Calcium Disorders

Dr. Sohail InamConsultant Endocrine & Diabetes

Prince Sultan Military Medical CityRiyadh

Calcium

Major intracellular ionImportant for cellular function– Intracellular signaling– Muscle action potential– Hormone secretion– Coagulation cascade

Major store is the bone (90%)

Calcium

Serum calcium is tightly regulatedNormal total Ca 2.2-2.5 mmol/l (8.5-10 md/dl)– Ionized (free)– Bound (Albumin and other proteins)

Corrected calcium for albumin

SerumCalcium

Urine calcium

300

100

600

600

980010000

1000

Dietary Calcium

FecalCalcium

800

200 Valuesmg/day

Regulation of calcium

Parathyroid hormoneVitamin DCalcitonin

Parathyroid gland

PTH

CalciumPhosphate

Reabsorbs CalciumExcretes Phosphate

Activates 1 alpha hydroxylase25 OH D3 → 1,25 Dihydoxy D3

PTH

• Stimulation– Hypocalcaemia & hypomagnesaemia– Decrease 1,25 D3– Hyperphosphatemia– adrenergic stimulation

• Inhibition– Hypercalcemia– Increased 1,25 D3– Hypophosphatemia

Vitamin D

291-315 nm

Vitamin D

25 OH D

1,25 dihydroxy D

↑Calcium↑Phosphate

↑AbsorptionCalcium

Phosphate

25 hydroxylase

1 alpha hydroxylase

1 alpha Hydroxylase

Activation– PTH– Low phosphate– Low calcium– IGF 1

Inhibition– 1,25 (OH)2 D3– High phosphate & High calcium– FGF23

Calcitonin

Inhibits release of Ca from boneIncreases Ca excretion by the kidneyStimulated by increase in Ca levels

Ca x PO4

PTH1,25-D3

SerumCalcium

Urine calcium

PTH1,25-D3

1,25-D3

CT

HYPOCALCEMIA

HypocalcemiaCauses

Hypoparathyroidism– Autoimmune– Surgical damage– Radiation damage– Infiltrative

Psudohypoparathyroidism (PTH resistance)CaSR mutation

HypocalcemiaCauses

Vitamin D– Deficiency– Inability to activate Vitamin D– Resistance

Renal diseaseMagnesium deficiency– Decrease PTH release– PTH resistance

HypocalcemiaCauses

Calcium sequestration– Pancreatitis– Osteoblastic metastasis– High phosphate– Hungry bone disease

DrugsCritical illness

HypocalcemiaSymptoms

Paresthesia– Peri-oral– Limbs

Muscle cramps & carpopedal spasmSeizuresLaryngeal spasmCardiac Psychiatric

HypocalcemiaSigns

Tetany– Carpopedal spasm– Chvestok’s sign– Trousseau's sign

PapilledemaCataractsExtrapyramidal ECG- Prolonged QTc

Investigations

Corrected calciumPhosphateAlkaline phosphataseRenal functionParathyroid hormoneVitamin DMagnesium

Hypocalcemia

PTH Low• Hypoparathyroidism• CaSR mutations• Magnesium deficiency• Hungry bone syndrome

PTH High• Vitamin D disorders• Renal disease• PTH resistance• Ca sequestration• Sepsis• Drugs• Magnesium deficiency

Hypocalcemia

Phosphate, Alkaline Phosphatase, Magnesium, Creatinine, Vitamin D

PTH

High Normal or low

↑ Phosphate ↓ Phosphate ↑ Phosphate ↓ Phosphate

Renal failurePTH resistance

Rhabdomyolysis

Vitamin D disorders HypoparathyroidismCaSR mutations

Hungry bone

Treatment

Severe symptomatic hypocalcemia– IV calcium (slow infusion)

Mild symptoms– Oral calcium

Vitamin D– Active form– Inactive form

TreatmentSpecific

MagnesiumHypoparathyroidism– Active form of vitamin D– PTH replacement

Renal failure– Phosphate binders– Active form of Vitamin D

HYPERCALCEMIA

HypercalcemiaMechanisms

Excess PTH hormonePTHrP– Tumors (Malignancy)– Pregnancy & lactation

Vitamin D mediated– Intoxication– Granulomatous disease– Hematological malignancies

HypercalcemiaMechsnisms

Excess Ca absorption (Milk Alkali)Increased osteoclast activation– Cytokines– Immobilization– Adrenal insufficiency– Thyrotoxicosis

↑ SerumCalcium

Urine calcium

Causes

HyperparathyroidismMalignancyVitamin D intoxicationMilk Alkali syndromeGranulomatous diseasesEndocrine

Causes

ImmobilizationDrugsParenteral nutritionFamilial hypocalciuric hypercalcemia

Clinical features

Polyuria & polydipsiaGIT– Anorexia– Abdominal pain– Constipation

NeuropsychiatricMusculoskeletal

Clinical features

Renal dysfunction– Nephrocalcinosis– Nephrolithiasis– Renal tubular acidosis

Cardiovascular– Arrthymias– Cardiac arrest

Hypercalcemia

High PTH• Hyperparathyroidism• Ectopic PTH secretion• FHH• Drugs

Low PTH• Malignancy• Vitamin D excess• Immobilization• Milk Alkali Syndrome• Granulomatous disease• Endocrine

Hypercalcemia

Confirm on repeat sample

Measure PTH

Normal or ↑ PTH

24 hour urineCalcium & creatinine

FHH Hyperparathyroidism

Low PTH (<20pg/ml)

MeasurePTHrP, Vit D metabolites, TFT

CXR, CT scan, Myeloma

Clinical evaluation & medication history

low Normalor high

HypercalcemiaPrinciples of Therapy

Increase renal Ca excretion– Saline diuresis (± frusemide)– Calcitonin– Dialysis

Reduce Ca efflux from bone– Calcitonin– Bisphosphonates– Denusamab

Treat underling cause

Treatment

Mild hypercalcemia (Ca <3)– Treat underlying cause

Moderate hypercalcemia (Ca 3-3.49)– Hydration– Bisphosphonate– Treat underlying cause

Treatment

Severe Hypercalcemia (severe symptoms, Ca>3.5)– IV hydration 0.9% NaCl– Calcitonin– Bisphosphonates– Low calcium bath dialysis– Treat underlying cause

Specific Treatment

Hyperparathyroidism– Surgery– Non-surgical ablation– Conservative approach– Calcimimetics

Steroids– Hematological malignancies– Vitamin D intoxication

Thank You