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CAUSES OF HYPERCALCAEMIA I. Hyperparathyroidism Malignancy. CAUSES OF HYPERCALCAEMIA II. Vitamin D intoxicosis Sarcoid TB Hyperthyroidism. CAUSES OF HYPERCALCAEMIA III. Rare: Addison’s disease milk-alkali syndrome acute renal failure phaeochromocytoma Vipoma thiazide diuretics
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CAUSES OF HYPERCALCAEMIA I • Hyperparathyroidism • Malignancy
CAUSES OF HYPERCALCAEMIA II • Vitamin D intoxicosis • Sarcoid • TB • Hyperthyroidism
CAUSES OF HYPERCALCAEMIA III • Rare: • Addison’s disease • milk-alkali syndrome • acute renal failure • phaeochromocytoma • Vipoma • thiazide diuretics • immobilisation • idiopathic hypercalcaemia of infancy
SYMPTOMS OF HYPERCALCAEMIA • lethargy & tiredness • polyuria, nocturia and polydipsia • nausea, vomiting and constipation • proximal muscle weakness • drowsiness, psychosis, coma • symptoms from renal calculi
PATHOPHYSIOLOGY OF HYPERCALCAEMIA I • Abnormal Bone Turnover: • Metastases • Thyrotoxicosis • Hyperparathyroidism • (Parathyroid hormone – related peptide)
PATHOPHYSIOLOGY OF HYPERCALCAEMIA II • Renal calcium retention: • PTH • PTH related – peptide • Raised serum calcium impairs glomerular filtration • Vomiting may lead to dehydration
PATHOPHYSIOLOGY OF HYPERCALCAEMIA III • Intestinal calcium absorption • increased levels of Vitamin D • sarcoid • TB • ectopic Vitamin D in acute lymphatic leukaemia
PRIMARY HPT – DIAGNOSIS • Hypercalcaemia • Inappropriate PTH • High 24H urinary calcium
FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA (FHH) • Normal or slightly raised PTH • High calcium • Low 24H urinary calcium • Mild HPT symptoms • No renal stones or bone disease • Recurrent pancreatitis • Autosomal dominant inheritance • No treatment available • Rarely infantile severe hypercalcaemia
CLUES TO THE DIAGNOSIS OF HYPERCALCAEMIA OF MALIGNANCY I • History: • weight loss • haemoptysis or haematuria • Examination: • lymphadenopathy • palpable mass
CLUES TO THE DIAGNOSIS OF HYPERCALCAEMIA OF MALIGNANCY II • Investigation: • anaemia • raised viscosity • low albumin • high globulin • abnormal LFTs • abnormal CXR
TREATMENT OF HYPERCALCAEMIA OF MALIGNANCY • Greater than 3.5 mmol/l – metabolic emergency • Treat underlying disease • Adequate hydration (6-8 litres per day) • Diphosphonates • Calcitonin • Corticosteroids (Reticulo-endothelial )
Primary Secondary (Tertiary) Primary Renal TYPES OF HPT
CAUSES OF PRIMARY HPT • Single adenoma 85% • Hyperplasia 10% • More than one adenoma 5% • Carcinoma less than 1%
PRIMARY HPT • 3 : 1 Female : Male • Greater than 50 years • 80% of asymptomatic non hospital patients • 270 new cases per million population per year • (150 per year in Gloucestershire)
LOCALISATION IN HPT • Surgeon • Ultrasound • MRI • Sestamibi • Selective venous sampling
MINIMALLY INVASIVE PARATHYROIDECTOMY • Pre-operative USS skin marking • Intra-operative PTH assay (EDTA bottle) • Intra-operative frozen section • 2 cm skin incision at marked site dissecting lateral to strap muscles
NON-SURGICAL THERAPEUTIC INTERVENTIONAL PROCEDURES • Selective arterial catheterisation and tumour ablation using angiographic contrast (65%) • Ultrasound-guided percutaneous fine needle ethanol injection (75%) • (No response to steroids)
CINACALCET HCL (2004) • Calcimimetic ie mimics the action of calcium • Allosteric activation of calcium sensory receptors in human tissues
CINACALCET • PTH • Ca • Cognitive parameters improved
CINACALCET • Hyperplasia all 4 glands • Unsuccessful surgery • Inoperability due to co-morbidity
HYPERPARATHYROIDISM OF CHRONIC RENAL FAILURE • Unusual in adult patients not on dialysis • Parathyroid bone disease (subperiosteal erosions) • Progressive soft tissue calcification • Rising serum calcium and PTH • Uncontrolled hyperphosphataemia • Primary HPT may cause renal failure • 40% require surgery after 15 years of dialysis
Mechanism of renal hyperparathyroidism • Chronic uraemia • Reduced 1.25OH 2D3 • Increased phosphate • Increased PTH
Treatment renal hyperparathyroidism • Phosphate binders • Vitamin D supplements • Calcium receptor agonists • Total parathyroidectomy
MEN Syndromes • MEN2A Phaeochromocytoma, MTC,hyperparathyroidism • MEN2B Hyperparathyroidism uncommon but mucosal neuromas,marfanoid habitus • MEN1 Pancreatic tumours (gastrinomas, insulinomas), anterior pituitary tumours and hyperparathyroidism