Open access peer-reviewed chapter - ONLINE FIRST
Thyroid disorders which increase or decrease the RAIU.
Abstract
Thyroid imaging tests provide more information about the thyroid gland’s size, shape, and function. After the thyroid blood tests which are the gold standard for the assessment of conditions like hypothyroidism or hyperthyroidism, imaging tests are recommended to establish a diagnosis. Although the diagnosis of hypothyroidism in itself is not an indication of thyroid imaging, thyroid radionuclide scanning may be useful in elucidating several pathophysiological aspects of hyperthyroidism and in determining the cause of abnormal thyroid function. This may be especially crucial in deciding whether a person will take thyroxine replacement therapy. However, it is important to recognize whether the cause of hypothyroidism is transient or drug-induced because this may require no treatment or only short-term thyroxine supplementation.
Keywords
- hypothyroidism
- RAIU
- RTCUT
- imagine tests
- thyroid scan
1. Introduction
Hypothyroidism is a clinical and biochemical disorder caused by a lack of thyroid hormones resulting in a slowing down of metabolic processes and potentially is fatal in severe cases if untreated. It may be due to a disease of either the thyroid gland (primary hypothyroidism), the pituitary gland (secondary), the hypothalamus (tertiary hypothyroidism) or rarely to a peripheral resistance to the actions of thyroid hormones [1].
The causes of hypothyroidism for primary hypothyroidism with goiter are hypertrophic form of Hashimoto’s thyroiditis, thyroid hormone biosynthesis disorders and subacute thyroiditis. For primary hypothyroidism without goiter, is atrophic form of Hashimoto’s thyroiditis, agenesis or hypoplasia of the thyroid, excessive iodine intake, inflammation, post thyroidectomy, post radioactive iodine therapy or post radiotherapy of the neck. It should be noted that TSH levels are high in these conditions. The causes of secondary hypothyroidism, in which TSH is invariably detected at low levels, are panhypopituitarism and isolated TSH deficiency. The causes of tertiary hypothyroidism are due to hypothalamic lesions where the TSH values are detected at low levels [1].
Nuclear medicine in the field of thyroid disorders provides important information for both diagnostic tests (in vitro and in vivo tests) and therapeutic interventions. Α scintigraphic study is an in vivo imaging diagnostic study, performed after administration of a gamma photon- or positron- emitting radionuclide, which demonstrates in two or three dimensions the distribution of the radioactive tracer in the target organ of the human body. The uptake and distribution of radiopharmaceutical in the thyroid gland depends upon three factors, the metabolism, the physiology, and the pathophysiology of the gland [1, 2].
There are many radiopharmaceuticals available in the Nuclear Physician’s quiver that provide them with the ability to study the biokinetic behavior of the non-radioactive tracer and to obtain functional quantitative and anatomical information about the thyroid gland. The most widely used radionuclides are 99 m-Technetium Pertechnetate, two isotopes of iodine I-123 and I-131, Thallium Chloride (201 T1) and Fluorine-18-fluorodeoxyglocose (FDG) [3].
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2. Diagnostic applications of radiopharmaceuticals
2.1 99mTechnetium pertechnetate
Is widely used for imaging the thyroid gland. Technetium does not exist in nature but was first discovered in 1937 by Carlo Perrier and Emilio Segre at Palermo University. They managed to isolate technetium-97 from a sample of molybdenum irradiated with deuterons in the cyclotron [4]. It belongs to group VIIA of the Mendeleev Table of the Elements. The pertechnetate monovalent ion ([99mTc]- Tc04)- has similar chemical and physical characteristics to the iodide ion (i. e. ionic size and negative charge) and similar biological distribution, thus competing with it and its active uptake in the thyroid gland, salivary glands, choroidal plexuses and stomach [5, 6].
99mTechnetium Pertechnetate is trapped by the thyroid parenchyma after being mediated by the NIS (sodium/iodide symporter), a transmembrane glycoprotein located on the basolateral membrane of follicular cells. However, unlike iodine, pertechnetate ion does not undergo organification and is not incorporated into the thyroid hormones; therefore, it remains in the gland for a relative short period. It has replaced the 131I-sodium iodide in the imaging of the thyroid gland for five decades because:
it has low cost
is readily available from portable generators with molybdenum-99,
the absorbed radiation dose to the thyroid gland is very low compared to 131I-sodium-iodine (it is about 2600 times lower per mCi),
it provides good image quality of the gland
it has short retention in the gland with short half-life (6 hours) and no β - radiation; therefore, imaging is performed about 20–30 min after the injection.
The administered dose for adults is 111–185 MBq (3–5 mCi) and for children is lower approximately 18,5–111 MBq (0.5–3 mCi) [6].
2.2 Radioiodine-123 and radioiodine-131
Radioiodine-123(Na[123I] I) due to its ideal characteristics, which are the short physical half-life (13 hours), the absence of β –emissions and the high ratio uptake in thyroid tissue compared to that in the surrounding tissues, is very suitable for scintigraphy. However, it has some disadvantages, being less readily available (produced by cyclotron) and more expensive than 99mTechnetium Pertechnetate. It has the same biokinetics as the stable iodine and is based on the basic principle of radiotracer and this fact allows the pathophysiological imaging and the quantitative study of (i) iodine behavior in the thyroid gland as well as in other organs related to the uptake, (ii) the organification of iodine into thyroid hormones, (iii) the metabolism and excretion of stable iodine. The administered dose is approximately 200–400 μCi (7.4–14.8 MBq). Radioiodine-123 has a preferable use for the detection of either ectopic thyroid tissue or lack of iodine organification.
Na[131I]I, is the first of all theragnostics radiopharmaceuticals used for to observe and quantify the iodine distribution and kinetics inside the thyroid gland, whereas β-particles emission was used to obtain the therapeutic effect. Based on its physical characteristics, the long half-life (8.02 days), the high absorbed radiation dose, the β-electrons emission and the emitting of an electromagnetic photon with a principal gamma-ray of 364 keV, it is no longer used for routine diagnostic scintigraphy. However, it is still usable for evaluating mediastinal masses and detecting of recurrences in differentiated thyroid cancer and metastases. The administered diagnostic dose is approximately 2–5 mCi (74–185 MBq).
Regarding its therapeutic properties, Na[131I]I is the preferable agent for the treatment of hyperthyroidism and thyroid cancer, due to the high activity of β- particles which drastically destroy thyroid tissue. The administered therapeutic dose is based on the uptake measurement, on the radioactivity (MBq) we want to be delivered per gram of tissue and the mass of the gland [6].
2.3 Thallium chloride (201 T1)
Its use is limited only in the imaging and confirmation of metastases from adenocarcinomas of the thyroid gland in some patients with total thyroidectomy without interrupting the replacement therapy, as it is required when using Na[131I]I in follicular carcinomas in order to increase TSH. It has a high importance of monitoring thyroidectomized patients having negative whole-body scintigraphy with iodine-131 and elevated thyroglobulin values which indicate the presence of metastases of differentiated cancer. It is disadvantaged in that its uptake is nonspecific and may be observed in benign as well as malignant conditions [6].
2.4 Fluorine-18-fluorodeoxyglocose (FDG)
It is only used in evaluating a variety of neoplasms including differentiated thyroid cancer, not visualized at radioiodine imaging, and to assess prognosis. It also has the advantage to detect the nonfunctioning as well as functioning thyroid cancers and to distinguish benign thyroid nodudes from cancer, based on the higher FDG metabolism seen in tumors [6].
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3. The in vivo tests of thyroid function
The purpose of the in vivo diagnostic tests for thyroid gland is:
to measure thyroid function with uptake tests with and
to obtain an image of the location, size, morphology and the evaluation of the functionality of the thyroid gland by scintigraphy using either 99mTechnetium Pertechnetate or Radioiodine-123, if the evaluation of the patient’s history, vitro tests and other diagnostic tests have been carried out previously [7].
Uptake Test: The uptake test refers to the percentage uptake of a radiopharmaceutical by the thyroid gland in relation to the administered dose at specified intervals. Several methods of functional assessment have been used in the past, which have gradually been limited and nowadays mainly the Radioiodine Uptake (RAIU) and the 99mTechnetium Pertechnetate Thyroid Uptake (RTCUT) have remained in use.
Radioiodine Uptake (RAIU) illustrates the functional state of thyroid gland and helps to determine the dose of 131-I in a post-operative therapy (ablation). The main indications for its performances are the confirmation of hyperthyroidism, the estimation of the therapeutic dose of 131-I, the determination of the thyroid tissue autonomy, and the clarification of the cause of thyrotoxicosis.
The RAIU test can also be performed with 123-I in conjunction with scintigraphy.
The factors affecting thyroid uptake of iodine are dietary restrictions, impaired kidney function, radiological studies with iodine-contrast, antithyroid medications, amiodarone and thyroid hormones. In addition, there are pathological disorders that either increase or decrease the RAIU (Table 1).
| Increase RAIU | Decrease RAIU |
|---|---|
| Hyperthyroidism | Blocked Trapping |
| Rebound effect from abrupt withdrawal of antithyroid drugs | Acute Subacute and Chronic lymphocytic thyroiditis |
| Enzyme disorders | Blocked Organification |
| Long-term antithyroid therapy (↑TSH ↓ T4) | Exogenous intake of thyroid hormones |
| Lithium | Ablation |
| Thyroiditis onset | Struma Ovari |
| Rebound effect from post thyroiditis | Antithyroid drugs |
Table 1.
The normal range for RAIU in thyroid gland is from 10 to 30%.
99mTechnetium Pertechnetate Thyroid Uptake (RTCUT), as a substitute for iodine indicates the temporary trapping that iodine would have had, not its organification. For this reason, RTCUTs values are indicative and not as precise as those of RAIU. It is performed in conjunction with scintigraphy within 20 minutes after the intravenous administration. The main indications for its performance are Grave’s disease, subacute thyroiditis, drug-induced thyrotoxicosis, evaluation and monitoring of hyperthyroidism, evaluation of hypothyroidism caused by an impairment of the organification, evaluation of treatment or withdrawal of treatment in persons receiving either methimazole, either propylthiouracil.
Τhe normal values of RTCUT at 20 minutes range from 0,24 to 3,34% [7].
Thyroid scan is a simple, non-invasive, cost effective tool for assessment of most thyroid disorders. The advantage of scintigraphy is that it can provide an immediate assessment of the morphological and functional status of the thyroid gland. Thyroid scan plays a complementary role in diagnosis of hypothyroidism in infancy to confirm the underlying etiology. It detects patients who should be given lifelong replacement therapy (hypo-plastic ectopic thyroid) and identifies patients who need reevaluation (non-visualization or dyshormonogenesis).
The clinical indications for thyroid scintigraphy are:
the evaluation of thyroid size, shape, position and function
further evaluation and identification of findings on physical examination
determination of functional status of thyroid nodules
follow up of radioiodine therapy for thyroid cancer
diagnosis and monitoring of thyroiditis
diagnosis, treatment, follow-up, and prognosis of the goiter
assessment of extrathyroidal tissue and mediastinal masses
screening after head and neck irradiation
99mTechnetium Pertechnetate imaging: An intravenous injection of 1–5 mCi (37–185 MBq) is administered and images are obtained 20 minutes p.i. in the anterior and the 45o right anterior oblique and 45o left anterior oblique views. The 99mTc Pertechnetate is actively transported and trapped into the follicular cells but it is not bound to tyrosine. Therefore, the study reflects the measurement of trapping.
Radioiodine 123 imaging: the tracer is administered orally in capsule form of 100–400 μCi (3,7–15 MBq) and images are obtained at 6 and 24 hours in the anterior and the 45o right anterior oblique and 45o left anterior oblique views. This isotope of iodine is handled by the body exactly like 127I (a nonradioactive iodine) and after administration it is absorbed by the intestine into the extrathyroidal iodide pool. Extrathyroidal iodine is actively transported across the membrane of the follicular cell where it binds to tyrosine, through interaction with thyroid peroxidase, it is organized and incorporated into thyroid hormone. Therefore, the study reflects the distribution of tissue that possesses the functions of trapping and organifying [7, 8, 9].
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4. Hypothyroidism nuclear medicine imaging
Iodine deficiency is the most common cause of hypothyroidism worldwide, while Hashimoto thyroiditis is the prevailing cause of hypothyroidism in developed countries (Table 2).
| Primary Hypothyroidism | Secondary Hypothyroidism |
|---|---|
|
|
Table 2.
Causes of primary and secondary hypothyroidism.
In the following paragraphs the imaging features of some of the above disorders and conditions will be dealt.
4.1 Αutoimmune thyroid diseases (AITDs)
AITDs are increasingly seen due to:
the widespread use of (i) anti-tumor targeted therapies such as tyrosine kinase inhibitors (TKIs) and (ii) immunotherapies with checkpoint inhibitors (CPIs)
SARS-CoV-2 infection
Lymphocytic infiltration of the thyroid gland is the hallmark of AITD.
NM techniques, such as radioiodine upta.ke (RAIU) and thyroid scintigraphy, using 99mTc-pertechnetate (Na[99mTc]TcO4) or 123-Iodine (Na[123I]I), play a clear role in the differential diagnosis [10].
4.1.1 Hashimoto thyroiditis (HT)
Being a subtype of autoimmune thyroiditis, it is also known as lymphocytic thyroiditis or chronic autoimmune thyroiditis. It typically affects middle-aged females (30–50-year age group with an F:M ratio of 10–15:1).
In developed countries, it is the most common cause of hypothyroidism. The inflammation enhanced by the lymphocytic infiltration of the gland induces (i) follicular cell destruction, necrosis, and apoptosis, (ii) fibrosis, (iii) a humoral antibody (Ab)-mediated response directed against TPO or/and Tg, (iv) hypothyroidism [11].
Imaging is usually not necessary to diagnose HT. In selected cases, it helps to estimate the size and composition of the gland, as well as to detect any co-existing nodules.
US
In the initial phase the gland is usually depicted enlarged and heterogeneous, while in chronic cases it may be atrophic. Diffuse hypoechoicity and development of micro-pseudonodules with surrounding echogenic septations (pseudolobulated changes) are frequently observed [12, 13]. The degree of echogenicity shows a satisfactory negative correlation with the degree of lymphocytic infiltration [14], but not with the biochemical indices of thyroid function [15]. Color Doppler usually shows normal or decreased flow, but occasionally it might appear hypervascular similar to a thyroid inferno; in HT hypervascularity does not reflect thyrotoxicosis. It is difficult to reliably sonographically differentiate HT from other thyroid pathology.
Annual ultrasound screening is recommended for early detection of nodules [16]. Nodular HT is associated with the presence of large nodules. Sometimes prominent reactive cervical nodes with normal morphologic features may be observed. The presence of any calcifications may either reflect the presence or indicate an increased risk of papillary thyroid carcinoma [17].
Thyroid scan
The pertechnetate thyroid scintigraphy illustrates the functional state of the thyroid gland. In the initial phase of the disease, a diffusely increased concentration of the radiopharmaceutical is observed in the thyroid, a finding that reflects the stimulation of the gland by TSH, produced by the pituitary gland and compensating for the early reduction of thyroid hormones. The image should be differentiated from Graves’ disease and color flow Doppler may contribute to the differential diagnosis [18]. As the disease progresses, the thyroid parenchyma is replaced by lymphocytes and fibrous tissue and the gland becomes unable to respond to stimulation by elevated TSH levels. In such cases, the common findings on pertechnetate thyroid scintigraphy include symmetrical enlargement of the gland’s borders, slightly inhomogeneous distribution of the radiopharmaceutical in the thyroid parenchyma, without the existence of defined focal findings [19]. This relative heterogeneity is attributed to the variable response of the follicles to their stimulation by TSH. In children and adolescents with HT, the distribution of the radiopharmaceutical is more homogeneous compared to the adult picture [20].
Iodine-123 thyroid scintigraphy is rarely needed in the investigation of HT [21].
FDG-PET scan shows a diffusely increased uptake and may reveal autoimmune thyroiditis as a consequence of cancer immunotherapy, especially when using CPIs.
4.2 Thyroiditis
4.2.1 Post-partum thyroiditis
It is a transient disorder, which occurs in women who have a high titer of antibodies against TPO, which are involved in enhancing the rebound stimulation of the immune mechanisms, after the period of relative immune-suppression, which is constituted by pregnancy [22]. It affects approximately 6–10% of births [23, 24]. 33–50% of pregnant women with elevated Ab-TPO in early pregnancy will develop transient, postpartum thyroiditis [25]. Ab-TPO and Ab-Tg cross the placenta, but do not appear to exert any adverse effect on the fetus [26]. Women with HLA haplotype DR-3, DR-4 or DR-5 are at increased risk of postpartum thyroiditis. In women with type 1 diabetes mellitus, the incidence of postpartum thyroiditis is three times that of the general population [27].
Ultrasound is the imaging test of choice; the gland often appears hypoechoic, but variable findings may be noted. Scintigraphically, a reduced uptake of the radiopharmaceutical by the thyroid parenchyma is observed [28]. The immunohistochemical pattern of the thyroid in postpartum thyroiditis resembles that of Hashimoto’s thyroiditis, except that Hurthle cells are not often seen.
About 20–25% of women with postpartum thyroiditis will develop hypothyroidism a few years later. A positive correlation has been observed between the probability of permanent hypothyroidism and the values of TSH and Ab-TPO. Also, subsequent pregnancy can cause recurrence of the disease in up to 70% of cases. Of the group of women with elevated Ab-TPO without postpartum thyroiditis in the initial pregnancy, 25% will develop the disease in a subsequent pregnancy [29].
4.2.2 Silent thyroiditis
It is a form of subacute thyroiditis associated with HLA-DR-3 and elevated levels of Ab-TPO and Ab-Tg. It is usually characterized by the recent onset of symptoms and the lack of thyroidal pain or tenderness. An initial transient hyperthyroid period is followed by hypothyroidism and finally the euthyroid state is attained.
Scintigraphically the thyroid parenchyma typically shows markedly reduced radiotracer uptake, while the gland may have normal to moderately enlarged size.
4.2.3 Riedel thyroiditis (RT)
It is a rare disease tending to affect middle-aged persons (30–60 years old with an F:M ratio of 3:1). Its etiology being rather obscure, RT seems to be characterized by a fibroinflammatory process derived from autoimmune signaling [30].
US
The thyroid gland appears diffusely hypoechoic and ischaemic due to extensive fibrosis; hyperechoic bands correspond to the fibrosis [31]. US elastography may reveal significant stiffness of the gland.
CT
Within the thyroid parenchyma, hypodense areas are observed, which remain unaltered after administration of a contrast agent [32]. CT imaging of the chest or abdomen may show more systemic involvement.
MRI
The main findings are: (i) hypointense images in T1- and T2-sequences, (ii) uniform enhancement of variable intensity can be observed following IV Gd administration.
Pertechnate Thyroid Scan
No radiotracer is detected within the affected tissue, which appears as a photopenic area.
FDG-PET Scan
Intense uptake is observed corresponding to the areas of inflammation–fibrosis in RT [33, 34].
4.2.4 Subacute thyroiditis (DE QUERVAIN)
It is a self-limited thyroiditis usually preceded by an upper respiratory tract viral infection. In the initial phase, patients present with a painful neck along with thyrotoxicosis, followed by a period of hypothyroidism. In most cases a euthyroid state is finally achieved without requiring a specific treatment.
US
The affected areas appear as irregularly confined lesions of decreased echogenicity and vascularity. They can be bilateral or unilateral. The gland size is usually normal but can occasionally be enlarged or smaller. After the resolution of the disease, the sonographic pattern and enlargement of the thyroid resolve with some strands of fbrosis refecting the residual thyroid damage.
Thyroid scan
In patients with the appropriate clinical setting and ultrasound findings, low or absent uptake of the radiotracer is observed, rendering difficult the clear delineation of the gland from the surrounding tissues.
4.2.5 Van Wyk-Grumbach syndrome
This syndrome is characterized by chronic hypothyroid autoimmune thyroiditis, delayed bone age and precocious puberty (usually early menarche and breast development, without pubic and axillary hair growth) due to the stimulation of ovarian FSH receptors by the excess of TSH.
Plain radiographs wrist and hand are used to detect delayed bone age.
4.3 Infiltrative thyroid disease
The imaging features of these entities are nonspecific and may pose diagnostic challenges being difficult to differentiate from primary thyroid malignancies, HT and other forms of thyroiditis [35].
4.3.1 Thyroid lymphoma
It is a rare disease (1–2 patients per 1,000,000 people) mainly affecting 50–70 year old females (F:M = 3). It commonly presents as a rapidly enlarging goiter with accompanying compressive symptoms and cervical lymphadenopathy. Hashimoto thyroiditis has been associated with an increased risk for thyroid lymphoma.
US
It may appear as nodular (hypoechoic mass) or diffuse (mixed echotexture) or mixed [36], while calcifications are uncommon 4.
CT
Its usual appearance is a goiter, hypodense compared to the adjacent muscles, which may show heterogeneous enhancement but still less than adjacent muscle [37].
MRI
The gland may appear iso- to hyper-intense on T1/T2 sequences. A pseudocapsule may be detected.
4.3.2 Thyroid amyloidosis
It is due to the deposition of amyloid protein and fat within the thyroid gland.
US
An enlarged gland showing complex or hypoechoic areas maybe extending to the mediastinum.
CT
A diffuse or/and multinodular thyroid enlargement at varying extents depending on the amount of fat and amyloid deposited within the thyroid parenchyma [38].
MRI
Proteinaceous substances within the nodules result in high intensity T1 images, fibrillar amyloid structures in increased signal on T2 images and fatty infiltration in increased T1 and T2 signals [39]. Cases with diffuse fatty infiltration can be difficult to differentiate from thyrolipomatosis.
4.3.3 Thyroid sarcoidosis
Involvement of the thyroid gland by sarcoidosis is very rare, affecting 4.5% of patients with sarcoidosis. It may present as (i) a gradual enlargement of the gland, eventually causing compressive symptoms, (ii) a multinodular goiter, (iii) cold solitary thyroid nodules, with or without cervical lymphadenopathy [40]. Its diagnosis may be elusive given the imaging similarities with other thyroid diseases and the limitations of FNA due to either the scattered pattern of granulomatous infiltration or the formation of hyperplastic papillary structures [41].
4.3.4 Thyroid tuberculosis
It is extremely unusual and the diagnosis can be easily disregarded as the clinical and imagological findings are usually non-specific. The gland may appear either diffusely enlarged or with a heterogeneous (micro)-nodular composition [42]. Cervical lymphadenopathy may also be present.
4.4 Congenital hypothyroidism
4.4.1 Introduction
The most common causes of congenital hypothyroidism [43, 44] are presented in Table 3. In developing countries, the main cause is the endemic lack of iodine in mother and fetus.
|
|
|
|
|
|
Table 3.
The most common causes of congenital hypothyroidism.
4.4.2 Imaging investigation in neonates with congenital hypothyroidism
After performing the screening test, as long as TSH < 10mIU/L, no further action is needed. Newborns with a moderate increase in TSH (10mIU/L < TSH < 20mIU/L) are invited for a confirmatory test of TSH and measurement of T4 and FT4 (blood collection by venipuncture); if hypothyroid hormone levels are confirmed, they are referred to a pediatric endocrinologist and treatment begins. Neonates with TSH > 20mIU/L are referred directly to a pediatric endocrinologist for further testing and treatment.
In cases of single measurement of TSH or total T4 (TT4), the following observations have emerged from their application in clinical practice: The measurement of TT4 is advantageous in the detection of cases with central hypothyroidism and is accompanied by fewer false positive results (TT4 does not change during the first 24–48 hours of life, as it has been observed with TSH). It is difficult to define a cutoff (threshold) low enough to avoid false-positive results and high enough to detect cases with an ectopic thyroid gland, resulting in about 7% false-negative results. The measurement of TSH has the advantage of having fewer false negative results and is furthermore highly recommended in the detection of congenital hypothyroidism due to iodine deficiency, as well as in cases with mild hypothyroidism [45].
Radiographs
The knee joints may be X-rayed to determine the bone age (bone epiphyses study).
US
It can provide additional information about (i) the anatomy of the gland, (ii) the presence of cysts or thymic tissue in the thyroid region in patients with thyroid dysgenesis, and (iii) allow the gland to be detected in some cases in the absence of radiopharmaceutical uptake during scintigraphic testing [46, 47]. In the latter cases, there arises a suspicion of some form of dyshormonogenesis (specifically that due to a reduced response to TSH) or of the transplacental passage of antibodies against TSH receptors. Antibodies against TSH receptors completely inhibit TSH-induced uptake of the radiopharmaceutical by the thyroid parenchyma [48]. The measurement of thyroglobulin can help detect residual functional thyroid tissue.
Thyroid scan
It is particularly useful in ruling out any dysgenesis and is much more sensitive than ultrasound in revealing ectopic thyroid tissue [49]. It is performed with either radioactive technetium (1–5 MBq/kg 99mTc-pertechnenate) or radioactive iodine-123 (0.1–0.3 MBq/kg 123I). 123I is the radionuclide of choice when ectopic or dystopic thyroid tissue is suspected, due to its superior properties such as higher gamma energy (159 keV) compared to 99mTechnetium (140 keV), thus allowing for better penetration of osseous structures and detection of retrosternal, intrathoracic and abdominal thyrogenous masses. Sensitivity and specifcity of scintigraphy gets further increased if SPECT/CT hybrid imaging is available for anatomic correlation and attenuation correction.
It appears that thyroid dysgenesis is a multigene (disruption of several genes is required to manifest the specific phenotype) and multifactorial (synergy of genetic and environmental factors is required) disease [50]. In 40–60% of cases there is residual thyroid tissue, but thyroid scintigraphy (even with 123I) has relatively limited sensitivity for its detection.
Except in the case of decreased response to TSH, in congenital hypothyroidism due to dyshormonogenesis, the thyroid gland is visualized in situ (and is often enlarged and/or shows increased radiopharmaceutical uptake).
In dyshormonogenesis due to iodine trapping disorder, hypothyroidism is accompanied by goiter and a low uptake of the radiopharmaceutical is observed in the thyroid parenchyma. As hypothyroidism is usually detected late, mental retardation coexists. Potassium iodide 1–5 mg is given and then thyroxine.
In the case of decreased response to TSH, the thyroid gland is not visualized on scintigraphy (same picture as that of agenesis), while the thyroid tissue is revealed on ultrasound examination and serum thyroglobulin is measured in approximately normal ranges [51]. The dissociation between the gland size and thyroglobulin concentration is partly explained by the fact that the regulation of thyroglobulin secretion is not solely dependent on TSH.
The use of recombinant TSH is a satisfactory alternative to scintigraphic study and potassium perchlorate discharge test, avoiding discontinuation of replacement therapy [52].
In conclusion, the combination of scintigraphy and thyroid ultrasound is the best imaging approach for congenital hypothyroidism [53].
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