hyper parathyroidism

1. 2012.12.08

2.  84–amino acid polypeptide hormone
 responsible for maintaining ECF [Ca2+]
 secretion is gulated directly by the ECF
[Ca2+]
 stimuli
 Decreased serum [Ca2+]
 Mild decreases in serum [Mg2+]
 An increase in serum phosphate
 only hormone which is up regulated when the
stimulus is low

3.  increase ECF [Ca2+] by
 increasing the release of calcium and phosphate
from bone matrix
 increasing calcium reabsorption by the kidney
 increasing renal production of 1,25-
dihydroxyvitamin D-3 (calcitriol), which increases
intestinal absorption of calcium
 causes phosphaturia, decreasing serum
phosphate levels

5.  4 glands - posterior to the thyroid gland
 Superior 2, inferior 2
 some times 3, 5, or, occasionally, more
glands
 inferior glands - derived from the third
pharyngeal pouch with the thymus
 migrate along with the thymus
 become situated more inferiorly than the
superior glands
 usually located near the inferior pole of the
thyroid
 Can go in to superior mediastinum

6.  superior glands - more consistent in location
 just superior to the intersection of the inferior
thyroid artery and the recurrent laryngeal nerve
 derived from the fourth pharyngeal pouch
 occasionally found within the substance of the
thyroid gland.

9.  Primary
 Secondary
 Tertiary

10.  unregulated overproduction of parathyroid
hormone (PTH) resulting in abnormal calcium
homeostasis
 21 cases per 100,000 person-years.
 The mean age at diagnosis - between 52 and
56 years
 female-to-male ratio of 3:1

11.  85% of cases, primary hyperparathyroidism is
caused by
 single adenoma
 hyperplasia
 15% of cases, multiple glands are involved
 Rarely, primary hyperparathyroidism is
caused by parathyroid carcinoma.
 aetiology of adenomas or hyperplasia is
unknown in most cases

12.  Familial
 multiple endocrine neoplasia syndromes (MEN 1
or MEN 2a)
 hyperparathyroid-jaw tumor (HPT-JT) syndrome
 familial isolated hyperparathyroidism (FIHPT)
 familial hypocalciuric hypercalcemia
 neonatal severe hyperparathyroidism

13.  normal feedback on parathyroid hormone
production by extracellular calcium is lost
 increase in the cell numbers is probably the
cause.
 chronic excessive resorption of calcium from
bone result in osteopenia

14.  may result in osteitis fibrosa cystica
 subperiosteal resorption of the distal phalanges
 tapering of the distal clavicles
 salt-and-pepper appearance of the skull
 brown tumors of the long bones
 chronically hypercalciuria predisposes to the
formation of renal stones.

15. symptoms of hyperparathyroidism are due to the
hypercalcemia
 muscle weakness
 fatigue
 volume depletion
 nausea and vomiting
 and in severe cases, coma and death
 neuropsychiatric manifestations
 depression
 confusion
 increase gastric acid secretion
 peptic ulcer disease
 rare cases of pancreatitis

16.  bones, stones, abdominal groans, and psychic
moans
 severe bone disease, kidney stones to
asymptomatic hypercalcemia
 Skeletal manifestations
 selective cortical bone loss
 bone and joint pain
 pseudogout
 chondrocalcinosis
 osteitis fibrosa cystica

17.  Renal manifestations
 polyuria
 kidney stones
 hypercalciuria
 nephrocalcinosis.
 Gastrointestinal manifestations
 anorexia
 nausea
 vomiting
 abdominal pain
 constipation
 peptic ulcer disease
 acute pancreatitis.

18.  Cardiovascular manifestations
 hypertension
 bradycardia
 shortened QT interval
 left ventricular hypertrophy
 Physical examination findings
 usually noncontributory

19.  causes of hypercalcemia + elevated
parathyroid hormone level are few
 familial benign (hypocalciuric) hypercalcemia
(FHH) (see Related disorders)
 lithium-induced hypercalcemia
 tertiary hyperparathyroidism.

20.  all potential causes of secondary
hyperparathyroidism should be excluded
 low calcium intake
 gastrointestinal disorders
 renal insufficiency
 vitamin D deficiency
 hypercalciuria of renal origin
 secondary and tertiary hyperparathyroidism are
typically diagnosed based on their clinical
context
 cancer-induced hypercalcemia
 low parathyroid hormone level
 possibly a high parathyroid hormone-related peptide
level

21. Laboratory studies
 total serum calcium and albumin levels or
ionized calcium levels
 hypercalcemia should be documented on more
than one occasion
 intact parathyroid hormone level is the core of
the diagnosis
 elevated intact parathyroid hormone level with
an elevated ionized serum calcium level is
diagnostic of primary hyperparathyroidism
 24-hour urine calcium measurement is necessary
to rule out FHH.

22.  other biochemical abnormalities
 mild hyperchloremic acidosis
 hypophosphatemia
 mild-to-moderate increase in urinary calcium
excretion rate.
Imaging studies
 make a decision about whether to pursue
surgical therapy
 If a limited parathyroid exploration is to be
attempted, a localizing study is necessary

23.  USS of the neck
 capable of a high degree of accuracy
 operator dependent
 not been reliable in detecting multigland
disease.
 Nuclear medicine scanning with radiolabeled
sestamibi

25.  CT scanning and MRI
 locate abnormal parathyroid glands
 Standard CT scanning has inadequate sensitivity.
 Newer techniques of CT scanning with dynamic
contrast images (4D-CT) accuracy 88%.
 MRI - particularly in cases of
 recurrent
 persistent disease
 ectopic locations such as the mediastinum.

26.  dual-energy radiographic absorptiometry
 demonstrate the skeletal involvement in primary
hyperparathyroidism
 Hyperparathyroidism affects the cortical bone at
the radius (distal third)
 skeletal radiographs
 salt-and-pepper degranulation in the skull
 subperiosteal bone resorption in the phalanges.
Procedures
 Bilateral internal jugular vein sampling
 localize ectopic parathyroid adenomas

27.  surgical excision of the abnormal parathyroid
glands
 the only permanent, curative treatment for
primary hyperparathyroidism.
 surgical treatment should be offered to all
patients with symptomatic disease.

28.  The indications for surgery
 1 mg/dL above the upper limit of the reference
range for serum calcium
 24 hour urinary calcium excretion greater than
400 mg
 30% reduction in creatinine clearance
 bone mineral density T-score below -2.5 at any
site
 age younger than 50 years

29.  monitoring of patients with asymptomatic
hyperparathyroidism
 serum calcium and creatinine levels every 6
months
 annual bone mineral density

30. Management of severe hypercalcemia in the
acute setting
 IV volume expansion
 sodium chloride and loop diuretics, once the
intravascular volume is restore
 Drugs (temporary measure prior to surgical
treatment )
 calcitonin
 IV bisphosphonate

31. Nonsurgical care
 should be carefully monitored
 maintain a moderate daily elemental calcium
intake of 800-1000 mg
 vitamin D intake appropriate for their age
and sex.
 participation in regular exercise activity
 avoid immobilization
 avoid thiazides, diuretics, and lithium

32. Pharmacotherapy
 Estrogen therapy in postmenopausal women
 Selective estrogen receptor modulators
raloxifene
 Bisphosphonates
 Calcimimetic drugs
 activate the calcium-sensing receptor and inhibit
parathyroid cell function - cinacalcet

33.  Other treatments
 Percutaneous alcohol injection to parathyroids
 ablation with ultrasound energy

34. surgical care
 should be offered to most patients
 standard operative approach is complete neck
exploration,identification of all parathyroid
glands and removal of all abnormal glands.
 85% of cases caused by a single adenoma
 full neck exploration might be an unnecessary
dissection
 directed parathyroidectomy
 preoperative imaging studies to localize the abnormal
gland
 removal only that gland

35. Localisation
 sestamibi scanning or ultrasonography.
 intraoperative parathyroid hormone assay
 radio-guided parathyroidectomy
 detecting the labeled sestamibi in the abnormal
gland using a handheld probe
 for familial disease
 total parathyroidectomy with
autotransplantation to the forearm and
cryopreservation of some parathyroid tissue

36.  in 4-gland hyperplasia
 3.5-gland (subtotal) parathyroidectomy
 50-70 mg of the most normal-appearing tissue is
left

37. Complications and postoperative care
 calcium levels must be monitored
 every 12 hours until stabilization
 many become hypocalcemic
 few become symptomatic
 treatment for hypocalcemia
 severe
 Symptomatic

38.  hypocalcemia after parathyroid surgery may
be due to hungry bone syndrome
 calcium and phosphorus are rapidly deposited in
the bone
 If hypoparathyroidism persists
 oral supplementation
 calcium
 vitamin

39.  overproduction of parathyroid hormone
secondary to a chronic abnormal stimulus for its
production
 Typically
 chronic renal failure
 vitamin D deficiency
 Secondary hyperparathyroidism (SHPT) develops
early in CKD before dialysis is required
 In chronic kidney disease, overproduction of
parathyroid hormone occurs in response
 Hyperphosphatemia
 Hypocalcemia
 impaired 1,25-dihydroxyvitamin D production

40. Medical management is the mainstay
 Correcting vitamin D deficiency
 Dietary phosphate restriction
 Phosphate binders
 calcium-based phosphate binders
 calcium carbonate
 calcium acetate
 non-calcium-based phosphate binders
 sevelamer hydrochloride
 lanthanum carbonate
 Calcium supplementation should be limited
to less than 2 g/d

41. Indications for surgery
 bone pain or fracture
 Pruritus
 Calciphylaxis
 Extraskeletal nonvascular calcifications
 elevated parathyroid hormone levels despite
appropriate medical therapy
 severe hyperparathyroidism
 persistent serum levels of intact parathyroid
hormone greater than 800 pg/mL

42.  Medical treatment is successful in most
patients
 Patients who require parathyroidectomy have
a 10% risk of recurrent or persistent disease

43.  development of autonomous hypersecretion
of parathyroid hormone causing
hypercalcemia
 aetiology is unknown
 may be due to monoclonal expansion of
parathyroid cells
 four-gland involvement occurs in most patients.

44. Pathophysiology
 observed in patients with chronic secondary
hyperparathyroidism and often after renal
transplantation.
 hypertrophied parathyroid glands fail to
return to normal
 continue to oversecrete despite serum
calcium levels normal or elevated
 dngerous - phosphate level is often elevated.
 diffuse calcinosis may occur.

45. Treatment
 Total parathyroidectomy with
autotransplantation
 subtotal parathyroidectomy

46. Familial benign (hypocalciuric)
hypercalcemia
 loss-of-function mutation of one allele of the
gene for the calcium-sensing receptor
 hypercalcemia, hypophosphatemia, and
hypermagnesemia
 can be distinguished from primary
hyperparathyroidism by low 24-hour urinary
calcium excretion
 Persons with FHH are asymptomatic.
 parathyroidectomy is not indicated

48. Hypercalcemia of malignancy
 caused by
 tumor release of parathyroid hormone -related
peptide
 over production of 1,25-dihydroxyvitamin D
 local osteolytic lesions
 low or undetectable intact parathyroid
hormone level

49. Calciphylaxis
 = uremic gangrene syndrome
 observed in patients with renal failure and
secondary or tertiary hyperparathyroidism.
 characterized by ischemic necrosis of the
skin due to calcium phosphate crystal
deposition and subsequent inflammation in
small-to-medium–sized vessels