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THYROID & PARATHYROID COLIN G. THOMAS, JR., MD
The Thyroid Gland <ul><li>130-201 Galen </li></ul><ul><li>1543  Vesalius </li></ul><ul><li>Wharton “Oblong Shield” </li></...
Historical Aspects of Goiter 200 BC <ul><li>Atharva Veda (Hindu): exorcism of goiter </li></ul>
1271 <ul><li>Marco Polo: “They are in general afflicted with tumors in the throat occasioned by the nature of the water wh...
 
Incidence of Thyroid Disorders in Connecticut (Annual physical Examination, 1544 Patients – One Year) <ul><li>#   % </li><...
Nodular Goiter <ul><li>Prevalence Rate: .08%/yr </li></ul><ul><li>Clinical incidence- Adults: 4-7% </li></ul><ul><ul><li>F...
 
Cancer Incidence and Deaths Estimated- U.S. 2005 <ul><li>Organ System New Cases Deaths   </li></ul><ul><li>Lung 172,570  1...
Thyroid Cancer <ul><li>1985 1994 1998 </li></ul><ul><li>New Cases 10,000 13,900 17,200  ( ↑ 72%) </li></ul><ul><li>Deaths ...
 
 
Evaluations of Nodular Thyroid Disease <ul><li>History- symptoms, duration, familial </li></ul><ul><li>Physical findings, ...
 
 
 
Diagnostic Studies- Thyroid Cancer <ul><li>Fine Needle Aspiration- Establishes Cytologic Diagnosis </li></ul><ul><li>Thyro...
 
 
 
 
 
 
 
 
Thyroid Cancer- Diagnosis <ul><li>Cytology </li></ul><ul><li>Scans </li></ul><ul><ul><li>Technetium </li></ul></ul><ul><ul...
Thyroid Cancers* <ul><li>Papillary 80% </li></ul><ul><li>Follicular 11% </li></ul><ul><li>H ürthle 3% </li></ul><ul><li>Me...
Biological Characterstics <ul><li>Thyrotropin Receptor- </li></ul><ul><ul><li>Adenylate Cyclase Systems </li></ul></ul><ul...
Thyroid Cancer A Spectrum of Neoplasms <ul><li>Surgical Treatment:  Reflect Biological Characteristics </li></ul>
 
Papillary Carcinoma <ul><li>Ames (Age, Distant Metastases, Extent,  Size) </li></ul><ul><li>89%- Low risk; Mortality 1.8% ...
 
 
 
 
Adjuvant Therapy <ul><li>Thyroxine  -> TSH Suppression </li></ul><ul><li>Radiodiodine (Ablation/Rx) </li></ul><ul><li>Thyr...
 
 
 
 
 
 
 
 
On a New Gland in Man and Several Mammals <ul><li>Ivar Sandstr Ő m </li></ul><ul><li>“ About three years ago (1877) I foun...
Ivar Sandstr Ő m <ul><li>“So much the greater was my astonishment therefore when in the first individual (patient) examine...
Herr Bleich, 40, Male, Mason <ul><li>April 1888 Fall, ? Femoral neck fracture </li></ul><ul><li>August 1888 Fall, Clavicle...
Herr Bleich: Autopsy (Pathological Institute of Strassburg) <ul><li>1889 Von Recklinghausen </li></ul><ul><li>Skeletal Fin...
Albert  ____ 38, Male, Street Car Conductor <ul><li>Chicken pox [5], Measles [6], Syphilis [19], Tuberculosis </li></ul><u...
Albert J ä hne RX: Von Recklinghausen’s Disease <ul><li>1924 Parathyroid Extract from animals, </li></ul><ul><li>Parathyro...
 
Elva Dawkins <ul><li>February 1928 </li></ul><ul><li>Fractured left humerus, tumor of  maxilla,  benign giant cell sarcoma...
Hyperparathyroidism <ul><li>Rarefaction of bone </li></ul><ul><li>Multiple cystic bone tumors, giant cell sarcoma </li></u...
 
Captain Charles Martell (1889-1932) <ul><li>1926 “Hyperparathyroidism” suggested by Dr.  Dubois, Bellvue Hospital </li></u...
1932  _____ ______ (J. Morelle) Louvain <ul><li>Diagnosis by Serendipity </li></ul>
Primary Hyperparathyroidism <ul><li>Abnormal relationship between calcium and </li></ul><ul><li>PTH levels with changes in...
 
Hyperparathyroidism <ul><li>Incidence  1:700  (0.14%) </li></ul><ul><li>Most common cause of Hypercalcemia in non-hospital...
Hyperparathyroidism (Classification) <ul><li>1 ° HPT- Idiopathic inappropriate  secretion of PTH </li></ul><ul><li>II. 2 °...
Hyperparathyroidism (Classification) <ul><li>IV. Ectopic Hyperparathyroidism </li></ul><ul><ul><li>(Humoral Hypercalcemia ...
 
Table 1. Symptoms and Signs of Hypercalcemia* <ul><li>  Percent </li></ul><ul><li>Symptoms </li></ul><ul><li>Fatigue 28 </...
Clinical Manifestations of Hyperparathyroidism <ul><li>Renal </li></ul><ul><ul><li>Hypercalciuria, negative calcium balanc...
Hyperparathyroidism in the Elderly ( ≥ 65) <ul><li>Incidence – 1.5% </li></ul><ul><li>40% - Hypercalcemia A Serendipitous ...
Evaluation of 1 ° Hyperparathyroidism <ul><li>SERUM ELECTROLYTES </li></ul><ul><li>BUN, CREATININE </li></ul><ul><li>iPTH ...
 
 
 
 
 
Asymptomatic Hyperthyroidism <ul><li>Natural History – Unknown </li></ul><ul><li>Rapid Progression to Severe Disease – Rar...
Table 1. Comparison of Old and New Criteria for Parathyroid Surgery in Patients with Asymptomatic Primary Hyperparathyroid...
Parathyroidectomy Indications <ul><li>Symptomatic Patients </li></ul><ul><li>Asymptomatic Patients </li></ul><ul><ul><ul><...
Effects of Successful Surgery on Problems Associated with Hyperparathyroidism <ul><li>Osteopenia: Increased bone mineral d...
Parathyroid Imaging- Localization <ul><li>Experienced Surgeon </li></ul><ul><li>Ultrasound </li></ul><ul><li>Scintigraphy ...
 
 
 
End Stage Renal Disease <ul><li>Eu- hypercalcemia </li></ul><ul><li>Hyperphosphatemia </li></ul><ul><li>↑  alkaline phosph...
Renal Osteodystrophy Indications for Parathyroidectomy <ul><li>Bone pain </li></ul><ul><li>Proximal myopathy </li></ul><ul...
 
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Thyroid and Parathyroid

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Transcript of "Thyroid and Parathyroid"

  1. 1. THYROID & PARATHYROID COLIN G. THOMAS, JR., MD
  2. 2. The Thyroid Gland <ul><li>130-201 Galen </li></ul><ul><li>1543 Vesalius </li></ul><ul><li>Wharton “Oblong Shield” </li></ul><ul><li>Gull – “Adult Cretinism” </li></ul><ul><li>Murray “Liquor Thyroidei” </li></ul><ul><li>Kocher – Nobel Prize </li></ul><ul><li>Kendall –Isolation of thyroxine </li></ul><ul><li>1951 Pitt-Rivers-isolation of T3 </li></ul>
  3. 3. Historical Aspects of Goiter 200 BC <ul><li>Atharva Veda (Hindu): exorcism of goiter </li></ul>
  4. 4. 1271 <ul><li>Marco Polo: “They are in general afflicted with tumors in the throat occasioned by the nature of the water which they drink.” </li></ul>
  5. 6. Incidence of Thyroid Disorders in Connecticut (Annual physical Examination, 1544 Patients – One Year) <ul><li># % </li></ul><ul><li>Simple goiter 29 1.88 </li></ul><ul><li>Graves’ disease 15 0.97 </li></ul><ul><li>Iatrogenic hyperthyroidism 2 0.10 </li></ul><ul><li>Hot nodule 9 0.58 </li></ul><ul><li>Multinodular goiter 13 0.84 </li></ul><ul><li>Thyroiditis 8 0.51 </li></ul><ul><li>Single cold nodule 8 0.51 </li></ul><ul><li>Hypothyroidism 6 0.39 </li></ul><ul><li>Cancer 0 0.00 </li></ul><ul><li>Total 90 5.78 </li></ul>
  6. 7. Nodular Goiter <ul><li>Prevalence Rate: .08%/yr </li></ul><ul><li>Clinical incidence- Adults: 4-7% </li></ul><ul><ul><li>Females > Males </li></ul></ul><ul><li>Incidence with ionizing radiation: 20-30% </li></ul><ul><li>Autopsy incidence: 50% </li></ul><ul><li>Occult cancer (Autopsy): 4-28% </li></ul>
  7. 9. Cancer Incidence and Deaths Estimated- U.S. 2005 <ul><li>Organ System New Cases Deaths </li></ul><ul><li>Lung 172,570 163,510 </li></ul><ul><li>Colon 104,950 56,290 </li></ul><ul><li>Rectum 42,000 7,000 </li></ul><ul><li>Pancreas 32,180 31,800 </li></ul><ul><li>Breast 212,930 40,870 </li></ul><ul><li>Stomach 24,000 14,000 </li></ul><ul><li>Thyroid 25,690 1,490 </li></ul><ul><li>Prostate 232,090 30,050 </li></ul>
  8. 10. Thyroid Cancer <ul><li>1985 1994 1998 </li></ul><ul><li>New Cases 10,000 13,900 17,200 ( ↑ 72%) </li></ul><ul><li>Deaths 1,100 1,120 1,200 (↑8%) </li></ul><ul><li>American Cancer Society 1998 </li></ul>
  9. 13. Evaluations of Nodular Thyroid Disease <ul><li>History- symptoms, duration, familial </li></ul><ul><li>Physical findings, i.e. topography, firmness, surface, lymphadenopathy </li></ul><ul><li>Thyroid functions tests- TFT (s) - TSH </li></ul>
  10. 17. Diagnostic Studies- Thyroid Cancer <ul><li>Fine Needle Aspiration- Establishes Cytologic Diagnosis </li></ul><ul><li>Thyroid function tests (TSH- 1 st in Thyroiditis) </li></ul><ul><li>Technetium Scan- reflects trapping function, “hot nodule” </li></ul><ul><li>Ultrasonography- reflects volume, composition, occult nodules </li></ul>
  11. 26. Thyroid Cancer- Diagnosis <ul><li>Cytology </li></ul><ul><li>Scans </li></ul><ul><ul><li>Technetium </li></ul></ul><ul><ul><li>Radioiodine </li></ul></ul><ul><ul><li>Sestamibi </li></ul></ul><ul><ul><li>MR/CT/PET </li></ul></ul><ul><li>Ultrasound </li></ul><ul><li>Frozen Sections </li></ul><ul><li>Fixed Sections </li></ul>
  12. 27. Thyroid Cancers* <ul><li>Papillary 80% </li></ul><ul><li>Follicular 11% </li></ul><ul><li>H ürthle 3% </li></ul><ul><li>Medullary 4% </li></ul><ul><li>Anaplastic 2% </li></ul><ul><li>*National Cancer Data Base </li></ul><ul><li>31,513 patients (1985-1995) </li></ul>
  13. 28. Biological Characterstics <ul><li>Thyrotropin Receptor- </li></ul><ul><ul><li>Adenylate Cyclase Systems </li></ul></ul><ul><li>Iodine Trapping/Organification </li></ul><ul><li>Thyroglobin Production </li></ul>
  14. 29. Thyroid Cancer A Spectrum of Neoplasms <ul><li>Surgical Treatment: Reflect Biological Characteristics </li></ul>
  15. 31. Papillary Carcinoma <ul><li>Ames (Age, Distant Metastases, Extent, Size) </li></ul><ul><li>89%- Low risk; Mortality 1.8% and </li></ul><ul><li>11% High Risk, Mortality 46% </li></ul>
  16. 36. Adjuvant Therapy <ul><li>Thyroxine -> TSH Suppression </li></ul><ul><li>Radiodiodine (Ablation/Rx) </li></ul><ul><li>Thyroxine ↓ -> TSH ↑ </li></ul><ul><li>Recombinant TSH </li></ul><ul><li>External Radiation (?) </li></ul><ul><li>Chemotherapy (?) </li></ul>
  17. 45. On a New Gland in Man and Several Mammals <ul><li>Ivar Sandstr Ő m </li></ul><ul><li>“ About three years ago (1877) I found on the thyroid gland of a dog a small organ, hardly as big as a hemp seed, which was enclosed in the same connective tissue capsule as the thyroid, but could be distinguished there from by a lighter color. A superficial examination revealed an organ of totally different than that of the thyroid and with a very rich versatility.” </li></ul>
  18. 46. Ivar Sandstr Ő m <ul><li>“So much the greater was my astonishment therefore when in the first individual (patient) examined I found on both sides at the inferior border of the thyroid gland an organ of the size of a small pea, which judging from its exterior did not appear to be a lymph gland nor an accessory thyroid gland and upon histological examination showed a rather peculiar structure.” </li></ul>
  19. 47. Herr Bleich, 40, Male, Mason <ul><li>April 1888 Fall, ? Femoral neck fracture </li></ul><ul><li>August 1888 Fall, Clavicle fracture </li></ul><ul><ul><ul><ul><ul><li>Hospitalized- Fracture of femur in bed. </li></ul></ul></ul></ul></ul><ul><li>July 1889 Bending of bones, bone pain </li></ul><ul><li>October 1889 Marasmus- Death </li></ul>
  20. 48. Herr Bleich: Autopsy (Pathological Institute of Strassburg) <ul><li>1889 Von Recklinghausen </li></ul><ul><li>Skeletal Findings: Widespread fibrosis, cysts, brown (giant cell) tumors </li></ul><ul><li>1933 Jung </li></ul><ul><ul><ul><li>“ Above the left Thyroid gland, a lymph gland, red-brown in color is present.” </li></ul></ul></ul>
  21. 49. Albert ____ 38, Male, Street Car Conductor <ul><li>Chicken pox [5], Measles [6], Syphilis [19], Tuberculosis </li></ul><ul><li>1921- Pain legs, hips, tiredness-pensioned </li></ul><ul><li>1923- X-Rays Bone cysts </li></ul><ul><li>1924- Diagnosis: Von Recklinghausen’s Disease </li></ul>
  22. 50. Albert J ä hne RX: Von Recklinghausen’s Disease <ul><li>1924 Parathyroid Extract from animals, </li></ul><ul><li>Parathyroid Transplantation (MANDL) </li></ul><ul><li>1925 Jellyfish stage: Parathyroid tumor removed 92.5 X 1.5 X 1.2 cm.) July 20 </li></ul><ul><li>1932 Recurrence: Two normal glands removed </li></ul><ul><li>1936 Death: No tumor at autopsy </li></ul>
  23. 52. Elva Dawkins <ul><li>February 1928 </li></ul><ul><li>Fractured left humerus, tumor of maxilla, benign giant cell sarcoma- left ulna </li></ul><ul><li>Dixon (student) studying nerve- muscle preparation </li></ul><ul><li>Calcium 16 mgs. %, phosphorus- 1.4 mgs. % </li></ul><ul><li>Walnut sized mass – left lobe of thyroid </li></ul><ul><li>July 1929, Paraparesis, UTI, renal function ↓ </li></ul>
  24. 53. Hyperparathyroidism <ul><li>Rarefaction of bone </li></ul><ul><li>Multiple cystic bone tumors, giant cell sarcoma </li></ul><ul><li>Muscular weakness and hypotonia </li></ul><ul><li>Abnormal excretion of calcium and formation of calcium stones </li></ul><ul><li>Abnormally high serum calcium </li></ul>
  25. 55. Captain Charles Martell (1889-1932) <ul><li>1926 “Hyperparathyroidism” suggested by Dr. Dubois, Bellvue Hospital </li></ul><ul><li>1926 May and June- Two normally parathyroid glands removed by Dr. E.P. Richardson, MGH </li></ul><ul><li>1932 (March) Neck exploration- Dr. Russell Patterson, New York </li></ul><ul><li>1932 Three neck explorations- Drs. Oliver Cope and E. D. Churchill, MGH </li></ul><ul><li>1932 (November) Mediastinal parathyroid adenoma partially excised- Dr. E. D. Churchill, MGH </li></ul><ul><li>1932 Death from tetany </li></ul>
  26. 56. 1932 _____ ______ (J. Morelle) Louvain <ul><li>Diagnosis by Serendipity </li></ul>
  27. 57. Primary Hyperparathyroidism <ul><li>Abnormal relationship between calcium and </li></ul><ul><li>PTH levels with changes in parathyroid </li></ul><ul><li>mass and calcium setpoints. </li></ul>
  28. 59. Hyperparathyroidism <ul><li>Incidence 1:700 (0.14%) </li></ul><ul><li>Most common cause of Hypercalcemia in non-hospitalized patients </li></ul><ul><li>Female greater than male </li></ul><ul><li>Most common in peri/post menapausal female </li></ul><ul><li>Rare in children </li></ul>
  29. 60. Hyperparathyroidism (Classification) <ul><li>1 ° HPT- Idiopathic inappropriate secretion of PTH </li></ul><ul><li>II. 2 ° HPT- Hypersecretion of PTH 2° to ↓ Ca++ </li></ul><ul><li>III. 3 ° HPT- Autonomous hypersecretion of PTH/2° HPT </li></ul>
  30. 61. Hyperparathyroidism (Classification) <ul><li>IV. Ectopic Hyperparathyroidism </li></ul><ul><ul><li>(Humoral Hypercalcemia of Cancer) </li></ul></ul><ul><li>Pseudo Hyperparathyroidism </li></ul><ul><ul><li>(Bone Resorption via Local Mechanism) </li></ul></ul><ul><ul><ul><li>Prostaglandinis E </li></ul></ul></ul><ul><ul><ul><li>Cytokines (Osteoclast Activating Factor) </li></ul></ul></ul><ul><ul><ul><ul><li>Interleukin-1 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Cachectin (Tumor Necrosis Factor α ) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lymphotoxin (Tumor Necrosis Factor β ) </li></ul></ul></ul></ul>
  31. 63. Table 1. Symptoms and Signs of Hypercalcemia* <ul><li> Percent </li></ul><ul><li>Symptoms </li></ul><ul><li>Fatigue 28 </li></ul><ul><li>Mental status change 24 </li></ul><ul><li>Depression 12 </li></ul><ul><li>Gastrointestinal 24 </li></ul><ul><li>Signs </li></ul><ul><li>Cardiovascular 14 </li></ul><ul><li>Nephrolithiasis 28 </li></ul><ul><li>Bone disease 47 </li></ul><ul><li>Pancreatitis 2 </li></ul><ul><li>Asymptomatic 11 </li></ul><ul><li>*Many patients had more then one symptom or sign. </li></ul><ul><li>Udelsman – Ann. Surg 2001; 113: 59-66 </li></ul>
  32. 64. Clinical Manifestations of Hyperparathyroidism <ul><li>Renal </li></ul><ul><ul><li>Hypercalciuria, negative calcium balance </li></ul></ul><ul><ul><li>Renal parenchymal calcification: nephrocalcinosis </li></ul></ul><ul><ul><li>Obstructive uropathy: nephrolithiasis </li></ul></ul><ul><li>Skeletal </li></ul><ul><ul><li>Increased bone resoption (also increased formation) </li></ul></ul><ul><ul><li>Greater loss of cortical than trabecular bone </li></ul></ul><ul><ul><li>Brown tumors presenting as lytic lesions (uncommon) </li></ul></ul><ul><li>Gastrointestinal </li></ul><ul><ul><li>Anorexia, nausea, vomiting, weight loss, constipation </li></ul></ul><ul><ul><li>Pancreatitis </li></ul></ul><ul><li>Neuromuscular </li></ul><ul><ul><li>CNS depression: lethargy, coma </li></ul></ul><ul><ul><li>Muscle weakness, hyporeflexia </li></ul></ul><ul><ul><li>Peripheral neuropathy: axonopathy </li></ul></ul>
  33. 65. Hyperparathyroidism in the Elderly ( ≥ 65) <ul><li>Incidence – 1.5% </li></ul><ul><li>40% - Hypercalcemia A Serendipitous Finding </li></ul><ul><li>Neuromuscular Symptoms </li></ul><ul><li>Easy Fatigability </li></ul><ul><li>Emotional Instability </li></ul><ul><li>Anorexia </li></ul><ul><li>Sudden Accentuated Aging </li></ul><ul><li>↓ Intellectual Capacity </li></ul><ul><li>Lack of Initiative </li></ul><ul><li>(From Tibblin, et. al.: Ann. Of Surg., 197:135, 1983.) </li></ul>
  34. 66. Evaluation of 1 ° Hyperparathyroidism <ul><li>SERUM ELECTROLYTES </li></ul><ul><li>BUN, CREATININE </li></ul><ul><li>iPTH </li></ul><ul><li>Alkaline Phosphatase </li></ul><ul><li>Bone Density Studies </li></ul><ul><li>Urinary Calcium </li></ul><ul><li>Localization Procedures </li></ul>
  35. 72. Asymptomatic Hyperthyroidism <ul><li>Natural History – Unknown </li></ul><ul><li>Rapid Progression to Severe Disease – Rare </li></ul><ul><li>20% Develop Complications in Ten Years </li></ul><ul><li>Accelerated Bone Loss – Mental Function/Well Being Compromised? </li></ul>
  36. 73. Table 1. Comparison of Old and New Criteria for Parathyroid Surgery in Patients with Asymptomatic Primary Hyperparathyroidism.* <ul><li>Variable 1990 Guidelines 2002 Guidelines </li></ul><ul><li>Serum calcium 1.0-1.6 mg/dl above 1.0 mg/ dl of upper </li></ul><ul><li>Concentration upper limit of limit of normal </li></ul><ul><li>normal </li></ul><ul><li>24- Hr urinary >400 mg >400 mg </li></ul><ul><li>Calcium excretion </li></ul><ul><li>Reduction in 30% 30% </li></ul><ul><li>Creatinine clearance </li></ul><ul><li>Bone mineral Z score below -2.0 in the T score below -2.5 at any </li></ul><ul><li>Density forearm site </li></ul><ul><li>Age <50 yr <50 yr </li></ul>
  37. 74. Parathyroidectomy Indications <ul><li>Symptomatic Patients </li></ul><ul><li>Asymptomatic Patients </li></ul><ul><ul><ul><li>Calcium ≥ 11 mgms. % ( 1 mg > Normal ) </li></ul></ul></ul><ul><ul><ul><li>Not Amenable to Surveillance </li></ul></ul></ul><ul><ul><ul><li>Decreasing Bone Density, Osteopenia Hypertension, Hypercalciuria Decreasing Renal Function </li></ul></ul></ul>
  38. 75. Effects of Successful Surgery on Problems Associated with Hyperparathyroidism <ul><li>Osteopenia: Increased bone mineral density in spin and hip (+ 10-15% within 1-2 yrs) </li></ul><ul><li>Hypercalciuria and nephrolithiasis are significantly reduced </li></ul><ul><li>Neuromuscular symptoms frequently improve </li></ul><ul><li>- Objective improvements documented in motor strength and fine motor control but not sensory function </li></ul><ul><li>Some aspects of psychiatric morbidity are subjectively improved </li></ul><ul><li>- Improved subjective scores of fatigue, depression, irritability, sleep disturbance and lack of concentration </li></ul><ul><li>- No changes in cognitive function or anxiety scores </li></ul><ul><li>Pre-existing hypertension is generally not improved but LVH may regress </li></ul>
  39. 76. Parathyroid Imaging- Localization <ul><li>Experienced Surgeon </li></ul><ul><li>Ultrasound </li></ul><ul><li>Scintigraphy (sestamibi:technetium 99m ) </li></ul><ul><li>Venous sampling (qPTH – pre-intraoperative) </li></ul><ul><li>Computerized tomography </li></ul><ul><li>Magnetic resonance imaging </li></ul><ul><li>Angiography (selective digital subtraction angiography) </li></ul><ul><li>Fine needle aspiration: cytology/iPTH </li></ul>
  40. 80. End Stage Renal Disease <ul><li>Eu- hypercalcemia </li></ul><ul><li>Hyperphosphatemia </li></ul><ul><li>↑ alkaline phosphatase </li></ul><ul><li>↑ iPTH </li></ul><ul><li>Osteodystrophy </li></ul>
  41. 81. Renal Osteodystrophy Indications for Parathyroidectomy <ul><li>Bone pain </li></ul><ul><li>Proximal myopathy </li></ul><ul><li>Persistent hypercalcemia </li></ul><ul><li>Calcinosis – unresponsive to Rx </li></ul><ul><li>Calciphylaxis </li></ul>
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