1. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Endocrine Surgery

2. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Primary Hyperparathyroidism (PHPT) iPTH Ca PHPT

3. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PHPT 0.1-3% of population. Common, over 100 000 new cases diagnosed/y in US. mm

4. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PHPT Single parathyroid adenoma (80%-90%) Double adenomas (2%-15%) Asymmetric 4-gland hyperplasia (10%-15%) Carcinoma (<1% of patients) mm

5. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Symptoms and Signs Moans, groans, stones, and bones Hypercalcemia Bone disease Nephrolithiasis Hypophosphatemia Proximal renal tubular acidosis Hypomagnesemia Hyperuricemia Gout Anemia mm

6. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Manifestations of Hypercalcemia CNS dysfunction Muscle weakness Bowel hypomotility and constipation Peptic ulcer disease Pancreatitis Acute and chronic renal insufficiency Nephrogenic diabetes insipidus Distal renal tubular acidosis Nephrolithiasis Shortening of the QT interval Corneal calcium deposition (band keratopathy) mm

7. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Imaging A.J. Coakley, A.G. Kettle and C.P. Wells et al., 99m Tc sestamibi a new agent for parathyroid imaging, Nucl Med Commun 10 (1989), pp. 791–794 mm commonly used for cardiac imaging Avidly taken up by parathyroid tissue Reoperative setting

8. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 2002 NIH Workshop on Asymptomatic PHPT Serum Ca > 1.0 mg/dL above the upper limit of normal. Hypercalciuria (urinary Ca excretion > 400 mg/day). Creatinine clearance that is <30% than that of age- matched normal subjects. Bone density at the hip, lumbar spine, or distal radius that is T score <-2.5. <50 years old. Difficult periodic follow-up. mm

9. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings IOPTH MEASUREMENTS Recorded before resection of any enlarged glands Just before excising the gland. Postexcision IOPTH levels were measured 10 min or longer after resection of the enlarged parathyroid gland(s). A decrease of 50% or more in the IOPTH level was used to define successful parathyroidectomy. mm

10. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Why should virtually all patients be considered for surgical intervention? mm Surgery offers the only cure Surgery is of benefit to symptomatic patients Surgery is of benefit to “asymptomatic” patients Increases bone density and decreases fracture rates

11. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Prolongs survival Improves neurocognitive symptoms 92% of patients claim to feel better after parathyroidectomy, even when only 75% claim they felt "bad" before the operation. Regression of left ventricular hypertrophy. Cure of diabetes. Surgical cure rates are high Surgery is safe mm Why should virtually all patients be considered for surgical intervention?

12. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Familial HPTH MEN type 1 MEN type 2A Familial Isolated PHPT mm

13. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Surgical approach for MEN1 Parathyroidectomy Thymectomy mm

14. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Subtotal Vs Total with autotransplantation Subtotal parathyroidectomy Total with autotransplantation mm

15. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MEN 2A HPT 20-35% MTC > 95% Pheochromocytoma 42-50% Cutaneous lichen amyloidosis mm

16. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings FIHPT Carefully screened for MEN, including a thorough FHx, ret oncogene testing, and exclude Pit &Panc neuroendocrine tumors. mm

17. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings FIHPT Profound hypercalcemia, Nephrolithiasis, and severe osteoporosis. No definite genetics have been identified Jaw tumors (FIH-JT) mm

18. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PHPT in MEN1 Concurrent ZE syndrome parathyroidectomy (reducing ca levels can reduce gastrin secretion) mm

19. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PHPT in MEN2A MEN-2A must be biochemically screened for the presence of pheochromocytoma before parathyroidectomy. If present, parathyroidectomy should be delayed until the pheochromocytoma is addressed. mm

20. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Demographics of Thyroid Cancer ACS est 20,700 new cases of thyroid cancer in U.S. in 2002 Cause-specific deaths in 2002 est to be 1300 Occult cancer in autopsy studies reported to 4-35% worldwide

21. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The New End Point The gland should be removed en bloc Care should be taken to remove the entire superior pole The RLN should be identified and followed to the point where it enters the larynx

22. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

23. Nodular hyperplasia Adenoma Cyst Hashimoto thyroiditis Malignancy Differential Diagnosis of a Thyroid Nodule

24. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Risk Factors for Thyroid Cancer History of head and neck radiation Male sex Family history of medullary carcinoma (MEN syndromes) Family history of papillary carcinoma Hoarseness (vocal cord paralysis) Fixation to adjacent structures Single, firm, cold nodule Nodule> 4cm Rapid tumor growth Enlarging thyroid nodule(s) on thyroid suppression Cervical lymphadenopathy

25. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings AGES AMESDAMESSAGMACIS Age DNA Size Metastasis(Dist ant) Grade Metastasis Age Extent Metastasis(Dist ant) GradeCompleteness of resection Invasion Size

26. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings TYPES Tumors of Follicular Cell Origin Differentiated Papillary Follicular Hürthle Cell Undifferentiated Anaplastic Tumors of Parafollicular or C-cell Origin Medullary Other Lymphoma Squamous cell carcinoma,secondary tumors

27. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MEN 2 MEN 2A : MTC > 95% of the patients Pheochromocytoma 42- 50% Hyperparathyroidism 20- 35% Cutaneous lichen amyloidosis MEN 2B: MTC 100% Pheochromocytomas 50% Ganglioneuromas of the lips, tongue, eyelids, and gastrointestinal tract Marfanoid physical (but not cardiac) features mm

28. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Biochemistry Parafollicular C cells CTN CEA Corticotropin mm Pathology: Amyloid

29. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings CLINICAL PRESENTATION Most has already metastasized at the time of diagnosis. CLN 15% symptoms of upper aerodigestive tract compression or invasion such as dysphagia or hoarseness 5% distant disease mm

30. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings CLINICAL PRESENTATION Calcitonin: Diarrhea facial flushing ACTH: Cushing's syndrome. mm

31. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Genetic screening Patients identified as carriers of a RET mutation will develop MTC and should undergo prophylactic Thyroidectomy. mm

32. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Treatment Total thyroidectomy CLN Dissection: from the level of the hyoid to the innominate vessels and laterally to the carotid arteries. mm

33. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MRND Preserve: SCM Spinal Accessoy N. IJV mm

34. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Pheo & Para in MEN2A MEN-2A must be biochemically screened for the presence of pheochromocytoma before parathyroidectomy. If present, parathyroidectomy should be delayed until the pheochromocytoma is addressed. mm

35. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

37. Causes of Cushing’s Syndrome mm Cushing’s disease68 Ectopic ACTH syndrome12 12 Ectopic CRH syndrome<1 <1 Adrenal adenoma10 Adrenal carcinoma8 Adrenal cortical hyperplasias 1 Pseudo-Cushing’s Syndrome 1 Major depression Alcoholism 1

38. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings S & S General Central obesity * Proximal muscle weakness Hypertension Headaches Psychiatric disorders Skin Wide (>1 cm) purple striae Spontaneous ecchymoses Facial plethora Hyperpigmentation Acne Hirsutism Fungal skin infections* mm

39. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings S & S Hypokalemic alkalosis Osteopenia Delayed bone age in children Menstrual disorders, decreased libido, impotence Glucose tolerance, diabetes mellitus Kidney stones Polyuria Elevated white blood cell count

40. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

41. Carcinoid Tumors

42. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Products of carcinoid tumors DopamineNeurokinin A HistamineNeurokinin B Polypeptides Corticotropin (ACTH) KallikreinGastrin Pancreatic polypeptideGrowth hormone BradykininPeptide YY MotilinGlucagon SomatostatinBeta-endorphin Vasoactive intestinal peptideNeurotensin Neuropeptide KChromogranin A Substance P Prostaglandins mm

43. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 5-HIAA Definitive diagnosis can be confirmed by the finding of elevated urinary 5-HIAA levels Asymptomatic patients,only 75% sensitive for detecting the presence of 1ry tumors without metastatic disease. mm

44. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Chromogranin A Elevated in > 80% of patients with carcinoid tumors. Elevated level is an independent predictor of an adverse prognosis. mm

45. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Diagnostic Modalities CT : hepatic and lymph node metastases SB follow-through: kinking of bowel smooth luminal filling defect Sensitivity:30- 40%. mm Capsule Endoscopy

46. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Diagnostic Modalities Somatostatin receptor scintigraphy: successfully localize primary and metastatic tumors in approximately 80% of patients useful staging procedure before surgical exploration to detect the extent of tumor burden and allow surgical planning. mm

47. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Surgery 1ry< 1 cm in diameter without evidence of regional lymph node metastasis: segmental intestinal resection is adequate. Lesions of TI or appendiceal lesios >2cm are best treated by R hemicolectomy. mm

48. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Gastrinoma Sporadic 75% MEN 1 25% mm Peptic acid hypersecretion: abdominal pain Diarrhea

49. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MEN 1 12% manifest all three Ps Screen in patient with PHPT who <50y PHPT Pancreatic neuroendocrine tumors: ZES (54%) Insulinoma (21%) Pituitary tumors mm

50. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Secretin test in gastrinoma mm

51. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Insulinoma distribution Location: Virtually all are intrapancreatic. Most are solitary (10% multiple) Diameter: 10% >2cm 10% malignant. 10% MEN-1 (Higher risk of recurrence). mm Another Rule of 10%

52. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Symptoms Whipple triad: symptoms of hypoglycemia (catecholamine release) low blood glucose level (40 to 50 mg/ dL) Relief of symptoms after intravenous administration of glucose Neuroglycopenic :confusion, visual change. Sympathoadrenal : palpitations, diaphoresis, and tremulousness. Seizure disorder is another common misdiagnosis. mm

53. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Localization Techniques True Positives(%) Ultrasonography23 Octreotide radioimaging (SRS)86(50%) CT 43 MRI 26 Endoscopic ultrasonography82 Selective angiography56 Provocative angiography 65 mm

54. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Surgery Benign: Enucleation: Malignant(10%): Cancer-type operation Metastatic, attempt to remove all primary and metastatic tumor to minimize persistent hyperinsulinism. mm

55. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Medical therapy Indications: insulinoma was missed during pancreatic exploration Pt not a candidate for or refuses surgery Metastatic disease. Diazoxide Octreotide mm