Various techniques are helpful in the investigation of primary hyperparathyroidism. Biochemical tests such as the estimations of serum levels of calcium, phosphates, alkaline phosphatase etc, are useful but are rather nonspecific. In the presence of metabolic bone disease skeletal radio-graphs are very helpful.
Adenoma exceeds all other etiologies as the principal cause of primary hyperparathyroidism, occurring in approximately 85% of all cases1. Various techniques have been useful in the preoperative localization of parathyroid adenomata. These include cineoesophagography2, thermography3, high resolution real time ultrasonography4,5 computed tomography6,7, arterio. graphy8,9, and selective venous sampling for differential parathyroid hormone analysis9.
A combination of parathyroid arteriography and venous sampling with parathyroid hormone assay is probably the most accurate method available9. These techniques are time consuming, costly, require high expertise and are not without associated morbidity. Their replacement by non4nvasive methods is desirable10.
Attempts at detecting parathyroid adenomas with Se-75 selenomethionine11 and Cs-131 cesium chloride12 have been unsatisfactory. Ti-201 has better imaging characteristics and in 1983, Young et al have demonstrated a high success rate with parathyroid scintigraphy using the dual isotope 11-201 & Tc-99m subtraction scanning13. Since then others14 have reported favourable results with this new technique.
Here we briefly review the role of the various nuclear medicine investigations in the J.P.M.A. September, 1987 diagnosis of primary hyperparathyroidism and the initial experience with the dual isotope scanning for the detection of parathyroid adenomas in Paldstan.
A 23 years old woman presented with persistent skeletal pains and a history of intermittent albuminuria for the past 5 years. Albuminuria was discovered on hospitalization for typhoid fever 5 years previously and subsequently recurred on several occasions, without any other positive fmdings relating to the urinary tract.
Skeletal pain of moderate to severe intensity initially appeared around the knees and shins, and later in the pelvis and legs, with no signs of joint or muscular involvement and it was not relieved by conventional analgesics. She also developed muscle weakness, easy fatigability and paraesthesias. An element of depression was also present.
The patient was a thinly built with a pulse rate of 74 beats/min and a BP of 120/80 mm Hg. Haemoglobin was 13.6 g/dl, total leucocyte count 10.2 x 1012/1 and erythrocyte sedimentation rate 16 mmin the first hour.
Because of a positive family history of joint pains, the possibility of functional element was considered. She however did not respond to conventional treatment and remained refractory.
Biochemical examination on several occasions, showed normal levels of serum calcium (9.2±1.2 mg/dl) and 24 hrs urinary calcium (165 mg/24hrs), but urinary Sulkowitch test was positive. Serum. inorganic phosphate levels were low (1.0 mg/dl) on one occasion, normal (3.4 mg/dl) on another. Serum alkaline phosphatase was slightly raised (52 U/i).
Although the biochemical tests proved equivocal, skeletal radiography revealed typical appearances of hyperparathyroidism such as mild sub-periosteal resorption of the proximal phalanges plus mild erosion of terminal phalangeal tufts, oval cystic lesions in the distal ends of the left ulna and radius, mild granular decalcification of the vault of the skull with areas of increased density, sclerosis of the vertebral margins and rarefaction of the centre of acetabulum.
Based on the above findings a diagnosis of primary hyperparathyroidism was made and surgical exploration of neck was performed on 16.7.84 but without positive results.
The skeletal pains persisted and the patient repeatedly returned for medical advice.
In Dec. 1985 the patient was referred to the Nuclear Medical Centre, Anned Forces Institute of Pathology, Rawalpindi, for investigations where whole body bone scintigraphy, estimation of levels of serum parathormone by means of radioimmunoassay, and parathyroid scanning were performed.
Parathyroid hormone is a polypeptide with 84 amino acids15 The first 34 amino acids on the N-terminal end confer biological activity to the molecule. As the intact PTH molecule is cleaved into smaller molecules soon after secretion the active 1-34 N-terminal fragment is present in the circulation alongwith the intact molecule and the inactive C-terminal fragment. The biologically active N-terminal fragments are rapidly cleared from the plasma and have a short half life (approx. 18-30 min), whereas the biologically inactive C-terminal fragments have a longer half life (about several days )16. Antibodies have been raised that recognise the intact molecule and/or the C and N fragments. While antibodies to the biologically active N-terminal fragment exist, the short half life of this part of the molecule linlits their usefulness in separating normals from patients of hyperparathyroidism. Since the C-terminal fragment has a longer half life, it more closely reflects the amount of hormone secreted by the parathyroid glands, even though It has no biologic activity. Furthermore it has been shown that over 80% of the immunoreactive flH in the serum of hyperparathyroid man consists of the C-terminal fragments17.
In patients with malignant disease and hypercalcemia, the so called ‘ectopic hyperparathyroidism PTH measurement using anti-C antibodies is helpful in distinguishing it from primary hyperparathyroidism18. Assays utilizing antisera with specificity towards the C-fragment exhibit the highest clinical correlation with parathyroid gland function and dysfunction19.
The excessive PTH secretion in hyperparathyroidism may result in an increase in bone resorption and bone formation. Increased radionuclide uptake on bone scan could be expected in sites of increased bone formation; these sites would include areas of trabecular bone (spine, ends of long bones etc.) with its more rapid metabolic turnover, certain areas of cortical bone including the lamina dura of the jaw and the phalanges (subperiosteal resorption) and areas of bone cyst and bone tumor involvement20 generally, the skeletal uptake of the radiotracer has been found to be variable and no pattern specific for hyperparathyroidism has been noted on bone scintigraphy21 While bone scan may be helpful in the delineation of sites as well as extent of bone pathology its role appears to be primarily academic in these disorders. Diagnosis and quantitation of disease severity and assessment of effects of therapy appear to be more easily elicited by the usual techniques of immunoreactive parathyroid RIA, serum calcium/phosphorus/alkaline phosphatase, X-rays etc.22
The earlier reports of successful visualisation of parathyroid adenomas by Se-75 selenomethionine11 resulted in an immediate interest in this new method of investigation but though the initial results were encouraging, various workers reported only a moderate degree of success using this method23,24. Digulio and Morales (1969) concluded that selenomethionine scintigraphy could usually localise tumors larger than 2 g but smaller lesions could not be seen25 Computer processing with thyroid image subtraction resulted in an improvement on the earlier results26. However th poor energy characteristics and the high radiation dose delivered by this isotope has caused most centres to abandon this technique. Earlier results with 1-131 labelled Toluidine blue and triple subtraction technique also showed some success27, but was later abandoned.
In 1983, Young et al reported a new method of parathyroid scintigraphy using dual isotope (Tc-99m, 11-201) subtraction scintigraphy13. They reported a high success rate with this method. They showed that solitary parathyroid adenomas larger than 5 mm in diameter could be reliably located not only in normal anatomical positions but also elsewhere in the neck, including those within the thyroid gland and in the cervical and upper mediastinal region. In addition to visualising the parathyroid adenomas they were also able to locate 20 out of 36 hyper. plastic parathyroid glands as well. Since then there has been a flurry of interest in this new method of parathyroid scintigraphy and various workers have reported similar results.
The preoperative localization of the parathyroid adenomas is athantageous for various reasons. It is particularly helpful in patients requiring second look surgery where residual abnormal parathyroids may be ectopically situated in the neck and/or mediastinum. Further prior knowledge as to the location of an abnormal parathyroid may result in a quicker and surer surgery.
Whether subtraction scanning is a more useful technique than selective venous sampling can only be confirmed by further experience. However Young et al ‘obtained 3 out of 4 positive scans in patients who required re-exploration and who had unsuccessful venous sampling.
Tc-99m/Tl-201 subtraction scintigraphy is a non-invasive technique which is simple to perform and provides a reliable method of preoperative screening of patients with primary hyperparathyroidism.
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