Hypercalcemia and Hypocalcemia

Question 1

what are the 3 organ systems involved with Ca homeostasis?

Answer 1

skeleton, the kidneys and the intestines.

Question 2

How does PTH act on the skeleton?

Answer 2

PTH directly stimulates osteoclastic

bone resorption, which releases ionized calcium and phosphate from the skeleton into the extracellular fluid.

Question 3

How does PTH act on the kidneys

Answer 3

PTH directly inhibits renal calcium excretion but promotes renal phosphate excretion

Question 4

how does PTH act on the intestines?

Answer 4

PTH stimulates conversion of 25 OH Vitamin D into 1,25 (OH)2 Vitamin by renal 1 alpha hydroxylase and thereby indirectly stimulates intestinal calcium and phosphorus absorption.

Question 5

How does 1,25 (OH)2 Vitamin D raise serum calcium levels? by

Answer 5

Directly enhancing intestinal calcium and phosphorus
absorption and by promoting osteoclastic bone resorption, an effect that occurs mainly at high 1,25 (OH)2 Vitamin D levels.

Question 6

What is the the storage form of vitamin D and thus inactive? is mostly inactive but is the major storage form of Vitamin D

Answer 6

25 OH Vitamin D

Question 7

What is the active form of vitamin D that promotes intestinal calcium and phosphorus absorption.

Answer 7

1,25 (OH)2 Vitamin D

Question 8

Where is Calcitonin produced?

Answer 8

produced by the parafollicular c-cells in the thyroid gland.

Question 9

The calcium sensor receptor (CaSR) is a 7 transmembrane G-protein coupled receptor that senses the extracellular calcium concentration and signals the intracellular compartment to respond appropriately. CaSRs are present on the surface of ____

Answer 9

parathyroid cells, parafollicular c-cells and renal tubular cells

Question 10

what does calcitonin do?

Answer 10

It lowers serum calcium by inhibiting osteoclastic bone resorption.

Question 11

PTH is elevated or high normal in _______ and the rare congenital disorder ______ . PTH levels are low in all other causes of hypercalcemia.

Answer 11

Primary Hyperparathyroidism,

Familial Hypocalciuric Hypercalcemia

Question 12

What are the causes of Primary Hyperparathyroidism (HPTH)?

Answer 12

Parathyroid adenoma ~85%
Parathyroid hyperplasia ~15% of cases;
Parathyroid Carcinoma < 1%

Question 13

Primary hyperparathyroidism is ____ in 90% of cases, and _____ in 10%

Answer 13

sporadic,

familial

Question 14

Almost all familial cases of HPTH

(familial HPTH, Multiple Endocrine Neoplasia 1, Multiple Endocrine Neoplasia 2A) result from _____

Answer 14

hyperplasia rather than an adenoma.

Question 15

What is the presentation Primary HPTH

Answer 15

osteoporosis/osteopenia, kidney stones, gastrointestinal pain and psychiatric disturbances;
“bones, stones, groans and moans”

Question 16

What is the treatment for Parathyroid hyperplasia?

Answer 16

Removal of 3 ½ parathyroid gland, with the remaining ½ gland being left in situ or auto-transplanted into a neck strap muscle or a forearm muscle

Question 17

Name 5 conditions of Hyperparathyroidism where Surgery is Recommended

Answer 17

1. Serum Calcium > 1 mg/dl above normal range
2. Creatinine Clearance < 60 ml/min
3. BMD T-Score < -2.5 or History of Fragility Fractures
4. History of Kidney Stones
5. Age < 50 Years

Question 18

what is the choice for treatment of primary Hyperparathyroidism when surgery is contraindicated

Answer 18

Suppression of PTH secretion by calcimimetic drugs that bind to the CaSR (cinacalcet)

Question 19

What is Secondary HPTH ?

Answer 19

Condition in which excessive PTH secretion occurs as a compensatory response to another primary disorder of calcium, vitamin D or phosphorus

Question 20

What is the key to the diagnosis of secondary HPTH?

Answer 20

Elevated serum PTH level in association with
low or low normal serum calcium, low 25 OH Vitamin D, an elevated or high normal serum phosphorus, or
significantly reduced estimated glomerular filtration rate (eGFR)

Question 21

Secondary Hyperparathyroidism: 4 Most Common Causes:

Answer 21

1. Calcium Deficiency
2. Vitamin D Deficiency
3. Idiopathic Hypercalciuria
4. Chronic Kidney Disease (Stages 4 and 5)

Question 22

Define Hypercalcemia of malignancy

Answer 22

Occurs when solitary, metastatic or hematologic malignancies secrete hormones, cytokines or other mediators that promote aggressive local or diffuse osteoclastic bone resorption, flooding the circulation with calcium and thereby causing hypercalcemia.

Question 23

The most common causes of hypercalcemia of

malignancy are ____

Answer 23

Carcinomas of the lung (especially squamous cell), breast, head and neck, kidney, bladder,
pancreas and ovary, multiple myeloma and lymphomas.

Question 24

what is the most commonly identified mediator in Hypercalcemia of Malignancy?

Answer 24

PTH Related Peptide (PTH-RP)

Question 25

What is Familial Hypocalciuric Hypercalcemia (Familial Benign Hypercalcemia)?

Answer 25

Rare autosomal dominant disorder that results from inherited inactivating mutations of the calcium sensor receptor (CaSR).

Question 26

parathyroid surgery should be avoided in what disease?

Answer 26

Familial Hypocalciuric Hypercalcemia

Question 27

Symptoms of hypocalcemia include ______

Answer 27

paresthesias, muscle cramps, muscle weakness, Chvostek’s sign (facial wink when tapping the facial nerve), and Trousseau’s sign (carpopedal spasm when a sphygmomanometer is maintained above systolic blood pressure for 2 minute

Question 28

PTH is low in ____ but tends to be high normal or elevated in all other causes of hypocalcemia

Answer 28

Hypoparathyroidism

Question 29

How does Hypomagnesemia cause hypocalcemia ?

Answer 29

Impairs PTH secretion and causes resistance to the peripheral actions of PTH

Question 30

Renal disease and liver disease cause hypocalcemia primarily by _____-

Answer 30

interfering with Vitamin D metabolism.

Question 31

How does Hypocalcemia occur in acute pancreatitis?

Answer 31

due to precipitation of calcium salts with products of

intra-abdominal lipolysis (saponification)

Question 32

How does severe renal disease or hypoparathyroidism lead to Vitamin D deficiency?

Answer 32

The deficiency results from inability to convert 25 OH Vitamin D into 1,25 (OH)2 Vitamin D, a process that requires both normal renal 1 alpha hydroxylase activity and PTH to activate the enzyme.

Question 33

Hypoparathyroidism occurs most often as a result of ____

Answer 33

damage to or removal of the all parathyroid glands during thyroid, parathyroid or head and neck surgery.

Question 34

What is Idiopathic hypoparathyroidism.

Answer 34

Autoimmune disorder that results in immune-mediated destruction of the parathyroid glands.

Question 35

What is the treatment of Hypoparathyroidism

Answer 35

supplementation with calcium, Calcitriol [since
endogenous 1,25 (OH)2 production is impaired], and the use of a thiazide diuretic (to reduce excessive urinary calcium excretion).

Question 36

what is Pseudohypoparathyroidism

Answer 36

Rare genetic disorder that results from an inherited inactivating mutation in the Gs alpha subunit or other downstream signaling element in the PTH receptor response pathway

Question 37

what are the clinical features of Pseudohypoparathyroidism

Answer 37

hypocalcemia, hyperphosphatemia and elevated serum PTH levels.
Many affected patients also have shortened metacarpals, especially the 4th and 5th metacarpals, a condition also know as Albright’s Hereditary Osteodystrophy