George 5-4-05 Hypercalcemia

8/12/2019 George 5-4-05 Hypercalcemia

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APPROACH TO HYPERCALCEMIA

Elizabeth George M.D.

Department of Medicine

University of Wisconsin-Madison

* No Financial Disclosures


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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


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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


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LEARNING OBJECTIVES (cont.)

Review medical therapy

Review surgical treatment

Role of gland localization techniques Merits of minimally invasive parathyroid

surgery


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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


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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)


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CASE REPORT - 1

Parathyroid scan (sestamibi)negative


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CASE REPORT - 1

Subtraction scan


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CASE REPORT - 1

Subtraction scan


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CASE REPORT - 1

Left upper lobe parathyroid adenoma


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CASE REPORT - 1

Rx Minimally invasive parathyroidectomy

Yielded an 880 mg parathyroid

adenoma


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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


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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


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CASE REPORT - 2

Metabolic evaluation for low bonedensity pursued

Results of bone density scan

t-score 1.3 (spine)

2. 8 (femur)


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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)


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CASE REPORT - 2Chest X-ray

multiple lung nodules


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CASE REPORT - 2

Chest X-ray

multiple lung nodules


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CASE REPORT - 2

CT scan chest

large 4.3 cm nodule R lung multiple nodules no adenopathy


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CASE REPORT - 2CT scan chest

large 4.3 cm nodule R lung multiple nodules no adenopathy


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CASE REPORT2

CT abdomen and pelvisnegative

Biopsy of lung mass

Well differentiated, low gradeneuroendocrine carcinoma (carcinoid)


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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


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WORK-UP (cont.)

History

Non specific GI complaints

Depression

Impairment of intellectual performance

Associated conditions

Pseudogout

Nephrolithiasis


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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


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WORK-UP (cont.)

Physical exam

Generally unrevealing

Band keratopathy with slit lamp

Breast mass Adenopathy

Bone tenderness


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WORK-UP (cont.)

Step 1

Confirm hypercalcemia

Ionized calcium

Serum albumin levels

Artifactualtourniquet

Step 2

Once obvious causes ruled out,

obtain serum intact PTH


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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)


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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


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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


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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


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MEDICAL THERAPY

Monitoring

Blood pressure

Biannual serum calciumAnnual serum creatinine

Annual bone density

Baseline abdominal radiographs for silentstones


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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


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SURGICAL THERAPY

Role of gland localization Pre-op localization mandatory when Minimally

Invasive Parathyroidectomy (MIP)procedure planned

Procedure used99Tc labeled sestamibi scan


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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


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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


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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


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MANAGEMENT OF HYPERCALCEMIAOF MALIGNANCY

Vigorous rehydration / saline diuresis

Bisphosphonates

Pamidronate Etidronate

Calcitonin

Definitive measure

Rx underlying tumor


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SUMMARY OF WORKUP FOR HYPERCALCEMIA


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SUMMARY OF WORKUP FOR HYPERCALCEMIA


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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.

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George 5-4-05 Hypercalcemia