Skip to main content

Advertisement

SpringerLink
Log in

Baseline renal dysfunction determines mortality following parathyroidectomy in primary hyperparathyroidism: analysis of Indian PHPT registry

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Primary hyperparathyroidism (PHPT) in India is mostly symptomatic with renal and skeletal complications. Evidence on mortality outcomes following parathyroidectomy from India, where the disease is predominantly symptomatic is limited.

Material and methods

This was a prospective study to evaluate mortality outcomes in the Indian PHPT registry over the past 25 years (n = 464). Pre- and postoperative parameters and mortality data were obtained from medical records and/or by verbal autopsy, a method validated by WHO for data collection in settings where several deaths are noninstitutional. Patients were divided into survivor (SG) and nonsurvivor groups (NSG) to ascertain differences in presentation and the effect of parathyroidectomy.

Results

The overall mortality was 8.8% at a median follow-up of 8 years (IQR 1–13) after parathyroidectomy. Chronic kidney disease was the most common background cause of death (43.5%), followed by pancreatitis (28.2%). NSG had significantly more frequent renal dysfunction (91.9% vs 73.9%), anaemia (50 vs 16.6%) and pancreatitis (24.3 vs 6.4%). PTH (61.9 vs 38.3 pmol/l) and baseline creatinine (97.2 vs 70.7 µmol/l) were significantly higher and eGFR lower (66.7 vs 90.7 ml/min/1.73m2) in the NSG than SG. By Cox proportional modelling, renal dysfunction [HR 2.88 (1.42–5.84)], anaemia [HR 2.45 (1.11–5.42)] and pancreatitis [HR 2.65 (1.24–5.66)] on univariate and renal dysfunction [HR 3.33 (1.13–9.77)] on multivariate analysis were significant for mortality. Survival curves demonstrated a significantly higher mortality with lower eGFR values.

Conclusions

Nonsurvivors in PHPT had greater prevalence and more severe baseline renal dysfunction than survivors. Survival after parathyroidectomy was significantly associated with estimated glomerular filtration rate at baseline.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

PTH:

Parathyroid hormone

PHPT:

Primary hyperparathyroidism

eGFR:

Estimated glomerular filtration rate

CKD:

Chronic kidney disease

CKD-EPI:

Chronic kidney disease-epidemiology collaboration

MDRD:

Modification of diet in renal disease

CCCR:

Calcium creatinine clearance ratio

USG:

Ultrasound

CT:

Computerised tomography

MRI:

Magnetic resonance imaging

99Tc:

Technetium

FDG Choline PET:

Fluorodeoxy glucose choline positron emission tomography

DEXA:

Dual energy Xray absorptiometry

OFC:

Osteitis fibrosa cystica

MEN1:

Multiple endocrine neoplasia type 1

ALP:

Alkaline phosphatase

References

  1. Rao SD (2018) Epidemiology of parathyroid disorders. Best Pract Res Clin Endocrinol Metab 32:773–780

    Article  Google Scholar 

  2. Singh P, Vadi SK, Saikia UN, Sood A, Dahiya D, Arya AK, Behera A, Mukherjee S, Arvindkumar SM, Bhadada SK (2019) Minimally invasive parathyroid carcinoma—A missing entity between parathyroid adenoma and carcinoma: Scintigraphic and histological features. Clin Endocrinol (Oxf) 91:842–850

    Article  CAS  Google Scholar 

  3. Bhadada SK, Arya AK, Mukhopadhyay S, Khadgawat R, Sukumar S, Lodha S, Singh DN, Sathya A, Singh P, Bhansali A (2018) Primary hyperparathyroidism: insights from the Indian PHPT registry. J Bone Miner Metab 36:238–245

    Article  CAS  Google Scholar 

  4. Shah VN, Bhadada SK, Bhansali A, Behera A, Mittal BR (2014) Changes in clinical & biochemical presentations of primary hyperparathyroidism in India over a period of 20 years. Indian J Med Res 139:694–699

    PubMed  PubMed Central  Google Scholar 

  5. Minisola S, Gianotti L, Bhadada S, Silverberg SJ (2018) Classical complications of primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab 32:791–803

    Article  Google Scholar 

  6. Arya AK, Bhadada SK, Mukherjee S, Singh P, Rana SS, Dahiya D, Sood A, Saikia UN, Prakash M, Bhasin DK, Behera A (2018) Frequency & predictors of pancreatitis in symptomatic primary hyperparathyroidism. Indian J Med Res 148:721–727

    Article  CAS  Google Scholar 

  7. Mithal A, Kaur P, Singh VP, Sarin D, Rao DS (2015) Asymptomatic primary hyperparathyroidism exists in North India: Retrospective data from 2 tertiary care centers. Endocr Pract 21:581–585

    Article  Google Scholar 

  8. Clifton-Bligh PB, Nery ML, Supramaniam R, Reeve TS, Delbridge L, Stiel JN, McElduff A, Wilmshurst EG, Robinson BG, Fulcher GR, Learoyd D (2015) Mortality associated with primary hyperparathyroidism. Bone 74:121–124

    Article  CAS  Google Scholar 

  9. Reid LJ, Muthukrishnan B, Patel D, Seckl JR, Gibb FW (2019) Predictors of nephrolithiasis, osteoporosis and mortality in primary hyperparathyroidism. J Clin Endocrinol Metab 104:3692–3700

    Article  Google Scholar 

  10. Collier A, Ghosh S, Nowell S, Clark D (2019) Increased Mortality in Patients with Primary Hyperparathyroidism: Does Surgery Make a Difference? Endocr Pract 25:335–339

    Article  Google Scholar 

  11. Yu N, Donnan PT, Flynn RW, Murphy MJ, Smith D, Rudman A, Leese GP (2010) Increased mortality and morbidity in mild primary hyperparathyroid patients. The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin Endocrinol (Oxf) 73:30–34

    Google Scholar 

  12. Wermers RA, Khosla S, Atkinson EJ, Grant CS, Hodgson SF, Joseph Melton L (1998) Survival after the diagnosis of hyperparathyroidism: a population-based study. Am J Med 104:115–122

    Article  CAS  Google Scholar 

  13. Hedbäck G, Oden A (1998) Increased risk of death from primary hyperparathyroidism-an update. Eur J Clin Invest 28:271–276

    Article  Google Scholar 

  14. Nilsson IL, Wadsten C, Brandt L, Rastad J, Ekbom A (2004) Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease. Surgery 136:981–987

    Article  Google Scholar 

  15. Chiodini I, Cairoli E, Palmieri S, Pepe J, Walker MD (2018) Nonclassical complications of primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab 32:805–820

    Article  CAS  Google Scholar 

  16. Clark EP, Collip JB (1925) A study of the Tisdall method for the determination of blood serum calcium with a suggested modification. J Biol Chem 63:461–464

    Article  CAS  Google Scholar 

  17. Christensen SE, Nissen PH, Vestergaard P, Heickendorff L, Brixen K, Mosekilde L (2008) Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods. Clin Endocrinol (Oxf) 69:713–720

    Article  CAS  Google Scholar 

  18. Thanseer NT, Bhadada SK, Sood A, Mittal BR, Behera A, Gorla AK, Kalathoorakathu RR, Singh P, Dahiya D, Saikia UN, Rao SD (2017) Comparative effectiveness of ultrasonography, 99mTc-sestamibi, and 18F-fluorocholine PET/CT in detecting parathyroid adenomas in patients with primary hyperparathyroidism. Clin Nucl Med 42:e491-497

    Article  Google Scholar 

  19. Fottrell E, Byass P (2010) Verbal autopsy: methods in transition. Epidemiol Rev 32:38–55

    Article  Google Scholar 

  20. Pepe J, Cipriani C, Sonato C, Raimo O, Biamonte F, Minisola S (2017) Cardiovascular manifestations of primary hyperparathyroidism: a narrative review. Eur J Endocrinol 177:R297-308

    Article  CAS  Google Scholar 

  21. Pepe J, Piemonte S, Cipriani C, Cilli M, Minisola S (2014) Emerging data on cardiovascular risk in primary hyperparathyroidism. Endocrine 47:345–347

    Article  CAS  Google Scholar 

  22. Bhadada SK, Bhansali A, Shah VN, Rao DS (2011) Changes in serum leptin and adiponectin concentrations and insulin resistance after curative parathyroidectomy in moderate to severe primary hyperparathyroidism. Singapore med J 52:890–893

    PubMed  CAS  Google Scholar 

  23. Agarwal G, Nanda G, Kapoor A, Singh KR, Chand G, Mishra A, Agarwal A, Verma AK, Mishra SK, Syal SK (2013) Cardiovascular dysfunction in symptomatic primary hyperparathyroidism and its reversal after curative parathyroidectomy: results of a prospective case control study. Surgery 154:1394–1404

    Article  Google Scholar 

  24. Putnam R, Dhibar DP, Varshney S, Behera A, Mittal BR, Bhansali A, Rao SD, Bhadada SK (2016) Effect of curative parathyroidectomy on insulin resistance. Indian J Endocrinol Metab 20:784–789

    Article  CAS  Google Scholar 

  25. Palmieri S, Roggero L, Cairoli E, Morelli V, Scillitani A, Chiodini I, Eller-Vainicher C (2017) Occurrence of malignant neoplasia in patients with primary hyperparathyroidism. Eur J Intern Med 43:77–82

    Article  Google Scholar 

  26. McCarty MF (2000) Parathyroid hormone may be a cancer promoter - an explanation for the decrease in cancer risk associated with ultraviolet light, calcium, and vitamin D. Medical Hypothesis 54:475–482

    Article  CAS  Google Scholar 

  27. Nilsson IL, Zedenius J, Yin L, Ekbom A (2007) The association between primary hyperparathyroidism and malignancy: nationwide cohort analysis on cancer incidence after parathyroidectomy. Endocr Relat cancer 14:135–140

    Article  Google Scholar 

  28. Yu N, Leese GP, Donnan PT (2013) What predicts adverse outcomes in untreated primary hyperparathyroidism? The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin Endocrinol (Oxf) 79:27–34

    Article  CAS  Google Scholar 

  29. Tang JA, Salapatas AM, Bonzelaar LB, Friedman M (2018) Parathyroidectomy for the treatment of hyperparathyroidism: Thirty-day morbidity and mortality. Laryngoscope 128:528–533

    Article  CAS  Google Scholar 

  30. Verdelli C, Corbetta S (2017) Mechanisms in endocrinology: kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects. Eur J Endocrinol 176:R39-52

    Article  CAS  Google Scholar 

  31. Agrawal K, Arya AK, Sood A, Kumari P, Singh P, Sapara M, Rastogi A, Behera A, Bhadada SK (2020) A detailed appraisal of renal manifestations in primary hyperparathyroidism from Indian PHPT registry: Before and after curative parathyroidectomy. Clin Endocrinol. https://doi.org/10.1111/cen.14311

    Article  Google Scholar 

  32. Nair CG, Babu M, Jacob P, Menon R, Mathew J (2016) Renal dysfunction in primary hyperparathyroidism; effect of parathyroidectomy: A retrospective cohort study. Int J Surg 36:383–387

    Article  CAS  Google Scholar 

  33. Bhadada SK, Bhansali A, Ahluwalia J, Chanukya GV, Behera A, Dutta P (2009) Anaemia and marrow fibrosis in patients with primary hyperparathyroidism before and after curative parathyroidectomy. Clin Endocrinol 70(4):527–532

    Article  Google Scholar 

  34. Misgar RA, Bhat MH, Rather TA, Masoodi SR, Wani AI, Bashir MI, Wani MA, Malik AA (2020) Primary hyperparathyroidism and pancreatitis. J Endocrinol Invest 43:1493–1498

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We wish to acknowledge the contribution of Ms Anmol in data collection during follow-up.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Liza Das, Sanjay Kumar Bhadada, Sapara Mohin Arvindbhai, Pinaki Dutta, Anil Bhansali, Priyanka Singh & Poonam Kumari

  2. Department of General Surgery, PGIMER, Chandigarh, India

    Divya Dahiya & Arunanshu Behera

  3. Department of Nuclear Medicine, PGIMER, Chandigarh, India

    Ashwani Sood

  4. Department of Radiology, PGIMER, Chandigarh, India

    Mahesh Prakash

  5. Division of Endocrinology, Diabetes, and Bone & Mineral Disorders, Bone & Mineral Research Laboratory, Henry Ford Hospital, Detroit, MI, USA

    Sudhaker D. Rao

Authors
  1. Liza Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanjay Kumar Bhadada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sapara Mohin Arvindbhai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Divya Dahiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arunanshu Behera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pinaki Dutta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anil Bhansali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ashwani Sood
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Priyanka Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mahesh Prakash
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Poonam Kumari
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sudhaker D. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LD did data compilation, analysis and interpretation of data, was involved in patient management and drafted the manuscript. SKB conceived the idea, supervised patient management and data compilation, was involved in data interpretation and edited the manuscript. ARB and DD performed surgery on the patients. PD supervised patient management and provided crucial insights. AB supervised patient management and edited the manuscript. AS provided scintigraphic and MP provided radiologic expertise. SMA, PS and PK helped in data collection and follow-up. DSR was involved in data interpretation and edited the manuscript. All authors approved the final version of the manuscript and take responsibility for the integrity of the data analysis.

Corresponding author

Correspondence to Sanjay Kumar Bhadada.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

774_2021_1256_MOESM1_ESM.tif

Supplementary file1 (TIF 50 KB) Flow diagram depicting the inclusion and exclusion criteria as applied to all patients enrolled in the Indian PHPT Registry

774_2021_1256_MOESM2_ESM.tif

Supplementary file2 (TIF 80 KB) Survival analysis comparing the probability of mortality in PHPT based on tertile of baseline PTH levels classified as (PTH 6.5-50pmol/l, PTH 50-100pmol/l, PTH>100pmol/l). There was no significant difference in mortality associated with PTH tertile; log rank test P = 0.961

Supplementary file3 (DOCX 17 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Das, L., Bhadada, S.K., Arvindbhai, S.M. et al. Baseline renal dysfunction determines mortality following parathyroidectomy in primary hyperparathyroidism: analysis of Indian PHPT registry. J Bone Miner Metab 40, 81–91 (2022). https://doi.org/10.1007/s00774-021-01256-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-021-01256-9

Keywords

Search

Navigation