Calcium and PTH

Question 1

Signs + sx of hypocalcemia

Answer 1

Mild hypocalcemia usually asymptomatic

Tetany, seizures, QT prolongation, Chvostek sign (facial twitching), Trousseau sign (spasm upon blood pressure cuff)

Question 2

Imaging findings for rickets (2)

Answer 2

1) Rachitic rosary
2) Epiphyseal widening + metaphyseal cupping/ fraying

Question 3

Functions of vitamin D

Answer 3

Generally increases both Ca2+ and phosphate levels in the serum

1) Increase aborption of Ca2+ and phosphate in the instestine
2) Increase renal absorption of Ca2+ and phosphate
3) Increase resorption of bone- provides Ca2+ and phosphate in the serum to mineralize new bone

Question 4

How does renal failure lead to hyperparathyroidism? (2 ways)

Answer 4

1) Secondary hyperparathyroidism: Renal failure results in phosphate retention, which binds Ca2+ and deposits it in ectopic tissues –> hypocalcemia –> increased PTH (secondary hyperparathyroidism)
2) Tertiary hyperparathyroidism: Chronic renal failure and untreated hyperparathyroidism- autonomous PTH secretion –> hypercalcemia

Question 5

Functions of PTHrP and when it’s commonly seen

Answer 5

Functions: same as PTH except doesn’t increase Vitamin D production + intestinal Ca2+ absorption

Commonly associated w/ cancers (e.g. small cell carcinoma of lung, renal cell carcinoma, breast CA)

Question 6

Synthesis of Vitamin D

Answer 6

D3 (from sun, ingestion of fish + plants) + D2 (from plants, fungi, yeasts) are converted to 25-OH in liver then subsequently to 1,25-(OH)₂vitamin D (active form) in kidney via 1alpha-hydroxylase

Question 7

Chvostek sign + Trousseau sign and what do they implicate

Answer 7

Chovestek sign: tapping of facial nerve (tap cheek) –> contraction of facial muscles

Trousseau sign: occlusion of brachial artery w/ BP cuff –> carpal spasm

indicative of hypocalcemia

Question 8

Causes of secondary hypoparathyroidism

Answer 8

1) Vitamin D deficiency (e.g. Renal failure, inadequate intake)
2) Deficient Vitamin D receptor
3) Albright Hereditary Osteodystrophy

Question 9

Lab findings of rickets/ osteomalacia (Vitamin D deficiency)

Answer 9

Low Vitamin D

Low serum Ca2+ and Phosphate

High PTH (secondary hyperparathyroidism due to low Ca2+)

high ALP (correlated w/ osteoblast activity)

Question 10

How alkalosis/ acidosis affects serum Ca2+ levels

Answer 10

Alkalosis- total Ca2+ levels the same; however, low H+ so more Ca2+ binds to albumin –> hypocalcemia

Acidosis- total Ca2+ level the same; however high H+ so less Ca2+ binds albumin –> hypercalcemia

Question 11

Rachitic Rosary

Answer 11

Rickets

Question 12

Functions of PTH (4)

Answer 12

Generally, increases serum Ca2+ levels and decreases phosphate levels

1) Bone resorption- stimulates osteoblasts to express RANKL, which binds RANK on osteoclasts, stimulating resorption
2) Increase Renal Ca2+ absorption
3) Increase intestinal Ca2+ absorption- stimulates 1alpha-hydroxylase in the kidney to form more active Vitamin D
4) Decrease phosphate reabsorption in PCT

Question 13

How does chronic renal failure lead to hyperparathyroidism/ hypercalcemia?

Answer 13

If secondary hyperparathyroidism not treated for a long time, parathyroid gland becomes autonomous w/o regulation via Ca2+ –> increase PTH secretion –> hypercalcemia

Question 14

What are the etiologies of Vitamin D related hypercalcemia and how does it results in high calcium levels?

Answer 14

1) Granulomatous disease (sarcoidosis)- granulomas express high 1-alpha-hydroxylase activity –> increase Vitamin D activation –> hypercalcemia (normal levels of Vitamin D but active forms increased)
2) Lymphomas– lymphocytes in lymphomas express high 1-alpha-hydroxylase activity –> increase Vitamin D activation –> hypercalcemia (normal levels of Vitamin D but active forms increased)
3) Excess Vitamin D ingestion– high levels of vitamin D + active form

Question 15

Imaging findings of osteomalacia

Answer 15

Osteopenia + “looser zones” (pseudofractures- decreased density of bones)

Question 16

Sx/ presentation of rickets (5)

Answer 16

1) Pigeon-breast deformity
2) Rachitic rosary
3) Bowing of legs (genu varum)
4) Frontal bossing
5) Craniotabes (soft skull)

Question 17

3 forms that Ca2+ exists in the blood

Answer 17

1) Ionized/ free (available Ca2+)- 45%
2) Bound to albumin- 40%
3) Bound to anions- 15%

Question 18

Etiology of DiGeorge

Answer 18

Develomental failure of 3rd and 4th pharyngeal pouches, leading to thymus and parathyroid aplasia.

Usually sporadic but can be due to 22q11.2

Question 19

Vitamin D’s effect on PTH

Answer 19

Inhibits transcription of PTH

Question 20

Lab findings for HHM (PTHrP) – blood Ca2+ and phosphate levels, PTH, urine Ca2+ and phosphate, and urine cAMP

Answer 20

Ca2+ is high, Phosphate is low

PTH is low

urinary cAMP is high (acts on PTH receptors in kideny)

Urine Ca2+ and phosphate are high

Question 21

Lab findings of Albright hereditary osteodystrophy

Answer 21

High PTH

Low Ca2+

Question 22

Main problem in pseudohypoparathyoridism type 1A (Albright hereditary osteodystrophy)

Answer 22

Unresponsiveness of kidney to PTH, resulting in hypocalcemia despite high PTH levels. Normally, Gsalpha gene (GNAS) is paternally imprinted in certain areas (e.g. renal cortex, endocrine organs), resulting in shutting off of his genes. In PTHR, father’s shuts off but mother’s is mutated –> kidney is unresponsive to PTH

Question 23

Defective mineralization of cartilaginous growth plates

Answer 23

Rickets

Question 24

Function of calcitonin

Answer 24

Decrease bone resorption

Question 25

Lab findings for familial hypocalciuric hypercalcemia (serum Ca2+, phosphate, PTH, calcitriol, urinary Ca2+)

Answer 25

Elevated serum PTH, Ca2+, Vitamin D

Low urinary Ca2+ excretion- Ca2+ sensing receptors in kidney inactivated –> excessive Ca2+ uptake

Question 26

Etiology + findings of osteitis fibrosa cystica

Answer 26

Etiology: primary hyperparathyroidism

Findings: Due to increased PTH, there is cystic bone spaces (cortical bone loss) w/ brown fibrous tissues that cause bone pain. Brown fibrous tissues due to BV that are affected, leading to hemorrahge –> hemosiderin deposits.

Question 27

How does presentation of HHM (PTHrP) of hypercalcemia differ from other causes of hypercalcemia?

Answer 27

Presents as an acute, severe hypercalcemia and is always symptomatic

Question 28

Source of calcitonin and stimulation

Answer 28

Source: parafollicular cells (C-cells) of thyroid

Stimulation: Increase in serum Ca2+

Question 29

Causes of primary hypoparathyroidism (4)

Answer 29

1) Accidental surgical excision of parathyroid
2) DiGeorge
3) AD hypoparathyroidism
4) Autoimmune destruction

Question 30

Causes of hypercalcemia

Answer 30

1) PTH dependent hypercalcemia: Primary hyperparathyroidism, renal failure (tertiary hyperparathyroidism)
2) PTH independent hypercalcemia: HHM (PTHrP), Bone mets, vitamin-D related, Medications (e.g. thiazides)

Question 31

Embryological origin of parathyroid gland

Answer 31

3rd and 4th pharyngeal pouches

Question 32

Main problem in pseudopseudohypoparathyroidism and how it’s differnet from Albright hereditary osteodystrophy

Answer 32

Defective GNAS from father- although Gsalpha from father is shut off in renal cortex and endocrine glands, it’s normally not shut off in the periphery. Results in same physical exam features as Albright hereditary osteodystrophy but normal PTH and Ca2+ levels.

Question 33

Decreased mineralization of osteoid

Answer 33

Osteomalacia

Question 34

Sx/ presentation of albright hereditary osteodystrophy

Answer 34

Short stature (due to PTH resistance and hypocalcemia)

shortened 4th digit

Question 35

Sx/ Presentation of osteomalacia

Answer 35

Increased fractures

Question 36

Lab findings in primary hyperparathyroidism (serum Ca2+, PTH, calcitriol, urine Ca2+ and phosphate, urine cAMP)

Answer 36

Elevated calcium and PTH

Decreased Phosphate

Elevated urine Ca2+ and phosphate*

Elevated urine cAMP

Question 37

Causes of primary hyperparathyroidism

Answer 37

Most often due to parathyroid adenoma/ hyperplasia (e.g. part of MEN)

Other causes: Familial hypocalciuric Hypercalcemia (FHH)

Question 38

Inactivating mutation of Ca2+ sensing receptor in multiple tissues, leading to hyperparathyroidism and hypercalcemia

Answer 38

Familial hypocalciuric hypercalcemia

Question 39

Mg2+ levels and PTH secretion and causes of low Mg2+

Answer 39

Low magnesium levels- stimulate PTH secretion

Very low magnesium levels- inhibit PTH secretion

Causes of low Mg2+: diarrhea, aminoglycosides, diuretics, alcohol abuse

Question 40

Sx/ Presentation + Imaging finding of DiGeorge

Answer 40

Sx/ Presentation: CATCH-22

• C: Conotruncal abnormalities (e.g. truncus arteriosus, tetralogy of Fallot); most common cause of death
• A: Abnormal facial features
• T: Thymic aplasia –> T cell deficiency (leads to recurrent viral + fungal infections)
• C: Cleft palate
• H: Hypoparathyroidism + hypocalcemia (due to parathyroid hypoplasia)
  22: 22q11.2 genetic microdeletion

Imaging: Absent thymic shadow on CXR

Question 41

Sx of hypercalcemia

Answer 41

Mild hypercalcemia is asymptomatic

Sever hypercalcemia- Stones, thrones, bones, groans, psychiatric overtones

• Stones: hypercalciuria leads to increased risk of calcium renal stones
• Thrones: polyuria
• Bones: Osteitis fibrosa cystica
• Groans: weakness + constipation, abdominal pain/ flank pain
• Psychiatric overtones: depression

Question 42

What are the causes of hypocalcemia?

Answer 42

1) Primary hypoparathyroidism- Accidental surgical excision of parathyroid glands, autoimmune desutrciton, DiGeorge (agenesis), AD Hypoparathyroidism
2) Secondary hyperparathyroidism- Vitamin D deficiency, Renal failure, deficienct Vitamin D receptor, Albright Hereditary Osteodystrophy