disorders of Calcium

Question 1

Calcium distribution

Answer 1

1. Bones and Teeth (~ 99%). 2. Intracellular Compartment (~ 1%). 3. Extracellular Fluids (< 1%) -Ionized Calcium - 48%, Protein Bound Calcium - 44%

Question 2

serum Ca limits

Answer 2

10.5mg/dl is upper limit and 8.5mg/dl is lower limit. At 9.0mg/dl Ca raising mechanisms are initiated. At 10.0mg/dl Ca lowering mechanisms are initiated

Question 3

PTH effects

Answer 3

Increases Serum Ca: increases bone resorption, increases Ca absorption from intestines, decreases Ca excretion by kidneys, increases Vit D production by kidneys and increases phosphate excretion by kidneys

Question 4

compare Vitamin D from skin vs diet

Answer 4

Skin: D3 cholecaldiferol. Diet: D2 ergocalciferol or D3 cholecalciferol

Question 5

Vitamin D effects

Answer 5

Increases Serum Ca: Increases bone resorption, increases Ca absorption from intestines and increases phosphate absorption

Question 6

Calcitonin effects

Answer 6

Decreases Serum Ca: decreases bone resporption

Question 7

List hypercalcemic disorders with elevated PTH

Answer 7

primary hyperparathyroidism, familial hypocalciuric hypercalcemia

Question 8

Classifications of primary hyperparathyroidism

Answer 8

Adenoma (85%), hyperplasia (15%), carcinoma (<1%)

Question 9

Clinical features of primary hyperparathyroidism

Answer 9

> 50% are asymptomatic. Skeletal dz, kidney dz, GI dz, psychiatric dz, arthritis, muscle weakness, band keratopathy, hypertension, anemia

Question 10

Hyperparathyroidism imaging

Answer 10

Brown tumor- osteoclastoma. Osteitis fibrosa cystica (bones appear large and hollow). Chondrocalcinosis

Question 11

Hyperparathyroidism physical exam findings

Answer 11

Band keratopathy of the eyes.

Question 12

Primary hyperparathyroidism diagnosis

Answer 12

Increased serum Ca, decreased serum phosphate, increased serum PTH

Question 13

Causes of primary hyperparathyroidism

Answer 13

sporadic (90%), famial (10%)- familial HPT, MENI, MENIIA

Question 14

Components and cause of MENI

Answer 14

Pituitary tuors, pancreatic islet tumors and parathyroid hyperplasia. Caused by germline mutation of Menin gene

Question 15

Components and cause of MENIIA

Answer 15

medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia. Caused by germline mutation of Ret gene (GDNF receptor)

Question 16

Treatment of primary hyperparathyroidism

Answer 16

1. surgery. 2. Calcimimetic drugs (cinacalcet). 3. anti-resorptive bone drug (bisphosphanate, denosumab)

Question 17

When is surgery recommended for primary hyperparathyroidism

Answer 17

Serum Calcium > 1 mg/dl Above Normal, Creatinine Clearance < 60 ml/min, BMD T-Score < -2.5 or Fragility Fracture, Kidney Stones, Age < 50 Years

Question 18

Management of mild asymptomatic primary hyperparathyroidism

Answer 18

Ca and Vit D supplements. Measure Serum Ca and creatinine every 6-12 month. Measure bone density every 1-2 years

Question 19

Secondary hyperparathyroidism

Answer 19

decreased calcium, increased phosphorus and/or decreased Vitamin D lead to increased PTH.

Question 20

What is hypercalcemia of malignancy

Answer 20

Elevated Ca and decreased PTH in the setting of cancer

Question 21

List mediators of hypercalcemia of malignancy

Answer 21

PTH related peptide, TGFBeta, TNF, Interleukin1 or 6, RANK-L, DKK-1, Vitamin D

Question 22

Diagnosis of hypercalcemia of malignancy

Answer 22

elevated serum Ca, decreased serum PTH, elevated PTH-RP or other mediator

Question 23

Treatment of hypercalcemia of malignancy

Answer 23

1. Promote Urine Calcium Excretion- Saline Infusion. 2. Inhibit Bone Resorption- IV Bisphosphonates, Denosumab, Calcitonin, Plicamycin. 3. Remove Calcium- Dialysis

Question 24

What is familial hypocalciuric hypercalcemia

Answer 24

Mutations lead to increased PTH secretion and decreased Ca excretion. This causes increased serum Ca. Urine Ca/ Creatinine clearance ratio is <0.01

Question 25

familial hypocalciuric hypercalcemia treatment

Answer 25

None needed. Avoid surgery

Question 26

Causes of hypocalcemia

Answer 26

1. decreased PTH: hypoparathyroidism. 2. Vit D deficiency. 3. hypomagnesemia. 4. renal or liver failure. 5. acute pancreatitis. 6. hypoproteinemia

Question 27

Clinical features of hypocalcemia

Answer 27

Paresthesias, Muscle Cramps, Muscle Weakness, Chvostek’s Sign (tapping facial nerve at masseter causes contraction of muscles of face) , Trousseau’s Sign (occlusion of brachial artery induces spasm of muscles of hand and forearm)

Question 28

Causes of Vitamin D deficiency

Answer 28

1. Poor intake or sunlight. 2. Renal dz. 3. hypoparathyroidism. 4. Congenital 1-alpha hydroxylase deficiency (Vit D dependent rickets type 1). 5. congenital Vit D receptor deficiency (Vit D dependent rickets type 2)

Question 29

Vit D deficiency labs

Answer 29

Decreased serum Ca, decreased Phosphate, increased alkaline phosphatase, increased PTH, decreased Vit D, decreased urine Ca

Question 30

Signs of Vit D deficiency

Answer 30

osteomalacia-pseudofracture (milkmans fracture or loosers line)

Question 31

Hypoparathyroidism labs

Answer 31

decreased Ca, increased phosphate, decreased PTH

Question 32

hypoparathyroidism treatment

Answer 32

Ca supplements, Calcitriol, thiazide diuretics

Question 33

Pseudohypoparathyroidism

Answer 33

Inactivating mutation of the Gs alpha subunit or other downstream PTH response element

Question 34

Pseudohypoparathyroidism signs

Answer 34

albrights hereditary osteodystrophy (short 4th and 5th metacarpals)

Question 35

Pseudohypoparathyroidism labs

Answer 35

decreased serum Ca, increased serum phosphate, increased serum PTH

Question 36

Pseudohypoparathyroidism treatment

Answer 36

calcium, calcitriol, thiazide diuretics