Asymptomatic Hypercalcemia Primary Hyperparathyroidism

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Asymptomatic HypercalcemiaPrimary
Hyperparathyroidism

• Wiam I Hussein, MD
• Angelo A Licata, MD, PhD
• Cleveland Clinic

Cleve Clin J Med 1998 65(5)237-240
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Causes of Hypercalcemia

• Primary hyperparathyroidism
• Humoral hypercalcemia of malignancy
• Familial hypocalciuric hypercalcemia
• Drug-induced hypercalcemia

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Primary Hyperparathyroidism

• accounts for gt70 of cases of asymptomatic
  hypercalcemia in ambulatory patients
• incidence 1 case / 800 persons / year
• most common in the 5th-6th decades
• 3 x more common in women than in man

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Primary Hyperparathyroidism

• asymptomatic in gt 50 of cases
• mainly a biochemical diagnosis
• serum calcium generally mildly elevated lt12.0
  mg/dl (normal range 8.5-10.5)
• PTH level is elevated in 90 of cases
• mild hyperchloremia and metabolic acidosis is
  common

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Primary Hyperparathyroidismcauses

• Solitary benign parathyroid adenoma
• Diffuse hyperplasia of all parathyroid glands
• Multiple parathyroid adenoma
• Parathyroid carcinoma

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Primary Hyperparathyroidismcauses

• Solitary benign parathyroid adenoma
• accounts for 80-85 of cases
• surgical removal produces long-term remission
• recurrence rate is 0.6 at 8-10 years

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Primary Hyperparathyroidismcauses

• Hyperplasia of all parathyroid glands
• accounts for 15 of cases
• may occur sporadically or as part of multiple
  endocrine neoplasm syndrome
• Type I (Werner Syndrome)pituitary, parathyroid,
  pancrease
• Type II (Sipple Syndrome)medullary thyroid
  cancer, pheochromocytoma, hyperparathyroidism

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Primary Hyperparathyroidismcauses

• Multiple parathyroid adenoma
• found in only 1 - 2 of cases
• sporadic or familial
• Parathyroid carcinoma
• very rare, lt 0.5 of cases
• average serum calcium is 14 mg/dl
• marked elevation in intact PTH
• aggressive surgical resection

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Surgery for Primary Hyperparathyroidism

• Serum calcium level gt 1 mg above upper limits of
  normal
• Urinary calcium excretion gt 400 mg/day
• Overt clinical manifestation
• classic neuromuscular disease
• nephrocalcinosis
• nephrolithiasis
• osteitis fibrosa cystica

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Surgery for Primary Hyperparathyroidism

• Cortical bone density in the distal radius lt2
  standard deviation (Z score lt -2 SD)
• Reduced creatinine clearance in theabsence of
  other cause
• age lt 50 years

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Humoral Hypercalcemiaof malignancy

• accounts for gt50 of cases of hypercalcemia in
  hospitalized patients
• most common malignant diseaseslung, breast,
  myeloma, lymphoma, renal cell carcinoma

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Humoral Hypercalcemiaof malignancy

• Mechanism of hypercacemia
• tumor secretion of PTH-related peptide,
  lymphotoxins, interlukin-1, 1,25 vit D
• hypercalcemia precedes the diagnosis of
  malignancy in lt 20
• majority of malignant disease is already advanced

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Familial Hypocalciuric Hypercalcemia

• A benign autosomal dominant condition caused by
  decreased renal clearance of calcium
• a very low fractional excretion of calcium
  (lt0.01), normal or mildly ? PTH levels, mild ?
  serum magnesium
• no treatment required

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Drug-induced Hypercalcemia

• estrogen
• tamoxifen (antiestrogen)
• lithium
• theophyllin
• thiazide diuretics
• vitamin A
• vitamin D

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References

• Consensus Development Conference Panel.Diagnosis
  and management of asymptomatic primary
  hyperparathyroidism consensus development
  conference statement.Ann Intern Med
  1991114593-597.
• Primary hyperparathyroidism.Primer on the
  metabolic bone diseases and disorders of mineral
  metabolism. 3rd ed 1996181-186.