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Because of better diagnostic tests and routine blood calcium determination, PHPT is diagnosed sooner and few patients have severe symptoms or dramatic associated metabolic problems. This, however, does not alter the need for treatment to prevent metabolic complications such as decreased bone density with osteopenia and osteoporosis, decreased creatinine clearance, and hypercalciuria. One reason why fewer patients present with severe metabolic problems is that most patients are easily treated.13 Currently, parathyroidectomy is the only definitive treatment for patients with PHPT. (The National Institutes of Health [NIH] consensus meeting in 2002 recommended parathyroidectomy for patients with evidence of the symptoms seen in Table 5-4. At previous consensus conferences, the need for a prospective randomized trial to define the disease's multisystem effects and to assess the long-term incidence and progression of complications in asymptomatic PHPT patients over 50 years was recognized.14)

An NIH-sponsored consensus conference was held in April 2002 to re-evaluate these guidelines, and a new consensus statement is forthcoming at the time of this publication. Many surgeons feel that the original guidelines need to be broadened to include nonspecific manifestations of the disease,

Figure 5-6. Subperiosteal resorption in a patient with hyperparathyroidism.

Table 5-2. DIFFERENTIAL DIAGNOSIS OF HYPERCALCEMIA

Cancer (especially breast), squamous cell lung, and multiple myeloma and lymphoma Endocrinopathies Hyperparathyroidism Hyperthyroidism Hypothyroidism VIPoma

Addison's disease Pheochromocytoma Granulomatous disease (especially sarcoidosis) Increased consumption of calcium, vitamin D, vitamin A, alkali, and thiazides Immobilization

High turnover bone disease (Paget's) Acute renal failure

Benign familial hypocalciuric hypercalcemia

Table 5-3. BIOCHEMICAL TESTING IN PRIMARY HYPERPARATHYROIDISM

i Phosphorus level (50% of patients) Chloride-to-phosphorus level > 33 (99%) T Uric acid levels (25%)

T Alkaline phosphatase owing to increased bone turnover (25%) T Alkaline phosphatase and subperiosteal resorption (75%

of patients presenting with "hypercalcemic crisis") Renal dysfunction and anemia (rare)

given that parathyroidectomy in primary hyperparathyroidism significantly improves vague, nonspecific symptoms. Since the 1990 consensus conference, it has been demonstrated that PHPT is associated with increased mortality and, if untreated, may reduce a patient's survival by approximately 10%. The new guidelines for asymptomatic PHPT management should bring new insight into our current treatment strategies.15

Although many patients with PHPT have mild clinical manifestations and a few are completely asymptomatic, both asymptomatic and symptomatic patients appear to benefit from parathy-roidectomy symptomatically,16-18 metabolically,19-21 and with improved survival.22-25 In a classic study at the Mayo Clinic of 147 patients with mild hyperparathyroidism (serum calcium < 11.0 mg/dL) followed nonoperatively for 10 years, 1 patient developed hypercalcemic crisis and 38 patients (26%) required parathyroidectomy. By the end of 10 years, half of the patients who were available to be followed up developed some symptoms or complications that warranted parathyroidectomy. Thirty-five of the patients died.26,27

Table 5-4. ASYMPTOMATIC HYPERPARATHYROIDISM CRITERIA FOR PARATHYROIDECTOMY; NIH CONSENSUS 1990

Virtually all patients < 50 yr of age

Symptomatic patients*

Serum calcium level > 11.5 mg/dL

Significant symptoms of metabolic complications

Renal insufficiency (i CrCl by more than 30% for age in absence of another cause) Hypercalcemic crisis Urinary calcium > 400 mg/24 h i Bone density > 2 SD compared with controls

CrCI = creatinine clearance.

*Fatigue, lethargy, musculoskeletal aches and pains, polydipsia, polyuria, nocturia, dyspepsia, and constipation not included.

Parathyroidectomy appears to decrease the risk of subsequent complications such as osteoporosis, renal dysfunction, nephrolithiasis and, perhaps, hypertension. Although some metabolic problems can be partially reversed after successful parathyroidectomy (osteoporosis, renal impairment, nephrolithiasis, and gout), others, such as hypertension, usually do not improve. Asymptomatic patients also appear to receive the same metabolic benefits on bone, renal dysfunction, and other systems as symptomatic patients.27-31 They also return more quickly to a normal life expectancy after successful parathyroidectomy.22-24 Parathyroidectomy prevents the subsequent development of hypercalcemic crises, eliminating the need to manage hypercalcemia when patients are hospitalized for other serious, unrelated medical problems.

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