Abstract
Background : More and more cases of hyperparathyroidism are being detected by screening for serum calcium concentration. The majority of the patients are asymptomatic or have vague symptoms which are difficult to ascribe to hyperparathyroidism. The aim of the study was to retrospectively analyze the patients undergoing parathyroidectomy in a teaching hospital.

Methods : A retrospective analysis of the patients who underwent parathyroidectomy in our institute was done. Demographic details, lobes involved, pathology, clinical features, investigations and anaesthetic management were analyzed.

Results : Patients with hypercalcaemia have variety of non-specific symptoms. Hypercalcaemia is manifested in almost all the systems. More than one system was involved in 82% patients. Of the 62 patients’ one patient presented during pregnancy, one had associated thyroid involvement and two patients had recurrence of symptoms after earlier parathyroidectomy.

Conclusions : Surgical procedures involving the parathyroid glands pose special problems to the anaesthesiologist. Careful attention to control of hypercalcaemia, perioperative rehydration, and evaluation of renal functions are mandatory. Intraoperative management is usually uncomplicated.

Introduction
First parathyroid surgery was performed in 1925 inspite of parathyroid glands being first described in 1850. Hypercalcaemia is responsible for the broad clinical spectrum of symptoms in these patients. With more clinical acumen and diagnostic facilities, more patients are subjected to parathyroid surgery. This study is a retrospective analysis of 62 cases subjected to parathyroidectomy in the last 15 years from 1989 to 2004 with reference to clinical features, investigations and anaesthesia management.

Material and Methods

A retrospective analysis of all the patients who underwent parathyroidectomy in our institute was done. Demographic details, glands involved, pathology, clinical features and investigations were analyzed. Our protocol for anaesthesia management for parathyroid surgery is also discussed.

Statistics
The data was analyzed and percentages were calculated.

Results
Table 1 shows that 76% of the patients undergoing parathyroidectomy were females and 63% of the patients were young adults belonging to the third or fourth decade. The youngest in our series was 15 year old girl and the eldest was 60 year old patient. Most of the patients were cachexic.
Table 2 shows that majority (82%) of the patients had primary hyperparathyroidism while the remaining were either secondary or tertiary hyperparathyroidism. Two patients had recurrence.

Table 1 : Demographic data   Number Percentage Gender Males 15 24 Females 47 76 Weight (Kg) Mean   46.49 ± 13.24 Age (yrs) 10-20 11 17 21-30 21 34 31-40 18 29 41-50 9 15 51-60 3 5

Table 2 : Site and diagnosis   Diagnosis Number % Primary Adenoma 42 68 Hyperparathyroidism Hyperplasia 7 11   Carcinoma 2 3 Secondary CRF 7 11 hyperparathyroidism Tertiary hyperparathyroidism   4 7

Table 3 : Clinical features System involved Number % Fractures 53 86 Neuromuscular 28 45 Chronic renal failure, Calculi, Nephrocalcinosis 20 23 Hypertension, Rheumatic, heart disease 19 31 Gall stones, Pancreatitis 16 26 Central nervous 3 5 Anaemia 3 5 Pregnant 1 2

Table 3 depicts the clinical features seen. Patients with hypercalcaemia have variety of non-specific vague symptoms. Hypercalcaemia does not spare any system. More than one system was involved in 82% patients. 39%, 24%, 15% and 4% patients respectively had two, three, four and five systems involved. One patient presented during pregnancy.

Hyperparathyroidism does not spare any bone or muscle. Joint pains, fractures and limb and vertebral deformities were commonly associated. These make them bed-ridden and along with anorexia, nausea, vomiting and constipation make them cachexic. Generalised body ache, weight loss and fatigue were extremely common. Renal calculi, chronic renal failure and nephrocalcinosis, was manifested in ten, seven and six patients respectively. Associated hypertension was seen in 14 patients while two patients had rheumatic heart disease. Four patients had gallstones and three patients had pancreatic calculi. Mental retardation, schizophrenia and involuntary movements were seen in one patient each. One patient presented during pregnancy and one had associated thyroid involvement.

Investigations
Preoperatively, hypercalcaemia was seen in 59 patients (95%) with a mean of 11.98 prior to surgery. The calcium levels were much higher at admission, the highest documented being 19.7 mg/dl. 25 patients had hypophosphataemia while parathyroid hormone was seen elevated in patients with a mean of 479.34 mg/dl. Radiological evaluation was depicted as fractures, osteopenia, osteoporosis, crowding of ribs and ricketic features in younger patients. Five patients had ECG changes in the form of first degree heart block and ST-T changes.

Protocol
In the endocrine department, the patients were completely evaluated and optimized. If the patient is symptomatic with serum calcium levels of more than 11 mg/dl, the first line of treatment is hydration with three to four litres of IV fluids followed by calcitonin as the second line of management. If serum calcium levels are above 13 mg/dl then IV palmidronate is administered. If the diagnosis of malignancy is established then steroids are given. They are then referred for surgery. Perioperative hydration was managed by giving normal saline. Calcium containing fluids are to be avoided. Extra care was taken while shifting patients from the trolley to the bed and during positioning. After aspiration prophylaxis with ondansetron the patients were premedicated with benzodiazepine like diazepam or midazolam and opioid like pentazocine or fentanyl. Anaesthesia was induced with intravenous anaesthetic agent. Intubation was performed on the operation table with gentle laryngoscopy and without over extension. The muscle relaxant used for intubation was suxamethonium and anaesthesia was maintained with oxygen, nitrous oxide, vecuronium and inhalational agent like halothane or isoflurane. After the completion of surgery reversal was done after satisfying the criteria. They were observed in the recovery room and then shifted to the ward.

Discussion
Anaesthesia implications
Anticipatory problems in giving anaesthesia for parathyroidectomy include presence of renal calculi, weakness, electrolyte imbalance, ECG changes and pathological fractures. Utmost care must be taken while shifting patients as most of these patients have osteoporosis and fractures. Monitoring of blood pressure, ECG, temperature and peripheral nerve stimulator (PNS) become essential. Requirement of anaesthetics in somnolent patients is less. Hydration is important for perioperative management of hypercalcaemia and flushing of kidneys. It is extremely vital to restore normal intravascular volume and electrolytes. Aspiration prophylaxis must be done in view of altered mental status due to hypercalcaemia. Intubation can be difficult and extension if needed must be given with care. Laryngoscopy in patients with unstable cervical spine may lead to quadriplegia. Careful positioning is necessary because of likely presence of osteoporosis and vulnerability to pathological fracture. The action of muscle relaxants is unpredictable. There may be increased sensitivity to suxamethonium and resistance to atracurium. Raised calcium may antagonize effects of non-depolarizing muscle relaxants. Co-existing skeletal muscle weakness may reduce the requirement of muscle relaxants. Hyperventilation with resultant respiratory alkalosis should be avoided as it reduces serum potassium level and leave action of calcium unopposed. One must maintain normoventilation. Postoperative compli-cations include nerve injury, bleeding, vocal cord palsy, hypocalcaemia and dyspnoea. There may be sudden fall in calcium levels after 30-36 hours of surgery. Calcium supplementation is hence to be continued postoperatively. Serum calcium levels are monitored every week for six weeks and later three monthly followed by six monthly intervals.

Surgery for hyper or hypo functioning endocrine organs present a number of perianaesthetic challenges, parathyroidec-tomy being no exception.¹ The prevalence of primary hyperparathyroidism in the general population is 0.15%. It is more common in women and 25% of cases appear during the childbearing years.² In our series, 76% of the patients undergoing parathyroidectomy were women with majority (68%) in the childbearing age.

In recent decades, primary hyperparathyroidism has changed its clinical presentation from a disease with bone and renal involvement to a frequently asymptomatic disorder detected on routine biochemistry. Classical primary hyperparathyroidism was a multisystem disorder with clear neurological, psychiatric, gastrointestinal and cardiovascular consequences. The nature and extent of involvement of these target organs now has become controversial.³ Patients with serum calcium levels above 14 mg% present with nausea, vomiting abdominal pain, constipation, polyuria, tachycardia and dehydration. Psychosis and obtundation are usually the end result of severe hypercalcaemia.⁴

The most common cause of hyperparathyroidism is a single parathyroid adenoma, accounting for about 80% of cases.⁹ In our series 68% accounted for single adenoma. If one fails to remove all lesions at first surgery second surgery is needed. In two patients in our series, as the symptoms recurred after getting operated earlier at other centres, they underwent repeat surgery. Unusual sites of parathyroid are in oesophagus, mediastinum and thyroid.⁴ Carcinoma of the parathyroid is responsible for less than 5% of the cases.6 We had 3% cases of carcinoma of parathyroid.

Between 1985 and 1990 in our institute, three and a half parathyroid glands were removed after confirming diagnosis with frozen section. Later, only the diseased lobes (adenoma) were removed.

Criteria for surgery include significant hypercalcaemia (> 1 mg/dl above upper limit of normal), marked hypercalciuria (> 400 mg/day), low bone density, unexplained renal insufficiency and episode of acute primary hyperparathyroidism. Elderly patients with primary hyperparathyroidism who are Vitamin D deficient should also be considered for surgery.⁷ Patients with mild uncomplicated primary hyperparathyroidism may be managed without surgical removal, if calcium is less than 11.5 mg/dl and bone and renal functions are normal.⁴ Surgery is indicated when cardiovascular and renal system is involved at serum calcium levels less than 12 mg/dl, but if serum calcium is more than 12 mg/dl or abnormal ECG or cardiovascular or renal impairment, surgery should be delayed.⁸ Many patients complain of non-specific neuropsychiatric symptoms. Weakness and easy fatigability is the common complaint. 45% of our patients had such complaints.

Renal stones in patients with hyperparathyroidism often contain apatite salts in addition to calcium oxalate because parathyroid excess may create renal tubular acidosis. Excess generation of 1, 25-dihydroxyvitamin D results in intestinal hyper absorption of calcium and secondary hyperoxaluria.⁹ Our series had 32% patients having renal involvement with 16% having renal calculi and 1.6% patients having renal tubular acidosis.

Patients with untreated mild asymptomatic hyperparathyroidism may be at risk for other complications such as increased morbidity and mortality from cardiovascular diseases. There is limited data on the incidence of cardiovascular abnormalities in mild primary hyperparathyroidism. However, primary hyperparathyroidism has been associated with increased risk of death from cardiovascular disease, hypertension, left ventricular hypertrophy, valvular and myocardial calcifications, impaired vascular reactivity, alterations in cardiac conduction, impaired glucose metabolism, dyslipidaemia, and alterations in body composition. The nature of some of these associations is in question, because cure of primary hyperparathyroidism does not always lead to improvement of the cardiovascular disorder e.g. hypertension. In contrast, currently available data suggest that left ventricular hypertrophy, impaired glucose metabolism and dyslipidaemia may improve after surgery and that successful parathyroidectomy could decrease the excess mortality in patients with primary hyperparathyroidism due to cardiovascular disease.¹⁰ Hypertension may not be cured after parathyroidectomy. We had 31% patients who had cardiac involvement of which 14 patients had hypertension.

Acute pancreatitis is one of the symptoms of primary hyperparathyroidism often caused by a parathyroid adenoma and curable by its excision.¹¹ We had three patients of pancreatitis whose symptoms of pancreatitis improved after parathyroidectomy. Gastrinoma is more severe in those with coexisting primary hyperparathyroidism and Zollinger-Ellison syndrome improves with treatment of primary hyperparathyroidism.³ We had five patients with gastro intestinal involvement.

Possible pathogenic links between anaemia and parathyroid hormone include reduced erythropoiesis due to calcitrol deficiency, and direct or indirect effects of parathyroid hormone on erythropoietin release, red blood cell production, survival, and loss.¹² We had three patients of anaemia with haemoglobin levels of less than 8 gm% which may also be due to malnourishment and the fact that they were bedridden. Severe parathyroid over function may contribute to the severity of anaemia in uraemic patients and diminish recombinant human erythropoietin responsiveness in a minority of patients. However, overall, the importance of hyperparathyroidism appears to be minor compared with other factors such as iron deficiency or inflammation. Patients with a family history of osteoporosis and those on heparin therapy have a tendency to develop symptoms of the disease in pregnancy.⁹ Maternal complications include acute pancreatitis, hypercalcaemia crisis, and toxaemia. If significant maternal hypercalcaemia is present, prematurity and neonatal hypocalcaemia is likely. Reported foetal complications include intrauterine growth retardation, low birth weight, preterm delivery, intrauterine foetal demise, postpartum neonatal tetany, and permanent hypoparathyroidism. Debate continues regarding the safety of surgery in the third trimester. A four-fold decrease in perinatal complications may be achieved with appropriate therapy.² Doses of vitamin D and calcium do not change during pregnancy; however, hypercalcaemia may develop in the postpartum period. Serum calcium should be determined at every trimester of pregnancy and at regular intervals after delivery, and in a significant number of patients, the dose of vitamin D should be reduced.⁹ Surgery is considered as the definitive treatment of choice and is considered safe and effective during the second trimester.¹³ Steroids may be useful in malignancy with hypercalcaemia crisis. Only one patient in our series needed prednisolone.

Intraoperative management is usually uncomplicated if one is extremely careful of adequate hydration and positioning. Severe hypocalcaemia may complicate the postoperative period, especially if severe bone disease is present. Postoperative tetany may occur that may need IV calcium gluconate. Lowest calcium is reached within four-five days. Lethal complication of severe hypocalcaemia is laryngospasm and hypocalcaemic seizure.⁴

We believe that early recognition and timely intervention can significantly reduce the incidence of complications. One must be diligent to diagnose and treat this entity promptly. Further efforts are necessary to characterize the cardiovascular and neuropsychological profiles of mild primary hyperparathyroidism and to determine the longitudinal course of such alterations.

Conclusion
Surgical procedures involving the parathyroid glands pose special problems to the anaesthesiologist. Careful attention to perioperative hydration, control of hypercalcaemia, and evaluation of renal functions are mandatory. Intraoperative management is usually uncomplicated.

References

1. Breivik H. Perianaesthetic management of patients with endocrine disease. Acta Anaesthesiol Scand 1996; 40 (8 Pt 2) : 1004-15.
2. Schnatz PF, Curry SL. Primary hyperparathyroidism in pregnancy: evidence-based management. Obstet Gynecol Surv 2002; 57 (6) : 365-76.
3. Silverberg J. Non-classical target organs in primary hyperparthyroidism. SJ Bone Miner Res 2002; 17 Suppl 2 : 117-25.
4. Benumof JL. Diseases of the Endocrine System. In: Asesthesia and Uncommon Diseases 224-233.
5. Mestman JH. Parathyroid disorders of pregnancy. Semin Perinatol 1998; 22 (6) : 485-96.
6. Stoelting. Endocrine disease. In: Anesthesia and coexisting diseases. 421-424.
7. Boonen S, Vanderschueren D, Pelemans W, Bouillon R. Primary hyperparathyroidism: diagnosis and management in the older individual. Eur J Endocrinol 2004; 151 (3) : 297-304.
8. Allman K, Wilson IH. In: Oxford’s Handbook of Anaesthesia. 2001; 82-84,304-305.
9. Rodman JS, Mahler RJ. Kidney stones as a manifestations of hypercalcemic disorders. Hyperparathyroidism and sarcoidosis. Urol Clin North Am 2000; 27 (2) : 275-85,viii.
10. Garcia de la Torre N, Wass JA, Turner HE. Parathyroid adenomas and cardiovascular risk. Endocr Relat Cancer 2003; 10(2) : 309-22.
11. Abdullah M. Pancreatitis in primary hyperparathyroidism. Med J Malaysia 2003; 58 (4) : 600-3.
12. Drueke TB, Eckardt KU. Role of secondary hyperparathyroidism in erythropoietin resistance of chronic renal failure patients. Nephrol Dial Transplant 2002; 17 Suppl 5 : 28-31.
13. Kort KC, Schiller HJ, Numann PJ. Hyperparathyroidism and pregnancy. Am J Surg 1999; 177 (1) : 66-8.