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APPROACH TO HYPERCALCEMIA

APPROACH TO HYPERCALCEMIA

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APPROACH TO HYPERCALCEMIA

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  1. APPROACH TO HYPERCALCEMIA Elizabeth George M.D. Department of Medicine University of Wisconsin-Madison * No Financial Disclosures

  2. WHY IS IT IMPORTANT? • Rising Incidence: 100,000 new cases / year in the United States • Asymptomatic Hyperparathyroidism is not a benign condition • Skeletal loss1 • Impaired renal function • May herald underlying occult malignancy2 / sarcoidosis

  3. LEARNING OBJECTIVES • To be able to interpret an abnormal calcium and diagnose its cause • Review key elements of diagnostic evaluation • Review indications for medical monitoring vs. surgical treatment 4,5 in patients with asymptomatic hyperparathyroidism

  4. LEARNING OBJECTIVES (cont.) • Review medical therapy • Review surgical treatment • Role of gland localization techniques • Merits of minimally invasive parathyroid surgery

  5. CASE REPORT - 1 • Ms. K is a 51 year old patient who came in for a routine exam • Past medical history • Menorrhagia • Carpal tunnel syndrome • Medications – MVI • Social / Family History - unremarkable • Review of systems • Mild depression – attributed to increased stress at work • Fatigue • Difficulty concentrating

  6. CASE REPORT - 1 • Physical exam – completely unremarkable • Laboratory Data: • CBC - normal • TSH - 2.06 (0.5 – 4.00) • BMP – normal except calcium 12.4 mg/dl (8.4 – 10.4 mg/dl) • Further work up • iPTH – 509 (12-72 pg/ml) • 24 hr urine calcium – 649.3 (50 – 400 mg/24 hr) • 1,25 dihydroxyvitamin D3 - 75 (22 – 67 ng/ml)

  7. CASE REPORT - 1 Parathyroid scan (sestamibi) – negative

  8. CASE REPORT - 1 Subtraction scan

  9. CASE REPORT - 1 Subtraction scan

  10. CASE REPORT - 1 Left upper lobe parathyroid adenoma

  11. CASE REPORT - 1 Rx • Minimally invasive parathyroidectomy • Yielded an 880 mg parathyroid adenoma

  12. CASE REPORT - 2 • Ms. C is a 67 year old patient who came in for a routine exam • Past medical history • HTN • TAH with BSO 20+ years ago • Hyperlipidemia • Medications • Propanalol • Triamterene / HCTZ • Lipitor • MVI • Calcium

  13. CASE REPORT - 2 • Social / Family History – nonsmoker, completely unremarkable family history • ROS – negative • Physical exam - normal • Screening • Mammogram – recent normal • Colonoscopy – current normal except hemorrhoids • Bone density scan (DEXA) ordered

  14. CASE REPORT - 2 • Results of bone density scan t-score – 1.3 (spine) – 2. 8 (femur) • Metabolic evaluation for low bone density pursued

  15. CASE REPORT - 2 • Calcium – 11. 5 (8.4 – 10.4 mg/dl) • Ionized calcium – 6.2 (4.6 – 5.4) • iPTH 41 (10 – 65.0 pg/ml) • 24 hr urine calcium – 129.5 (100 – 300 mg/24 hr) • 1,25 dihydroxy vitamin D – 38 (15 – 60 ng/ml)

  16. CASE REPORT - 2 Chest X-ray • multiple lung nodules

  17. CASE REPORT - 2 Chest X-ray • multiple lung nodules

  18. CASE REPORT - 2 CT scan chest • large 4.3 cm nodule R lung • multiple nodules • no adenopathy

  19. CASE REPORT - 2 CT scan chest • large 4.3 cm nodule R lung • multiple nodules • no adenopathy

  20. CASE REPORT – 2 • CT abdomen and pelvis – negative • Biopsy of lung mass • Well differentiated, low grade neuroendocrine carcinoma (carcinoid)

  21. WORK-UP OF HYPERCALCEMIA IN AN ASYMPTOMATIC PATIENT Re-review History • Classic presentation very rare • Stones • Bones • Abdominal groans • Psychic moans • Subtle manifestations more common • Fatigue • Weakness • Arthralgias

  22. WORK-UP (cont.) • History • Non specific GI complaints • Depression • Impairment of intellectual performance • Associated conditions • Pseudogout • Nephrolithiasis

  23. WORK-UP (cont.) • Review medications • Thiazides • Theophylline • Lithium • Antacids • Food additives • Health food store preparations • Pursue symptoms of underlying malignancy • Breast • Lung • Hematological • Past History of Neck irradiation3

  24. WORK-UP (cont.) • Physical exam • Generally unrevealing • Band keratopathy with slit lamp • Breast mass • Adenopathy • Bone tenderness

  25. WORK-UP (cont.) • Step 1 • Confirm hypercalcemia • Ionized calcium • Serum albumin levels • Artifactual – tourniquet • Step 2 • Once obvious causes ruled out, obtain serum intact PTH

  26. WORK-UP (cont.) • Serum Parathyroid Hormone levels - ELEVATED • Primary hyperparathyroidism – 75-80% (sporadic) • Familial (MENI and MENII) • Familial hypocalciuric hypercalcemia • Ectopic PTH secretion by tumors (rare)

  27. WORK-UP (cont.) • Normal / Low • Malignancy associated • Osteolytic • Humoral • Vitamin D mediated • Intoxication • Granulomatous disorders • Thyrotoxicosis • Prolonged immobilization • Pagets • Acute renal failure • Milk alkali syndrome

  28. MEDICAL vs. SURGICAL Rx FOR ASYMPTOMATIC HYPERPARATHYROIDISM Indications for medical monitoring • Mildly elevated calcium • No previous episodes of life threatening hypercalcemia • Normal renal function • Normal bone status

  29. INDICATIONS FOR SURGICAL TREATMENT (J. Clin Endocrinology Metab, Dec. 2002, 87(12): 5353-5361) • Overt clinical manifestations • Serum calcium > 1mg/dl above upper limits of normal • 24 hr urine calcium > 400mg • Bone density < 2.5 SD below peak bone mass (t score < -2.5) • Age < 50 years • Medical surveillance not desirable / not possible

  30. MEDICAL THERAPY Monitoring • Blood pressure • Biannual serum calcium • Annual serum creatinine • Annual bone density • Baseline abdominal radiographs for silent stones

  31. MEDICAL MANAGEMENT • Avoid prolonged immobilization • Maintain adequate hydration • Avoid a diet with restricted or excess calcium • Caution with loop/thiazide diuretics • Estrogen therapy – limited data • Bisphosphonates, calcitonin only in symptomatic patients who are non surgical candidates

  32. SURGICAL THERAPY Role of gland localization • Pre-op localization mandatory when Minimally Invasive Parathyroidectomy (MIP) procedure planned • Procedure used – 99Tc labeled sestamibi scan

  33. SURGICAL THERAPY (cont.) Minimally Invasive Parathyroidectomy (MIP) • Pre-op localization • Intra-op PTH level obtained before and after adenoma removed • If PTH levels fall by greater than 50% operation terminated • IF PTH Levels fall by less than 50%, full neck exploration performed

  34. SURGICAL THERAPY (cont.) Conventional • Full exploration of neck • Rationale -15-20% patients have > 1 gland removed • Requires highly skilled surgeon • Complications- rate 1-4% • Vocal cord paralysis • Permanent hypoparathyroidism • Bleeding • Laryngospasm

  35. POST OPERATIVE MONITORING • Watch for symptomatic hypocalcemia • Provide oral calcium and 1,25 (OH)2 D3, once oral intake established • Check serum calcium at intervals of several days

  36. MANAGEMENT OF HYPERCALCEMIA OF MALIGNANCY • Vigorous rehydration / saline diuresis • Bisphosphonates • Pamidronate • Etidronate • Calcitonin • Definitive measure • Rx underlying tumor

  37. SUMMARY OF WORKUP FOR HYPERCALCEMIA

  38. SUMMARY OF WORKUP FOR HYPERCALCEMIA

  39. References • Khosla S. et al., Primary hyperparathyroidism and the risk of fracture” A population based study, J. Bone Miner Res, 1999; 14: 1700-1707. • Ralston SH, et al., Cancer associated hypercalcemia: Morbidity and mortality. Ann Intern Med, 1990; 112: 499-504. • Schneider AB, Gierlowski TC, Shore-Freedman et al., Dose response relationships for radiation induced hyperparathyroidism, J Clin Endo Metab, 1995; 80: 254-257. • Potts JT Jr (editor), Proceedings of the NIH consensus development conference on diagnosis and management of asymptomatic primary hyperparathyroidism, J. Bone Miner Res, 1991; 6 (suppl) s9-s13. • J Clin Endo Metab, 2002; 87 (12); 5353-5361.