causes of hypercalcaemia i hyperparathyroidism malignancy

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 )

TYPES OF HPT

• Primary• Secondary• (Tertiary)

• Primary• Renal

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