Skip to main content

Persistent secondary hyperparathyroidism caused by parathyromatosis and supernumerary parathyroid glands in a patient on haemodialysis



Secondary hyperparathyroidism (SHPT) is a common high-risk factor for mortality in end-stage renal disease, and parathyromatosis and supernumerary parathyroid glands are very rare causes of persistent SHPT. Preoperative diagnosis and removal of all hyperplastic parathyroid glands are challenging. We report a rare case of persistent SHPT due to parathyromatosis and supernumerary parathyroid glands and successful management by multiple imaging modalities.

Case presentation

A 53-year-old Chinese woman on haemodialysis experienced discomfort due to itching and bone pain due to persistent SHPT after parathyroidectomy. The supernumerary parathyroid glands and parathyromatosis were detected by multiple imaging modalities, including 99mTc-sestamibi (99mTc-MIBI) scans, ultrasonography and four-dimensional computed tomography (4D-CT) and then excised; pathological confirmation was performed. During follow-up, her serum calcium and parathyroid hormone levels were stable in the appropriate ranges, and no complications arose.


Because of persistent SHPH after parathyroidectomy in patients with haemodialysis, multiple imaging modalities, including 99mTc-MIBI scans, 4D-CT and ultrasonography, are helpful for detecting supernumerary parathyroid glands and parathyromatoses. Accurate preoperative localization of this rare lesion is important for management, enabling the removal of all affected parathyroid tissues.

Peer Review reports


Secondary hyperparathyroidism (SHPT), a common and serious complication of end-stage renal disease (ESRD), is characterized by increased parathyroid hormone (PTH), calcium and phosphate levels, with substantial mortality [1, 2]. Surgical parathyroidectomy is crucial for patients who are resistant to medical treatment [2]. Furthermore, resection of all hyperplastic parathyroid glands is important, as remnant parathyroid glands can be continuously stimulated, leading to persistent or recurrent SHPT, which occurs in 0.4–25% of cases [3, 4]. Persistent or recurrent SHPT is attributed to various causes, including failure to identify or entirely remove hyperplastic parathyroid, ectopic, supernumerary parathyroid glands and, very rarely, parathyromatosis [5,6,7,8]. Parathyromatosis is very rare and is defined as multiple nests of hyperfunctioning parathyroid tissue [9]. Preoperative diagnosis and subsequent treatment are challenging. We report a case of persistent SHPT after parathyroidectomy due to parathyromatosis and supernumerary parathyroid glands in a patient with haemodialysis. SHPT was discovered by multiple imaging modalities and successfully managed.

Case presentation

A 53-year-old Chinese woman had ESDR secondary to obstructive kidney disease and was treated with haemodialysis three times a week regularly since October 2008. She received a living donor kidney graft in May 2008 that was lost 5 months later because of rejection. SHPT was diagnosed based on elevated PTH and hypercalcaemia in July 2014. Although she had taken a vitamin D analogue (calcitriol and caltrate) and phosphate binder (lanthanum carbonate), her PTH and serum calcium levels gradually increased. Since October 2015, the patient had constantly experienced generalized itching. The results of the laboratory tests were as follows (normal ranges in parentheses): serum PTH, 942 pg/mL (10–65); serum calcium, 2.64 mmol/L (2.03–2.54); serum phosphate, 3.17 mmol/L (0.87–1.45); serum alkaline phosphatase, 77 U/L (40–150). Four-dimensional computed tomography (4D-CT, which originates from the number of phases of imaging, typically 3, and the change over time, the fourth dimension) of the parathyroid demonstrated four enhanced nodules consistent with orthotopic parathyroid glands (Fig. 1). No remarkable signs of ectopic or supernumerary parathyroid glands were observed. In November 2015, parathyroidectomy was performed to remove the four parathyroid glands, and the right inferior parathyroid gland was transplanted into the nondominant right forearm. On the first postoperative day, tests revealed PTH of 212 pg/mL, serum calcium of 2.43 mmol/L, and serum phosphate of 1.44 mmol/L, with alleviation of itching. Pathological findings showed parathyroid nodular hyperplasia without evidence of malignancy. Eighteen months after the surgery, she presented with recurred itching and bone pain. Serum calcium and PTH levels were 2.56 mmol/L and 1631 pg/mL, respectively. Planar 99mTc-sestamibi (99mTc-MIBI) scanning failed to localize the lesion. However, ultrasonography identified a remnant parathyroid gland in the left inferior thyroid, and she subsequently underwent percutaneous ethanol injection therapy (PEIT). On the third day of PEIT, her PTH and serum calcium levels decreased to 447 pg/mL and 2.15 mmol/L, respectively. In August 2019, the patient again experienced itching and bone pain and was admitted due to elevated serum calcium of 3.08 mmol/L and an elevated PTH level of 1593 pg/mL. Physical examination revealed a well-healed cervical surgical scar without a palpable mass. 99mTc-MIBI single-photon emission computed tomography/computer tomography (SPECT/CT) indicated focal tracer uptake in the left inferior clavicle head (Fig. 2), consistent with the findings of 4D-CT and ultrasonography. A right nodule without tracer uptake was located subcutaneously in the anterior sternocleidomastoid muscle, which was also identified by serial 4D-CT (Fig. 3). A 99mTc-MIBI planar scan also demonstrated focal tracer uptake in the autografted site in the early and delayed phases (Fig. 4), accompanied by a hypoechoic mass on ultrasonography. Three nodules were identified during bilateral neck exploration and then removed (the right subcutaneous nodule, right inferior and left inferior clavicle head were 1.0 × 0.8 cm, 0.6 × 0.5 cm and 1.5 × 1.0 cm, respectively). On the first day after the operation, the PTH level in a blood specimen obtained from the right arm was 11,226 pg/mL, whereas it was 1029 pg/mL from the left arm. In September 2019, surgery to remove the nodules in the autografted site was performed. The next day, her PTH level had decreased to 6.9 pg/mL. Pathological results showed all four nodules to be hyperplastic parathyroid, with several small nodular foci of atypical hyperplastic parathyroid tissue in the fat adjacent to the right inferior remnant parathyroid (Fig. 5). According to the clinical course and pathological findings, parathyromatosis and supernumerary parathyroid glands were confirmed. During 6 months of follow-up, her itching and bone pain improved, and she exhibited appropriate calcium (2.04–2.38 mmol/L) and PTH (84.4–145.0 pg/mL) levels under regular haemodialysis (Table 1).

Fig. 1

Axial arterial-phase computer tomography images (A-C) demonstrate four enhanced orthotopic parathyroid glands (the arrows) located posterior or inferior to the thyroid gland

Fig. 2

The 99mTc-MIBI SPECT/CT image indicates a low-density lesion with high tracer uptake at the site of the inferior clavicle head (red arrows: A, axial image; B, SPECT; C, fusion image)

Fig. 3

Serial arterial-phase axial 4D-CT of the parathyroid shows the growth of the right nodule (red arrows) located subcutaneously in the anterior sternocleidomastoid muscle (A, pre-operative; B, 18 months after surgery; C, 46 months after surgery). The 99mTc-MIBI SPECT/CT image reveals the lesion without tracer uptake (red arrows: D, axial image; E, SPECT; F, fusion image)

Fig. 4

99mTc-MIBI planar early (A) and delayed (B) static images demonstrate focal tracer accumulation (red arrows) at the site of autograft

Fig. 5

Histopathology (haematoxylin-eosin staining× 50) reveals hyperplastic parathyroid tissues composed of chief cells (A, red circles: microscopic nests of hypercellular parathyroid in the right inferior neck adipose tissue; B, supernumerary parathyroid gland; C nodule located in right forearm; D, subcutaneous nodule located anterior sternocleidomastoid muscle)

Table 1 Changes in laboratory values in response to therapeutic interventions during the last 6 years

Discussion and conclusions

Parathyromatosis and supernumerary parathyroid glands are very rare causes of persistent SHPT after parathyroidectomy in patients undergoing haemodialysis. The form of parathyromatosis is speculated to be either the spillage and seeding of the parathyroid tissue during parathyroid surgery (type 2) or the development of embryonic rests of parathyroid tissue under physiological stimuli (type 1) [9,10,11,12]. In our case, one of the causes of the persistent hyperparathyroidism was considered to be type 2 parathyromatosis because both implanted autografts in the forearm and un-implanted subcutaneous seeding were observed. The existing factor of metabolic derangements in ESRD continues to stimulate the growth of implants [13]. Different stages of parathyroid hyperplasia may exist in the same patient because of the heterogeneity of the parathyroid glands with regard to different expression of calcium-sensing receptors, even under the same stimuli. We considered that rupture of the capsule may have occurred during the first parathyroidectomy, as a growth in the right subcutaneous anterior sternocleidomastoid muscle was revealed during serial 4D-CT. According to the literature, most cases are female subjects with ESRD in their fifth to sixth decade of life, which fits the profile of our patient [14]. The other cause of persistent hyperparathyroidism is the supernumerary parathyroid glands, which were overlooked in situ during the first operation; they were located in the left inferior clavicle head. Supernumerary parathyroid glands, which are found in approximately 13% of autopsy and 30–39% of re-operative cases [5, 15,16,17], may result from separation of the parathyroid anlage during embryologic migration, and most glands are located in the thymus or superior mediastinum [18]. Knowledge of the anatomy and embryology of parathyroid glands and meticulous handling of parathyroid glands to avoid rupture and spillage during surgery are essential for successful parathyroidectomy. Although complete surgical extirpation of all offending parathyroid nodules is the best option for patients with haemodialysis, it often does not occur [7]. Indeed, the greatest difficulty lies in precise preoperative localization and removal of all disseminated tiny and unexpected nodules of parathyroid tissue [14]. Preoperative imaging can help to identify supernumerary glands and parathyromatosis, but only 40% of patients are preoperatively diagnosed [7]. Moreover, there is no universally accepted consensus for preoperative localization, as different imaging modalities (ultrasonography, 99mTc-MIBI SPECT/CT, 4D-CT) have various advantages and disadvantages. Depending on the clinical scenario, physicians should choose a suitable image modality. At our institution, US and 99mTc-MIBI SPECT/CT are the first-line modalities for re-operation location of parathyroid lesions. When the first-line imaging modalities are negative or discordant, 4D-CT or MRI is used. Fortunately, all of the affected parathyroid nodules were successfully identified and managed in our patient, as also occurred in the rare accounts in the literature [18,19,20]. Ultrasonography can sometimes identify scattered hypoechoic, hypervascular cervical nodules that appear nonspecific and do not conform to typical anatomic locations of the parathyroid glands [8]. Nonetheless, this modality is operator dependent and unable to assess mediastinal sites, with difficulty in imaging of far-posterior lesions [21]. Overall, 99mTc-MIBI SPECT/CT can provide both functional and anatomic information and improve the detection of ectopic/supernumerary glands or far-posterior lesions, which ultrasonography is prone to miss. This technique can also reveal uptake foci and has superior (95%) positive predictive value [22]. Similar to other studies, some of the lesions in our patients were localized by 99mTc-MIBI SPECT/CT [5, 19, 21, 23]. 4D-CT is a relatively new imaging modality that is characterized by unique perfusion. In a study of 58 patients who had recurrent hyperparathyroidism, the sensitivity of localization of hyperfunctioning parathyroid tissue was 77.4% for 4D-CT compared to 46.0% for 99mTc-MIBI imaging [24]. In our study, serial 4D-CT located the supernumerary parathyroid glands and revealed the growth of parathyromatosis in the subcutaneous anterior sternocleidomastoid muscle in the patient, which was consistent with the literature [18, 21, 24, 25].

Regardless, the treatment and control of supernumerary parathyroid glands and parathyromatosis remain a challenge, as complete excision of all foci is very difficult. When multiple surgeries fail, medical treatment, including suppression of PTH production with cinacalcet and stabilization of bone mineral density with bisphosphonate, should be considered [8, 14, 26]. In conclusion, parathyromatosis and supernumerary parathyroid glands are very rare causes of persistent hyperparathyroidism in patients undergoing haemodialysis. Multiple imaging modalities are valuable for precise preoperative localization of affected parathyroid tissues and may help with subsequent treatment.

Availability of data and materials

Not applicable.



Secondary hyperparathyroidism




Four-dimensional computed tomography


End-stage renal disease


Single-photon emission computed tomography/computer tomography


  1. 1.

    Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, et al. Diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder: synopsis of the kidney disease: improving global outcomes 2017 clinical practice guideline update. Ann Intern Med. 2018;168:422–30.

    Article  Google Scholar 

  2. 2.

    Lau WL, Obi Y, Kalantar-Zadeh K. Parathyroidectomy in the management of secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2018;13:952–61.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Aly A, Douglas M. Embryonic parathyroid rests occur commonly and have implications in the management of secondary hyperparathyroidism. ANZ J Surg. 2003;73:284–8.

    Article  Google Scholar 

  4. 4.

    Zhang L, Xing C, Shen C, Zeng M, Yang G, Mao H, et al. Diagnostic accuracy study of intraoperative and perioperative serum intact PTH level for successful parathyroidectomy in 501 secondary hyperparathyroidism patients. Sci Rep. 2016;6:26841.

    CAS  Article  Google Scholar 

  5. 5.

    Tai TS, Hsu YH, Chang JM, Chen CC. Recurrent tertiary hyperparathyroidism due to supernumerary parathyroid glands in a patient receiving long-term hemodialysis: a case report. BMC Endocr Disord. 2019;19:16.

    Article  Google Scholar 

  6. 6.

    Schneider R, Waldmann J, Ramaswamy A, Fernandez ED, Bartsch DK, Schlosser K. Frequency of ectopic and supernumerary intrathymic parathyroid glands in patients with renal hyperparathyroidism: analysis of 461 patients undergoing initial parathyroidectomy with bilateral cervical thymectomy. World J Surg. 2011;35:1260–5.

    Article  Google Scholar 

  7. 7.

    Matsuoka S, Tominaga Y, Sato T, Uno N, Goto N, Katayama A, et al. Recurrent renal hyperparathyroidism caused by parathyromatosis. World J Surg. 2007;31:299–305.

    Article  Google Scholar 

  8. 8.

    Tublin ME, Yim JH, Carty SE. Recurrent hyperparathyroidism secondary to parathyromatosis: clinical and imaging findings. J Ultrasound Med. 2007;26:847–51.

    Article  Google Scholar 

  9. 9.

    Reddick RL, Costa JC, Marx SJ. Parathyroid hyperplasia and parathyromatosis. Lancet. 1977;1:549.

    CAS  Article  Google Scholar 

  10. 10.

    Lentsch EJ, Withrow KP, Ackermann D, Bumpous JM. Parathyromatosis and recurrent hyperparathyroidism. Arch Otolaryngol Head Neck Surg. 2003;129:894–6.

    Article  Google Scholar 

  11. 11.

    Stehman-Breen C, Muirhead N, Thorning D, Sherrard D. Secondary hyperparathyroidism complicated by parathyromatosis. Am J Kidney Dis. 1996;28:502–7.

    CAS  Article  Google Scholar 

  12. 12.

    Fitko R, Roth SI, Hines JR, Roxe DM, Cahill E. Parathyromatosis in hyperparathyroidism. Hum Pathol. 1990;21:234–7.

    CAS  Article  Google Scholar 

  13. 13.

    Meakin JL, Milne CA, Hollomby DJ, Goltzman D. Total parathyroidectomy: parathyroid hormone levels and supernumerary glands in hemodialysis patients. Clin Invest Med. 1989;7:21–5.

    Google Scholar 

  14. 14.

    Hage MP, Salti I, El-Hajj FG. Parathyromatosis: a rare yet problematic etiology of recurrent and persistent hyperparathyroidism. Metabolism. 2012;61:762–75.

    CAS  Article  Google Scholar 

  15. 15.

    Mariette C, Pellissier L, Combemale F, Quievreux JL, Carnaille B, Proye C. Reoperation for persistent or recurrent primary hyperparathyroidism. Langenbeck's Arch Surg. 1998;383:174–9.

    CAS  Article  Google Scholar 

  16. 16.

    Akerstrom G, Malmaeus J, Bergstrom R. Surgical anatomy of human parathyroid glands. Surgery. 1984;95:14–21.

    CAS  PubMed  Google Scholar 

  17. 17.

    Pattou FN, Pellissier LC, Noël C, Wambergue F, Huglo DG, Proye CA. Supernumerary parathyroid glands: frequency and surgical significance in treatment or renal hyperparathyroidism. World J Surg. 2000;24:1330–4.

    CAS  Article  Google Scholar 

  18. 18.

    Daphnis E, Stylianou K, Katsipi I, Stratigis S, Karamitopoulou E, Karkavitsas N, et al. Parathyromatosis and the challenge of treatment. Am J Kidney Dis. 2006;48:502–5.

    Article  Google Scholar 

  19. 19.

    Cao H, Zeng M, Fang H, Tang L, Liu W. Parathyromatosis type 2 detected by 99mTc-MIBI SPECT/CT. Gland Surg. 2019;8:806–9.

    Article  Google Scholar 

  20. 20.

    Bunch PM, Kelly HR. Preoperative imaging techniques in primary hyperparathyroidism a review. JAMA Otolaryngol Head Neck Surg. 2018;144:929–37.

    Article  Google Scholar 

  21. 21.

    Haciyanli M, Karaisli S, Gucek HS, Atasever A, Arikan ED, Gur EO, et al. Parathyromatosis: a very rare cause of recurrent primary hyperparathyroidism-case report and review of the literature. Ann R Coll Surg Engl. 2019;101:178–83.

    Article  Google Scholar 

  22. 22.

    Wei WJ, Shen CT, Song HJ, Qiu ZL, Luo QY. Comparison of SPET/CT, SPET and planar imaging using 99mTc-MIBI as independent techniques to support minimally invasive parathyroidectomy in primary hyperparathyroidism: a meta-analysis. Hell J Nucl Med. 2015;18:127–35.

    PubMed  Google Scholar 

  23. 23.

    Pinnamaneni N, Shankar PR, Muthukrishna A. 99mTc MIBI SPECT findings in Parathyromatosis-a rare entity causing recurrent hyperparathyroidism. Clin Nucl Med. 2013;38:443–5.

    Article  Google Scholar 

  24. 24.

    Wei AE, Garrett MR, Gupta A. Parathyromatosis: a rare case of recurrent hyperparathyroidism localized by four-dimensional computed tomography. AACE Clinical Case Rep. 2019;5:384–7.

    Article  Google Scholar 

  25. 25.

    Hamidi M, Sullivan M, Hunter G, Hamberg L, Cho NL, Gawande AA. At el. 4D-CT is superior to ultrasound and Sestamibi for localizing recurrent parathyroid disease. Ann Surg Oncol. 2018;25:1403–9.

    Article  Google Scholar 

  26. 26.

    Aksoy-Altinboga A, Sari AA, Rezanko T, Haciyanli M, Calli AO. Parathyromatosis: critical diagnosis regarding surgery and pathologic evaluation. Korean J Pathol. 2012;46:197–200.

    Article  Google Scholar 

Download references


Not applicable.


Not applicable.

Author information




JY examined and drafted the manuscript. JZ and HL contributed to the interpretation of the clinical data. NL helped draft the manuscript. MD is the corresponding author and organized the study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Meng-jie Dong.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University.

Consent for publication

Written informed consent to publish was obtained from the patient for publication of the case report.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

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

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, J., Zhang, J., Liu, Nh. et al. Persistent secondary hyperparathyroidism caused by parathyromatosis and supernumerary parathyroid glands in a patient on haemodialysis. BMC Nephrol 21, 257 (2020).

Download citation


  • Persistent secondary hyperparathyroidism
  • Parathyromatosis
  • Supernumerary parathyroid glands
  • Haemodialysis