George 5-4-05 Hypercalcemia
-
Upload
muhammad-hanif -
Category
Documents
-
view
218 -
download
0
Transcript of George 5-4-05 Hypercalcemia
-
8/12/2019 George 5-4-05 Hypercalcemia
1/39
APPROACH TO HYPERCALCEMIA
Elizabeth George M.D.
Department of Medicine
University of Wisconsin-Madison
* No Financial Disclosures
-
8/12/2019 George 5-4-05 Hypercalcemia
2/39
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 occultmalignancy2/ sarcoidosis
-
8/12/2019 George 5-4-05 Hypercalcemia
3/39
LEARNING OBJECTIVES
To be able to interpret an abnormalcalcium and diagnose its cause
Review key elements of diagnostic
evaluation Review indications for medical
monitoring vs. surgical treatment 4,5in
patients with asymptomatichyperparathyroidism
-
8/12/2019 George 5-4-05 Hypercalcemia
4/39
LEARNING OBJECTIVES (cont.)
Review medical therapy
Review surgical treatment
Role of gland localization techniques Merits of minimally invasive parathyroid
surgery
-
8/12/2019 George 5-4-05 Hypercalcemia
5/39
CASE REPORT - 1
Ms. K is a 51 year old patient who came infor a routine exam
Past medical history1. Menorrhagia
2. Carpal tunnel syndrome
MedicationsMVI
Social / Family History - unremarkable
Review of systems Mild depressionattributed to increased
stress at work
Fatigue
Difficulty concentrating
-
8/12/2019 George 5-4-05 Hypercalcemia
6/39
CASE REPORT - 1
Physical examcompletely unremarkable
Laboratory Data: CBC - normal
TSH - 2.06 (0.54.00) BMPnormal except calcium 12.4 mg/dl
(8.410.4 mg/dl)
Further work up
iPTH509 (12-72 pg/ml) 24 hr urine calcium649.3 (50400 mg/24 hr)
1,25 dihydroxyvitamin D3 - 75 (2267 ng/ml)
-
8/12/2019 George 5-4-05 Hypercalcemia
7/39
CASE REPORT - 1
Parathyroid scan (sestamibi)negative
-
8/12/2019 George 5-4-05 Hypercalcemia
8/39
CASE REPORT - 1
Subtraction scan
-
8/12/2019 George 5-4-05 Hypercalcemia
9/39
CASE REPORT - 1
Subtraction scan
-
8/12/2019 George 5-4-05 Hypercalcemia
10/39
CASE REPORT - 1
Left upper lobe parathyroid adenoma
-
8/12/2019 George 5-4-05 Hypercalcemia
11/39
CASE REPORT - 1
Rx Minimally invasive parathyroidectomy
Yielded an 880 mg parathyroid
adenoma
-
8/12/2019 George 5-4-05 Hypercalcemia
12/39
CASE REPORT - 2
Ms. C is a 67 year old patient who came infor a routine exam
Past medical history1. HTN
2. TAH with BSO 20+ years ago
3. Hyperlipidemia
Medications Propanalol
Triamterene / HCTZ Lipitor
MVI
Calcium
-
8/12/2019 George 5-4-05 Hypercalcemia
13/39
CASE REPORT - 2
Social / Family Historynonsmoker,completely unremarkable family history
ROSnegative
Physical exam - normal
Screening Mammogramrecent normal
Colonoscopycurrent normal except hemorrhoids Bone density scan (DEXA) ordered
-
8/12/2019 George 5-4-05 Hypercalcemia
14/39
CASE REPORT - 2
Metabolic evaluation for low bonedensity pursued
Results of bone density scan
t-score 1.3 (spine)
2. 8 (femur)
-
8/12/2019 George 5-4-05 Hypercalcemia
15/39
CASE REPORT - 2
Calcium11. 5 (8.410.4 mg/dl) Ionized calcium6.2 (4.65.4)
iPTH 41 (1065.0 pg/ml)
24 hr urine calcium129.5(100300 mg/24 hr)
1,25 dihydroxy vitamin D38
(1560 ng/ml)
-
8/12/2019 George 5-4-05 Hypercalcemia
16/39
CASE REPORT - 2Chest X-ray
multiple lung nodules
-
8/12/2019 George 5-4-05 Hypercalcemia
17/39
CASE REPORT - 2
Chest X-ray
multiple lung nodules
-
8/12/2019 George 5-4-05 Hypercalcemia
18/39
CASE REPORT - 2
CT scan chest
large 4.3 cm nodule R lung multiple nodules no adenopathy
-
8/12/2019 George 5-4-05 Hypercalcemia
19/39
CASE REPORT - 2CT scan chest
large 4.3 cm nodule R lung multiple nodules no adenopathy
-
8/12/2019 George 5-4-05 Hypercalcemia
20/39
CASE REPORT2
CT abdomen and pelvisnegative
Biopsy of lung mass
Well differentiated, low gradeneuroendocrine carcinoma (carcinoid)
-
8/12/2019 George 5-4-05 Hypercalcemia
21/39
WORK-UP OF HYPERCALCEMIA INAN ASYMPTOMATIC PATIENT
Re-review History Classic presentation very rare
Stones
Bones Abdominal groans
Psychic moans
Subtle manifestations more common
Fatigue Weakness
Arthralgias
-
8/12/2019 George 5-4-05 Hypercalcemia
22/39
WORK-UP (cont.)
History
Non specific GI complaints
Depression
Impairment of intellectual performance
Associated conditions
Pseudogout
Nephrolithiasis
-
8/12/2019 George 5-4-05 Hypercalcemia
23/39
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
-
8/12/2019 George 5-4-05 Hypercalcemia
24/39
WORK-UP (cont.)
Physical exam
Generally unrevealing
Band keratopathy with slit lamp
Breast mass Adenopathy
Bone tenderness
-
8/12/2019 George 5-4-05 Hypercalcemia
25/39
WORK-UP (cont.)
Step 1
Confirm hypercalcemia
Ionized calcium
Serum albumin levels
Artifactualtourniquet
Step 2
Once obvious causes ruled out,
obtain serum intact PTH
-
8/12/2019 George 5-4-05 Hypercalcemia
26/39
WORK-UP (cont.)
Serum Parathyroid Hormone levels -ELEVATED
Primary hyperparathyroidism75-80%
(sporadic) Familial (MENI and MENII)
Familial hypocalciuric hypercalcemia
Ectopic PTH secretion by tumors (rare)
-
8/12/2019 George 5-4-05 Hypercalcemia
27/39
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
-
8/12/2019 George 5-4-05 Hypercalcemia
28/39
MEDICAL vs. SURGICAL Rx FORASYMPTOMATIC HYPERPARATHYROIDISM
Indications for medical monitoring
Mildly elevated calcium
No previous episodes of life threateninghypercalcemia
Normal renal function
Normal bone status
-
8/12/2019 George 5-4-05 Hypercalcemia
29/39
INDICATIONS FOR SURGICAL TREATMENT(J. Clin Endocrinology Metab, Dec. 2002, 87(12): 5353-5361)
Overt clinical manifestations
Serum calcium > 1mg/dl above upper limitsof 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 / notpossible
-
8/12/2019 George 5-4-05 Hypercalcemia
30/39
MEDICAL THERAPY
Monitoring
Blood pressure
Biannual serum calciumAnnual serum creatinine
Annual bone density
Baseline abdominal radiographs for silentstones
-
8/12/2019 George 5-4-05 Hypercalcemia
31/39
MEDICAL MANAGEMENT
Avoid prolonged immobilization
Maintain adequate hydration
Avoid a diet with restricted or excess
calcium
Caution with loop/thiazide diuretics
Estrogen therapylimited data
Bisphosphonates, calcitonin only insymptomatic patients who are non surgicalcandidates
-
8/12/2019 George 5-4-05 Hypercalcemia
32/39
SURGICAL THERAPY
Role of gland localization Pre-op localization mandatory when Minimally
Invasive Parathyroidectomy (MIP)procedure planned
Procedure used99Tc labeled sestamibi scan
-
8/12/2019 George 5-4-05 Hypercalcemia
33/39
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
-
8/12/2019 George 5-4-05 Hypercalcemia
34/39
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
-
8/12/2019 George 5-4-05 Hypercalcemia
35/39
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
-
8/12/2019 George 5-4-05 Hypercalcemia
36/39
MANAGEMENT OF HYPERCALCEMIAOF MALIGNANCY
Vigorous rehydration / saline diuresis
Bisphosphonates
Pamidronate Etidronate
Calcitonin
Definitive measure
Rx underlying tumor
-
8/12/2019 George 5-4-05 Hypercalcemia
37/39
SUMMARY OF WORKUP FOR HYPERCALCEMIA
-
8/12/2019 George 5-4-05 Hypercalcemia
38/39
SUMMARY OF WORKUP FOR HYPERCALCEMIA
-
8/12/2019 George 5-4-05 Hypercalcemia
39/39
References
1. Khosla S. et al., Primary hyperparathyroidism and the risk offracture A population based study, J. Bone Miner Res, 1999; 14:1700-1707.
2. Ralston SH, et al., Cancer associated hypercalcemia: Morbidityand mortality.Ann Intern Med, 1990; 112: 499-504.
3. Schneider AB, Gierlowski TC, Shore-Freedman et al., Doseresponse relationships for radiation induced
hyperparathyroidism, J Clin Endo Metab, 1995; 80: 254-257.4. Potts JT Jr (editor), Proceedings of the NIH consensus
development conference on diagnosis and management ofasymptomatic primary hyperparathyroidism, J. Bone Miner Res,1991; 6 (suppl) s9-s13.
5. J Clin Endo Metab, 2002; 87 (12); 5353-5361.