E-Poster Presentation 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

Recurrent hyperparathyroidism following successful four gland parathyroidectomy and normalisation of pth in a renal transplant patient (#133)

Ryan Petrucci 1 , Tamara Preda 1 2 , DP Johnston 3 , Alar Enno 4
  1. Department of Endocrine, Head and Neck Surgery, Liverpool Hospital, Sydney, NSW, Australia
  2. School of Medicine, Notre Dame University, Sydney, NSW, Australia
  3. Clear View Medical Imaging, Sydney, NSW, Australia
  4. Department of Anatomical Pathology, Liverpool Hospital, Sydney, NSW, Australia

Introduction

According to the Australian Bureau of Statistics 2011-12 Australian Health Survey, an estimated 10% of Australian adults over the age of 18 years had biomedical signs of chronic kidney disease (CKD) (1). The Kidney Disease: Improving Global Outcomes guidelines recommend that patients with stage 3 CKD undergo screening for secondary hyperparathyroidism (2).

Endocrine and biochemical anomalies associated with renal hyperparathyroidism relate to bone mineral/metabolic and cardiovascular disease.  Secondary hyperparathyroidism (SHPT) in CKD patients is associated with increased fractures, hyperphosphataemia, anaemia, vascular and tissue calcification; these are important to treat before renal transplantation (3).  There is also some evidence to suggest hypertension improves post parathyroidectomy in these patients and is a further benefit of parathyroidectomy prior to renal transplant (4).

Medical management for secondary hyperparathyroidism can be divided into pharmacological and surgical. Pharmacological agents include Vitamin D, Calcimimetics and phosphorus binders.  Surgical options include total and subtotal parathyroidectomy (3).  Internationally used guidelines such as The National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) recommend parathyroidectomy for patients who are refractory to medical management (5). 

Background

We present the case of a chronic renal failure patient who developed recurrent hyperparathyroidism despite previous ‘total’ parathyroidectomy and subsequent renal transplant.

Case Report

A 62 year old man was referred by his treating physicians to an endocrine surgeon with presumed tertiary hyperparathyroidism. He had a history of total parathyroidectomy and bilateral cervical thymectomy 17 years prior for secondary hyperparathyroidism with underlying chronic renal failure due to IgA nephropathy as a child.

Review of the histopathology report from this surgery confirmed removal of 4 hyperplastic parathyroid glands weighing between 0.285-0.815 grams.

 5f4882b1b1b19-Figure+1.png

Figure 1- A low power (x10 magnification) image of the hyperplastic fat depleted parathyroid gland. There is adjacent normal parathyroid tissue visible.

 

The operation report noted four parathyroid glands in their expected locations in the neck. Comment was made that bilateral inferior parathyroids were found in the thyrothymic tract and were noted to be larger than their superior counterparts. The lower limit of dissection was the left brachiocephalic vein posterior to the manubrium (demarcated by surgical clips).

Following his original surgery PTH dropped from 93pmol/L to 4.6pmol/L with laboratory reference range 1.6 -6.9 pmol/L. This result was consistent with biochemical cure.

5 years after parathyroid surgery the patient underwent a renal transplant with excellent renal function for 8 years. His renal function then deteriorated culminating in a return to peritoneal dialysis (oliguric but not anuric).  At the time of surgical review laboratory test results showed a PTH 120pmol/L (RR 1.6-6.9pmol/L), corrected serum calcium 2.60mmol/L (RR 2.15-2.55mmol/L) and eGFR 7 mL/min/1.73m2. These results were indicative of tertiary hyperparathyroidism.

Imaging investigations were undertaken in order to localise the functioning parathyroid tissue responsible for elevation of PTH levels.  A neck ultrasound did not detect any mass lesions. A SESTAMIBI-SPECT CT reported no focal uptake in or around the thyroid. A 12mm thoracic para-aortic nodule was seen in the left anterior/superior mediastinum adjacent to the aortic arch with moderate focal uptake (figure 2).

 

 

 5f4882b1b1b19-Figure+2.png

Figure 2- Sestamibi Parathyroid scan showing uptake in a mediastinal ectopic parathyroid gland situated adjacent to the arch of the aorta

 

The patient was referred for 4D Parathyroid CT. Non-contrast images were obtained given the patient was not anuric. A a mildly lobulated rounded lesion adjacent to the aortic arch in the superior mediastinum measuring 15 x 11mm with a single punctate focus of calcification was reported (figures 3 and 4). 

 

 5f4882b1b1b19-Figure+3.png

Figures 3 – Axial CT image of mediastinal mass highlighted with the green arrow.

 

 

 5f4882b1b1b19-Figure+4.png

Figure 4- Coronal CT image of mediastinal mass highlighted with the green arrow

 

The patient was referred on to a cardiothoracic surgeon and a thoracoscopic excision of the lesion was undertaken in March 2020. The tumour was located in accordance with the imaging on the left side of the aortic arch and noted to be intimately associated with the phrenic nerve.

The surgical specimen was sent for histological assessment and reported a 1.7g fat depleted parathyroid gland with focal fibrosis and haemorrhage in keeping with an adenoma; no atypia. 

Post-operative PTH dropped to 18.9pmol/L compared to 119pmol/L, which was taken 2 months prior to surgery.  Post-operative corrected serum calcium normalised to 2.19 mmol/L.  He was commenced on Calcium and 1,25 dihydroxycholecalciferol supplements to maintain normal corrected serum calcium levels and for treatment of bone disease.

He has been listed for a second renal transplant.

 

Discussion

Recurrent hyperparathyroidism although not common is of clinical significance due to its deleterious effects.  Recurrence in patients who have undergone total parathyroidectomy has been attributed to incomplete cervical parathyroidectomy or supernumerary glands.  A large-scale follow up study of 519 patients who underwent total parathyroidectomy showed a recurrence rate of 2.4% with 50% of these cases diagnosed with supernumerary mediastinal parathyroid glands (6).  These patients required re-do surgery after imaging localisation.

Approximately 2-13% of the population have supernumerary (5 or 6) parathyroid glands (7,8).  Ectopic parathyroids are defined as functional parathyroid glands located outside the normal anatomical position due to aberrant migration during foetal development. (9). They are found most commonly in the thymus, within the thyroid or in the mediastinum (6).

In CKD patients with secondary hyperparathyroidism it can take 6-12 months for PTH levels to normalise post transplant (10). Patients who continue to suffer from SHPT or recurrent disease need proper investigation and either pharmacological or surgical treatment.  The current quoted prevalence of parathyroidectomy for this subgroup of patients is 1-5.6% (10).

In regards to this case it appears that the patient had an adequate PTH response to total parathyroidectomy initially.  However, over time recurrent hyperparathyroidism manifested and was determined to be due to an ectopic supernumerary parathyroid gland.  Whilst rare, this highlights the need for ongoing surveillance of renal hyperparathyroidism patients with consideration to the presence of supernumerary glands. Dual localisation with SESTAMIBI and CT is optimal when a non-neck location is likely.

 

Conclusion

  • This case demonstrates that it is worthwhile to follow up patients who have been treated for secondary hyperparathyroidism, particularly once in receipt of renal transplant. Biochemical surveillance is simple and effective in detecting recurrence.
  • Cross sectional thoracic imaging can and should be used to detect and localise supernumerary glands not apparent at the time of original surgery.
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