Currently the main indication for a thyroid scan is given by frank or subclinical hyperthyroidism aiming to verify the presence of glandular hyperfunction which may either be diffuse or focal (autonomous nodule). Though, in clinical practice low TSH values may not relate to a functionally autonomous thyroid nodule, while scintigraphically “hot nodules” may be found in patients with a normal thyroid hormonal profile. In the latter cases, given the well documented literature of “hot” nodules in scintigraphy with radiopertechnetate but “cold” in scintigraphy with radioiodine, scans performed both with ^99mTc and ¹³¹I were compared. In our nuclear medicine unit we wanted to quantify these mismatches, comparing scintigraphic results to hormonal dosages and ultrasound thyroid examination.

Eighty-four consecutive patients undergone thyroid scan with ^99mTc were included in this study. Six/84 patients also underwent a¹³¹I scan to compare discordant TSH value and thyroid scan result.

The images were acquired 20-40 minutes after IV administration of 3 mCi (111 MBq) of ^99mTc-pertechnetate by GE Discovery ST gamma camera, equipped with low energy high resolution collimators (about 500 k counts planar acquisitions, matrix 128×128, zoom 2). Scans with ¹³¹I were performed 24 hours after administration of 50 μCi (1.8 MBq) of ¹³¹I by a single-head gamma camera GE Millennium MG equipped with “general purpose” collimators for high energy (about 50 k counts planar acquisitions, matrix 128×28, zoom 2).

Scintigraphic scans were evaluated keeping into account thyroid hormone serum values from several laboratories (TSH, FT3, FT4) and the report of thyroid ultrasound examination (Figures 2a and 2b) performed previously, respectively within 6 months and 1 year from the scintigraphy.

Figure 1: Appearance of a “hot” nodule in the upper right lobe with a low concentration in the remaining parenchyma at ⁹⁹mTc-scintigraphy (a) and (b) only a weakly increased uptake of iodine-131 by the same nodule at ¹³¹I-scintigraphy; in this case the TSH was 2.46 with FT3 and FT4 in normal range.

Figure 2: Ultrasound images of the thyroid in Figure 1: a) axial view; b) sagittal view. The hot nodule seen in figures 1a and 1b was evaluated with ultrasound: there was an intranodular increased vascularity at the Doppler assessment.

Patients previously under levothyroxine or anti-thyroid (propylthiouracil or methimazole) therapy, within respectively 60 and 3 days from the scintigraphy, were also excluded from the present study. Only patients with a single nodule >15 mm, in example scintigraphic spatial lower limit, evaluated by US of the neck, were included.

The significance of the association between two variables in a contingency table performing two-tail P value calculus obtained from X², or through Fisher’s exact test in a 2×2 table when sample sizes were small, was studied. A hypothesis was considered valid when P value ≤ 0.05. All the data were processed using R Development Core Team.

Among the 84 patients studied (21 Males, 63 Females), 31/84 showed a TSH below normal, 52/84 had TSH within normal limits and 1/84 had TSH higher than higher limit. The hormone values considered, even though made in different laboratories, were performed 10-90 days before the scintigraphy (median 60 days, interquartile range 28-98 days).

There were no significant differences in the percentage of males and females among the entire population (25% male, 75% female) and groupings for normal TSH (25% male, 75% females) and lower than normal (26% male, 74% females) and within the same subgroups.

Among patients with low TSH, 8/31 had also free fractions (both FT3 and FT4 or one of the two) that exceeded the normal limits.

The highest number of discordance between scintigraphic results and hormonal levels was found in cases with TSH below lower limit (15/31, 48.4%), as the scan did not show focal hyperfunction in these patients has not been revealed the presence of focal hyperfunction as might be expected; only a subset (8 patients) in which the low TSH was associated with the presence of free fractions higher than normal, there was not any discordance.

T-test was used to evaluate whether the two groups of patients with TSH below normal belonged to different populations: the test was significant (p<0.01); excluding the 8 patients who also had FT3 and / or FT4 above the normal, the difference was not significant (p=0.355).

In the group with normal TSH, eleven patients (11/52, 21%) showed the unexpected finding of “hot” nodule. None of these patients had TSH values lower normal limits, eventually suggesting an area of functional autonomy: the lowest value of TSH in this group was 0.64 g/ dl (reference interval 0.27-4.20). Six of these had a thyroid nodule with more evident increased uptake and subsequently have also performed a scintigraphy with ¹³¹I for comparison; in one case a significantly different biodistribution was found between radiopertechnetate and radioiodine therefore further evaluation by fine needle aspiration cytology was scheduled, which then showed a picture of benign nodular hyperplasia.

Finally, the total number of discordancies was observed in 26 out of 84 patients (31%), of which 18% (15 patients) is due to non-detection of “hot” nodules and 13% (11 patients) to unexpected discovery of this same type of formations.

Data presented in this study and previously demonstrated [1-3] support the use of thyroid scintigraphy to determine the functional status of thyroid tissue. This was true especially in cases with TSH below the normal range, when no focal autonomous tissue was found (48.4%, almost one out of two). When taking into account only those patients with normal FT3 and FT4, the percentage of expected discordance is even higher (65%); in these cases the average of TSH between patients with or without hot nodules was not significant (p=0.355).

The presence of chronic thyroiditis at the beginning or expanding pool of iodide cannot fully explain this phenomenon; further studies are needed to identify the coexistence of factors other than those already known, that play a role in regulating TSH.

It is interesting to consider the percentage of cases (13% of all cases, 21% of patients with TSH in normal range) where the opposite applies, i.e. unexpected “hot” nodule with hormonal values perfectly normal.

In 6 patients with a thyroid nodule “hot” bulky and visible at ^99mTc scan (Figure 1b), it has set the specific diagnostic doubt that it could be cold at iodine-131 scan, as it is well described [4-13] the dissociation between uptake of the radiopharmaceutical (present in the scans with radiopertechnetate) and organification, an exclusive iodine feature, present in some nodules then found to be well-differentiated thyroid cancer (papillary or follicular carcinoma). Only in one case there was a substantially different scintigraphic appearance of a thyroid nodule (Figures 1a and 1b), that appeared to be “hot” and associated with a low concentration in the remaining parenchyma examination at ^99mTc scan and only a weakly increased uptake than the rest of the gland with ¹³¹I. The subsequent evaluation by fine needle aspiration cytology, while showing intranodular increased vascularity at the Doppler assessment, did not detect cellular atypia suspicious for malignancy (TIR2 by “consensus” cytological SIAPEC 2007).

It can therefore be assumed that the nodules that turned out to be “hot” with technetium-99m, even when not associated with increased production of thyroid hormones, are considered as areas of focal hyperplasia of benign type; sometimes they also have a hypervascular pattern at the Doppler evaluation, therefore suggesting a low dietary iodine intake [14]. Infact a thyroid receiving a low intake of iodine cannot produce enough thyroid hormone to trigger the pituitary feedback, even in areas of functional autonomy. All these findings indicate the importance of performing a thyroid scan in iodine deficiency areas as a first-line investigation.

This work was supported by grant from “Università di Roma Tor Vergata”, Italy.