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Gosmanov Flashcards

1
Q

How do you differentiate DKA from HHS? What 4 features will they BOTH have?

A
  • (+) beta-hydroxybutarate -> residual insulin in HHS will suppress ketone body formation (unlike in DKA)
  • Both of these will have:
    1. Elevated serum osmolarity,
    2. Glucose elevation,
    3. High glucagon (bc body thinks there is no glucose in the body bc none in the cells), and
    4. Elevated TGs (insulin activates LPL, so higher TGs in pts without insulin)
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2
Q

Describe the pathogenesis of DKA.

A
  • INC glucose production (liver) + DEC glucose uptake (peripheral tissue) = HYPERGLYCEMIA, leading to osmotic diuresis and volume depletion
    1. Vol depletion -> less blood to kidneys, less glucose excreted, worse hyperglycemia
  • INC FFA release (adipose) + INC ketogenesis (liver) = KETOACIDOSIS, leading to DEC alkali reserve and metabolic acidosis
    1. Body thinks it needs to make more fuel to survive bc can’t access glucose -> driven by elevation of counter-regulatory hormones (e.g., glucagon, cortisol, and epinephrine)
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3
Q

Describe the pathogenesis of HHS.

A
  • INC glucose production (liver) + DEC glucose uptake (peripheral tissue) = HYPERGLYCEMIA, leading to osmotic diuresis and volume depletion
    1. Vol depletion -> less blood to kidneys, less glucose excreted, worse hyperglycemia
  • REMEMBER: pts w/HHS don’t have same red flags as pts with DKA, so they slowly build up glucose until they are obtunded -> often older patients with sudden onset of mental status changes
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4
Q

70-y/o male found down on the street. Blood glucose reading HI (>600). On admission to local ED, serum blood glucose was 1050 mg/dL. You suspect pt has non-ketotic, hyperosmolar, hyperglycemia. Which of the following is true of his condition?

A. He will have moist oral mucosa

B. He will have undetectable insulin level

C. His last insulin injection was 24 hours ago

D. His serum osmolarity is very high

E. His BP is high

A
  • D. His serum osmolarity is very high
  • BP will be low-normal or low in these patients
  • Oral mucosa will be dry because little remaining fluid in the body
  • Insulin levels ARE detectable
  • NOTE: DKA pts may also look dehydrated bc they will have N/V, but may not be as dehydrated as HHS bc they come more quickly to the hospital, and are treated more acutely
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5
Q

What are the diagnostic criteria for DKA?

A
  • Plasma glucose >250
  • pH <7.3
  • Bicarbonate <18
  • Urine ketone and serum ketone (+)
  • Variable effective serum osmolarity and alteration in sensoria/mental obtundation
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6
Q

What is the diagnostic criteria for HHS?

A
  • Higher plasma glucose, pH, and bicarb than DKA
  • Ketones can be positive (via nitroprusside rxn)
  • HIGH serum osmolarity (due to high glucose)
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7
Q

What are some of the common precipitating causes for HHS and DKA?

A
  • Failure to take insulin
  • Infection
  • New diabetes
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8
Q

What are the signs and symptoms of DKA?

A
  • SIGNS: hypothermia, tachycardia, tachypnea, Kussmaul breathing (rapid, deep hyperventilation), ileus, acetone breath, altered sensorium
  • SYMPTOMS: polydipsia, polyuria, weakness, weight loss, N/V, abdominal pain
  • Onset is relatively short, ranging from hours to a day or two
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9
Q

What are the signs and symptoms of HHS?

A
  • SIGNS: hypothermia, hypotension, tachycardia, altered sensorium
    1. Related to the severity of the hyperglycemia
  • SYMPTOMS: polydipsia, polyuria, weakness, poor appetite, symptoms of accompanying illness, mental status changes
    1. HHS pts (T2D) may think INC thirst, urination is part of their normal health maintenance, and may not be regularly checking their sugars
  • Onset is prolonged, ranging from days to weeks
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10
Q

What initial lab studies should be done on pts with suspected DKA/HHS?

A
  • Immediate blood glucose and serum ketones (beta-hydroxybutarate) by finger stick or from plasma
  • Additional: ABGs, CBC with differential, CMP (glu, electrolytes, bicarbonate, PO4, Mg, BUN, creatinine), serum ketones, urinalysis
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11
Q

What are the lab values for unequivocal DKA?

A
  • Blood glucose: 450
  • pH: 7.28
  • Bicarbonate: 14
  • Anion gap: 18
  • The larger the anion gap, the more alkali reserve you have used up
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12
Q

Why is beta-hydroxybutarate so important anyways?

A
  • This is the first test to dx DKA because pH and other factors can vary due to combo acid-base disorder (key diagnostic feature of DKA)
    1. Nitroprusside rxn a semi-quantitative est of acetoacetate and acetone, but NOT B-OH-B
  • Now have a device for these patients to use at home to check these levels
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13
Q

30-y/o F w/hx of T1D admitted to ICU for tx of DKA. On admission, blood glucose 820, bicarbonate 6, anion gap 25, potassium 3, serum osmolarity 330, pH 7.10, and creatinine 2.0. Which of the following statements about her DKA is correct?

A. Plasma K will INC during DKA treatment

B. Her last insulin injection was >24 hrs ago

C. Initial IV bolus of fluids should include hypotonic fluids

D. Insulin admin should begin regardless of K level

E. Subcu insulin is a preferred route of insulin admin in DKA

A
  • B. Her last insulin injection was > 24 hrs ago
  • Plasma potassium will DEC or stay the same, so you should give potassium with insulin
  • Should give isotonic fluids (normal saline) to maintain the circulation
    1. Can give hypotonic fluids later to get water back into the extravascular compartment
  • Do NOT give insulin subcu (skin is fluid deprived) —> IV is the BEST DELIVERY in pts with DKA
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14
Q

What are the differences in therapy of DKA and HHS? Similarities?

A

DIFFERENCES

  • DKA: insulin more important than fluids
    1. Frequent titration of insulin to avoid hypoglycemia
  • HHS: fluids more important than insulin (give physiologic amts of insulin)
    1. Insulin doesn’t work as well in pts who are volume depleted -> give more isotonic fluids

SIMILARITIES

  • Give isotonic first, then hypotonic in both cases; give boluses -> more, and longer time for HHS
  • Spectrum of potassium presentation:
    1. Normal/low K bc they lose it through kidneys
    2. High K concentration if renal insufficiency
    3. -> do no harm first, then help pt
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15
Q

What are the changes in metabolic and acid-base parameters during DKA tx (graphs)?

A
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16
Q

Why is admission serum K usually elevated in DKA?

A
  • Shift of K+ from IC to EC space (due to acidosis)
  • Giving these pts insulin will activate the Na/K pump, however, moving the K+ IC, so you need to give these pts K before insulin if their K is <3.5 (HHS or DKA)
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17
Q

Why is hyponatremia common in pts with DKA?

A
  • INC serum glucose
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18
Q

How do you calculate anion gap and total/effective serum osmolality?

A
  • Anion gap = Na - (Cl + HCO3)
  • Total osmolality = 2Na + glu/18 + BUN/2.8
  • Effective osmolality = 2Na + glu/18
    1. Note: corrected Na = (1.6xglu - 100)/100
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19
Q

What is the order of rapidity for Calcitriol effects on the body?

A
  • Renal reabsorption first
  • Bone mobilization second
  • Intestinal effect
  • REMEMBER: PTH INC 1-alpha-hydroxylase in the kidney
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20
Q

Describe Ca distribution in the body. What do we measure clinically?

A
  • Total body calcium: about 1kg
    1. 99% in bone (hydroxyapatite)
    2. 1% EC and soft tissues
    3. 0.1% IC
  • Serum Ca:
    1. 40% protein-bound
    2. 10% complexed (citrate or phosphate ions)
    3. 50% ionized -> free Ca that is bioavailable
  • Clinically, we measure TOTAL SERUM CALCIUM
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21
Q

Briefly describe Ca intake/output (image).

A
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22
Q

What are the 3 primary effects of PTH (image)?

A
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23
Q

How does PTH limit phosphate reabsorption?

A
  • DEC type 2 Na/Pi transporter in proximal tubule
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24
Q

What is the workup for hypercalcemia?

A
  • History and physical
  • Check albumin and total Ca x 2
    1. If albumin is low, total Ca will also be low (need to adjust for albumin level)
  • Check PTH
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25
Q

What are the PTH-dependent causes of hypercalcemia?

A
  • Primary hyperparathyroidism: main cause
    1. Tertiary hyperparathyroidism
  • Familial hypocalciuric hypercalcemia (FHH)
  • Medication-induced: Lithium of HCTZ-mediated -> looks just like primary, but pt. will be on one of these meds
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26
Q

What are the PTH-independent causes of hypercalcemia?

A
  • Tumor-induced: PTHrP or bone metastases
  • Granulomatous diseases (TB, sarcoid, lymphoma): ↑ 1,25 vit.D
    1. Activation of local 1-alpha-hydroxylase, INC expression of Ca transporters in the intestine
  • Multiple myeloma
  • Hyperthyroidism/adrenal failure: osteoclastic activity of the thyroid hormones
  • Immobilization: rapid bone turnover -> may be seen after spinal cord injury or long bone fracture in children and adolescents
  • Medication-induced: vitamin D toxicity, vitamin A toxicity, milk-alkali syndrome
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27
Q

What are the causes of primary hyperparathyroidism?

A
  • 80-85% adenoma
  • 15% hyperplasia -> MEN1, MEN2A, HPT- jaw tumor syndrome, familial HPT
  • <1% parathyroid carcinoma
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28
Q

Sporadic primary hyperparathyroidism epi and clinical features?

A
  • Risk factors: age, race (AA > W > H), sex (F > M)
    1. Almost 3x as common in women than men
  • Etiology unknown (adenoma, hyperplasia)
  • Clinical features: serendipity
    1. Stones
    2. Abdominal moans
    3. Psychic groans
    4. Bones
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29
Q

What are the symptoms in primary hyperparathyroidism?

A
  • Symptoms are non-specific, and majority of patients are asymptomatic
  • Fatigue/weakness, musculoskeletal pain, pruritis
  • Polydipsia/polyuria, renal failure/kidney stones
  • Constipation, anorexia/nausea/dyspepsia, pancreatitis
  • Depression/memory loss
  • Osteoporosis/fracture, HTN
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30
Q

What is the biochemical and imaging workup for primary HPT?

A
  • BIOCHEMICAL:
    1. Ca, albumin (ionized Ca)
    2. PTH
    3. 25-OH Vitamin D
    4. 24-hr urine Ca to differentiate from FHH -> no interventions recommended in FHH, but just observe them
    a. Urine Ca in pts w/1o hyperPTH normal or slightly elevated; very important for milder cases to collect the 24-hour urine Ca
  • IMAGING: make biochem dx first, then do imaging
    1. Thyroid US, 99Tc-sestamibi scan: localization studies to help surgeon know where to go (minimally invasive)
    2. DXA: bone scan
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31
Q

When would you do a parathyroidectomy in primary HPT?

A
  • One criteria suffices for parathyroidectomy:
    1. Ca > 1.0mg/dL above upper limit of normal
    2. Age <50
    3. Osteoporosis
    4. Renal insufficiency
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32
Q

What is the conservative mgmt strategy for primary HPT?

A
  • Adequate hydration
  • Bisphosphonates in pts with osteoporosis
  • Maintenance of Vit D status (20-30ng/mL)
  • Cincalcet: calcimimetic that activates CaSR in PTH gland -> for those who do NOT qualify for sx, and have moderate hypercalcemia (Ca >12.5mg/dL)
  • Annual follow-up: Ca/PTH, renal function, DXA
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33
Q

What is FHH?

A
  • Familial hypocalciuric hypocalcemia:
    1. Inactivating mutation of CaSR, 100% penetrance: need a higher Ca to shut down PTH production
    a. Also have lesions in kidneys, impairing Ca excretion
    2. Mildly elevated serum Ca, high-normal/mildly elevated PTH, hypocalciuria
    3. ASYMPTOMATIC
    4. Work-up: serum Ca, PTH, 24-hr urine Ca (<50-100mg/24-hr), can also ask relatives to check serum Ca, genetic testing
    5. NO TX is indicated
  • Note: some pts early in primary hyperPTH will present in a similar manner (normal PTH, and mildly elevated Ca)
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34
Q

What is tertiary hyperparathyroidism?

A
  • Occurs in the face of long-standing 2o hyperPTH
  • Parathyroid glands develop hyperplasia due to chronic low calcium and/or high phosphorous levels
  • At one point, these glands become autonomous (recall Primary HPT)
    1. In the setting of end-stage renal disease
    2. Post-kidney transplant
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35
Q

Hypercalcemia of malignancy etiology and clinical presentation

A
  • Etiology: breast, lung, lymphoma, thyroid, kidney, prostate, multiple myeloma, pancreas, etc.
    1. Most common: breast, squamous cell carcinoma
  • PTH LEVEL WILL BE SUPPRESSED (bc PTHrp binds to the same receptor -> INC IC cAMP)
  • Clinical presentation: consistent w/signs and sxs of hypercalcemia and potential diagnosis of malignancy
    1. Polyuria, dehydration, confusion, abdominal and musculoskeletal pains, fatigue, N/V
    2. Weight loss, pulm symptoms, LAD, history of cancer, anemia, abnormal chest X-ray
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36
Q

How can hyperCa occur in malignancy w/o INC in PTHrp?

A
  • Bony metastases can increase calcium levels
  • Humoral factors (cytokines, TNFa) can activate osteoclasts
  • Multiple myeloma can cause significant bone destruction resulting in hypercalcemia
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37
Q

Pt presents with low BP, high HR, high creatinine, and hypercalcemia. What is the most appropriate next step?

A
  • NORMAL SALINE INFUSION
  • Signs of dehydration: LOW BP, high HR, and high creatinine, suggesting kidney injury
    1. Need to maintain vol to keep this patient alive
  • Hypercalcemia can cause polyuria and dehydration
  • Calcitonin injections are 2nd or 3rd line therapy (will kick in within 24 hours)
  • Diuretic therapy only in pts that still have high calcium after volume repletion
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38
Q

How do granulomatous disorders cause hypercalcemia (image)?

A
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39
Q

How do you treat acute hyperCa?

A
  • Address volume status: normal saline
  • Saline Diuresis ± Furosemide: *only after volume status is corrected
  • Calcitonin: 3-4 days
  • Bisphosphonates: Pamidronate IV - works for 2-3 wks or Zoledronic acid IV - works for 1-3 months
  • Glucocorticoids: *useful in myeloma, granulomatous disease, vitamin D toxicity -> DEC activity of 1-alpha-hydroxylase
  • Dialysis
40
Q

What are the major causes of 2o PTH elevation?

A
  • Hypocalcemia
  • Hyperphosphatemia
  • Vitamin D deficiency
41
Q

Why are parathyroidectomy pts discharged on Ca supplements?

A
  • Takes time for the other glands to “wake up” after parathyroidectomy
42
Q

How can renal disease cause PTH elevation (image)?

A
43
Q

Describe the metabolic pathway of Vit. D (image).

A
44
Q

How should you approach a patient with 2o hyperPTH?

A
  • Symptoms non-specific and likely related to underlying disease causing elevated PTH, but not due to PTH itself
  • Evaluate key elements of the Ca axis: serum PTH, Ca (with albumin), Phosphorous, Creatinine, Vit D
    1. Do NOT collect 24-hour urine for calcium
  • No indications for imaging studies if Ca is normal
  • Treat underlying reason(s), and make sure Vit. D is always replete
45
Q

How common is Vit. D deficiency? Tx?

A
  • Severe Vit. D deficiency is rare
  • Presenting complaints in mild-to-mod Vit. D def are very non-specific: musculoskeletal pains, fatigue
  • 50% of pts with osteoporosis have vit. D deficiency
  • Vitamin D replacement (>800 units/day) showed ~20% reduction in risk of fractures
    1. Benefits of Vit. D replacement for prevention of cancer, DM, infections, HTN controversial
    2. J-shape association between mortality and vitamin D levels
46
Q

What are the clinical signs of hypocalcemia?

A
  • Agitation
  • Hyperreflexia
  • Convulsions
  • HTN
  • Long QT
  • Trousseau’s sign (BP cuff); Chvostek’s sign (facial N)
47
Q

What should be on your differential for hypocalcemia?

A
  • HypoPTH: 1o process as low PTH DEC Ca
    1. Post-thyroidectomy
    2. Idiopathic: Abs to PTH
    3. Autoimmune
    4. Parathyroid agenesis, e.g., DiGeorge
    5. HypoMg, hyperMg, hypophosphatemia
  • HyperPTH: 2o process (PTH INC due to low Ca from other causes)
    1. Renal failure
    2. Vit D deficiency
    3. Vit D or PTH resistance syndromes
48
Q

What are some “other causes” of hypoPTH?

A
  • Acute pancreatitis: free fatty acids chelate calcium
  • Massive transfusion: infusion of citrate will complex with calcium leading to decreased ionized calcium
  • Tumor lysis syndrome or rhabdomyolysis: phosphate release binds to ionized calcium
  • Severe sepsis: Cytokine-mediated
  • Medications: phosphate, bisphosphonates
  • Hungry bone syndrome
49
Q

How do you work-up hypocalcemia? Low PTH causes? High PTH causes?

A
  • H&P
  • Check albumin and total Ca x 2
  • Check PTH
    1. Low PTH:
    a. Hypoparathyroidism
    b. Magnesium deficiency
    c. Phosphate excess
    2. High PTH:
    a. Severe Vit. D deficiency
    b. Renal failure
    c. Vit. D or PTH resistance
50
Q

PseudohypoPTH

A
  • Idiopathic inherited forms of PTH resistance
  • Elevated PTH (1000s), hypoCa, hyperphosphatemia and/or specific morphological features including:
    1. Short stature, rounded face, foreshortened 4th and other metacarpals, obesity (Albright`s Hereditary Osteodystrophy- AHO)
  • Molecular defect - inability of PTH stimulate IC signaling events (cAMP pathway) due to mut in Gsa subunit or elements downstream to cAMP signaling
  • Variability in AHO and PTH renal resistance, so the condition is subclassified
51
Q

PseudohypoPTH classification (chart)

A
52
Q

How do you treat hypocalcemia?

A
  • Acute Hypocalcemic Crisis:
    1. Always correct magnesium if low (responsible for PTH production)
    2. Calcium Gluconate: 1-2 ampules over ~10-20 minutes, followed by infusion, if indicated
  • Long-term Management:
    1. Oral Calcium salts
    2. Vitamin D
    a. Ergocalciferol/Cholecalciferol (act in 10-14 days) -> effective only if PTH is present
    b. Calcitriol – active vitamin D
    3. Hydrochlorothiazide: INC reabsorption of Ca in the distal tubule
53
Q

Alcoholic comes in malnourished, with low everything. What do you replace first?

A
  • Magnesium
  • This will help PTH go up, then Ca and phosphorous levels will correct
  • Obviously, this is an extreme hypothetical (I’m sure fixing K+ would be more important)
54
Q

MEN1 patients are most likely to present with?

A

PRIMARY hyperPTH

55
Q

What is MEN?

A
  • Multiple endocrine neoplasia: syndrome in which 2 or more endocrine tumors occur in a single patient
    1. Auto dominant (e.g., DNA deletion): germline or sporadic mutations (2nd hit hypothesis)
    2. Different penetrance (varying phenotype)
    3. Benign and malignant
    4. Functionally active and inactive
56
Q

MEN1: affected gene, presentation, symptoms, screening, therapy.

A
  • Parathyroidectomy improves hypercalcemia, and reduces gastrin
57
Q

What is the typical timeline of the MEN1 phenotype?

A
  • Hypercalcemia due to 1o HPT by age 40 (19-40): most likely to present with this
  • Pituitary tumors dx on average at age 38 (12-83)
  • Pancreatic tumors:
    1. Insulinoma at age 25
    2. Gastrinoma at age 35
58
Q

MEN2A: affected gene, presentation, symptoms, screening, therapy.

A
59
Q

MEN2B: affected gene, presentation, symptoms, screening, therapy.

A
  • Affected gene
  • Presentation/penetrance
  • Signs/symptoms
  • Screening
  • Therapy
60
Q

What do you see here?

A
  • Some of the clinical features of MEN2B
  • Mucosal neuromas
  • Marfanoid habitus
61
Q

What are the 2 types of bone?

A
  • Cortical bone: outer, dense shell -> about 80% of total skeletal mass
  • Trabecular bone: network of connecting plates inside the cortical shell -> about 20%
62
Q

Cortical bone

A
  • Dense outer shell of compact bone; defines bone shape -> 80% of skeletal mass
  • Essential functions
    1. Provides biomechanical strength
    2. Attachment site for tendon and muscle
    3. Protection against excess trauma
  • Turnover rate of 2-3% per year
63
Q

What do you see here? How is this affected by age?

A

Cortical bone thinning and INC porosity -> INC significantly with age

64
Q

Trabecular bone

A
  • A sponge-like network of delicate plates of bone known as trabeculae -> 20% of skeletal mass
  • Essential functions:
    1. Mineral metabolism
    2. Strength and elasticity
  • Higher turnover rate compared to cortical bone
65
Q

What are these?

A

Resorption pits from osteoclasts

66
Q

What is the bone remodeling sequence in healthy pts (image)?

A
67
Q

Describe the RANK/RANKL/OPG pathway.

A
  • RANK: Receptor activator of NFkB
    1. Expressed by osteoclasts and their precursors
  • RANKL = RANK Ligand (paracrine effect)
    1. Expressed by osteoblast/stromal cells
    2. Promotes osteoclast differentiation, maturation, and prolongation of lifespan through RANK
  • OPG: Osteoprotegerin
    1. Secreted by osteoblast/stromal cells “Decoy” receptor for RANK
    2. Blocks RANKL signaling
68
Q

What are the biochemical markers of bone turnover?

A
  • BONE FORMATION:
    1. Bone-specific alkaline phosphatase
    2. Osteocalcin
    3. Carboxyterminal propeptide of type I collagen (P1NP)
  • BONE RESORPTION:
    1. N-telopeptide
    2. Carboxyterminal of type I collagen (CTX-1)
69
Q

Osteoporosis definition

A
  • Skeletal disorder characterized by compromised bone strength predisposing to an INC risk of fracture
  • Bone strength primarily reflects the integration of bone density and bone quality -> less bone mass and bone quality in osteoporosis
  • We have tools to determine bone mass, but not really bone quality.
  • Bone resorption >>>> bone formation
70
Q

Describe the multiple factors involved in the relationship b/t bone strength and fracture risk.

A
  • Genetics is very important: 75% of our bone mass is genetically predisposed; other 25% is diet and exercise
  • Accrual of bone density occurs in teens and young adulthood
  • Balance: age, meds can affect this -> fall prevention is very important for pts with osteoporosis
  • Marginal benefits seen with hip protectors, soft tissue padding (for big bone fractures; risk for small, distal fractures)
71
Q

What msmts should clinical evaluation of a pt with osteoporosis include?

A
  • Calcium
  • Phosphorous
  • DXA
  • 25-OH Vitamin D: 1/2 life of active Vit D is so short, so 25-OH Vit D measured
  • Do work-up sequentially —> Ca first, then PTH measurement (i.e., only if the Ca is high)
72
Q

How can you evaluate bone mass in osteoporosis?

A
  • Central DXA (dual energy x-ray absorptiometry): gold standard to measure bone mineral density
  • BMD is an important predictor of fractures
  • Very low level of radiation exposure, and no side effects
73
Q

What is the relationship of BMD to fracture risk?

A
  • DEC BMD = INC fracture risk
  • Each S.D. decrease corresponds to roughly a doubling of fracture risk
  • For a T-score of -2 there is a 4x risk of fracture and so on
74
Q

How does the WHO diagnose osteoporosis? Why is this relevant?

A
  • T-score equal or less than -2.5 is diagnostic of osteoporosis
    1. Low-trauma fracture when T-score is more than -2.5 is also consistent with osteoporosis
  • Cost-effective to initiate treatment in these patients; we call these pts osteoporotic -> REMEMBER THIS
  • If you break a bone in a non-traumatic way, no matter what your bone density is, it is still osteoporosis -> if pt has osteopenic bone density range, but gets a non-traumatic fracture (fall from the same height), this is STILL OSTEOPOROSIS
    1. This is also true even if at -0.5; bone density measurements are not perfect
75
Q

What is a pathologic fracture?

A
  • Bone breaking when coughing or sneezing, or breaking back when changing tire
  • Can be related to metastatic process into the bones
76
Q

When are BMD measurements useful?

A
  • To diagnose osteoporosis
  • To decide when to start treatment
  • To monitor response to treatment
77
Q

What is the impact of vertebral fractures on subsequent fracture risk?

A
78
Q

How does age affect fracture risk?

A
  • Age predisposes to fracture risk
  • Bone density picks up something important, but cannot describe all of the processes that are happening in bone
79
Q

What meds INC risk of fracture?

A
  • Glucocorticoids
  • Long-acting benzodiazepines: anti-anxiety
  • Tricyclic antidepressants and antipsychotics
  • PPIs
  • SSRIs
  • Anticonvulsants (long- term therapy)
  • Aromatase inhibitors
  • Androgen deprivation therapy
80
Q

What are the 9 independent risk factors for fracture according to the WHO?

A
  • Femoral neck T-score
  • Age
  • Previous low trauma fracture
  • Low BMI
  • Current cigarette smoking -> do NOT use any tobacco
  • High alcohol intake: more frequent falls, and hypogonadal (low testosterone and estradiol)
    1. Estradiol activates osteoblasts, and INH osteoclasts; any condition that affects testosterone levels can affect bones -> only 3 drinks and above is detrimental to your health
  • Steroid use
  • Rheumatoid arthritis
  • Family history of fracture: 75% of bone genetically determined
  • FRAX (online) tool used to identify pts with high enough risk for tx
81
Q

What are the red flags suggesting low BMD and potential endocrine-mediated secondary causes?

A
  • Chronic steroid use -> Cushing`s syndrome
  • Obesity, accelerated weight gain, buffalo hump -> Cushing`s syndrome or disease
  • Hypercalcemia -> primary hyperparathyroidism or malignancy-mediated
  • Arthralgias, large hands and feet, obstructive sleep apnea -> acromegaly
  • Kidney stones -> secondary hyperparathyroidism from hypercalciuria
  • Low libido, erectile dysfunction, loss of muscle mass -> hypogonadism
  • Suppressed TSH -> hyperthyroidism (also associated with osteoporosis)
  • Idiopathic or post-menopausal osteoporosis is always a diagnosis of exclusion
82
Q

How do you treat idiopathic osteoporosis?

A
  • Optimize lifestyle:
    1. Stop tobacco/ETOH
    2. INC physical activity
    3. Adequate Ca: 1200mg/d
    4. Optimize Vit. D. level: >30mg/dL
    5. Fall prevention
  • Pharmacological therapy:
    1. Antiresorptive agents
    2. Anabolic agents: help to build up new bone
83
Q

Which osteoporosis pts do you treat with meds?

A
  • T-score <=(-)2.5 after age 50
  • Treat osteopenia with history of fragility fracture
  • Use FRAX score to decide who to treat of those younger than 50 with a T-score <=(-)2.5 or older than 50 with a T-score >=(-)2.5
  • 10-yr risk of >3% for hip fracture, or >20% for major osteoporotic fracture is sufficient to initiate pharma treatment
84
Q

What are the 6 other disturbances in bone metabolism?

A
  • Osteomalacia/Ricketts
  • Paget disease of bone
  • Osteopetrosis
  • Osteogenesis imperfecta
  • Osteitis fibrosa cystica
  • Fibrous dysplasia
85
Q

Is osteoporosis associated with bony pain?

A

NO

86
Q

What is the storage and transport form of Vit. D?

A

25-OH-D2

  • Low serum phosphorous, low serum Ca, low FGF23, and high PTH favor production of 1,25-OH-D3
87
Q

Osteomalacia/Rickets

A
  • Failure of mineralization: defect in inorganic component of bone or inadequate mineralization of the bone matrix

􏰄- Osteomalacia is softening of adult bone, and rickets is softening of growing bone

  1. Osteomalacia: low phosphorous & low Vit D
    - Most comm cause of defect in bone mineralization is severe vitamin D deficiency (via nutrition, lack of sunlight, or liver disease)
  2. Hypovitaminosis D —> suspect when below 5-10ng/mL: Ca transport in gut stimulated by Vit D >10ng/mL, but not really when below that
88
Q

What are the 2 rare forms of Vit-D dependent rickets?

A
  • Type I Vitamin D Dependent Rickets
    1. Autosomal recessive
    2. Defect in activity of 1 alpha-hydroxylase (very low levels of 1,25 (OH) D)
  • Type II Vitamin D Dependent Rickets
    1. Autosomal recessive
    2. Defect in receptor response to 1,25 dihydroxyvitamin D (high circulating levels of 1,25 (OH) D)
89
Q

What is Paget disease of bone?

A
  • Excessive bone resorption followed by excessive bone formation -> excess # of osteoclasts with more nuclei than usual
    1. Osteoblasts are in excess but morphologically normal
  • Bone formed is not normal; there is too much bone of poor quality -> enlarged skull, deformities in extremities, bony pains
    1. Complications: fxs, hearing loss, bone tumors
  • Image: cortical thickening, expansion, and mixed areas of lucency and sclerosis (contrasted with normal bone in the proximal half)
90
Q

Lab evaluation in Paget?

A
  • Increased Bone Specific Alkaline Phosphatase (CMP)
  • Usually measure total serum Alkaline Phosphatase so routine lab work will show increase in the total enzyme level
  • Ca, phosphorous, Vit D, and renal function should be normal (you check these to rule out other causes)
91
Q

Osteopetrosis (marble bone disease)

A
  • Too much bone, but of poor quality
  • Laboratory studies are usually normal and DXA shows very high (positive) bone mineral density (BMD) values
  • Fractures can occur in spite of high BMD: have negative T-scores
92
Q

Osteogenesis imperfecta (brittle bone disease)

A
  • Low levels of type I collagen synthesis by fibroblasts, and mutations within the pro-alpha1 and pro-alpha 2 type I collagen genes
  • Heritable disorder
  • Patients have: 1) skeletal pains, 2) recurrent fractures, 3) skeletal deformities
  • Blue sclera in some cases
93
Q

Osteitis fibrosa cystica: epi, histo, clinical, radiology, labs.

A
  • Bone disease of hyperparathyroidism: high bone turnover state
  • Epi: can be seen in 1o hyperparathyroidism and ESRD pts w/very high PTH levels -> now in <10% of pts bc early dx of conditions with elevated PTH
  • Histo: INC in # of bone-resorbing osteoclasts, marrow fibrosis, and cystic lesions that may contain fibrous tissue (brown tumors)
  • Clinical: bone pain and sometimes pathologic fractures -> osteoporosis due to preferential loss of cortical bone
  • Radiology: most sensitive and specific finding is subperiosteal resorption of cortical bone, best seen in high-resolution films of the phalanges (bones of hands and feet); similar process in the skull leads to a salt-and-pepper appearance (see attached images)
    1. Bone cysts or brown tumors may present as osteolytic lesions
  • Labs: elevated PTH, elevated Ca in primary HPT and normal or low-normal Ca in ESRD; elevated markers of bone turnover, incl alkaline phosphatase
94
Q

What is fibrous dysplasia?

A
  • Sporadic disorder w/1 (monostotic) or more (polyostotic) expanding fibrous skeletal lesions of bone-forming mesenchyme -> do NOT differentiate into osteoblasts, so imperfect bone
    1. Fibroblast-like cells w/features of osteoblasts in some areas -> produce ECM that organizes into woven bone
  • NOT hereditary -> exact mechanism unknown
  • Polyostotic form assoc w/cafe au lait spots and hyperfunction of endocrine system as pseudo-precocious puberty of ovarian origin is known as McCune-Albright syndrome (MAS)
  • Molecular defect: activating muts in GNAS1 gene that encodes α subunit of stimulatory G protein (Gsα)
  • Postzygotic muts in early devo, but variable, explaining mosaic pattern of skin/bone changes -> muts of GsαPCR may cause autonomous function in:
    1. Bone (PTH hormone receptor)
    2. Skin (MSH receptor)
    2. Various endocrine glands, incl ovary (FSH receptor), thyroid (TSH receptor), adrenal (ACTH receptor), and pituitary (GHRH receptor)
95
Q

Presentation and evaluation of fibrous dysplasia

A
  • Monostotic form most common, and dx in pts bt 20-30-y/o w/o assoc skin lesions
  • Polyostotic form in kids <10-y/o, and may progress w/age -> lesions most comm involve maxilla, o/craniofacial bones, ribs, and metaphyseal or diaphyseal portions of the proximal femur or tibia

􏰇- Symptoms: expanding bone lesions may cause pain, deformity, fractures, and nerve entrapment

􏰇- Signs: may have café au lait spots (flat, hyper-pigmented skin lesions w/rough borders), most common endocrinopathy is isosexual pseudo-precocious puberty in girls

  1. Other, less common endocrine disorders incl thyrotoxicosis, Cushing’s, acromegaly, hyperparathyroidism, hyperprolactinemia
    - Labs: hypophosphatemia may be due to FGF-23 made by abnormal fibrous tissue; Ca, PTH, Vit D are normal, markers of bone turnover can be elevated

􏰇- Radiology: well-defined fibrous dysplastic lesions in long bones -> radiolucent areas with thin cortices and a ground-glass appearance (may be lobulated with trabeculated areas of radiolucency)

Endocrine (12 decks)

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