Hypercalcemia Ayesha Shaikh Emory Family Medicine Residency Program
Introduction 62 years old Nepali female Cc: Hypertension, indigestion and fatigue since past many years.
HPI 1- Hypertension for 10 years , treated with Amlodipine 5 mg in Nepal. CXR and blood tests normal at the time of immigration 1 month ago. Denies 2- Epigastric abdominal pains since past many years, non radiating, dull, 4/10, unrelated to the type or timing of food ingestion. Denies nausea, vomiting, diarrhea, constipation. 3- Fatigue for many years. No change in weight, mood or limitations in daily activity. Denies depressive symptoms. One prior FPC visit at Dunwoody Clinics for Medicines refill and necessary labs ordered.
PMH: Hypertension, no prior hospitalizations • PSH: none • SH: recent immigrant, lives with family consisting of children and grand children. Good social support system. Daily chores. Denies smoke or alcohol. • ROS: Irritable mood, • Meds: Amlodipine 5 mg No OTC medicine use NKDA
Physical exam • Petit elderly female, no acute distress • Vitals: Height: 5’ 1 Weight: 100 lbs BMI:20 T: 98.6 P: 61 BP: 154/98 RR: 12 Chest CVS Abd: normal inspection, palpation, percussion and auscultation Neuro: Cranial nerves intact, no motor or sensory deficit. Gait normal, reflexes 2+ ENT: Non palpable thyroid gland
CBC: normal BMP: Na: 141 K 4.3, Bun/creat: 10/0.80 Glucose: 95 Calcium: 11.0 albumin: 4.6 Chloride: 107 CO2 21 LFT: WNL TSH: 0.86 Lipid profile: T.Chol 186 TG 87 LDL 117 HDL 52 Urine Microalbumin/cr 0.2/30= 7 EKG Previous labs! Calcium 10.9 Labs and tests
Assessment and Plan • Hypertension: Amlodipine 5 mg • Hypercalcemia: Fup labs PTH • Gastritis: Pepcid • Backache: Lumbar spine X ray • Health maintenance: Flu vaccine and plan RPE visit.
Test results • PTH: 127 (ref 10-65 pg/ml) • Lumber DJD • Parathyroid scan: Right lower Parathyroid adenoma • Follow up: Blood pressures > 150/90 mmhg, increased amlodipine dose and added HCTZ later • Endocrinology referral for primary hyperparathyroidsism
Endocrinology workup • Exclude underlying secondary hyperparathyroidism, since low vitamin D levels very common in mountains of Himalayas. • 25 hydroxyVitaminD levels =10 (30-80) • Vitamin D replacement: 50,000 units /week for 8 weeks. Recheck calcium and Vit D levels thereafter
Hypercalcemia • Introduction: 1/500, incidental finding • The skeleton contains 98 percent of total body calcium; the remaining 2 percent circulates throughout the body • One half of circulating calcium is free (ionized) calcium, the only form that has physiologic effects. • The remainder is bound to albumin, globulin, and other inorganic molecules • Corrected calcium = (4.0 mg/dl - [plasma albumin]) X 0.8 + [serum calcium]
Defination • Normal serum calcium levels are 8 to 10 mg/dL (2.0 to 2.5 mmol/L) • Normal ionized calcium levels are 4 to 5.6 mg /dL (1 to 1.4 mmol per L) • Hypercalcemia is defined as total serum calcium > 10.2 mg/dl(>2.5 m mol/L ) or ionized serum calcium > 5.6 mg/dl ( >1.4 m mol/L )
Defination • Severe hypercalemia is defined as total serum calcium > 14 mg/dl (> 3.5 mmol/L) • Hypercalcemic crises is present when severe neurological symptoms or cardiac arrhythmias are present in a patient with a serum calcium > 14 mg/dl (> 3.5 mmol/L) or when the serum calcium is > 16 mg/dl (> 4 mmol/L)
Pathophysiology Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3 (calcitriol), and calcitonin control calcium homeostasis in the body • Hypercalcemia is caused by Increased bone resorption, increased gastrointestinal absorption of calcium, and decreased renal excretion of calcium
Pathophysiology • Calcitonin Inhibits osteoclast resorption , promotes Ca++ and PO4 excretion • PTH-related peptide (PTHrP) binds the PTH receptor and mimics the biologic effects of PTH on bones and the kidneys
Clinical manifestations • Hypercalcemia leads to hyperpolarization of cell membranes • Patients with levels of calcium between 10.5 and 12 mg /dl can be asymptomatic. When the serum calcium level rises above this stage, multisystem manifestations become apparent
Evaluation • Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions
Evaluation • Primary hyperparathyroidism : PTH↑ • MALIGNANCY : 1.solid tumors(humoral hypercalcemia):PTHrP↑ , PTH↓ 2.Multiple myeloma and breast cancer(osteolytic hypercalcemia ) : alkaline phosphatase ↑,PTH↓
Evaluation • Granulomatous(sarcoidosis, tuberculosis, Hodgkin's lymphoma): calcitriol (1,25-OH vitamin D3 ) ↑, PTH↓ • Familial hypocalciuric hypercalcemia : 24-hour urinary calcium↓, PTH ↑
TREATMENT Clinical indications for surgery in patients with primary hyperparathyroidism • Significant symptoms of hypercalcemia • Nephrolithiasis • Decreased bone mass • Serum Calcium > 12 mg/dl • Age< 50 years • Infeasibility of longterm follow up
Pharmacologic options • Normal Saline 2-4 L IV daily for 1-3 days • Enhances filtration and excretion of CA++. • Indication: Ca > 14 mg/dl, moderate Calcium with symptoms • Caution: may exacerbate heart failure in elderly patients. Lowers Calcium by 1-3 mg/dl
Pharmacologic options • Furosemide 10-20 mg IV as necessary • Inhibits calcium resorption in distal renal tubule. • Indication: following aggressive hydration • Caution: hypokalemia, dehydration if used before intravascular volume is restored
Pharmacologic options • Bisphosphonates • Pamidronate • Zoledronic acid • Inhibits osteoclast action and bone resporption • Indication: hypercalcemia of malignancy
Treatment • Calcitonin : inhibition bone resorption and increases renal calcium excretion 4 to 8 IU per kg IM or SQ every 6 hours for 24 hours • Plicamycin (Mitharmycin) : decreases bone resorption 25 mcg per kg per day IV over 6 hours for 3 to 8 doses • Gallium nitrate : inhibition bone resorption 100 to 200 mg per m2 IV over 24 hours for 5 days • Glucocorticoids : Inhibits vitamin D conversionto calcitriol Hydrocortisone, 200 mg IV daily for 3 days • Hemodialysis : used in patients with renal failure
Medical management of primary hyperparathyroidism • medical therapy with drugs have not been shown to affect the eventual outcome • estrogens (premarin 1.25mg/day) preserve bone mass in post-menopausal females • well-hydrated by drinking 2 - 3 litres of fluid, and 8 - 10 g of salt daily • dietary restriction of calcium is not necessary , thiazide diuretics must not be used • oral phosphate should only be used if symptomatic hypercalcemia cannot be corrected surgically
Medical management of hypercalcemia in cancer patients • 2 - 3 litres per day + 8 - 10g of salt/day • Pamridonate can be used prn every few weeks to keep the serum calcium in the normal range • Prednisone (20 - 50 mg bid) is only useful in certain malignancies eg. multiple myeloma and certain lymphomas
Treatment • Medical management of other disorders : --prednisone and low-calcium diet ( < 400 mg/day ) • Medical management of hypercalcemia in sarcoidosis : --a low dose of prednisone (10 - 20 mg/day) is usually adequate
References • Carroll M, Schade D. A Practical Approach to Hypercalcemia. American Family Physician. May 1, 2003. • Taniegra E. Hyperparathyroidism. American Family Physician. January 15, 2004.