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Hypercalcemia

Hypercalcemia

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Hypercalcemia

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  1. Hypercalcemia

  2. Case • 56 Y O F with generalized body pain for 1 day • Also decreased PO intake • Expressive aphasia due to CVA, cannot give further history • PMH to de discussed later… • PE: • Vitals stable • Moderate respiratory distress • Somnolent but arousable • Breath sounds only in R chest

  3. Case, Continued • Labs: • Chem: 138/3.5/94/33/40/0.5 <114 – baseline BUN 7 • Ca 19.8 – 11.9 one week prior • CXR: complete opacification of L hemi-thorax. Volume loss, scarring and bronchiectasis in R lung • Next: What’s the first test you would order? • And what’s the diagnosis?

  4. Answers • PTH < 3 when repeat Ca 18.6 • History of NSCLS, squamous cell carcinoma, with intrabronchial invasion Important concepts in endocrine: 1- Two labs values are better than one; 3 is even better! 2- Timing 3- Inappropriately “normal” values

  5. Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism. Holick MF. N Engl J Med 2007;357:266-281.

  6. Diagnostic Work Up PTH PTH-independent • Hypercalcemia of Malignancy • Vit D Intoxication • Granulomatous Disease • Hyperthyroidism • Vit A Intoxication • Adrenal Insufficiency • Milk-Alkali Syndrome • Thiazide Diuretics • Immobilization PTH-dependent • Primary Hyperparathyroidism • Familial HypocalciuricHypercalcemia • LithuimToxocity • Tertiary Hyperparathyroidism

  7. Why is PTH so important?

  8. General Rules • PHPT is at least twice as common as all other causes combined • Specially if pt seems well, hyperCa was found incidentally or is mild, stable or known to be of long duration • More than 90% of pts referred to endocrine have PHPT • Among ill or hospitalized pts, malignancy is the cause in more than 50% of cases • Confirm elevated Ca levels by repeating test and checking ionized Ca • History, PE, prior lab values, ….

  9. Primary Hyperparathyroidism • Primary abnormality of parathyroid tissue • Inappropriate secretion of PTH • What is appropriatehypersecretion of PTH in response to hypocalcemia? • Excessive PTH  • Increased renal Ca reabsorption • Phosphaturia • 1,25-OH2-Vit D synthesis • Bone resorption

  10. Primary Hyperparathyroidism • Etiology • One or more parathyroid adenomas (75-80%) • Diffuse hyperplasia of all glands (20%) • Parathyroid carcinoma (1-2%) • “Classic” manifestations • Bone: increased resorption • Renal: recurrent Ca stones, nephrocalcinosis, impaired concentrating ability, renal failure • GI: nausea, vomiting, constipation, abd pain, pancreatitis • Neuropsychiatric symptoms *

  11. “Contemporary” PHPT • Many pts are incidentally found, asymptomatic • Some have nl Ca and elevated PTH, found during work up of osteopenia • Natural course variable: bone loss, kidney disease, mortality • Management: observation vs. surgery

  12. Hypercalcemia of Malignancy • Most malignancies produce hyperCa only when far advanced • Pts usually die 1-2 months after hypercalcemia is discovered • Polydipsia, polyuria, constipation, nausea, vomiting, but especially dramatic changes in mental status • Mechanism • Local osteolytichypercalcemia: bone mets, most often in MM and breast cancer • Humoralhypercalcemia of malignancy: mediated by PTHrP, mimics all actions of PTH. Squamous cell cancers (lung, H&N, esophagus, cervix), breast cancer, RCC, bladder.

  13. Vit D Intoxication • Needs ingestion of about 100,000 IU of vit D per day • In US most often Iatrogenic • Hypercalcemia can be severe and prolonged (fat stores) • 25-OH-Vit D levels dramatically elevated • 1,25-OH2-Vit D normal or even low due to down regulation of renal 1α-hydroxylase by low PTH levels

  14. Granulomatous Disease • Sarcoidosis, TB, fungal infections, HIV-related PCP infection, Crohn’s disease • Unregulated production of active Vit D by macrophages • Pts unusually sensitive to vit D an can become hypercalcemic after exposure to ultraviolet light, or oral vit D intake

  15. Misc. Causes • Hyperthyroidism • Ca rarely >11 • Direct action of thyroid hormone to promote bone resorption • Vit A Intoxication • Requires ingestion of > 10x RDA (5000 IU/d) • Also Accutane (acne) and Retin-A (acute promyelocytic leukemia) • Adrenal Insufficiency • Thiazide Diuretics: in PHPT, sarcoidosis, excessive Ca intake

  16. Misc. Causes • Milk-Alkali syndrome • Hypercalcemia, metabolic alkalosis, renal failure • First described when milk and Na bicarb were used to treat PUD • Now seen with increasing use of Ca bicarb for PUD and osteoporosis • Immobilization • Spinal cord injury or excessive casting • Increased bone resorption • Peak Ca in 4 week, can last up to one year

  17. Management • Severe hypercalcemia > 14 mg/dl • Unusual in PHPT, unless a secondary mechanism is present • Dehydration from nausea, vomiting, diuretics • Immobilization • Large PO calcium intake • Severe acute hypercalcemia usually result of malignancy • Should we treat?

  18. Treatment: 1, 2, 3, … • Correct Intravascular volume depletion: NS 2-4 lit/d • Discontinue diuretics • +/_ furoemide • Bisphosphonates: first choice in management of severe hypercalcemia caused by osteolytic bone resorption • Not in milk-alkali syndrome • Ca decreases within 24 h, reaches nadir within 1 week • Use half the dose in moderate renal insufficiency (GFR>30) • Effect lasts 1 week to several months

  19. Treatment • Calcitonin: inhibits osteoclast function • Use with bisphosphonates for more rapid onset of action (a few hours) • Ca decreases by 1-2 mg/dl • Effect lasts a few days • Steroids: PO or IV • Consider early in Vit D mediated hypercalcemia, including granulomatous disease and lymphoma

  20. Treatment

  21. Follow Up • Ca repeated, 18.6 with PTH < 3 • PTHrP 55 (15-27) • 25-OH-Vit D and 1,25-OH2-Vit D <8 • IV hydration • Calcitonin 200 IU q 12 (Ca 17.6 after 1st dose) • Pamidronate 60mg IV infusion • 48 hours after admission Ca 12.9 • Transferred to pall care, expired 6 d after admission

  22. Case 1 • 49 yo F with laryngeal Ca s/p laryngectomy/chemo and RT with resultant hypothyroidism and hypoparathyroidism on replacement p/w weakness • Ca 15.6 • PTH < 3 • Cr 1.3 (baseline 0.8) • CO2 36 • Dx?

  23. Case 2 • 74 Y o M with colorectal Ca, dementia, dependant on ADL’sp/w AMS • Ca 14.2 – Hgb 9 – Cr 5.1 • PTH 21.4 • SPEP: no M spike, UPEP not sent • PTHrP 23 • 25-OH-Vit D 35.7, 1,25-OH2-Vit D 16 • Dx? • Ca 9.8 after hydration

  24. Case 3 • 84 Y O F with Ehlers-Danlos syndrome, professor of pediatric neurology at Einstein p/w AMS • Ca 16.2 • PTH<3 • SPEP, UPEP negative • 25-OH-Vit D 127 • Has been taking Vit D 5000 IU daily for “years”

  25. Case 4 • 82 Y of with HTN, endometrial Ca, COPD, morbid obesity p/w inability to walk and b/l knee pain • Ca 16.9 • PTH 7.7 • Cr 1.6 (taking NSAIDs), Hgb 10.6 • 25-OH-Vit D 27.2, 1,25-OH2-Vit D < 8 • SPEP: + M spike – serum free lambda >12,000 • Bone survey: lucency in calvarium, b/l femur and humerus • Rx with IV hydration and steroids (semi-chemo)