Topic : Hypercalcemia

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


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




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.

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Topic : Hypercalcemia