Primary hyperparathyroidism

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???? ???? ????? ???? 2007
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• ???? ?? 55
• Ca-11.8 mg/dl
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• P-2.6 mg/dl
• Alb-4 g/dl

• ???? ?? 68
• Ca-14.1 mg/dl
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  ?????
• Ca of breast
• P-2.4 mg/dl
• Alb-3 g/dl

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Extracellular Calcium (8.5-10.5 mg/dl)

• Ionized 50
• Albumin bound 40
• Complexed 10 (citrate, phosphate)
• Lab measures - Total Calcium
• Normal range - 8.5-10.5 mg/dl
• In correlation to free, ionized Calcium
• When Albumin level is 4 mg/dl

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Example

• Patient 1
• Ca 10.7
• Albumin 4
• Patient 2
• Ca 10.7
• Albumin 3
• Is their ionized calcium level the same ?

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Correction of Total Calcium According to Albumin

• In order to estimate the ionized calcium, we
  should correct the total calcium level
• For each 1g/dl of albumin below 4
• Correct serum calcium by increase 0.8 mg/dl
• Patient 1 Ca 10.7, Albumin 4
• gt no correction
• Patient 2 Ca 10.7, Alb 3 -gt corrected 11.5
  
• gt elevated

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The concentration of calcium is maintained
within a narrow range because of its critical
role in a variety of cellular functions
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• Ca-11.8
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• P-2.6, Alb-4

• ???? ?? 68
• Ca-14.1
• ??????? ???? ??????, ?????, ????????, ?? ?????
  ?????
• Ca of breast
• P-2.4, Alb-3
• ???? ????? mg/dl 14.9

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Calcium Homeostasis (Normal level 8.5-10.5 mg/dl)
Duodenum Proximal jejunum 0.4-1.5 g
99 of the body calcium resides in the
skeleton 1000-2000 g
Absorption requires gastric acid!!!
65 of filtered calcium is reabsorbed in the
proximal tubule Only 2-3 is secreted
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Calcium Homeostasis
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Calcium-Regulated PTH Release
PTH release of max
Hypocalcemia 7.5-8 mg/dl
Calcium level
Normal Calcium 8.5-10.5 mg/dl
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Parathyroid Hormone (PTH)

• Single chain polypeptide 84 amino acids
• 1-34AA are Critical for the biologic activity

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Calcium Sensing Receptor
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Important Hormones in Calcium Homeostasis

1. PTH parathyroid gland ?
2. bones increase bone resorption
3. intestine Ca absorption (indirect D)
4. kidneys Increase Ca reabsorption 1,25(OH)D
5. 1,25(OH)D3 kidneys ?
6. intestine Ca absorption
7. bone mineralization
8. PTHrP malignancies ?
9. Calcitonin Parafollicular C cells of thyroid
   inhibits bone resorption

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?????? ?????? - ?????????

• ???? ?? 55
• Ca-11.8
• ??????? ?????, ??? ???
• ?????? ?????? ??????
• ????? ???? ???
• P-2.6, Alb-4

• ???? ?? 68
• Ca-14.1
• ??????? ???? ??????, ?????, ????????, ?? ?????
  ?????
• Ca of breast
• P-2.4, Alb-3
• ???? ????? 14.9

• ?? ?????? ?
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Whenever hypercalcemia is confirmed, a definitive
diagnosis should be made
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Differential Diagnosis of Hypercalcemia

• Primary Hyperparathyroidism
• Malignant diseases
• Vitamin D dependant
• Granulomatous disease, lymphomas
• Vitamin D intoxication
• Familial benign Hypocalciuric Hypercalcemia
• Endocrine diseases hyperthyroidism, Addison
• Drug induced (lithium, thiazides)
• Miscellaneous

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Severity Index of Hypercalcemia

• Calcium level
• 8.5 - 10.5 mg/dl normal
• 10.5 - 12 mg/dl mild, usually asymptomatic
• 12 - 15 mg/dl moderate
• 15 mg/dl hypercalcemic crisis
• How fast was the change in Ca

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Hypercalcemia Clinical Features

• Acute or severe
• Neurological fatigue, decreased concentration,
  depression, confusion, coma.
• Cardiovascular short QT, bradycardia
• Renal stones, polyuria, failure
• GIT nausea, vomiting, constipation

• Chronic
• Asymptomatic.
• Renal stones, polyuria, failure
• Bones osteoporosis, fractures, (osteitis
  fibrosa cystica)

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Hypercalcemia Arrhythmias
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Primary Hyperparathyroidism

• Most common cause of hypercalcemia in
  asymptomatic patients
• Incidence 1/500-1/1000
• Most frequent age 50-60 y
• Women men ration 31
• Majority - postmenopausal women

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PHPT - Etiology

• Adenoma - benign, solitary 80
• Double adenoma 3-5
• Hyperplasia 4 glands 12-15SporadicallyFamil
  ial MEN I, MEN IIa, FHH
• Carcinoma lt 0.5

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PHPT - Signs Symptoms

• Asymptomatic most common (80)
• Kidneys nephrolithiasis 20
• nephrocalcinosis
• Skeletal disease osteitis fibrosa cystica lt
  5 osteoporosis
• Neuromuscular easy fatigability, proximal
  muscle weakness
• Gastrointestinal vague abdominal complaints

Stones, bones, abdominal groans, and psychic moans
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Hyperparathyroidism - Bones
Osteitis fibrosa cystica
osteoporosis
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PHPT - Laboratory

• Ca ? (lt11.5 mg/dl)
• PTH ? (10 65 pg/dl)
• 1,25(OH)2D3 ?- N
• P ?
• Alkaline phosphatase ? - N
• 24 urine calcium excretion ? (40 )

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Primary Hyperparathyroidism - Treatment

• Acute therapy of hypercalcemia
• Rehydration restore renal function
• Renal excretion of calcium diuresis
• Calcitonin
• Long term treatment
• Surgery curative, the only definite treatment
• follow-up
• medications

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Indications for Surgery in Asymptomatic
HyperparathyroidismNIH Consensus Statement 5/2002

• Serum Ca gt 11.5 mg/dl (8.5-10.5)
• Age lt 50 years
• 24 hours urine Ca gt 400 mg
• Osteoporosis (any site)
• Nephrolithiasis
• Creatinine clearance reduced by 30

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Preoperative Localization Techniques

• Preoperative localization tests should not be
  used to make, confirm or exclude the diagnosis of
  PHPT
• Tc-99m sestamibi scan - 80-85
• US - 60-70
• CT, MRI

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Surgical Treatment - Parathyroidectomy

• Success rate gt95
• Important highly experienced surgeon
• Conservative approach
• removal of adenoma biopsy of another
  gland
• Current approach
• mini-invasive parathyroidectomy
• After parathyroidectomy
• Lab - Normal Calcium, PTH
• BMD increased 10-20
• Nephrolithiasis no recurrence

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Medical Treatment

• The only definite treatment is surgery
• Calcium intake 1000-1200 mg/day
• Avoid vitamin D deficiency
• Treatment of osteoporosis
• Calcimimetics (not approved yet)

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Calcimimetics

• Mimic effect of calcium on calcium sensing
  receptor
• Act as Ca sensing receptor agonists
• Inhibit PTH secretion
• Decrease serum calcium level
• Further studies are needed
• Not in clinical use

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????? ????? 1- ?????

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• Ca-11.8
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• ??? ????
• P-2.6, Alb-4

• ?? ?????? ?????? ????? ?
• ??? ???? ?? ?????? ?

PTH !!!
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????? ????? 1- ?????

• ???? ?? 55
• Ca-11.8
• ??????? ?????, ??? ???
• P-2.6, Alb-4
• PTH 157 (12-72)

Primary Hyperparathyroidism
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????? ????? 1 - ?????

• ???? ?? 55
• Ca-11.8
• P-2.6, Alb-4
• PTH 157 (12-72)
• ?????? ???? ??????
• BMD ????, ??? ???? ?????

Primary Hyperparathyroidism
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Hypercalcemia of Malignancy - Etiology

• PTHrP humural hypercalcemia of malignancy
• squamous cell tumors, renal, breast
• (Not related to bony metastases)
• Cytokines osteoclast activating factor
• Multiple Myeloma, leukemia, lymphoma
• 1,25(OH)2D3 lymphoma

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PTHrP is responsible for most instances of
hypercalcemia of malignancy
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Hypercalcemia of Malignancy

• Most common in hospitalized patients
• Grave prognosis, time to death lt6m
• Malignancy apparent 98
• Labs PTHrP related
• Ca ?, P?
• PTH ?
• 1,25(OH)2D3 N
• Labs vitamin D related
• Ca ?, P ?
• PTH ?
• 1,25(OH)2D3 - ?

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Hypercalcemia of Malignancy - Treatment

• Primary disease long term
• Hydration normal saline
• Forced diuresis (loop diuretic)
• Bisphosphonates - intravenous
• (Pamidronate, zolendronic acid)
• Glucocorticoids
• (vitamin D related hypercalcemia)
• Calcitonin (very rapid, short term)

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????? ????? 2- ?????

• ???? ?? 68
• Ca-14.1
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  ?????
• Ca of breast
• ?? ?????? ??????
• P-2.4, Alb-3
• ??? ???? ???? ????? 14.9 mg/dl

• ?? ?????? ?????? ????? ???????

PTH !!!
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????? ????? 2- ?????

• ???? ?? 68
• Ca-14.1
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• Ca of breast
• ?? ?????? ??????
• P-2.4, Alb-3
• PTH 5 (12-72)

Hypercalcemia of Malignancy, PTHrP
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????? ????? 2 - ?????

• 1???? ?? 68
• Ca-14.1
• Ca of breast ?????? ??????
• PTH 5 (12-72)

Hypercalcemia of Malignancy, PTHrP
??????, ???????? bisphosphonates
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Differential Diagnosis
PHPT malignancy
Clinical manifestations Usually asymptomatic Sick, apparent malignancy
Ca Mildlt12 Higher
PTH Elevated Suppressed
PTHrP Low Elevated
1,25(OH)2D3 High N
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Evaluation of Hypercalcemia
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Whenever hypercalcemia is confirmed, a definitive
diagnosis should be made
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Calcium -Physiological Functions

• Skeletal mineralization
• Neuromuscular activity
• Heart contraction
• Signal transduction
• Stability to plasma membranes
• Cofactor in coagulation