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Topic : Hypercalcemia
R2 Supaporn Bumrungthaichaichan
Calcium homeostasis
Harrison’s Endocrinology second edition
Calcium
• concentration of ionized calcium in the ECF must be
maintained within a narrow range
• calcium ion plays a critical role in normal cellular function
and signaling, regulating diverse physiologic processes such as
o neuromuscular signaling
o cardiac contractility
o hormone secretion
o blood coagulation
Harrison’s Endocrinology second edition
feedback mechanisms
• involve parathyroid hormone (PTH) and the active vitamin D
metabolite 1,25-dihydroxyvitmin D [1,25(OH)2D].
• These feedback mechanisms are orchestrated by integrating signals
between
o parathyroid glands
o kidney
o intestine
o bone
Harrison’s Endocrinology second edition
Harrison’s Endocrinology second edition
Harrison’s Endocrinology second edition
Vitamin D
• Vitamin D intoxication
o Usually 25-Hydroxy vit D 2 over counter supplement
o Ix 25-Hydroxy vit D 3 high
Granulomatous disease
• Sarcoidosis ,TB, Leprosy , lymphomas ,Wegener’s granulomatosis
• Macrophage produce 1 alpha hydroxylase enzyme caused by
enhanced conversion of 25(OH)D to the potent 1,25(OH)2D,
enhances intestinal calcium absorption, resulting in hypercalcemia
and suppressed PTH.
Endocrine disorder
• Hyperthyroid
• Adrenal insuffficiency
• Pheochromocytoma
Drugs
• Thiazide diuretics increase renal Ca reabsorption at distal tubule
• Calcium and vit D
• Lithium<900-1500 mg/d> กระตุน้ ใหห้ลัง่ PTH และ รบกวน CaSR และลดการขบั Ca ท่ีไต
• Vitamin A >50000IU/day increase bone resorption
Others
• exogenous calcium overload, as in milk-alkali syndrome
• total parenteral nutrition with excessive calcium+vitD
supplementation caused aluminium intoxication
• Immobilized increase bone resorption ตรวจพบ PTH Vit D ต ่า
Clinical Manifestations of Hypercalcemia
Renal “stones”
Skeleton “bones”
Gastrointestinal “abdominal moans”
Neuromuscular “psychic groans”
Cardiovascular
Other
Nephrolithiasis
Bone pain Nausea, vomiting
Confusion, stupor, coma
Cardiac arrhythmias
Itching
Nephrogenicdiabetes insipidus
Osteitisfibrosacystica
Anorexia, weight loss
Impaired concentration and memory
Shortened QT interval
Keratitis, conjunctivitis
Dehydration Osteoporosis Constipation Lethargy and fatigue
Hypertension
Nephrocalcinosis
Arthritis Abdominal pain
Muscle weakness
Vascular calcification
PancreatitisPeptic ulcer disease
Corneal calcification (band keratopathy)
Hyperparathyroidism
Primary
• Primary hyperparathyroidism results from a hyperfunction of the
parathyroid glands themselves. There is over secretion of PTH due to a
parathyroid adenoma, parathyroid hyperplasia or, rarely, a parathyroid
carcinoma.
Tertiary
• Tertiary hyperparathyroidism is seen in patients with long-term
secondary hyperparathyroidism which eventually leads to hyperplasia
of the parathyroid glands and a loss of response to serum calcium
levels. This disorder is most often seen in patients with chronic renal
failure and is an autonomous activity.
Primary hyperpararhyroid
• Asymptomatic : check up
• Symptomatic 50%
o Renal calculi
o Bone pain
o Fracture
o Pancreatitis
o PU
o Neuromuscular and neuropsychiatric
• MEN 1 , MEN 2A
• PE normal or neck mass<carcinoma>
Criteria for Surgery in Primary Hyperparathyroidism*
Symptomatic
• Hyperparathyroid crisis (discrete episode of life-threatening
hypercalcemia)
• Nephrolithiasis
• Reduced cortical bone density (measure with dual x-ray
absorptiometry or similar technique)
• Classic neuromuscular symptoms
• Proximal muscle weakness and atrophy, hyperreflexia, and gait
disturbance
• Osteitis fibrosa cystica
•
Criteria for Surgery in Primary Hyperparathyroidism*
If aymptomatic 1,2,3,5
• 1 :Serum total calcium level > 12 mg per dL (3 mmol
per L) at any time
• 2 :Bone mass T score more than 2.5 standard deviations
below age-matched controls Z score less than 2.5 :
Male <50yr or premenopause
• 3 :Impaired renal function GFR<60ml/min
• 5 :Age younger than 50
•
Osteitis fibrosa cystica
• hyperparathyroidism, which is a surplus of parathyroid hormone
from over-active parathyroid glands.
stimulates the activity of osteoclasts, cells that break down bone, in a
process known as osteoclastic bone resorption.
Osteitis fibrosa cystica
Osteitis fibrosacystica
Salt and papper appearance
Acro osteolysis
Subperiosteal resorption of radial aspect
Trabecular bone resorption
Loss of lamina dura
Familial hypocalciuric hypercalcemia (FHH)
• Autosomal dominant
• Mutation of Calcium sensing receptor
• mildly elevated PTH levels and hypercalcemia
• parathyroid surgery is ineffective in this condition.
• A calcium/creatinine clearance ratio (calculated as urine
calcium/serum calcium divided by urine creatinine/serum
creatinine) of <0.01
• family history of mild, asymptomatic hypercalcemia.
• Ectopic PTH secretion is extremely rare.
Types of Hypercalcemia Associated with Cancer.
Stewart AF. N Engl J Med 2005;352:373-379.
Pharmacologic Options for the Treatment of HypercalcemiaAGENT MODE OF ACTION INDICATION IN HYPERCALCEMIA
CAUTIONS
Normal saline 2 to 4 L IV daily for 1 to 3 days
Enhances filtration and excretion of Ca+
Moderate↑Ca++ with symptoms
Severe↑Ca++ > 14 mg per dL (3.5 mmol per L)
May exacerbate heart failure in elderly patientsLowers Ca++ by 1 to 3 mg per dL (0.25 to 0.75 mmol per L)
Furosemide (Lasix) 10 to 20 mg IV as necessary
Inhibits calcium resorption in the distal renal tubule
Following aggressive rehydration
↓K+, dehydration if used before intravascular volume is restored
Bisphosphonates
Pamidronate(Aredia), 60 to 90 mg IV over 4 hoursZoledronic acid (Zometa), 4 mg IV over 15 minutes
Inhibits osteoclast action and bone resorption
Hypercalcemia of malignancy
Nephrotoxicity, ↓Ca++, ↓PO4, rebound↑Ca++ in hyperparathyroidismMaximal effects at 72 hours
Calcitonin (Calcimaror Miacalcin) 4 to 8 IU per kg IM or SQ every 6 hours for 24 hours
Inhibits bone resorption, augments Ca++
Initial treatment (after rehydration) in severe/Ca++excretion
Rebound↑Ca++ after 24 hours, vomiting, cramps, flushingRapid↑Ca++ within 2 to 6 hours
Pharmacologic Therapy for Hypercalcemia Associated with Cancer.
Stewart AF. N Engl J Med 2005;352:373-379.