MJA: Delbridge et al., Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes

Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes

Leigh W Delbridge, Nidal A Younes, Ana I Guinea,
Thomas S Reeve, Phillip Clifton-Bligh and Bruce G Robinson

MJA 1998; 168: 153-156
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Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details
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Abstract
Objective: To examine changes over the past three decades in the indications for, and outcomes of, surgery for primary hyperparathyroidism.
Design: Survey of a prospective hospital database.
Setting: Royal North Shore Hospital (a tertiary referral and university teaching hospital), Sydney, New South Wales, January 1962 to December 1996.
Patients: All 733 patients who underwent neck exploration for primary hyperparathyroidism.
Results: The annual number of parathyroidectomies increased virtually exponentially, from a mean of two in 1962-1969 to 73 in 1996. In the 1960s and 1970s, the most common indication for surgery was the presence of renal calculi (58% and 43%, respectively), but in the 1980s there was a marked increase in presentation of asymptomatic disease after biochemical screening (19%). In the 1990s, low bone mineral density detected by osteodensitometry has become the most common indication for surgery (31%). After initial operation, 11 patients (2%) had persistent hypercalcaemia, with five of these cured by reoperation -- an overall failure rate of 1%.
Conclusions: Surgery for primary hyperparathyroidism has become increasingly common, with low bone mineral density replacing renal calculi as the most common indication for surgery. Neck exploration in experienced hands results in an overall cure rate of 99%.
Introduction
The past few decades have seen dramatic changes in the apparent incidence, presentation and management of primary hyperparathyroidism. With advances such as ready access to serum calcium and parathyroid hormone measurements, the condition is being increasingly recognised and treated, and new patterns of presentation are being seen. The classic bone disease osteitis fibrosa cystica, the principal manifestation early this century, is now rare.¹ A clinical picture has emerged characterised either by an absence of symptoms or by subtle and vague symptoms,^2-4 such as fatigue, weakness, and variable aches and pains, with the condition often suspected only because of an incidental finding of an elevated serum calcium level on biochemical testing. The recent introduction of bone mineral density screening by osteodensitometry seems also to have increased detection of cases of primary hyperparathyroidism.⁵
Our aim was to examine the changes over the past three decades in presentation and management of primary hyperparathyroidism at a single large referral centre, and to analyse the indications for, and outcomes of, surgery for this condition.
Methods
Subjects were all patients who underwent surgery for primary hyperparathyroidism in the Endocrine Surgical Unit at Royal North Shore Hospital, Sydney, New South Wales, from January 1962 (date of the first parathyroidectomy at the unit) until December 1996. Information was obtained from the prospective database of all endocrine surgical procedures maintained at that hospital since January 1957. The database was searched for any follow-up to December 1997.
The diagnosis of primary hyperparathyroidism was based on the finding of an elevated serum calcium concentration and, when available, an inappropriately normal or elevated parathyroid hormone concentration. Before 1972, parathyroid hormone assays were not available, and the diagnosis was based on a combination of biochemical, radiological and clinical changes (eg, renal stones, urinary tract infection, abdominal pain and neuropsychological disturbances). Patients with secondary or tertiary hyperparathyroidism were excluded from the study.
Information was obtained on the presentation, indications for surgery, operative details, postoperative complications, histopathological results and surgical outcomes. Persistent hyperparathyroidism was defined as hyper calcaemia continuing after surgery. Recurrent hyperparathyroidism was defined as hypercalcaemia returning after a minimum of six months of postoperative normocalcaemia.
Results
Between January 1962 and December 1996, 733 patients underwent neck exploration for primary hyperparathyroidism at Royal North Shore Hospital. They comprised 161 males (22%) and 572 females (78%), with an age range of 9-96 years (median age, 53 years for males and 60 years for females).
Annual numbers of operations for primary hyperparathyroidism are shown in Figure 1. The number has risen virtually exponentially, from one to four annually in the 1960s, to 73 in 1996.

Indications for surgery: These are shown in Box 1. The presence of renal calculi was the principal indication for surgery between 1962 and 1969, accounting for 58% of operations, but has progressively decreased in importance, accounting for only 15% of operations between 1990 and 1996.
Numbers of asymptomatic patients (in whom none of the recognised symptoms of primary hyperparathyroidism could be identified preoperatively) increased in the 1970s and 1980s, but remained low overall (105 patients, 14%).
Between 1990 and 1996, the most marked change was the increase in patients with low bone mineral density detected on screening for osteoporosis (by osteodensitometry or quantitative computed tomography) as the principal indication for surgery. In the 1990s, it was the most common indication (31% of cases), followed by neuromuscular or neuropsychiatric symptoms (20%) and renal calculi (15%), with only 14% of cases considered truly asymptomatic.
Surgical and pathological findings: At surgery, single-gland disease (presence of only one enlarged gland) was found in 556 patients (76%), two-gland disease in 40 (5%), three-gland disease in two (0.3%), four-or-more-gland disease in 121 (17%), carcinoma in two (0.3%), cyst in seven (1%), and no parathyroid abnormality in five (0.7%).
Complications of surgery: Postoperative hypocalcaemia requiring calcium supplementation was seen in 81 patients (11%), but only two of these had permanent hypoparathyroidism. Eight patients developed a wound infection (1%), eight required reoperation for haemorrhage (1%), six had a permanent vocal cord palsy (1%), and one required a temporary tracheostomy because of intraoral haemorrhage caused by injury to the tongue. One patient with pre-existing ischaemic heart disease died in the immediate postoperative period.
Outcomes of surgery: Hypercalcaemia was cured immediately in 716 of the 733 patients. In six of the remaining 17, initial neck exploration showed no abnormalities, and they were subsequently shown to have conditions other than hyperparathyroidism, for which surgery was not indicated: sarcoidosis (three), familial hypocalciuric hypercalcaemia (two), and persistent hypercalcaemia with no apparent cause (one).
Eleven patients had persistent hypercalcaemia caused by primary hyperparathyroidism after initial surgery, giving an initial cure rate of 98%. Details of initial and subsequent surgery for these 11 are shown in Box 2. Five were cured by re-exploration of the neck, two remained hypercalcaemic after a further unsuccessful re-exploration, and four had not undergone further surgery (two refused and two were awaiting further assessment). Thus, the overall cure rate for surgery was 99%.
Hypercalcaemia was known to have recurred in two patients, at a mean of 10.5 years after successful surgery. Recurrence was associated with multiple endocrine neoplasia Type 1 syndrome (MEN1) in one of these patients and was cured by removal of the remnant and autotransplantation. The second patient had mild asymptomatic hyperparathyroidism for which reoperation was not indicated.
Discussion
We found that, as expected, surgery for primary hyperparathyroidism became increasingly common at Royal North Shore Hospital over the past three decades. In the 1990s, low bone mineral density replaced renal calculi as the most common indication for surgery. Initial neck exploration resulted in cure in 98% of cases.
Primary hyperparathyroidism occurs relatively frequently in the community, with an incidence of at least 1 in 1000 individuals,⁶ and may be as frequent as 1 in every 500 women over the age of 50 years.⁷ The very small numbers of patients being diagnosed and treated as recently as two decades ago related to lack of ready access to serum calcium and parathyroid hormone measurements, as well as lack of awareness of the disease.
Surgery is indicated in patients with symptoms or a high serum calcium level, and in asymptomatic patients who are not suitable for conservative management.⁸ The commonest indication for surgery now is the presence of low bone mineral density (36% of operations in 1996). Recovery of bone mass has been documented after successful parathyroid surgery in many series, even in patients with mild or asymptomatic hyperparathyroidism.⁵
The presence of renal calculi remains a major indication for surgery. Although the percentage of patients undergoing neck exploration for this indication has declined significantly each decade, the actual numbers have, in fact, steadily increased. Renal calculus formation is reduced after successful parathyroid surgery,⁹ although preformed stones or those associated with idiopathic hypercalciuria may continue to be passed.¹⁰
Marked muscular atrophy is rarely seen nowadays, but muscular weakness contributing to a general feeling of tiredness and malaise is noticed in most patients with primary hyperparathyroidism.¹¹ We found neuromuscular disease was the primary indication in 11% of our patients. Abnormalities included muscular atrophy, generalised weakness and fatigue, which are thought to be related to low plasma phosphate level and possibly hypokalaemia. Many patients with these symptoms have reported improvement after parathyroidectomy.^12,13
Neuropsychiatric symptoms were the primary indication for surgery in only 9% of patients in this series, but may be found (if sought) in significant numbers of patients with primary hyperparathyroidism (reported incidence, 30%- 100%).¹⁴ Symptoms include depression, anxiety, fatigue, lassitude, concentration difficulties, and failing memory. They have been reported to improve or disappear in most patients after surgery.^12,15 A recent study showed that the most dramatic changes are reductions in body pain and improvements in vitality and emotional function.¹⁶
Similarly, although abdominal symptoms (which may be related to peptic ulcer disease, pancreatitis or constipation) were the primary indication for surgery in only 5% of our patients, they may be seen in up to 20% of patients with primary hyperparathyroidism.¹⁷
In our series, 14% of patients appeared asymptomatic. The proportion of patients with primary hyperparathyroidism reported to be asymptomatic varies greatly, from 2% to 80%,^3,17-19 possibly depending on the care with which they are evaluated. Indeed, vague psychiatric and neuromuscular symptoms and generalised weakness may be fully appreciated only in retrospect, once normocalcaemia has been achieved by surgery.²⁰
It is important to consider surgery even in the asymptomatic, as there is increasing evidence that primary hyperparathyroidism affects longevity. Several studies have shown that untreated individuals with mild hypercalcaemia have a reduced survival rate.²¹ A study of 441 patients followed up for a mean of eight years showed that successful parathyroid surgery reduced the risk of dying,²¹ while a more recent study of 896 patients confirmed this result and showed that the duration of hyperparathyroidism is also a factor, with early surgery reducing the risk of dying.²² A National Institutes of Health consensus statement from 1990 addressing the management of asymptomatic primary hyperparathyroidism recommends that "all patients with primary hyperparathyroidism should be considered to be candidates for surgery".⁸
The aim of surgery in primary hyperparathyroidism is to identify and remove all abnormal parathyroid tissue. As multiple-gland disease is common (22% of patients in this series), the mainstay of good surgical technique is to identify all (four or more) parathyroid glands in order to differentiate normal from abnormal glands (see Figure 2). We believe that current passing interest in "minimal access" parathyroid surgery (endoscopic or unilateral minimal incisions based on preoperative localisation) is misguided. Such techniques should be avoided as they will inevitably increase failure rates from unsuspected multiple-gland disease for, at best, a very marginal cosmetic advantage.

Localisation techniques such as ultrasonography, computed tomography and scintigraphy with sestamibi have not shown sufficient sensitivity and specificity to justify routine use before initial operation and are certainly not cost-effective.^23,24 False positive and false negative results from preoperative localisation tests may add confusion, especially for the inexperienced surgeon. Indeed, surgery undertaken by those not experienced in the procedure has been shown to be associated with a high failure rate and need for reoperation, as well as increased complications.²⁵ For example, a Scandinavian study showed that surgery performed in units doing fewer than 10 parathyroidectomies per year resulted in only 70% of patients achieving long-term normocalcaemia,²⁵ whereas in experienced units a success rate of 98% should be achieved.
Acknowledgements
We wish to acknowledge the following additional physicians and endocrinologists who have contributed at least several patients each to this study: Dr J Beattie, Dr D Darnell, Dr T Diamond, Dr G Fulcher, Dr S Grant, Dr I Hales, Dr A Jameson, Dr A Joasoo, Dr F Lomas, Assoc Prof JD Wilson, Dr A McElduff, Dr J Miller, Professor S Posen, Dr M Prowse, Dr P Rohl, Dr M Rosman, Dr J Stiel, Dr R Slobodniuk, Dr C White and Dr E Wilmshurst. We also thank the many other physicians and endocrinologists who have each contributed one or two patients.
References

Welbourn RB. The history of endocrine surgery. New York: Praeger, 1990.
Heath H. Clinical spectrum of primary hyperparathyroidism: Evolution with changes in medical practice and technology. J Bone Miner Res 1991; 6: S63-S70.
Heath H, Hodgson SE, Kennedy MA. Primary hyperparathyroidism: incidence, morbidity and potential economic impact in a community. N Engl J Med 1980; 302: 189-193.
Chan AK, Duh Q-Y, Katz MH, et al. Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy. Ann Surg 1995; 222: 402-414.
Warner J, Clifton-Bligh P, MacElduff A, et al. Longitudinal changes in forearm bone mineral content in primary hyperparathyroidism. J Bone Miner Res 1991; 6 Suppl 2: 91-95.
Christenson T, Hellstrom K, Wengle R, et al. Prevalence of hypercalcemia in a health screening in Stockholm. Acta Med Scan 1976; 200: 131-137.
Boonstra CE, Jackson JE. Serum calcium survey for hyperparathyoidism: results in 5000 clinical patients. Am J Clin Pathol 1971; 55: 523-526.
Consensus Development Conference Panel. Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement. Ann Int Med 1991; 114: 593-597.
Deaconson TF, Wilson SD, Lemann J Jr. The effect of parathyroidectomy on the recurrence of nepherolithiasis. Surgery 1987; 102: 910-913.
Posen S, Clifton-Bligh P, Reeve TS, et al. Is parathyroidectomy of benefit in primary hyperparathyroidism? QJM 1985; 54: 241-251.
Turken SA, Cafferty M, Silverberg SJ, et al. Neuromuscular involvement in mild asymptomatic primary hyperparathyroidism. Am J Med 1989; 87: 553-557.
Delbridge LW, Marshman D, Reeve TS. Neuromuscular symptoms in elderly patients with hyperparathyroidism: improvement with parathyroid surgery. Med J Aust 1988; 149: 74-76.
Kristoffersson A, Bostrom A, Soderberg T. Muscle strength is improved after parathyroidectomy in patients with hyperparathyroidism. Br J Surg 1992; 79: 165-168.
Joborn C, Hetta J, Palmer M, et al. Psychiatric symptomatology in patients with primary hyperparathyroidism. Ups J Med Sci 1986; 91: 77-87.
Joborn C, Hetta J, Lind L, et al. Self rated psychiatric symptoms in patients operated on because of primary hyperparathyroidism and in patients with longstanding mild hypercalcemia. Surgery 1989; 105: 72-78.
Burney R, Jones K, Coon J, et al. Assessment of patient outcomes after operation for primary hyperparathyroidism. Surgery 1996; 120: 1013-1019.
Kaplan EL, Yashiro T, Salti G. Primary hyperparathyroidism in the 90s. Ann Surg 1991; 215: 300-317.
Ljunghall S, Hellman P, Rasted J, Akersorm G. Primary hyperparathyroidism: epidemiology, diagnosis, and clinical picture. World J Surg 1991; 15: 681-687.
Van Heerden JA, Grant CS. Surgical treatment of primary hyperparathyroidism: an institutional perspective. World J Surg 1991; 15: 688-692.
Harrison BJ, Wheeler MH. Asymptomatic primary hyperparathyroidism. World J Surg 1991; 15: 724-729.
Palmer M, Adami H-O, Bergstrom R, et al. Mortality after operation for primary hyperparathyroidism. A follow-up of 441 patients operated on during 1956-1979. Surgery 1987; 102: 1-7.
Hedback G, Oden A, Tisell L. The influence of surgery on the risk of death in patients with primary hyperparathyroidism. World J Surg 1991; 15: 399-407.
Miller DC. Preoperative localisation and interventional treatment of parathyroid tumours: when and how. World J Surg 1992; 15: 706-715.
Serpell JW, Cambell PR, Young AE. Pre-operative localisation of parathyroid tumours does not reduce operating time. Br J Surg 1991; 78: 589-590.
Malmaaeus J, Granberg PO, Halvorsen J, et al. Parathyroid surgery in Scandinavia. Acta Chir Scand 1988; 154: 409-413.

(Received 1 Jul, accepted 26 Nov, 1997)

Authors' details

Department of Surgery, University of Sydney, and Royal North Shore Hospital, Sydney, NSW.
Leigh W Delbridge, MD, FRACS, Professor of Surgery;
Nidal A Younes, MD, Fellow in Endocrine Surgery; currently, Surgeon, University of Jordan Hospital, Amman, Jordan;
Ana I Guinea, BSc(Psych)(Hons), Psychologist;
Thomas S Reeve, MD, FRACS, Emeritus Professor.

Department of Endocrinology, University of Sydney, and Royal North Shore Hospital, Sydney, NSW.
Phillip Clifton-Bligh, FRACP, Clinical Associate Professor in Medicine;
Bruce G Robinson, MD, FRACP, Professor of Medicine (Endocrinology), University of Sydney, and Kolling Institute of Medical Research, Sydney, NSW.

Reprints will not be available from the authors. Correspondence: Professor L W Delbridge, Department of Surgery, Royal North Shore Hospital, St Leonards, NSW 2065.
E-mail: leighd AT med.su.oz.au


Abstract	*Objective:* To examine changes over the past three decades in the indications for, and outcomes of, surgery for primary hyperparathyroidism. *Design:* Survey of a prospective hospital database. *Setting:* Royal North Shore Hospital (a tertiary referral and university teaching hospital), Sydney, New South Wales, January 1962 to December 1996. *Patients:* All 733 patients who underwent neck exploration for primary hyperparathyroidism. *Results:* The annual number of parathyroidectomies increased virtually exponentially, from a mean of two in 1962-1969 to 73 in 1996. In the 1960s and 1970s, the most common indication for surgery was the presence of renal calculi (58% and 43%, respectively), but in the 1980s there was a marked increase in presentation of asymptomatic disease after biochemical screening (19%). In the 1990s, low bone mineral density detected by osteodensitometry has become the most common indication for surgery (31%). After initial operation, 11 patients (2%) had persistent hypercalcaemia, with five of these cured by reoperation -- an overall failure rate of 1%. *Conclusions:* Surgery for primary hyperparathyroidism has become increasingly common, with low bone mineral density replacing renal calculi as the most common indication for surgery. Neck exploration in experienced hands results in an overall cure rate of 99%.
Introduction	The past few decades have seen dramatic changes in the apparent incidence, presentation and management of primary hyperparathyroidism. With advances such as ready access to serum calcium and parathyroid hormone measurements, the condition is being increasingly recognised and treated, and new patterns of presentation are being seen. The classic bone disease osteitis fibrosa cystica, the principal manifestation early this century, is now rare.¹ A clinical picture has emerged characterised either by an absence of symptoms or by subtle and vague symptoms,^2-4 such as fatigue, weakness, and variable aches and pains, with the condition often suspected only because of an incidental finding of an elevated serum calcium level on biochemical testing. The recent introduction of bone mineral density screening by osteodensitometry seems also to have increased detection of cases of primary hyperparathyroidism.⁵ Our aim was to examine the changes over the past three decades in presentation and management of primary hyperparathyroidism at a single large referral centre, and to analyse the indications for, and outcomes of, surgery for this condition.
Methods	Subjects were all patients who underwent surgery for primary hyperparathyroidism in the Endocrine Surgical Unit at Royal North Shore Hospital, Sydney, New South Wales, from January 1962 (date of the first parathyroidectomy at the unit) until December 1996. Information was obtained from the prospective database of all endocrine surgical procedures maintained at that hospital since January 1957. The database was searched for any follow-up to December 1997. The diagnosis of primary hyperparathyroidism was based on the finding of an elevated serum calcium concentration and, when available, an inappropriately normal or elevated parathyroid hormone concentration. Before 1972, parathyroid hormone assays were not available, and the diagnosis was based on a combination of biochemical, radiological and clinical changes (eg, renal stones, urinary tract infection, abdominal pain and neuropsychological disturbances). Patients with secondary or tertiary hyperparathyroidism were excluded from the study. Information was obtained on the presentation, indications for surgery, operative details, postoperative complications, histopathological results and surgical outcomes. Persistent hyperparathyroidism was defined as hyper calcaemia continuing after surgery. Recurrent hyperparathyroidism was defined as hypercalcaemia returning after a minimum of six months of postoperative normocalcaemia.
Results	Between January 1962 and December 1996, 733 patients underwent neck exploration for primary hyperparathyroidism at Royal North Shore Hospital. They comprised 161 males (22%) and 572 females (78%), with an age range of 9-96 years (median age, 53 years for males and 60 years for females). Annual numbers of operations for primary hyperparathyroidism are shown in Figure 1. The number has risen virtually exponentially, from one to four annually in the 1960s, to 73 in 1996. *Indications for surgery:* These are shown in Box 1. The presence of renal calculi was the principal indication for surgery between 1962 and 1969, accounting for 58% of operations, but has progressively decreased in importance, accounting for only 15% of operations between 1990 and 1996. Numbers of asymptomatic patients (in whom none of the recognised symptoms of primary hyperparathyroidism could be identified preoperatively) increased in the 1970s and 1980s, but remained low overall (105 patients, 14%). Between 1990 and 1996, the most marked change was the increase in patients with low bone mineral density detected on screening for osteoporosis (by osteodensitometry or quantitative computed tomography) as the principal indication for surgery. In the 1990s, it was the most common indication (31% of cases), followed by neuromuscular or neuropsychiatric symptoms (20%) and renal calculi (15%), with only 14% of cases considered truly asymptomatic. *Surgical and pathological findings:* At surgery, single-gland disease (presence of only one enlarged gland) was found in 556 patients (76%), two-gland disease in 40 (5%), three-gland disease in two (0.3%), four-or-more-gland disease in 121 (17%), carcinoma in two (0.3%), cyst in seven (1%), and no parathyroid abnormality in five (0.7%). *Complications of surgery:* Postoperative hypocalcaemia requiring calcium supplementation was seen in 81 patients (11%), but only two of these had permanent hypoparathyroidism. Eight patients developed a wound infection (1%), eight required reoperation for haemorrhage (1%), six had a permanent vocal cord palsy (1%), and one required a temporary tracheostomy because of intraoral haemorrhage caused by injury to the tongue. One patient with pre-existing ischaemic heart disease died in the immediate postoperative period. *Outcomes of surgery:* Hypercalcaemia was cured immediately in 716 of the 733 patients. In six of the remaining 17, initial neck exploration showed no abnormalities, and they were subsequently shown to have conditions other than hyperparathyroidism, for which surgery was not indicated: sarcoidosis (three), familial hypocalciuric hypercalcaemia (two), and persistent hypercalcaemia with no apparent cause (one). Eleven patients had persistent hypercalcaemia caused by primary hyperparathyroidism after initial surgery, giving an initial cure rate of 98%. Details of initial and subsequent surgery for these 11 are shown in Box 2. Five were cured by re-exploration of the neck, two remained hypercalcaemic after a further unsuccessful re-exploration, and four had not undergone further surgery (two refused and two were awaiting further assessment). Thus, the overall cure rate for surgery was 99%. Hypercalcaemia was known to have recurred in two patients, at a mean of 10.5 years after successful surgery. Recurrence was associated with multiple endocrine neoplasia Type 1 syndrome (MEN1) in one of these patients and was cured by removal of the remnant and autotransplantation. The second patient had mild asymptomatic hyperparathyroidism for which reoperation was not indicated.
Discussion	We found that, as expected, surgery for primary hyperparathyroidism became increasingly common at Royal North Shore Hospital over the past three decades. In the 1990s, low bone mineral density replaced renal calculi as the most common indication for surgery. Initial neck exploration resulted in cure in 98% of cases. Primary hyperparathyroidism occurs relatively frequently in the community, with an incidence of at least 1 in 1000 individuals,⁶ and may be as frequent as 1 in every 500 women over the age of 50 years.⁷ The very small numbers of patients being diagnosed and treated as recently as two decades ago related to lack of ready access to serum calcium and parathyroid hormone measurements, as well as lack of awareness of the disease. Surgery is indicated in patients with symptoms or a high serum calcium level, and in asymptomatic patients who are not suitable for conservative management.⁸ The commonest indication for surgery now is the presence of low bone mineral density (36% of operations in 1996). Recovery of bone mass has been documented after successful parathyroid surgery in many series, even in patients with mild or asymptomatic hyperparathyroidism.⁵ The presence of renal calculi remains a major indication for surgery. Although the percentage of patients undergoing neck exploration for this indication has declined significantly each decade, the actual numbers have, in fact, steadily increased. Renal calculus formation is reduced after successful parathyroid surgery,⁹ although preformed stones or those associated with idiopathic hypercalciuria may continue to be passed.¹⁰ Marked muscular atrophy is rarely seen nowadays, but muscular weakness contributing to a general feeling of tiredness and malaise is noticed in most patients with primary hyperparathyroidism.¹¹ We found neuromuscular disease was the primary indication in 11% of our patients. Abnormalities included muscular atrophy, generalised weakness and fatigue, which are thought to be related to low plasma phosphate level and possibly hypokalaemia. Many patients with these symptoms have reported improvement after parathyroidectomy.^12,13 Neuropsychiatric symptoms were the primary indication for surgery in only 9% of patients in this series, but may be found (if sought) in significant numbers of patients with primary hyperparathyroidism (reported incidence, 30%- 100%).¹⁴ Symptoms include depression, anxiety, fatigue, lassitude, concentration difficulties, and failing memory. They have been reported to improve or disappear in most patients after surgery.^12,15 A recent study showed that the most dramatic changes are reductions in body pain and improvements in vitality and emotional function.¹⁶ Similarly, although abdominal symptoms (which may be related to peptic ulcer disease, pancreatitis or constipation) were the primary indication for surgery in only 5% of our patients, they may be seen in up to 20% of patients with primary hyperparathyroidism.¹⁷ In our series, 14% of patients appeared asymptomatic. The proportion of patients with primary hyperparathyroidism reported to be asymptomatic varies greatly, from 2% to 80%,^3,17-19 possibly depending on the care with which they are evaluated. Indeed, vague psychiatric and neuromuscular symptoms and generalised weakness may be fully appreciated only in retrospect, once normocalcaemia has been achieved by surgery.²⁰ It is important to consider surgery even in the asymptomatic, as there is increasing evidence that primary hyperparathyroidism affects longevity. Several studies have shown that untreated individuals with mild hypercalcaemia have a reduced survival rate.²¹ A study of 441 patients followed up for a mean of eight years showed that successful parathyroid surgery reduced the risk of dying,²¹ while a more recent study of 896 patients confirmed this result and showed that the duration of hyperparathyroidism is also a factor, with early surgery reducing the risk of dying.²² A National Institutes of Health consensus statement from 1990 addressing the management of asymptomatic primary hyperparathyroidism recommends that "all patients with primary hyperparathyroidism should be considered to be candidates for surgery".⁸ The aim of surgery in primary hyperparathyroidism is to identify and remove all abnormal parathyroid tissue. As multiple-gland disease is common (22% of patients in this series), the mainstay of good surgical technique is to identify all (four or more) parathyroid glands in order to differentiate normal from abnormal glands (see Figure 2). We believe that current passing interest in "minimal access" parathyroid surgery (endoscopic or unilateral minimal incisions based on preoperative localisation) is misguided. Such techniques should be avoided as they will inevitably increase failure rates from unsuspected multiple-gland disease for, at best, a very marginal cosmetic advantage.

	Localisation techniques such as ultrasonography, computed tomography and scintigraphy with sestamibi have not shown sufficient sensitivity and specificity to justify routine use before initial operation and are certainly not cost-effective.^23,24 False positive and false negative results from preoperative localisation tests may add confusion, especially for the inexperienced surgeon. Indeed, surgery undertaken by those not experienced in the procedure has been shown to be associated with a high failure rate and need for reoperation, as well as increased complications.²⁵ For example, a Scandinavian study showed that surgery performed in units doing fewer than 10 parathyroidectomies per year resulted in only 70% of patients achieving long-term normocalcaemia,²⁵ whereas in experienced units a success rate of 98% should be achieved.
Acknowledgements	We wish to acknowledge the following additional physicians and endocrinologists who have contributed at least several patients each to this study: Dr J Beattie, Dr D Darnell, Dr T Diamond, Dr G Fulcher, Dr S Grant, Dr I Hales, Dr A Jameson, Dr A Joasoo, Dr F Lomas, Assoc Prof JD Wilson, Dr A McElduff, Dr J Miller, Professor S Posen, Dr M Prowse, Dr P Rohl, Dr M Rosman, Dr J Stiel, Dr R Slobodniuk, Dr C White and Dr E Wilmshurst. We also thank the many other physicians and endocrinologists who have each contributed one or two patients.
References	Welbourn RB. The history of endocrine surgery. New York: Praeger, 1990. Heath H. Clinical spectrum of primary hyperparathyroidism: Evolution with changes in medical practice and technology. J Bone Miner Res 1991; 6: S63-S70. Heath H, Hodgson SE, Kennedy MA. Primary hyperparathyroidism: incidence, morbidity and potential economic impact in a community. N Engl J Med 1980; 302: 189-193. Chan AK, Duh Q-Y, Katz MH, et al. Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy. Ann Surg 1995; 222: 402-414. Warner J, Clifton-Bligh P, MacElduff A, et al. Longitudinal changes in forearm bone mineral content in primary hyperparathyroidism. J Bone Miner Res 1991; 6 Suppl 2: 91-95. Christenson T, Hellstrom K, Wengle R, et al. Prevalence of hypercalcemia in a health screening in Stockholm. Acta Med Scan 1976; 200: 131-137. Boonstra CE, Jackson JE. Serum calcium survey for hyperparathyoidism: results in 5000 clinical patients. Am J Clin Pathol 1971; 55: 523-526. Consensus Development Conference Panel. Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement. Ann Int Med 1991; 114: 593-597. Deaconson TF, Wilson SD, Lemann J Jr. The effect of parathyroidectomy on the recurrence of nepherolithiasis. Surgery 1987; 102: 910-913. Posen S, Clifton-Bligh P, Reeve TS, et al. Is parathyroidectomy of benefit in primary hyperparathyroidism? QJM 1985; 54: 241-251. Turken SA, Cafferty M, Silverberg SJ, et al. Neuromuscular involvement in mild asymptomatic primary hyperparathyroidism. Am J Med 1989; 87: 553-557. Delbridge LW, Marshman D, Reeve TS. Neuromuscular symptoms in elderly patients with hyperparathyroidism: improvement with parathyroid surgery. Med J Aust 1988; 149: 74-76. Kristoffersson A, Bostrom A, Soderberg T. Muscle strength is improved after parathyroidectomy in patients with hyperparathyroidism. Br J Surg 1992; 79: 165-168. Joborn C, Hetta J, Palmer M, et al. Psychiatric symptomatology in patients with primary hyperparathyroidism. Ups J Med Sci 1986; 91: 77-87. Joborn C, Hetta J, Lind L, et al. Self rated psychiatric symptoms in patients operated on because of primary hyperparathyroidism and in patients with longstanding mild hypercalcemia. Surgery 1989; 105: 72-78. Burney R, Jones K, Coon J, et al. Assessment of patient outcomes after operation for primary hyperparathyroidism. Surgery 1996; 120: 1013-1019. Kaplan EL, Yashiro T, Salti G. Primary hyperparathyroidism in the 90s. Ann Surg 1991; 215: 300-317. Ljunghall S, Hellman P, Rasted J, Akersorm G. Primary hyperparathyroidism: epidemiology, diagnosis, and clinical picture. World J Surg 1991; 15: 681-687. Van Heerden JA, Grant CS. Surgical treatment of primary hyperparathyroidism: an institutional perspective. World J Surg 1991; 15: 688-692. Harrison BJ, Wheeler MH. Asymptomatic primary hyperparathyroidism. World J Surg 1991; 15: 724-729. Palmer M, Adami H-O, Bergstrom R, et al. Mortality after operation for primary hyperparathyroidism. A follow-up of 441 patients operated on during 1956-1979. Surgery 1987; 102: 1-7. Hedback G, Oden A, Tisell L. The influence of surgery on the risk of death in patients with primary hyperparathyroidism. World J Surg 1991; 15: 399-407. Miller DC. Preoperative localisation and interventional treatment of parathyroid tumours: when and how. World J Surg 1992; 15: 706-715. Serpell JW, Cambell PR, Young AE. Pre-operative localisation of parathyroid tumours does not reduce operating time. Br J Surg 1991; 78: 589-590. Malmaaeus J, Granberg PO, Halvorsen J, et al. Parathyroid surgery in Scandinavia. Acta Chir Scand 1988; 154: 409-413. (Received 1 Jul, accepted 26 Nov, 1997)

Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes

Abstract

Introduction

Methods

Results

Discussion

Acknowledgements

References

Authors' details

Other articles have cited this article: