ArticlesPreoperative imaging of parathyroid glands with technetium-99m-labelled sestamibi and iodine-123 subtraction scanning in secondary hyperparathyroidism
Introduction
Although haemodialysis prolongs the lives of uraemic patients, secondary hyperparathyroidism causes substantial morbidity (especially progressive osteodystrophy and vascular and soft-tissue calcification). The mechanisms underlying secondary hyperparathyroidism in renal failure are not completely clear.1, 2, 3, 4 The relative importance of the three primary factors, hypocalcaemia, low calcitriol concentrations, and high plasma phosphate concentrations, continues to be debated. What is clear, however, is that the initial stimuli leading to parathyroid-cell hypertrophy are followed by cell proliferation. The extent of parathyroid growth then becomes a major determinant of parathyroid hormone (PTH) hypersecretion.3 Factors such as low numbers of calcitriol receptors on parathyroid cells from uraemic patients4 and increased PTH secretory set-point due to low expression of calcium receptors5 may accelerate parathyroid growth. Parathyroid growth can progress from diffuse hyperplasia to nodular asymmetrical glandular enlargement. The emergence of monoclonal adenoma like formations is common, probably as the result of gene mutations in one or more cells in a nodule.6
Medical therapy, including calcitriol pulses, may ultimately fail to control the disturbances of parathyroid-cell and calcium and phosphate metabolism, or expose the patients to an unacceptable risk of vascular and soft-tissue calcification. Since the average duration of dialysis treatment is increasing, the proportion of patients who require surgery to correct parathyroid overfunction is growing.7 Despite increasing experience in parathyroid surgery, the rate of surgical failure after a first cervicotomy ranges from 10% to 30%.8, 9, 10 The main cause of surgical failure is incomplete identification of all parathyroid tissue.8, 9 Persistent disease can be identified by plasma PTH measurements in the year after surgery. Late recurrence can be due to regrowth of parathyroid tissue that was left in place, or transplanted to the forearm, to prevent hypoparathyroidism. The total rate of surgical failure is much higher than that reported for primary hyperparathyroidism, which is less than 8% in experienced hands.11 Surgical morbidity and mortality rates are also higher in patients with renal failure than in patients operated on for primary hyperparathyroidism.12, 13
Few surgeons believe that preoperative imaging can improve the success rate of first surgery in uraemic patients, in whom all parathyroid glands should be searched for. A few investigators have routinely combined computed tomography, thallium-201 scanning, and ultrasonography, but the sensitivity for enlarged parathyroid glands was only 70%.14
Parathyroid imaging with technetium-99m-labelled sestamibi,15 a new cardiac, parathyroid, and potential tumour-imaging agent, is more sensitive than previous imaging methods in primary hyperparathyroidism. 16, 17, 18, 19, 20 Reported sensitivity in primary hyperplasia, however, is variable. When 99mTc-sestamibi is used as a single tracer with imaging at two time-points (the double-phase method), sensitivity for primary hyperplasia is low.18 Similarly, this technique is not very sensitive for hyperplastic glands in uraemic patients.21, 22 The use of either iodine-123 or 99mTc-pertechnetate scanning, in addition to 99mTc-sestamibi scanning, greatly improves sensitivity in both primary hyperplasia23, 24, 25 and secondary hyperparathyroidism.26, 27 The addition of the thyroid tracer permits thyroid delineation and subsequent image subtraction.
The main difficulty with subtraction imaging is that the patient must remain absolutely still during the period needed to scan the thyroid, inject 99mTc-sestamibi, and record the image of the latter tracer. In a study on primary hyperparathyroidism, we used a subtraction scanning method in which the distribution images from 123 I and 99mTc-sestamibi are recorded simultaneously.28 Simultaneous double-window acquisition prevents artifacts on subtraction images due to movement of the patient and shortens the imaging time. We found overall sensitivity of 94% for the dualisotope technique with simultaneous recording compared with 79% for the single-tracer technique (p<0·04). Specificity was also improved (95vs98%).28 We have investigated the potential benefit of 99mTc-sestamibi/123 I parathyroid scanning in patients with secondary hyperparathyroidism referred for first parathyroid surgery.
Section snippets
Patients and methods
During a 2-year period, 11 consecutive uraemic patients, scheduled for parathyroid surgery, prospectively underwent imaging and subtotal parathyroidectomy. Mean age was 47·8 years (range 19-84). There were seven men and four women. None of the patients had undergone parathyroid surgery previously. Ten patients had been on dialysis for an average of 8·7 years (range 2-15); the other patient (patient 6) had undergone successful renal transplantation 3 years earlier. Surgical parathyroidectomy was
Results
99mTc-sestamibi/123 I subtraction scanning identified 42 hot-spots that suggested enlarged parathyroid glands (table). In two patients the preoperative scan showed five hot-spots, suggesting the presence of supernumerary parathyroid glands. In patient 3, the extra image was on the right side of the thyroid bed (figure). In patient 7, the fifth focus was below the the thyroid lobe, at the cervicomediastinal inlet (figure). Preoperative imaging suggested enlargement of the four parathyroid glands
Discussion
99mTc-sestamibi/123 I subtraction scintigraphy reliably detected enlarged parathyroid glands in all 11 uraemic patients, and preoperatively identified parathyroid glands in unusual numbers or locations. There were no false-positive images, and the only surgical failure could be explained by the scintigraphic findings.
The persistence of secondary hyperparathyroidism is a major problem encountered by all experienced surgeons30 Whatever kind of parathyroidectomy is done (subtotal or total with
References (36)
- et al.
Pathogenesis of secondary hyperparathyroidism
Am J Kidney Dis
(1994) The hyperparathyroidism of chronic renal failure: a disorder of growth
Kidney Int
(1997)- et al.
Relationship between intact 1-84 parathyroid hormone and bone histomorphic parameters in dialysis patients without aluminum toxicity
Am J Kidney Dis
(1995) The pathogenesis of parathyroid gland hyperplasia in chronic renal failure
Kidney Int
(1995)- et al.
Pathogenesis and medical treatment of secondary hyperparathyroidism
Semin Surg Oncol
(1997) - et al.
Reduced immunostaining for the extracellular Ca-sensing receptor in primary and uremic secondary hyperparathyroidism
J Clin Endocrinol Metab
(1996) - et al.
Monoclonality of parathyroid tumours in chronic renal failure and in primary parathyroid hyperplasia
J Clin Invest
(1995) - et al.
Histopathology, pathophysiology, and indications for surgical treatment of renal hyperparathyroidism
Semin Surg Oncol
(1997) - et al.
Reoperations for persistent and recurrent secondary hyperparathyroidism
Ann Surg
(1988) - et al.
Reoperation for secondary hyperparathyroidism in chronic renal failure
Nephrol Dial Transplant
(1991)
Short and long term efficacy of total parathyroidectomy with immediate autografting compared with subtotal parathyroidectomy in hemodialysis patients
J Am Soc Nephrol
Late results of operation for primary hyperparathyroidism in 441 patients
Surgery
Surgical treatment of renal hyperparathyroidism
Surg Gynecol Obstet
Subtotal parathyroidectomy in dialysis dependent and post renal transplant patients
Arch Surg
Evaluation of image-diagnosing methods of enlarged parathyroid glands in chronic renal failure
World J Surg
99mTc sestamibi-a new agent for parathyroid imaging
Nucl Med Commun
Parathyroid imaging with technetium-99m-Sestamibi: preoperative localization and tissue uptake studies
J Nucl Med
Prospective evaluation of the efficacy of technetium 99m sestamibi and iodine 123 radionuclide imaging of abnormal parathyroid glands
Surgery
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