Total body water is normal

Term
What's the Tx for hypoparathyroidism?
Definition

Severe - IV calcium gluconate

Mild-Moderate - oral calcium

 

Can also give Vit D supplementation (calcitriol)

Term
What bone abnormality to pts with hyper-PTHism get?
Definition

Osteitis Fibrosa Cystica (brown tumors) - predisposes to pathologic fractures

  -This is a disorder in which bone turnover is increased due to increased PTH signalling to the osteoclasts (by way of osteoblasts) to increase bone resorption

Term
What is the main way you can differentiate primary hyperparathyroidism from familial hypocalciuric hypercalcemia?
Definition

Look at the urine calcium:

  -primary hyper-PTHism - high urine calcium b/c although PTH causes increased Calcium reabsorption in DCT, there's so much Calcium released from bone that it overwhelms DCT

  -FHHC - low urine calcium (<100 mg in 24 hrs)

     -Pathophys - FHHC is caused by an increased set point in Calcium sensing receptors in kidney -> increased calcium reabsorption

Term
Aside from serum calcium, phosphate, and PTH levels, what serum test (it's actually a ratio) can help diagnose hyperparathyroidism?
Definition

Chloride:Phosphorus ratio of >33 is diagnostic of primary hyper-PTHism (33-to-1 rule)

  -Chorlide is high secondary to renal bicarb wasting (direct effect of PTH)

  -Phosphorus is low due to direct effect of PTH

Term

What's the initial screening test of choice for Cushing's syndrome, and what's the cut off value?

 

 

Definition

Overnight (low-dose) dexamethasone suppression test

   -Give 1 mg dexameth at 11pm, and measure cortisol at 8am next day

        -If <5 -> appropriately suppressed, so Cushings excluded

        -If >5 -> pt has Cushings syndrome. Need further testing (ACTH levels (first), and high dose Dexameth suppression test (second)) to determine the cause of Cushings

Another good screening test is 24 hr urinary free cortisol level

 

Note:

  -Screening test for Addisons is cosyntropin (ACTH) stimulation

test

  -Screening test for Conn's Syndrome is measuring aldosterone:renin ratio (if elevated investigate further). Confirm Dx with saline infusion test (should suppress aldosterone in nml pts)

Term

What electrolyte and volume status abdnormality might you see in pts with Cushing's Syndrome?

 

What muscle disease might you see in pts with Cushing's syndrome?

 

Qid 4419

Definition

Corticosteroids have weak mineralcorticoid activity, thus pts might have hypernatremia, hypokalemia, hypervolemia

 

Corticosteroids can also cause myopathy 2/2 decreased protein synthesis, increased protein degredation, and mitochondrial alterations

  -p/w diffuse weakness and rhabdomyolysis, especially in the proximal LE mm

Term

What is the screening test of choice for pheochromocytoma?

 

Side Question:

What does it mean if a pheochromocytoma pt has elevated epinephrine?

Definition

Urine screen for metanephrines (best indicator) and/or vanillylmandelic acid

 

 

If elevated epinephrine, this means tumor must be adrenal or close to adrenal (organ of Zuckerlandl) b/c non-adrenal tumors can't methylate NE -> Epi

Term
What is a standard medical treatment in prep for preoperative removal of pheochromocytoma?
Definition
Phenoxybenzamine (irreversible alpha-1 blocker) administration
Term

What is the screening test for primary hyperaldosteronism?

 

How do you Dx it?

Definition

Screening - plasma aldosterone:renin ratio; ratio is >30 in pts with primary hyperaldosteronism

 

Dx made by Saline infusion test. If saline infusion doesn't suppress aldosterone levels -> diagnosis confirmed!


To determine the cause of primary hyperaldosteronism:

  -CT/MRI of adrenals--may demonstrate adenoma or hyperplasia

  -Adrenal vein sampling, CT is equivocal

  -Iodocholesterol scanning--a functional approach to differentiating btwn adenoma and hyperplasia

         -This is an important distinction b/c HTN 2/2 hyperplasia is not benefited with bilateral adrenalectomy, where as HTN 2/2 adenoma is cured by bilateral adrenalectomy

Term

What performing a cosyntropin stimulation test on a pt with suspected primary adrenal insufficiency, what would you expect the cortisol level to be after administration?

 

What about for suspected secondary adrenal insufficiency?

Definition

Primary - cortisol will NOT increase since this a problem with the adrenal gland

 

Secondary - cortistol will NOT increase right away since the gland had atrophied due to lack of ACTH for long period of time. If test is repeated for 4-5 days, the adrenals eventually respond normally

Term
What lab value needs to be documented to Dx congenital adrenal hyperplasia?
Definition

High levels of 17-hdyroxyprogesterone

 

Pt's DHEA (a downstream product of 17-hydroxypregnolone) may be normal

Term

For pts with DM, what things need to be screened every year?

 

Every visit?

 

Every 6 months?

Definition

Q year - microalbuminuria, BUN/creatinine, eye screen by ophthamologist, cholesterol level

 

Q visit - foot exam, BP

 

Q 6 months - check for neuropathy

Term
Why should you NOT place a diabetic on non-selective beta blocker therapy?
Definition

For 2 reasons:

1) If they overdose on insulin and become hypoglycemic, the early Sx of hypoglycemia (tremor, sweating, palpitations) may be absent, so pt will present later when blood glucose levels are dangerously low


2) Blockade of beta2-R -> inhibition of hepatic gluconeogenesis and peripheral glycogenolysis and lypolysis -> worsening of hypoglycemia


Thus DM pt should be instead be placed on selective beta1 blocker

Term

What lab value must be checked before placing a pt on metformin?

 

What's the most grave adverse effect of metformin?

 

Who should metformin NOT be given to?

 

Definition

Check serum creatinine before and during therapy, b/c it's contraindicated in renal failure

 

Grave SE is lactic acidosis

 

Metformin should not be given to renal failure pts, or alcoholics or CHF pts (the latter two b/c of the lactic acidosis)

Term

What are 4 side effects of glitazones (e.g. rosiglitazone)?

 

Definition

1) Weight gain

2) Edema - worsened by concurrent use of insulin

3) Hepatotoxicity

4) CV toxicity - can precipitate CHF!!!

Term
When do you know whether to treat DMII with exogenous insulin vs oral hypoglycemic agents?
Definition

Oral hypoglycemic agents are effective in DMII w/ moderate hyperglycemia (fasting glucose btwn 140-240). Start with either metformin or sulfonylurea

 

Exogenous insulin is typically given when pt has severe hyperglycemia (fasting glucose >240 mg/dL)

 

-This should make logical sense since in early disease, the pancrease still retains the ability to increase insulin production when blood glucose is high (thus the use of oral hypoglycemics); however, in later disease the beta-cells are destroyed and/or lose their capacity for insulin secretion (w/ deposition of amyloid w/in beta cells), thuse the need for exogenous insulin

Term

When giving radiocontrast to DM patients what can you give them to avoid toxicity?

 

What medication needs to be held when giving radiocontrast and why?

Definition

Give generous hydration before administering contrast to avoid precipitating renal failure

 

Hold metformin for 48 hrs after radiocontrast is given to prevent renal damage, and to make sure renal function has returned to baseline before resuming it

 

Term
What are 3 instances where a DM pt suffering from hypoglycemia might not show autonomic (Epi mediated) signs of hypoglycemia, such as sweating, tremor, increased BP and HR, anxiety, palpitations?
Definition

1) If the pt is on a non-selective beta-blocker

  -This suppressess the autonomic response to hypoglycemia mediated by Epinephrine -> blunted signs of hypoglyecemia

  -Also beta-2 blockade suppresses gluconeogenesis -> worsening of hypoglycemia

2) DM pts with severe neuropathy may not show autonomic response -> neuroglyopenic Sx (HA, visual disturbances, confusion, seizures, coma)

3) Longstanding disease (separate from the neuropathy), pt's response to hypoglycemia my be blunted

Term

What lab value will help you distinghuish between an insulinoma vs sulfonylurea abuse as the cause of a pt's hypoglycemia?

 

Definition

Proinsulin level (prohormone precursor to insulin)

  -It'll be high in insulinoma

  -It'll be normal in sulfonylurea abuse

Term
What is Whipple's Triad?
Definition

-Hypoglycemic Sx brought on by fasting (diaphoresis, palpitations, tremors, high BP and/or HR)

-Blood glucose <50mg/dL

-Glucose administration brings Sx relief

Term

What is the first test you do when you suspect a pt with Zollinger Ellison Syndrome (gastrinoma)?

 

What's the medical Tx of choice?

 

What in the way of management should always be done with ZES pts?

Definition

Fasting serum gastring level

  -If this is non-diagnostic, then a secretin stimulation test should be done

Medical Tx of choice - high dose PPIs

 

All ZES pts should undergo exploration in attempt at curative resection (20% of pts are cured with this)

Term

What are the cutaneous manifestations of glucagonoma?

 

What is the severity of diabetes melitus a/w glucagoma?

 

Definition

-Necrotizing migratory erythema (red blistering rash that spreads across the skin of lower abd, buttocks, perineum, and groin)

-Glossitis, stomatitis

 

DM in glucagonoma pts is mild

Term
What is the triad of Sx seen in pts with Somatostatinoma?
Definition

Gallstones due to inhibition of CCK release -> gallbladder stasis

DM due to supression of insulin release

Steatorrhea due to suppression pancreatic and intestinal fluid secretion -> malabsorption

 

Recall: Somatostatin inhibits the release of all GI hormones (CCK, secretin, VIP, GIP, Motilin) as well as other pancreatic hormones (insulin and glucagon)

Term

What are the clinical features of a VIPoma?

 

NSIM?

Definition

WDAH Sydnrome:

Watery diarrhea - leads to dehydration, hypokalemia, metabolic acidosis

Hypokalemia

Achlorhydria - VIP inhibits gastric acid secretion

 

Also see hyperglycemia, hypercalcemia, WL, facial flushing, and redness


NSIM:

1) correct dehydration with IVF

2) give meds to slow diarrhea, like octreotyde (somatostatin analogue)

3) if metastasis hasn't occured -> surgery!

Term

What is the first step in the evaluation of a pt with a thyroid nodule?

 

COPY INTO INTERNAL MEDICINE

Definition

Order a TSH

  -If low, get a radionuclide scan to confirm nodule is hot

  -If nml or high, do an U/S to assess if nodule is benign or malignant (solid or cystic)

     -If benign looking -> routine f/u

     -If malignant looking -> FNA

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