Treatment of Asymptomatic Hyperparathyroidism

The changing presentation of 1 ° HPT is a result of the increased recognition of a milder form of the disease. The intention of the NIH consensus guidelines for parathyroidectomy was to

Preop Postop 3 months 1 year

FIGURE 44-1. The Parathyroidectomy Assessment of Symptoms (PAS) scores for primary hyperparathyroidism (HPT).The HPT patients were significantly more symptomatic than the thyroid comparison group preoperatively (P < .05). After surgery, the HPT patients demonstrated a significant decrease in their PAS scores (P < .05). The thyroid comparison group demonstrated no change in their PAS scores throughout the study.

Preop Postop 3 months 1 year

FIGURE 44-1. The Parathyroidectomy Assessment of Symptoms (PAS) scores for primary hyperparathyroidism (HPT).The HPT patients were significantly more symptomatic than the thyroid comparison group preoperatively (P < .05). After surgery, the HPT patients demonstrated a significant decrease in their PAS scores (P < .05). The thyroid comparison group demonstrated no change in their PAS scores throughout the study.

Preop

Postop 3 month 12 month

FIGURE 44-2. The Parathyroidectomy Assessment of Symptoms (PAS) scores for primary hyperparathyroidism (HPT). Group A had at least one of the National Institutes of Health (NIH) criteria for parathyroidectomy present preoperatively. Group B patients had none of the NIH criteria present and were "asymptomatic." Group C consisted of the thyroid comparison group. Groups A and B were significantly more symptomatic than group C preoperatively (P < .05). After surgery, there was no difference in the PAS scores between any of the three groups.

Preop

Postop 3 month 12 month

FIGURE 44-2. The Parathyroidectomy Assessment of Symptoms (PAS) scores for primary hyperparathyroidism (HPT). Group A had at least one of the National Institutes of Health (NIH) criteria for parathyroidectomy present preoperatively. Group B patients had none of the NIH criteria present and were "asymptomatic." Group C consisted of the thyroid comparison group. Groups A and B were significantly more symptomatic than group C preoperatively (P < .05). After surgery, there was no difference in the PAS scores between any of the three groups.

help guide the clinician to the appropriate treatment for patients with mild 1° HPT.10 Parathyroidectomy remains the only definitive treatment of HPT, reversing the manifestations of the disease and correcting the biochemical abnormalities in over 95% of patients.9-36-37 There is little debate about the need for parathyroidectomy in overtly symptomatic patients. Other criteria developed at the NIH conference included age younger than 50, marked hypercalcemia (>2.85 mmol/L), marked hypercalciuria (>10 mmoiy day), reduction in creatinine clearance, and bone loss more than 2.5 standard deviations compared to healthy controls. These criteria were thought to reflect the physiologic end-organ effects of HPT and thus were likely to identify the patients at risk for developing complications of the disease. Additional criteria for surgery that are utilized by some authors include vertebral bone osteopenia, vitamin D deficiency, recent fracture history, and perimenopausal status for women.12 Although rare, there are patients with 1° HPT in whom vertebral osteopenia is more marked than cortical bone loss. Parathyroidectomy has been shown to result in a significant improvement in vertebral bone density and only a modest increase in cortical bone density at 10-year follow-up.38-39 It appears that the patients with significant vertebral osteopenia would benefit the most from parathyroidectomy. Receptors for vitamin D metabolites in the parathyroid glands have been shown to suppress parathyroid hormone (PTH) secretion. It has been postulated that vitamin D deficiency results in even higher PTH levels in patients with HPT. Correcting the vitamin D deficiency may be associated with a worsening hypercalcemia, and thus these patients would benefit from parathyroidectomy before addressing their vitamin D deficiency.12-40 Although the increased risk of fracture in HPT is not clearly established in the literature, fractures, particularly cortical fractures, suggest an accelerated course of the disease and therefore

FIGURE 44-3. The item-specific Parathyroidectomy Assessment of Symptoms (PAS) scores for the nonspecific symptoms of hyperparathyroidism (HPT). A, PAS scores of the HPT patients, demonstrating a significant improvement in all five items at 1-year follow-up (P < .05). B, PAS scores of the thyroid patients, demonstrating no difference in their scores for all five items at 1-year follow-up.

Forgetful Depressed

Preop

FIGURE 44-3. The item-specific Parathyroidectomy Assessment of Symptoms (PAS) scores for the nonspecific symptoms of hyperparathyroidism (HPT). A, PAS scores of the HPT patients, demonstrating a significant improvement in all five items at 1-year follow-up (P < .05). B, PAS scores of the thyroid patients, demonstrating no difference in their scores for all five items at 1-year follow-up.

have been utilized as an indication for surgery by some authors.12,41"44

Using the NIH definition of symptomatic disease, approximately 50% of patients with Io HPT have at least one of the NIH criteria for parathyroidectomy.13 For the remaining 50% of patients, some authors have suggested conservative management with yearly monitoring of physiologic parameters such as serum calcium, BMD, and renal function.611'13'28-45 In the prospective trial involving Io HPT patients randomly assigned to surgery versus observation, Silverberg and colleagues found that 37% (22 of 60) of the observation group demonstrated progression of their disease.28 The majority of these patients were found to have a decrease in their BMD over time, in contrast to the parathyroidectomy group, who demonstrated a significant increase in their BMD. Of the 60 patients in the observation arm, 52 were considered asymptomatic. At 10-year follow-up, 38 of these asymptomatic patients demonstrated no significant progression of their disease. This study illustrated that there is a subgroup of patients with Io HPT that, when followed closely, demonstrates little progression in the physiologic parameters affected by HPT, such as BMD and renal function. It is, however, likely that the investigators have underestimated the population of symptomatic patients and failed to study the impact of the nonspecific symptoms on the patients overall.

There continues to be considerable debate among surgeons and endocrinologists concerning the appropriate treatment of mild, nonprogressive Io HPT. Outcome studies that assess the impact of parathyroidectomy beyond the physiologic parameters of the disease have clearly demonstrated an improvement in the patients' well-being and general health. These studies, however, have been for the most part surgical studies and, because of the inherent referral basis, still do not clearly resolve the debate. Until a randomized study is performed that includes both classic and nonclassic symptoms and measures not only the impact on the physiologic parameters but also the impact on the patient's health-related QOL, the debate over the management of Io HPT will continue.

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