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Flashcards in Parathyroid Gland Deck (56):
1

Calcium distribution in the body and types

- 99% in bones
- 1% in intracellular compartment as free Ca++ and protein bound
- 0.1% in interstitial fluid as free Ca++
- less than 0.5% in plasma:
* 50% of it as free Ca++
* 40% of it as protein bound Ca++
* 10% of it complexed to anions like phosphate and and citrate
Note: acidosis will increase free Ca++ by decreasing protein-bound Ca++, alkalosis will decrease free Ca++ by increasing protein-bound Ca++. Acidic environment will free Ca++ and phosphate from bones

2

Bone Remodeling
(Regulation and Indices)

- It is regulated by the balance in activity of both osteoblasts and osteoclasts
- Increased serum osteocalcin and alkaline phosphatase (ALP), and increased urinary excretion of hydroxyproline indicate high bone remodeling

3

Osteoblasts
(Secretory products)

- Receptor Activator Nuclear Factor Kappa Beta ligand (RANK-L) which promotes bone resorption
- Osteoprotegerin (OPG) which is an endogenous blocker of RANK-L thereby inhibits bone resorption

4

Osteoclasts
(Regulators)

- Osteoclast precursors are differentiated to mature osteoclasts by RANK-L that binds to RANK on them, also by IL-1, IL-6 and TNF-alpha secreted by T-lymphocytes
- This differentiation is blocked by OPG secreted from osteoblasts that blocks RANK-L and also by estrogen that inhibits the secretion of cytokines from T-lymphocytes

5

Osteoblasts
(Regulators)

- Parathyroid hormone (PTH) induces them to secret RANK-L
- Estrogen induces them to secret OPG
Note: high glucocorticoids will increase RANK-L and decrease OPG inducing bone resorption

6

Weight-bearing Stress
(Effects)

Increases the mineralization of bones through unwell-understood mechanism

7

Weight-bearing Stress Absence
(Effects and Lab findings)

- Being sedentary, bedridden or weightless will promote demineralization of bones
- Plasma Ca++ in the upper range of normal, decreased plasma PTH, and increased urinary Ca++

8

Bone Demineralization and Remodeling
(Markers and Indices)

- Increased serum osteocalcin and alkaline phosphatase (osteoblastic activity)
- Increased urinary hydroxyproline (breakdown product of collagen)

9

Parathyroid Hormone (PTH)
(Factoids)

- It is a peptide
- Works through cAMP
- It increases serum Ca++
- It needs adequate amount of serum Mg++ for release

10

Parathyroid Hormone (PTH)
(Effects on Kidneys)

- Increases Ca++ reabsorption at the DCT
- Decreases phosphate reabsorption at the PCT
- Increases excretion of cAMP and hydroxyproline
- Stimulates 1-alpha hydroxylase that will produce Calcitriol (active vitamin D) in PCT

11

Parathyroid Hormone (PTH)
(Effects on Bones)

- Induces bone resorption (not when given as bolus) by increasing RANK-L by osteoblasts leading to an increase in serum Ca++ and Pi
- Increases plasma alkaline phosphatase and osteocalcin

12

Parathyroid Hormone (PTH)
(Stimulants)

Decrease in serum Ca++ (parathyroid gland has CaSR which senses the calcium plasma levels)

13

Parathyroid Hormone (PTH)
(Source)

Chief cells of parathyroid gland

14

Parathyroid Hormone (PTH)
(Regulation)

- It will be increased by decreased serum Ca++ and Mg++ and increased serum phosphate
- It will be decreased by major decrease in serum Mg++

15

Decreased serum Mg++
(Common Causes)

- Diarrhea
- Aminoglycosides
- Diuretics
- Alcohol abuse

16

Vitamin D
(Types and Sources)

- D2 (ergocalciferol) from plants, fungi and yeasts
- D3 (cholecalciferol) from skin exposure to sun (UVB converts 7-dehydrocholesterol to D3 in keratinocytes of the 2 inner most epidermal layers [stratum basale and stratum spinosum]), fish and plants
- 25-hydroxycholecalciferol from hydroxylation of D2 or D3 by 25-hydroxylase in liver (best indicator of total body stores)
- 1,25-dihydroxycholecalciferol (calcitriol or active vitamin D) from hydroxylation of 25-hydroxycholecalciferol by 1-alpha-hydroxylase in renal PCT

17

Vitamin D (Calcitriol)
(Effects)

- Increase synthesis of calbindin proteins in small intestine which increase the absorption of dietary Ca++ and phosphate
- Enhances bone mineralization
- Enhances PTH action at renal DCT

18

Vitamin D (Calcitriol)
(Regulation)

- Increase in PTH, decrease in Ca++ and phosphate will increase calcitriol
- Calcitriol feedback inhibits its own production

19

Vitamin D (Calcitriol)
(Effects of High levels)

- Increases bone resorption and release of Ca++ and phosphate from bone
- It requires concurrent presence of PTH for this effect to tack place

20

1-alpha hydroxylase
(Regulation)

- It will be increased by low phosphate and high PTH
- It will be decreased by high calcitriol

21

Hypercalcemia
(Effects)

- Decrease neural excitability causing lethargy,confusion and constipation
- Muscle weakness (blocks fast Na+ channels)
- Reduced deep tendon reflexes
- Decrease QT interval and sometimes Osborn wave (as in hypothermia)
- Nephrogenic DI (inactivates ADH)

22

Hypercalcemia
(Causes)

- Primary, Secondary and Tertiary hyperparathyroidism
- Lithium (decreases responsiveness of parathyroid gland to Ca++)
- Sarcoidosis and other granulomatous disorders (due to increased 1-alpha hydroxylase activity in granulomas)
- High bone turnover like in Thyrotoxicosis, Multiple myeloma, prolonged immobilization, Paget's disease and vitamin A intoxication
- Ectopic hormonal activity due to PTHrP like in lung squamous cell carcinoma, breast cancer, ovarian small cell carcinoma, and renal cell carcinoma
- Milk-alkali syndrome
- Thiazide diuretics
- Aluminum intoxication
- Rebound hypercalcemia after rhabdomyolysis
- Adrenal insufficiency
- Zollinger-Ellison syndrome

23

Primary Hyperparathyroidism
(Causes)

- Single parathyroid adenoma (80%)
- Primary parathyroid hyperplasia as in MEN 1 or MEN 2A (15%)
- Parathyroid carcinoma (rare)
- Familial Hypocalciuric Hypercalcemia (FHH)

24

Hypercalcemia
(Treatment)

- Hydration (with saline), increased salt-intake and forced diuresis (using loop diuretics)
- Bisphosphonates like Etidronate, Pamidronate, Alendronate and Zoledronic acid (take 2-3 days for full activity)
- Calcitonin (works quickly)
- Prednisone if the cause is sarcoidosis or any granulomatous disease

25

Primary Hyperparathyroidism
(Lab Findings)

- Hypercalcemia
- Hypophosphatemia
- Calciuria (polyuria)
- Increased phosphate excretion in urine
- Increased PTH

26

Primary Hypoparathyroidism
(Lab Findings)

- Hypocalcemia
- Hyperphosphatemia
- Decreased PTH
- Low Ca++ and low phosphate in urine

27

Hypocalcemia
(Effects)

- Tetany
- Increased neural excitability (convulsions)
- Hyperactive deep tendon reflexes
- Increased QT interval (intermittent) which predispose to Torsade de pointe
- Decreased cardiac output due to decrease in both heart rate and contractility
- Life threatening complications are laryngospasm and cardiac arrhythmias

28

Hypocalcemia
(Presentation)

- On-off petechiae that later become confluent and appear as purpura in dependent parts of the body
- Oral, peri-oral, and acral parasthesias (the earliest symptoms)
- Carpopedal or generalized tetany
- Trousseau sign (carpal spasm by inflating a cuff around the arm and keep it above systolic pressure)
- Chvostek's sign (facial spasm by tapping the facial nerve just anterior to the ear lobe)
- Convulsions
- Cardiac arrhythmias
- Slit lamp examination shows early cataracts

29

Primary Hypoparathyroidism
(Causes)

- Accidental surgical removal during thyroid surgery or when it is removed on purpose to correct hyperparathyroidism
- Autoimmune destruction of the parathyroid gland
- Hypomagnesemia
- DiGeorge's syndrome

30

Hypocalcemia
(Causes)

- Primary hypoparathyroidism
- Pseudohypoparathyroidism
- Alkalosis (via hyperventilation)
- Transfusions of citrated blood
- Rhabdomyolysis or tumor lysis (subsequent hyperphosphatemia)
- Chronic renal failure (hyperphosphatemia)
- Vitamin D deficiency
- Eating disorders and prolonged vomiting
- Exposure to mercury and hydrofluoric acid
- Excessive dietary Mg++ and Zinc
- Prolonged use of laxatives or medications that contain magnesium
- Chelation therapy especially EDTA
- Bisphosphonates, Denosumab and Calcitonin
- Pancreatitis (one of the complications)
- Neonatal hypocalcemia (very low birth weight [less than 1500 gram] and/or gestational age less that 32 weeks)

31

Calcium in the blood
(Normal ranges)

- Total Ca++ is 8.5-10.5 mg/dL
- Ionized Ca++ is 4.65-5.25 mg/dL
- You should either measure the ionized Ca++ or calculate what is called corrected Ca++ after measuring the total one depending on the albumin level
* Corrected Ca++ = Measured total Ca++ (mg/dL) + 0.8 * (4 - serum albumin [g/dL])

32

Secondary Hyperparathyroidism
(Lab Findings)

- Hypocalcemia
- Hypophosphatemia
- Low Ca++ and High phosphate in urine
- High PTH

33

Secondary Hypoparathyroidism
(Lab Findings)

- Hypercalcemia
- Hyperphosphatemia
- High Ca++ and Low phosphate in urine
- Low PTH

34

Secondary Hyperparathyroidism
(Causes)

- Vitamin D deficiency
- Malabsorption syndromes

35

Secondary Hypoparathyroidism
(Causes)

- Vitamin D excess
- Thiazide diuretics

36

Diagnosis of Parathyroid disorders

- If plasma Ca++ and Phosphate go in the opposite direction it is a primary disorder except chronic renal failure
- If plasma Ca++ and Phosphate go in the same direction it is a secondary disorder except chronic renal failure

37

Chronic renal failure
(Consequences on Ca++ homeostasis)

- It is the most common cause of secondary hyperparathyroidism
- There will be impairment of phosphate excretion, this will lead to elevated plasma phosphate which in turn will lower free Ca++; therefore will increase PTH secretion

38

Hypocalcemia
(Treatment)

- If acute and mild to moderate give 10% calcium gluconate
- If acute and severe give calcium chloride
- If chronic maintenance doses of both Ca++ and vitamin D (calcitriol) are given

39

Osteoporosis
(Definitions)

- If bone density is more than 2.5 standard deviation (SD) below average, it is osteoporosis
- If bone density is 1 to 2.5 SD below average, it is osteopenia

40

Bone Mass
(Effectors)

- Hereditary variations
- Physical activity
- Nutrition
- Estrogens

41

Secondary Osteoporosis
(Causes)

- Thyrotoxicosis
- High glucocorticoids

42

Osteoporosis
(Treatment)

- Bisphosphonates is the mainstay of treatment
- Denosumab (RANK-L inhibitor)
- Teriparatide (synthetic PTH) given as intermittent boluses which stimulate osteoblastic bone formation
- Calcitonin
- Raloxifene (selective-estrogen receptor modifier)

43

Paget's disease
(Physical and Lab findings)

- Skin overlying thighs, lower back and skull is warm to touch, with loss of hearing in 30-40% of cases involving the skull
- Increased serum alkaline phosphatase, but normal serum Ca++ and phosphate
- Increased urine hydroxyproline

44

Paget's disease
(Treatment)

- Most patients are asymptomatic and require no treatment
- Bisphosphonates like Etidronate, Pamidronate and Alendronate
- Calcitonin
- NSAIDs and acetaminophen for pain management

45

Calcitonin
(Source)

Parafollicular cells (C cells) of thyroid gland

46

Calcitonin
(Function)

Decrease bone resorption of Ca++ (not important in normal Ca++ homeostasis)

47

Calcitonin
(Regulation)

Increase in serum Ca++ will stimulate its release

48

Hypercalcemia
(Presentation)

- Confusion, stupor, lethargy and constipation
- Osteoporosis
- Nephrolithiasis, DI, and renal insufficiency
- Short QT syndrome and Hypertension
- Acute pancreatitis
- Peptic ulcer disease (Ca++ stimulates gastrin)

49

Primary Hyperparathyroidism
(Imaging)

- DEXA densitometry is better than x-ray to test bone effects of high PTH
- Neck sonography or nuclear scanning before surgery

50

Primary Hyperparathyroidism
(Treatment)

- Surgical removal of the involved gland(s)
- If surgery is not possible, give Cinacalcet (an inhibitor of PTH release)

51

Primary Hyperparathyroidism
(Presentation)

- Most often asymptomatic,but may presents the same way as hypercalcemia presentation
- Osteitis fibrosa cyctica (cyctic bone spaces filled with brown fibrous tissue consisting of osteoclasts and deposited hemosiderin from hemorrhages and causes bone pain)

52

Tertiary Hyperparathyroidism
(Definition)

Refractory hyperparathyroidism resulting from chronic renal disease (very high PTH with high Ca++)

53

Secondary Hyperparathyroidism due to renal insufficiency
(Treatment)

- Treat the hypercalcemia
- Give oral phosphate binders like aluminum hydroxide, calcium salts, sevelamer hydrochloride, and lanthanum carbonate in addition to restriction of dietary phosphate
- Give Cinacalcet

54

Osteoporosis
(Diagnosis)

- Checking the bone mineral density (BMD) using Dual-energy x-ray absorptiometry (DEXA) usually in vertebral bodies, proximal femur and distal radius
- Rule out secondary causes by doing CBC, TFTs, CMP,, 24-hour urine Ca++, serum 25-hydroxycholecalciferol, testosterone (in men), and SPEP/UPEP (to rule out multiple myeloma)
- X-rays: global demineralization is apparent only after > 30% of bone density is lost

55

Paget's disease
(Diagnosis)

- Radionuclide bone scan in early disease (most sensitive)
- Plain x-ray films are critical with the classical signs being: thickened bone cortex, thickened trabeculae, and expansion of femoral head ("mosaic" lamellar bone pattern)

56

Paget's disease
(Complications)

- Pathological fractures
- High-output cardiac failure
- Osteosarcoma (up to 1%)