Virtual Rounds Presentation A Case of Hypercalcemia Heather Taylor November 9, 2010

57 year old Caucasian female Generally healthy Hypercalcemia 57 year old Caucasian female Generally healthy

Hypercalcemia Chief Complaint: review lab results (June 30) History of Illness: seen by GP in April c/o bilateral shoulder pain. Recently started exercise program O/E full ROM but weakness rotator cuff muscles & tender supraspinatus. Xrays -> bilateral calcification in rotator cuff Ca+ 2.88 May 5th PTH normal. Repeat calcium normal. Dx rotator cuff tendonitis. Plan: repeat calcium. Exercise. NSAIDS. May 20th calcium 3.01 PTH normal

Hypercalcemia June 30th Presented at clinic for lab results. c/o “normal aches and pains”, itchy eyes, drippy nose Sent for TSH, PTHrp, ionized calcium, Vit D 1,25 & Vit D 25 July 8th : c/o hx crampy abdominal pain, constipation, nausea, fatigue, skin “feels dry”, headache, irritability, leg weakness & trouble concentrating; sx for 2-3 weeks, thought was dehydrated so took Pedialyte...sx improved. similar episode 4 months ago, lasted only 2 days.

Hypercalcemia Past Medical History: lichen sclerosis. Mild depression Allergies: palm oil -> wheezing Meds: Trazadone 50 mg po HS. No antacids. Calcium 1 gm/day. Vit D 800 IU/day Family History: older sister with lupus. Younger sister with arthritis. 4 sisters & niece with thyroid problems. Father, 2 sisters, daughter with depression. Mother deceased breast cancer age 62. younger sister with early CRC Social History: quit smoking 25 yrs ago. Drinks 1-5 beer &/or wine a day; can take it or leave it. CAGE neg

Hypercalcemia Physical Exam General Appearance: alert, slim 57 yr old female; appears her stated age. No acute distress. BP 112/65 HR 68, regular RR 16 EENT: normal. No enlarged nodes. Thyroid not enlarged. Chest clear CVS: S1S2 normal. No murmurs Abd: soft, nontender. No masses. Neuro: CN II-XII normal. 5+ strength bilateral UE, LE. DTR 2+ Labs: Calcium 3.25 ionized calcium 1.89 TSH, CBC, PTH, CK, lytes, Bun, creatinine Vit D normal

Hypercalcemia Differential Dx: ? Plan: ? Refer to Internal Medicine Pt went to Prince George for 3 wks.

Hyperparathyroidism & malignancy make up 90% of cases Hypercalcemia Results when calcium entering circulation exceeds calcium excreted in urine or deposited in bone Due to: increased bone resorption, increased GI absorption, decreased renal excretion. Hyperparathyroidism & malignancy make up 90% of cases

Causes of increased bone resorption Hypercalcemia Causes of increased bone resorption Primary hyperparathyroidism: (usually not > 3.25) increased PTH -> increased bone resorption & increased serum calcium increased calcium absorption in GI tract 2nd ary hyperparathyroidism: often assoc with CKD; low or normal calcium; can increase with prolonged disease 3. Malignancy: hypercalcemia associated with many tumors eg. Bone mets, multiple myeloma PTHrp assoc with nonmetastatic solid tumors 4. Thyrotoxicosis: mild hypercalcemia in 15-20% of pts

Causes of increased calcium absorption Hypercalcemia Causes of increased calcium absorption High calcium intake alone rarely causes hypercalcemia (elevated serum calcium -> PTH ) High calcium intake plus reduced urinary excretion -> CKD: decreased calcium excretion/elevated serum phosphate/decreased calcitriol synthesis Milk-Alkali syndrome: excess milk or calcium carbonate -> hypercalcemia, metabolic alkalosis & renal insufficiency

Excessive Vit D: increases calcium absorption & bone resorption Hypercalcemia Excessive Vit D: increases calcium absorption & bone resorption 1,25 -> results from: a) excess intake calcitriol eg. tx for hypoparathyroidism, or hypocalcemia/2nd’ary hyperparathyroidism of renal failure. Lasts 1-2 days; tx with salt & fluids, stopping calcitriol. Increased endogenous production eg pts with lymphoma, chronic granulomatous disorders (sarcoidosis, Wegeners) high 25OHD from excess Vit D or calcidiol intake lasts longer; more aggressive tx needed

Other less common causes of hypercalcemia Lithium -> increased PTH secretion Thiazide diuretics -> decreases urinary calcium excretion Pheochromocytoma -> rare; ?due to concurrent hyperparathyroidism Adrenal insufficiency Rhabdomyolysis & diuretic phase of ARF Theophylline toxicity Familial hypocalciuric hypercalcemia Metaphyseal chondrodysplasia: rare form of dwarfism

Hypercalcemia Diagnostic Approach Clinical & lab evaluation to distinguish between hyperparathyroidism & malignancy PTH-mediated: 1’ary hyperparathyroidism, familial hyperparathyroid syndromes Non PTH-mediated: malignancy, Vit D excess, granulomatous dx 1. Repeat sample to confirm hypercalcemia 2. Clinical evaluation, duration of high calcium, presence of sx, FH, & meds may give clues. 3. PTH: frankly elevated or in upper half of normal -> primary hyperparathyroidism 4. PTH < 20 pg/ml: look for other causes. 5. PTHrp & Vit D metabolites

Symptoms of hypercalcemia Polyuria, altered mentation, nausea, vomitting, constipation Life-threatening -> arrythmia, ++volume depletion due to polyuria Chronic mild hyperparathyroidism Usually no symptoms Increased risk osteopenia, renal calculi, nephrocalcinosis

Interpretation of serum calcium Hypercalcemia Interpretation of serum calcium Hypercalciumemia due to ionized (free) calcium 40-45% calcium bound to albumin Increased protein-binding can cause elevation in serum total calcium but not ionized calcium. Occurs in pts with hyperalbuminemia due to severe dehydration & rarely MM. Hypoalbuminemia -> normal total calcium, but elevated ionized calcium.

Degree of hypercalcemia useful < 2.75 mmol/L more likely primary hyperparathyroidism > 3.25 mmol/L more common with malignancy 10-20% of pts with 1’ary hyperparathyroidism have PTH in upper end of normal

Know when to check calcium Know what to look for if elevated Hypercalcemia Key Points Know when to check calcium Know what to look for if elevated Comprehensive hx can give clues

Hypercalcemia Questions? Thank you!