Acute transient thyroid swelling following fine-needle aspiration: a case series and a systematic review
Original Article

Acute transient thyroid swelling following fine-needle aspiration: a case series and a systematic review

Da-Kun Zhang# ORCID logo, Xin-Yan Zhu# ORCID logo, Jing-Bo Guan, Zhi-Xuan Li, Yun-Lin Li, Jie Gao

Department of Ultrasound, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China

Contributions: (I) Conception and design: DK Zhang, XY Zhu; (II) Administrative support: DK Zhang; (III) Provision of study materials or patients: JB Guan, ZX Li; (IV) Collection and assembly of data: YL Li, J Gao; (V) Data analysis and interpretation: DK Zhang, XY Zhu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

Correspondence to: Da-Kun Zhang, PhD. Department of Ultrasound, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing 100091, China. Email: zdk002@163.com.

Background: Acute transient thyroid swelling (ATTS) is a rare complication of fine-needle aspiration (FNA) of thyroid nodules. Most cases were in spontaneous remission. However, it is fatal in rare cases. However, there are few literature reports, so it is of great significance to improve the clinical understanding of ATTS. Therefore, this study aimed to present 10 institutional cases and a systematic review of 18 literature cases to delineate clinical features, imaging findings, and management approaches.

Methods: Twenty-eight clinical cases (10 cases from institutional archives and 18 cases from literature search) were included in the retrospective analysis. Data collection continued until August 1, 2024.

Results: ATTS following FNA is a rare complication. Among the 28 total cases (10 institutional, 18 literature), 89% were female. Bilateral goiter occurred in 71%. Symptoms typically emerged within one hour following FNA, resolving spontaneously within 24 hours in 79% of cases. Neck pain/swelling (54%) was common; severe complications (dyspnea, cardiac arrest) were rare (3%). Ultrasound revealed unilateral/bilateral goiter with linear/patchy hypoechoic areas and preserved vascularity. Non-pharmacological management sufficed for most patients.

Conclusions: ATTS following FNA is self-limiting, with distinct ultrasound findings. Clinicians should prioritize airway management in severe cases and avoid unnecessary interventions in mild presentations.

Keywords: Acute transient thyroid swelling (ATTS); complication; fine-needle aspiration (FNA); ultrasound; case series

Submitted Feb 17, 2025. Accepted for publication Apr 17, 2025. Published online May 27, 2025.

doi: 10.21037/gs-2025-66

Highlight box

Key findings

• This study aimed to conduct a systematic review of 10 institutional cases and 18 literature cases to describe the clinical characteristics, imaging findings and treatment methods of acute transient thyroid swelling (ATTS).

What is known and what is new?

• ATTS is a rare but potentially important complication of fine-needle aspiration (FNA) in thyroid nodules. Despite its clinical relevance, there are few reports and case summary analyses in the literature.

• ATTS after FNA is self-limited and fatal in rare cases, with obvious ultrasonic manifestations.

What is the implication and what should change now?

• This study helps clinicians identify and pay attention to ATTS after FNA. Clinicians can select the appropriate treatment methods in time.

Introduction

Thyroid nodules are a common type of thyroid disease (1,2). According to different diagnostic techniques, the prevalence rate in the general population ranges from 2% to 65%. According to TIDE (Thyroid Disorders, Iodine Status, and Diabetes Epidemiological survey) research report, the prevalence rate of thyroid nodules with diameter >0.5 cm is 20.43% (3). Among them, the overall number of new cases and crude incidence rate (CIR) of thyroid cancer worldwide are on the rise (4). Fine-needle aspiration (FNA) is the gold standard for evaluating the benign and malignant thyroid nodules, and the incidence of complications is low (0.15%) (5). However, in recent years, cases of acute transient thyroid swelling (ATTS) after thyroid FNA have gradually emerged. ATTS is rare and self limiting. It is characterized by unilateral or bilateral rapid enlargement of the thyroid gland, accompanied by unique ultrasound findings. We systematically describe its clinical features, imaging findings and treatment by conducting a systematic review of 10 cases in our hospital and 18 cases in the literature. We present this article in accordance with the PRISMA and the AME Case Series reporting checklists (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-66/rc).

Methods

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patients to publish this study and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Institutional cases

We analyzed and summarized the information from 10 cases of ATTS following FNA at our hospital between May 2018 and August 2024. This is a public tertiary hospital.

Characteristics of ATTS encompass (I) swift bilateral or unilateral enlargement of thyroid nodules during or after FNA; (II) a momentary and self-restricting nature; (III) distinctive ultrasound patterns depicting patchy and fissure-like appearances in the thyroid gland with either double or single lobes.

Follow-up

After FNA, the patients were evaluated and monitored every 0.5 hours until their ultrasound images returned to normal. The evaluation included the evaluation of thyroid ultrasound images and thyroid discomfort symptoms. The treatment strategy is observation and pressure treatment.

Literature

For the review, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the PubMed, Embase, the Cochrane Library and Web of Science databases up to August 1, 2024 and performed a systematic review of ATTS following FNA using the following mesh terms in the title: “thyroid swelling”, “FNA”, “thyroid nodule”. These terms were combined with the term “acute transient thyroid swelling” and “fine-needle aspiration”. Items from the preliminary search were screened for duplicate items and then assessed for eligibility to be included. Two reviewers independently extracted articles with demographic and clinical characteristics. Finally, 18 relevant cases were extracted.

Collected clinical data were entered into a Microsoft Excel database, including year of publication, county, the first author, sex, age, history of allergy, nodule characteristics, symptom, onset of swelling, duration of swelling, needle gauge, degree of swelling, treatment, and cytological diagnosis.

The included studies in this paper are case reports, case series and non-controlled studies. The quality evaluation is carried out by using the JBI literature quality evaluation tool on descriptive studies (Table 1).

Table 1

Quality assessment tools for case series

Entry Evaluation results
Yes No Not clear Not applicable
1. Are there a clear case inclusion criteria? √
2. Is it ensured that standard and reliable methods are adopted to determine the disease or health problem of the case? √
3. Is it ensured that effective methods are taken to diagnose diseases or health problems? √
4. Is the inclusion of subjects in the case consistent? √
5. Is the inclusion of research objects in the case comprehensive? √
6. Whether the demographic information of the research object is clearly reported? √
7. Is the clinical information of the subjects clearly reported? √
8. Whether the outcome or follow-up results of the case are clearly reported? √
9. Is the geographic and sociological information of the case clearly reported? √
10. Is the statistical analysis method appropriate? √

Inclusion criteria: (I) prospective or retrospective studies of acute goiter after FNA of thyroid nodules published before August 1, 2024; (II) complete case information.

Exclusion criteria: (I) acute goiter caused by other causes; (II) incomplete case information.

Results

Institutional cases

All ten cases in our study were female, with a median age of 40 years (ranging from 27 to 54 years). Among them, one case had elevated thyroid peroxidase antibodies, one case had elevated serum T3, and eight exhibited normal thyroid function. The average size of the punctured nodules was 8.7 mm (ranging from 2 to 19 mm). Bilateral involvement was observed in four cases, while unilateral involvement was noted in six cases. The average degree of thyroid swelling was 1.6 times (ranging from 1.1 to 3 times). Nine cases were asymptomatic, while one case reported swelling pain at the puncture site. Two cases underwent pressure treatment, while eight received no specific intervention, and the average recovery time for acute goiter was 5.2 hours (ranging from 1 to 23 hours). All ten cases exhibited the “crack sign” changes in the thyroid as observed through ultrasound. Pathological analysis revealed that four cases had benign outcomes and six cases had malignant findings (Table 2 and Figure 1).

Table 2

Institutional cases of ATTS after FNA

Case Sex Age (years) History of allergy Nodule characteristics Symptom Onset of swelling Duration of swelling Needle gauge Degree of swelling Treatment Cytological diagnosis
1 F 40 None 4 mm, R lobe Asymptomatic During FNA 4 h 25 R lobe 2.8 Observation method Benign
2 F 35 None 5 mm, L lobe Asymptomatic During FNA 2 h 25 Bilateral 3 pressure treatment Benign
3 F 54 None 7 mm, L lobe Asymptomatic During FNA 16 h 25 L lobe 1.6 pressure treatment PC
4 F 35 None 16 mm, R lobe Swelling During FNA 1.5 h 25 L lobe 1.2 Observation method Atypical cells
5 F 41 None 17 mm, R lobe Asymptomatic During FNA 23 h 25 R lobe 1.2 Observation method Benign
6 F 37 None 2 mm, L lobe Asymptomatic During FNA 1 h 25 R lobe 1.1 Observation method PC
7 F 42 None 3 mm, R lobe Asymptomatic During FNA 1 h 25 Bilateral 1.1 Observation method PC
8 F 50 None 7 mm, R lobe Asymptomatic During FNA 1 h 25 Bilateral 1.1 Observation method Benign
9 F 27 None 19 mm, L lobe Asymptomatic During FNA 1.5 h 25 L lobe 1.3 Observation method PC
10 F 40 None 7 mm, R lobe Asymptomatic During FNA 1 h 25 Bilateral 1.1 Observation method PC

F, female; FNA, fine-needle aspiration; L, left; PC, papillary carcinoma; R, right.

Figure 1 Ultrasonographic features of ATTS following FNA. (A) Arrow indicates the targeted nodule for puncture; (B) arrow demonstrates the position of the fine needle during aspiration; (C) the cross-section and (D) the longitudinal section show that the thyroid gland was unilaterally swollen with patchy hypoechoic areas, displaying the “crack sign”; (E) there was no significant blood flow changes in the enlarged thyroid. ATTS, acute transient thyroid swelling; FNA, fine-needle aspiration.

Combined analysis

Among the 28 patients, 25 were female (89%), while three were male (11%). Bilateral goiter was present in 20 individuals (71%), and eight individuals (29%) exhibited unilateral goiter. ATTS manifested in 14 cases (50%) during the puncture process and in 14 cases (50%) at the conclusion of the puncture. Treatment approaches included medication in seven cases (25%) (involving pain relief, nonsteroidal anti-inflammatory drugs, or hormones), physical therapy in four cases (14%) (such as compression or ice compress) and endotracheal intubation therapy in one case (4%), while 16 patients (57%) did not receive any specific treatment. Within 24 hours, 22 patients (79%) returned to normal, and six patients (21%) experienced normalization after ≥24 hours. Symptoms of pain and swelling were reported in 15 cases (54%); symptoms of severe dyspnea and cardiac arrest were reported in one case (3%), while 12 cases (43%) were asymptomatic (Tables 2,3). The ultrasonic manifestations were: unilateral or bilateral goiter with linear, fissure-like low echo areas or patchy low echo areas, with no significant change in thyroid blood flow.

Table 3

Cases of ATTS after FNA in literature

Study Country Sex Age (years) History of allergy Nodule characteristics Symptom Onset of swelling Duration of swelling Needle gauge Degree of swelling Treatment Cytological diagnosis
Haas SN, 1982 (6) UK F 47 None 30 mm, R lobe Moderate pain 2–3 min after FNA 1 h 22 Bilateral 2.5 Ice compress N/A
Dal Fabbro S, 1987 (7) Italy F 63 N/A 38 mm, R lobe Slight pain Just after FNA A few hours 22 Bilateral 3 Ice compress FC
Van den Bruel A, 2008 (8) Belgium M 56 None 20 mm, L lobe Neck pain During FNA 4 h 24 Bilateral 3 Observation method Medullary carcinoma
Norrenberg S, 2011 (9) Belgium F 27 None 10 mm, L lobe Pain During FNA 3 h 21 Bilateral 2 NSAIDs FC
Belgium F 46 None 15 mm, R lobe Severe pain Within 5 min after FNA 4 days 21 Bilateral 2.9 Pireparacetamol Medullary carcinoma
Nakatake N, 2012 (10) Japan F 58 None 9 mm, L lobe Slight pain 1 h after FNA A few hours 22 Bilateral 3 Observation method Benign
Japan M 31 None 15 mm, R lobe Neck pain 1.5 h after FNA A few hours 22 Bilateral 2 Observation method Benign
Japan F 45 None 24 mm, L lobe Asymptomatic 2 h after FNA A few hours 22 Bilateral 2.5 Observation method Benign
Yamada K, 2015 (5) Japan F 50s None 14 mm, R lobe Pain and tenderness Just after FNA 1.5 h 22 R lobe 3 Observation method N/A
Japan F 60s None 24 mm L/15 mm, R Pain, slight dyspnea 2 h after FNA A few hours 22 Bilateral 12 NSAIDs R PC, L benign
Japan F 70s Penicillin and pyrazolone drugs 1.1 cm, L/1.9 cm, R Swelling 1.5 h after FNA 2 weeks 22 Bilateral 5 Steroids Benign
Japan F 40s None 6 mm, R lobe Asymptomatic During FNA 5.5 months 22 Bilateral 2 Observation method PC
Tang WK, 2017 (11) China F 68 None 26 mm, R lobe Swelling and tenderness 2–3 min after FNA 22 h 21 Bilateral 5 Observation method FN
Zhu T, 2021 (12) China F 30 None 13 mm, L/5 mm, R Asymptomatic During FNA 0.5 h 23 L lobe 1.5 Observation method L benign, R atypical cells
Imaoka K, 2021 (13) Japan F 26 None 14 mm, L lobe Swelling and tenderness 3 h after FNA 18 h 23 Bilateral N/A Steroids and H1 antihistamines PC
Kim YK, 2022 (14) Korea F 65 N/A 19.1 mm, L lobe Neck pain, swelling, and shortness of breath 1 h after FNA 24 h N/A Bilateral 3 Dexamethasone N/A
Zeng W, 2022 (15) China M 56 None 39 mm, R lobe Pain 0.5 h after FNA 7 days N/A Bilateral 4.9 Dexamethasone and furosemide Benign
Yoshizawa S, 2023 (16) Japan F 81 None L lobe Severe dyspnea, cardiac arrest 1.5 h after FNA 4 days 21 Bilateral N/A Endotracheal intubation Benign

F, female; FC, follicular carcinoma; FN, follicular neoplasm; FNA, fine-needle aspiration; L, left; M, male; N/A, not available; NSAID, non-steroidal anti-inflammatory drug; PC, papillary carcinoma; R, right.

Discussion

FNA is a straightforward, efficient, and safe technique for identifying the characteristics of thyroid nodules. Common complications encompass local pain (92%) and mild bleeding (3–26%) (15,17). The incidence of ATTS subsequent to thyroid FNA is infrequent, and was first reported by Haas in 1982 (6). Currently, only a limited number of cases have been reported. This summary and analysis of cases from our hospital and literature aim to enhance awareness among clinical and ultrasound practitioners regarding this uncommon complication and offer valuable clinical insights.

Etiology and pathogenesis

The mechanism behind ATTS after FNA remains unclear, and three current hypotheses have been proposed. The first hypothesis involves vasodilation and capillary leakage (5,15). Some scholars posit that puncturing thyroid nodules triggers local release of calcitonin-related peptide (CGRP), a potent endogenous vasodilator produced by the nervous system, which is known for causing vasodilation and is highly expressed in medullary thyroid cancer. Therefore, the levels of serum calcitonin measured increase (8). However, Norrenberg et al. argue that the CGRP hypothesis may not account for all cases (9). In this study, only two cases involved medullary carcinoma, providing insufficient evidence to support this notion. The alternative theory suggests that repeated punctures could lead to vascular injury, inducing local release of vasodilators and consequent vascular leakage. The second hypothesis is a hypersensitivity reaction mediated by thyroglobulin. Puncture disrupts thyroid follicles, leading to the release of thyroglobulin into the circulation. Thyroglobulin or other molecules may then trigger a self-reactive response within the thyroid (12,15). Mast cells become activated upon contact of the suction needle with the patient’s skin, leading to the release of histamine and other inflammatory mediators. Histamine can bind to four types of receptors. Among them, the binding of histamine to H1 receptors causes vasodilation and increased blood flow, leading to high permeability of postcapillary venules (18,19). This activation contributes to changes in vascular permeability, ultimately resulting in thyroid swelling. After the stimulus is removed, the patient undergoes self-recovery, and the substances in the body are gradually eliminated. Hence, vascular leakage alone cannot account for the short-term spontaneous recovery observed in ATTS after puncture (9). The third hypothesis involves intrathyroidal hemorrhage, which could result from focal thin-walled vascular rupture or vascular fistula within the thyroid parenchyma (20). However, the study by Dal Fabbro et al. on surgical exploration of patients with thyroid cancer-induced goiter after a puncture revealed no apparent hematoma signs outside or within the thyroid gland (7). The second hypothesis is favored, as the other two fail to explain the short-term recovery of diffuse bilobar goiter and goiter post-puncture. In our ten cases, an interesting observation is that some patients were punctured twice in different parts and on different days, but not all of them had ATTS, which requires further analysis and research.

Sonographic findings

ATTS subsequent to FNA typically presents the following ultrasonic features (10,15,17):

  • Unilateral or bilateral acute enlargement of the thyroid gland.
  • Linear, fissure-like hypoechoic areas or patchy hypoechoic areas within the thyroid gland. During or at the end of the thyroid puncture, it was found that the thyroid was diffusely distributed in one or both sides with strip-shaped low echo passing through the normal thyroid tissue, which was similar to the appearance of “plaque” or “crack”, indicating that there was thyroid parenchyma edema, which was characterized by transient rapid appearance and regression, accompanied by goiter, and this phenomenon was related to thyroid fine-needle puncture.
  • Generally, no significant alterations in thyroid blood flow are observed.
  • Most of them had no severe complications such as tracheal obstruction.
  • The thyroid gland typically recovers within a short timeframe.

Among the 28 patients, 20 exhibited bilateral thyroid swelling, while eight had unilateral thyroid swelling, with bilateral occurrences being more prevalent.

A study has reported a 1.5 to 5 times increase in the degree of ATTS (average 2.5 times) (15). In our study, the thyroid volume in the 28 patients increased by 1.1 to 12 times (average 2.7 times). ATTS manifested in 14 cases after the conclusion of the puncture, occurring within 0 to 3 hours (average 1.01 hours). Inadequate time allowance following thyroid puncture may lead to the oversight of certain cases. Therefore, it is advisable to observe patients for a minimum of one hour post-puncture to promptly identify potential adverse reactions.

Prognosis and outcome

This study reports a case of severe complication, including dyspnea and cardiac arrest (16). The patient was an 81-year-old female who developed severe dyspnea 1.5 hours after FNA followed by cardiac arrest. Cardiopulmonary resuscitation and intubation were performed, and the thyroid function returned to normal after recovery. The patient was successfully discharged. Therefore, for patients with severe complications, early identification and active management of airway patency are key to treatment. It is also important to inform patients that complications may be delayed. For mild complications and asymptomatic patients, common treatment methods include drug therapy, physical therapy, and observation methods. Drug therapy comprises pain relief, nonsteroidal anti-inflammatory drugs, or hormone drugs, while physical therapy involves compression or ice compression. The observation method entails monitoring the self-recovery of the thyroid gland without specific treatment measures. It remains unclear from the literature whether steroid use affects the course or duration of ATTS, though case reports suggest that intravenous hydrocortisone administration may expedite recovery within 20 hours (13). In our study, seven cases (25%) received drug treatment, and 20 cases (71%) were managed without drugs. The recovery time with drug treatment ranged from several hours to one week (11,14). Conversely, all ten of our cases were treated without drugs, with an average recovery time of 5.2 hours. Therefore, for patients with mild symptoms, we recommend non-pharmacological treatment with continuous observation until the swelling significantly alleviates or disappears. For rare severe complications, active management is required to ensure airway patency. In our institutional case series, ATTS was identified during FNA in all patients, whereas only 4 of 18 patients reported in the literature developed ATTS during FNA procedures. Notably, we observed that ultrasonographic manifestations of ATTS preceded clinical symptoms in all cases. Among our 10 patients, unilateral or bilateral thyroid involvement was first detected through the emergence of linear or patchy hypoechoic areas on real-time ultrasound monitoring during FNA, with subsequent gradual thyroid enlargement. Only one patient developed palpable swelling, while the majority remained asymptomatic throughout the observation period. This discrepancy may be attributed to the procedural differences between institutions: our FNA operators are ultrasound specialists who maintain continuous imaging surveillance during procedures, potentially enhancing sensitivity to early sonographic changes. In contrast, clinicians performing FNA at other institutions may prioritize clinical symptom monitoring over imaging findings during the intervention. Therefore, real-time dynamic ultrasound detection during and after FNA may help to identify ATTS. Among the cases, 22 (79%) returned to normal within <24 hours, while six cases (21%) normalized in ≥24 hours. Prolonged observation intervals in some cases may contribute to extended recorded recovery times for thyroid swelling.

Limitations

This study searched the main databases, but some cases may have still been omitted. The incidence of acute goiter after FNA is low, and the observation time after puncture is not sufficient, resulting in some cases not being found, so these cases may not fully reflect the clinical manifestations, treatment and prognosis of the disease. There may be some heterogeneity among the cases selected in this study, such as the differences in the experience of thyroid fine needle puncture operators and the differences in ultrasound equipment, which need further study in the future.

Conclusions

ATTS following FNA is rare, self-limiting, and sonographically distinct. Clinicians should recognize its benign course in most cases while prioritizing airway management in severe presentations.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA and the AME Case Series reporting checklists. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-66/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-66/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-66/prf

Funding: This work was supported by the CACMS Innovation Fund (No. CI2021A03317).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-66/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patients to publish this study and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Zhang DK, Zhu XY, Guan JB, Li ZX, Li YL, Gao J. Acute transient thyroid swelling following fine-needle aspiration: a case series and a systematic review. Gland Surg 2025;14(5):888-896. doi: 10.21037/gs-2025-66

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