Hypercalcemia: Types and Management

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 wanes 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.