JOURNAL OF BONE A N D MINERAL RESEARCH Volume 6, Supplement 2, 1991 Mary Ann Liebert. Inc., Publishers

Conservative Management of Primary Hyperparathyroidism DAVID A . HEATH and EILEEN M. HEATH

ABSTRACT The personal management of patients seen with primary hyperparathyroidism over the past 10 years has been reviewed; 248 cases were identified of which 122 have been managed conservatively. These patients were mainly asymptomatic. Apart from 4 who developed renal stones, which were spontaneously passed, there was no clinical or biochemical evidence that patients sustained adverse consequences by conservative management. These studies support the need for further studies of the conservative management of asymptomatic hyperparathyroidism.

INTRODUCTION E HAVE IDENTIFIEDall patients seen in the outpatient clinic of one us (DAH) with a serum calcium of 2.60 mmol/liter or higher during the period January 1980 through December 1989. Patients were referred either by their general practitioner or by another consultant in a different hospital, following the identification of hypercalcemia. Patients referred by their general practitioner almost invariably had the hypercalcemia discovered by chance during routine investigations. Referrals by consultants were more likely to have been referred with specific symptoms. Virtually all patients investigated for hyperparathyroidism during this period were initially seen as outpatients. Records of all patients were reviewed. When patients had been discharged to the referring clinician, attempts were made to obtain their current clinical and biochemical status. During this period, a policy was followed of recommending parathyroidectomy for all patients with complications and definite symptoms of the disease. Asymptomatic patients or patients with mild nonspecific symptoms were offered parathyroidectomy only if young. The threshold for being young declined during the 10 year period from around 60 to 40 years. Patients following successful parathyroidectomy were usually returned t o the referring clinician after one or two postoperative visits. No attempt was made to ascertain the long-term results of parathyroid sur-

gery. Patients living outside Birmingham who were managed conservatively were returned to their referring clinician with recommendations of annual clinical biochemical review. A diagnosis of hyperparathyroidism was made on the basis of hypercalcemia associated with an elevated or high normal serum parathyroid hormone concentration.

RESULTS Only 8% of outpatients had a nonparathyroid cause for the hypercalcemia (Table 1). Previous studies have shown that malignancy is associated with hypercalcemia, typically when the malignant process is advanced and disseminated.''] Patients referred for outpatient evaluation are usually in reasonable health, explaining, in part, the low incidence of hypercalcemia of malignancy in this series. Previous studies have documented that nonparathyroid, nonmalignant causes of hypercalcemia are rare. Of the 248 cases of hyperparathyroidism, 126 were treated either initially or ultimately with surgery; in 122, a conservative policy was maintained. Table 2 indicates the symptoms of the two groups. Surgically treated patients without symptoms were either below 40 years of age or below 60 years during the early period of review. The most common problems in men were renal stones and in women, tiredness and lethargy. In the conservatively managed group, most were considered asymptomatic or to have symptoms unrelated to hypercalcemia. Five patients had

Department of Medicine, Queen Elizabeth Hospital, Birmingham, England.

S117

HEATH AND HEATH

S118

renal stones, 2 developing them during conservative management (see later). In the remaining 3, the patients either refused surgery or the renal stones occurred many years before the diagnosis of hyperparathyroidism. Patients undergoing conservative management were subdivided into three groups: (A) patients known to be alive and well during the past year; (B) patients who died; and (C) patients who could not be traced and who either died or moved to a different part of the country. Table 3 documents the details of the patients who proceeded to parathyroidectomy. To enable a comparison with the conservative managed patients, their age was calculated as of October 1990. Men were generally younger than the women, although biochemically they were similar. Of surgical patients 80% underwent parathyroidectomy within 1 year of being seen. In 23 cases surgery occurred more than 1 year after initial referral. These 23 included 3 patients who initially refused surgery; 2, however, developed renal stones during planned conservative therapy. In both, the stones presented 3 years after conservative management was initiated and were passed without surgical intervention. After parathyroidectomy was subsequently carried out, no further stones were passed. In the remaining patients, patients only gradually accepted the observation that their nonspecific symptoms, usually considered normal aging, were sufficiently marked to justify an operation.

Table 4 documents the details of the patients managed conservatively. Apart from the paucity of symptoms of the disease, they appear biochemically and in all other respects to be similar to the cases treated surgically. Group A patients show no suggestion of biochemical deterioration over 6 years. No patient was seen in whom a rise in serum calcium or in serum creatinine prompted a change in policy. In addition to the two patients who developed renal stones during follow-up, two additional patients developed a stone, which was passed spontaneously after 6 and 8 years of observation. One previously had an unsuccessful parathyroidectomy at another hospital and refused a further neck exploration. She is currently well at the age of 80. Because of arthritis, age, and general health, surgery has not been recommended for the other patient. A total of 15 patients are known to have died during follow-up (group B). This group was on average 11 years older than group A and 14 years older than the surgical group. In none was the cause of death attributable to hyperparathyroidism or any of its known complications. Most had known active medical problems when the hyperparathyroidism was discovered. Group C constitutes 13 patients who cannot currently be traced. As their mean age is similar to that of the group B patients, it is likely that a number of these patients have died, especially as several were known to have other significant medical problems.

DISCUSSION OF TABLE 1. CAUSESAND MANAGEMENT HYPERCALCEMIC PATIENTS

Before the advent of biochemical screening, many patients with hyperparathyroidism had significant complications of the disorder, especially bone disease and renal stones. Parathyroidectomy was generally recommended for most patients with these complications. Biochemical screening revealed many cases of hyperparathyroidism with few or no symptoms. Many of these patients were elderly. The experience reported in this study reflects an evolving attitude by one of us (DAH) toward more conservative management over the 10 year period reviewed here. Although patients were not entered into a formal, prospective study of conservative management, information gained from this study adds further evidence to that already available that suggests that conservative manage-

248 126 122 21 5 4 4 2 1 1 1 1

Hyperparat hyroidism Operative management Conservative management Other causes of hypercalcemia Familial benign hypercalcemia Vitamin D poisoning Malignancy Thyrotoxicosis Milk alkali syndrome Addison’s disease Transient, unexplained Unknown

TABLE 2. FEATURES OF

PATIENTS

TREATED SURGICALLY OR CONSERVATIVELY

Surgically treated Features Renal stones Tiredness, lethargy None Other

(n

Male 26) (To)

=

42 8 12 38

Conservative treatment

Female (n

= 94) (To)

21 53 12 14

(n

Male = 30) 6 3 88 3

(n

Female = 92) (YO)

3 8 76 13

CONSERVATIVE MANAGEMENT OF PRIMARY HYPERPARATHYROIDISM TABLE 3. PATIENT CHARACTERISTICS OF OPERATED PATIENTS~

S11Y

tively, no patient requested surgery merely to correct a biochemical abnormality or to remove a tumor from the neck. Surgery was not initiated once a certain value of serum calMean age, yearsb cium was reached, and no case was identified in whom Males, n = 26 50.65 f 17.26 there was a progressive rise in calcium or loss of renal Females, n = 99 63.93 f 14.35 function over time. The plan for conservative management All patients, n = 126 61.41 f 15.17 was extremely simple, involving inquiry as to the patients' Age at parathyroidectomy, years well-being associated with annual documentation of the Males, n = 26 44.58 + 17.14 serum biochemistry. Regular abdominal x-rays were not Females, n = 95 58.42 + 12.96 used to identify renal calculi. Four renal stones became All patients, n = 121 54.95 f 15.64 clinically apparent during the follow-up period amounting Initial calcium, mmol/literc to over 700 patient-years. The occurrence of only four 2.84 f 0.45 Males, n = 24 stones suggests that such patients are at low risk for this Females, n = 89 2.88 f 0.63 complication. Provided there was not a significant inci2.87 f 0.43 All patients, n = 113 dence of clinically silent stones, it is hard to justify reDischarge calcium, mmol/liter peated abdominal x-rays. In a survey of all cases of hyper2.38 f 0.15 Males, n = 25 parathyroidism seen in a 5 month period in Birmingham, 2.38 k 0.23 Females, n = 78 only 7% of new cases had a renal stone.'" This supports 2.38 f 0.17 All patients, n = 103 the view offered that renal stones have become relatively Initial creatinine, Fmol/literd uncommon in hyperparathyroidism Males, n = 23 93.65 f 37.61 Of the patients in this series, 45% were considered 83.35 f 27.67 Females, n = 81 asymptomatic. This is very similar to the series reported All patients, n = 102 86.18 + 29.42 from the Mayo Clinic after the introduction of biochemiDischarge creatinine, pmol/liter cal screening.'s1 A more extensive review of the symptoms Males, n = 24 96.58 f 34.81 of this series has been given elsewhere.14) When all individFemales, n = 75 100.08 f 66.07 uals with hypercalcemia in Birmingham were investigated, All patients, n = 99 99.23 f 59.86 57% of all new cases of hyperparathyroidism were thought to be asymptomatic."' In normal circumstances mild hyaAll error denotations are standard deviations. percalcemia is often overlooked by clinicians. In addition, hAge in October 1990 to enable comparison with conservative management patients. symptomatic patients are much more likely to be referred 'Normal range for total serum calcium 2.20-2.60 mmol/ for treatment. These two facts almost certainly explain the liter. difference between the two local series. dNormal range for serum creatinine 50- I25 pmol/liter. The average age of all conservatively managed patients at diagnosis was around 60 years; they were followed for an average of 5 years. Because of coincidental diseases in ment is an acceptable form of treatment for older, asymp- many, it is not surprising that a number of patients died tomatic patients. 1 4 ) during follow-up. A total of 15 patients are known to have Throughout the study period the methods for diagnosis died and another 13 may have died, although some of of hyperparathyroidism were identical for both surgical these almost certainly moved to other parts of the country. and nonsurgical patients. The decision to recommend op- No example of a recognizable complication of hypercalerative or conservative management was made only after cemia or hyperparathyroidism was identified as a cause of death. The known causes of death span the common the diagnosis of hyperparathyroidism was secure. This study describes two groups of patients with primary causes of death seen in nonhyperparathyroid elderly pahyperparathyroidism, one treated surgically and the other tients. The English cross-sectional life tables published by conservatively. The major indication for surgery was the the registrar general predict 12 deaths for a group of this presence of a complication of the disease, usually renal age. The occurrence of 15 known deaths and the possibility stones, or significant symptoms, usually tiredness and leth- of a further 13 deaths in patients drawn exclusively from a argy. The recognition of tiredness and lethargy as a major hospital population, known in many cases to have degensymptom of hyperparathyroidism has occurred over the erative diseases on entry to the study, does not seem exceslast 20 years. The prevalence varies between series, in part sive. It is thus unlikely that untreated hyperparathyroidism because in some it is assumed to be a feature of normal had any marked influence on mortality. A subtle effect inaging; in others it is classified as a neuropsychiatric symp- creasing the risk of common causes of death, for example, tom.'" Tiredness and lethargy was assumed to be signifi- cancer or cardiovascular disease, could not have been decant when patients recognized that it was interfering with tected by this study. their quality of life. At that stage, surgery was advised. The current study suggests that conservative manageThe time taken to recognize the significance of the symp- ment can be considered in many patients with asymptotoms by the patient was the major cause of a delayed refer- matic or minimally symptomatic hyperparathyroidism. In ral for surgery. Although the surgical option was offered some, a decision to operate may evolve, but in many, conto all patients who were subsequently managed conserva- servative treatment can be continued.

s120

HEATH A N D HEATH TABLE4. CONSERVATIVE MANAGEMENT ~~

Group A:

Group B: alive 1990

Mean age, years Males Females All patients First high calcium to referral, years Total follow-up, years Personal follow-up, years Initial calcium, mmol/liter Males Females All patients Latest calcium Males Females All patients Initial creatinine, pmol/liter Males Females All patients Latest creatinine Males Females All patients

n = 22 n = 71

n = 93 n = 93

n = 93 n = 89 n = 21

n = 71 n = 92

n = 19 n = 68

n = 87 n = 20 n = 68

n = 88

n

=

55.32 f 20.52 66.72 k 11.20 64.67 f 13.16 1.16 k 1.84 6.86 rt 4.23 5.14 f 3.67

n = 15 n = 15

whereabouts unknown

75.87 f 11.19

n = 13 72.62 f 9.56

1.73 f 6.0 f 4.51 f

2.40 3.78 2.84

n

n = 15 n = 14

n

=

13

0.92 f 1.50 2.8 k 2.19 2.0 f 2.18

2.83 k 0.17 2.80 k 0.17 2.81 f 0.17

n = 15

2.87

k

0.18

n

=

12

2.77 f 0.17

2.71 5 0.24 2.75 k 0.19 2.73 f 0.20

n = 10

2.76 f

0.13

n = 9

99.75 k 10.31 83.74 k 18.76 87.38 f 18.43

n = 15

103.93 f 22.77

n = 11

94.0 f 18.0

n = 9

166.89

n = 9

88.0 f 13.0

17 109.88 94.19 97.53

n = 63 n = 80

Group C: dead

k k k

23.72 27.33 27.24

The previous experience of conservative management, which has been reviewed by us and other studies, has found it to be S a f e . ( 4 ~ If there are disadvantages to censervative management, they are likely to be subtle and reonly by a large controlled trial of surgical and conservative management. Further prospective studies are required to give additional information of the long-term efficacy of conservative management and to delineate what measurements are indicated in long-term care.

REFERENCES 1. Fisken RA, Heath DA, Bold AM 1980 Hypercalcaemia-a hospital survey. Q J Med 49:405-418. 2. Fisken RA, Heath DA, Somers S, Bold AM 1981 Hypercal-

caemia in hospital patients: Clinical and diagnostic aspects.

k

151.17

=

13

n = 13

2.70

k

0.16

Lancet 1:202-207. 3. Mundy GR, Cove DH, Fisken R, Somers S, Heath DA 1980 Primary hyperparathyroidism: Changes in the pattern of clinical presentation. Lancet 1:1317-1320. 4. Heath DA 1989 Primary hyperparathyroidism-clinical presentation and factors influencing clinical management. Endocrinol Metab Clin North Am Hodgson SF, Kennedy MA ,980 Primary hy5 . Heath HW perparathyroidism: Incidence, morbidity and potential economic impact on the community. N Engl J Med 302:189-193.

Address reprint requests to: Dr. David Heath Department of Medicine Queen Elizaberh Hospital Edgbaston Birmingham B15 2TH, England

Conservative management of primary hyperparathyroidism.

The personal management of patients seen with primary hyperparathyroidism over the past 10 years has been reviewed; 248 cases were identified of which...
317KB Sizes 0 Downloads 0 Views