Endocrinology - Bone/calcium disorders Flashcards
describe normal calcium physiology?
- calcium absorbed from the duodenum
- stored in the bone
- excreted by the kidneys
what two hormones increase serum calcium level?
1,25 OH Vitamin D
PTH
how does vitamin D increase calcium?
- sunlight into the skin
- hydroxylates first in the liver to form 25 OH-D
- hydroxylate in the kidney to form 1,25 OHD
- increases calcium and phosphorous absorption in the gut.
how does PTH increase calcium in the blood?
- stimulates the release of bone calcium stores by indirect stimulation of osteoclasts
- increase renal tubular calcium resorption and renal tubular phosphorous excretion
- increases production of 1,25 OHD by increasing activity of kidney hydroxylase
describe the normal relationship with calcium and PTH?
- serum free calcium negatively feedbacks on the parathyroid
- high serum calcium decrease PTH and low serum increases PTH
what decreases serum calcium?
- calcitonin from thyroid parafollicular cells antagonizes PTH. It slows down osteoclasts causing decrease in bone resorption and increases renal calcium clearance.
- excess steroids decrease bone protein matrix and causes calciuria
- Estrogen decreases bone resorption and may increase osteoblastic activity.
what is the most common cause of primary hyperparathyroidism? what do you typically see?
- 80% caused by parathyroid adenomas
- complain of bone pain, decreased density of cortical bone with increased risk of fractures
- bones, stones, abdominal moans, and psychic groans
what is the classic radiogrpahi finding on hand films with primary hyperparathyroid excess?
- subperiosteal bone resorption is otherwise known as osteitis fibrosis cystica
- Can see a moth eaten appearance to the radial side of phalangeal cortices
how is the dx of primary hyperparathyroid made?
- normal or an elevated intact PTH
- elevated calcium
- low-normal phosphorous
what do you order to measure vitamin D deficiency?
25 hydroxyvitamin D
what medications can cause hypercalcemia?
- thiazides
- Lithium
lab values for secondary hyperparathyroidism?
- low calcium
- high PTH
what suggests hypercalcemia of malignancy?
- high calcium
- low intact PTH
what is the medical management of primary hyperparathyroidism? monitor?
- monitor calcium and creatinine yearly
- bone density scans every 1-2 years
- check 25 OH vitamin D levels and supplement if <20
- no specific drug tx.
what are the indications for parathyroid surgery in primary hyperparathyroidism?
- symptomatic patients
- osteoporosis
- CKD 3
- serum calcium >1mg/dl
what is typically the cause for secondary hyperparthyroidism?
- chronic renal failure or vitamin D deficiency
- overproduction of parathyroid hormones secondary to chronic abnormal stimulus for production
when do you see tertiary hyperparathyroidism?
seen in patients with chronic secondary hyperparathyroidism and often after renal transplantation
what vitamin abormalities cause hypercalcemia?
- vitamin D excess
- vitamin A excess (causes calcium release from bones)
what labs should you get if you suspect benign familial hypocalciuric hypercalcemia?
- measure calcium and creatinine in the urine
- if ratio of calcium: creatinine clearance is <0.01, dx is FHH
- if ratio of calcium: creatinine clearance is >0.02, dx is NOT FHH and dx likely primary hyperparathyroidism
what 4 groups of malignancies are associated with hypercalcemia?
myeloma, some solid tumors, granulomatous diseases, and tumors with bone metastases
how do granulomatous diseases cause hypercalcemia? examples? tx?
- macrophages and lymphocytes have unregulated 1alpha - hydroxylase, converting 25 OH Vit D to 1,25 OH vit D.
- these include sarcoidosis, tuberculosis, beryllioiss, histoplasmosia and leprosy
- treat with steroids if safe.
what is the medical treatment of hypercalcemia?
- fluids to treat volume depletion caused by salt wasting associated with high urinary calciums
- bisphosphonates to interfere with bone resorption in areas with high turnover.
- calcitonin to lowers blood calcium by inhibit osteoclast activity and inhibiting renal tubular cell resorption of calcium and phosphate
- pamidronate and zoledronic acid but watch for jaw osteonecrosis.
ddx for hypocalcemia?
- hypoparathyroidism due to decreased PTH secretion
- hypomagnesemia
- vitamin D deficiency
- acute pancreatitis
- severe hypophosphatemia
- pseduohypoparathyroidism
how can hyerphosphatemia cuase hypocalcemia?
severe hyperphosphatemia chelates calcium with the phosphorous
classic presentation of pseduo-pseduohypoarathyroidism?
shortened 4th MCP and short stature with normal biochemical profile
what is osteomalacia?
condition of demineralized bone with hypocalcemia most commonly caused by vitamin D deficiency.
classic presentation of osteomalacia in kids? adults?
- In kids, rickets causing listlessness, irritability and bowing of the legs
- adults have bone pain and proximal muscle weakness.
- “bilateral symmetric pseduofractures” is pathognomonic.
labs with osteomalacia from vitamin D deficiency Po4, Ca, alk phos, iPTH, 25 OH, 1,25 OH?
- PO4 - low
- Ca low
- Alk phos - high
- iPTH - low
- 25-OH D low
- 1,25 OH - N/A
labs for chronic renal failure with Po4, Ca, alk phos, iPTH, 25 OH, 1,25 OH?
- PO4 - high
- Ca low
- Alk phos - N/A
- iPTH - high
- 25-OH D normal
- 1,25 OH - low
labs for primary hyperparathyroidism Po4, Ca, alk phos, iPTH, 25 OH, 1,25 OH?
- PO4 - N/A
- Ca high
- Alk phos - high
- iPTH - low
- 25-OH D - n/a
- 1,25 OH - N/A
labs for hypercalcemia of malignancy Po4, Ca, alk phos, iPTH, 25 OH, 1,25 OH?
- PO4 - n/a
- Ca high
- Alk phos - high
- iPTH - low
- 25-OH D - N/A
- 1,25 OH - N/A
what is MEN 1? what labs do you suspect it?
- Parathyroid hyperplasia, pituitary adenomas, pancreatic islet tumors causing hypersecretion of either insulin or gastrin
- suspect with hypoglycemia and hypercalcemia
- strong FH of peptic ulcer disease
what do you see with men 2A? when do you suspect it?
- medullary thyroid cancer, pheochromocytoma, parathyroid hyperplaslasia.
- look for hypercalcemia, elevated calcitonin, hypertension
what do you see with Men 2B?
- medullary thyroid cancer, pheochromocytoma, mucosal neuromas.
- see hypertension, elevated calcitonin, with abnormal physical appearance with multiple neuromas, blubbery lips, marfanoid habitus