Nuclear Medicine Companion: A Case-Based Practical Reference for Daily Use

By Abdelhamid H. Elgazzar and Ismet Sarikaya

This book provides all the information required for the optimal use of nuclear medicine techniques, which are undergoing rapid development yet remain underutilized. Each chapter focuses on one particular clinical system or disease area. The first section of each chapter illustrates normal patterns observed on commonly and uncommonly performed scans as a reference and explains when and how the procedures should be performed. The following section illustrates both the imaging patterns of different diseases and the diagnostic role of individual studies. Comparisons with other modalities are provided, and the rationale for and effective utilization of each study are discussed. The volume includes  near 250 case reviews. In addition, the normal patterns on relevant morphologic modalities are documented in an appendix. The book is directed at Nuclear Medicine physicians and technologists with different levels of training and expertise and also at radiologists who practice nuclear medicine and radiology residents.

• Language: English
• Publisher: Springer
• Release date: May 28, 2018
• ISBN: 9783319761565

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© Springer International Publishing AG, part of Springer Nature 2018

Abdelhamid H. Elgazzar and Ismet SarikayaNuclear Medicine Companionhttps://doi.org/10.1007/978-3-319-76156-5_1

1. Endocrine System

Abdelhamid H. Elgazzar¹  and Ismet Sarikaya¹

(1)

Department of Nuclear Medicine, Kuwait University, Safat, Kuwait

1.1 Endocrine System Imaging Studies and Normal Patterns

1.1.1 Thyroid Scan and Uptake

Indication

Thyroid scan and uptake evaluate the functional (hyper, hypo, or normal function) and structural (enlargement, nodules, ectopy) status of the thyroid gland. These are used to differentiate Graves’ disease from toxic nodular goiter, thyroiditis, and factitious hyperthyroidism, determine the functional status of the thyroid nodule(s), locate ectopic thyroid tissues, evaluate babies with congenital hypothyroidism, and determine if a neck mass contains thyroid tissue.

Procedure

Thyroid hormone supplements, antithyroid medications, iodine-containing foods and medications, and iodine procedures should be avoided for a certain time as they interfere with radioactive iodine uptake by the thyroid gland. Many patients stop taking thyroid hormones 3–4 weeks and antithyroid medications 3–5 days before the test, but this should be consulted with the referring physician before stopping these medications. Patients should not have radiological studies involving iodine contrast in the last 4–8 weeks. Iodine-containing solutions, vitamins, and medications should not be taken 1–2 weeks before the study.

Thyroid scintigraphy is commonly performed with Tc-99m pertechnetate. In routine studies, either Tc-99m pertechnetate thyroid scintigraphy and Iodine-131 (I-131) thyroid uptake or Iodine-123 (I-123) uptake and scan are performed. Although I-123 is the ideal agent for thyroid uptake and scan, it is less commonly used due to its high cost and less availability. I-131 is no longer used for thyroid imaging due to its high radiation dose to the thyroid but routinely used for thyroid uptake and detection of metastases and recurrences of differentiated thyroid cancer.

If Tc-99m pertechnetate is used, thyroid images are obtained 15–20 min after the intravenous injection of 185 MBq (5 mCi) for adults. Patient drinks some water to clear esophageal activity and optionally lemon to clear salivary gland activity. The patient is placed in supine position with pillow under shoulders and chin up (Water’s position). Anterior and anterior oblique views are obtained using a pinhole collimator equipped with 5 mm insert. Anterior image with markers at the suprasternal notch and thyroid cartilage including the salivary glands is acquired for 100 kct. Anterior and left and right anterior oblique images with the gland in the center and occupying two thirds of field of view (FOV) are acquired for 150–200 kct or 5 min. Another image with a marker at the palpable nodule may be obtained. Images are acquired using 256 × 256 matrix with 20% energy window centered at 140 keV. If the images show midline radioactivity which may be due to radioactive saliva in the esophagus, the patient is asked to drink water, and the imaging is repeated.

If I-123 is used, the adult activity is 3.7–11.1 MBq (100–300 μCi). The images are obtained 24 h after oral administration of activity, and thyroid uptake measurements are performed at 4–6 h and 24 h.

I-131 activity for thyroid uptake study is 0.37 MBq (10 μCi). Thyroid uptake is measured at 24 h after oral administration of I-131. I-131 is not recommended in children.

In uptake studies, a thyroid uptake probe is directed at the region of the thyroid bed in the extended neck, and 1 min neck, thigh, standard, and background counts each are measured from a 20–30 cm distance.

Radioactive iodine uptake (RAIU) is measured using the following formula:

$$ \mathrm{RAIU}\ \left(\right)=\frac{\mathrm{Neck}\ \mathrm{counts}-\mathrm{Thigh}\ \mathrm{counts}}{\mathrm{Standard}\ \mathrm{counts}-\mathrm{Bkgcounts}}\times 100 $$

Case 1.1 Normal Thyroid Scan (Fig. 1.1)

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Fig. 1.1

Tc-99m pertechnetate pinhole thyroid scan in anterior (with marker), anterior, right and left anterior oblique views

Normal Findings In a normal thyroid scan, there is homogeneous distribution of radiotracer in the thyroid gland which appears like a butterfly. Uptake in the salivary glands and soft tissues is noted if Tc-99m pertechnetate is used. Salivary gland uptake is not seen on I-123 images.

Normal RAIU is 6–18% at 4 h and 10–35% at 24 h with range differing according to patient population and technique used [1].

Companion Points The thyroid gland develops from the foramen cecum of the tongue, to which it is connected by the thyroglossal duct. It descends during fetal life to reach the anterior neck by about the 7th week [2]. The normal adult thyroid gland weighs 14–18 g. Synthesis of thyroid hormones takes place in the thyroglobulin (Tg), a glycoprotein, which is produced in the thyroid cells and extruded into the colloid. Iodine combines with thyrosine in Tg to form monoiodothyrosine and diiodothyrosine. Subsequently, the iodothyrosines are coupled with the formation of thyroxine (T4) and triiodothyronine (T3). The coupling reaction is mediated by peroxidase. Thyrotropin-releasing hormone (TRH) originating from the hypothalamus stimulates the secretion and synthesis of thyroid-stimulating hormone (TSH, thyrotropin), by the anterior pituitary. TSH increases the transport of iodide, synthesis of hormone, and release of T3, T4, and Tg.

There are many anatomic variations of the thyroid gland which include shape and size of the lobes and isthmus, presence of pyramidal lobes, and presence of levator glandulae thyroideae [3]. The left lobe is usually smaller than the right. Pyramidal lobe is present in about half of the thyroid glands and more prevalent on the left side of the median plane. Isthmus may be incomplete. Levator glandulae thyroideae is a fibromuscular band which is usually on the left side connecting the pyramidal lobe and the hyoid bone.

Developmental abnormalities of the thyroid gland include agenesis, dysgenesis (hemiagenesis or ectopy), and abnormalities due to persistence of the thyroglossal duct [4, 5].

Tc-99m pertechnetate has a short half-life of 6 h and main gamma energy of 140 keV. It is readily available and cheaper than I-123. It is only trapped by the thyroid gland but not organified and therefore only reflects the iodine uptake.

I-123 is expensive and not readily available. It has a half-life of 13 h, and its main gamma energy is 159 keV. It is both trapped and organified by the thyroid gland like nonradioactive iodine. It is taken up by thyroid follicular cells via sodium-iodine symporter, organified and incorporated into thyroid hormones.

Thyroid images should be interpreted in association with clinical and laboratory data (thyroid function tests) as well as the result of thyroid uptake especially in cases of hyperthyroidism due to Graves’ disease since near normal image appearance can be present in this condition.

1.1.2 Radioactive Iodine Whole Body Scan

Indication

Whole body scan with radioactive iodine (I-131 or I-123) is used to determine the presence and extent of residual functioning thyroid tissue after total thyroidectomy and after I-131 ablation and detect functioning differentiated thyroid cancer residues, recurrences, or metastases.

Procedure

The physician should obtain and record a pertinent, standard history and examination findings as well as results of laboratory tests (Tg, anti-Tg, and TSH). A measurement of serum TSH prior to the study is used to ensure maximum stimulation of any functional thyroid tissue. TSH should be >30 μLU/mL.

The study is performed 4–8 weeks post near total thyroidectomy. The patient must be off thyroid hormones, 4 weeks for T4 and 2 weeks for T3. Alternately the patient will have intramuscular Thyrogen injections (0.9 mg) for 2 days prior to dosing [6]. Thyrogen helps to increase the sensitivity of testing while allowing patients to avoid the potentially debilitating symptoms associated with thyroid hormone withdrawal. If the patient had intravenous iodinated contrast agents (intravenous pyelogram, computed tomography (CT) with contrast, or angiogram), the study should be delayed for 4 weeks. For intrathecal contrast (myelogram), this duration is 8 weeks; however, the adverse effect on the study may last as long as a year.

The patient should be fasting overnight or at least 3 h before oral administration of the radioactive iodine and for 3 h afterward. Low iodine diet is preferred starting 10 days before the test and continued throughout the period of imaging and for 1–2 days after treatment. The following foods and ingredients should be avoided: iodized salt, sea salt, seafood and sea products, dairy products, egg yolks or whole eggs, red dye #3 (erythrosine or E127), soybeans, foods containing high salt, iodine-containing vitamins and food supplements, and iodine-containing medications (e.g., iodinated contrast, amiodarone, and betadine). A pertinent menstrual history and pregnancy test as well as nursing and lactation history should be obtained. TSH, serum Tg, and anti-Tg antibody levels should be obtained before radioactive iodine administration as well as 72 h after Thyrogen administration.

For I-131, 74–185 MBq (2–5 mCi) of activity is administered orally. A large field-of-view gamma camera with 3/8 in. or greater crystal thickness equipped with high-energy, parallel-hole collimator and pinhole collimator with 10 mm insert is used with 20% energy window centered at 364 keV.

For I-123 study, 14.8–185 MBq (0.4–5.0 mCi) mCi of activity is administered orally. A large field-of-view camera equipped with a low-energy collimator with 20% energy window centered at 159 keV is used.

Whole body and neck images are obtained at 48 h for I-131 and 24 h for I-123. Using pinhole collimator, an anterior image of the neck is obtained for 10 min. Anterior and posterior whole body images are obtained from top of the head to the knees, 1024 × 256 matrix, 5–6 cm/min scan speed for I-131 and 10 cm/min for I-123. Delayed images may be acquired if necessary.

Single photon emission computed tomography (SPECT) or SPECT/computed tomography (CT) images improve tumor localization and are optional.

Thyroid uptake measurement may be used to determine the mass of remaining thyroid tissue or tumor (anterior image of the neck at 24 h using parallel-hole collimator).

Three milliliters of blood samples before ingestion of the radiopharmaceutical and at 24, 48, and 72 h after administration may be collected for dosimetric calculations.

In post-ablation/therapy patients, whole body images should be performed 7 days following I-131 administration [7].

Case 1.2 Normal Whole Body I-131 Scan (Fig. 1.2)

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Fig. 1.2

I-131 post-thyroidectomy whole body image in anterior view at 48 h

Normal Findings Normal distribution of radioactive iodine includes the thyroid gland, salivary glands, stomach, liver, bowel, and urinary collecting system and bladder. Mild background uptake in soft tissues is also present. Note the lack of thyroid uptake in Fig. 1.2 due to thyroidectomy and also lack of liver uptake. Liver uptake is seen in the presence of functioning thyroid tissue.

Companion Points I-131 decays by beta emission and has physical half-life of 8 days with main gamma energy of 364 keV. It delivers higher radiation dose to thyroid as compared to Tc-99m pertechnetate and I-123. It has low cost and is readily available. It is widely used for imaging and ablation/treatment purposes in patients with differentiated thyroid cancer.

Sources of error on images include local contamination of activity (in clothing, the skin, the hair, collimator, imaging table); activity in the esophagus; asymmetric salivary gland uptake; uptake in the ectopic thyroid, lactating or non-lactating breast, and thymus; inflammatory uptake in various tissues; uptake in some benign non-thyroidal tumors; and various other reasons [8, 9]. To reduce contamination problems, patients are instructed to take a shower and wear clean clothes before arriving for imaging.

Before starting imaging, patients should be given a glass of water to reduce salivary activity in the mouth and esophagus and also dry swallows during imaging.

In patients with normal or remnant thyroid, mild diffuse physiologic activity is seen in the liver due to metabolism of thyroid hormones. In patients without thyroid remnant, radioiodinated Tg released from functioning cancer tissue is regarded as the cause of diffuse hepatic uptake of radioactive iodine [9, 10].

1.1.3 MIBG Scintigraphic Imaging

Indication

This study is used to localize tumors of neuroectodermal origin such as pheochromocytomas, paragangliomas, and neuroblastomas.

Procedure

The radiopharmaceuticals used for this study are I-131 metaiodobenzylguanidine (MIBG) and preferably I-123 MIBG when available.

Many drugs are known to interfere with the uptake and/or vesicular storage of MIBG, and instruction should be given to the patient to avoid those drugs for certain duration before the study. Tricyclic antidepressants and related drugs should be stopped 6 weeks prior to the study; antihypertensives such as labetalol, calcium channel blockers, and reserpine for 2 weeks; sympathomimetics and cold decongestants for 2 weeks; cocaine for 2 weeks; and caffeine for 5 days. The detailed list of these medications can be obtained at the European Association of Nuclear Medicine (EANM) guidelines [11].

To block thyroid gland uptake of free iodide, the patient should be instructed to use saturated solution of potassium iodide (SSKI) or Lugol’s iodine solution. The doses for adults are 1 drop of SSKI or 3–5 drops of Lugol’s iodine solution diluted in water orally three times a day, beginning the day before injection of the radiopharmaceutical and continuing for 1–2 days for I-123 MIBG and 2–3 days for I-131 MIBG. The dose of these solutions should be adjusted in pediatric patients per weight. If there is iodine allergy or emergency, potassium perchlorate is started 4 h before radiotracer injection and continued for 2 days with a dose of 400–600 mg/day [11].

The adult doses of radiopharmaceuticals are 37 MBq (1 mCi) for I-131 MIBG and 370 MBq (10 mCi) for I-123 MIBG. The radiopharmaceuticals should be injected slowly over 20–30 s.

For I-131 MIBG, imaging starts at 24 h or 48 h after injection. Anterior and posterior whole body images are obtained using high-energy parallel-hole collimator with 20% window width centered at 364 keV, 6 cm/min scan speed, and 1024 × 256 matrix size.

For static views, 100–150 kct is acquired with 256 × 256 matrix size. For better detection of abdominal tumors, delayed imaging at 72 h or later may be necessary using the same parameters.

For I-123 MIBG, acquisition starts at 24 h postinjection, although it can start as early as 3–4 h post administration of activity. Images are obtained using low-energy high-resolution (LEHR) parallel-hole collimator with 20% window width centered at 159 keV, 256 × 256 matrix size and 500 kct for static views, and 8 cm/min scan speed and 1024 × 256 matrix size for whole body imaging. SPECT or SPECT/CT acquisition is a useful option in I-123 MIBG studies that facilitates better localization of lesions.

Breast feeding should be discontinued at least 48 h after injection of I-123 MIBG and terminated for I-131 MIBG.

Case 1.3 Normal MIBG Study (Fig. 1.3)

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Fig. 1.3

I-123 MIBG whole body image in anterior view at 24 h post administration of the radioisotope

Normal Findings Normally there is no visualization or faint uptake in the adrenal glands. Normal adrenal uptake is more commonly seen with I-123 MIBG than I-131 MIBG. Normal physiologic distribution also includes the salivary glands, liver, spleen, heart, lung, and bladder. Mild activity may be seen in the thyroid (due to incomplete blockade), brown fat, bowel, uterus, and skeletal muscles [12].

Companion Points MIBG is noradrenaline and guanethidine analog which enters neuroendocrine cells by an active uptake mechanism via the epinephrine transporter and is stored in the neurosecretory granules [11]. Neuroendocrine cells are the cells receiving neuronal input and then releasing molecules such as hormones to the blood. MIBG is taken up by adrenal medulla and sites containing neuroectodermal tissue.

MIBG scintigraphy is used to image neuroendocrine tumors, particularly the neuroectodermal (sympathoadrenal) system tumors such as pheochromocytomas, paragangliomas, and neuroblastomas. MIBG is also localized in other neuroendocrine tumors to a lesser degree, such as carcinoids, and medullary thyroid carcinoma. It is also used for the evaluation of myocardial norepinephrine receptors in cardiomyopathies/heart failure.

A normal adrenal medulla is seen in approximately 30% of patients, with an uptake less than that of the liver. Normal adrenals are more commonly seen in I-123 MIBG studies than I-131 MIBG.

No uptake should be seen in the bone and bone marrow in a normal study. This is particularly important when evaluating children with neuroblastoma.

I-123 MIBG is preferred over I-131 MIBG, particularly in pediatric patients, due to lower radiation exposure and superior image quality [13]. The 159 keV gamma energy of I-123 permits higher activities to be injected, and it is more suitable for SPECT imaging as compared to 364 keV photons of I-131 [14]. Uptake in the left lobe of the liver may be higher than the right lobe with unknown mechanism [15]. Most of the radiolabeled MIBG is excreted via the kidneys and minimal with salivary and fecal excretion [16]. Uptake in the salivary glands, heart, liver, spleen, and brown fat is due to rich sympathetic innervation in these tissues.

1.1.4 Indium-111 Pentetreotide: Somatostatin Receptor Imaging

Indication

Indium-111 (In-111) pentetreotide (octreotide, Octreoscan) is used for the detection, localization, staging, and follow-up of neuroendocrine tumors (NETs). The study also helps determine the somatostatin receptor (SSTR) status of the tumor to select patients who may benefit peptide therapy [17]. It may also be used in some non-neuroendocrine tumors such as lymphoma and active inflammatory disorders such as sarcoidosis due to SSTR expression [18, 19].

Procedure

No special patient preparation is needed. However if the patient is on octreotide therapy, the therapy should be discontinued 2–7 days for short-acting therapeutic agents and 4–6 weeks for long-acting agents. Patient hydration is also important to enhance renal clearance. Laxatives are used by some, and in such option it is administered the day before and the day of radiopharmaceutical injection to enhance bowel clearance. Per pentetreotide package insert, an intravenous line is recommended in any patient suspected of having an insulinoma and an intravenous solution containing glucose should be administered just before and during administration of In-111 pentetreotide [20].

Patient is injected intravenously with 111–222 MBq (3–6 mCi) In-111 pentetreotide. Large field-of-view gamma camera, dual headed, with LEHR collimator is preferable. Energy window is centered on 173 and 247 keV, 20% window width for each. Four hours later, patient is instructed to void and lie down supine on the table, and acquisition starts with whole body imaging obtained 10 cm/min in 1024 × 512 matrix size. Planar images of the abdomen and pelvis are obtained using 500 kct or 15 min with 256 × 256 matrix size. SPECT images are obtained in the abdomen and pelvis using 35–45 s/projection with 180° and 128 × 128 matrix size, both detectors close to the patient. Twenty-four hours later, whole body and SPECT or SPECT/CT images are obtained. Although SPECT/CT provides better anatomic localization of the lesions, it should be used judiciously to limit the radiation dose to the patient. If SPECT/CT camera is not available, fusing SPECT images with previously or recently taken CT may help to localize lesions. Forty-eight- and seventy-two-hour images may be needed to confirm a lesion suspected at earlier images or when residual bowel or gallbladder activity causes confusion.

Case 1.4 Normal Pentetreotide Study (Fig. 1.4)

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Fig. 1.4

In-111 pentetreotide whole body images in anterior and posterior views at 24 h post-isotope administration

Normal Findings Normal distribution of In-111 pentetreotide includes intense uptake in the spleen (arrow) as well as uptake in the liver and activity in the kidneys and urinary bladder. Bowel activity is seen usually at 24 h. The pituitary and the thyroid glands may be faintly visualized. Biliary excretion of the tracer occurs with occasional visualization of the gallbladder. Note that the right kidney is smaller than the left in this case.

Companion Points Somatostatin is a regulatory peptide which is secreted by various tissues, mainly the digestive system (delta cells in pancreatic islets, duodenum, and pyloric antrum) and also the nervous system (neuroendocrine cells).

Somatostatin exhibits various neuroendocrine, gastrointestinal, and neuromodulatory effects. Major action of somatostatin is inhibition of hormone secretion from the pituitary gland, the pancreas, and other endocrine tissues and exocrine secretions in various sites.

SST exerts its effects through binding to SSTR subtypes. There are five SSTR subtypes: SSTR1, SSTR2 (A and B), SSTR3, SSTR4, and SSTR5. SSTRs belong to the G protein-coupled receptor family and are widely expressed in normal tissues and solid tumors [21].

In-111 pentetreotide is a radiolabeled somatostatin analog used to detect and localize primary or metastatic neuroendocrine and other tumors with high density of SSTR (mostly subtypes 2 and 5), such as carcinoids, pancreatic islet cell tumors (gastrinomas, glucagonoma, vasoactive intestinal polypeptide-secreting tumor), pituitary tumors, adrenal medullary tumors (pheochromocytomas, paragangliomas, neuroblastomas), and small cell lung carcinoma.

The presence of unlabeled somatostatin either from octreotide therapy or production of somatostatin by the tumor itself may lower tumor detectability. In patients receiving octreotide therapy, decreased tracer localization to the spleen is usually seen [22].

Nonspecific uptake of the tracer may be seen in lactating breast tissue as well as in multiple nonneoplastic disorders such as autoimmune diseases, bacterial pneumonia, cerebrovascular accident, fibrous dysplasia, granulomatous diseases, and postradiation inflammation [22].

Tc-99m-labeled somatostatin analog, Tc-99m tektrotyd, is a new radiotracer which is currently not commonly used.

1.1.5 Ga-68 DOTA-Conjugated Peptides: Somatostatin Receptor Imaging

Indication

Positron-emission tomography (PET) SSTR imaging is used for the detection, localization, staging, and follow-up of NETs. It can also be used to determine SSTR status of the tumor and for selecting patients with metastatic disease for SSTR radionuclide therapy with Lutetium-177 (Lu-177)- or Yttrium-90 (Y-90)-labeled somatostatin analogs [23].

Procedure

Cold octreotide therapy should be discontinued as described in In-111 pentetreotide imaging procedure. Semiautomated or fully automated systems are used for radiolabelling of DOTA-conjugated peptides. The recommended dose of Gallium-68 (Ga-68) DOTA peptides is usually 132–222 MBq (4–6 mCi). The images are acquired between 45 and 90 min, usually 60 min, following injection of radiotracer. PET images are acquired from the head to mid-thighs, with 3D acquisition, 3–4 min/bed. Low-dose CT is also obtained for attenuation correction (AC) (10–20 mA and 80–140 kVp).

Case 1.5 Normal Ga-68 DOTANOC PET Scan (Fig. 1.5)

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Fig. 1.5

Ga-68 DOTANOC PET maximum intensity projection (MIP) image

Normal Findings Normal distribution of Ga-68 DOTA peptides includes intense uptake in the spleen with uptake in the pituitary gland (arrow), liver, adrenals, and pancreatic head and activity in the kidneys, bowel, and bladder. Salivary and thyroid glands show mild uptake. The prostate gland and breast glandular tissue may show diffuse low uptake. Physiological uptake in the pancreatic head (uncinated process) may mimic focal tumor. Uptake in adrenals may be prominent.

Companion Points Ga-68 is obtained by ⁶⁸Germanium (⁶⁸Ge)/⁶⁸Ga radionuclide generator system. Mother radionuclide has a long half-life of 270.8 days. Half-life of Ga-68 is 68 min.

DOTA is a universal chelator capable of forming stable complexes with radiotracers of the metal group. There are three Ga-68 conjugated peptides: Ga-68 DOTATOC, Ga-68 DOTATATE, and Ga-68 DOTANOC. The US Food and Drug Administration (FDA) approved the use of Ga-68 DOTATATE to locate SSTR-positive NETs in adult and pediatric patients. The main difference among Ga-68-labeled DOTA peptides is their variable affinity to SSTR subtypes. DOTATATE preferentially binds to SSTR 2, DOTATOC to SSTRs 2 and 5, and DOTANOC to SSTRs 2, 3, and 5.

As compared to Octreoscan, PET imaging with Ga-68 DOTA peptides, particularly with DOTATATE, detects more lesions, shows higher uptake in lesions, and provides shorter time of acquisition and lower radiation exposure [24, 25].

1.1.6 Parathyroid Scintigraphy

Indication

The study is used for localization of parathyroid adenoma or hyperplasias in patients with biochemically proven hyperparathyroidism.

Procedure

Tc-99m sestamibi is currently the preferred radiotracer for parathyroid imaging. Tc-99m tetrofosmin can also be used. Dual time acquisitions at 15 min and 2–3 h following iv administration of 740 MBq (20 mCi) Tc-99m sestamibi static images are obtained from the neck using pinhole collimator and from the mediastinum using parallel-hole collimator.

SPECT, particularly SPECT/CT, better locates the parathyroid pathologies. The SPECT images are acquired using 64 frames (32 × 2 in case of using dual-head camera), 30 s each, with 128 × 128 matrix and a circular orbit of 360°. A low-dose CT is also obtained. The field of view encompasses the neck and thorax. SPECT or SPECT/CT is usually obtained 2–3 h after injection of radiotracer.

Dual isotope subtraction studies with Thallium-201 (Tl-201) with Tc-99m pertechnetate or Tc-99m sestamibi with Tc-99m pertechnetate or I-123 have also been used. Obtaining thyroid scan on the same day or another day helps to reduce false-positive results.

Case 1.6 Normal Tc-99m Sestamibi Parathyroid Study (Fig. 1.6)

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Fig. 1.6

Tc-99m sestamibi early image of the anterior neck and mediastinum with parallel-hole collimator (a), and early (b) and delayed (c) pinhole neck images are shown

Normal Findings On normal Tc-99m sestamibi images, there is mild to moderate thyroid uptake which washes out on the delayed images. Normal parathyroid glands cannot be visualized by parathyroid scintigraphy. Physiologic activity is observed in parotid and submandibular salivary glands, heart, and active muscles. The bone marrow is slightly visualized. In pediatric patients, the thymus may be visualized. Brown fat activity may also be seen.

Companion Points Tc-99m sestamibi scan is the current method of choice for parathyroid imaging. It is the most sensitive and cost-effective modality for preoperative localization of hyperfunctioning parathyroid tissue.

The rationale behind preoperative localization imaging is the fact that a single parathyroid adenoma is the underlying pathology in more than 80% of cases of primary hyperparathyroidism; hence there would be no need to explore both sides of the neck with potentially increased morbidity.

Due to a wide variation in scintigraphic techniques, the reported sensitivities of Tc-99m sestamibi scan range from 80 to 100%. Although the exact mechanism is not fully understood, mitochondria have been implicated in its uptake by parathyroid cells [26, 27].

P-glycoprotein, a membrane transport protein encoded by the multidrug resistance gene (MDR), may also be additionally responsible for uptake, since it transports other products with structural similarity to Tc-99m sestamibi [28].

Parathyroid scintigraphy is not a screening study to be used in each patient with hypercalcemia of unknown etiology. It should be reserved for localization in patients with biochemically proven hyperparathyroidism. Since parathyroid glands can be found ectopically, the search for abnormal parathyroid lesions should include the mediastinal area.

SPECT/CT is more accurate than planar and SPECT imaging in localizing hyperfunctioning parathyroid tissues, particularly ectopic tissues [29].

Localization of intraoperative gamma probe has recently gained popularity [30]. The patient is injected with Tc-99m sestamibi approximately 2 h before surgery, and a gamma probe is used to detect high level of activity after surgical exploration.

1.1.7 Adrenal Cortical Scintigraphy

Indication

Adrenal cortical scan is used to distinguish unilateral from bilateral adrenocortical disease in cases with hypercortisolism, hyperaldosteronism, and hyperandrogenism and identify ectopic adrenal cortical tissue or adrenal remnants.

Procedure

In patients with primary aldosteronism or hyperandrogenism, suppression of normal adrenal cortex is achieved by oral administration of 1 mg dexamethasone four times a day beginning 7 days before and for the duration of the study. This is not required in patients with hypercortisolism. Diuretics, spironolactone, and antihypertensive drugs are stopped at least 48 h. SSKI is given orally in a dose of one drop three times a day starting 2 days before and continuing for 14 days to suppress the thyroid uptake of free radioiodine. Patients allergic to iodine can take potassium perchlorate (200 mg every night after meals), starting 1 day before injection of radiotracer for 10 days. A laxative should be given starting 48 h prior to imaging and continuing till final imaging to diminish bowel activity. The radiopharmaceutical is I-131 6ß-iodomethyl-19-norcholesterol (NP-59). The dose of NP-59 is 37–55.5 MBq (1–1.5 mCi) and injected intravenously over 2 min. Suppressed patients should be imaged on days 3, 4, 5, and 7. If adrenals are not seen by day 7, dexamethasone should be stopped and the patient imaged on day 10. Non-suppressed patients are imaged on days 5 and 7. Using high-energy parallel-hole collimator and 364 keV energy with 20% window width, at least 100 kct per image is obtained from the adrenals in anterior and posterior projections. In case of hyperandrogenism, the pelvis and genitalia should be included. To better locate the adrenals, SPECT/CT images may be obtained or after the completion of the posterior NP-59 image or the patient is left in the same position, and a low-dose dynamic renal imaging radiopharmaceutical is injected to image the kidneys, and spot image is obtained in Tc-99m window for subsequent image fusion. If the gallbladder is being confused with the right adrenal gland, lateral view images after cholecystokinin (CCK) or SPECT/CT images are obtained.

Case 1.7 Normal Adrenal Cortical Scintigraphy (Fig. 1.7)

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Fig. 1.7

Anterior and posterior views of the abdomen at 72 h after administration of I-131 6ß-iodomethyl-19-norcholesterol and patient preparation with dexamethasone suppression. Note no adrenal glands are visualized

Normal Findings In a suppressed study, the normal adrenal glands are not seen on early images (day 5 and before) but typically seen after day 5. The normal adrenal glands are usually visualized on the unsuppressed exam. In normal individuals, the right adrenal gland is located more superiorly and posteriorly than the left in the majority of cases. The shape of the left adrenal gland is typically oval, while the right tends to be more rounded. Apparent asymmetrical uptake may result from anatomical position (the right being closer to the camera) or summation of activities from underlying liver. Inspection of both anterior and posterior views should help exclude these possibilities. Uptake is also identified in the liver, gallbladder, and colon.

Companion Points The adrenal cortex has three main layers including inner layer zona reticularis producing androgen, mid layer zona fasiculata producing cortisol, and outer layer zona glomerulosa producing aldosterone. Zona fasiculata and zona reticularis are regulated by the hypothalamic-pituitary-adrenal axis. Adrenocorticotropic hormone (ACTH) secreted from the anterior pituitary gland in response to corticotropin-releasing hormone from the hypothalamus stimulates adrenal cortisol production.

NP-59 is a cholesterol analog that is bound to and transported by low-density lipoproteins (LDL) to specific LDL receptors on adrenocortical cells. Endogenous hypercholesterolemia may limit the number of receptors available for radiocholesterol localization through competitive inhibition. Once liberated from LDL, NP-59 is esterified but is not further converted to steroid hormones [31].

Adrenal imaging is useful in differentiation of the various forms of Cushing’s syndrome. Cushing’s syndrome is characterized by elevated steroid levels, and related symptoms could be secondary to oversecretion of ACTH (pituitary, ectopic, or exogenous), adrenal adenoma, bilateral autonomous hyperplasia, carcinoma, or exogenous steroid administration. NP-59 imaging findings for Cushing’s syndrome include bilateral symmetric visualization (ACTH-dependent corticoadrenal hyperplasia), bilateral asymmetric visualization (ACTH-independent adrenocortical hyperplasia), or unilateral adrenal visualization (solitary adrenocortical adenoma) [32, 33]. Bilateral non-visualization of the glands suggests the presence of an adrenocortical carcinoma after excluding exogenous administration of glucocorticoids or the presence of high serum lipoprotein [32, 34]. NP-59 scan can also be used for the detection of functioning remnants in Cushing’s patients’ persistent hypercortisolism following bilateral adrenalectomy.

Primary hyperaldosteronism (Conn’s syndrome) is due to autonomous adrenocortical adenoma in majority of the patients. It can also be secondary to bilateral hyperplasia and rarely from adrenal carcinoma. Secondary hyperaldosteronism occurs secondary to overactivity of the renin-angiotensin-aldosterone system. Aldosterone-producing adenomas are visualized as unsuppressable tissue after dexamethasone administration on NP-59 scan. In primary hyperaldosteronism, early unilateral adrenal visualization before day 5 suggests the presence of a solitary adrenal adenoma, and early bilateral visualization before day 5 suggests the presence of bilateral hyperplasia [32, 35]. Early bilateral visualization can also be observed in secondary hyperaldosteronism.

Adrenal hyperandrogenism and hyperestrogenism are rare diseases. NP-59 scan may be useful in a manner similar to that for primary hyperaldosteronism with same interpretative criteria.

Primary or secondary Addison’s disease (hypocorticism) causes bilateral non-visualization of the adrenal glands [36].

C-11 metomidate PET was reported to be a specific and sensitive method for diagnosing adrenocortical tumors, but it was unable to distinguish benign adrenal neoplasms from adrenocortical carcinoma [37].

1.2 Endocrine System Case Studies

1.2.1 Thyroid Nodules

1.2.1.1 Solitary Cold Nodule

Case 1.8 Solitary Cold Nodule

Clinical History Thirty-seven-year-old female with neck swelling and palpable thyroid nodule (Fig. 1.8).

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Fig. 1.8

Tc-99m pertechnetate anterior marker, anterior, right anterior oblique, and left anterior oblique pinhole images of the thyroid gland illustrating solitary cold nodule in the lower pole of the left lobe

Findings There is a large cold nodule in the lower pole of the left lobe, illustrating a solitary cold thyroid nodule.

Companion Points Thyroid nodules are common, and the prevalence is greater in countries affected by iodine deficiency. Routine autopsy surveys and the use of sensitive imaging techniques produce a much higher incidence. The incidence of thyroid nodules in apparently normal thyroid glands is greater than 50% in autopsy series [38]. High-resolution ultrasound can detect thyroid nodules in 19–68% of randomly selected individuals, particularly in women and the elderly [39, 40].

Most thyroid nodules are benign, particularly in multinodular goiter. The prevalence of thyroid nodules within a given population depends on a variety of factors that include age, sex, diet, iodine deficiency, and therapeutic and environmental radiation exposure. Thyroid nodules are more common in females, and this predisposition exists throughout all age groups.

Thyroid nodules are classified into cold, warm, and hot according to their ability to accumulate the radioactive isotope. A known limitation of thyroid scan includes inability to delineate thyroid nodules at the periphery or isthmus of the thyroid gland and characterize subcentimetric nodules.

Cold nodules account for more than 80% of all thyroid nodules [41]. Common causes of solitary cold thyroid nodules are cyst, adenoma, thyroiditis, cancer, and hematoma. Uncommon causes are lymph node, abscess, metastasis, and parathyroid pathology. Thyroid cancer is found in approximately 10% of cold nodules that are solid or mixed with solid and cystic components. Purely cystic nodules are almost always benign.

FNA biopsy is the most important tool in the assessment of solitary cold thyroid nodules. More than 75% of malignant thyroid nodules are differentiated thyroid cancer of the follicular epithelium (papillary or follicular) with excellent prognosis. Two to fourteen percent of thyroid carcinomas are anaplastic or undifferentiated carcinoma, and 5–10% are medullary thyroid carcinomas [41, 42]. Lymphoma and metastases to thyroid are much less common.

1.2.1.2 Hot Nodules

Case 1.9 Solitary Hot Nodule

Clinical History Twenty-three-year-old female with palpable thyroid nodule and hyperthyroid symptoms. TSH was 0.01 (normal 0.27–4.2 μLU/mL), and T4 was 10.77 (normal 7.8–16 pmol/L) (Fig. 1.9).

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Fig. 1.9

Tc-99m pertechnetate anterior marker, anterior, right anterior oblique, and left anterior oblique pinhole images of the thyroid gland illustrating solitary hot nodule in the right lobe of the thyroid gland

Findings There is heterogeneous distribution of activity in the thyroid gland with a large hot nodule involving the lower two thirds of the right lobe. There is significantly reduced uptake in the remaining parts of the thyroid gland, secondary to suppression. If the reduced uptake in the thyroid background is heterogeneous, or there are prominent cold areas, a thyroid ultrasound should be performed to find out coexisting cold nodules.

Twenty-four-hour RAIU was 28% (normal 10–35%).

Case 1.10 Multiple Hot Nodules

Clinical History Forty-seven-year-old male with weight loss, tremor, and heat intolerance. TSH was 0.02 (normal 0.27–4.2 μLU/mL), and T4 was 10.1 pmol/L (normal 7.8–16 pmol/L) (Fig. 1.10).

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Fig. 1.10

Tc-99m pertechnetate anterior marker, anterior, right anterior oblique, and left anterior oblique pinhole images of the thyroid gland illustrating multiple hot nodules

Findings There is heterogeneous distribution of activity in the thyroid gland with focal areas of increased activity in the midportion and lower pole of the right lobe as well as in the midportion of the left lobe. Decreased activity in the remaining portions of the gland is due to suppression, but this may obscure the visualization of coexisting cold nodules. Four- and twenty-four-hour radioactive iodine uptake values were 11% and 29%, respectively (normal 4 h uptake (6–18%) and 24 h uptake (10–35%)). Findings are consistent with multiple hot nodules (toxic multinodular goiter).

Companion Points Nodular goiters with resulting hyperthyroidism are categorized as toxic nodular goiters which include solitary autonomously functioning thyroid nodule (toxic adenoma) and toxic multinodular goiter (Plummer’s disease). Toxic autonomous nodules are localized lesions of the thyroid gland characterized by growth and increased iodine uptake and function, all independent from TSH control. These nodules represent a heterogeneous anatomic and clinical entity. The nodule function is determined by high serum thyroid hormone levels and/or low TSH (measured by ultrasensitive assay).

Etiology and pathogenesis of these nodules is not yet completely clarified. Both genetic and environmental factors determine nodule growth and function. Thyroid cells, in fact, are genetically heterogeneous and may have intrinsic characteristics that may promote the growth of cellular clones having mitotic and functional activity that is partially independent of TSH. In these particular cell clones, environmental factors like iodine deficiency or other goitrogens may favor the growth of autonomous nodules and also, by activating their function, may induce toxicity.

The autonomous thyroid nodules need to be treated only when they become toxic. In this case either surgical excision or radioactive iodine treatment can be used [43]. The condition may present as hyperthyroidism of different degrees, and patients may be euthyroid. Among euthyroid patients, the characteristic abnormalities are present on scanning and absent response to TRH indicating that pituitary TSH suppression is present in all subjects. Accordingly autonomous nodules in the euthyroid subjects are associated with elevated T3 levels sufficient to produce pituitary suppression but not high enough to be associated with the clinical manifestations of hyperthyroidism [44].

Hot nodules represent 3–20% of thyroid nodules [41]. Autonomous toxic nodule presents as palpable or sonographically confirmed nodule with increased activity on a thyroid scan and suppression of the remaining gland. When the nodule grows to a size of 2.5–3.0 cm, it produces enough thyroid hormones that cause clinical thyrotoxicosis with suppression of TSH preventing the tracer uptake in the nonautonomous portion of the gland. Smaller hot nodules may result in subclinical hyperthyroidism, which can be confirmed by suppressed TSH and normal T4. Hot nodules are very unlikely to be malignant (less than 1%). Occasionally hot nodule(s) can be seen, but the remainder of the gland is not suppressed or partially suppressed. This can be caused by nodules producing insufficient thyroid hormones to suppress TSH. When remainder of the gland is not suppressed, nodules are usually small.

Owl’s scintigraphic pattern is caused by a focus of functioning tissue overlapping a large cold area in a nodule that has cystic, degenerative, and necrotic changes in the middle of a benign and malignant pathology. It has been described as a thyroid cyst, autonomous nodule, and papillary carcinoma of the thyroid gland [45]. Hyperfunctioning nodules can appear scintigraphically as owl’s eye pattern due to intra-nodular degeneration, with residual hyperfunctioning tissue within or overlapping the degenerative area. Degenerative changes in autonomous thyroid nodules are common. A cold area of the autonomous nodules has been reported in up to 58% of cases including the pattern of owl’s eye.

I-131 therapy is the usual treatment of choice for toxic nodules. The nodules take up the radioactive iodine preferentially, with little taken up by the normal suppressed gland. Typically empirically 925 MBq (25 mCi) of I-131 is given for the treatment if there are multiple hot nodules. Smaller doses, 550 MBq (15 mCi) can be given for a solitary small hot nodule [46]. Higher