188. Calcium/Parathyroid/Bone Pathophysiology Flashcards
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
Primary hyperparathyroidism
Caused by DiGeorge Syndrome and Velo-cardio-fascial syndrome
Congenital hypoparathyroidism
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
Osteoporosis
Osteopenia T-score
< -1 and < -2.5
Osteoporosis T-score
> -2.5
Severe bone manifestation of primary hyperparathyroidism
- periosteal resorption in distal phalanges
- bone cysts, brown tumors in severe cases
Osteitis Fibrosa Cystica
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
Vit D deficiency
Autosomal recessive mutation of both CaSR alleles that are inactivated
Severe hypercalcemia occurs
Hypocalciuria
PTH elevated
Neonatal severe hyperparathyroidism
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
Loop
To diagnose vitamin D deficiency what do you measure?
25-OH Vit D
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
Observe
Surgery
Cinacalcet
Factor primarily involved with chondrocyte replication at the growth plate
Binds to PTH receptor
Highly expressed in fetus and breast milk
PTHrP
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
Renal failure
Calcium solubility
Treatment for __:
- postmenopausal women
- men over 50yo
Anti-resorptive:
- bisphosphonates
- denosumab
- SERMs
- Estrogen
- Calcitonin
Anabolic therapy:
- Teriparatide
- Abaloparatide (PTHrP analog)
Osteoporosis
What kind of cancers lead to tumor cell production of osteolytic factors causing hypercalcemia
Multiple myeloma
Breast cancer
Prostate cancer
Lymphoma
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
Hypocalcemia
~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%)
Parathyroid adenoma
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
Familial Hypocalciuric Hypercalcemia
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
1alpha-hydroxylase
Severity of Paget’s disease correlates with rise in __
Not specific only to bone
- can be from liver or intestines as well
Alk Phos
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
Paget’s disease
Clinical features:
- Nephrolithiasis, nephrocalcinosis
- arthralgias, myalgias, weakness
- Abdominal pain, constipation
- neurologic impairment: mild to severe
- Polyuria
- Shortened QT interval
Hypercalcemia
Correct for albumin below 4.0
__ calcium = total measure calcium + ((4-albumin) x .8)
Corrected
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
Albumin
Treatment of hypocalcemia
Calcium (IV, oral)
Vitamin D
Hypocalcemia treatment used in cases of hypoparathyroidism, vitamin D resistant rickets, renal failure
Calcitriol
Defect in bone mineralization
Due to any of the below:
- vit D deficiency
- calcium deficiency
- phosphate deficiency (malabsorption or phosphorous wasting conditions)
Rickets (kids) and osteomalacia (adults)
What’s the characteristic skull finding of primary hyperparathyroidism?
Salt and pepper skull
What should you calculate from a 24 hour urine collection when trying to make the diagnosis of FHH:
- <1% in FHH
FeCa - fractional excretion of calcium
Hypercalcemia: etiologies
VITAMINS TRAP
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
Primary hyperparathyroidism leads to bone manifestations
- osteoporosis, fractures, low bone mineral density
Leads to more __ bone loss than __
Cortical
Trabecular
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
Bisphosphonates
Calcitonin
Serum calcium is preserved at expense of __
Bone
PTH secretion is dependent on what ion?
With low levels of this, functional hypoparathyroidism occurs
Magnesium
PTHrP is commonly produced by what kind of cancers?
Squamous cell carcinoma of lung
Head and neck carcinomas
Carcinomas of kidney and ovary
Clinical features:
- skeletal deformities
- bone pain, fragility, fractures
- -> effect of secondary hyperparathyroidism
- Muscular hypotonia, weakness
Rickets and osteomalacia
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
Primary Hyperparathyroidism
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
Humoral Hypercalcemia of malignancy
Stones, bones, groans, and psychogenic overtones
Hypercalcemia
Chronic low vitamin D –> decrease in Ca2+ absorption from gut –> decrease in serum Ca2+ and increase in PTH (secondary hyperparathyroidism) –> what two things increase?
Increase in urinary Ca2+ reabsorption and PO4 excretion
Increased bone resorption
Hypocalcemia, hypophosphatemia present only if severe, longstanding __
Vitamin D deficiency
Treatment of Rickets/Osteomalacia:
Vitamin D3 - cholecalciferol Vitamin D2 - ergocalciferol Calcium Calcitriol Phosphate
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
Hearing loss
Osteosarcoma
It is important to distinguish primary hyperparathyroidism from what genetic disease?
Both have high serum calcium and normal to elevated PTH
Familial Hypocalciuric Hypercalcemia
