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Endocrine > 188. Calcium/Parathyroid/Bone Pathophysiology > Flashcards

188. Calcium/Parathyroid/Bone Pathophysiology Flashcards

1
Q

Clinical features:

  • High serum calcium with normal to elevated PTH
  • often low phosphorous levels present

High or normal urine calcium

  • high serum calcium spills over into urine –> polyuria
  • urine calcium should not be low
  • -> kidney stones or calcium deposits in kidney
A

Primary hyperparathyroidism

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2
Q

Caused by DiGeorge Syndrome and Velo-cardio-fascial syndrome

A

Congenital hypoparathyroidism

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3
Q

Skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture

Bone strength reflects the integration of two main features:

  • bone density
  • bone quality
A

Osteoporosis

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4
Q

Osteopenia T-score

A

< -1 and < -2.5

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5
Q

Osteoporosis T-score

A

> -2.5

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6
Q

Severe bone manifestation of primary hyperparathyroidism

  • periosteal resorption in distal phalanges
  • bone cysts, brown tumors in severe cases
A

Osteitis Fibrosa Cystica

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7
Q

Major causes:

  • lack of intake/exposure to sun
  • decreased skin synthesis
  • decreased bioavailability from intestinal malabsorption or obesity (increased Vit D deposition in fat)
  • increased intestinal losses
A

Vit D deficiency

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8
Q

Autosomal recessive mutation of both CaSR alleles that are inactivated

Severe hypercalcemia occurs

Hypocalciuria

PTH elevated

A

Neonatal severe hyperparathyroidism

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9
Q

Therapy for hypercalcemia:

  • hydration
  • then, add __ diuretics if indicated to induce calciuresis
  • IV bisphosphonates - inhibit osteoclasts, long time to kick in
  • Calcitonin - quick onset of action
  • glucocorticoids
  • dialysis
A

Loop

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10
Q

To diagnose vitamin D deficiency what do you measure?

A

25-OH Vit D

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11
Q

Therapy for primary HPT:

If asymptomatic then __

If symptomatic and/or progression likely: __

__ are used to lower calcium by decreasing PTH secretion by acting on CaSR
- use in symptomatic patients who can’t undergo surgery

A

Observe
Surgery
Cinacalcet

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12
Q

Factor primarily involved with chondrocyte replication at the growth plate

Binds to PTH receptor

Highly expressed in fetus and breast milk

A

PTHrP

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13
Q

Loss of renal responsiveness to PTH results in increased urinary calcium loss and decreased phosphorous excretion

  • develop secondary hyperparathyroidism from __
  • causes hypocalcemia

Hyperphosphatemia reduces __ __

Reduced 1alpha-hydroxylase activity with reduced 1,25 diOH Vit D production

A

Renal failure

Calcium solubility

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14
Q

Treatment for __:

  • postmenopausal women
  • men over 50yo

Anti-resorptive:

  • bisphosphonates
  • denosumab
  • SERMs
  • Estrogen
  • Calcitonin

Anabolic therapy:

  • Teriparatide
  • Abaloparatide (PTHrP analog)
A

Osteoporosis

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15
Q

What kind of cancers lead to tumor cell production of osteolytic factors causing hypercalcemia

A

Multiple myeloma
Breast cancer
Prostate cancer
Lymphoma

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16
Q

Clinical features:

  • neuromuscular irritability
  • parasthesias (perioral or fingers)
  • Chvostek’s sign
  • Trousseau’s sign (prostate cancer as well)
  • laryngospasm
  • bronchospasm
  • prolonged QT interval
  • seizures
  • tetany
A

Hypocalcemia

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17
Q

~85% of primary hyperparathyroidism is due to benign, solitary __ __

~5%: 2 present

~10%: multiple gland hyperplasia (sporadic vs. MEN I/IIa)

Malignancy v rare (<1%)

A

Parathyroid adenoma

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18
Q

Autosomal dominant mutation where one allele of CaSR is inactivated
- resistant to calcium negative feedback

Mild hypercalcemia occurs

Hypocalciuria - kidney resorbs more calcium than it shoudl

PTH slightly elevated

A

Familial Hypocalciuric Hypercalcemia

19
Q

In cancers, there is ectopic Vitamin D 1,25 hydroxy production causing hypercalcemia
- this is due to ectopic production of __

Seen in Leukemia, lymphoma, renal cell cancer
- and sarcoidosis and TB

Measure 1,25 hydroxy level

A

1alpha-hydroxylase

20
Q

Severity of Paget’s disease correlates with rise in __

Not specific only to bone
- can be from liver or intestines as well

A

Alk Phos

21
Q

Hyperdynamic bone remodelin g
- increased osteoclast and osteoblast activity

Affects 1-3% population over age 55yo in US

Etiology: vital (paramyxovirus)

Often asymptomatic
- detection by elevated alk phos or incidental radiologic finding

A

Paget’s disease

22
Q

Clinical features:

  • Nephrolithiasis, nephrocalcinosis
  • arthralgias, myalgias, weakness
  • Abdominal pain, constipation
  • neurologic impairment: mild to severe
  • Polyuria
  • Shortened QT interval
A

Hypercalcemia

23
Q

Correct for albumin below 4.0

__ calcium = total measure calcium + ((4-albumin) x .8)

A

Corrected

24
Q

Most commonly, a low reported calcium is not true hypocalcemia

Low __ leads to low total serum calcium measurement but the free (ionized) calcium is normal

A

Albumin

25
Q

Treatment of hypocalcemia

A

Calcium (IV, oral)

Vitamin D

26
Q

Hypocalcemia treatment used in cases of hypoparathyroidism, vitamin D resistant rickets, renal failure

A

Calcitriol

27
Q

Defect in bone mineralization

Due to any of the below:

  • vit D deficiency
  • calcium deficiency
  • phosphate deficiency (malabsorption or phosphorous wasting conditions)
A

Rickets (kids) and osteomalacia (adults)

28
Q

What’s the characteristic skull finding of primary hyperparathyroidism?

A

Salt and pepper skull

29
Q

What should you calculate from a 24 hour urine collection when trying to make the diagnosis of FHH:
- <1% in FHH

A

FeCa - fractional excretion of calcium

30
Q

Hypercalcemia: etiologies

VITAMINS TRAP

A 
Vitaminosis D and A 
Immobility 
Thyrotoxicosis 
Adrenal insufficiency 
Milk Alkali Syndrome, multiple myeloma 
Infections (granulomatous: Tb, fungal) 
Neoplasms 
Sarcoidosis 
Thiazides and other meds 
Rhabdomyolysis/Renal FHH 
AIDS
PTH, paraproteinemias
31
Q

Primary hyperparathyroidism leads to bone manifestations
- osteoporosis, fractures, low bone mineral density

Leads to more __ bone loss than __

A

Cortical

Trabecular

32
Q

Treatment of Paget’s:

  • NSAIDs/Physical therapy for pain
  • __ therapy is highly effective in normalizing alk phos levels and diminishing disease progression
  • __ shown to decrease disease progression
A

Bisphosphonates

Calcitonin

33
Q

Serum calcium is preserved at expense of __

A

Bone

34
Q

PTH secretion is dependent on what ion?

With low levels of this, functional hypoparathyroidism occurs

A

Magnesium

35
Q

PTHrP is commonly produced by what kind of cancers?

A

Squamous cell carcinoma of lung
Head and neck carcinomas
Carcinomas of kidney and ovary

36
Q

Clinical features:

  • skeletal deformities
  • bone pain, fragility, fractures
  • -> effect of secondary hyperparathyroidism
  • Muscular hypotonia, weakness
A

Rickets and osteomalacia

37
Q

Most common outpatient cause of hypercalcemia

Most common in patients over 50 years old

Onset in childhood can suggest hereditary disorder such as MEN I or IIa

A

Primary Hyperparathyroidism

38
Q

Most common cause of hypercalcemia in the inpatient setting

Measure PTHrP - first mechanism of action

Local bone resorption - second mechanism of action

Ectopic Vitamin D - third mechanism of action

A

Humoral Hypercalcemia of malignancy

39
Q

Stones, bones, groans, and psychogenic overtones

A

Hypercalcemia

40
Q

Chronic low vitamin D –> decrease in Ca2+ absorption from gut –> decrease in serum Ca2+ and increase in PTH (secondary hyperparathyroidism) –> what two things increase?

A

Increase in urinary Ca2+ reabsorption and PO4 excretion

Increased bone resorption

41
Q

Hypocalcemia, hypophosphatemia present only if severe, longstanding __

A

Vitamin D deficiency

42
Q

Treatment of Rickets/Osteomalacia:

A 
Vitamin D3 - cholecalciferol 
Vitamin D2 - ergocalciferol 
Calcium 
Calcitriol 
Phosphate
43
Q

Clinical features of Paget’s disease:

  • characteristic features on radiographs and bone scan
  • degenerative changes –> pain, nerve compression/entrapment, and __

Labs: normal serum calcium, normal phosphorous, normal PTH, elevated Alk phos

Bony deformities
Pathologic fracture with minimal trauma
Increase bone vascularity - high output CHF
Small risk of __ development

A

Hearing loss

Osteosarcoma

44
Q

It is important to distinguish primary hyperparathyroidism from what genetic disease?

Both have high serum calcium and normal to elevated PTH

A

Familial Hypocalciuric Hypercalcemia

Endocrine (26 decks)

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