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Homeostasis
Parathyroid gland
o Four glands; located posterior to the thyroid gland
o Produce parathyroid hormone
Parathyroid hormone
o Acts directly on the bone to induce calcium release
o Acts on the kidney to enhance calcium reabsorption and
increase synthesis of 1,25-dihydoxyvitamin D
1,25-dihydroxyvitamin D
o Increase gastrointestinal calcium absorption
PARATHYROID HORMONE
I. PHYSIOLOGY
Overall effects:
o Increase rate of dissolution of bone mineral
o Reduce renal clearance of calcium
o Increase efficiency of intestinal calcium absorption by
stimulating production of 1,25 (OH)2D
Renal effects:
o Proximal tubule Inhibition of phosphate transport
o Distal tubule Augmentation of calcium reabsorption
o Stimulation of renal 25(OH)D-1a-hydroxylase
Bone effects:
o increase osteoblasts and osteoclasts; increase bone
remodeling
o Continuous exposure increased osteoclast-mediated
bone resorption
o Intermittent exposure net stimulation of bone
formation
o Osteoblasts have PTH receptors, crucial to boneforming effect
o Osteoclasts lack PTH receptors, activated by
osteoblast-derived cytokines
Both PTH and PTHrP bind to and activate the PTH/PTHrP receptor
o PTH1R respond equivalently to both
o PTH2R (human) respond efficiently to PTH (but not to
PTHrP)
CALCITONIN
Hyperparathyroidism
o A frequent cause of asymptomatic hypercalcemia
Malignancy
o Second most common cause of hypercalcemia in the
adult
o Symptoms bring the patient to the physician
o Interval between detection of hypercalcemia and death is
often <6 months
Other causes
o Excessive vitamin D action
o Impaired metabolism of 1,25 (OH)2D
o High bone turnover
o Renal failure
Clinical manifestations
o Fatigue, depression
o Mental confusion
o Anorexia, nausea, vomiting
o Increased urine output
o Short QT interval and cardiac arrhythmias
Severe hypercalcemia ( 3.7-4.5 mmol/L)
o Coma and cardiac arrest can occur
I. PRIMARY HYPERPARATHYROIDISM
1. Natural History and Incidence
Minimal or no symptoms
2. Etiology
SOLITARY ADENOMAS
Parathyroid carcinoma
o Often not aggressive
o Usually more severe clinically
o Associated with serum calcium values of 3.5-3.7 mmol/L
4. Signs and Symptoms
Kidney manifestations
o Calcium deposition in the renal parenchyma
o Recurrent nephrolithiasis
Bone manifestations
o Osteitis fibrosa cystica
CNS manifestations
o Proximal muscle weakness
o Atrophy of muscles
o Complete regression of neuromuscular disease after
surgery (distinguishing feature)
GI manifestations
o Duodenal ulcers secondary to Zollinger-Ellison
syndrome in MEN1
Parenteral calcium
When hypocalcemia is
symptomatic
0.5 2 mg/kg/hr
Mechanisms of hypercalcemia
o Humoral hypercalcemia of malignancy
Undetectable PTH
PTH resistance
o Major factor in developing hypocalcemia
o Leads to parathyroid gland enlargement
FGF23
o Potent inhibitor of renal 1-a hydroxylase
Renal osteodystrophy
o Bone disease seen in secondary hyperparathyroidism
and CKD
Calcium carbonate
Sevelamer
Tertiary hyperparathyroidism
o Severe hyperparathyroidism no longer responsive to
medical therapy
o Surgery necessary to control this condition
TREATMENT OF HYPERCALCEMIC STATES
I. HYDRATION, INCREASED SALT INTAKE, MILD AND FORCED
DIURESIS
Pamidronate
o Single IV bolus (30 90 mg)
o Normalize calcium within 24-48 h
o Effect lasts for weeks
Zoledronate
o 4 or 8 mg / 5 min infusion
o More rapid and sustained effect than pamidronate
III. CALCITONIN
Tachyphylaxis
o No longer effective after 24 hours
IV. OTHER THERAPIES
Glucocorticoids
o Effective in multiple myeloma, Hodgkins lymphoma,
leukemia
o Also effective in sarcoidosis and vitamin D
intoxication
Dialysis
o Treatment of choice for severe hypercalcemia in renal
failure
Phosphate therapy
o Limited role in certain circumstances
o IV phosphate one of the most dramatically effective
treatments but is toxic
HYPOCALCEMIA
Chronic hypocalcemia
o Muscle spasms, carpopedal spasms, facial grimacing
o Respiratory arrest may occur
o Increased intracranial pressure and papilledema
o Mental changes
I. PTH ABSENT
Hereditary hypoparathyroidism
o Basal ganglia calcification and extrapyramidal
syndromes are more common and earlier in onset
DiGeorge syndrome
o Defective development of both thymus and parathyroid
gland
o Severe infections, hypocalcemia and seizures
Kenney-Caffey syndrome
o Short stature, osteosclerosis and thick cortical bones
Sanjad-Sakati syndrome
o Growth failure seen in Middle Eastern patients
Kearns-Sayre syndrome
o Ophthalmoplegia and pigment retinopathy
MELAS syndrome
o Mitochondrial encephalopathy, lactic acidosis, stroke-like
syndrome
o Hemochromatosis
o Infection usually does not cause hypoparathyroidism
Transient hypoparathyroidism
o Frequent following parathyroid surgery
3. Treatment
Thiazide diuretics
o Lower urine calcium
o Prevent nephrocalcinosis and nephrolithiasis
PTH therapy
o Not approved as of yet