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Hypercalcemia: Types and Management

by Michael Lazarus

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    00:01 Malignancy associated hypercalcemia is the most common cause of non-parathyroid hormone induced hypercalcemia.

    00:08 It is typically severe in that patients present with elevated calcium greater than 14 mg/dL.

    00:16 It's often the result of a tumor-produced PTH-related protein or PTHrP leading to extensive resorption of the bone.

    00:24 Renal carcinoma, breast cancer and squamous cell cancers are associated with PTHrP release.

    00:32 Rarely, local mediated osteolysis from its extensive skeletal metastases, typically in multiple myeloma and breast cancer may cause the efflux of calcium from bone resulting in significant hypercalcemia.

    00:46 Let's talk about the management of hypercalcemia.

    00:49 This is really dependent on the severity of the elevation of calcium.

    00:53 If it is mild, say under 12 mg/dL, treatment of the underlying disorder, for example, hyperparathyroidism, once you perform a parathyroidectomy.

    01:04 This is usually sufficient and continuous monitoring of patient's calcium continuous after to surgery.

    01:11 Treating calcium levels above 12 mg/dL usually requires hospitalization especially if patient's asymptomatic.

    01:19 The key features to look at for are the presence of kidney disease and mental status changes.

    01:25 Initial treatment of severe hypercalcemia consist of aggressive hydration to replete volume loss and to increase the kidney's excretion of calcium.

    01:35 Loop diuretics are not recommended unless the patient manifest with kidney failure or heart failure.

    01:42 For the acutely symptomatic patient, subcutaneous calcitonin should be applied as well.

    01:49 Bear in mind that the half-life of the drug weigh ins withing 48 hours Calcium levels should be re-checked and re-dosing may be considered.

    01:57 Long-term management of hypercalcemia may require intravenous bisphosphonate therapy to prevent mobilization of calcium from the skeleton but also requires adequate kidney function.

    02:08 Always check the creatinine before prescribing a bisphosphonate.

    02:13 Glucocorticoids and restriction of calcium and vitamin D intake are also beneficial in vitamin D dependent hypercalcemia.

    02:22 Hemodialysis is reserved for the treatment of severe hypercalcemia in patients who are unable to produce urine and would not respond to fluid resuscitation or diuretics.

    02:33 Vitamin D-dependent hypercalcemia is associated with normal to elevated serum phosphorus.

    02:39 Vitamin D enhances intestinal absorption of phosphorus and suppresses PTH secretion which reduces kidney phosphorus excretion.

    02:49 This is in fact, the opposite in hyperparathyroidism where one sees reductions in serum phosphorus.

    02:58 In vitamin D-dependent hypercalcemia, the pathophysiology going on is the unregulated conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.

    03:10 This is seen classically in the granulomatous diseases which include: fungal infections, tuberculosis, sarcoid and lymphomas.

    03:20 What occurs is increased intestinal absorption of calcium.

    03:24 Patients present with hypercalcemia.

    03:28 These conditions are associated with inappropriately normal or frankly elevated 1,25-dihydroxyvitamin D level and a supressed PTH.

    03:39 Decreased serum and urine calcium after intake of calcium and vitamin D is restricted.

    03:45 Or rapid decrease in calcium after glucocorticoid therapy is consistent with these disorders.

    03:52 Of note here that the treatment of hypercalcemia and sarcoidosis is to give steroids.

    03:58 Let's talk about medication-induced hypercalcemia.

    04:02 PTH mediated hypercalcemia occurs with lithium.

    04:06 Non-PTH mediated hypercalcemia occurs with thiazide diuretics, classically.

    04:12 And then excessive ingestion of calcium or vitamin D can also elevate serum calcium levels and should always be ruled out on history.

    04:22 Let's go through a summary of the causes of hypercalcemia that we've discussed.

    04:26 Primary hyperparathyroidism most commonly from a parathyroid adenoma is the most common cause of outpatient hypercalcemia.

    04:37 In this case, the PTH is elevated in 80%, the phosphorus is classically low and the vitamin D levels are high.

    04:44 Creatinine is usually normal and the parathyroid hormone releasing peptide is negative.

    04:50 Clinical clues are symptoms and signs of hypercalcemia and xrays which are classic findings including osteitis fibrosa cystica.

    04:59 Humeral hypercalcemia of malignancy is the most common cause if in-patient hypercalcemia.

    05:06 In this condition, the PTH level is low, the phosphorus level is normal or low, vitamin D levels are normal or low and the creatinine can be increased depending upon whether or not there is calciuresis.

    05:20 Parathyroid hormone releasing peptide is positive.

    05:23 Symptoms and signs of malignancy will be found clinically.

    05:27 weight loss, bone pain, etc., may also be manifestations.

    05:31 Multiple myeloma is a clinical condition in which parathyroid hormone manifest as low, Serum phosphorus may be high, vitamin D levels are usually normal.

    05:43 Creatinine is elevated if the condition also affects the kidney.

    05:46 and parathyroid hormone releasing peptide is negative.

    05:50 Symptoms and signs of malignancy are usually the common presentation usually with bone pain and weight loss.

    05:57 Granulomatous diseases as we discussed, the classic example being sarcoidosis.

    06:02 Here, the parathyroid hormone is low, the phosphorus levels are high, vitamin D levels are high, Creatinine, if the kidney is affected by the underlying condition will manifest as an increased creatinine or alternatively, if the patient has a very high level of calcium and they are dehydrated, may manifest with the pre-renal state which would be another cause of an elevation of creatinine.

    06:28 And then finally, PTHrP will be negative.

    06:32 The clinical features of sarcoidosis and TB vary but mostly affect the lungs.

    06:38 Hyperthyroidism, interestingly enough, will not cause any derrangements in PTH, phosphorus, vitamin D or creatinine.

    06:47 The PTHrP will be negative but they may be the direct stimulation of osteoclasts by thyroid hormone leading to hypercalcemia.

    06:56 And then finally, the very rare condition of familial hypocalciuric hypercalcemia where all of the tests are negative.

    07:04 One makes the diagnosis by checking a 24-hour urine calcium excretion.

    07:09 Here, this will be low in the setting of an elevated serum calcium.

    07:13 Checking a family history is usually indicated and these patients will then require managements depending upon the severity of the hypercalcemia.


    About the Lecture

    The lecture Hypercalcemia: Types and Management by Michael Lazarus is from the course Metabolic Bone Disorders. It contains the following chapters:

    • PTHrP Check
    • Management of Hypercalcemia
    • Vitamin D-dependent Hypercalcemia
    • Medication-induced Hypercalcemia
    • Summary of Hypercalcemia

    Included Quiz Questions

    1. Squamous cell carcinoma
    2. Small cell carcinoma
    3. Adenocarcinoma
    4. Medullary carcinoma
    5. Anaplastic carcinoma
    1. Bisphosphonates
    2. Diuretics
    3. Antibiotics
    4. Parasympathomimetics
    5. Sympatholytics
    1. Fungal infections
    2. Viral infections
    3. Bacterial infections
    4. Protozoal infections
    5. Parasitic infections
    1. Thiazide diuretics
    2. Loop diuretics
    3. Potassium-sparing diuretics
    4. Carbonic anhydrase inhibitors
    5. Osmotic diuretics

    Author of lecture Hypercalcemia: Types and Management

     Michael Lazarus

    Michael Lazarus


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