Predictive value of technetium-99m sodium pertechnetate thyroid scintigraphy in determining the permanence of congenital hypothyroidism

INTRODUCTION

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, affecting both pre-term and term infants with an incidence of 1:2404 in Hong Kong.^[1] Early diagnosis of primary CH and timely thyroxine replacement therapy for neonates with confirmed CH have been proven effective to avoid intellectual disability. Technetium-99m (^99mTc) sodium pertechnetate thyroid scintigraphy is a recommended imaging technique for evaluating the location of functioning thyroid tissue. It can also help determine the cause of CH, such as dyshormonogenesis, ectopia, or athyreosis. The latest consensus guidelines endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology recommend the use of imaging to differentiate CH into its subtype at the time of diagnosis,^[2] in addition to biochemical tests and ultrasonography of the neck.^[3,4] At our center, [^99mTc] pertechnetate thyroid scans are performed for newborns with biochemically confirmed CH before starting thyroid hormone replacement therapy. We aim to investigate the predictive value of [^99mTc] pertechnetate thyroid scintigraphy for the permanence of CH.

MATERIAL AND METHODS

Analysis of thyroid scintigraphy

Two nuclear medicine physicians with at least 5 years of experience in molecular imaging evaluated the [^99mTc] pertechnetate thyroid scintigraphy using the viewer (Xeleris version 4.1 Functional Imaging Workstation, GE Healthcare, US). Thyroid eutopia was defined as the visualization of bilateral thyroid activity in the anatomical thyroid bed [example in Figure 1a], and thyroid dysgenesis encompassed thyroid ectopia, hemiagenesis, and athyreosis [examples in Figure 1b-f].

Close

Figure 1:

(a) [^99mTc] pertechnetate thyroid scan showed marked bilateral thyroid lobe activity in the neck. This suggested thyroid eutopia. (b and c) [99mTc] pertechnetate thyroid scan showed a marked focal activity in the sublingual region, while there was no activity in the anatomical thyroid bed. This suggested thyroid dysgenesis (thyroid ectopia). (d) [^99mTc] pertechnetate thyroid scan showed an absent left thyroid lobe, as evidenced by ultrasonography. This suggested thyroid dysgenesis (hemiagenesis). There was tubular activity in the upper to mid-neck, persistent after drinking water (images not shown), likely representing thyroglossal duct. (e and f) [^99mTc] pertechnetate thyroid scan showed no thyroid activity in the neck and the absence of thyroid tissue was confirmed with ultrasonography. This suggested thyroid dysgenesis (athyreosis).

Export to PPT

RESULTS

Subgroup analysis of scintigraphic thyroid eutopia

Among patients with thyroid eutopia on the scintigraphy, 52 patients (70.3%) presented with transient CH, whereas 22 patients (29.7%) had permanent CH. Patients with permanent CH exhibited significantly higher TSH levels (31.9 mIU/L vs. 17.9 mIU/L, P = 0.011). Gender, gestational age, and fT4 levels were not significantly associated with permanent CH (P = 0.354, P = 0.163, and P = 0.969, respectively). Subgroup analyses of the thyroid eutopia group are presented in Table 3. A ROC curve analysis [Figure 2] was conducted to determine the optimal cutoff value of TSH level for predicting the permanence of CH in patients with thyroid eutopia on [^99mTc] pertechnetate thyroid scintigraphy. The area under the curve (AUC) was found to be 0.688 (95% confidence interval: 0.566–0.811, P = 0.003). With a cutoff value of TSH level 18.72 mIU/L, it showed a sensitivity of 77.3% and specificity of 53.8% to predict permanent CH in patients in thyroid eutopia group.

Table 3: Subgroup analysis of thyroid eutopia group.

	Transient CH	Permanent CH	P-value
Number of patients	52	22
Gender			P=0.354
Female	25	8
Male	27	14
Gestational age			P=0.163
<38 weeks	15	3
≥38 weeks	37	19
TSH level (mIU/L)	17.9	31.9	P=0.011
fT4 (pmol/L)	15.9	16.1	P=0.969

Bold indicates statistically significant results (P<0.05). CH: Congenital hypothyroidism, TSH: Thyroid-stimulating hormone, fT4: Free thyroxine

Close

Figure 2:

A receiver operating characteristic (ROC) curve analysis to determine the optimal cutoff value of thyroid stimulating hormone (TSH) level for predicting the permanence of congenital hypothyroidism in patients with thyroid eutopia on [^99mTc] pertechnetate thyroid scintigraphy. The area under the curve (AUC) was found to be 0.688 (95% confidence interval: 0.566– 0.811, P=0.003), with a cutoff TSH level of 18.72 mIU/L, showing sensitivity of 77.3% and specificity of 53.8%.

Export to PPT

DISCUSSION

CH is a relatively common endocrine disorder characterized by deficient thyroid hormone production in newborns.^[5,6] It is crucial to detect and treat CH early to prevent adverse outcomes, especially intellectual disability, as thyroid hormones play a vital role in normal growth, brain development, and metabolism.^[6] Transient CH refers to a temporary impairment in thyroid hormone production that resolves spontaneously over time. The etiology of transient CH can vary and includes conditions such as prematurity, iodine deficiency or exposure, maternal antibodies or intakes of antithyroid medications, loss of function mutations, and hepatic hemangiomas.^[7] On the other hand, permanent CH refers to a lifelong insufficiency of thyroid hormone production. Permanent CH can result from various etiologies, including thyroid dysgenesis, such as aplasia or hypoplasia of the thyroid gland, or genetic defects affecting thyroid hormone synthesis or iodine transport.^[6] Newborn screening programs have been instrumental in the early detection of CH, typically through measuring TSH levels from umbilical cord blood. Elevated TSH levels prompt further diagnostic evaluation, including serum T4 measurement and imaging.^[8] The cutoff values of TSH to diagnose CH generally range from 10 to 20 mIU/L in different countries,^[2] but as low as 5.5 mIU/L is taken in Turkey.^[9] In our center, patients with persistently elevated TSH level higher than 6 mIU/L will be investigated and treated with levothyroxine, compatible with the consensus guidelines.^[2]

Ultrasonography of the neck and thyroid scintigraphy with [^99mTc] pertechnetate or [¹²³I]iodine is considered the standard imaging techniques for investigating the etiology of CH, with thyroid scintigraphy being recommended particularly when thyroid dysgenesis is suspected.^[8] In this study, we aimed to investigate the predictive value of [99mTc] pertechnetate thyroid scintigraphy in patients with primary CH, specifically in predicting the clinical outcome as transient CH or permanent CH. The results demonstrated that thyroid scintigraphy is a useful tool for evaluating the etiology of CH.

Our findings showed that patients with thyroid dysgenesis, including ectopic thyroid glands, hemiagenesis, and athyreosis, required permanent thyroid hormone replacement therapy. In contrast, patients with scintigraphic evidence of a normal bilobed thyroid in the anatomical thyroid bed (eutopia) could be further stratified based on their TSH levels. A cutoff TSH level of 18.72 mIU/L was found to predict the need for lifelong thyroid hormone replacement therapy with a sensitivity of 77.3% and specificity of 53.8%. However, gender, gestational age, and fT4 levels did not show significant differences between the transient and permanent thyroxine replacement groups in patients with eutopic thyroid.

Most of the patients in our study presented with eutopic thyroid, and a significant proportion of them (70.3%) were successfully weaned off levothyroxine, indicating transient CH. Among the patients requiring permanent thyroid hormone replacement therapy, a subset showed eutopic thyroid (66.7%), whereas others had thyroid dysgenesis (33.3%). These findings differ from previous literature, which reported a higher percentage, up to 85%, of thyroid dysgenesis among patients with permanent CH and a lower percentage of transient CH (10%) among all patients diagnosed with CH.^[10] This discrepancy may be attributed to our center’s management approach, which treats patients with persistent mild CH (TSH >6 mIU/L) by following consensus guidelines and administers levothyroxine with monitoring of TSH level, conventionally for 3 years to prevent mental retardation associated with CH,^[2] and as a result, our study may include more patients with eutopic thyroid and transient CH in comparison with previous studies.

This research confirmed previous findings that thyroid dysgenesis is more common in females and is associated with higher TSH levels and lower fT4 levels compared to eutopic thyroid cases.^[4,11,12] However, we did not consider levothyroxine dosages in our analysis, which shows the predictive value for the permanence of CH in previous studies,^[9,13] as our primary aim was to investigate the association between scintigraphic findings at diagnosis and the permanence of CH.

There were limitations to our study. First, it was a single-center retrospective study, which may limit the generalizability of the findings. In addition, the study primarily included Chinese subjects and the applicability of the results to other populations and ethnicities may be limited. Moreover, our sample size is not large, probably explained by the fact that a number of patients had lost follow-up in our hospital within 3 years.

CONCLUSION

Our study highlights the value of [^99mTc] pertechnetate thyroid scintigraphy in evaluating the etiology of CH. The scintigraphic findings can help differentiate between thyroid dysgenesis and eutopic thyroid and predict the need for permanent thyroid hormone replacement therapy. These results provide insights into the clinical outcome prediction of CH with thyroid scintigraphy, and it can aid in individualized treatment decisions for patients with CH. Further studies involving larger and more diverse populations are warranted to validate these findings and explore additional factors that may influence the clinical outcomes of CH.