CIS: Calcium/Bones/PTH Diseases Flashcards
most common cause of hypercalcemia?
primary hyperparathyroidism:
- single parathyroid adenoma (most common 80%)
- double adenoma seen in 20%
- carcinoma seen in < 1%
- MEN 10% of cases
- usually asymptomatic hypercalcemia or w/ renal stones
- see phosphate and bicarb wasting: can result in non-anion gap metabolic acidosis as well as secondary osteoporosis
tertiary hyperparathyroidism
- become PTH and calcium independent
- kidney is in failure (results in decreased vitamin D, decreased calcium, increased phosphate) and PTH glands get so hyperplastic that they become autonomous –> always pumping out PTH –> excess hypercalcemia
- seen most freq. in transplanted kidneys
aluminum and CKD?
aluminum containing phosphate binders are given during dialysis - increased aluminum levels also leads to osteomalacia seen in CKD
familial benign hypocalciuric hypercalcemia
- autosomal dominant inherited disorder: loss of fn mutation in CaSR (PTH doesn’t sense Ca2+ concentration - despite fact that its high, it doesn’t feed back to gland)
- results in decreased calcium excretion in urine and high calcium in the serum
- usually have normal or mildly elevated PTH
Note: both this and primary hyperPTH have elevated PTH levels and hypercalcemia - however if 24 hour urine level is low then its familial, if the 24 hour level is high then its primary hyperPTH
sx of hypercalcemia?
“stones, bones, groans, moans with fatigue overtones”
fatigue, polyuria, weakness, anorexia, nausea, vomiting, constipation, abdominal pain, kidney stones, lethargy, mental status changes
severe: coma and arrythmias
- neuromuscular: parasthesias, weakness, dimished DTR’s
- CNS: malaise, fatigue, depression
- CV: HTN, prolonged P-R interval, short Q-T interval, bradyarthmias
- renal: polyuria, polydipsia
- GI: w/l, nausea, vomiting, constipation
- eyes: band keratopathy (calcium in corneas)
- calciphylaxis (small vessel thrombosis and skin necrosis)
- osteitis fibrosa cystica: see bone resorption radiologic changes as dark spots = bone resorption
management of hypercalcemia?
- IV fluids
- Loop diuretic meds (furosemide) - helps flush xs calcium from system and keep kidneys functioning = forced diuresis
- IV bisphosphonates: group of drugs that prevents bone breakdown
- Calcitonin: reduces bone resabsorption
- glucocorticoids: steroids help counter effects of too much vitamin D in blood caused by hypercalcemia
- cinacalet: calcimimetic that activates CaSR - primarily used to tx secondary hyperPTH in renal disease or hypercalcemia w/ PTH carcinoma
- Hemodialysis to remove excess waste and calcium from blood if kidneys are damaged and no response w/ other txs
causes of hypocalcemia?
- decreased PTH
- hypoparathyroidism
- post surgery
- Mg+ deficiency
- AI
- tumor - PTH resistance
- pseudohypoparathyroidism: end ogan resistance to actions of PTH
- hypomagensemia
don’t need to know PGA APECED
- normal/high PTH :
- Vit D deficiency
- loop diuretics
causes for hypercalcemia?
look at chart
osteomalacia
adult form of Vit D deficiency
- “soft bones” - remodeled bone does not mineralize
- have pain in the bones and hips, bone fractures, and muscle weakness
first thing need to check when someone has low calcium?
- need to check albumin levels - need to correct calcium for albumin
- there is often people with low calcium, d/t them having low albumin
for every 1 decrease in albumin (from 4) you add .8 to calcium.
- then need to measure PTH, creatinine and phosphorus
- elevated PTH, elevated creatinine, elevated phosphorus = secondary hyperPTH
- elevated PTH, normal creatinin, elevated phosphrus = PTH resistance (pseudohypoparathyroidism)
Paget’s disease
- focal disorder of bone remodeling that leads to greatly accelerated rates of bone turnover
- results in disruption of normal architecture
- see gross deformities: enlargement of skull, bowing of long bones (i.e. hats don’t fit)
- etiology: probably osteoclast abnormality
sx:
- often asymptomatic, though may present w/ h/a, bone pain and deformity
- warmth of skin over involved bone
- high output cardiac failure
- entrapment neuropathies and hearing loss
- kyphosis
- fractures with only slight trauma
increased vascularity:
- may cause warmth over skin of affected bone
- high output cardiac failure
- vascular steal from spinal cord –> paralysis
radiograph:
- see increased vascularity in the bones: show as more clear areas within the bones
3 phases: osteolytic phase, mixed phase, osteoblastic phase = all of which form incorrectly, and are messed up
treatment?
- don’t tx if asymptomatic
- no cure
- bisphosphonates are tx of choice (decreased resorption of bone)
- calcitonin sometimes used as well
lab findings?
- elevated serum alk phos (d/t increased activity of bone break down)
osteoporosis?
- silent skeletal disorder characterized by compromised bone strength and increased risk of fracture
- most often seen in post menopausal women: natural occurring process after age 30
- it is asymptomatic - but problems come d/t microfractures which cause pain
risk factors:
- female, white/asian, small body size/weight, menopause, inadequate calcium intake, smoking, excessive alcohol, eating disorders, glucocorticoids, heparin
- excessive physical activity causing amenorrhea (cause of early osteoporosis)
indications for measure BMD (bone mass density)?
- screen women age >65 or women who have risk factors and are in menopause or have fractures
DEXA scan results: T scores
-1 to 1 = 1 std of young 30 y/o healthy population (T score -1 = 10% bone density loss) - this is considered normal
- normal = T score >-1
- osteopenia = T score -1 to -2.5
- osteoporosis = T score < -2.5
- established osteoporosis = T score<-2.5 and osteoporotic fracture
Z score: person is compared to population of women of their own age
T score: compared against average of healthy 30 y/o women
meds for osteoporosis?
- bisphosphonates are most often used - though after 7 year of use will have increased fractures
- MOA: bind to bony surface and inhibit osteoclastic bone resorption
- SE: erosive esophagitis (take it and stay up for one hour), little absorption (don’t eat for an hour), can’t be used w/ renal failure, osteonecrosis of jaw, atypical fractures (if use is continued for 7+ years) - hormone replacement therapies: BAD!
- increased risk of CV disease, breast cancer, stroke, DVT, and PE. - SERMs - raloxifene: estrogen like effects but inhibits effects of estrogen on breast and uterus
- Increased BMD, decreases risk of vertebral fractures, but not hip fractures
- No increased risk of CV disease and decreases breast cancer risk. Increases risk for DVT/PE.
calcitonin vs. PTH?
PTH: increases calcium released from bones, increases calcium uptake in intestine and increased kidney reabsorption
- High ionized Ca+ causes reduced PTH secretion
- Low Mag also decreases PTH secretion
calcitonin: (if calcium levels are too hight) increased calcium deposition in bones, decreased calcium uptake in intestines, decreased kidney calcium reabsorption
where does conversion of vitamin D occur?
- Vitamin D3/D2 converted to 25, hydroxyvitamin D3 in liver
- conversion to 1,25dihydroxyvit D occurs in kidney
flow chart of hypercalcemia?
look at it!
osteitis fibrosa cystica
xs PTH causes:
- chronic bond resorption
- demineralization
- pathologic fractures
- cystic bone lesions
causes of acquired hypoPTH?
- surgery: thyroid or parathyroid or radiation
- exposure to heavy metals (wilson, hemochromatosis)
- granulomas
- tumors/infection
- Reidels thyroiditis
- PGA APECED
- abnormal caSR
Congenital Hypoparathyroidism
Abnormal calcium-sensing receptors suppress the parathyroid glands
- Hypocalcemia without elevated PTH
- Autosomal dominate hypocalcemia with hypercalciuria
- Affects 1 in 70,000 infants with seizures
Barakat or HDR Syndrome
- Hypoparathyroidism, Deafness, Renal dysplasia
- Autosomal dominate mutation of GATA3
- Hypocalcemia and high frequency deafness from birth
- Later mental retardation & hypocalcemic tetany
DiGeorge’s Syndrome
Congenital cardiac and facial anomalies:
- tetralogy of fallot
- abnormal fascies
- thymic aplasia
- cleft palate
- hypocalcemia: AI hypoPTH
Deletion of Chromosome 22
Presents with Hypocalcemia with tetany
Pseudohypoparathyroidism
- see increased PTH, low calcium levels
= end organ reistance to PTH - if tubular resistance to PTH –> hypercalciuria
Albright Hereditary Osteodystrophy:
- Short stature, obese
- Bradydactyly, round faces
- Dermal ossifications
- Mental retardation
Vit D deficiency?
Rickets in children: - soft spot on baby's head - bony necklace - curved bones - big lumpy joints - bowed legs w/ knees bent Cause: lack of vitamin D, calcium or phosphate
hypo-magenesemia
- necessary cofactor for PTH secretion
- Participates in the PTH affect on the bone and kidneys
- seen in chronic GI disease, nutritional deficiency, ** alcoholism, cis-platinum therapy
sx of hypocalcemia?
acute: Muscle cramps Tetany Irritability Carpopedal spasm Convulsions Perioral tingling Tingling in hands/feet
Chronic: Lethargy Personality changes Anxiety state Blurred vision (cataracts) Parkinsonism Mental retardation
Signs:
- Chvostek sign: Facial muscle contraction on tapping the facial nerve in front or ear
- Trousseau phenomenon: Carpal spasm after application of BP cuff due to tetany (specific)
nonspecific signs:
Candidiasis, brittle nails, dry skin
Cararacts, loss of eyebrows
Hyperactive DTRs
hypocalcemia, elevated PTH, normal Cr and P-
o vitamin D excess: 1,25 dehydroxy vitamin loads elevated (xs see elevated final product)
- seen w/ vit D resistance, meds, malabsorption
o vit D deficiency: 25, hydroxyl vitamin D level is low (defificiency check precursors)
recommendations for postemenopausal women w/ T score <-1 and risk factors?
Vitamin D supplementation (400-800 IU daily) Exercise Cessation of smoking Fall prevention Limitation of alcohol and caffeine ? Medications
30 minutes of weight bearing or resistance exercise at least 4 times per week
comparing the osteos?
osteoporosis: decreased bone mass
osteopetrosis: thick dense bones
osteomalacia/rickets: soft bones w/ elevated calcium
paget’s disease: abnormal bone architecture
osteitis fibrosa cystica: elevated calcium and brown tumors
calcium correction
calculate for hypocalcemia: calcium is 5.6
albumin level is 1.8
o calcium correction: 5.6 + 0.8 (4-1.8) = 7.36 (thus have true hypocalcemia)
