Hypercalcemia

1. Physiology Hypercalcemia Hyperparathyroidism Hypocalcemia Hypoparathyroidism

2. Hormones/Peptides that impact on Bone Health PTH Vitamin D Calcitonin

3. 25 hydroxylase D3 1,25, Dihydroxy D3 Increases absorption of Ca in GI tract PTH Stimulates Osteoblasts (anabolic) Stimulates Osteoclasts (catabolic) Stimulates renal 1 alpha hydroxylase Decreases renal tubular re absorption of Phosphorus *phosphaturia

4. Calcitonin Inhibits Osteoclasts No effect on GI tract Decreases renal tubular re absorption of calcium (Calciuria)

5. 1, 25 Di(OH) D3 For calcification of osteoid to form bone Increases calcium absorption from the GI tract Decreases renal tubular re absorption of calcium and Phosphorus (phosphaturia and calciuria)

6. PTH Calcitonin 1,25 (OH)2 D3 Promotes calcification of osteoid Bone Resorption Increases calcium and Phosphorus excretion Phosphaturia Increases calcium reabsorption Increases calcium excretion Renal No direct action Indirectly through 1,25,(0H) 2 D3 Gut calcium absorption None

7. Low calcium Increases PTH High calcium Decreases PTH Control of PTH secretion Ambient calcium level

8. High PO4 Increases PTH Control of PTH secretion Ambient Phosphorus level

9. Decreases PTH Low Mag Control of PTH secretion Ambient Magnesium level

10. Physiology Hypercalcemia Hyperparathyroidism Hypocalcemia Hypoparathyroidism

11. A 54 year old woman is found to have a serum calcium level of 10.6 on routine screening. She is totally asymptomatic. She has a history of hypertension. The only medications she takes are lisinopril and simvastatin. She has had no history of renal stones in the past. The repeat calcium level is 10.5 mg. The albumin is 4.2 mg and the liver function, alkaline phos and CMP are normal. You would recommend which of the following? A. Serum phosphorus level B. Intact PTH level. C. 25 hydroxy vitamin D3 level D. Isotopic bone scan E. 24 hour urine for phosphorus

12. Hypercalcemia Confirm by repeat testing Correct for albumin if necessary Check renal function Look for background medications HCT Lithium calcium vitamin D vitamin A Obtain Intact PTH level

13. Hypercalcemia NORMAL HIGH LOW Malignancy Primary HP Lithium FHH ESRD Sarcoid Vit D excess Hyperthyroidism Intact PTH

14. Hypercalcemia in malignancy 1. Metastases to bones 2. Humoral hypercalcemia of cancer 3. Concomitant hyperparathyroidism

15. Humoral Hypercalcemia of cancer Bone resorbing peptides secreted by neoplasms in the absence of bone mets Several humoral factors PTHrP Osteoclastic activating factor 1,25-Dihydroxy cholecalciferol Prostglandins PTH Usual life expentancy- 2 to 6 months

16. High calcium Very Low PTH < 20 pg Causes of Non Parathyroid mediated Hypercalcemia Malignant disease Mutiple myeloma Sarcoidosis Excessive calcium intake Hypervitaminosis D Hyperthyroidism Addison’s disease

17. Bone scan alkaline phos CBC 1,25-Di hydroxy cholecalciferol Chest X-ray SPEP Bone marrow Ace, LFT PTHrP Hypercalcemia with a low PTH CRK

18. Hypercalcemia Mild (10.3-11 mg) Modest 11-13 mg severe > 13 mg Symptomatic Acute chronic Nausea Vomiting Constipation Polyuria Dehydration Obtundation Arrythmia Arrest

19. Hypercalcemia- Treatment Hydration Normal saline diuresis to promote calciuresis with natriuresis Calcitonin injections for rapid action Pamidronate or Zaludronic acid (Zometa) Intrravenous Dialysis

20. Physiology Hypercalcemia Hyperparathyroidism Hypocalcemia Hypoparathyroidism

21. In the case presented earlier of the asymptomatic 54 year old woman with a serum calcium level of 10.6 mg the intact PTH was 112 pg (n=20-60) Your next step would be to: A. Recommend isotopic bone scan B. Recommend a sestamibi scan C. Recommend a 1,25 Dihydroxy D3 level D. Recommend a DEXA scan E. Recommend 24 hour urine phosphorus

22. Primary Hyperparathyroidism is no longer a disease of “stones, bones, and abdominal groans” Asymptomatic Fatigue Weakness Tired depressed Non specific presentation

23. Causes of Primary Hyperparathyroidism Single adenoma Hyperplasia (4 gland hyperplasia or multiple adenomas) Primary hyper parathyroidism Parathyroid carcinoma

24. True or False? Except in the very old or the very ill Primary Hyperparathyroidism always requires surgical intervention

25. Obvious indications for surgery Hx of renal calculi Osteoporosis calcium levels above 12 mg

26. The 54 year old woman with asymptomatic, incidentally discovered mild hypercalcemia of 10.6 mg undergoes a DEXA scan. The T score in the hip is -1.9 but the T score in the hip is -2.9. She attained menopause at age 48 and was never on HRT Your recommendation is: A. Start alendronate 70 mg once a week B. Start low dose calcium and vitamin D C. Recommend surgical exploration D. Start sensipar 30 mg daily E. Conservative follow up and repeat DEXA in 6 months

27. What are the indications for surgery in asymtomatic Hyperparathyroidism?

28. Asymptomatic Hyperparathyroidism Indications for Surgical Intervention 1. Abnormal BMD 2. Declining Creatinine Clearance 3. Increased urinary Calcium excretion 4. Progressive increase in serum calcium 5. Past hx of hypercalcemic crisis

29. The patient was referred to surgery. Which of the following statements is correct? A. She does not need any localizing procedures B. A sestamibi scan is indicated. C. An MRI of the neck is superior to isotopic scans D. An Ultrasound of the neck is indicated. E. Isotopic scans have a sensitivity of 95% for detecting parathyroid adenomas

30. True or false? You need to contact all her children to recommend genetic screening and counseling.

31. Pituitary hyperfunction Pancreatic islet hyperfunction Hyperparathyroidism (hyperplasia) MEN 1 Pheochromocytoma ( bilateral) Medullary carcinoma if the thyroid Hyperparathyroidism (hyperplasia) MEN 2 MEN 2 b Somatic features plus any or all of MEN 2

32. Physiology Hypercalcemia Hyperparathyroidism Hypocalcemia Hypoparathyroidism

33. Phosphorus Phosphorus Renal failure Hypopara Tumor lysis Rhabdomyolysis HYPOCALCEMIA Malabsorption Vit D deficiency Dilantin ETOH “Hungry Bones”

34. HYPOCALCEMIA Malabsorption Vit D deficiency Low magnesium Normal Phoshorus

35. A 42 year old woman is seen in the ER for twitching and involuntary movements of the fingers. She had a Roux-en-Y gastric by pass procedure 1 year ago. She was placed on calcium and D but she was erratic and non compliant. Her serum calcium is 6.2 mg,and the Phosphorus is 5.3 mg and the creatinine level is normal. On exam she has positive Chvostek and Trousseau signs. Which of the following needs to be done? A. TSH and free T4 B. Albumin level C. PTH level D. Magnesium level E. Vitamin D level

36. peripheral Central Low Magesium Diminishes the action of PTH on the bone causing “skeletal resistance” to PTH Diminishes the ability of parathyroids to respond to hypocalcemia PTH can be low PTH can be high

37. Acute effects of Hypocalcemia Neuro muscular irritabilty Overt or Latent Tetany Convulsions Larygeal spasm Abdominal pain mimicking surgical abdomen EKG changes

38. Chronic effects of Hypocalcemia Diarrhea Dental issues Dry skin Fatigue Coagulopathies Cardiomyopathy

39. Physiology Hypercalcemia Hyperparathyroidism Hypocalcemia Hypoparathyroidism

40. Elevated Low HYPOPARATHYROIDISM Pseudo hypoparathyhroidism Auto immune Surgical PTH

41. Autoimmune Hypoparathyroidism Sporadic Part of the Pluri Glandular Autoimmune Syndromes (PGA) Addison’s Type 1 Diabetes Hypothyroidism Gonadal deficiency Autosomal recessive

42. Autoimmune Hypoparathyroidism Onset at younger age Hypocalcemia can be severe Growth retardation can be associated Intellectual retardation has been described Often masquerades as epilepsy Behavioral changes can be associated Often the first manifestation of the PGA syndromes

43. Pseudo Hypoparathyroidism Congenital resistance to PTH Lack of receptors Lack of binding Lack of Post receptor effects Mechanisms Lack of G protein- inabilty of PTH to generate cyclic AMP

44. Pseudo Hypoparathyroidism In the complete form Resistance to PTH at both the renal and skeletal levels Renal Resistance Skeletal Resistance

45. Pseudo Hypoparathyroidism Since PTH can not work on its target receptors the effects are similar to hypoparathyroidism Low calcium High Phosphorus Plus Renal Resistance Somatic features Short stature Brachydactyly (short 4th or 5th MC) Facies- hyperteleorism Subcutaneous calcification Intellectual maldevelopment Skeletal Resistance

46. Since PTH can not work on its target receptors the effects are similar to hypoparathyroidism Low calcium High Phosphorus Pseudo Hypoparathyroidism Renal Resistance Diagnostic features High PTH level Elsworth Howard test Lack of increase in urinary cyclic AMP excretion or a Phosphaturic response following exogenous administration of PTH Skeletal Resistance

47. Treatment of Hypocalcemia Acute: Intravenous calcium gluconate Chronic: Oral calcium elemental 1000 mg Calcitriol 0.25 mcg - 1 mcg Phosphate binders

48. Idiopathic Hypoparathyroidism Pseudo Hypoparathyroidism Pseudo Pseudo Hypoparathyroidism Pseudo Hypo Hyperparathyroidism Pseudo Idiopathic Hypoparathyroidism Auto immune failure of parathyroids Renal and skeletal resistance to PTH Somatic features of PsedoPseudo but normal Calcium Renal Resistance to PTH but retains skeletal sensitivity- OFC The PTH secreted by the parathyroids is bio ineffective