calcium homeostasis II

Question 1

Clinical manifestations of hypercalcemia

Answer 1

again determined by Ca level and chronicity
neuropsyche: lethargy, depression
dry skin
band keratopathy (ophthalmologic)
CV: HTN and bradycardia
GI: nausea, constipation
(bone loss may be a cause)
renal: polyuria, polydipsia, nephrolythiasis, renal failure

Question 2

organ based DDx for hypercalcemia

Answer 2

Parathyroid gland (primary or related to lithium), kidney (thiazide diuretics), cancer (depends on PTHrP or incr. 1a hydroxylase activity), granulomatous disorders, intestine, bone endocrine (including pheos or adrenal insuffiency), rhabdomyolysis

Question 3

molecular DDx for hypercalcemia

Answer 3

1. calcium sensor: loss of function, familial hypocalciuric hypercalcemia,
2. Parathyroid hormone receptor

Question 4

What are some reasons for primary hyperparathyroidism?

Answer 4

1. solitary parathyroid adenomas or adenomas in multiple glands
   both may be mono or oligo clonal
   polyclonal is often seen in chronic stimulatory states: lithium tx, Ca receptor inactivation, chronic hypocalcemia
2. very very rarely parathyroid carcinoma
3. hyperfunction in multiple glands
4. neonatal
5. familial hypocalciuric hypercalcemia
   some level of hyperparathyroidism is very common (about 1/1000)

Question 5

clinical manifestations of pirmary hyperparathyroidism

Answer 5

hypercalcemia, hypercalciuria, incr. bone turnover, fatigue and weakness, nephrolithiasis, cardiac abnormalities

Question 6

DDx of primary hyperparathyroidism

Answer 6

cancer (esp. with low PTH, though don’t forget that hyperparathyroidism and cancer may occur in the smae patient), milk-alkali syndrom, thiazides and lithium, familial hypocalciuric hypercalcemia

Question 7

What is familial hypocalciuric hypercalcemia

Answer 7

monoallelic inactivating mutation of the calcium sensing receptor in the parathyroid gland and the kidney
family hx of hypercacemia-usually asymptomatic
low urine calcium excretion with a low calcium:creatinine clearance ration
most pts have normal PTH
benign condition that does not require a thyroidectomy

Question 8

How is familial hypocalciuric hypercalcemia diagnosed

Answer 8

look at urinary calcium excretion
most patients with hperparathyroidism have elevated urine calcium
if it Ca excretion is low, consider familial hypocalciuric hypercalcemia
FHH excrete < 100 mg Ca/day
Ca/Cr clearance <0.01

Question 9

treatment of primary hyperparathyroidism

Answer 9

symptomatic: surgical resection
asymptomatic: surgical resection if the patient has decreased bone mass density, even if not yet symptomatic. the benefits of improved bone density persist for 10 yrs at least.
surgery for pts under 50
if asymptomatic and no decreased bone density, no treatment is necessary

Question 10

surveillance for pts with asymptomatic hyperparathyroidism

Answer 10

serum calcium and creatinine done annually

bone density ever 1-2 yrs

Question 11

drug therapy for hyperparathyroid

Answer 11

bisphosphates

or newer approaches- calcium-sensing receptor activtors, calcitriol analogues, PTH receptor blockers

Question 12

Secondary and tertiary hyperparathyroidism

Answer 12

due to hypocalcemia from vit d deficiency or renal insuffiency
surgery if there is severe pruritis, renal osteodystrophy, ectopic soft tissue calcifications

Question 13

pseudohypoparathyroidism

Answer 13

hypocalcemia, hyperphosphatemia, high PTH
target organ unresponsiveness to PTH
imprinting problem: worse if inherited from mom
(if inherited from dad it is pseudo pseudohypoparathyroidism)
may also be resistant to other hormoes like TSH, LH, FSH
have albright osteodystrophy

Question 14

Jansen’s metaphyseal chondrodysplasia

Answer 14

point mutations in the PTH/PTHrP receptor gene
constitutively active receptor with cAMP accumulation even without ligand
short stature
high Ca, low phosphate, suppressed PTH