deck_5446052

Question 1

Notes on calcium balance in the body

Answer 1

Humans generally take in 1000mg of Ca daily, 30% of which is absorbed in the duodenum to disperse in the serum. The intestine put out an additional 150 mg/day into the GI to be excreted and the kidneys put out 150 mg/day in urine.

Question 2

Where are calcium-sensing receptors found?

Answer 2

parathyroid, kidney, C cells in the thyroid, and in boneThis is Gs coupled receptor

Question 3

How do CaSRs work? Drugs to stimulate?

Answer 3

high calcium levelsbinds to reduce PTH secretion via internal cascadeDrugs to stimulate: Cinacalcet

Question 4

How should the workup of a patient with hypercalcemia begin?

Answer 4

1) H&E2) Check albumin and total calcium TWICE to reduce risk of lab error3) Check PTH

Question 5

What conditions associated with hypercalcemia are PTH dependent?

Answer 5

-hyper parathyroidism-familial hypocalciuric hypercalcemia (FHH)-Medication-induced (lithum or HCTZ mediated)

Question 6

What conditions associated with hypercalcemia are PTH independent?

Answer 6

-tumor induced (PTHrP or bone metastases)-granulomatous diseases (TB, sarcoidosis, lymphoma) associated with increased VitD-MM-Hyperthyroidism/adrenal failure-ImmobilizationMed-induced (vitD/A toxicity, milk-alkali syndrome)

Question 7

How is primary hyperparathyroidism defined?

Answer 7

high PTH AND high calcium, low phosphate, and increased cAMP in urine

Question 8

What the main causes of primary hyperparathyroidism?

Answer 8

80-85% adenoma15% hyperplasia (MEN1/2A, HPT-Jaw Tumor Syndrome, familial HPT)1% Parathyroid carcinoma

Question 9

Is sporadic primary hyperparathyroidism more common in men or women?

Answer 9

Women

Question 10

Risk factors for sporadic primary hyperparathyroidism?

Answer 10

age, race (AA>W>H), female

Question 11

What are the symptoms of primary hyperparathyroidism?

Answer 11

Stones, abdominal moans (constripation, nausea), psychic groans (depression, memory loss), and bones (osteoporosis/fractures)the MAJORITY are asymptomatic, or have vague symptoms/general unwellness

Question 12

What things should be included in a primary hyperPTN workup?

Answer 12

calcium, albumin (or ionized calcium), PTH, 25-OH vitD,24 hr urine calcium (to differentiate from FHH)Imaging: thyroid US to start, Tc-sestamibi scan, DEXA scan

Question 13

What is the preferred Tx of primary parathyroidism?

Answer 13

parathyroidectomy

Question 14

What criteria would suggest the need for parathyroidectomy?

Answer 14

calcium 1+ mg/dL above UNLage under 50 yoosteoporosisRenal insufficiency

Question 15

How is primary HPT managed?

Answer 15

-adequate hydration-bisphosphonates-maintain vit D range (20-30 ng/mL)

Question 16

What is an option for patients who can not or do not want surgery and have moderate hypercalcemia?

Answer 16

Cinacalcet

Question 17

What causes familial hypocalciuria hypercalcemia (FHH)?

Answer 17

Inactivating mutations in CaSR (100% penetrant) leading to mildly elevated serum Ca and PTH and hypocalciuria.

Question 18

How does FHH present?

Answer 18

mostly asymptomatic

Question 19

What labs suggest FHH?

Answer 19

elevated PTH and calcium and24hr urine calcium less than 50-100 mg/24 hr

Question 20

Tx of FHH?

Answer 20

None

Question 21

How does secondary hyperPTH present in labs?

Answer 21

Normal calcium with elevated PTH secondary to the parathyroid gland trying to return calcium to a normal range

Question 22

What are the major causes of secondary hyperPTH?

Answer 22

hypocalcemiahyperphosphatemiavitD deficiency

Question 23

What kinds of diseases can produce an inability of the GI to absorb calcium from the GI and thus stimulate secondary hyperPTH?

Answer 23

stomach or intestine bypass for obesity surgery (gastric stapling/bypass)-celiac or crohn’s disease

Question 24

What causes tertiary hyperPTH?

Answer 24

parathyroid glands develop hyperplasia due to chronic low calcium and/or high phosphorus levels after years of seconday hyperPTH.At one point, these glands become autonomous

Question 25

How does hypercalcemia of malignancy present?

Answer 25

They will be sick, not with vague symptoms but signs of hypercalcemia (polyuria, dehydration, abdominal and MSK pain) and symptoms of malignancy (weight loss, anemia, etc.)the PTH level will be suppressed!

Question 26

What cancers are most associated with paraneoplastic hypercalcemia?

Answer 26

breast, renal, and squamous cell carcinomas 

Question 27

What causes hypercalcemia from malignancy?

Answer 27

Mostly from PTH-related protein (PTHrp) binds to the PTH receptor and function similar to PTH to increase cAMPOther causes:-bony metastases can increase calcium levels-humoral factors (cytokines, TNFa) can activate osteoclasts-MM can cause significant bone destruction 

Question 28

How do granulomatous diseases cause hypercalcemia?

Answer 28

overexpression of 1,25(OH)2D by MACROPHAGES which causes elevated calcium and phosphate but supressed PTH

Question 29

How does hypercalcemia lead to dehydration?

Answer 29

calcium inhibits ADH action to express AQP2

Question 30

How is acute hypercalcemia treated?

Answer 30

-address volume status (hydrate)-saline diuresis and furosemide after volume status is correctedcalcitonin (only works for 36-48 hrs)Bisphosphonates (panidronate IV works for 2-3 wks or Zoledronic acid IV-works for 1-3 months)glucocorticoids (myelona, granulomatous disease, and vitD toxicity) anddialysis 

Question 31

What are the signs of hypocalcemia?

Answer 31

agitationhyperreflexiaconvulsionsHTNQT prolongation

Question 32

Causes of hypocalcemia caused by hypoparathyroidism?

Answer 32

post-thyroidectomy 'stunning'Idiopathic- Abs to PTH-autoimmune parathyroid agenesis (DIGeorge syndrome)hypomagnesaemia, hyperphosphatemia

Question 33

Other rare causes of hypocalcemia?

Answer 33

acute pancreatitis in which free fatty acids chelate calciummassive transfusion in which infusion of citrate will complex calcium TLS or rhabdomyolysis in which phosphate released binds to ionized calciumSevere sepsisMeds- phospahte, bisphosphonatesHungry bone syndrome

Question 34

What is Hungry bone syndrome?

Answer 34

in cases of chronic hyperparathyroidism where the bone is continuously being resorbed, when calcium is given, bone very actively tries to take it up resulting in hypocalcemia

Question 35

Ddx with hypocalcemia and low PTH?

Answer 35

hypoparathyroidismMagnesium deficiency (diarrhea, malabsorption, alcoholism)

Question 36

Ddx with hypocalcemia and high PTH?

Answer 36

vitD deficiencyrenal failurevitD or PTH resistance phosphate excess

Question 37

What is pseudohypoparathyroidism?

Answer 37

decreased end organ responsiveness to PTH (PTH resistance)

Question 38

What causes pseudohypoparathyroidism?

Answer 38

molecular defects in the ability of PTH stimulate intracellular signaling pathways due to mutations in Gs alpha subunit (GNAS1) or downstream elements

Question 39

How does pseudohypoparathyroidism present in labs?

Answer 39

LABS: highly elevated PTH with hypocalcemia, hyperphosphatemia

Question 40

How does pseudohypoparathyroidism present clinically?

Answer 40

short stature, rounded face, foreshortened 4th/5th metacarpals, obesity (Albright's Hereditary Osteodystrophy)- only some subtypes

Question 41

What is PHP 1a? MOI?

Answer 41

Defect in Gs alpha subunit signaling causes unresponsiveness of the kidneys to PTH leading to decreased urinary cAMP and PO4, AHO phenotype and other hormonal defects such as decreased mentation, olfaction, TSH, glucagon, and LH/FSHDefect must be inherited from mother due to imprintingMOI: AD

Question 42

What is PHP 1b?

Answer 42

Same as PHP 1a but no AHO

Question 43

What is PHP 1c?

Answer 43

Same as PHP1a but the defect is downstream to Gs alpha subunit. AHO phenotype present

Question 44

What is Pseudopseudohypoparathyroidism?

Answer 44

physical exam feastures of AHO but without end-organ PTH resistance. Occurs when defective Gs protein alpha-subunit is inherited from the FATHER

Question 45

What is PHP2?

Answer 45

Defect in PKA that leads to normal urinary cAMP, decreased urinary phosphate, and no AHO phenotype

Question 46

How is acute hypocalcemia crises treated in the short term?

Answer 46

–Always correct Magnesium if low–Calcium Gluconate•1 - 2 ampules over ~10 – 20 minutes•Followed by infusion if indicated

Question 47

How is hypocalcemia treated in the long term?

Answer 47

–Oral Calcium salts–Vitamin D replaced•Ergocalciferol/Cholecalciferol (act in 10-14 days) - effective only if PTH is present•Calcitriol – active vitamin D–Hydrochlorothiazide – increases reabsorption of Calcium in the distal tubule