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Hypercalcemia secondary to Primary Hyperparathyroidism

Hypercalcemia secondary to Primary Hyperparathyroidism

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Hypercalcemia secondary to Primary Hyperparathyroidism

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  1. Hypercalcemia secondary to Primary Hyperparathyroidism Emily Kingsley, MD Med-Peds II

  2. 90% of cases of hypercalcemia are due to hyperparathyroidism and malignancy • HyperPTH: asymptomatic with chronic hypercalcemia, postmenopausal woman, normal physical examination, family history of hyperparathyroidism, and evidence of multiple endocrine neoplasia • Malignancy: Higher concentrations of and more rapid increases in serum calcium and subsequently are more symptomatic • Ambulatory: Healthy patients, usually due to primary hyperparathyroidism • Hospital: Usually due to malignancy

  3. Primary Hyperparathyroidism • Usually due to parathyroid adenoma • Typically have only small elevations in serum calcium concentrations (less than 11 mg/dL) and sometimes values are high-normal • May require multiple measurements • Parathyroid crisis: uncommon but acute onset of severe, symptomatic hypercalcemia

  4. Secondary HyperPTH • Seen in severe chronic kidney disease • Usually low or normal serum calcium values • Few with hypercalcemia have decreased bone turnover • Tertiary HyperPTH: Parathyroid hyperplasia to autonomous overproduction of PTH

  5. Malignancy • Mechanism of increased bone resorption depends on the cancer • Bony mets: direct induction of osteolysis by tumor cells through the use of cytokines (TNF, IL-1) • Nonmetastatic solid tumors: PTHrP • Lymphoma: PTH-independent extrarenal production of calcitriol from mononuclear cells • Hypercalcemia with values above 13mg/dL • Unusual in hyperparathyroidism

  6. Other causes of hypercalcemia • Thyrotoxicosis: usu. mild hypercalcemia • Immobilization • Paget disease of bone • Hypervitaminosis A • Hypervitaminosis D • Calcitriol used with renal failure has short half life • Calcidiol has longer half life so symptomatic pts. may need steroids and bisphosphonate • Sarcoidosis, Wegener’s granulomatosis

  7. Milk Alkali Syndrome: can occur in the setting of excess calcium carbonate supplementation to treat osteoporosis or dyspepsia • Lithium: increased secretion of PTH due to an increase in the set point at which calcium suppresses PTH release • Thiazide diuretics • Pheochromocytoma • Adrenal insufficiency • Theophylline toxicity • Familial hypocalciuric hypercalcemia: loss-of-function mutation in the calcium-sensing sensor on the parathyroid cells and in the kidneys

  8. Clinical Manifestations • Ranges from asymptomatic to obtundation and coma • Mild hypercalcemia (calcium <12 mg/dl): Asymptomatic or nonspecific symptoms (constipation, fatigue, and depression) • Moderate hypercalcemia (calcium 12 to 14 mg/dL): • may be well-tolerated chronically • Acute rise to these concentrations may cause marked symptoms: polyuria, polydipsia, dehydration, anorexia, nausea, muscle weakness, and changes in sensorium. • Severe hypercalcemia (calcium >14 mg/dL): progression of symptoms

  9. NEURO/PSYCH Anxiety Depression Cognitive dysfunction Lethargy Stupor Coma GI Constipation Anorexia Nausea Pancreatitis Peptic ulcer disease MSK Bone pain Profound muscle weakness CARDIAC Shortening of the QT interval Bradycardia Hypertension RENAL Polyuria: decr. concentration in distal tub. Nephrolithiasis Acute/Chronic renal insuffic. Serum calcium of 12 to 15 mg/dL can lead to a reversible fall in GFR from direct renal vasoconstriction Long-standing hypercalcemia and hypercalciuria: Calcification, degeneration, and necrosis of the tubular cells →Tubular atrophy and interstitial fibrosis and calcification (nephrocalcinosis). …Bones, stones, moans, and groans

  10. Assessment Normal or • Correction for the measured calcium concentration in hypoalbuminemia Ca = Serum Ca + 0.8 * (Normal Albumin – Pt Albumin) Primary HyperPTH PTHrP Vitamin D levels TSH SPEP/UPEP Vitamin A levels Calcium PTH Malignancy Vit D intoxication Granulomatous dis.

  11. Haden, ST, Brown, EM, Hurwitz, S, et al. The effects of age and gender on parathyroid hormone dynamics. Clin Endocrinol 2000; 52:329.

  12. 25-OH Vitamin D: Usually due to ingestion • 1,25-OH Vitamin D: Ingestion, granulomatous diseases, lymphoma, primary hyperparathyroidism • Increased: Recommend CXR → Sarcoidosis, Lymphoma Granulomatous dis. Milk Alkali Syndrome Vitamin D intoxication Metastatic bone dis. Thyrotoxicosis Immobilization Normal or Phosphate HyperPTH PTHrP malignancy -Inhibition of renal proximal tubular Phosphate resorption

  13. Treatment of Hypercalcemia • Degree of hypercalcemia and rate of rise determine symptoms and urgency of treatment • Calcium >14mg/dL: Require treatment regardless of symptoms • Calcium 12-14mg/dL: • Chronically maybe be tolerated • Acutely may lead to AMS

  14. Isotonic Saline Treats volume depletion from calcium-induced urinary salt wasting Increases renal perfusion and urinary calcium clearance Administration: Initial rate of 200-300ml/hr adjusted for urinary output of 100ml/h Limited in those with cardiac or renal disease Should be discontinued with development of edema Goal: Euvolemia Rarely normalizes calcium level Ways to Correct Hypercalcemia

  15. Bisphosphonates • Analogs of inorganic pyrophosphate that absorb to the surface of bone hydroxyapatite inhibiting calcium release by interfering with osteoclast-mediated bone resorption • More potent than Saline and Calcitonin • Administration: IV Zoledronic acid preferred due to potency and short administration time (15 min.) • Single dose due to risk of osteonecrosis of jaw with repeat doses • Effect: Seen in 2-4 DAYS

  16. Calcitonin • Decrease bone reabsorption by interfering with osteoclast maturation • Increase renal calcium excretion • Administration: IM or subcut, nasal not effective • Effect: Rapid with lowering within 4-6 HOURS • Decreases the serum calcium up to a maximum of 1 to 2 mg/dL • Efficacy limited to 48 HOURS

  17. Glucocorticoids • Useful with calcidiol ingestion • Useful with hypercalcemia from increased calcitriol production seen in granulomatous disease and lymphoma • Decreases calcitriol production by activated mononuclear cells in the lung and lymph nodes • Administration: 20-40mg/day • Effect: Seen in 2-5 days

  18. Dialysis • Indications: • Severe hypercalcemia (18 to 20 mg/dL) with neurologic symptoms • Limited use of IV hydration: • Renal insufficiency • Heart failure

  19. In Sum… • Mild (<12mg/dl): No therapy • Avoid thiazide diuretic, lithium, calcium ingestion (>1000mg/day), volume depletion, prolonged bedrest • Moderate (12-14mg/dl): Treat if symptomatic or an acute rise • Severe (>14mg/dl): IV saline (immediate effect), calcitonin (immediate effect), bisphosphonate (delayed but most effective) • Primary hyperparathyroidism: Parathyroidectomy

  20. And the calcium lived happily ever after… (What would a Med-Peds presentation be without a Sponge Bob reference?!?!)

  21. HUNGRY BONE SYNDROME • Develops in those with bone disease preoperatively due to a chronic increase in bone resorption from high levels of PTH • Sudden withdrawal of PTH causes increased osteoblast-mediated bone formation and marked net increase in bone uptake of calcium, phosphate, and magnesium • Syndrome most likely to be present if if the serum calcium concentration <8.5 mg/dL and the serum phosphate concentration <3.0 mg/dL on the 3rd postoperative day

  22. Hypocalcemia • Tetany, seizures, heart failure • Treatment: • Oral calcium (2 to 4 g per day): Between meals to avoid phosphate binding • IV calcium: With rapid reduction in serum calcium OR symptoms related to hypocalcemia OR plasma calcium concentration below 7.5 mg/dL • Hypophosphatemia: With significant bone disease • Replacement only in severe hypoPO4 (below 1 mg/dL): Combines with calcium to further reduce calcium concentration • BUT with lack of severe bone disease: See increase in phosphate due to reversal of PTH-induced phosphate loss in the urine • Hypomagnesemia • Can contribute refractory hypocalcemia by diminishing PTH secretion and inducing PTH resistance • Hyperkalemia

  23. THANK YOU!

  24. References • Bilezikian, J. Clinical review 51: Management of hypercalcemia. J Clin Endocrinol Metab1993; 77: 1445-1449. • Haden, ST, Brown, EM, Hurwitz, S, et al. The effects of age and gender on parathyroid hormone dynamics. Clin Endocrinol 2000; 52:329. • Marx, S. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med 2000; 343: 1863-1875. • Up-To-Date. www.utdol.com