1. CAUSES OF HYPERCALCAEMIA I Hyperparathyroidism Malignancy

2. CAUSES OF HYPERCALCAEMIA II Vitamin D intoxicosis Sarcoid TB Hyperthyroidism

3. CAUSES OF HYPERCALCAEMIA III Rare: Addison’s disease milk-alkali syndrome acute renal failure phaeochromocytoma Vipoma thiazide diuretics immobilisation idiopathic hypercalcaemia of infancy

4. SYMPTOMS OF HYPERCALCAEMIA lethargy & tiredness polyuria, nocturia and polydipsia nausea, vomiting and constipation proximal muscle weakness drowsiness, psychosis, coma symptoms from renal calculi

6. PATHOPHYSIOLOGY OF HYPERCALCAEMIA I Abnormal Bone Turnover: Metastases Thyrotoxicosis Hyperparathyroidism (Parathyroid hormone – related peptide)

7. PATHOPHYSIOLOGY OF HYPERCALCAEMIA II Renal calcium retention: PTH PTH related – peptide Raised serum calcium impairs glomerular filtration Vomiting may lead to dehydration

8. PATHOPHYSIOLOGY OF HYPERCALCAEMIA III Intestinal calcium absorption increased levels of Vitamin D sarcoid TB ectopic Vitamin D in acute lymphatic leukaemia

9. PRIMARY HPT – DIAGNOSIS Hypercalcaemia Inappropriate PTH High 24H urinary calcium

10. 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

12. CLUES TO THE DIAGNOSIS OF HYPERCALCAEMIA OF MALIGNANCY I History: weight loss haemoptysis or haematuria Examination: lymphadenopathy palpable mass

13. CLUES TO THE DIAGNOSIS OF HYPERCALCAEMIA OF MALIGNANCY II Investigation: anaemia raised viscosity low albumin high globulin abnormal LFTs abnormal CXR

14. 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 )

15. TYPES OF HPT Primary Secondary (Tertiary) Primary Renal

16. CAUSES OF PRIMARY HPT Single adenoma 85% Hyperplasia 10% More than one adenoma 5% Carcinoma less than 1%

20. PRIMARY HPT 3 : 1Female : Male Greater than 50 years 80% of asymptomatic non hospital patients 270 new cases per million population per year (150 per year in Gloucestershire)

21. LOCALISATION IN HPT Surgeon Ultrasound MRI Sestamibi Selective venous sampling

23. 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

27. 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)

28. CINACALCET HCL (2004) Calcimimetic ie mimics the action of calcium Allosteric activation of calcium sensory receptors in human tissues

29. CINACALCET PTH Ca Cognitive parameters improved

30. CINACALCET Hyperplasia all 4 glands Unsuccessful surgery Inoperability due to co-morbidity

31. 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

32. Mechanism of renal hyperparathyroidism Chronic uraemia Reduced 1.25OH 2D3 Increased phosphate Increased PTH

33. Treatment renal hyperparathyroidism Phosphate binders Vitamin D supplements Calcium receptor agonists Total parathyroidectomy

34. MEN Syndromes MEN2A Phaeochromocytoma, MTC,hyperparathyroidism MEN2B Hyperparathyroidism uncommon but mucosal neuromas,marfanoid habitus MEN1 Pancreatic tumours (gastrinomas, insulinomas), anterior pituitary tumours and hyperparathyroidism