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 (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 – (50 – 400 mg/24 hr)
1,25 dihydroxyvitamin D (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 – (100 – 300 mg/24 hr)
1,25 dihydroxy vitamin D – (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 Associated conditions
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 Step 2 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 Vitamin D mediated
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): )
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 % 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:
Ralston SH, et al., Cancer associated hypercalcemia: Morbidity and mortality. Ann Intern Med, 1990; 112:
Schneider AB, Gierlowski TC, Shore-Freedman et al., Dose response relationships for radiation induced hyperparathyroidism, J Clin Endo Metab, 1995; 80:
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);