Indications for Operative Treatment

As discussed earlier, the clinical profile of primary hyperparathyroidism has undergone a distinct change over the past few decades, particularly with the introduction of automated blood chemistry panels. The 1990 National Institutes of Health Consensus Development Conference on the Management of Asymptomatic Primary Hyperparathyroidism was convened to set forth evidence-based diagnosis and management guidelines for this group of patients. The panel recognized surgery as the only definitive treatment for primary hyperparathyroidism and recommended parathyroidectomy for any individual with overt complications and symptoms such as nephrolithiasis, fractures, and neuromuscular syndrome. In addition, surgery was recommended for asymptomatic patients with1 (1) serum calcium more than 1 to 1.6 mg/dL (0.25 to 0.4 mM) above the accepted normal reference range; (2) 24-hour urine calcium greater than 400 mg (10 mM); (3) a 30% reduction in creatinine clearance compared with age-matched normal individuals;

(4) bone mineral density more than 2 standard deviations (SD) below that of age-, gender-, and race-matched controls;

(5) age younger than 50 years; and (6) in whom medical surveillance is not possible or desirable.

The vague neurobehavioral axis symptoms (weakness, increased fatigue without overt muscle weakness) were deemed nonspecific and not sufficient in and of themselves to recommend surgery, unless these symptoms were thought to be related to hyperparathyroidism.

The panel also recommended that patients not undergoing surgery understand the importance of regular, long-term follow-up and undergo (1) biannual measurements of blood pressure, serum calcium serum creatinine and creatinine clearance and (2) annual abdominal radiography (and/or ultrasonography), 24-hour urine calcium test, and bone mass measurement. Patients were also to be advised on the importance of adequate mobility and seeking prompt medical attention for any intercurrent illness causing dehydration, both of which can worsen existing hypercalcemia.

Since the last consensus meeting in 1990, there has been an accumulation of data on the natural history of asymptomatic hyperparathyroidism and the long-term effects of untreated hyperparathyroidism. Moreover, localizing studies are more accurate, readily available, and utilized. Several minimally invasive surgical approaches have also been developed, as have novel medical therapies. Therefore, a follow-up Workshop on Asymptomatic Primary Hyperparathyroidism: A Perspective for the 21st Century was held at the National

Institutes of Health in April 2002 to re-evaluate the recommendations of the previous consensus meeting. The revised recommended indications for surgery along with the reasons for the change are as follows43:

1. Serum calcium greater than 1 mg/dL (0.25 mM) above the upper reported normal reference range

The range was lowered because the panel believed that even patients with this degree of elevation of serum calcium were at risk for developing symptoms and complications of hyperparathyroidism.

2. 24-hour urine calcium excretion 400 mg/day (unchanged)

3. A 30% decrease in creatinine clearance compared with age-matched control subjects (unchanged)

4. Bone density at the lumbar spine, hip, or distal radius greater than 2.5 SD below peak bone mass (T-score less than -2.5)

Hyperparathyroidism classically leads to loss of cortical bone mass. However, a subset of patients with primary hyperparathyroidism have marked bone density loss at sites of cancellous bone such as the spine, and parathyroidectomy has been demonstrated to increase bone mass at these sites.44,45 T-scores, which represent deviations from an individual's optimal bone mass, seem to be a more reasonable indicator of fracture risk than Z-scores, which compare bone mineral density with that of age- and sex-matched cohorts. Hence, the panel recommended bone mineral density measurement at three sites and a change to T- rather than Z-score measurements.

5. Age younger than 50 years (unchanged)

6. Patients for whom medical surveillance is not possible or desirable (unchanged)

The panel also cautioned against the use of neuropsychological abnormalities, cardiovascular disease, gastrointestinal symptoms, menopause, and elevated serum or urine indices of increased bone turnover as sole indications for parathyroidectomy. Rather, these factors should be weighed in the context of the individual patient. Although bisphosphonates and cal-cimimetics show promise, data are insufficient to recommend medical management in patients with asymptomatic primary hyperparathyroidism and only parathyroidectomy offers curative treatment. The new recommendations for follow-up of patients not undergoing surgery are compared with the previous recommendations in Table 40-4.

TABLE 4(M. A Comparison of the 1990 and 2002 Consensus Development Conference Guidelines for the Management of Patients with Asymptomatic Primary Hyperparathyroidism Who do not Undergo Surgery

Measurement

1990

2002

Serum calcium 24-hr urinary calcium Creatinine clearance Seium creatinine Bone density

Abdominal radiograph {± ultrasonography)

Biannually

Annually

Annually

Not recommended Annually (forearm) Annually

Biannually Not recommended* Not recommended* Annually^

Annually (spine, hip, and forearm) Not recommended*

•Except at the time of initial evaluation.

'If the serum creatinine concentration suggests a change in the creatinine clearance, when the Cockcroft-Gault equation is applied, further, more direct, assessments of the creatinine clearance are recommended.

From Bilezikian JP, Potts JT Jr, Fuleihan Gel-H, et al. Summary statement from a workshop on asymptomatic primary hyperparathyroidism: A perspective for the 21st century. J Bone Miner Res 2002;17(Suppl 2):N211.

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