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

Labs and tests

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
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

LFT: WNL

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)

Hormone Parathyroid hormone increase Ca++, decrease PO4 levels in blood Calcitriol (vitamin D) Ca++, PO4 levels increases in blood

Effect on bones Effect on gut Supports osteoclast resorption Indirect effects via increase calcitriol from 1hydroxylation

Effect on kidneys Supports Ca++ resorption and PO4 excretion, activates 1hydroxylation No direct effects

No direct effects Supports osteoblasts

Increases Ca++ and PO4 absorption

Calcitonin Inhibits causes Ca++, osteoclast PO4 levels resorption decrease in blood when hypercalcemia is present

No direct effects

Promotes Ca++ and PO4 excretion

Pathophysiology
Parathyroid hormone (PTH), 1,25dihydroxyvitamin 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 hypercalcemiaassociated 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.