Hypercalcemia

• Hyperparathyroidism: high PTH, low serum Phos, high urine Ca

  • High PTH levels cause phosphate wasting by the kidney leading to low serum phosphorus levels

  • Primary: parathyroid adenomas, parathyroid hyperplasia

    • Can be associated with MEN type 1

  • ***

  • Must be distinguished from FHH

• Familial hypocalciuric hypercalcemia (FHH): inappropriately normal PTH, low urine Ca

  • Caused by inactivating mutations in parathyroid gland's calcium sensing receptor (CaSR)

  • Serum calcium usually mildly elevated

Non-PTH dependent (PTH appropriately suppressed):

• Prolonged immobilization: low PTH

  • Lack of mechanical stress on bone leads to decreased bone formation

    • Imbalance of bone resorption vs formation -> excess calcium released from the bone

  • Children and adolescents are at increased risk compared to adults because they have higher burn turnover

• Vitamin D toxicity

• Malignancy

• Granulomatous disease (e.g., sarcoidosis)

  • Lesions contain macrophages with 1⍺-hydroxylase activity

• Subcutaneous fat necrosis

  • Lesions have increased 1⍺-hydroxylase activity

• Hypophosphatemia

  • Stimulates 1⍺-hydroxylase activity in the kidney, increasing levels of 1,25-dihydroxyvitamin D (active form of vitamin D), and increasing calcium absorption

• Williams syndrome

  • Mechanism unknown

• Common symptoms include:

  • Decreased appetite (anorexia)

  • Fatigue

  • Weight loss

  • Dehydration

• May also have:

  • Polyuria, polydipsia

  • Kidney stones

  • Nausea/vomiting

  • Constipation

  • Fatigue

  • Depression

  • Confusion

Labs:

• Albumin

  • Calcium binds protein: may have higher total calcium levels if albumin is high, and vice versa

    • Use equation to correct calcium levels, or obtain ionized calcium

• Ionized calcium (iCa)

• Parathyroid hormone (PTH)

• Phosphorus

• Magnesium

• 25-OH vitamin D

• 1,25-OH₂ vitamin D

• Urine calcium/creatinine (UCa/Cr) ratio

• Treat underlying cause

• Stabilization and reduction of the calcium level

  • Adequate hydration

  • Increasing urinary calcium excretion

  • Inhibition of osteoclast activity in the bone

• First line: hyperhydration with isotonic saline (3 L/m²/day)

  • Increasing sodium excretion will increase calcium excretion

• Second line: calcitonin (2-4 U/kg SC/IM q12h) or bisphosphonates (0.5 mg/kg); consider when calcium >14

• Third line: prednisone 2 mg/kg

  • Decreases calcium absorption

Hypervitaminosis A

• Vitamin A is a subclass of a family of lipid-soluble compounds referred to as retinoic acids that plays a crucial role in cellular differentiation and integrity in the eye

• Etiology of how hypervitaminosis A influences hypercalcemia and bone metabolism has not been completely delineated

• Acute toxicity: occurs in adults when a single dose of >660,000 IU (>200,000 mcg) of vitamin A is ingested

• Symptoms include nausea, vomiting, vertigo and blurry vision

• Chronic toxicity: ingestion of vitamin A in amounts higher than 10 times the DRI (i.e., toxicity may occur with chronic ingestion of approximately 33,000 internaitonal units (10,000) mcg of retinol in adults

  • May only require 1,500 mcg in children***?

• Present with ataxia, alopecia, dry skin, hyperlipidemia, hepatotoxicity, bone and muscle pain, visual impairments, and hypercalcemia

Williams syndrome

• Caused by the spontaneous deletion of 26-28 genes on chromosome #7

• Cardiovascular anomalies: supravalvular aortic stenosis, peripheral artery stenosis, septal defects

• Endocrine disorders: hypercalcemia, hypothyroidism, type II DM, early puberty

• Renal and urinary tract abnormalities: nephrocalcinosis, CAKUT, dysfunctional voiding, UTI

• Intellectual disability, SNHL, hypotonia, hyperextensible/contractured joints, constipation, feeding difficulties

Medullary nephrocalcinosis

• Nephrocalcinosis refers to generalized calcium deposition (calcium oxalate and calcium phosphate) in the kidney

• Risk factors: medications (loop diuretics, aminoglycosides), prematurity, diseases that cause hypercalcemia, hyperphosphatemia, hypercalciuria, hyperphosphaturia, hyperoxaluria

• The most common cause is increased urinary excretion with or without hypercalcemia

• Diagnosis is made by imaging (ultrasound or CT), typically incidentally

• Common causes

  • Hypervitaminosis D, Cushing's syndrome, sarcoidosis, sickle cell disease, primary hyperoxaluria, hyper/hypothyroidism, hyperparathyroidism, malignancy, *** (UTD table)

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