Hypercalcaemia

1. Hypercalcaemia

2. Calcium Metabolism • Intestine Bone kidney (2.1-2.6 mmol/l) • 97% of reservoir in bone, chronic regulation. • Kidney involved in minute to minute flux.Filters 8000mg daily. • Net intestinal absorption is 200mg daily.. • If long term calcium losses exceed net calcium absorption the deficit is resorbed from bone leading to demineralisation.

3. Calcium Metabolism - PTH • Parathyroid Hormone (PTH), 84 AA structure. Secreted from parathyroid gland in response to hypocalcemia. • Amino terminal (1-34 AA) contains the biological activity. • PTH acts on receptors in target tissues leading to stimulation of adenylaye cyclase activity.

4. Effects of PTH • Increases calcium reabsorption by the kidney. • Decreases phosphate reabsorption by the kidney. • Increases osteoclastic bone resorption.

5. Calcium Metabolism- Vitamin D • Vitamin D formed in skin(D3 or cholecalciferol) by uv light. Major source of vitamin D (90%). Also present in diet. This is the inert form • Hydroxylated in the liver to 25-OH-VitD. • Renal hydroxylation to 1,25 dihydroxy vitamin D (very active metabolite). Renal also produces 24,25 dihydroxy vit D. (inactive) • Calcium deficiency leads to 1,25 Dit D production • 1,25 vit D acts on small intestine to increase calcium absorption. • Also acts on bone to cause resorption.

6. Three forms of calcium in serum • Ionised (physiological form). • Protein-bound (50%), mainly to albumin • Complexed to citrate and phosphate(1-2%).

7. COMMON (97%) of all cases Primary Hyperparathyroidism Malignancy LESS COMMON Familial benign hypercalcaemia (FBH) Sarcoidosis Thyrotoxicosis Vitamin D poisoning Acute renal failure Causes of Hypercalcaemia

8. Causes of Hypercalcemia-RARE • Immobilisation • VIPomas • Tuberculosis • Milk-alkali syndrome • Addison’s Disease • Lithium • Thiazide diuretics • Parenteral feeding

9. Symptoms • Tiredness and lethargy • Proximal muscle weakness • Polyuria, nocturia and thirst • Nausea Vomiting and constipation • Depression, psychosis and impaired consciousness.

10. Signs • Proximal muscle weakness • Signs of Dehydration • Altered mental state.

11. Primary HPT • 500 cases/million • More common in females • Incidence increases with age • Autonomous production of PTH • Benign Adenoma • Asymptomatic pick-up.

12. Hyperparathyroidism in other syndromes (RARE) • MEN Type 1 (Parathyroid adenoma, Pituitary adenoma, and pancreatic islet cell tumours). • MEN Type 2 (Parathyroid adenoma, medullary thyroid carcinoma and phaeochromocytoma)

13. Primary HPT - Diagnosis • Persistent Hypercalcaemia. • Low serum phosphate. • High normal or elevated PTH concentration. • 24h urinary Calcium excretion • Sestemebi scan

14. Primary HPT- treatment • Parathyroidectomy. • Serum calcium should be normal within 24h. • Postoperative hypocalcaemia. • Recurrent laryngeal nerve injury.

15. Familial Benign Hypercalcaemia (FBH). • Familial, AD. Family history important. • Often come to light after failed parathyroidectomy • Benign. Asymptomatic. • Low urinary calcium excretion.

16. Hypercalcaemia of malignancy • Carcinomas of breast, lung, head and neck,renal. • Usually squamous carcinomas. • PTHrP increased • PTH normal • Low serum albumin, high ESR, anemia. • Myeloma, local bone resorption.

17. Sarcoidosis • Small numbers of patients with sarcoidosis develop hypercalcaemia. • May develop after prolonged sun exposure. • 1,25 diOH Vit D high, prodiced by alveolar macrophages. PTH is normal. • Corrected by Steroids

18. Thyrotoxicosis • Severe thyrotoxicosis • Increased calcium release from bone (Thyroxine acts on bone) • PTH is normal • Takes 4-6 weeks to resolve with antithyroid treatment • Persistent hypercalcaemia usually means concomitant HPT.