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Hypercalcemia - DDX. Parathyroid relatedPrimary Hyperpara, Li tx, Familial Hypocalcuric HypercalcemiaMalignancySolid tumor, HematologicExcessive Vitamin DIntoxication, Granulomatous DiseaseHigh bone turnoverHyperthyroid, Immobilization, Vit ARenal Failure2ndary Hyperpara, Aluminum, Milk-Alk

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2. Hypercalcemia - DDX Parathyroid related Primary Hyperpara, Li tx, Familial Hypocalcuric Hypercalcemia Malignancy Solid tumor, Hematologic Excessive Vitamin D Intoxication, Granulomatous Disease High bone turnover Hyperthyroid, Immobilization, Vit A Renal Failure 2ndary Hyperpara, Aluminum, Milk-Alkali

3. Hypercalcemia Workup Calcium and Phosphorus Serum PTH obtain 1st if elevated in the setting of hypercalcemia, then hyperparathyroidism is dx If low, check PTHrP, Vitamin A & D, TSH, Cortisol, ACE, 24h urine calcium clearance, review meds.

4. Ivar Sandstrom Sweedish Medical Student Discovered Parathyroid gland In 1880 Last major organ Identified in humans

5. Parathyroid Hormone Secreted from the chief cells of the parathyroid gland as an 84 amino acid protein.

6. Calcium Receptor

7. Calcium Phos PTH Vitamin D Axis

8. Hyperparathyroid - Symptoms ~80% asymptomatic Stones (Kidneys) Calcium deposition and nephrolithiasis Urinary tract obstruction Bones Osteitis Firosa Cystica Increased osteoclasts Increased bone turnover Reduced cortical bone density Moans Fatigue, Depression, Confusion

9. Hyperparathyroid Symptoms (cont) Other N/V, Constipation, Polyuria Short QT Severe Parathyroid Crisis Renal Failure from nephrocalcinosis Coma, Cardiac Arrest

10. Primary Hyperparathyroid Causes Solitary Adenoma Parathyroid Carcinoma (rare) Multiple endocrine neoplasia (rare) Hypersecretion of PTH Hypercalcemia, HypOphosphatemia

11. Primary Hyperparathyroid Diagnosis Elevated serum PTH immunoassay (high sens), high calcium, low or normal phos (decr prox tubular reabsorption) Elevated 1,25(OH)2D (low spec) Imaging 99m-technetium sestamibi Ultrasound

12. Parathyroid Imaging

13. Primary Hyperparathyroid Treatment Surgical Indications Ca > 11.5, T-score < -2.5, renal stones Medical Replace volume Facilitate calciuresis (loop diuretics) Bisphosphonates decrease bone reabsorption. Calcitonin Hormonal Therapy Raloxifene, other SERMs Cinacalcet (not FDA approved)

14. Secondary Hyperparathyroid Vit. D deficiency Primary decreased calcium absorption in elderly Increased phosphate in acute or chronic renal failure Renal Osteodystrophy Osteomalacia (low Ca, vit D) Osteitis fibrosa cystica (high PTH) Adynamic Bone Disease (low PTH)

15. Secondary Hyperparathyroid Treatment Phos Binders Vitamin D analogs negative feedback on PTH gene transcription Limited use in setting of hypercalcemia Cinacalcet (Sensipar)

16. Tertiary Hyperparathyroid Tertiary Hyperparathyroidism is essentially secondary hyperparathyroidism that is no longer responsive to medications. Also occurs after renal transplant, where hypertrophied glands continue to oversecrete PTH (set point alteration) May require surgery

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