Consultation note
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Patient Name:
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Dr. ___________ has asked for consultation on this patient regarding regarding _______________.

Thank you for inviting us to see this patient.

Chief complaint: ___ year old male/female presents today for evaluation and treatment of hypercalcemia.
Patient admits/denies the use of thiazides, lithium

Patient admits/denies to have history of cancer

Patient admits/denies to Family History (FH) of cancer or hypercalcemia (familial hypercalciuric hypercalcemia is autosomal dominant)

Patient admits/denies the use of tobacco

Patient admits/denies symptoms of : lethargy, depression, paranoia, psychosis, confusion, obtundation, coma, less commonly headache

Patient admits/denies symptoms of : constipation, nausea, vomiting, anorexia, less commonly indigestion, peptic ulcer disease

Patient admits/denies symptoms of : diabetes insipidus (polydipsia, polyuria, nocturia)

Patient admits/denies symptoms of : proximal muscle weakness, less commonly myopathy, weakness, osteoporosis, pseudogout, bone pain, arthralgias

Patient admits/denies symptoms of : pruritus

Mild hyperparathyroidism associated with fatigue, daytime sleepiness, muscle weakness and lack of emotional and sexual interest

]My key findings of the ROS, Past Hx, Family Hx, and social Hx are:
ROS: Review of 12 systems was negative with exception of those things mentioned above in the HPI and weightloss/weight gain, headache, fever, chills, heat/cold intolerance, chest pain, dyspnea, cough, sinus/allergy complaints, frequent infections, nausea, vomiting, diarrhea, constipation, erectile dysfunction, genitourinary complaints, muscle aches or pains, numbness or tingling, easy bruisability or bleeding, hair changes/alopecia, skin changes/ulcers, tremors, depression or anxiety.

Patient denies weightloss/weight gain, headache, fever, chills, heat/cold intolerance, chest pain, dyspnea, cough, sinus/allergy complaints, frequent infections, nausea, vomiting, diarrhea, constipation, erectile dysfunction, genitourinary complaints, muscle aches or pains, numbness or tingling, easy bruisability or bleeding, hair changes/alopecia, skin changes/ulcers, tremors, depression or anxiety.

Past Medical History:

Past Surgical History:

Family History:

Social History:
Diet:
Exercise:
Smoking:
Recreational Drug use :
Education:
Occupation:
Lives with ____ where ____

Home Meds:

Allergies:

My key findings of this patient's Physical Exam are:
VITALS:
Pulse:
Blood Pressure:
Respirations:
Temperature:
Weight:
Height:
BMI:

GENERAL: sitting up/reclined in bed, awake, alert, and oriented, hypertension, bradycardia, orthostatic hypotension
HEAD: normocephalic, atraumatic, no temporal wasting, negative chvostek sign
NOSE, MOUTH: lips and mucous membranes are moist, normal color of buccal mucosa
EYES: EOMI, PERLA, no proptosis, band keratopathy
NECK: supple, thyroid normal in size, thyroid small, thyroid low set, no thyromegaly or masses, palpable parathyroid
RESPIRATORY: clear to ascultation bilaterally, breast and axillary masses
CARDIOVASULAR: S1S2, no murmurs/rubs/gallops
GI: soft, non-tender, + bowel sounds
LYMPHATIC: no cervicoclavicular adenopathy appreciated
MUSCULOSKELETAL: moving all extremities
EXTREMITIES: no edema present, fractures, calcification, clubbing may be associated with lung cancer
NEUROLOGIC: monofilament sensed in all areas of the foot, vibratory sensation intact, fine/crude touch intact, pulses palpable, DTRs 2+, CN grossly intact
DERMATOLOGY: no xanthomas appreciated, no skin ulcers, no calluses, no onchyomycosis/dermatophyosis, no striae,
PSYCHIATRY: patient answers questions appropriately, appropriate affectcoherent thoughts without flight of ideas

Labs:
Na
K
Cl
CO2
BUN
Creat
Gluc
Ca
Mg
Phos
WBC
Hgb
PCV
Plt
SGOT
SGPT
GGT
Alb
TBil
AlkP
CPK
CKMB
TropnT

Bone and Mineral
Intact PTH:
Ionized Calcium:
Ca:
Mg:
Phosphorus:
25-OH Vitamin D:
1,25-OH Vitamin D:

Thyroid:
TSH:
FT4:
TT4:
QT3:
Athyp:
AthyG:
Calcitonin:
Thyroglobulin:

Assessment:

Hypercalcemia occurs when calcium entry into blood or extracellular fluid exceeds renal calcium excretion. Calcium entry into blood or extracellular fluid comes from 3 sources. Calcium release from bone - examples include malignancy, Paget's disease of bone, immobilization, hyperthyroidism, calcium absorption from intestine (typically due to increased vitamin D) - examples include vitamin D toxicity, granulomatous disease, calcium resorption in kidney - examples include hyperparathyroidism and thiazide diuretics. Reduced renal excretion - examples include familial hypocalciuric hypercalcemia and hypophosphatemia

Causes:

Primary hyperparathyroidism accounts for 50% of patients with hypercalcemia - sporadic, hyperplasia, adenoma, familial

Tertiary hyperparathyroidism - persists despite renal transplant due to long-standing parathyroid hyperplasia

Multiple endocrine neoplasia - Type I and Type IIa

Malignancies (may cause hypercalcemia through bone metastases or "humoral" factors such as PTH-related protein, IL-1, TGF-beta), Bone metastases - most commonly secondary to breast cancer (bone sialoprotein released), myeloma, lymphoma, Tumors which secrete PTH-related peptide, Squamous cell lung carcinoma, Hypernephroma (renal cell carcinoma), Pancreatic cancer, squamous cell carcinoma of cervix or esophagus, head and neck tumors, islet cell carcinoma, multiple myeloma - T cell makes osteoclast-activating factor, lymphomas - monocytes make 1,25 vitamin D; lymphoproliferative osteoclast activating factor (IL1, TGF-beta), ovarian cancer.

Drugs - thiazide toxicity, diuretics, lithium, theophylline toxicity

Vitaminosis - vitamin D toxicity, vitamin A toxicity

Increased bone turnover - hyperthyroidism, Paget's disease of bone, prolonged immobilization (especially children)

Infectious diseases: hepatitis, AIDS, CMV, disseminated candidiasis, nocardia asteroides infection

Granulomatous diseases (activate vitamin D by way of 1-alpha hydroxylase), sarcoidosis, tuberculosis, other granulomatous diseases - leprosy, coccidioidomycosis, histoplasmosis, beryliosis, candidiasis, cryptococcosis, cat-scratch disease (case report in JAMA 1998 Feb 18;279(7):532 )

Miscellaneous causes: phosphorus depletion syndrome, adrenal insufficiency, pheochromocytoma, William's syndrome (idiopathic, infants), familial hypocalciuric hypercalcemia (autosomal dominant), systemic lupus erythematosus, recovery from acute renal failure due to rhabdomyolysis (2-3 weeks after acute muscle injury), milk-alkali syndrome

Milk-alkali syndrome has reappeared as a result of increasing use of calcium carbonate antacids and is reported to be third most common cause of hypercalcemia in hospitalized patients without end-stage renal disease.

Complications: Dehydration, proximal muscle weakness, cardiovascular - coronary artery calcification (especially in patients with diabetes), cardiac valve annulus calcification, arrhythmias (rare), atrioventricular (AV) block, hypertension, sensitization to digoxin, gastrointestinal - pancreatitis, peptic ulcer disease, gastrointestinal bleeding, renal - nephrocalcinosis, nephrolithiasis, renal insufficiency, neurologic - mental confusion, coma, ophthalmologic - band keratopathy in medial and lateral margins of cornea, metastatic calcifications - case presentation of calciphylaxis.

Diagnostic Plans:
Serum calcium > 10.2 mg/dL (2.55 mmol/L) in women and 10.5 mg/dL (2.63 mmol/L) in men

Mild hypercalcemia 10.2-12 mg/dL (2.55-3 mmol/L)

Moderate hypercalcemia 12-13.5 mg/dL (3-3.38 mmol/L)

Severe hypercalcemia > 13.5 mg/dL (3.38 mmol/L)

Serum calcium level may be inaccurate in patients with abnormal serum protein levels

  corrected serum calcium = serum calcium + 0.8 (4 - albumin [in mg/dL])

  for patients with hypergammaglobulinemia (e.g. multiple myeloma), additional correctional factor is 0.16 times the change in globulin level

Tests:  calcium/ionized calcium, albumin, phosphate, magnesium, alkaline phosphate, electrolytes, blood urea nitrogen, creatinine, intact parathyroid hormone (iPTH) - elevated in primary hyperparathyroidism, may be normal (but "normal" levels are abnormal in the presence of hypercalcemia), decreased in all other causes of hypercalcemia except familial hypocalciuric hypercalcemia, lithium, thiazide use, may be elevated in renal insufficiency due to reduced clearance. 5f primary hyperparathyroidism ruled out, screen for malignant disease, chest x-ray - may show lung or bone disease, bone scan, mammography, colonoscopy, PSA, prostate exam, pap smear. Consider checking 24 hour urine calcium and creatinine, 1,25(OH2) vitamin D (calcitriol), elevated in vitamin D toxicity and granulomatous diseases, decreased in accelerated bone turnover (e.g. Paget's disease, immobilization), serum and urine electrophoresis if multiple myeloma suspected, parathyroid hormone-related peptide (PTHrP), which is the hormone that causes tumor-related hypercalcemia in many cases; PTHrP increased with breastfeeding. Vitamin A - elevated in vitamin A toxicity. Thyroid function tests. Cosyntropin stimulation test - if adrenal insufficiency suspected. Plasma free metanephrines or 24-hour urine metanephrines and/or catecholamines - if pheochromcytoma suspected

Serum calcium should be above the testing laboratory reference range on two separate determination prior to initiating a hypercalcemia evaluation.  All initial hypercalcemia results should be repeated with careful attention paid to obtaining the specimen under optimal drawing conditions and both results should be corrected for albumin. Morning specimen after fasting. Patient in sitting position (not prone before or during phlebotomy).

•  Corrected calcium calculators can be found at GlobalRPh or The Nephron Information Center

Calcium-PTH Nomogram - PTH values should be evaluated in relation to serum calcium; e.g., a PTH value of 60 pg/mL is inappropriate for a 10.1 mg/dL (2.53 mmol/L) calcium even though they both fall within their respective reference ranges. To assess if ratio Calcium/PTH is appropriate use the Calcium-PTH Nomogram

•  Hypercalcemia - Increased Parathyroid Hormone (PTH): in asymptomatic (excluding lethargy and depression) patients with a history of chronic hypercalcemia, an elevated PTH almost always indicates primary hyperparathyroidism. •  PTH infrequently elevated in other hypercalcemic conditions; e.g., following lithium therapy, Familial hypocalciuric (benign) hypercalcemia, Ectopic production PTH by non-parathyroid neoplasms, urinary calcium elevated in 40% of PHPT patients, Phosphaturia is PTH-induced, Urinary calcium, calcium clearance, and magnesium helpful in distinguishing PHPT patients from those rare patients with familial hypocalciuric hypercalcemia who have inappropriately normal or occasionally modestly elevated levels of PTH

•  Hypercalcemia - Decreased Parathyroid Hormone (PTH) Low or Undetectable Intact PTH = Nonparathyroid Cause, malignancy is the most likely diagnosis in hypercalcemic patients with a low or undetectable PTH, especially in those with a short history or no history of hypercalcemia, Parathyroid Hormone-Related Protein [PTHrP] mediates hypercalcemia in humoral hypercalcemia of malignancy and its measurement may occasionally be helpful in the differential diagnosis of hypercalcemia.

•  1,25-Dihydroxyvitamin D [1,25(OH)2D] may be elevated in: Sarcoidosis and other granulomatous diseases, Subset of patients with lymphoma and other lymphoproliferative disorders, Iatrogenic 1,25(OH)2D intoxication

•  Note: 1,25(OH)2D also elevated ~1/3 PHPT patients

•  Vitamin D or 25[OH]D intoxication can be confirmed by a careful history and/or an elevation in 25[OH]D

Elevated fibroblast growth factor 23 (FGF 23) may suggest malignancy; FGF 23 > 200 relative units/mL found in 4 of 7 patients with humoral hypercalcemia of malignancy, 1 of 11 patients with hyperparathyroidism, and none of 11 healthy controls

Consider DEXA bone densitometry since osteoporosis may be a complication of hypercalcemia

Therapeutic Plans:
Depends on underlying etiology

Hypercalcemia from vitamin A or vitamin D toxicity may take weeks to resolve

Familial hypocalciuric hypercalcemia is benign, does not require treatment

Discontinue medications known to cause or worsen hypercalcemia (e.g. thiazides)

Primary treatment approaches for hypercalcemia: mobilization, hydration, calciuresis - hydration plus loop diuretic

Treatment based on severity of hypercalcemia

Mild - serum calcium 10.5-12 mg/dL (2.63-3 mmol/L): no specific treatment necessary, monitor blood pressure, serum calcium, renal function, urinary calcium, abdominal radiographs and measurements of bone density

Moderate - serum calcium 12-13.5 mg/dL (3-3.38 mmol/L): decision to treat may be based on symptoms, hydration and salt replacement with IV saline, loop diuretic may be required, especially in cases of congestive heart failure or renal insufficiency, bisphosphonate may be required

Severe - serum calcium > 13.5 mg/dL (3.38 mmol/L) : should be aggressively treated, treatment of underlying disease, usually secondary to malignancy, if elevated PTH, urgent parathyroidectomy should be performed, hydration and salt replacement with IV normal saline (2.5-4 L/day) with loop diuretic (e.g. furosemide 10-40 mg IV every 6-12 hours), monitoring of hemodynamic and electrolyte status, inhibition of bone resorption of calcium with bisphosphonate or other agent, zoledronic acid (Zometa) and pamidronate (Aredia) are bisphosphonates that offer single-dose therapies, calcitonin and glucocorticosteroids may have adjunctive role in selected cases, consider dialysis in severe cases

Diet: low calcium diet not generally thought to be effective, poorly accepted by patients, no studies found to support or refute use of low calcium diet

Activity: mobilization, may be complicated if pathologic fracture

Medications: treatment of acute hypercalcemia (if calcium > 13.5 mg/dL [3.38 mmol/L] or symptomatic), vigorous IV normal saline solution, IV furosemide 10-40 mg every 4-6 hours, especially if congestive heart failure or central venous pressure > 15 mmHg, monitor electrolytes, renal function, Ca, Mg, PO4, inhibitors of bone resorption are drugs of choice - bind hydroxyapatite, inhibit osteoclasts, bisphosphonates, osteonecrosis of the jaw has been reported with bisphosphonate use, primarily in cancer patients receiving intravenous bisphosphonates; pamidronate (Aredia) :single dose 90 mg IV infusion over 24 hours (30-60 mg over 4 hours may be used in mild to moderate hypercalcemia), administration in large volumes of fluid (500 mL or more) recommended (precipitated calcium bisphosphonate carries the risk of nephrotoxicity), •  trial of lower doses diluted in larger volumes of fluid may be attempted in patients with renal insufficiency; dose may be raised if renal function remains stable, maximum effect within 4-5 days of infusion, effect may last for a month, drug of choice in malignancy, FDA approved as single IV therapy, no nephrotoxicity even in patients with severe renal insufficiency, when infused over several hours, pamidronate available generically. Zoledronic acid 4 mg IV for initial treatment, 8 mg IV for relapse or refractory hypercalcemia. Zolderonic acid (Zometa) is new IV bisphosphonate that is more effective and more convenient than pamidronate (Aredia) for treating hypercalcemia of malignancy, can be given over 15 minutes instead of 2 hours, monitor serum creatinine. Zoledronic acid more effective in response rate and duration of response than pamidronate. Zometa labeling updated with information on patients with advanced cancer and creatinine clearance 60 mL/minute or lower; table in prescribing information provides dosing for mild and moderate renal impairment; serum creatinine should be checked before each dose and drug withheld if renal deterioration. Infusion over 15 minutes associated with reduced renal toxicity compared to infusion over 5 minutes. Adverse effects of zoledronate 4 mg IV over 5 minutes include 44% transient fever, 29% nausea, 27% constipation, 22% anemia, 22% dyspnea, 8% renal toxicity; similar to pamidronate; renal toxicity increased with 8 mg and decreased with 15 minute infusion; other adverse effects reported include hypophosphatemia, hypocalcemia, bone pain, arthralgias, myalgias, redness and swelling at injection site.

Calcitonin use reserved for very severe cases as adjunctive therapy to slower acting bisphosphonates, 4 units/kg subcutaneously or intramuscularly every 12h (following skin testing), inhibits osteoclasts and enhances renal excretion of calcium, more rapid onset of action (decreases calcium within hours, peak effect within 12-24 hours), effect modest and transient, tolerance develops after first 1-3 doses, can be given in combination with corticosteroids in patients with renal failure.

Glucocorticoids: hydrocortisone 3-5 mg/kg/day IV then prednisone 30 mg PO twice daily, effective in breast cancer, myeloma, sarcoidosis, vitamin D toxicity

Calcium carbonate 500 mg 2-3 times daily has been suggested, but insufficient evidence to support widespread use, recommendation to achieve recommended calcium intake via diet and not calcium supplements, calcium carbonate may exacerbate hypophosphatemia, oral phosphates 1-3 g/day in divided doses, contraindicated in renal failure or hyperphosphatemia (be careful)

Cinacalcet (Sensipar) FDA approved for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. Cinacalcet may reduce rates of fracture and cardiovascular hospitalization ( level 2 [mid-level] evidence ) (* further peer review in progress). Systematic review of 7 randomized placebo-controlled trials of cinacalcet for secondary hyperparathyroidism for patients with end-stage renal disease on dialysis although 846 patients received cinacalcet, different numbers used for different analyses, cinacalcet more effective than at meeting parathyroid hormone levels. Calcimetics (mainly cinacalcet) associated with improvements in biochemical measures of secondary hyperparathyroidism but no evidence of improvements in clinical outcomes, most patients also treated with vitamin D and phosphate binders, no substantial differences in clinical outcomes other than adverse effects. CCinacalcet lowers parathyroid hormone levels in hemodialysis patients with uncontrolled secondary hyperparathyroidism ( level 3 [lacking direct] evidence ) ; 741 such patients randomized to cinacalcet vs. placebo for 26 weeks, cinacalcet 30 mg once daily increased up to 180 mg once daily to achieve intact parathyroid hormone levels < 250 pg/mL, mean parathyroid hormone levels decreased 43% vs. increased 9% ( N Engl J Med 2004 Apr 8;350(15):1516 ), editorial can be found in N Engl J Med 2004 Apr 8;350(15):1565, commentary can be found in N Engl J Med 2004 Jul 8;351(2):188. Cinacalcet (Sensipar) will probably become standard of care for hypercalcemia due to secondary hyperparathyroidism (chronic kidney disease on dialysis) or parathyroid carcinoma; available in 30, 60 and 90 mg tablets; recommended initial dose 30 mg once daily, increase every 2-4 weeks to achieve target parathyroid hormone levels, thirty 30-mg tablets costs $290.10; peak plasma levels 2-6 hours after oral dose; common adverse effects are nausea and vomiting, other adverse effects are hypocalcemia and seizures ( The Medical Letter 2004 Sep 27;46(1192):80)

Surgery: partial or total parathyroidectomy may be performed by surgeon experienced in parathyroid surgery

Patient Education:

Expect transient, mild hypocalcemia following successful surgery for primary hyperparathyroidism

Consider follow-up DEXA bone densitometry

Return to Clinic:
We have discussed our diagnostic and treatment plans with the patients and family/friends that were present. All questions have been answered to the patient's satisfaction.

Thank you for inviting to see this consult!

Written by ___ _____________________ Time out_______

•  275.42 hypercalcemia

•  252.0 hyperparathyroidism

•  252.00 hyperparathyroidism, unspecified

•  252.01 primary hyperparathyroidism

•  252.02 secondary hyperparathyroidism, non-renal

•  252.08 other hyperparathyroidism

•  588.81 secondary hyperparathyroidism (of renal origin)