Asymptomatic Hyperparathyroidism Does It Exist

With the earlier detection of the disease, the presenting clinical manifestations of 1 ° HPT have changed drastically since the first successful parathyroidectomy in 1925. The classic symptoms of severe bone pain from osteitis fibrosa cystica, nephrolithiasis, significant myopathy, and significant neuropsychiatrie impairment are seen in less than 20% of the patients who currently present with 1° HPT.6 Unlike the presentation in the days of von Recklinghausen and Albright, today only 15% to 20% of patients with 1° HPT present with nephrolithiasis and less than 3% of patients display evidence of osteitis fibrosa cystica.5"9

This change in the presentation of 1° HPT led to a 1990 National Institutes of Health (NIH)-sponsored consensus conference that developed guidelines for surgery in HPT.10 The consensus panel agreed that parathyroidectomy was indicated in all symptomatic patients as well as in all "asymptomatic" patients with risk factors for progression of their disease such and marked hypercalcemia, hypercalciuria, or renal insufficiency, marked bone mineral density (BMD) loss, and those younger than 50 years.10 In a reconvening of the NIH consensus panel in 2002, very little had changed. The new guidelines reduced the limits of hypercalcemia to 0.25 mmol above the normal reference, and altered the criteria of BMD loss from z scores to t scores.10" The panel continued to recommend surgical intervention for all symptomatic patients and those who demonstrated end-organ physiologic effects of the disease. The controversy lies in the NIH consensus panel's definition of an asymptomatic patient. If one limits the definition of symptomatic HPT to the classic symptoms, including nephrolithiasis, significant myopathy, and evidence of osteitis fibrosis cystica, it is true that the majority of patients today with 1° HPT (over 80%) are asymptomatic.6'10"14 Asymptomatic, however, implies free of symptoms and complications of the disorder. Today, there is considerable evidence that many patients with HPT suffer from vague, nonspecific, but nonetheless real manifestations of the disease.615"23 Surgeons have long observed improvement in many of these nonspecific symptoms following parathyroidectomy. Furthermore, many patients with 1° HPT do not realize until after parathyroid surgery just how severe their symptoms Were.1517'18-24'25

Joborn and colleagues investigated psychiatric symptoms in 59 consecutive patients with 1° HPT.26 Utilizing a Comprehensive Psychopathological Rating Scale, they found that the majority of patients with HPT had considerable psychiatric symptoms compared with healthy control subjects. The most pronounced symptoms were fatigue, lassitude, failing memory, difficulty concentrating, sadness, and inner tension. After successful parathyroidectomy, there was a marked improvement in the mental health of these patients. This was one of the first surgical studies that tried to quantify the nonclassic symptoms and the surgical effect in patients with 1° HPT.

In a population-based screening study from Sweden, Lundgren and coworkers found that fewer than 24% of their 1° HPT patients suffered from the classic symptoms. However, the patients with 1° HPT had more psychiatric complaints of lassitude, fatigue, irritability, and lack of sexual interest than their age-matched control subjects.27

Others have demonstrated similar results, with the HPT patients' experiences with more symptoms than population norms. Chan and colleagues reported a case-control series of 121 patients from 1986 to 1991 with 1° HPT utilizing a preoperative symptom questionnaire that was filled out at their first visit to the surgeon and again when they were recalled in June 1991. They found that the majority of the 1 ° HPT patients were indeed symptomatic preoperatively (95%) and that most patients experienced a subjective improvement in their preoperative symptoms following parathyroidectomy.18

More recently, Hasse and associates15 set out to answer the question of just "how asymptomatic is asymptomatic 1° HPT?" In their cohort study of 582 consecutive patients with 1° HPT, 86 patients who were considered asymptomatic preoperatively participated in the follow-up questionnaire given at a median of 72 months postoperatively. The follow-up assessment consisted of the Short Form 36-item (SF-36) quality of life (QOL) instrument and a graded questionnaire that included 19 classic and nonclassic symptoms. They found that in retrospect only 9.3% of the asymptomatic patients were truly asymptomatic. Postoperatively, 81% of the asymptomatic patients reported an improvement in their preoperative state. From this study, it would appear that apparently asymptomatic 1° HPT patients realized symptoms only in retrospect and that these symptoms could not be predicted preoperatively, because they become apparent only after treatment.

These studies all suggest that asymptomatic 1° HPT patients might have the same subjective benefit from parathyroidectomy as symptomatic patients. Asymptomatic 1° HPT patients treated conservatively have no frame of reference to validate whether or not they are truly asymptomatic. In an observational study by Silverberg and colleagues of 121 1° HPT patients, they claimed that 101 (83%) were asymptomatic.28 Patients were randomly assigned. Half (61) underwent parathyroidectomy with a normalization of their biochemical values and an increase in their BMD. The remaining 60 patients underwent observation and, during the 10-year follow-up period, 22 (37%) demonstrated a progression of their disease. Despite these results, they concluded that with clinical follow-up most asymptomatic patients with 1° HPT could be monitored safely without parathyroidectomy. The authors commented that the nonspecific manifestations of 1° HPT were not included in their criteria for symptomatic disease because quantitative measures of these manifestations were not yet available. It is, therefore, likely that the number of patients who were symptomatic in their observation group and the number of patients who demonstrated progression of their disease were underestimated. Silverberg's study, like many others in the literature, illustrates the need for validated instruments that can measure the impact of intervention on these nonspecific manifestations of HPT.24

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