Should primary hyperparathyroidism be treated surgically in elderly patients older than 75 years?

Should primary hyperparathyroidism be treated surgically in elderly patients older than 75 years ? Jean-Paul Chigot, MD, FACS, Fabrice Menegaux, MD, and Homayoun Achrafi, MD, Paris, France Background. Diagnosis of primary hyperparathyroidism (PHPT) is increasingly suspected in elderly patients after the discovery of hypercalcemia by routine measurement of serum calcium levels. Surgery is commonly accepted as the optimal treatment of PHPT. We wanted to assess risk and results of neck exploration in elderly patients with PHPT. Methods. We performed a retrospective study of the charts of 78 patients older than 75 years (mean age, 79.1 years) with P H P T who underwent neck exploration during a 75-year period. Results. The most common presenting symptoms were neurologic and psychiatric disorders (47 patients). Preoperative localization investigations, performed in 72 patients, were successful in 42 of them (sensivity, 58%). Single adenoma, double adenomas, and hyperplasia were found in 74 patients (95%), three patients, and one patient, respectively. Overall postoperative mortality was 3.8% (three patients) with no death since 798d. Significant complications occurred in three patients (4%) : one myocardial infarction, one pulmonary embolism, and one cerebral hemorrhage. Average length of postoperative hospital stay was 4 days. Among patients who could be followed up (65 cases with a mean follow-up of 3 years), 94% reported an improvement in their symptoms. This was especially marked for fatigue and intellectual function. Conclusions. These data support a liberal approach regarding surgical treatment in elderly patients with PHPT. (SURGERY 7995; 117:397-401.) From the Department of General and Gastrointestinal Surgery, H3pital de la Pitib, Paris, France

IT HAS BECOMEOBVIOUSthat patients who are currently seen with primary hyperparathyroidism ( P H P T ) are older than those in previous reports), 2 This is the reflection of the widespread measurement of serum calcium levels with detection of an unusual hypercalcemia. Clinical symptoms are different in elderly than in younger patients with prevalence of neurologic and psychiatric disorders, fatigue, and diffuse osteoarticular pain. 3"5 Despite age and frequent concomitant diseases, early neck exploration with excision of the adenoma has been considered a safe procedure with a high success rate. We report our experience of such surgery in patients older than 75 years at the Piti~ Hospital from 1978 to 1992.

PATIENTS AND METHODS From January 1978 to December 1992, 542 patients underwent operation for P H P T at the Piti~ Hospital. Accepted for publication Sept. 2, 1994. Reprint requests: Jean-Paul Chigot, MD, FACS, Department of General and Gastrointestinal Surgery, H6pital de la Piti~, 47-83 boulevard de l'Hc3pital,75651 Paris Cedex 13, France. Copyright 9 1995 by Mosby-Year Book, Inc. 0039-6060/95/$3.00 + 0 11/56/60469

Seventy-eight of these patients (14.4%) were 75 years of age or older. Mean age was 79.1 years, ranging from 75 to 90 years (Fig. 1). There were 64 women and 14 men (gender ratio, 4.6). For each patient we examined medical history, preoperative symptoms, laboratory values, localization procedures and their accuracy, operative procedure and postoperative complications, pathologic findings, and immediate and long-term disease status. Follow-up was obtained by review of the medical report and direct contact with the patient and family physician. Only 17 patients were free of any notable concomitant disease. The remaining 61 patients (78%) had at least one factor in their past medical history that could be considered as a surgical risk. Cardiovascular diseases had been documented in 44 patients (56%); 39 patients had a treated arterial hypertension, 12 patients had coronary insufficiency (including four myocardial infarctions), five patients had cardiac failure, and three had cardiac arrhythmia. Diabetes mellitus was diagnosed in 10 patients, chronic respiratory failure in seven, decreased renal function in six, and neurologic disorders in six. Various coexistent diseases such as varicosities of the lower limbs, arteritis, cirrhosis, rheumatoid arthriSURGERY

397

398

Chigot, Menegaux, Achrafi

Surgery April 7995 Table I. Presenting symptoms of P H P T

Number of patients 60

50 40

30 20 10 0 75-79

80-84

85-89

>90

Age (years)

Fig. 1. Age of patients at time of operation for primary hyperparathyroidism.

tis, malignancies, or glaucoma were present in 12 patients. Cervical investigations were performed in 72 patients to localize hypertrophic parathyroids: ultrasonography (n--71), 99mtechnetium-Z~ subtraction scintigraphy (n = 18), conventional selective parathyroid angiography (n = 1), and computed tomography (n = 3). No previous neck exploration had been performed, and all patients underwent operation under general anesthesia with tracheal intubation. None of the patients required sternotomy. No negative neck explorations were performed. All four parathyroids were observed in the majority of patients (62 patients), and enlarged parathyroids were excised. Operative specimens were routinely examined histologically. Thyroid was not homogeneous in 28 patients, and an additional procedure was performed on thyroid in 19 patients: two subtotal thyroidectomies and one lobectomy with enucleation of a contralateral nodule for 12 multinodular goiters, three total lobectomies with isthmectomies and 11 enucleations for 14 benign thyroid nodules, and two total thyroidectomies for differentiated thyroid cancer. RESULTS

The most common presenting symptoms were fatigue with difficulty in walking in 27 patients and neuropsychiatric complaints (Table I). These included depression (n = 8), personality changes, memory impairment, and inappropriate behavior. Neurologic symptoms included psychomotor disorders, pseudopolyneuritis, or pseudomyopathic presentation. Other common presenting symptoms were osteoarticular pain (17 patients), peptic ulcer (five patients), and urinary tract calculi

Circumstances of discovery

No. of patients

Neurologic/psychiatric disorders Fatigue Depression Psychiatric disorders Neurologic disorders Osteoarticular symptomatology Bone pain or fractures Joint pain Routine investigations Anemia Weight loss Abdominal discomfort Vomiting Peptic ulcer Renal manifestations

47 27 8 8 4 17 12 5 12 4 4 2 2 5 2

% 60

22 15

6 3

(two patients). Routine measurement of serum calcium levels led to the diagnosis of P H P T in 12 patients (15%). Careful preoperative and postoperative evaluations have shown that only a few patients (6 of 78, [8%]) could be considered truly asymptomatic. Total preoperative serum calcium levels ranged from 2.56 to 4.20 mmol/L (normal values, 2.25 to 2.65 mmol/L) with a mean ( _+SD) of 3.06 _+ 0.32 mmol/L. Serum phosphorus levels ranged from 0.33 to 1.12 mmol/L (normal values, 0.80 to 1.40 mmol/L) with a mean (+SD) of 0.74 _+ 0.16 mmol/L. Parathyroid hormone levels, measured 48 times, were elevated in 46 patients and normal in two patients (normal values, 10 to 60 pg/ml), ranging from 45 to 1176 pg/ml with a mean value (_+SD) of 271 _+ 329 pg/ml. Serum albumin levels ranged from 28 to 47 g m / L (mean • SD, 38 -+ 5 gm/L; normal values, 37 to 46 gm/L); serum creatinine level ranged from 52 to 350 #mol/L (mean _+ SD, 110 +_ 53 #mol/L; normal values, 60 to 120/~mol/L); serum alkaline phosphatase levels ranged from 58to 1292 I U / L (mean • SD; 203 • 215 IU/L; normal values, 30 to 100 IU/L); and urinary cyclic adenosine monophosphate level ranged from 1.08 to 4.50 #mol/mmol creatinine (mean _+ SD, 3.05 _+ 1.77 /~mol/mmol creatinine; normal values, 0.25 to 0.50 #mol/mmol creatinine). The site of the lesion was suspected in 57 patients (79%), but this proved to be false positive in 16 of them. Therefore preoperative topographic diagnosis was established in 42 patients (58% of investigated patients and 54% of the total study group) (Table II). Pathologic examination of the removed parathyroid revealed hyperplasia in one patient. The remaining 77 patients involved one (74 patients) or two (3 patients) adenomas of the following types: chief cell (n = 44), in-

Surgery Volume 117, Number 4

Chigot, Menegaux, Achrafi

Number of patients

399

Number of patients

+1

9

1978-1985 -

(n=30) =

'~1

9

1978-1985

"+++++'

(n=30)

20

10 1

0

---,

1-5

6-9

10-14

16-19

20-24

25-29

Duration of Hospitalization (days)

Fig. 2. Duration of hospitalization (excluding postoperative mortality). termediate (n = 18), oxyphilic (n = 5), mixed (n -- 6), or not defined (n = 7). Sites of the 80 adenomas (in 77 patients) were left superior (n = 15), left inferior (n = 19), right superior (n = 17), and right inferior (n = 29). Mean weight of the excised parathyroid was 1520 mg (range, 75 to 11,800 mg). The postoperative course was uneventful in 70 patients (89.7%). Mean ( + SD) serum calcium level on postoperative day 3 was 2.25 _ 0.20 mmol/L (range, 1.86 to 2.90 mmol/L). Only one patient required transient calcium replacement for symptomatic hypocalcemia. Three postoperative deaths (between postoperative days 1 and 10) occurred during the first period (1978 to 1984), two from pneumonia and one from pulmonary embolism. One of the patients who died of pneumonia had severe and long-standing hyperparathyroidism, and autopsy revealed calcified lungs. The other one was 85 years old, had been hospitalized 6 weeks before operation, and had coronary insufficiency and chronic respiratory failure. In the patient who died of pulmonary embolism on postoperative day 10, autopsy revealed the presence of a tumor of the inferior vena cava extending to the right atrium so that mortality directly related to surgery was only 2.6%. Significant complications occurred in three patients (4%): one cerebral hemorrhage with hemiplegia regressing in a few days, one pulmonary embolism, and one myocardial infarction. These three patients (75, 77, and 80 years of age) had several factors of surgical risk: hypertension (n = 2), coronary insufficiency (n = 2), cardiac failure (n = 1), and Parkinson's disease (n = 1). Other minor complications occurred in three patients, two wound infections that required only local care and one urinary infection. We did not observe any cervical

1 -5

6-9

10-14

15-19

>20

Duration of Postoperative Hospitalization (days)

Fig. 3. Duration of postoperative hospitalization (excluding postoperative mortality).

hematoma requiring evacuation or recurrent laryngeal nerve injury. No permanent hypoparathyroidism occurred. The mean length of hospitalization was 7 days (range, 3 to 27 days), and mean postoperative stay in the hospital was 4 days (range, 2 to 17 days). A very marked decrease in length of hospitalization has been observed during the later years (1986 to 1992) when compared with the earlier period (1978 to 1985), as illustrated in Figs. 2 and 3. Mean follow-up was 3 years (range, 1 to 160 months) for 65 patients; the remaining 13 patients had been lost from follow-up. Improvement in symptoms, essentially neurologic and psychiatric disorders, and osteoarticular pain were considered highly marked in 57 patients and marked in four others. Of special interest is that careful questioning of patients and their families showed that in patients with neuropsychiatric disorders a uniform improvement occurred in mentation and behavior pattern. In some eases it was so important that it allowed patients, living in an institution until then, to return home. Results were slight or nil in the remaining four patients (good results 94%). These four poor results occurred in patients in whom the predominant symptom was diffuse osteoarticular pain. Serum calcium level measured during the long-term follow-up was invariably normal except in one case highly suspect of recurrence. In this patient hypercalcemia recurred 2 years after excision of a chief cell parathyroid adenoma. At the present time, 10 years after operation, hypercalcemia remains well tolerated and reoperation has been avoided in view of the

400

Chigot, Menegaux, Achrafi

Surgery April 1995

Table II. Localization of enlarged parathyroids

Investigation

True positive

False positive

False negative

Total*

Ultrasonography'[" Scintigraphyl: Selective arteriography Computed tomography

39 13

13 2 1

19 3

72 18 1 3

3

*Number of combined investigations: three investigations in one patient (ultrasonography, scintigraphy, and computed tomography); two investigations in 19 patients: ultrasonography and scintigraphy (16 patients), ultrasonography and computed tomography (2 patients), ultrasonography and arteriography (1 patient). tSensitivity of ultrasonography, 67%. :~Sensitivity of scintigraphy, 81%; sensitivity of combined ultrasonography-scintigraphy, 85%.

advanced age of the patient (93 years old). The patient whose histologic lesion was hyperplasia has experienced no recurrence of hypercalcemia with a follow-up of 6 years. DISCUSSION Incidence of P H P T increases with age, 1 and estimates in the geriatric population vary between 1.5% and 3%2, 6 with an annual incidence higher than 1.5% after 60 years of age. A female predominance is usual in a group of this age (80% of our patients were women). P H P T is responsible for increased mortality, essentially as a result of cardiovascular disease, even if hypercalcemia is moderate. 3 Symptoms of the disease differ from those seen in younger patients, z's Most of the elderly patients complain of general tiredness with reduced muscular strength and display psychiatric symptoms: depression, difficulty in concentrating, personality changes, psychomotor retardation, memory impairment, and occasionally overt psychosis. Hyperparathyroidism must be eliminated before attributing these symptoms to idiopathic senile dementia, which is clearly more common at this age. 6, 7 The severity of such symptoms is not correlated with the degree of hypercalcemia. Other symptoms are less common, even though osteoarticular pain remains a classic symptom through which the disease is discovered. Renal manifestations rarely lie at the origin of the diagnosis of P H P T in the geriatric population; their incidence tends to decrease progressively in favor of hypercalcemia discovered during investigation of other conditions. 8 Truly asymptomatic H P T is uncommon (8% in our series). Careful clinical assessment shows that mild symptoms are present in the majority of elderly patients. Preoperative localization of enlarged parathyroid glands was obtained in one half of our patients; the combination of ultrasonography and scintigraphy was the most sensitive. This low sensitivity, which is distinctly under the norm reported in the literature, 9 is probably due to the fact that most of the ultrasonograms, which are highly operator dependent, had been performed outside of our institution. In fact, we wonder

whether such preoperative localization is important because it is essential to visualize all the parathyroids during operation to eliminate a double adenoma, which is not rare (from 3.2% to 9%). 6, 10 Some teams have therefore given up preoperative morphologic investigations. We think that the best indications for preoperative ultrasonography are the evaluation of patients with acute hypercalcemic crisis and in high risk patients for whom decision for surgery may be helped by the demonstration of a typical adenoma. The situation is different in recurrences, TM 12 where preoperative localization is required. Emphasis should be placed on noninvasive investigations, with ultrasonography first and foremost and, according to each case, 99mtechnetium-Z~ or 99mtechnetium-methoxyisobutyl isonitrile scintigraphy, computed tomography, 6' 11 and magnetic resonance imagingJ 3 Although the natural history of primary P H P T is not fully known and life expectancy is difficult to predict in the elderly, surgical treatment should always be discussed. Ablation of the enlarged parathyroid under local anesthesia has been reported. 14 The main criticism is the unilateral neck exploration, even though patients with P H P T have a single adenoma in the majority of eases. Contraindications to surgery are rare. However, in some selected patients who are very poor surgical candidates, nonsurgical ablation of parathyroid tumors may be discussed. In cervical adenomas percutaneous alcohol injection may be used, 15 but disadvantages of this method include a poor success rate and a relatively high risk of temporary or permanent damage of the inferior laryngeal nerve. In mediastinal adenomas angiographic ablation may be used, 16 but the long-term cure rate is also much lower than after operation. In our series postoperative mortality (3.8%) was relatively high for a benign disorder, but the mean age of our patients was far older (approximately 10 years older) than in other series. Moreover, no death has occurred since 1984 probably because of a better selection of patients for surgery. Overall morbidity was comparable with an incidence of major complications of 4% 3 and a shorter length of hospitalization, z, 17

Surgery Volume 117, Number 4 T h e mean follow-up of our patients was 36 months (excluding 13 patients who were lost from follow-up) with a symptomatic improvement in 94% of cases (a similar percentage to those in other series), 2,17,18 this was particularly marked in regard to fatigue and intellectual function, with restoration of a feeling of wellbeing described by many patients. Among those patients who could be followed up, 15 have died since operation from other causes (five cardiac failures, three myocardial infarctions, two postoperative deaths for a nonrelated disease, three cerebrovascular accidents, and two cancers). T h e y had nevertheless benefited from a mean of 4.5 years (range, 5 to 98 months) of survival m a r k edly improved because of the elimination of hypercalcemia. O u r results also confirmed the efficacy of surgical treatment regarding neurologie and psychiatric disorders.3, 4 T h e improvement in bone and joint pains was less marked but clearly existed. 8 In contrast, the correlation between P H P T and hypertension (present in 50% of our patients) has already been reported but without any specific explanation, 1 and as was the ease with our patients, no significant change was noted in blood pressure after treatment of P H P T . z' 4 CONCLUSION Frequency of P H P T diagnosis is increasing in the elderly. Joint and bone pains previously attributed to diffuse osteoarthritis and, especially neurologic and psychiatric disorders such as depression with fatigue or confusional syndrome with impaired intellectual function should now be investigated by the measurement of serum calcium levels. If serum calcium level is high or if hyperealcemia is discovered, measurement of serum parathormone levels confirms the diagnosis. Cervieotomy for excision of the parathyroid adenoma leads to a very marked improvement of symptoms in the great majority of cases. Postoperative histories from patients and their families are highly demonstrative in this respect, confirming a net transformation in their general condition. T h u s we consider parathyroid surgery the treatment of choice in elderly patients with P H P T . REFERENCES

1. Heath HH III, Hodgson SF, Kennedy MA. Primary hyperparathyroidism: incidence, morbidity, and potential economic impact in a community. N Engl J Med 1980;302:189-93.

Chigot, Menegaux, Achrafi

401

2. Tibblin S, P/dsson N, Rydberg J. Hyperparathyroidism in the elderly. Ann Surg 1983;197:135-8. 3. Akerstr6m G, Rastad J, Ljunghall S, Johansson H. Clinical and experimental advances in sporadic primary hyperparathyroidism. Aeta Chir Seand 1990;156:23-8. 4. Nudelman I, Deutsch AA, Reiss R. Surgical treatment of primary hyperparathyroidism in the elderly patient. Isr J Med Sci 1983;19:150-2. 5. Villiaumey J, Hioco D, Chanzy MO, Chigot JP, Melliere D, Proye C. Le nouveau visage clinique de l'hyperparathyroi'die primitive. Cireonstances de diagnostic et caract~res symptomatiques aetuels: r~sultats d'une enqu~te multieentrique. Rev Rhumatisme 1988;55:561-8. 6. Brothers TE, Thompson NW. Surgical treatment of primary hyperparathyroidism in elderly patients. Aeta Chit Stand 1987; 153:175-8. 7. Joborn C, Hetta J, Palmer M, ,kkerstr/~mG, Ljunghall S. Psychiatric symptomatology in patients with primary hyperparathyroidism. Ups J Med Sei 1986;91:77-88. 8. Peskin GW, Greenburg AG, Salk RP. Expanding indications for early parathyroidectomy in the elderly female. Am J Surg 1978;136:45-8. 9. Stark DD, Gooding GAW, Moss AA, Clark OH, Ovenfors CO. Parathyroid imaging: comparison of high-resolution CT and high-resolution sonography. AJR 1983;141:633-8. 10. Russel CF, Edis AJ. Surgery for primary hyperparathyroidism: experience with 500 consecutive cases and evaluation of the role of surgery in the asymptomatic patient. Br J Surg 1982;69: 244-7. 11. Uden P, Aspelin P, Berglund J, et al. Pre-operative localization in unilateral parathyroid surgery. A cost-benefitstudy on ultrasound, computed tomography and scintigraphy. Acta Chir Stand 1990;156:29-35. 12. Levin KE, Gooding GAW, Okerlund M, et al. Localizing studies in patient with persistent or recurrent hyperparathyroidism. SURGERY1987;102:917-25. 13. Auffermann W, Gooding GAW, Okerlund M, et al. Diagnosis of recurrent hyperparathyroidism: comparison of MR to other imaging techniques. Am J Roentgenol 1988;150:1027-33. 14. Chapuis Y, Icard Ph, Fulla Y, et al. Parathyroid adenomectomy under local anesthesia with intra-operative monitoring of UcAMP and/or 1-84 PTH. World J Surg 1992;16:570-5. 15. Karstrup S, Holm HH, Glenthoja A, Hegedus L. Non surgical treatment of primary hyperparathyroidism with sonographically guided percutaneous injection of ethanol: results in a selected series of patients. Am J Roentgenol 1990;154:108790. 16. Miller DL, Doppman JL, Chang R, et al. Angiographic ablation of parathyroid adenomas: lessonsfrom 10 years experience. Radiology 1987;165:601-9. 17. Lifschitz BM, Barzel US. Parathyroid surgery in the aged. J Gerontol 1981;36:573-5. 18. Mannix H Jr, Pyrtek LJ, Crombie HD, Canalis E. Hyperparathyroidism in the elderly. Am J Surg 1980;139:581-3.