JOURNAL OF BONE AND MINERAL RESEARCH Volume 6, Supplement 2, 1991 Mary Ann Lieberl, Inc., Publishers
Surgical Therapy of Patients with Primary Hyperparathyroidism: Long-Term Benefits SAMUEL A. WELLS, JR.
ABSTRACT Primary hyperparathyroidism was thought 30 years ago to be a rare disease, and the diagnosis was most often made in patients presenting with either bone disease or kidney stones. Today the minority of patients with hyperparathyroidism present with such symptoms, a fact accounted for by the introduction into general medical practice three decades ago of laboratory technology for efficiently determining the serum concentrations of various blood minerals, including calcium. Hypercalcemia was detected more frequently, and it was realized that most patients with hyperparathyroidism either had minor symptoms, such as constipation, polyuria, tiredness, and muscle weakness, or they were “asymptomatic” and indistinguishable from normal subjects. It was thought that primary hyperparathyroidism was a progressive disease and that sooner or later all patients would become symptomatic and require parathyroidectomy. Since this operation was curative in a high percentage of cases, it was recommended for virtually all patients once the diagnosis was established. In this contribution the long-term benefits of parathyroidectomy in patients with and without symptoms from primary hyperparathyroidism are reviewed. It is concluded that a multicenter prospective randomized trial is needed to resolve the indications for operative and nonoperative management of patients with this disease.
INTRODUCTION (PHPT) is a disease predominantly of postmenopausal females that affects approximately 1 in lo00 members of the U.S. population.‘’) Surgery is currently the treatment of choice for almost all patients with PHPT, and the large majority of cases are cured by parathyroidectomy. Whether all patients with hyperparathyroidism should be subjected to this operation has become controversial because the natural history of the disease in patients with minimal or no symptoms is unknown. Unfortunately, there are no prospective randomized trials comparing surgical therapy to nonoperative therapy in patients with asymptomatic PHPT. Until the late 1960s when automated methods for determining blood elements were introduced and widely practiced, the diagnosis of P H P T was relatively rare and most patients were diagnosed because of either renal stones or bone disease. Of the 64 patients reported by Albright and
P
RIMARY HYPERPARATHYROIDISM
Reifenstein in 1948,(*)80% had renal stones, 55% had bone disease, and only 2% were asymptomatic. In series of patients with P H P T reported from 1948 to the present (Table l),(3-1s) the incidence of bone disease and of renal stones progressively decreased (from a combined frequency of 60-90% to a combined frequency of 7-20Vo) and the incidence of asymptomatic patients increased (from 0 to 80%). Today the diagnosis of P H P T is often suspected because patients are found to have an elevated serum calcium concentration on routine blood analysis. Many such patients are described as “asymptomatic”; however, if carefully questioned they often describe such symptoms as muscle weakness, tiredness, constipation, polyuria, and depression. These nonspecific complaints associated with P H P T often disappear or significantly improve after parathyroidectomy. It is therefore important that the term “asymptomatic” P H P T refer to a disease state in patients who have none of the major or minor symptoms commonly associated with the disease. This is particularly true of elderly patients in whom symptoms, such as
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
S143
WELLS
s144
SERIESOF HYPERTHYROIDISM TABLE1. VARIOUSREPORTED
Number of patients
Series Surgical screening Albright and Reifenstein, 1948'2' Black, 195313' McGeown and Morrison, 195914' Hellstrom and Ivemark, 196215) Dent, 196216' Pyrah et al., 1966"' Britten et al., 1973LR' First decade Second decade Final 5 years Mallette et al., 197419) Barnes, 1984'10' Adami et al., 1984'") Niederle et al., 1987'12' Kristoffersson et al., 1987'"' Nikkila et al., 1989'14' Combined medical and surgical Heath et al., 1980"' 1965- 1974 1974- 1976 Mundy et al., 1980'15' Population screening Christenssen et al., 1976'16'
64 112 53 138 80 68
Patients with renal disease
Patients with bone disease
Asymptomatic patients
(%la
(%)
VOO)
81 79 91 86 68 68
54 28 8 43 31 54 100 10 5
0 0 0 0
0 -
11
1
49 47 57 159 328 212 311 61
80 50 39 23 45 51 32 18
49 29 13
39
51
10
51 111
4 7
8
18 51
0
57
56
8
12
80
14 5 15
-
23 40 -
4 18
38
aRenal stones or nephrocalcinosis. Source: Modified after Heath.'""'
muscle weakness and fatigue, may markedly limit routine activity. We review the long-term benefits of parathyroidectomy in patients with P H P T and consider the effectiveness of parathyroidectomy on: hypercalcemia, bone disease, kidney disease, muscle weakness, and psychiatric complaints.
HY PERCALCEMIA The sine qua non of cure in patients with P H P T is the permanent return of the serum calcium concentration to normal after parathyroidectomy. In reported series of patients followed after parathyroidectomy, the serum calcium concentration returns to normal in 85-95'70 of cases."6-zz) The cure rate depends on whether patients have single-gland or multiple-gland disease. In patients with P H P T due to a single enlarged parathyroid gland, the cure rate approaches 100%. In the study of Sivula and Ronni-Si~ula"~)of 287 patients having surgery for P H P T from 1956 to 1979, single-gland disease was present in 243 cases and multiple-gland disease was present in 44 cases. At the follow-up study (from 4 to 24 years after the initial
operation; mean 13 years) recurrent hypercalcemia was present in 2 (0.82%) of the patients with single-gland disease and in 18 (41%) of the patients with multiple-gland disease. In the study of Rudberg and of 441 patients with P H P T followed from 4 to 27 years after surgery, persistent hypercalcemia (almost always indicative of an incomplete neck exploration) was present immediately postoperatively in 8% of patients. Recurrent hypercalcemia, developing after a 6 month period of postoperative normocalcemia, occurred in 3 % of patients with singlegland disease and in 16% of patients with multiple-gland disease. Other i n ~ e s t i g a t o r s ( ~reported ~ . ~ ~ ) similar findings in that approximately 5-9% of patients having parathyroidectomy for P H P T have either persistent or recurrent hyperparathyroidism postoperatively. It is important to note that patients with P H P T and either two or three enlarged parathyroid glands found and resected at neck exploration have an incidence of recurrent hyperparathyroidism that is somewhat intermediate between that found in patients with single-gland disease and that found in patients with enlargement of all four parathyroid glands.(27' The incidence of permanent hypoparathyroidism in patients undergoing parathyroidectomy ranges between l and 7qo.'18.2'l
S145
BENEFITS OF SURGERY FOR HYPERPARATHYROIDISM
BONE DISEASE Patients with P H P T rarely present with advanced bone disease in the form of osteitis fibrosa cystica generalisata, and most often conventional radiography studies of the skeleton are normal. However, on careful examination by various imaging techniques it is possible to detect the presence of bone mineral loss in many asymptomatic patients. The studies evaluating bone disease in asymptomatic patients with P H P T are controversial, and there is no general agreement regarding the incidence of bone mineral loss and the rate at which it progresses. Furthermore, the specific bone changes that indicate the need for parathyroidectomy have not been clearly established. It is known that cortical bone, compared to cancellous or trabecular bone, is more often affected in patients with PHPT. It was early appreciated that patients with P H P T were at increased risk for bone fractures and the incidence in the series of Hellstrom and Ivemark“) and Pyrah and c o - ~ o r k e r s (was ~ ) 10%. Dauphine and associates(’R) reported vertebral crush fractures in 14 (4.4%) of 319 patients followed over a 3 year period. Similarly, in the study of Kochersberger and associates,(2P)the preoperative lateral chest roentgenograms of 191 patients with hyperparathyroidism were compared by “blinded” analysis to those of 192 carefully matched control patients who underwent cholecystectomy. Overall, 38 (20%) patients in the P H P T group were found to have vertebral fractures compared to 25 (13%) of the control patients. Wilson and however, in a study of data collected prospectively over a 10 year period on 174 patients with mild asymptomatic PHPT, found a prevalence of vertebral fracture of 1.7%. In white women, the group at greatest risk, the prevalence was 2.8%, a rate not significantly different from that previously observed in healthy white women.(3’)The reasons for the differences of these various investigators are unknown, and this is clearly an area in which additional carefully controlled studies are needed. Several investigators have evaluated bone mineral content (BMC) preoperatively and at varying intervals postoperatively (Table 2). Martin and associate^,^^') in a study of 30 patients undergoing surgery for PHPT, demonstrated a significant
loss (compareJ to age- and sex-matched normal subjects) in BMC of the distal radius. The BMC was significantly increased 1 year after surgery but was still below normal. measured cortical BMC in Mautalen and the radius before and after parathyroidectomy in 35 patients with overt P H P T and average serum calcium concentrations of 12.3 mg per 100 ml. In 14 patients studied 926 months after parathyroidectomy, the average incremenl in BMC was 9.9%; however, no further gain was observed after 2 years, indicating that bone mineral content remained markedly diminished and cortical bone loss was mostly irreversible. measured BMC in 45 patients Alhava and with PHPT. They found that the statistically significant demineralization present at the time of surgery reversed postoperatively, until at 4 years the values in patients almost reached those in control subjects. However, after 5 years the bone demineralization again increased. Martin and associate^^^') in a second study evaluated the radial BMC in 71 patients with P H P T before and after resection of a single parathyroid adenoma. Although BMC‘ increased during the first year after surgery, it remained more than 1 standard deviation (SD) below normal in 61 To of the patients. Thereafter, the monthly increment rate of BMC decreased rapidly with time and only minor increases occurred. Even though these and other studies demonstrate that in patients with P H P T there is an increase in the BMC following parathyroidectomy, the bone reparation is incomplete and bone mineral content remains below normal even though the hyperparathyroidism is cured. It has not been unequivocally shown in patients with asymptomatic P H P T that a decrease in BMC is associated with an increased fracture rate. Moreover, Rao and associates’36)studied 174 patients with asymptomatic PHPT. The patients had serum calcium concentrations below 12 mg per 100 ml, and forearm BMC was not more than 2 SD below the mean expected for age, sex, and ethnicity. Of these patients 80 were followed without any interventional therapy for 1-1 1 years (mean 46 months), during which time there was no change in any of the biochemical measurements and no decline in bone density other than that expected for age.
TABLE 2. EFFECTOF PARATHYROIDECTOMY ON BONEDISEASE Author
N
BMCa
FoIIo W - UP (years)
Result, Preop-Postop (or0 of normality)
Martin et al.c31)
30
SPA
1
13.2-80.6 k 11.7 < 0.05) 71.9 f 13.8-78.0 f 10 (p < 0.01) Increased mineralization to 4 years then progressive demineralization 74.5 k 14-80.4 k 12.5 ( P < 0.05) 73.8
&
(p
Mautalen et al.(33)
14
DPA
1.8
Alhava et al.(34)
45
DPA
1.5-1 1.5
Martin et al.(35)
71
SPA
1-12
aBMC, bone mineral content; SPA, single-photonabsorptiornetry; DPA, dual-photon absorpti-
ornetry.
WELLS
S146
KIDNEY DISEASE
cysti~a,‘~’)and profound weakness was described in of the first parathyroidectomy for Mandl’s case Patients with P H P T and renal stone disease are clearly PHPT. Subsequently there have been many descriptions of candidates for parathyroidectomy as the incidence of stone muscle weakness in patients with hyperparathyroidism; disease is markedly decreased following parathyroidec- however, it was not until the report of Patten and associtomy (Table 3).(37-4*) In many of the quoted studies it was a t e ~ ( ’ ~that ) histopathologic abnormalities were noted. noted that recurrent stone formation was uncommon in These investigators found weakness, easy fatigability, and patients with single-gland disease but relatively common in muscular atrophy. Electromyograms were abnormal, and patients with multiple-gland disease, or parathyroid hyper- muscle biopsy showed atrophy of both type I and type I 1 muscle fibers. Patients who were treated successfully plasia. From the early studies of Hellstrom and I ~ e m a r k , (it~ ) showed significant improvement within weeks after surwas shown that patients with preoperative renal insuffi- gery. ciency secondary to hyperparathyroidism often have proDelbridge and associates(’’) studied a consecutive series gressive deterioration of renal function postoperatively. of 100 patients undergoing parathyroidectomy for P H P T Also, it has generally been noted that a reduced creatinine and evaluated their neuromuscular symptoms. Of these paclearance in patients with P H P T rarely improves following tients 42 were 60 years of age or older, and 21 of them had parathyroidectomy. It has also been demonstrated that preoperative neuromuscular symptoms ranging from coma renal dysfunction in patients with P H P T is not progressive to muscular weakness. All the patients were rendered norpostoperatively except in the presence of such complicating mocalcemic following parathyroidectomy, and most of the factors as chronic urinary tract infection with pyelonephri- symptoms improved in the postoperative period. Of the 17 tis and severe hypertension.(43)In asymptomatic patients patients with muscle weakness, 15 reported a significant with P H P T there are rarely significant abnormalities in improvement, and 14 of the 15 patients complaining of fakidney function. There may be abnormal renal concen- tigue and lethargy reported an improvement. Similar findtrating capacity, but this usually returns to normal postop- ings have been reported by other investigators. ( 4 2 . 5 2 ~ 5 J ) Joborn and associates(’*)and Wersall-Robertson and aseratively. sociate~‘’~) evaluated muscle strength with a muscle dynamometer preoperatively and postoperatively in 16 and 13 HYPERTENSION patients with PHPT. Both groups found that their patients’ muscle strength was significantly improved followThe relationship of hypercalcemia and hypertension in ing parathyroidectomy. In a similar study, Kristofferson patients with P H P T is unknown and somewhat controverand measured maximal expiratory and inspirsia1.(44-47)Reports in the literature suggest that patients atory pressures before and 6- 12 months following parathywith P H P T have an increased incidence of high blood roidectomy for PHPT. There was a highly significant (p < pressure; however, the majority of studies show that the 0.02) improvement ( > 27%) in the maximal expiratory hypertension is not improved following parathyroidecpressures, but not the inspiratory pressures, of the patients tomy. It is generally thought that the presence of hypertenwith hyperparathyroidism (Table 4). sion is not an indication for surgery in patients with It is of interest that Turken and evaluated PHPT. 42 asymptomatic patients with mild P H P T (serum calcium 0.1 mg per 100 ml) and found no concentration 11.1 MUSCLE DISEASE evidence of muscle weakness or atrophy, hyperreflexia, abnormal gait, tongue fasciculations, or objective changes in Muscle weakness and atrophy were noted in von Reck- mental status. However, the patients complained of weaklinghausen’s original description of osteitis fibrosa ness and easy fatigability, muscle cramps, and paresthesia. TABLE3. EFFECTOF PARATHYROIDECTOMY Author
N
McGeo~n‘~~) Johansson et aI.(”)
56 84
ON
RENALSTONE DISEASE
Time
Recurrent
(years)
stones
5
8/56 0/19
Surgical Therapy of Patients with Primary Hyperparathyroidism: Long-Term Benefits SAMUEL A. WELLS, JR.
ABSTRACT Primary hyperparathyroidism was thought 30 years ago to be a rare disease, and the diagnosis was most often made in patients presenting with either bone disease or kidney stones. Today the minority of patients with hyperparathyroidism present with such symptoms, a fact accounted for by the introduction into general medical practice three decades ago of laboratory technology for efficiently determining the serum concentrations of various blood minerals, including calcium. Hypercalcemia was detected more frequently, and it was realized that most patients with hyperparathyroidism either had minor symptoms, such as constipation, polyuria, tiredness, and muscle weakness, or they were “asymptomatic” and indistinguishable from normal subjects. It was thought that primary hyperparathyroidism was a progressive disease and that sooner or later all patients would become symptomatic and require parathyroidectomy. Since this operation was curative in a high percentage of cases, it was recommended for virtually all patients once the diagnosis was established. In this contribution the long-term benefits of parathyroidectomy in patients with and without symptoms from primary hyperparathyroidism are reviewed. It is concluded that a multicenter prospective randomized trial is needed to resolve the indications for operative and nonoperative management of patients with this disease.
INTRODUCTION (PHPT) is a disease predominantly of postmenopausal females that affects approximately 1 in lo00 members of the U.S. population.‘’) Surgery is currently the treatment of choice for almost all patients with PHPT, and the large majority of cases are cured by parathyroidectomy. Whether all patients with hyperparathyroidism should be subjected to this operation has become controversial because the natural history of the disease in patients with minimal or no symptoms is unknown. Unfortunately, there are no prospective randomized trials comparing surgical therapy to nonoperative therapy in patients with asymptomatic PHPT. Until the late 1960s when automated methods for determining blood elements were introduced and widely practiced, the diagnosis of P H P T was relatively rare and most patients were diagnosed because of either renal stones or bone disease. Of the 64 patients reported by Albright and
P
RIMARY HYPERPARATHYROIDISM
Reifenstein in 1948,(*)80% had renal stones, 55% had bone disease, and only 2% were asymptomatic. In series of patients with P H P T reported from 1948 to the present (Table l),(3-1s) the incidence of bone disease and of renal stones progressively decreased (from a combined frequency of 60-90% to a combined frequency of 7-20Vo) and the incidence of asymptomatic patients increased (from 0 to 80%). Today the diagnosis of P H P T is often suspected because patients are found to have an elevated serum calcium concentration on routine blood analysis. Many such patients are described as “asymptomatic”; however, if carefully questioned they often describe such symptoms as muscle weakness, tiredness, constipation, polyuria, and depression. These nonspecific complaints associated with P H P T often disappear or significantly improve after parathyroidectomy. It is therefore important that the term “asymptomatic” P H P T refer to a disease state in patients who have none of the major or minor symptoms commonly associated with the disease. This is particularly true of elderly patients in whom symptoms, such as
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
S143
WELLS
s144
SERIESOF HYPERTHYROIDISM TABLE1. VARIOUSREPORTED
Number of patients
Series Surgical screening Albright and Reifenstein, 1948'2' Black, 195313' McGeown and Morrison, 195914' Hellstrom and Ivemark, 196215) Dent, 196216' Pyrah et al., 1966"' Britten et al., 1973LR' First decade Second decade Final 5 years Mallette et al., 197419) Barnes, 1984'10' Adami et al., 1984'") Niederle et al., 1987'12' Kristoffersson et al., 1987'"' Nikkila et al., 1989'14' Combined medical and surgical Heath et al., 1980"' 1965- 1974 1974- 1976 Mundy et al., 1980'15' Population screening Christenssen et al., 1976'16'
64 112 53 138 80 68
Patients with renal disease
Patients with bone disease
Asymptomatic patients
(%la
(%)
VOO)
81 79 91 86 68 68
54 28 8 43 31 54 100 10 5
0 0 0 0
0 -
11
1
49 47 57 159 328 212 311 61
80 50 39 23 45 51 32 18
49 29 13
39
51
10
51 111
4 7
8
18 51
0
57
56
8
12
80
14 5 15
-
23 40 -
4 18
38
aRenal stones or nephrocalcinosis. Source: Modified after Heath.'""'
muscle weakness and fatigue, may markedly limit routine activity. We review the long-term benefits of parathyroidectomy in patients with P H P T and consider the effectiveness of parathyroidectomy on: hypercalcemia, bone disease, kidney disease, muscle weakness, and psychiatric complaints.
HY PERCALCEMIA The sine qua non of cure in patients with P H P T is the permanent return of the serum calcium concentration to normal after parathyroidectomy. In reported series of patients followed after parathyroidectomy, the serum calcium concentration returns to normal in 85-95'70 of cases."6-zz) The cure rate depends on whether patients have single-gland or multiple-gland disease. In patients with P H P T due to a single enlarged parathyroid gland, the cure rate approaches 100%. In the study of Sivula and Ronni-Si~ula"~)of 287 patients having surgery for P H P T from 1956 to 1979, single-gland disease was present in 243 cases and multiple-gland disease was present in 44 cases. At the follow-up study (from 4 to 24 years after the initial
operation; mean 13 years) recurrent hypercalcemia was present in 2 (0.82%) of the patients with single-gland disease and in 18 (41%) of the patients with multiple-gland disease. In the study of Rudberg and of 441 patients with P H P T followed from 4 to 27 years after surgery, persistent hypercalcemia (almost always indicative of an incomplete neck exploration) was present immediately postoperatively in 8% of patients. Recurrent hypercalcemia, developing after a 6 month period of postoperative normocalcemia, occurred in 3 % of patients with singlegland disease and in 16% of patients with multiple-gland disease. Other i n ~ e s t i g a t o r s ( ~reported ~ . ~ ~ ) similar findings in that approximately 5-9% of patients having parathyroidectomy for P H P T have either persistent or recurrent hyperparathyroidism postoperatively. It is important to note that patients with P H P T and either two or three enlarged parathyroid glands found and resected at neck exploration have an incidence of recurrent hyperparathyroidism that is somewhat intermediate between that found in patients with single-gland disease and that found in patients with enlargement of all four parathyroid glands.(27' The incidence of permanent hypoparathyroidism in patients undergoing parathyroidectomy ranges between l and 7qo.'18.2'l
S145
BENEFITS OF SURGERY FOR HYPERPARATHYROIDISM
BONE DISEASE Patients with P H P T rarely present with advanced bone disease in the form of osteitis fibrosa cystica generalisata, and most often conventional radiography studies of the skeleton are normal. However, on careful examination by various imaging techniques it is possible to detect the presence of bone mineral loss in many asymptomatic patients. The studies evaluating bone disease in asymptomatic patients with P H P T are controversial, and there is no general agreement regarding the incidence of bone mineral loss and the rate at which it progresses. Furthermore, the specific bone changes that indicate the need for parathyroidectomy have not been clearly established. It is known that cortical bone, compared to cancellous or trabecular bone, is more often affected in patients with PHPT. It was early appreciated that patients with P H P T were at increased risk for bone fractures and the incidence in the series of Hellstrom and Ivemark“) and Pyrah and c o - ~ o r k e r s (was ~ ) 10%. Dauphine and associates(’R) reported vertebral crush fractures in 14 (4.4%) of 319 patients followed over a 3 year period. Similarly, in the study of Kochersberger and associates,(2P)the preoperative lateral chest roentgenograms of 191 patients with hyperparathyroidism were compared by “blinded” analysis to those of 192 carefully matched control patients who underwent cholecystectomy. Overall, 38 (20%) patients in the P H P T group were found to have vertebral fractures compared to 25 (13%) of the control patients. Wilson and however, in a study of data collected prospectively over a 10 year period on 174 patients with mild asymptomatic PHPT, found a prevalence of vertebral fracture of 1.7%. In white women, the group at greatest risk, the prevalence was 2.8%, a rate not significantly different from that previously observed in healthy white women.(3’)The reasons for the differences of these various investigators are unknown, and this is clearly an area in which additional carefully controlled studies are needed. Several investigators have evaluated bone mineral content (BMC) preoperatively and at varying intervals postoperatively (Table 2). Martin and associate^,^^') in a study of 30 patients undergoing surgery for PHPT, demonstrated a significant
loss (compareJ to age- and sex-matched normal subjects) in BMC of the distal radius. The BMC was significantly increased 1 year after surgery but was still below normal. measured cortical BMC in Mautalen and the radius before and after parathyroidectomy in 35 patients with overt P H P T and average serum calcium concentrations of 12.3 mg per 100 ml. In 14 patients studied 926 months after parathyroidectomy, the average incremenl in BMC was 9.9%; however, no further gain was observed after 2 years, indicating that bone mineral content remained markedly diminished and cortical bone loss was mostly irreversible. measured BMC in 45 patients Alhava and with PHPT. They found that the statistically significant demineralization present at the time of surgery reversed postoperatively, until at 4 years the values in patients almost reached those in control subjects. However, after 5 years the bone demineralization again increased. Martin and associate^^^') in a second study evaluated the radial BMC in 71 patients with P H P T before and after resection of a single parathyroid adenoma. Although BMC‘ increased during the first year after surgery, it remained more than 1 standard deviation (SD) below normal in 61 To of the patients. Thereafter, the monthly increment rate of BMC decreased rapidly with time and only minor increases occurred. Even though these and other studies demonstrate that in patients with P H P T there is an increase in the BMC following parathyroidectomy, the bone reparation is incomplete and bone mineral content remains below normal even though the hyperparathyroidism is cured. It has not been unequivocally shown in patients with asymptomatic P H P T that a decrease in BMC is associated with an increased fracture rate. Moreover, Rao and associates’36)studied 174 patients with asymptomatic PHPT. The patients had serum calcium concentrations below 12 mg per 100 ml, and forearm BMC was not more than 2 SD below the mean expected for age, sex, and ethnicity. Of these patients 80 were followed without any interventional therapy for 1-1 1 years (mean 46 months), during which time there was no change in any of the biochemical measurements and no decline in bone density other than that expected for age.
TABLE 2. EFFECTOF PARATHYROIDECTOMY ON BONEDISEASE Author
N
BMCa
FoIIo W - UP (years)
Result, Preop-Postop (or0 of normality)
Martin et al.c31)
30
SPA
1
13.2-80.6 k 11.7 < 0.05) 71.9 f 13.8-78.0 f 10 (p < 0.01) Increased mineralization to 4 years then progressive demineralization 74.5 k 14-80.4 k 12.5 ( P < 0.05) 73.8
&
(p
Mautalen et al.(33)
14
DPA
1.8
Alhava et al.(34)
45
DPA
1.5-1 1.5
Martin et al.(35)
71
SPA
1-12
aBMC, bone mineral content; SPA, single-photonabsorptiornetry; DPA, dual-photon absorpti-
ornetry.
WELLS
S146
KIDNEY DISEASE
cysti~a,‘~’)and profound weakness was described in of the first parathyroidectomy for Mandl’s case Patients with P H P T and renal stone disease are clearly PHPT. Subsequently there have been many descriptions of candidates for parathyroidectomy as the incidence of stone muscle weakness in patients with hyperparathyroidism; disease is markedly decreased following parathyroidec- however, it was not until the report of Patten and associtomy (Table 3).(37-4*) In many of the quoted studies it was a t e ~ ( ’ ~that ) histopathologic abnormalities were noted. noted that recurrent stone formation was uncommon in These investigators found weakness, easy fatigability, and patients with single-gland disease but relatively common in muscular atrophy. Electromyograms were abnormal, and patients with multiple-gland disease, or parathyroid hyper- muscle biopsy showed atrophy of both type I and type I 1 muscle fibers. Patients who were treated successfully plasia. From the early studies of Hellstrom and I ~ e m a r k , (it~ ) showed significant improvement within weeks after surwas shown that patients with preoperative renal insuffi- gery. ciency secondary to hyperparathyroidism often have proDelbridge and associates(’’) studied a consecutive series gressive deterioration of renal function postoperatively. of 100 patients undergoing parathyroidectomy for P H P T Also, it has generally been noted that a reduced creatinine and evaluated their neuromuscular symptoms. Of these paclearance in patients with P H P T rarely improves following tients 42 were 60 years of age or older, and 21 of them had parathyroidectomy. It has also been demonstrated that preoperative neuromuscular symptoms ranging from coma renal dysfunction in patients with P H P T is not progressive to muscular weakness. All the patients were rendered norpostoperatively except in the presence of such complicating mocalcemic following parathyroidectomy, and most of the factors as chronic urinary tract infection with pyelonephri- symptoms improved in the postoperative period. Of the 17 tis and severe hypertension.(43)In asymptomatic patients patients with muscle weakness, 15 reported a significant with P H P T there are rarely significant abnormalities in improvement, and 14 of the 15 patients complaining of fakidney function. There may be abnormal renal concen- tigue and lethargy reported an improvement. Similar findtrating capacity, but this usually returns to normal postop- ings have been reported by other investigators. ( 4 2 . 5 2 ~ 5 J ) Joborn and associates(’*)and Wersall-Robertson and aseratively. sociate~‘’~) evaluated muscle strength with a muscle dynamometer preoperatively and postoperatively in 16 and 13 HYPERTENSION patients with PHPT. Both groups found that their patients’ muscle strength was significantly improved followThe relationship of hypercalcemia and hypertension in ing parathyroidectomy. In a similar study, Kristofferson patients with P H P T is unknown and somewhat controverand measured maximal expiratory and inspirsia1.(44-47)Reports in the literature suggest that patients atory pressures before and 6- 12 months following parathywith P H P T have an increased incidence of high blood roidectomy for PHPT. There was a highly significant (p < pressure; however, the majority of studies show that the 0.02) improvement ( > 27%) in the maximal expiratory hypertension is not improved following parathyroidecpressures, but not the inspiratory pressures, of the patients tomy. It is generally thought that the presence of hypertenwith hyperparathyroidism (Table 4). sion is not an indication for surgery in patients with It is of interest that Turken and evaluated PHPT. 42 asymptomatic patients with mild P H P T (serum calcium 0.1 mg per 100 ml) and found no concentration 11.1 MUSCLE DISEASE evidence of muscle weakness or atrophy, hyperreflexia, abnormal gait, tongue fasciculations, or objective changes in Muscle weakness and atrophy were noted in von Reck- mental status. However, the patients complained of weaklinghausen’s original description of osteitis fibrosa ness and easy fatigability, muscle cramps, and paresthesia. TABLE3. EFFECTOF PARATHYROIDECTOMY Author
N
McGeo~n‘~~) Johansson et aI.(”)
56 84
ON
RENALSTONE DISEASE
Time
Recurrent
(years)
stones
5
8/56 0/19
