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Audit on Referral for Parathyroidectomy in Patients with Asymptomatic Primary Hyperparathyroidism (PHPT) and Follow up of Patients who did not have Surgery in a District General Hospital in the United Kingdom

Indrajit Talapatra (MRCP) and Ian Patrick Michael O’Connell (FRCP)
Royal Albert Edward Infirmary, Wigan, UK

Aims of the audit

(1)To find out if the International Workshop/NIH Guidelines were followed while referring patients with asymptomatic primary hyperparathyroidism (PHPT) for parathyroid surgery
(2)To find out if the International Workshop/NIH Guidelines were followed while reviewing the patients with asymptomatic PHPT in our out-patients who did not have surgery

Method

Case notes of patients with PHPT seen in the out-patients for follow up between 1st February and 15th April 2016 were studied for the purpose of the audit

Criteria:

The International Workshop /NIH Guidelines were followed for the purpose of the audit.

Introduction

Guidelines for referral for surgery in asymptomatic PHPT
The initial Guidelines were produced in 1990 and subsequently were revised in 2002, 2008 and 2013 (Ref: 1-5). The last international workshop was held in Florence in 2013. The latest Guidelines (2013) for referral for parathyroidectomy in asymptomatic PHPT include (Ref: 1):
(1)Serum Calcium 1.0 mg/dl or 0.25 mmol/l above the upper limit of normal
(2) DEXA Scan: T score < -2.5 at lumbar spine, total hip, femoral neck, or distal 1/3 of radius

(3) Vertebral fracture Assessment (VFA) by X ray, CT, MRI. This criterion was not present in the previous Guidelines

(4) Creatinine Clearance <60cc/min (In 1990 and 2002 the Guidelines stated that the referral for patathyroid surgery should be done if eGFR was reduced by >30% and in 2008 the Guidelines mentioned that referral was needed if eGFR was < 60 cc/min)

(5) 24 hours urine calcium >400 mg or >10 mmol (Normal: 2.5-7.5 mmol/day) and increased stone risk by biochemical stone risk analysis (The criterion for measurement of 24 hours urine calcium was not mentioned in the Guidelines of 2008; however it was present in the Guidelines of 1990 and 2002)

(5) Renal stones or Nephrocalcinosis by Xray, Ultrasound or CT

(6) Age less than 50 years

The 2013 Guidelines for monitoring patients with PHPT who did not have parathyroid surgery include:
(1)Measurement of serum calcium annually (The Guidelines from 1990 and 2002 stated that serum calcium had to be monitored bi-annually. However the Guidelines from 2008 mentioned about measuring serum calcium annually)
(2) DEXA, every 1-2 years at 3 sites; X ray or VFA of spine if clinically indicated such as loss of height or backache. The Guidelines from 1990 and 2002 mentioned about doing follow up- DEXA every 1 year and the Guidelines of 2008 stated that follow up- DEXA was needed every 1-2 years. There was no mention of VFA by X ray, CT or MRI in the previous Guidelines

(3) Serum Creatinine and eGFR annually (Annual measurement of eGFR was not mentioned in the 2002 and 2008 Guidelines; however it was mentioned in the Guidelines of 1990)

(4) If renal stones are suspected, biochemical stone profile such as 24 hours urine calcium and renal imaging by x ray, ultrasound, or CT are required. This criterion was not mentioned in the previous Guidelines

Results

Total number of subjects = 22
Male: Female = 6: 16
Age:<40 yrs =1; 40-50 yrs= none; 50- 60 yrs =2; 60- 70 yrs =2; 70-80 yrs =8; 80-90 yrs =6; > 90 yrs = 3
No of patients who had DEXA scan (21 out of 22), renal imaging (21 out of 22), 24 hours urine calcium/calcium excretion index (19 out of 22; 5 patients had calcium excretion index; 14 had 24 hours urine calcium), eGFR ( all 22 patients), Creatinine Clearance (none) and VFA of spine by X ray, CT or MRI (none)
15 out of 22 patients fulfilled the criteria for referral for parathyroidectomy .Out of these 15 patients 7 were referred for surgery.
(1)No of patients with asymptomatic PHPT and Calcium >2.85 mmol/l and were referred for surgery: 13 patients had serum calcium >2.85 mmol/l and 5 were referred (38.46%); Reasons: (Amongst patients not referred- 3 patients had various co-morbidities, 3 patients did not want referral and in 2 patients reasons were not known)
(2)Patients with T score of < -2.5 and were referred for surgery: 9 patients had osteoporosis and 4 were referred (44.44%)
(3)Patients with urine calcium of >10 mmol/24 hours and referred for surgery: 1 patient had urine calcium greater than 10 mmol/d and was referred for surgery
(4)Patients with nephrolithiasis or nephrocalcinosis and referred for surgery: 3 patients had nephrolithiasis and 2 were referred (66.67%)
(5)Whether creatinine clearance or eGFR was calculated in these patients and whether those with < 60 cc per minute were referred for surgery: eGFR was done in all 22 patients but Creatinine Clearance in none; 11 had low eGFR and 2 were referred
(6)Whether those aged less than 50 years were referred for surgery: 1 female was aged 38 years and was referred for surgery

Results amongst those not referred for surgery:
(1)Whether those who were not referred for surgery had their serum calcium monitored annually: 15 out of 15 patients had serum calcium monitored more frequently than annually
(2)Whether the patients not referred for surgery had their DEXA scan of the spine repeated after 1-2 yrs: 2 out of 14 (14.29%); 1 did not have DEXA scan at all as mentioned before
(3)Whether eGFR was done annually in those not referred: 15 out of 15 patients had eGFR done more frequently than annually
(4)Whether serum creatinine was done annually: 15 out of 15 patients had serum creatinine done more frequently than annually
(5)Whether 24 hours urine calcium was done annually: none out of 15
(6)Whether renal imaging was done annually: none out of 15
(7) VFA by X ray, CT or MRI done for follow up: none out of 15

Summary

(1)15 out of 22 patients fulfilled at least one criterion for referral for surgery, 7 patients were referred
(2)13patients had serum calcium >2.85 mmol/l, of them 5 were referred
(3)9patients had osteoporosis and 4 were referred
(4)1patient had urinary calcium > 10 mmol/24 hrs and was referred
(5)3patients had nephrolithiasis and 2 were referred
(6)Creatinine Clearance was done in none of the patients
(7)Amongst those not referred serum calcium, creatinine and eGFR were done more frequently than annually in all patients; however only 2 had DEXA scan repeated in the next 1-2 years and none had renal imaging or 24 hours urinary calcium done as follow up.
It appears from the audit that we did not do too well on various criteria for referral for parathyroidectomy in asymptomatic PHPT and also in case of follow up of patients who did not have surgery. However it has to be kept in mind that many of these patients were elderly and had various co-morbidities and hence were not suitable for surgery and also all patients did not agree with referral for surgery. Patients with high calcium who are awaiting surgery or deemed unfit for surgery or who have declined surgery are treated with Cinacalcet.

Conclusions and Recommendations

(1)All patients fulfilling at least one criterion for referral for surgery and having no co-morbidity should be referred for surgery after discussion with them and if they agree
(2)All patients with serum calcium > 2.85 mmol/l should be referred for surgery, if there is no contraindication
(3)All patients should have DEXA scan, renal imaging and 24 hours urinary calcium and all those with osteoporosis, renal calculi and 24 hours urine calcium >10 mmol should be referred for surgery, if there is no contraindication
(4)Patients <50 years should be referred for surgery
(5)Those not referred for surgery should have serum calcium, creatinine and eGFR done annually, DEXA scan after1-2 years and renal imaging and 24 hours urinary calcium if clinically indicated
We have not been measuring the Creatinine Clearance as a criterion for referral for surgery (either in the laboratory or by Cockcroft-Gault formula). The Guidelines of the previous years included eGFR as a criterion for referral for surgery; however both eGFR and Creatinine Clearance can be low owing to other causes.
Other recommendations (not part of this audit) prior to referral for surgery:
(1)Measurement of Vitamin D is needed in all patients with PHPT and supplementation of Vitamin D is necessary if it is low
(2)Sestamibi scan should be done in our hospital (according to the advice from the tertiary hospital) prior to rererral for parathyroidectomy

References:

(1)Khan A A, Bilezikian J P, Potts J T. The diagnosis and management of asymptomatic primary hyperparathyroidism revisited. J Clin Endocrinol Metab 2009; 94:333–334.
(2)Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr (2014). Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab 2014; 99(10):3570-3579
(3)Silverberg SJ, Clarke BL, Peacock M, et al.Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.J Clin EndocrinolMetab 2014;99:3580–3594.

(4)Udelsman R, Åkerström G, Biagini C, et al.The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.J Clin Endocrinol Metab 2014;99:3595–3606.
(5)Marcocci C, Bollerslev J, Khan AA, Shoback DM.Medical management of primaryhyperparathyroidism:proceedings of theFourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism. J Clin Endocrinol Metab 2014;99:3607–3618. .

Published August 2016

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