Imaging Analysis

Utility of 4D-CT imaging in the diagnosis of a parathyroid adenoma

A 53-year-old white woman was referred for the evaluation of osteoporosis. She had no complaints at the time of initial evaluation and was not taking any medications besides a multivitamin. She did not smoke cigarettes or use an excess of alcohol. She has been physically active with good sun exposure as a physical activity teacher and coach. She is very flexible and has had multiple bilateral shoulder subluxations and dislocations since her childhood but no history of fractures or loss of height. She had a surgical menopause after oophorectomy for bilateral ovarian cysts when aged 45 years with no estrogen replacement therapy. She did not have a history of renal stones or a family history of osteoporosis.

Exam revealed a thin woman (BMI, 21) with remarkable hyperextensibility of her joints and cubitus valgus. She did not have blue sclera or kyphosis. Lab testing revealed an inappropriately elevated parathyroid hormone of 103 pg/mL relative to other normal tests including a serum calcium of 9.3 mg/dL, ionized calcium 5 mg/dL, phosphorous 2.9 mg/dL, 25 OH vitamin D 41 ng/mL, blood urea nitrogen 21 mcg/dL and creatinine 0.8 mcg/dL. Her 24-hour urine calcium was 197 mg with a normal calculated fractional calcium excretion of 1.3%. Her urinary N-terminal telopeptide was at the upper limit of normal at 63 nM BCE/mM. A clinical diagnosis of Ehlers-Danlos syndrome (EDS; hypermobility type) was made. Causes of her osteoporosis were defective bone mineralization from the EDS, excessive bone resorption from her postmenopausal state and an elevated PTH level. The perplexing finding of an elevated PTH despite normocalcemia, normal 25 OH vitamin D and renal function was investigated further.

Kishore M. Lakshman, MD, MPH
Kishore M. Lakshman
Stephanie L. Lee, MD, PhD
Stephanie L. Lee

A neck ultrasound in endocrine clinic with a high resolution linear probe did not detect any masses suggestive of a parathyroid adenoma. A Technetium (Tc)-99m sestamibi scintigraphy with single-photon emission CT imaging was not suggestive of parathyroid gland enlargement (figure 1). Next, a 4D-CT scan of the neck was performed (figure 2). After a bolus IV contrast injection, multiple axial images were obtained after a 22-second, 52-second and 82-second delay. The scan revealed a 0.6 cm x 0.3 cm mass located posterior to the superior aspect of the right thyroid gland and medial to the internal carotid artery. This oblong-shaped mass was slightly hypodense to muscle on noncontrast phase, then initially hyperenhancing and subsequently relatively hypoenhancing on later post-contrast images (figures 2A, B, C). The patient was referred for parathyroidectomy. The surgeon located a 130-mg right superior parathyroid adenoma at the site indicated by the 4D-CT scan. The intraoperative PTH values dropped from 1,192 pg/mL to 121 pg/mL, reflecting a 90% decrease, and the final pathology corroborated an adenoma.

The last decade has witnessed the development of unilateral minimally invasive parathyroidectomy that relies on accurate preoperative localization of the parathyroid lesion. After biochemical confirmation of primary hyperparathyroidism, the initial imaging modality to locate a parathyroid adenoma is typically a parathyroid nuclear scintigraphy scan often with Tc-99m sestamibi scintigraphy or a neck ultrasound; their sensitivities are debated and are in the 60% to 80% range for Tc-99m and 30% to 70% for neck ultrasound. The sensitivity is lower in challenging situations such as multigland disease, ectopic parathyroid glands, supernumerary glands and previous neck exploration. In this particular case, the parathyroid adenoma was located deep and posterior to the superior pole of the thyroid, a location not easily seen by ultrasonography.

Figure 1. Tc-99m sestamibi parathyroid planar scan
Figure 1. Tc-99m sestamibi parathyroid planar scan. Anterior view of the neck and chest performed five minutes (early) and two hours (late) after injection of isotope. There was symmetric uptake of isotope in the thyroid in the early scan and uniform washout of tracer without area of retention on the delayed (late) image or by SPECT images. This imaging test did not reveal the location of the right upper 130 mg parathyroid adenoma.

Photos courtesy of: Stephanie L. Lee

Figure 2. Axial 4D - CT scan
Figure 2. Axial 4D - CT scan. A. Initial non-contrast enhanced axial image of the upper neck at the level of the upper pole of the right thyroid gland (T) shows the normal neck anatomy including right internal jugular vein (JV), tracheal (TR) and carotid artery (c). The parathyroid adenoma indicated by the green arrow is not readily apparent. B. Axial early (~20 seconds) post contrast-enhanced image shows the characteristic hyperenhancing right parathyroid adenoma (green arrow), medial to the right internal carotid artery (c) and posterior to the superior pole of the right thyroid lobe (T). C. After a delay of ~50 seconds, the enhancement of the mass (green arrow) is diminished but persists typical of a parathyroid adenoma.

4D-CT, also referred to as multidimensional CT, is emerging as a second-line localization technique. It has the same capacity as a 3D-CT in demonstrating anatomical detail, but the fourth dynamic dimension of contrast enhancement with time improves the sensitivity to detect small parathyroid adenomas. Parathyroid adenomas typically enhance avidly on early-phase imaging, and the hyperenhancement persists despite a long delay after contrast administration. The degree of early enhancing and slow washout of contrast correlates with metabolic activity of the parathyroid adenoma. This characteristic gives 4D-CT the double advantage of demonstrating gland functionality and excellent anatomy of the gland and its surrounding structures. One study’s results demonstrated that 4D-CT had improved sensitivity (88%) vs. sestamibi imaging (65%) and ultrasound (57%) in localizing hyperfunctioning parathyroid glands. A disadvantage of the technique is the radiation exposure from the multiple series of images of the neck.

A potential challenge while interpreting a 4D-CT includes differentiating parathyroid adenomas from normal lymph nodes and vascular structures. Lymph nodes do not show hyperenhancement and are most often isoenhancing relative to adjacent muscles. Vascular structures can be identified by carefully tracking them in the CT performed during early arterial phase enhancement. A direct advantage of 4D-CT vs. parathyroid sestamibi scans is its ability to detect smaller parathyroid adenomas and parathyroid hyperplasia, especially in the postoperative neck. The location of parathyroid adenomas missed by conventional methods and detected by 4D-CT include ectopic adenomas and those located in the tracheoesophageal groove, carotid sheath and mediastinum. 4D-CT is a valuable modality with the ability to detect small parathyroid adenomas or hyperplastic glands with a high sensitivity, and to provide precise anatomical localization to plan the best surgical approach. The 4D-CT scan is highly recommended in challenging cases of hyperparathyroidism when conventional imaging with neck ultrasound and parathyroid sestamibi are unrevealing.

Kishore M. Lakshman, MD, MPH, is a Fellow in Endocrinology, Section of Endocrinology, Diabetes and Nutrition, and Stephanie L. Lee, MD, PhD, is Associate Chief, Section of Endocrinology, Diabetes and Nutrition, and Associate Professor of Medicine, both at Boston Medical Center.

For more information:

  • Bergenfelz AO. Langenbecks Arch Surg. 2009;394:851-860.
  • Lumachi F. Endocr Relat Cancer. 2001;8:63-69.
  • Philip M. J Surg Educ. 2008;65:182-185.
  • Randall GJ. Am J Roentgenol. 2009;193:139-143.

A 53-year-old white woman was referred for the evaluation of osteoporosis. She had no complaints at the time of initial evaluation and was not taking any medications besides a multivitamin. She did not smoke cigarettes or use an excess of alcohol. She has been physically active with good sun exposure as a physical activity teacher and coach. She is very flexible and has had multiple bilateral shoulder subluxations and dislocations since her childhood but no history of fractures or loss of height. She had a surgical menopause after oophorectomy for bilateral ovarian cysts when aged 45 years with no estrogen replacement therapy. She did not have a history of renal stones or a family history of osteoporosis.

Exam revealed a thin woman (BMI, 21) with remarkable hyperextensibility of her joints and cubitus valgus. She did not have blue sclera or kyphosis. Lab testing revealed an inappropriately elevated parathyroid hormone of 103 pg/mL relative to other normal tests including a serum calcium of 9.3 mg/dL, ionized calcium 5 mg/dL, phosphorous 2.9 mg/dL, 25 OH vitamin D 41 ng/mL, blood urea nitrogen 21 mcg/dL and creatinine 0.8 mcg/dL. Her 24-hour urine calcium was 197 mg with a normal calculated fractional calcium excretion of 1.3%. Her urinary N-terminal telopeptide was at the upper limit of normal at 63 nM BCE/mM. A clinical diagnosis of Ehlers-Danlos syndrome (EDS; hypermobility type) was made. Causes of her osteoporosis were defective bone mineralization from the EDS, excessive bone resorption from her postmenopausal state and an elevated PTH level. The perplexing finding of an elevated PTH despite normocalcemia, normal 25 OH vitamin D and renal function was investigated further.

Kishore M. Lakshman, MD, MPH
Kishore M. Lakshman
Stephanie L. Lee, MD, PhD
Stephanie L. Lee

A neck ultrasound in endocrine clinic with a high resolution linear probe did not detect any masses suggestive of a parathyroid adenoma. A Technetium (Tc)-99m sestamibi scintigraphy with single-photon emission CT imaging was not suggestive of parathyroid gland enlargement (figure 1). Next, a 4D-CT scan of the neck was performed (figure 2). After a bolus IV contrast injection, multiple axial images were obtained after a 22-second, 52-second and 82-second delay. The scan revealed a 0.6 cm x 0.3 cm mass located posterior to the superior aspect of the right thyroid gland and medial to the internal carotid artery. This oblong-shaped mass was slightly hypodense to muscle on noncontrast phase, then initially hyperenhancing and subsequently relatively hypoenhancing on later post-contrast images (figures 2A, B, C). The patient was referred for parathyroidectomy. The surgeon located a 130-mg right superior parathyroid adenoma at the site indicated by the 4D-CT scan. The intraoperative PTH values dropped from 1,192 pg/mL to 121 pg/mL, reflecting a 90% decrease, and the final pathology corroborated an adenoma.

The last decade has witnessed the development of unilateral minimally invasive parathyroidectomy that relies on accurate preoperative localization of the parathyroid lesion. After biochemical confirmation of primary hyperparathyroidism, the initial imaging modality to locate a parathyroid adenoma is typically a parathyroid nuclear scintigraphy scan often with Tc-99m sestamibi scintigraphy or a neck ultrasound; their sensitivities are debated and are in the 60% to 80% range for Tc-99m and 30% to 70% for neck ultrasound. The sensitivity is lower in challenging situations such as multigland disease, ectopic parathyroid glands, supernumerary glands and previous neck exploration. In this particular case, the parathyroid adenoma was located deep and posterior to the superior pole of the thyroid, a location not easily seen by ultrasonography.

Figure 1. Tc-99m sestamibi parathyroid planar scan
Figure 1. Tc-99m sestamibi parathyroid planar scan. Anterior view of the neck and chest performed five minutes (early) and two hours (late) after injection of isotope. There was symmetric uptake of isotope in the thyroid in the early scan and uniform washout of tracer without area of retention on the delayed (late) image or by SPECT images. This imaging test did not reveal the location of the right upper 130 mg parathyroid adenoma.

Photos courtesy of: Stephanie L. Lee

Figure 2. Axial 4D - CT scan
Figure 2. Axial 4D - CT scan. A. Initial non-contrast enhanced axial image of the upper neck at the level of the upper pole of the right thyroid gland (T) shows the normal neck anatomy including right internal jugular vein (JV), tracheal (TR) and carotid artery (c). The parathyroid adenoma indicated by the green arrow is not readily apparent. B. Axial early (~20 seconds) post contrast-enhanced image shows the characteristic hyperenhancing right parathyroid adenoma (green arrow), medial to the right internal carotid artery (c) and posterior to the superior pole of the right thyroid lobe (T). C. After a delay of ~50 seconds, the enhancement of the mass (green arrow) is diminished but persists typical of a parathyroid adenoma.

4D-CT, also referred to as multidimensional CT, is emerging as a second-line localization technique. It has the same capacity as a 3D-CT in demonstrating anatomical detail, but the fourth dynamic dimension of contrast enhancement with time improves the sensitivity to detect small parathyroid adenomas. Parathyroid adenomas typically enhance avidly on early-phase imaging, and the hyperenhancement persists despite a long delay after contrast administration. The degree of early enhancing and slow washout of contrast correlates with metabolic activity of the parathyroid adenoma. This characteristic gives 4D-CT the double advantage of demonstrating gland functionality and excellent anatomy of the gland and its surrounding structures. One study’s results demonstrated that 4D-CT had improved sensitivity (88%) vs. sestamibi imaging (65%) and ultrasound (57%) in localizing hyperfunctioning parathyroid glands. A disadvantage of the technique is the radiation exposure from the multiple series of images of the neck.

A potential challenge while interpreting a 4D-CT includes differentiating parathyroid adenomas from normal lymph nodes and vascular structures. Lymph nodes do not show hyperenhancement and are most often isoenhancing relative to adjacent muscles. Vascular structures can be identified by carefully tracking them in the CT performed during early arterial phase enhancement. A direct advantage of 4D-CT vs. parathyroid sestamibi scans is its ability to detect smaller parathyroid adenomas and parathyroid hyperplasia, especially in the postoperative neck. The location of parathyroid adenomas missed by conventional methods and detected by 4D-CT include ectopic adenomas and those located in the tracheoesophageal groove, carotid sheath and mediastinum. 4D-CT is a valuable modality with the ability to detect small parathyroid adenomas or hyperplastic glands with a high sensitivity, and to provide precise anatomical localization to plan the best surgical approach. The 4D-CT scan is highly recommended in challenging cases of hyperparathyroidism when conventional imaging with neck ultrasound and parathyroid sestamibi are unrevealing.

Kishore M. Lakshman, MD, MPH, is a Fellow in Endocrinology, Section of Endocrinology, Diabetes and Nutrition, and Stephanie L. Lee, MD, PhD, is Associate Chief, Section of Endocrinology, Diabetes and Nutrition, and Associate Professor of Medicine, both at Boston Medical Center.

For more information:

  • Bergenfelz AO. Langenbecks Arch Surg. 2009;394:851-860.
  • Lumachi F. Endocr Relat Cancer. 2001;8:63-69.
  • Philip M. J Surg Educ. 2008;65:182-185.
  • Randall GJ. Am J Roentgenol. 2009;193:139-143.