Download - APPROACH TO HYPERCALCEMIA
APPROACH TO HYPERCALCEMIAElizabeth George M.D.
Department of MedicineUniversity of Wisconsin-Madison
* No Financial Disclosures
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
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
LEARNING OBJECTIVES (cont.)
Review medical therapy Review surgical treatment
– Role of gland localization techniques– Merits of minimally invasive
parathyroid surgery
CASE REPORT - 1 Ms. K is a 51 year old patient who
came in for a routine exam Past medical history
1. Menorrhagia2. Carpal tunnel syndrome
Medications – MVI Social / Family History - unremarkable Review of systems
– Mild depression – attributed to increased stress at work
– Fatigue– Difficulty concentrating
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)
CASE REPORT - 1
Parathyroid scan (sestamibi) – negative
CASE REPORT - 1Subtraction scan
CASE REPORT - 1Subtraction scan
CASE REPORT - 1Left upper lobe parathyroid adenoma
CASE REPORT - 1
Rx – Minimally invasive
parathyroidectomy– Yielded an 880 mg parathyroid
adenoma
CASE REPORT - 2 Ms. C is a 67 year old patient who
came in for a routine exam Past medical history
1. HTN2. TAH with BSO 20+ years ago3. Hyperlipidemia
Medications– Propanalol – Triamterene / HCTZ– Lipitor– MVI– Calcium
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
CASE REPORT - 2
Metabolic evaluation for low bone density pursued
Results of bone density scan t-score – 1.3 (spine)
– 2. 8 (femur)
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)
CASE REPORT - 2Chest X-ray
multiple lung nodules
CASE REPORT - 2Chest X-ray
multiple lung nodules
CASE REPORT - 2CT scan chest
large 4.3 cm nodule R lung multiple nodules no adenopathy
CASE REPORT - 2CT scan chest
large 4.3 cm nodule R lung multiple nodules no adenopathy
CASE REPORT – 2
CT abdomen and pelvis – negative Biopsy of lung mass
– Well differentiated, low grade neuroendocrine carcinoma (carcinoid)
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
WORK-UP (cont.)
History– Non specific GI complaints– Depression– Impairment of intellectual performance
Associated conditions– Pseudogout– Nephrolithiasis
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
WORK-UP (cont.)
Physical exam– Generally unrevealing– Band keratopathy with slit lamp– Breast mass– Adenopathy– Bone tenderness
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
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)
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
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
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
MEDICAL THERAPY
Monitoring Blood pressure Biannual serum calcium Annual serum creatinine Annual bone density Baseline abdominal radiographs for
silent stones
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
SURGICAL THERAPY
Role of gland localization Pre-op localization mandatory when Minimally
Invasive Parathyroidectomy (MIP) procedure planned Procedure used – 99Tc labeled sestamibi scan
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
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
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
MANAGEMENT OF HYPERCALCEMIA OF MALIGNANCY
Vigorous rehydration / saline diuresis Bisphosphonates
– Pamidronate– Etidronate– Calcitonin
Definitive measure– Rx underlying tumor
SUMMARY OF WORKUP FOR HYPERCALCEMIA
SUMMARY OF WORKUP FOR HYPERCALCEMIA
References
1. Khosla S. et al., Primary hyperparathyroidism and the risk of fracture” A population based study, J. Bone Miner Res, 1999; 14: 1700-1707.
2. Ralston SH, et al., Cancer associated hypercalcemia: Morbidity and mortality. Ann Intern Med, 1990; 112: 499-504.
3. Schneider AB, Gierlowski TC, Shore-Freedman et al., Dose response 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 of asymptomatic primary hyperparathyroidism, J. Bone Miner Res, 1991; 6 (suppl) s9-s13.
5. J Clin Endo Metab, 2002; 87 (12); 5353-5361.