Ectopic production of parathyroid hormone in a patient with CKD.
Yogita Aggarwal, Specialist Registrar in Renal Medicine
Introduction: Symptomatic ectopic parathyroid production is not common, but when it does occur then ectopic parathyroid tissue should be considered as a cause alongside ectopic endogenous production from mitotic lesions. The case presented is that of symptomatic hyperparathyroidism due to ectopic parathyroid adenomas in a patient with known end stage renal failure who had had a previous total parathyroidectomy for tertiary hyperparathyroidism.
The case: A 50 year old female of Caribbean descent, who had suffered from chronic kidney disease secondary to chronic pyelonephritis for over 30 years, had developed symptomatic tertiary hyperparathyroidism.
The patient had reached end-stage renal failure in 1989 and received peritoneal dialysis for 5 years before accepting a cadaveric renal transplant graft in 1994. After an episode of earlier graft rejection, the patient’s creatinine settled to ‘a best’ of 200mmol/L. The graft failed in 2002 and the patient returned to peritoneal dialysis.
In 1991, the patient underwent a complete parathyroidectomy as management for tertiary parathyroid disease. The parathyroid hormone (PTH) level pre-operatively was 142pmol/l (1.3-7.6 pmol/l). The pre-operative MIBI scan demonstrated uptake in the parathyroid glands. The surgery was successful and histology confirmed that 4 adenomatous parathyroid glands had been removed. 1 week post operatively the parathyroid hormone level was still detectable at 7pmol/l.
In 2007, after the patient had been re-established on to peritoneal dialysis, it was noted that the parathyroid hormone level had gradually risen to 80pmol/l despite optimisation of phosphate control, vitamin D levels, and the use of calcimimetics such as Cinacalcet. The serum corrected calcium levels were normal. A MIBI scan completed at her local hospital picked up an area of uptake in the chest, see below (figure 1).
Figure 1: MIBI scan showing parathyroid adenoma (small pink dot above the heart). NB MIBI is also taken up by cardaic tissue hence the heart is also pink in this picture.
The patient also complained of generalised bony pains & imaging with a plain X-ray of the hands showed evidence of bony destruction in her phalanges (figure 2).
Figure 2: Radiograph showing bony detruction of phalanges
The patient’s serum alkaline phosphatase level was also noted to be 7 times the upper limit of the normal range.
Repeat nuclear medicine imgaing in the form of a SPECT scan showed new areas of increased uptake in the mediastinum and in the oropharynx (figure 3).
Fugure 3: SPECT imaging scans showing areas of increased uptake in the mediastinum and oropharynx
A CT showed an 18mm enhancing lesion vascular mass in her chest and a 10 x 18 x 25mm soft tissue mass within pre-vertabral soft tissue at the level of the oropharynx. A working diagnosis of ectopic parathyroid adenomas causing symptomatic tertiary hyperparathyroid disease was hypothesized. Histological diagnosis was required to rule out a mitotic aetiology (figure 4).
Figure 4: CT scans showing discrete lesions in the mediastinum (left-hand image) and the oropharynx (right-hand image).
Given that the serum alkaline phosphatase levels (indicative of the degree of bone turnover), the patient was deemed to be at high risk of developing ‘hungry bone syndrome’ (reviewed by Witteveen et al 2013) post operatively and was therefore preconditioned with high doses of vitamin D analogues in order to avoid this.
The patient underwent surgery with the cardiothoracic and ENT teams to remove both lesions in a single operation. The oropharyngeal lesion was removed endoscopically and the mediastinal lesion was removed through open surgery. Both lesions are shown in figure 5.
Figure 5: Macroscopic histological specimens of both lesions after removal.
The procedure passed without complication, and post-operative PTH levels were undetectable.
Despite aggressive post-operative electrolyte monitoring, the patient’s discharge was delayed due to the patient developing severe hypocalcaemia (due to hungry bone syndrome) and required intravenous calcium repolacement (through central venous access) and monitoring in the renal high dependency unit.
Discussion: The parathyroid glands are formed early in the embryological development of a fetus. They originate from tissue found at the base of the brain which goes on to form the thymus and thyroid glands, as well as the parathyroid glands. During gestation, the parathyroid glands migrate down to lie around the thyroid gland, but some do not migrate or migrate abnormally so that they remain high in the neck or descend too far into the chest.
Parathyroid glands that migrate too far and end up in the chest are about 15 times more common than parathyroid glands that don’t migrate far enough and end up high in the neck.
The parathyroid glands do not descend correctly in around 5% of the population, but this only becomes a problem if the glands behave metabolically abnormally. In the context of CKD in those patients undergoing parathyroidectomy, one study found that 13% of glands were noted to be in an ectopic location.
With relevance to the patient: This patient had four hyperplastic parathyroid glands removed in order to manage resistant tertiary parathyroidism disease in 1991. The 2 adenomatous lesions found in 2007 may have been supernumerary parathyroid glands which had abnormally descended but remained as micro glands due to negative feedback from the concurrent tertiary hyperparathyroid state the patient was in. Once the patient had had a total parathyroidectomy, they became stimulated to autonomous parathyroid hormone production due to the ongoing metabolic abnormalities associated with end stage renal disease (uraemia, persistent hypocalcaemia or hyperphosphataemia). Further MIBI scans are associated with a high false positive and false negative pick up rate depending on the site and size of the lesion. Thus the initial MIBI scans in 1991 may have failed to pick up the ectopic lesions.
- Ectopic parathyroid glands are not uncommon and are only problematic if they result in hyperparathyroidism.
- The post-operative parathyroid hormone level after the surgery in 2000 were still detectable 1 week after surgery indicting the possibility of remnants of the parathyroid gland or ectopic parathyroid hormone producing cells.
- Due to the metabolic disturbances found in end stage renal failure, recurrent hyperparathyroidism is possible if ectopic or remnant parathyroid tissue remains post parathyroidectomy.
- False negative rate of MIBI scanning of the parathyroid glands can be as high as 22%
- Albright F, Reifenstein EC Jr. (1948) The parathyroid glands and metabolic bone disease, Williams & Wilkins, Baltimore 1948.
- Andrade JS, Mangussi-Gomes JP, Rocha LA et al. (2014). Localization of ectopic and supernumerary parathyroid glands in patients with secondary and tertiary hyperparathyroidism: surgical description and correlation with preoperative ultrasonography and Tc99m-Sestamibi scintigraphy. Brazilian journal of otorhinolaryngology 80(1):29-34
- Brasier AR and Nussbaum SR (1988). Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med. 84(4):654.
- De Francisco A, Fresnedo G, Rodrigo E et al. (2002) Parathyroidectomy in dialysis patients Kidney International 61, S161–S166
- Goodman WG, Frazao JM, Goodkin DA et al. (2000) A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism. Kidney Int. 58(1):436
- Merlino JI, Ko K, Minotti A, McHenry CR. (2003) The false negative technetium-99m-sestamibi scan in patients with primary hyperparathyroidism: correlation with clinical factors and operative findings.Am Surg. 69(3):225-9; discussion 229-30.
- Norman. J. (2013) Hyperparathyroidism Blog from the Experts at the Norman Parathyroid Center (as last accessed on 20th March 2015)