Hyerparathyroidism

hyper parathyroidism

1. Hyperparathyroidism 2012.12.08

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

3. Parathyroid hormone 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

4. Anatomy and Embryology 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

5. 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.

6. Hyperparathyroidism Primary Secondary Tertiary

7. Primary Hyperparathyroidism 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

8. 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

9. 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

10. Pathophysiology 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

11. 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.

12. 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

13. Clinical presentation 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

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

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

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

17. 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

18. 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.

19. 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

20. 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

21. 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 .

22. 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

23. Treatment 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.

24. 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

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

26. 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

27. 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

28. 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

29. Other treatments Percutaneous alcohol injection to parathyroids ablation with ultrasound energy

30. 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

31. 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

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

33. 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

34. 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

35. Secondary hyperparathyroidism 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

36. 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

37. 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

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

39. Tertiary Hyperparathyroidism 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.

40. 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.

41. Treatment Total parathyroidectomy with autotransplantation subtotal parathyroidectomy

42. Related Disorders 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

43. Multiple endocrine neoplasia

44. 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

45. 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

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