Original Article |
Corresponding author: Albena Botushanova ( abotushanova@abv.bg ) © 2022 Albena Botushanova, Veselin Popov, Zhanet Grudeva, Aleksandar Botushanov, Dimitar Troev.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Botushanova A, Popov V, Grudeva Z, Botushanov A, Troev D (2022) The role of 18F-FDG PET/CT and single isotope 99mTc-tetrofosmin scintigraphy combined with SPECT in diagnosis of multiple endocrine neoplasia type 1 syndrome. Folia Medica 64(1): 181-186. https://doi.org/10.3897/folmed.64.e62733
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We present a case of a 47-year-old woman with type 1 multiple endocrine neoplasia, primary hyperparathyroidism, insulinoma, and nonfunctioning pituitary adenoma. In July 2017, the patient was referred to the Department of Nuclear Medicine of St George University Hospital in Plovdiv for a PET/CT scan because of persistent hypoglycemic episodes and high serum insulin levels. A whole-body PET/CT examination was performed 65 min after intravenous application of 188 MBq 18F-FDG on a hybrid PET/CT scanner (Biograph mCT 64, Siemens). We detected a low metabolically active lesion 10 mm in diameter (SUVmax - 2.00), located below the left thyroid lobe suspicious for parathyroid adenoma. In the remaining scanned areas there were no PET/CT data for other areas with increased glucose metabolism with malignant characteristics that could be associated with the underlying disease.
For further characterisation of the lesion, two months later we performed a single-isotope dual-phase 99mTc-tetrofosmin scintigraphy combined with an early SPECT technique on a SPECT gamma camera (SYMBIA E DUAL). The examination visualized a zone of hyperfixation located dorsally to the caudal portion of the left thyroid lobe associated with a hyperfunctioning parathyroid adenoma.
This case allowed us to compare two nuclear medicine modalities with different equipment and radiopharmaceuticals – PET/CT with 18F-FDG and single-isotope dual-phase 99mTc-tetrofosmin scintigraphy combined with an early SPECT in one and the same patient. Different factors can explain the acquired different diagnostic information.
99mTc-tetrofosmin scintigraphy, PET/CT 18F-FDG, primary hyperparathyroidism, SPECT
Multiple endocrine neoplasia (MEN) is characterized by the presence of benign or malignant tumours involving two or more endocrine glands. The clinical picture depends on the type of the affected endocrine glands. Each of the syndromes has autosomal dominant pattern of inheritance with high penetrance and variable expression. The most common tumours seen in MEN 1 involve the parathyroid glands, islet cells of the pancreas and the pituitary gland. The clinical diagnosis is made in the presence of two affected glands or one with an accompanying family history. The frequency according to literature data varies from 2-20/100000 people.[
Primary hyperparathyroidism (PHPT), which is due to autonomic overproduction of parathyroid hormone (PTH) by one or more abnormal parathyroid glands, is the most common manifestation of MEN 1. In the majority of cases it is asymptomatic. Most of the patients with PHPT have no clinical symptoms and the disease is diagnosed by detected changes in serum calcium, phosphate, and PTH levels.[
We present a case of a female patient with multiple endocrine neoplasia (MEN) – type 1 in whom whole body PET/CT examination with 18F-FDG showed a lesion with low metabolic activity, suspicious for parathyroid adenoma, behind the left thyroid lobe, which was lately confirmed with single-isotope dual-phase 99mTc-tetrofosmin scintigraphy in combination with an early SPECT technique.
The patient was a 47-year-old woman diagnosed over the years with MEN 1 - hormonally inactive pituitary microadenoma, hyperparathyroidism and recurrent hypoglycemic episodes accompanied with high serum insulin levels. The patient has been diagnosed, treated, and followed-up for many years in the Clinic of Endocrinology and Metabolic Diseases at St George University Hospital from where she was referred to the Department of Nuclear Medicine for topical diagnosis. The initial manifestation of the disease dates back to 1999 and was associated with frequent episodes of hypoglycemia with frequent hypoglycemic comas. Due to the lack of any detectable local changes in the pancreas from the performed imaging studies and the presumed presence of beta-cell hyperplasia, a therapeutic resection of the tail and part of the body of the pancreas was performed. Postoperatively, a reduction of the hypoglycemic episodes was reported. Later on, primary hyperparathyroidism was diagnosed due to aggravating bone pain, bilateral nephrolithiasis, and changes in the calcium-phosphate metabolism. In 2000, a surgical removal of an adenoma of the right lower parathyroid gland was performed simultaneously with right lobectomy of the thyroid gland due to benign nodular transformation. The MRI examination of the hypothalamic-pituitary area, performed in 2006, revealed a 4-mm microadenoma of the pituitary gland, functionally assessed as hormonally inactive. The patient’s case was originally presented from an endocrinological point of view at the XI National Congress of Endocrinology. [
Due to persistence of clinical and paraclinical data for hyperparathyroidism in 2007, a MRI revealed a formation located in the upper anterior mediastinum. On July 4, 2007, the patient underwent a new operation with extirpation of a parathyroid adenoma 15×10 mm in size. The histological examination showed parathyroid adenoma composed of chief cells and oxyphil cells.
In July 2017, elevated values of total calcium of 2.59 mmol/l (2.2-2.6) and PTH 184 pg/ml (11-67) with a low level of serum phosphate 0.75 mmol/l (0.77-1.45) were registered again. Ultrasound of the cervical region did not reveal any lesions suspicious for parathyroid adenoma, and the patient was left untreated. Because of the appearance again of clinically presented hypoglycemic episodes, with increasing intensity and frequency, accompanied by high levels of serum insulin, despite the previously performed resection of the tail and part of the body of the pancreas, the patient was referred to the Department of Nuclear Medicine at St George University Hospital, Plovdiv for a PET/CT scan. The examination was performed following a strict protocol for preparation of the patient: a fasting period of at least 6 hours, no intake of alkaloid beverages, sweet liquids, without tobacco smoking and strenuous physical activity one day before and on the day of the study. Blood glucose was measured and intravenous catheter was placed. The radiopharmaceutical 18F-fluorodeoxyglucose (FDG) was used for the examination. The patient underwent PET/CT whole-body scan on a hybrid apparatus PET/CT (Biograph mCT64, Siemens,), 65 minutes after intravenous administration of 188 MBq 18F-FDG. A lesion located dorsally of the left thyroid lobe was detected with dimensions of 10 mm and low metabolic activity, SUVmax - 2.00, suspicious for a parathyroid adenoma. (Fig.
Because the patient had already undergone two surgical removals of parathyroid adenomas in the past and the inconclusive results received by the ultrasound examination of the neck, to elucidate the nature of the discovered lesion behind the left lobe of the thyroid gland, two months later we performed a single-isotope dual-phase 99mTc-tetrofosmin scintigraphy, combined with an early SPECT technique on a SPECT gamma camera “SYMBIA E DUAL”. After administration of 740 MBq 99mTc-tetrofosmin strictly intravenously to the patient, early (20 min) and late (120 min) planar images of the neck and upper mediastinum were obtained. In addition to this procedure, immediately after the early planar images, without changing the position of the patient, we performed SPECT technique. The examination was performed in a tomographic mode with a low-energy collimator in a circular orbit of 360 degrees, “Step and shot” registration, matrix 128×128, 60 projections for 32 seconds at an interval of 30 degrees, for a total of 30 minutes.
We processed the results both from the early phase (20 min) and the late phase (120 min) images together with the images obtained from early SPECT (20 min).
In the early phase (20 min) images, an intensive accumulation of the radiopharmaceutical was registered in the thyroid gland with relatively higher uptake in the caudal part of the left thyroid lobe. (Fig.
Hybrid axial РЕТ/СТ image - a lesion located dorsally of the left thyroid lobe is visualized with low metabolic activity, SUVmax - 2.00 which is suspected for a parathyroid adenoma.
The early phase (20 min) shows an intense accumulation of the radiopharmaceutical in the thyroid gland with relatively increased uptake in the lower part of the left thyroid lobe. The late phase (120 min) shows a delayed washout of the radiopharmaceutical from the thyroid gland while registering a focus of residual activity in the caudal part of the left thyroid lobe.
This case allowed us to compare the results of two nuclear medicine modalities using different equipment and radiopharmaceuticals – PET/CT with 18F-FDG and single-isotope dual-phase scintigraphy with 99mTc-tetrofosmin combined with an early SPECT technique in one and the same patient. Several factors can explain the difference in the obtained diagnostic information.
In the last few years, reports of the use of PET/CT in the detection of parathyroid adenomas have become more frequent. PET with 18F-fluorodeoxyglucose (18F-FDG) was used to detect increased metabolic activity of adenomas with variable success. Some data show that 18F-FDG PET is more sensitive, but less specific than scintigraphy with 99mTc-sestamibi combined with SPECT.[
Beggs and Hain used 11C-methionine to examine 51 patients with suspected parathyroid adenomas in whom other imaging methods gave negative or questionable results. Results showed sensitivity of 83% and specificity of 100% with an accuracy of 88%.[
99mTc-tetrofosmin has some similar properties to 99mTc-sestamibi, although the mechanism of accumulation is different. Its retention occurs mainly in the cytosol rather than in the mitochondria. When used for parathyroid scintigraphy, 99mTc-tetrofosmin shows slower washout from the thyroid gland which makes it unsuitable for single-isotope dual-phase scintigraphy.[
Hiromatsu et al.[
The diagnostic value of 99mTc-tetrofosmin for localization of abnormal parathyroid glands in patients with hyperparathyroidism has been studied by Valleios et al.[
In their study, Gallowitsch et al.[
Dual-isotope subtraction scintigraphy with 99mTc-tetrofosmin/99mTc-pertechnetate and SPECT are highly sensitive methods for localization of parathyroid adenomas and their combination can further improve diagnostic accuracy.[
99mTc-tetrofosmin, like 99mTc-Sestamibi, is not ideal for localization of hyperplastic glands in secondary hyperparathyroidism because of its low sensitivity.
The various devices (SPECT gamma camera and PET/CT), radiopharmaceuticals - 18F-FDG and 99mTc-tetrofosmin and hybrid methods for examination used in the nuclear medicine have their advantages and disadvantages. In our patient, the use of the single-isotope dual-phase 99mTc-tetrofosmin scintigraphy combined with SPECT technique proved to have higher sensitivity and specificity compared to PET/CT with 18F-FDG. In the cases with clinical and laboratory data for PHPT where there is no possibility for accurate localization of the pathologically changed parathyroid glands by the other diagnostic modalities, 99mTc-tetrofosmin scintigraphy is the method of choice, especially in cases of atypical localization of hyperfunctioning parathyroid adenomas or in cases with a recurrent disease.