Definition (Am Fam Physician 2003;67:1959; Curr Opin Pediatr 2010;22:508)
• In newborns, serum Ca (corrected for albumin) normal up to 11.3 mg/dL. In children up to 5 yr, normal up to 10.8 mg/dL. In older children and adults, mild hyperCa 10.5–12 mg/dL; mod 12–14 mg/dL, and severe (life-threatening >14 mg/dL
Pathophysiology (Lancet 1998;352:306)
• As above, 1° control of body Ca++ mediated by PTH, 1,25(OH)2 vit D, and calcitonin
• ↑ serum Ca++ 2/2 ↑ bone resorption, ↑ GI absorption, and ↓ renal excretion and can be mediated by inapprop ↑ PTH levels, and ↑ vit D levels (vit D toxicity)
• Renal excretion is 1° means for dealing w/ large fluxes of Ca++ but limited (only 10% of Ca reabsorp controlled by vit D and PTH, rest coupled to Na reabsorp). Regulation of intestinal absorp provides long-term homeostasis
Etiology (Am Fam Physician 2003;67:1959; Curr Opin Pediatr 2010;22:508)
• Ddx at all ages includes hyperPTH, ↑ vit D activity, ↑ bone turnover, ↓ renal clearance, increased Ca intake, malignancies; see chart for details
• Malignancy can cause hyperCa by 2/2 osteolytic lesions (e.g., sarcoma, neuroblastoma, rhabdomyosarcoma, other metastatic disease) or humoral production (e.g., PTHrP from squamous cell Ca, RCC, dysgerminoma, leukemia; or calcitriol from Hodgkin’s)
• ↑ vit D activity: Toxicity 2/2 O/D, excess vit D 2/2 granulomatous dz (sarcoidosis, TB, berylliosis, P. jiroveci PNA, Wegner dz)
• ↑ bone turnover; i.e., thyrotoxicosis, vit A toxicity, pheochromocytoma, immobility
• ↓ renal clearance; AI, thiazide diuretics
Clinical Manifestations (Lancet 1998;352:306)
• Symptoms include “stones, bones, moans (abdominal), and psychiatric overtones”
• “Stones”: Nephrolithiasis 2/2 increased urinary calcium excretion, can result in nephrocalcinosis and nephrogenic diabetes insipidus
• “Bones”: Osteoporosis, osteitis fibrosa cystica (2/2 hyperPTH w/ subperiosteal resorption, bone cysts), arthritis
• “Abdominal moans”: N/V, abdominal pain, anorexia, and weight loss; extreme manifestations include pancreatitis and peptic ulcer disease
• “Psychiatric overtones”: ↓ concentration/memory, confusion, Δ MS, lethargy, coma. Muscle weakness. Impaired vision 2/2 to corneal calcifications
• Cardiac sequelae include HTN, ↓ QTc, and rarely cardiac arrhythmias
Diagnostic Studies (Lancet 1998;352:306; Am Fam Physician 2003;67:1959)
• Check serum Ca++, albumin, ionized Ca++ (where available), phosphate, Alk Phos, basic serum electrolytes w/ BUN/Cr, TSH, PTH (and if suspected PTHrP), 1,25(OH)2 vit D, 25-OH vit D, 24 hr urine calcium/creatinine, and EKG
• Consider U/A, KUB, and renal US if concern for nephrolithiasis
Management (Am Fam Physician 2003;67:1959; Curr Opin Pediatr 2010;22:508)
• Mild asymptomatic hyperCa: IVF (with KCl), mobilization
• Symptomatic or severe hyperCa: IVF followed by furosemide (monitor K+), calcitonin (short-acting; tachyphylaxis after 24 hr), cardiac monitoring
• HyperCa resistant to IVF and loop diuretics: Consider bisphosphonates (but long-term effects on bone metabolism poorly studied in children) or glucocorticoids (dec vit D and Ca absorption)
• Williams syndrome, IHH, or FHH: Low-Ca, low-vitamin-D diet (consider Calcilo XD low-Ca, low-vitamin-D infant formula)
• 1o hyperPTH: Consult endocrine surgery for parathyroidectomy
• In resistant situations, can use dialysis w/ low Ca++ bath or EDTA chelation