approach to hypercalcemia, causes, investigation, pathophysiology, management

approach to hypercalcemia, causes, investigation, pathophysiology, management

1. Approach to Hypercalcemia CME Guide: Dr. B. D. Jha Dr. Praveen Kumar Giri Dr . Sahana Tamrakar Presented by: Gaurav Thakuri MBBS (NEPALESE ARMY INSTITUTE OF HEALTH SCIENCES)

2. Abnormalities in Serum Calcium Level Hypercalcemia Hypocalcemia Serum total calcium level > 10.5 m g / dL < 8.5 mg/dL Symptoms ‘Stones, bones, psychiatric moans, and abdominal groans’ Twitching and muscle cramps, tingling of fingers and toes, and numbness around mouth Signs Chovstek’s sign Trousseau’s sign Symptoms and signs are due to ↑ in free ionized calcium in blood ↓ in free ionized calcium in blood

3. Causes of Hypercalcemia Increased intestinal absorption Increased renal reabsorption Increased bone resorption Excess PTH Excess PTH Excess PTHrP Excess PTHrP Excess calcitriol Excess calcitriol Excess calcitriol Excess calcium supplementation Thiazide diuretics Immobilization Milk-alkali syndrome Familial hypocalciuric hypercalcemia Multiple myeloma Acromegaly Addison's disease

4. Causes of Excess PTH I nc reas e d pr od u ction o f PT H b y p a r athyro i d glan d - h y p erparat h yro i dism Primary h y p e r p ara t h y r o i dism Secondary hyperparathyroidism Tertiary h y p e r p ara t h y r o i dism Parathyroid pathology Pathology in tissues other than parathyroid gland Autonomous hyperfunction of parathyroid gland even after correction of causes of secondary hyperparathyroidism Parathyroid hyperplasia, adenoma, and carcinoma as single entity or as a part of multiple endocrine neoplasia (MEN) Chronic renal failure Chronic renal failure after renal transplantation Vitamin D deficiency Lithium

5. Chronic Renal Failure Decrease in renal mass (small kidneys) D e cr e a se i n gl o me r u l ar fil t r ation r a te Decrease production of calcitriol ↓ filtration of phosphate leading to ↓ phosphate excretion and ↑ plasma phosphate ↓ intestinal absorption of calcium ↓ plasma calcium ↓ plasma calcium ↑ P TH rele ase b y par athy r oid g la nds (Se cond a r y h y pe rpar a t hyroi d i s m ) ↑ PTH ↓ Calcitriol ↑ Bone resorption ↓ Bone remodeling (new bone formation is stopped) leading to osteomalacia R en al o s teod y strop h y

6. Causes of Excess PTHrP Squamous cell carcinoma of lung Squamous cell carcinoma of esophagus Renal carcinoma Breast carcinoma Ovarian carcinoma Humoral hypercalcemia of malignancy Hypercalcemia in cancer patients due to elevated circulating levels of biologically active substances like PTHrP P a r a n e op l astic s y ndr ome A group of sign and symptoms caused by a biologically active substance that is produced by a tumor

7. Causes of Excess Calcitriol Excess vitamin D supplementation Increased production of calcitriol Lymphoma Granulomatous diseases Lymphoma cells produce 1  - hydroxylase Granuloma cells produce 1  - hydroxylase Sarcoidosis Tuberculosis Hist o plasmosis

8. Causes of Hypercalcemia in Malignancies (Cancers) Three mechanisms Excess PTHrP Excess calcitriol Excess osteoclastic activity Solid tumors Lymphoma Multiple myeloma due to release of paracrine factors that activate osteoclasts Skeletal metastasis from a cancer (e.g., breast cancer)

9. PRIMARY HYPERTHYROIDISM AND MALIGNANCIES ACCOUNT 90% OF CASES OF HYPERCALCEMIA

10. Causes of Hypercalcemia Increased intestinal absorption Increased renal reabsorption Increased bone resorption Excess PTH Excess PTH Excess PTHrP Excess PTHrP Excess calcitriol Excess calcitriol Excess calcitriol Excess calcium supplementation Thiazide diuretics Immobilization Milk-alkali syndrome Familial hypocalciuric hypercalcemia Multiple myeloma Acromegaly Addison's disease

11. STEP 1:CORRECT CALCIUM FOR LOW ALBUMIN

12. STEP 2: PERFORM PHYSICAL EXAM AND CHEST XRAY STEP 3: MEASURE PTH

13. TRAITS MALIGNANCY PRIMARY HYPERTHYROIDISM SEVERITY MILD TO SEVERE USUALLY MILD ONSET DAYS TO WEEKS WEEKS TO MONTHS EXAMINATION LYMPHADENOPATHY, CLUBBING NORMAL PREVALENCE COMMON AMONG INPATIENTS COMMON AMONG OUTPATIENTS CALCIUM PRESENTATION >12.5 MG/D <12.5 MG/DL

14. ECG CHANGES

15. MANAGEMENT ENSURE ADEQUATE HYDRATION PRIOR TO LASIX ADMINISTRATION LASIX IN DRIP NOT IN BOLUS

16. BISPHOSPHONATES DRUG ROUTE INDICATION S/E PAMIIDRONATE IV HYPERCALCEMIA FLU LIKE SYMP RENAL FAILURE OSTEONECROSIS MSK PAIN ZOLENDRONATE IV HYPERCALCEMIA OSTEOPOROSIS PAGETS DISEASE FLU LIKE SYMP RENAL FAILURE OSTEONECROSIS MSK PAIN ALENDRONATE PO OSTEOPOROSIS MSK PAIN ESOPHAGITIS

17. OTHERS CALCITONIN STEROIDS : PREDNISONE

18. SPECIFIC TREATMENT SURGICAL TREATMENT IN PRIMARY HYPERPARATHYROIDISM SPECIFIC TREATMENT IN CASES OF MALIGNANCY AND GRANULOMATOUS CONDOTIONS

19. •Harrison's Principles of Internal Medicine, 18th edition, Anthony S.Fauci , MD, Eugene Braunwald , MD, Dennis L. Kasper, MD, Stephen L. A step-wise approach vol II second edition Guyton and hall textbook of medical physiology 13 th edition http://www.youtube.com/@ StrongMed All images are copyright to their respective owners. All product names, logos and brands used are properties of their respective owners.