Overview of calcium homeostasis and disorders

1. PROF. AIHANUWA EREGIE
MBBS, MD, FMCP, FACE, FEMSON
PROFESSOR OF MEDICINE
CONSULTANT PHYSICIAN & ENDOCRINOLOGIST
UNIVERSITY OF BENIN TEACHING HOSPITAL
BENIN CITY
27th January 2023

2. PRESENTATION FORMAT
 CALCIUM : DEFINITION, REQUIREMENTS & FUNCTIONS/ ROLES
 CALCIUM HOMEOSTASIS/ CALCIUM METABOLISM
 DISORDERS OF CALCIUM METABOLISM
 HYPOCALCAEMIA & HYPOPARATHYROIDISM
 HYPERCALCAEMIA, HYPERPARATHYROIDISM & FAMILIAL HYPOCALCIURIC
HYPERCALCAEMIA
 DIAGNOSIS: CLINICAL FEATURES & INVESTIGATIONS
 TREATMENT
 COMPLICATIONS

3. CALCIUM
 Calcium: a mineral that is essential to formation and
maintenance of bones and teeth, circulatory &
cardiovascular health, nerve and brain function,
hormone release, muscle contraction and blood
clotting.
 Calcium: also acts as an enzyme activator
 Sources: Milk & Dairy products, green leafy
vegetables, Seafood , Almonds, Blackstrap molasses,
Broccoli, enriched Soy and Rice milk products, Figs,
Soybeans and Tofu.

4. DAILY REQUIREMENTS
Age (in years) Calcium Requirement
 1 – 3 500mg
 4 - 8 800mg
 9 - 18 1300mg
 19 - 50 1000mg
 51+ 1500mg
 *Pregnant and lactating women are recommended a daily
calcium intake of 1000mg.

6. CALCIUM METABOLISM
Absorption from GI tract is by passive diffusion and
active transport
Most of the calcium is reabsorbed by the kidney –
net loss is about 2%
Calcium is controlled by both PTH and Calcitonin

7. FACTORS AFFECTING CALCIUM METABOLISM
 VITAMIN D
 PARATHYROID HORMONE
 CALCITONIN
 DIET
 Dietary Fibre e.g Wheat bran could prevent calcium absorption because of its
content of Phytate
 Dietary Na & Protein: increased calcium excretion with increased intake
 Caffeine: small effect on calcium absorption - temporary increased calcium
excretion and may modestly decrease calcium absorption.
 DRUGS e.g Tetracycline, Quinolone antibiotics, Phenytoin, Thyroid
hormone, Androgens, Oestrogens, Fluoride, PGE-2, IL-1, Il-6

8. VITAMIN D METABOLISM
The active form of vitamin D is 1,25-dihydroxycholecalciferol. Its
production in the kidney is catalyzed by 1 α-hydroxylase
1 α-hydroxylase activity is increased by :
Decreased serum Ca2+
Increased PTH level
Decreased serum phosphate

9. ACTION OF 1,25-DIHYDROXYCHOLECALCIFEROL(CALCITRIOL)
 Increases intestinal Ca2+ absorption
 Increases intestinal phosphate absorption
 Increase renal reabsorption of Ca2+ and phosphate
 Increases resorption of bone

10. PARATHYROID HORMONE (PTH)
 PTH: 84-amino-acid hormone.
Secretion:
 Secretion: from the chief cells of the parathyroid glands.
Function: increases renal phosphate excretion and increases plasma calcium by
 Increasing osteoclastic resorption of bone (occurring rapidly).
 Increasing intestinal absorption of calcium (a slower response).
 Increasing synthesis of 1,25-(OH)2D3 (stimulating GIT absorption).
 Increasing renal tubular reabsorption of calcium
 Regulation
 Low serum [Ca2+] → Increased PTH secretion
 High serum [Ca2+] → Decreased PTH secretion

11. CALCITONIN
Produced by :
 thyroid C cell.
Function:
Inhibition of osteoclastic bone resorption .
Increasing the renal excretion of calcium and
phosphate.
Stimulant ??

13. FORMS OF CALCIUM
• Most Calcium: Calcium hydroxyapatite Ca10(PO4)6(OH)2.
• Calcium in the plasma:
45% in ionized form (the physiologically active form)
45% bound to proteins (predominantly albumin, the major reservoir)
10% complexed with anions (citrate, sulfate, phosphate)
• Disorders that alter plasma pH or serum albumin concentration must be considered
when circulating calcium concentrations are being evaluated.
• A decrease in albumin concentration of 1 g/dl results in a decrease in protein-bound
and hence total calcium concentration of about 0.8 mg/dl.
• The fraction of ionized calcium is inversely related to plasma pH
• Binding of calcium to albumin is strongly pH-dependent between pH 7 and pH 8; an
acute increase or decrease in pH of 0.1 pH units will increase or decrease, respectively,
protein bound calcium by about 0.12 mg/dl

14. HYPOCALCAEMIA

15. HYPOCALCAEMIA
 Total serum Calcium concentration < 8.5 mg/dL (in the
presence of normal plasma protein concentrations) OR
Ionized calcium < 4.5 mg/dL
 Hypocalcaemia: Acquired OR Hereditary

16. AETIOLOGY OF HYPOCALCAEMIA
 Decreased GI Absorption
 Poor dietary intake of calcium ,impaired absorption
 Increased Urinary Excretion
 Decreased Bone Resorption/ Increased Mineralization
 Low PTH, PTH deficiency or resistance
 Vitamin D deficiency or resistance
 Hypoalbuminaemia
 Hypomagnesaemia, Hyperphosphataemia
 Medication/ Surgical Effects

17. AETIOLOGIC CLASSIFICATION OF HYPOCALCAEMIA
 PARATHYROID HORMONE DEFICIENCY
(HYPOPARATHYROIDISM: PRIMARY OR SECONDARY)
 PARATHYROID HORMONE RECEPTOR DEFECTS
(PSEUDOHYPOPARATHYROIDISM)
 MITOCHONDRIAL DNA MUTATIONS
 MAGNESIUM DEFICIENCY
 EXOGENOUS INORGANIC PHOSPHATE EXCESS
 VITAMIN D DEFICIENCY

18. HYPOPARATHYROIDISM
 Aplasia or hypoplasia of parathyroids
 Suppression of neonatal PTH secretion due to maternal
hyperparathyroidism
 Pre-pro-parathyroid hormone gene mutation
 Ca2+-sensing receptor activating mutation
 Autoimmune Parathyroiditis
 Surgery e.g Thyroidectomy, Parathyroidectomy
 Infiltrative lesions

19. AETIOLOGY OF PRIMARY HYPOPARATHYROIDISM
Congenital malformation (e.g DiGeorge syndrome)
resulting from developmental abnormalities of the
3rd & 4th branchial arches
Parathyroid Hypoplasia or Aplasia
Autoimmunity e.g Autoimmune polyglandular
syndrome type 1, which may destroy the
parathyroid gland
PTH gene mutations

20. PSEUDOHYPOPARATHYROIDISM (PHP)
 Pseudohypoparathyroidism: autosomal dominant condition that may
present at birth or later.
 Pseudohypoparathyroidism: one of four forms, all with hypocalcaemia
and hyperphosphataemia (1a – 1c, & 2).
 Other clinical manifestations of Pseudohypoparathyroidism associated
with Albright Hereditary Osteodystrophy include short stature, stocky
body habitus, round facies, short fourth and fifth metacarpals,
calcification of the basal ganglia, subcutaneous calcification, and, often,
developmental delay.

21. PSEUDOPSEUDOHYPOPARATHYROIDISM (PPHP)
 Rare genetic disorder, usually inherited in an AD fashion from the father
(genomic imprinting)
 Genetic changes in the GNAS gene
 Features (Similar to PHP 1a, which is inherited AD, from Mother; main
difference is resistance to PTH and Obesity); PHPP has normal Ca homeostasis
 Short stature
 Round face
 Short metacarpals, hardening of joints and soft tissues


22. COMPARISON OF FEATURES OF PSEUDOHYPOPARATHYROIDISM (PHP)
AND PSEUDOPSEUDOHYPOPARATHYROIDISM (PPHP) contd.
AHO = Albright’s Hereditary Osteodystrophy
PTH = parathyroid hormone
NL = normal
R = receptor
Gs alpha = alpha subunit of the stimulatory guanine nucleotide binding
protein
+ means present; - means decreased
PHP = Pseudohypoparathyroidism;
PPHP = Pseudopseudohypoparathyroidism

23. COMPARISON OF FEATURES OF PSEUDOHYPOPARATHYROIDISM
(PHP) AND PSEUDOPSEUDOHYPOPARATHYROIDISM (PPHP)
PHP 1a PHP 1b PHP 2 PPHP
AHO + - - -
Serum calcium ↓ ↓ ↓ NL
cAMP Response to PTH ↓ ↓ ↓ NL
Urinary Phosphate ↓ ↓ (↓) NL NL
Response to PTH
Hormone Resistance PTH, TSH and other
Gs-alpha coupled
hormones
PTH target tissues
only
PTH target tissues
only
None
Molecular Defect Reduced functional
Gs-alpha levels
Abnormalities in Gs-
alpha gene
transcription
Unknown Gs-alpha

24. CALCIUM DEFICIENCY DISEASES
Rickets : softening of bones in children, potentially leading to fractures and
deformity. The predominant cause is Vitamin D deficiency; lack of calcium
in the diet may also lead to Rickets
 Osteomalacia: softening of the bones due to defective bone
mineralization; signs = diffuse body pains, bone fragility. Common cause =
Vitamin D def, which is normally obtained from the diet and/or sunlight
exposure
Osteoporosis: characterized by low bone mass & structural deterioration of
bone tissue, leading to bone fragility & increased risk of fractures of the hip,
spine and wrist. Men as well as women are affected by osteoporosis. Women
are more affected

25. CLINICAL FEATURES OF HYPOCALCAEMIA
 CNS: Confusion, disorientation, irritability, hallucinations, extrapyramidal
manifestations, dementia, overt psychosis, paraesthesiae, perioral anaesthesia,
movement abnormalities (e.g Choreoathetosis, Dystonic spasm,
Parkinsonism, Hemiballismus)
 Neuromuscular: Smooth & skeletal muscle contractions/ cramps, carpopedal
spasms (tetany), laryngospasms
 Head & Neck: Scar on the neck, subcapsular cataracts, papilloedema
 RS: Inspiratory or expiratory wheeze, laryngeal stridor, bronchospasms
 GIT: Dysphagia, biliary & intestinal colic
 CVS: Tachycardia, Bradycardia, S3, signs of Heart Failure
 Skin & its appendages: Coarse hair/ alopecia, dry skin, psoriatic patches,
eczema
 Positive Chvostek & Trousseau signs

26. DIAGNOSIS OF HYPOCALCAEMIA
 Serum Albumin (low levels cause reduced total Ca but not ionized): 1g/ dL
reduction in Albumin reduces total Ca by 0.8mg/ dL [Causes of false low Ca
include Heparin, Oxalate, Citrate & Hyperbilirubinaemia)
 ** Preferably measure Ionized Calcium
 Corrected Ca (mg/dL) = Measured total Ca (mg/dL) + 0.8 (4.0 – Serum Albumin
[g/dL]), where 4.0 represents the average albumin level
 E/U/Cr: low Ca & elevated phosphates seen in Hypoparathyroidism or
Pseudohypoparathyroidism; low Ca, high phosphate & PTH in Renal failure;
measure Mg
 LFTs: normal or slightly decreased AlkPhos in PTH def; increased in Osteomalacia
& Rickets. (Bone biopsy Osteomalacia)

27. DIAGNOSIS OF HYPOCALCAEMIA contd.
 PTH LEVELS: low- normal levels in Hereditary or Acquired Hypoparathyroidism
& severe Hypomagnesaemia
 Vitamin D Metabolites: Low 25(oh) Din Vit D def from poor intake, lack of
exposure to sunlight & Malabsorption & low 1, 25 (OH)2 D assoc. with high PTH
suggests ineffective PTH due to lack of Vit. D as in CRF, Vit D dependent Rickets
type 1 & Pseudohypoparathyroidism
 ECG: Prolonged QT, ventricular arrythmias
 IMAGING STUDIES: plain X-rays (Looser zones in pubic rami, ribs & upper
femur in Rickets & Osteomalacia) ,Osteoblastic metastasis ; CT scans (basal
ganglia calcification in Idiopathic Hypoparathyroidism)

28. DIFFERENTIAL DIAGNOSES
 ACUTE KIDNEY INJURY
 ACUTE PANCREATITIS
 HYPERPARATHYROIDISM
 HYPERPHOSPHATAEMIA
 HYPOPARATHYROIDISM
 HYPOMAGNESAEMIA
 METABOLIC ALKALOSIS
 HYPOALBUMINAEMIA

29. MANAGEMENT OF HYPOCALCAEMIA
 MILD: Oral repletion with elemental calcium 1 – 3g/dL in otherwise healthy
asymptomatic adults
 SEVERE
 Supportive treatment: IV fluid replacement, Oxygen therapy etc.
 IV replacement in symptomatic/ severe hypocalcaemia with Cardiac arrhythmias or
Tetany: Give 100 – 300mg of elemental Calcium in 50 – 100ml in 5% D/W over 5 – 10
minutes – raises Ionized Ca to 0.5 – 1.5 mmol & should last 1- 2 hours [10 ml Ca
Gluconate contains 90mg elemental Ca; 10 ml Ca Chloride contains 272 mg
elemental Ca. Use IV Ca Chloride with caution, preferably via a central vein. Measure
serum Ca 4 – 6 hrly.] to maintain Ca levels 8 – 9 mg/dL]
 Continuous ECG monitoring
 Start Oral Ca & Vit. D early

30. MANAGEMENT OF HYPOCALCAEMIA contd.
 CHRONIC: treatment depends on the cause
 Hypoparathyroidism & Pseudohypoparathyroidism: Oral Ca Supplements,
Thiazides
 Nutritional Vit D def 2o poor sun exposure or oral intake: UV or sunlight
exposure
 Nutritional Rickets: Vit D2
 Vit D def: Increase Dietary Calcium > 1000mg/ day
 CKD & Hypocalcaemia: Reduce dietary intake to 400 – 800mg/ day to
prevent Hyperphosphataemia
 Severe Hypoparathyroidism: 0.5 – 2 mcg Calcitriol or 1-alpha hydroxyvitamin
D3.
 Recombinant human parathyroid hormone (rhPTH) as adjunct to Calcium &
Vit D

31. Long-term treatment of Hypoparathyroidism
involves administering vitamin D, preferably as
1,25-dihydroxyvitamin D, and calcium.
Therapy is adjusted to keep the serum calcium in
the lower half of the normal range to avoid
episodes of hypercalcemia that might produce
Nephrocalcinosis and to avoid Pancreatitis.

32. HYPERCALCAEMIA

33. DEFINITION
 Hypercalcaemia: corrected total serum calcium value above the
upper limit of the normal range or an elevated ionized calcium
value.
 The skeleton contains 99% of total body calcium. The remaining
1% circulates through out the body.
 Among circulating calcium, 50% is free (ionized), 40% protein-
bound, and 10% complexed to phosphate, citrate, bicarbonate,
sulfate, and lactate. Only elevations in the free calcium are
associated with symptoms and signs

34. CLASSIFICATION
 According to level of corrected total serum calcium
 Mild Hypercalcaemia: >10.5 mg/dL - <12 mg/dL [2.6 –
2.9mmol/L]
 Moderate Hypercalcaemia: 12 to 14 mg/dL [3.0 – 3.4 mmol/L]
 Severe Hypercalcaemia >14 mg/dL [> 3.4 mmol/L]
Corrected Calcium = (4.0 mg/dL – [Serum Albumin]) x 0.8 +
[Observed Calcium] Normal 8 – 10mg/ dL
Calcium levels 2.2-2.6 mmol/L
Adjusted Calcium levels (40-albumin) x 0.02 + albumin

35. AETIOPATHOGENESIS
 ↑ PTH release – Primary Hyperparathyroidism, Paraneoplastic syndrome,
CRF
 ↑ bone breakdown – Paget’s Disease, Malignancy, Thyrotoxicosis,
Immobilization
 ↑ Ca2+ ingestion – Milk-alkali syndrome
 Iatrogenic – Vitamin D, Lithium, Thiazide diuretics, cuffed sample
 Increased absorption – Adrenal gland failure
 Ectopic production of Calcitriol – Granulomatous disease (TB, Sarcoidosis)
 ↓ blood volume - Dehydration

36. AETIOLOGY
 PRIMARY HYPERPARATHYROIDISM: most common cause in OPD
 MALIGNANCY-ASSOCIATED HYPERCALCAEMIA e.g Paraneoplastic syndrome
(PTHrP), Squamous cell CA of lungs, head & Neck, bony metastasis, Renal Cell &
Breast CA, Multiple Myeloma, Lymphoma; most common cause in in-patients
 Calcium & Vitamin D (Hypervitaminosis D) over-supplementation
 Sarcoidosis & other granulomatous disorders
 ENDOCRINOPATHIES/ ENDOCRINE TUMOURS: Thyrotoxicosis, Adrenal
Insufficiency,. Phaeochromocytoma ( associated with MEN-2), VIPomas.
 Drugs: Thiazides, Lithium, Oestrogen, Tamoxifen & Indapamide
 Hypervitaminosis A
 Milk Alkali Syndrome (Rare nowadays)
 Immobilization, Dehydration
 Acute Renal Failure due to Rhabdomyolysis; Chronic Renal Failure
 Familial benign hypocalciuric hypercalcaemia
 Paget’s disease
 Cuffed specimen

37. HYPERPARATHYROIDISM.
Hyperparathyroidism: two major forms viz
Primary: most common cause of hypercalcaemia,
represents autonomous production of PTH.
Secondary: caused by any chronic condition associated
with chronic depression in the calcium levels
Tertiary: rarely occurs

38. PRIMARY HYPERPARATHYROIDISM
 Most common cause in the outpatient setting
 Renal calculi seen in 15-20%
 Classic bone disease (brown tumours, osteitis fibrosa cystica,
subperiosteal resorption) is rarely seen
 Increased risk for vertebral fractures

39. FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA (FHH)
 Rare, autosomal dominant condition, caused by an inactivating
disorder of calcium-sensing receptors (CaSR); 3 subtypes (1 – 3)
 PTH normal to mildly elevated, mild hypercalcaemia
 Fractional excretion of calcium is lower than 1%, despite
hypercalcaemia.
 Genetic testing is not often required
 ClCa / ClCr= (Uca X SCr) X (Sca X UCr)
 A ratio of 0.01 or less is typically with FHH

40. FEATURES OF HYPERCALCAEMIA: “Bones, Stones, Groans, Moans,
Thrones & Psychic overtones”
• CNS
• GI
• SKELETON
• KIDNEY
STONES BONES
GROANS
MOANS

41. “Bones, Stones, Groans, Moans, Thrones & Psychic
overtones”
 Bones: Bone pains, Osteoporosis, Osteomalacia, Arthritis.
Pathological Fracture
 Stones: Renal Stones
 Moans: Fatigue, Malaise
 Thrones: Polydipsia, Polyuria, Constipation (sitting on the
toilet as on a throne)
 Psychic overtones: Lethargy, Confusion, Depression,
Memory loss

43. FEATURES OF HYPERCALCAEMIA
 Asymptomatic.
 Polyuria, Polydipsia, Pyrexia
 CNS effects: Lethargy, confusion, depression, anxiety, disorientation, cognitive
dysfunction, psychosis, ataxia, stupor, coma
 Neuromuscular & Skeletal effects: Weakness, muscle twitching, proximal
myopathy, hypertonia, bone pains, fractures, arthritis, Osteoporosis, Osteitis
fibrosa cystica
 CV effects: Hypertension, bradycardia (& eventually asystole)
 Renal effects: Stones, decreased GFR, polyuria, Nephrocalcinosis
 GIT effects: Nausea, vomiting, constipation, anorexia , Pancreatitis, abdominal
pain, peptic ulcers
 Eye findings: e.g. Band Keratopathy
 Systemic metastatic calcification.

44. CARDIOVASCULAR SYSTEM
 Increases myocardial contractility and irritability
 Shortened QT interval
 Prolonged PR
 Wide QRS complexes
 Calcium deposition in coronary arteries and
myocardial fibers
 Hypertension

45. INVESTIGATIONS
 General:
 Serum Calcium [corrected Ca; r/o severe acidosis or alkalosis
(measure ionised Ca) or dehydration], Phosphate, Alkaline
phosphatase
 Parathyroid Hormone
 Vitamin-D
 Total protein & Albumin
 ECG: short QT interval, J waves, widening T waves
 Specific : vary according to cause e.g. E/U/Cr, USS, AXR, CT, MRI,
DEXA, Sestamibi Scan + SPECT etc.

46. INVESTIGATIONS contd.
 True Hypercalcaemia: measure PTH
 If PTH high or inappropriately normal for the serum Ca level,
suspect
 Primary Hyperparathyroidism
 Tertiary Hyperparathyroidism
 Familial Hypocalciuric Hypercalcemia (FHH)
 Lithium-associated Hypercalcaemia
 Ectopic PTH secretion – rare

47. INVESTIGATIONS contd.
 If PTH suppressed, consider
 History of malignancy – malignancy associated hypercalcaemia
 Humoral Hypercalcaemia of malignancy [PTH –related peptide(PTHrP)]
 • 1,25 (OH)2 D (haematologic malignancies)
 • Osteolytic metastases
 • Multiple myeloma

48. INVESTIGATIONS contd.
 If PTH suppressed & no history/suspicion of malignancy: Measure 25
(OH)Vit D & 1,25 (OH)2 Vit D
 Increased 25 (OH) Vit D: Vitamin D intoxication
 Increased 1,25 (OH)2 Vit D: Granulomatous disease
 Normal vitamin D
 Milk- alkali Syndrome (Ca supplementation)
 Hypervitaminosis A
 Hyperthyroidism
 Adrenal insufficiency
 Others

49. GENERAL PRINCIPLES OF TREATMENT
 Aim: Lower Serum Calcium; Treat underlying cause
 Correction of dehydration/volume depletion
 Correction of any electrolyte abnormalities
 Discontinuation of medications that may cause calcium
elevation
 Reduction of dietary calcium in states of intestinal
hyperabsorption (vitamin D intoxication and milk alkali)
 Weight bearing or mobilization

50. TREATMENT OF MILD HYPERCALCEAMIA
 Mild Hypercalcaemia
 Adequate hydration (at least 6 – 8 glasses of water/ day) to
minimize risk of Nephrolithiasis.
 Avoid aggravating factors e.g. thiazide diuretics, volume depletion,
prolonged bed rest or inactivity, and a high calcium diet (>1000
mg/day).
 D/C Calcium Supplements
 Additional therapy depends mostly upon the cause of the
hypercalcaemia
 Asymptomatic or mildly symptomatic patients do not require
immediate treatment

51. TREATMENT OF MODERATE HYPERCALCAEMIA
 Moderate Hypercalcaemia
 Asymptomatic or mildly symptomatic individuals with chronic
moderate hypercalcemia (calcium between 12 and 14 mg/dL) may
not require immediate therapy.
 It is important to note that an acute rise to these concentrations
may cause marked changes in sensorium, which requires more
aggressive therapy.
 In these patients, treatment with saline hydration and
Bisphosphonates

52. TREATMENT OF SEVERE HYPERGLYCAEMIA
 Severe hypercalcaemia: aggressive therapy.
 Volume expansion with isotonic saline at an initial rate of 200 to 300
mL/hour; adjust to maintain urine output at 100 to 150 mL/hour.
 In the absence of RF or HF, do not use loop diuretics to directly increase
calcium excretion, because of potential complications.
 Salmon Calcitonin (4 IU/kg), can be repeated every 6 to 12 hours (4 to 8
IU/kg).; repeat serum Ca after several hours.
 Bisphosphonates: Zoledronic acid (ZA; 4 mg intravenously [IV] over 15
minutes) or Pamidronate (60 to 90 mg over two hours), [preferably ZA
for its superiority in reversing hypercalcaemia related to malignancy.]
 Calcimimetics: Cinacalcet, Etelcalcetide

53. TREATMENT contd.
 Calcitonin + IV saline: substantial reduction in Ca within 12 - 48 hours.
 Bisphosphonates: effective 2nd – 4th day, thereby maintaining control of the
hypercalcaemia: reduce dose in renal impairment
 Additional, more aggressive measures are necessary in the rare patient with
very severe, symptomatic hypercalcemia
 IV Denosumab: SC 120mg q. 4 weeks. Useful in malignancy-associated
hypercalcaemia and in those refractory to Bisphosphonates; associated with
risk of Osteonecrosis of the jaw and thigh fractures
 Dialysis (in addition to the above Rx): HD or PD for Ca 18 - 20 mg/dL +
neurologic symptoms but a stable circulation OR in those with severe
hypercalcaemia complicated by renal failure.
 Surgery

54. Intervention Mode of Action Onset of
Action
Duration of Action
Isotonic Saline Restores Intravascular Volume, increases urinary Ca excretion Hours During Infusion
Calcitonin Inhibits bone resorption 4 – 6 hours 48 hours* (limited
efficacy, tachyphylaxis)
Bisphosphonates Inhibits bone resorption by interfering with osteoclast
recruitment and function
24 – 72
hours
2 – 4 weeks
Loop Diuretics Increases urinary calcium excretion by inhibition of calcium
reabsorption in the Loop of Henle
Hours During therapy (not for
routine use; prevent
fluid overload in HF/
CKD pts.)
Glucocorticoids Decreases intestinal calcium absorption, decreases
production of 1,25 (OH)2 Vit D by activated mononuclear
cells in patients with Lymphoma or Granulomatous diseases
2 – 5 days Varied duration (days –
weeks)
Denosumab Inhibits bone resorption via inhibition of Receptor Activator
of Nuclear factor Kappa-B Ligand (RANKL)
4 – 10 days 4 – 15 weeks
Calcimimetics
e.g Cinacalcet,
Etelcalcetide
Calcium-sensing receptor agonists, reduces PTH (Parathyroid
Cancer, Secondary Hyperparathyroidism in CKD)
2 – 3 days During therapy
Dialysis Removes Calcium (use a low or no calcium dialysate) Hours Reduction during
dialysis

55. THERAPY DOSE ROUTE MONITOR/ COMMENT
NORMAL SALINE 200 – 300ml/hr IV Cardiopulmonary function, CVP, CXR
FRUSEMIDE 20-80 mg q. 2-4 hr OR 40 mg/h
CI
IV Serum & urine electrolytes. Replace K,
Mg, & PO4 based on serum levels &
urinary losses
SALMON CALCITONIN 4-8 IU/kg q. 6-12 hr IM, Sc Allergic rxn. 1 IU intradermally b4 Rx.
Effective only in the 1st 48-72 hrs.
ZOLEDRONATE 4 mg IV q. 15 min every 2-4 wks
PRN
IV Malignancy-assoc. hypercalcaemia.
Caution:
CKD & Myeloma.
CINACALCET 30-90 mg b.i.d.- q.i.d. PO (with
meals)
PTH, Ca, PO4 at least 12 hrs after dose.
GALLIUM NITRATE 200 mg/m2/day CI over 4 hrs ;
PRN x 5/7 days
IV Avoid in RF. Monitor Cr, PO4, & CBC.
DIALYSIS Low or no calcium dialysate HD or PD Crisis or refractory cases. Useful in RF

56. Therapy Advantages Limitations
CALCITONIN Safe, nontoxic; rapid Ca lowering by
max. 1 - 2 mg/dL (0.3 - 0.5 mmol/L) in
4 – 6 hrs. Most useful with hydration.
Efficacy: limited to the 1st 48hrs hours, even
with repeated doses, (tachyphylaxis, perhaps
due to receptor downregulation.)
BISPHOSPHONATES Effective: Rx of hypercalcaemia
resulting from excessive bone
resorption of any cause. More potent
than Calcitonin & Saline in Rx of
Moderate or Severe hypercalcemia.
Their maximum effect occurs in 2 - 4 days;
usually given in conjunction with saline and/or
Calcitonin, which reduce calcium concentration
more rapidly. Bisphosphonates have potential
nephrotoxicity.

57. GLUCOCORTICOIDS
 Vitamin D intoxication or endogenous production of Calcitriol
(Sarcoidosis, TB)
 Prednisone 20-40 mg
 Lowers calcium in 2-5 days

58. COMPLICATIONS
 Renal –Nephrocalcinosis, Renal failure
 GI - Peptic ulcer disease, Pancreatitis, Constipation
 Neuro - Corneal calcification, Confusion, Depression, Dementia,
Paraesthesiae, Syncope & Coma
 Cardiac – Arrhythmias, Cardiac failure
 MSK – Bone pain, Osteoporosis & Fractures
 Death

59. DIFFERENTIAL DIAGNOSIS OF HYPERCALCAEMIA
Hypermagnesaemia
Hyperphosphataemia

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