Management of Lingual Thyroid with Second Thyroid Anomaly: An Institutional Experience

Abstract

Patients diagnosed with Lingual thyroid (LT) may have second thyroid anomaly (STA).Given rarity of dual ectopics/anomalies, standardized management recommendations are lacking. We aimed to describe our experience in management of LT with STA and suggest a management algorithm. We conducted a retrospectivechart review of patients diagnosed with LT between Jul-2013 and Dec-2019. Data regarding demographics, clinical presentation, endocrine-profile, associated STA treatment received, and outcomes were collected and analyzed. Eight patients (female-7 cases, male-1 case, adult-4 cases, children-4 cases, mean age-18.1 years, range 6–43 years) with LT were identified. Four(50%) cases had STA in addition to LT (thyroglossal cyst in two-cases, sublingual thyroid in one-case and sub-mental thyroid in one-case) and presented as neck mass. Diagnosis was confirmed with flexible-nasopharyngoscopy,ultrasonography,thyroid-scintigraphy and computed-tomography. Ectopic thyroid(s) was/were only functional thyroid gland with absence of normal thyroid in all cases. Two- cases had symptomatic for LT and were managed by coblation assisted excision of LT in one and I¹³¹ ablation in one-case.All adult patients were hypothyroidand received thyroxin.All pediatric cases were euthyroidand received no surgical intervention for LT.Three patients required surgery for STA; Sistrunk surgery in two and excision of submental thyroid in one. All cases were asymptomatic. These results were utilized to suggest a management algorithm for LT with STA. LT patients with STA are more symptomatic and required more surgical interventions in compare to isolated LT. When appropriate, excision of STA with/without intervention for LT and thyroxin is advocated as the treatment modality of choice in LT patients with STA.

Introduction

Lingual thyroid (LT) glands are a rare developmental abnormality resulting from failure of migration of developing thyroid gland from its origin at the base of the tongue (BOT) to its normal anatomical position in the anterior neck. A thyroglossal duct cyst is the most common cause for congenital midline neck mass and may contain ectopic rests of thyroid tissue within its walls [1, 2]. BOT is a frequent site for ectopic thyroid tissue [1, 2].

Simultaneous occurrence of a thyroglossal duct cyst and a lingual thyroid in the absence of an orthotopic thyroid gland has been reported [3–5]. The second ectopic thyroid tissue may be present in the sublingual or sub-mental location [6]. The reported incidence of LT is between 1 in 300 and 1 in 1,00,000 population and it is more common in female gender [7, 8]. The orthotopic thyroid tissue in the neck is absent in a majority of cases (70%) of LT [9]. Most of patients with LT are either hypothyroid or euthyroid but rare cases of hyperthyroidism have been reported [10].

Most of the LT thyroids are detected incidentally on physical examination or imaging studies while others may present with obstructive symptoms like dysphagia, breathing difficulty or with features of hypothyroidism. Asymptomatic LT does not require any treatment except active surveillance [11]. The patient with LT may be symptomatic because of either change in the size leading to obstructive features or hormonal imbalance.

The treatment options for symptomatic TL are thyroid hormone suppression therapy [12] radioactive iodine therapy [13, 14] and surgical resection. Here, we present 8 cases of LT managed in a tertiary health care center from eastern part of India. We also described the difference in presentation and management of LT in pediatric age group and adult and proposed a management algorithm for patients with dual thyroid ectopic/anomaly based on our experience as there no standard guidelines are available regarding the management of the second thyroid ectopic/anomaly.

Materials and Methods

We conducted a retrospective chart review of patients diagnosed with LT between Jul-2013 and Dec-2019. Data regarding demographics, clinical presentation, technetium 99 m thyroid scintigraphy and computed tomography (CT) findings, endocrine- profile, treatment received, and outcomes of treatment were collected and analyzed. Ectopic thyroid was classified on basis of physical examination of oropharynx and neck, fiber-optic-laryngoscopy (FOL), and the location of high radioisotope uptake on anterior and lateral views of the thyroid scan. The ectopic thyroid tissue was classified into lingual thyroid (located in the midline of the tongue base), sublingual thyroid (located between the geniohyoid and mylohyoid), submental (located inferior to mylohyoid muscle in submental triangle), perihyoid (located in the neck around the hyoid bone) and thyroglossal cyst (cystic mass presented in midline of neck with/without thyroid tissue). “The Institutional Ethics Committee” at our institution approved the study. Descriptive statistics were used to analyze the data.

Results

A total of eight patients were identified. The male to female ratio was 1:7. Out of eight cases, four were adults and four were children. Mean age of presentation is 18.1 years (median 13.5, range: 6–43 years). Four (50%) cases had second ectopic thyroid tissue/anomaly in addition to LT. The second thyroidanomaly was thyroglossal cyst in two cases,sublingual thyroid in one case and submental thyroids in one case. These four cases presented as neck swelling. Six cases were asymptomatic for LT and two cases were symptomatic for LT. One case had dysphagia, breathing difficulty and recurrent bleeding and another case had dysphagia and globus sensation in throat as main symptom (Table 1). All patents underwent FOL, ultrasonography (USG) of neck, CT neck and Tc⁹⁹ thyroid scan to confirm the diagnosis (Figs. 1, 2). The ectopic thyroid(s) was/were only functional thyroid gland in all cases. The normal thyroid gland in the neck was absent in all cases. All four adult patients had hypothyroidism and they received thyroxine. All four pediatric cases were euthyroid and were asymptomatic for LT. They did not require any surgical intervention for LT (Table 2).

Table 1.

Showing various characteristics and parameter of the patients

Parameters	Case-1		Case-2	Case-3	Case-4	Case-5	Case-6	Case-7	Case-8
Age/sex	6/F		8/F	7/F	32/F	43/M	22/F	18/F	11/F
Present-ation specific to lingual thyroid	Asym-ptomatic		Asympto-matic	Asymptomatic for lingual thyroid but had a second thyroid anomaly (thyroglossal cyst )presented with a midline neck swelling at subhyoid level	Symptomatic with dysphagia ,breathing difficulty, Snoring, with intermittent bleeding	Asymptomatic for lingual thyroid but had a second sublingual ectopic thyroid tissue presented as a submental swelling	Sympto-matic with dysphagia and globus sensation in throat	Asymptomatic for lingual thyroid but had a second ectopic thyroid tissue presented as a submental swelling with short stature	Asymptomatic for lingual thyroid but had a second thyroid anomaly ( thyroglossal cyst )presented with a midline swelling at subhyoid level
Examina-tion findings (FOL, Examina-tion of neck)	Smooth hypervascular mucosa covered globular mass at tongue base	Smooth hypervascular mucosa covered globular mass at tongue base		1. Smooth hypervascular mucosa covered globular mass at tongue base 2. Midline neck swelling at subhyoid level	Smooth hypervascular globular mass at tongue base with ulceration of overlying mucosa	1. Smooth hypervascular mucosa covered globular mass at tongue base 2. Submental swelling	Smooth hypervascular mucosa covered globular mass at tongue base	1. Smooth hypervascular mucosa covered globular mass at tongue base 2. Submental swelling	1. Smooth hypervascular mucosa covered globular mass at tongue base 2. Midline neck swelling at subhyoid level
Thyroid scan	Intense focus of tracer uptake at base tongue  No uptake in neck	Intense focus of tracer uptake at base tongue  No uptake in neck		Intense focus of tracer uptake at base tongue  No uptake in neck	Intense focus of tracer uptake at base tongue  No uptake in neck	Intense focus of tracer uptake at base tongue and sublingual region	Intense focus of tracer uptake at base tongue  No uptake in neck	Intense focus of tracer uptake at base tongue and submental region	Intense focus of tracer uptake at base tongue  No uptake in neck
CECT	Hyperintense mass at base tongue	Hyperintense mass at base tongue		Hyperintense mass at base tongue and cystic lesion in the neck	Hyperintense mass at base tongue	Hyperintense mass at base tongue and sublingual region	Hyperintense mass at base tongue	Hyperintense mass at base tongue and submental region	Hyperintense mass at base tongue and cystic lesion in the neck
Hormonal status	Euthyroid	Euthyroid		Euthyroid	Hypothyroid	Hypothyroid	Hypothyroid	Hypothyroid	Euthyroid
Orthotopic thyroid	Absent	Absent		Absent	Absent	Absent	Absent	Absent	Absent
Presence of other ectopics	No	No		Yes, thyroglossal cyst at subhyoid level	No	Yes, sublingual region	No	Yes, submental region	Yes, thyroglossal cyst at subhyoid level
Treatment received	Reassurance and regular follow up	Reassurance and regular follow up		Excision of thyroglossal cyst (Sistrunk surgery),no intervension for lingual thyroid	coblation assisted peroral excision of lingual thyroid plus HRP(thyroxin)	HRP(thyroxine)	I131 Ablation with HRP(thyroxin)	Transcervical excision of submental swelling but no intervensionfor lingual thyroid plus HRP	Excision of thyroglossal cyst (Sistrunk surgery),no intervension for lingual thyroid
Follow up	5 years	4.5 years		3.8 years	3 years	4 years	3.8 years	2.8 years	3 years
Outcome	Asymptomatic	Asymptomatic		Asymptomatic	Hypothyroidism worsened after urgery and on HRP without any recurrence of symptoms	On HRP without any recurrence of symptoms	On HRP without any recurrence of symptoms	On HRP without any recurrence of symptoms	Asymptomatic

Fig. 1.

Patient no.4 (a), (b). Computed tomographic (CT) axial section and sagittal CT reconstruction showing lingual thyroid. (c) Tc99-scan (anterior-view) showing dense uptake at tongue base and no uptake in neck. (SSN-suprasternal-notch). (d) surgically excised lingual thyroid

Fig. 2.

Patient no.5 (a) Endoscopic view of lingual thyroid (b). Photograph showing sub-mental swelling caused by sublingual-thyroid. (c), (d). Computed-tomographic (CT): sagittal CT reconstruction and axial section showing dual ectopics;lingual thyroid dual(blue-arrow)and and sublingual thyroid(green-arrow)

Table 2.

Difference between ETT in children and adult

Parameter	Child	Adult
Mean age range	8years, 6–11 years	28.7years 18–43 years
Gender	All were female	Three were female and one was male
Symptoms	All cases were asymptomatic for LT	One case (25%) had obstructive symptoms with hemorrhage
Hormonal Status	All were euthyroid	All were hypothyroid
Presence of second ectopic/anomaly of thyroid	Present in two cases(50%) in form of thyroglossal duct cyst and presented as midline neck swelling	Present in two cases(50%) in form of sublingual thyroid and submental thyroid and presented as submental/submandibular swelling
Treatment received
(i). For lingual thyroid	Required no surgical intervention for LT in all cases	One patient (25%) required trans-oral coblation assisted excision of LT
(ii). For second anomaly	Sistrunk surgery in 2 cases	Excision of submental thyroid in one cases

Those two- cases with symptomatic LT were managed by coblation assisted excision of LT in one and I¹³¹ ablation in one-case. A single dose of 15 mCi of I¹³¹ was administered after withdrawal of levothyroxine. There were no post-therapy complication and patient had resolution of obstructive symptoms. Three patients required surgery for STA; Sistrunk surgery in two and excision of submental thyroid in one. The cases were followed up regularly with clinical examination, FOL examination and serial serum TSH estimation. The mean follow up period was 3.17 years (range: 2.8yeras to 5 years). All cases were asymptomatic at last follow up. These results were utilized to suggest a management algorithm for LT with STA.

Discussion

Epidemiology

Ectopic thyroid is a rare entity. Ectopic thyroid tissue may be present at the tongue base in 10% of the population but only 0.01% of these cases present with obstructive symptoms [15]. LT is predominately (82.7–100%) found in female [11, 16]. In our series, seven out of 8(87.5%) patients were female. The reported mean presenting age is 40.5 years. Ectopic thyroid tissue has a bimodal age distribution with peaks occurring at 12.5 and 50 years corresponded to the hormonal stresses of puberty and menopause, respectively [11]. In our series, the overall mean presenting age was 18.1 years, and the mean age for pediatric cases was 8 years and adult cases was 28.7 years.

Aetiology

The exact aetio-pathogenesis of LT is not clear but genetic alteration in the genes encoding the transcription factors TTF-1, TTF-2, and PAX-8 has been proposed to contribute to the abnormal thyroid morphogenesis and differentiation [17].The whole of the gland may be present at base of tongue (BOT) or part of it present at BOT. The other part may migrate incompletely presenting at sublingual, submental and perihyoid location. Ectopic thyroid tissue has been found anywhere along the line of the obliterated thyroglossal duct,usually from tongue to the diaphragm [18]. Ectopic thyroids may be classified as lingual (at base of tongue), sublingual, prelaryngeal and mediastinal [19]. The base of tongue is the most common site and accounts for 90% of ectopic thyroid cases [20]. The orthotopic thyroid gland in pretracheal region may be absent and the ectopic thyroid tissue is the only functional tissue in 96.5–100% of cases [11, 16]. We also report similar prevalence (100%) as reported literature.

Associated Second Thyroid Ectopic/Anomaly along with LT

In our series, four (50%) cases had second ectopic thyroid tissue in addition to LT. The second ectopic thyroids were thyroglossal cyst in two cases, sublingual thyroid in one case and submental thyroid in one case. Two of these four patients were hypothyroid and all were symptomatic for second ectopic and presented as neck swelling. Three cases of simultaneous occurrence of thyroglossal duct cyst and lingual thyroid in the absence of an orthotopic thyroid gland has been reported in literature [3–5]. Here,we report another two cases of concurrent LT and thyroglossal duct cyst without orthotopic thyroid gland. Jain et al [21] reported four cases of dual ectopia, ectopic thyroid tissue was found in the sublingual location in all the cases, with second ectopic tissue being found in the suprahyoid orsubhyoid locations.

Clinical Presentation

Most of the LT cases are asymptomatic and usually detected incidentally during routine oropharyngeal examination for upper respiratory infections, during tonsillectomy or while undergoing endoscopy for other upper areodigestive lesions [16]. The diagnosis of LT was incidental in 31% (9/29) of patient in a case series reported by Leon et al. [16].

Few of them may present with obstructive symptoms like dysphagia, dyspnea, dysphonia, and obstructive sleep apnea and recurrent bleeding [11, 16, 22]. The obstructive symptoms are more common in the adult patients with TL [11]. In a case series of LT in adult reported by Dziegielewski et al. [11], 80% of their patients were symptomatic. In our series only one adult patient was having obstructive symptoms because of LT. This may be explained by the fact that as age of the person increases, the demand for thyroid hormone increases [11]. The LT tries to compensate to that by undergoing enlargement. This happens more during physiologic stress such as puberty and pregnancy.

Most patients with sublingual thyroid or thyroglossal cyst presented with a neck swelling. Occasionally Ectopic thyroid was detected during evaluation for short stature. The reported incidence of hypothyroidism in TL is between 72–100% [11, 16]. In the present study, 50% of patients had overt hypothyroidism. The incidence of hypothyroidism is more common in adult LT in comparison to pediatrics LT because during physiologic changes such as puberty, menses or pregnancy, the demand for thyroid hormone increases [11]. In our study all adult cases had hypothyroidism.

The pathophysiology of hypothyroidism in ectopic thyroid is explained by inadequate blood supply to support normal thyroid function [23]. Genetic factors leading to abnormal function and morphology may also contribute to hypothyroidism in these patients.

Diagnostic Work up and Imaging Studies

Lingual thyroids are not easily visible transorally and require endoscopic (FOL) examination. The other ectopic may detected during a routine neck examination. Further work up includes thyroid function test i.e., serum level of TSH, FT4, FT3 and thyroid scintigraphy to determine gland function.

Radionuclide thyroid imaging using technetium Tc 99 m pertechnetate helps to locate both orthotopic and ectopic thyroid tissue. Technetium Tc 99 m pertechnetate is now preferred to iodine 131 because it is not organified in the thyroid and it reduces exposure to radiation as the radionuclide image can be rapidly obtained [24]. Nuclear scan not only localizes the thyroid tissue but also gives idea about functionality of that thyroid tissue. Contrast enhanced CT of the neck provides information regarding the size and extent of LT and also confirms the presence of second or third ectopic thyroid tissue in the neck. FNAC of the ectopic thyroid is rarely required whenever presence malignancy is suspected.

Base of tongue is the most common site for ectopic thyroid tissue. In an earlier study done by Noyek et al [20] reported that this location accounted for approximately 90% of ectopic thyroid cases (4 of 4). But Rajuet al [22] in recent study reported a much lower incidence of LT (47%) original 04. The most common site for ectopic thyroid was sublingual location (53%) in their series original [22]. The common second ectopic thyroid tissue associated with LT is sulingual, suprahyoid or subhyoid thyroid tissue [21]. In our study, all cases had LT with sublingual thyroid in one case, submental thyroid in one case and thyrglossal cyst in two cases.

The most common developmental disorder of the thyroid is thyroglossal cyst [21]. The common presenting symptom was a painless midline neck swelling. The thyroid scan usually reveals no functioning thyroid tissue in the cyst and a normal thyroid gland. But simultaneous occurrence of a thyroglossal duct cyst and a lingual thyroid in the absence of an orthotopic thyroid gland is extremely rare and only three cases were reported in English literature [3–5]. Here we report two cases of concurrent lingual thyroid and thyroglossal duct cyst without orthotopic thyroid gland. The LT was the only functioning thyroid in these two cases. These two cases presented with midline neck swelling and were asymptomatic for LT.

Previous reports have shown that lingual thyroid may be the only functioning thyroid tissue in 70–81% of cases [22, 25]. In our series, the ectopic thyroid(s) was the only functioning thyroid tissue in all patients. As many as 70–100 percent of patient with LT may not have orthotopic thyroid gland in neck [22], [25]. In this study the normal thyroid was absent in all cases.

Treatment

The management of LT is controversial. The treatment options for LT include clinical surveillance, levoxine suppressive therapy, surgery and radioactive iodine ablation. The treatment plan must be individualized depending upon the size of the ectopic thyroid, the functional status of the thyroid, and the presence of compressive/obstructive symptoms [26]. Leon et al [16] and Dziegielewski et al [11] individually has recommended management algorithm for LT depending on hormonal status of the patient and presence of symptoms specific to LT.

(i) Clinical surveillance: observation and regular follow up with serial endoscopy and TSH level monitoring is the most appropriate approach in asymptomatic euthyroid patients in whom LT was detected incidentally [26].In our series 4 cases were asymptomatic and euthyroid and were followed up regularly.

(ii) levoxine suppressive therapy: levothyroxine treatment is recommended for patients with hypothyroidism [11, 16]. 65–86% LT can be treated medically [16, 22]. Even in euthyroid patients, levothyroxine is helpful in reducing the obstructive symptoms by decreasing size of the ectopic thyroid. Levothyroxine treatment has been recommended irrespective of thyroid functional status [11, 16, 27] in patients with mild obstructive symptoms. In our study, approximately 50% of patients were treated with levothyroxine.

(iii) Surgery: 14–21% of LT may require surgery [11, 16, 28]. Surgery is recommended for patients with a large LT causing obstructive symptoms such as dyspnea, swallowing difficulty, dysphonia, and bleeding or for patients with histologically proven malignancy. Leon et al [16] recommends total excision LT while Dziegielewski et al [11] recommends trans-oral subtotal excision of LT using CO2 laser or electro-cautery to maintain the contour and bulk of the tongue base. Contour and bulk of the tongue base is of paramount in retaining swallowing function. If the only functioning LT was excised, then all patients require thyroxine supplementation postoperatively. The excised ectopic thyroid may be transplanted in anterior rectus sheath, under the strap muscles as a therapeutic measure to avoid postoperative thyroxine supplementation [25, 29].

The earlier Surgical approches for the treatment of LT include tongue-splitting for trans-oral excision [30], preoral approach via a mandibular midline osteotomy [31], suprahyoid pharyngotomy [31], [combined approach (Transoral and Transcervical approach) [32]. All of these approaches violates the anatomy of neck, tonue and mandible and need tracheotomy and intensive care for airway. The complications of external approach include injury of the lingual nerve, fistula formation, deep cervical infection, and visible scar. The external approaches gives good visualization for excision of larger and more posteriorly located LT and bleeding can be better controlled by these approaches.

New minimally invasive procedures, such as transoral ultrasonic resection, transoral laser microsurgery, radiofrequency ablation, coblation assisted excision and transoral robotic surgery, are being introduced to treat symptomatic patients [29, 33–37]. One of our patient with symptomatic LT with hypothyroidism did not responded to levothyroxine therapy and she underwent coblation assisted excision of LT by transoral. The advantage of this approach is no need for external incision and tracheotomy. Limited exposure is the main disadvantage of this approach [37].

(iv) Radioactive iodine ablation: ablative Radioactive iodine I131 therapy is an alternative approach for patients with symptomatic LT who are deemed unfit for surgery or who refused surgery or had recurrent disease after its excision [25, 38]. One patient was treated with radioactive iodine for LT in our series.

Management of Second Thyroid Anomaly Associated with LT

The management of second ectopic thyroid tissue or second thyroid developmental anomalies associated with LT is not standardized owing to rarity of the disease. The reported common second thyroid developmental anomalies associated with LT are ectopic thyroid tissue located at sublingual location or in the neck and thyroglossal cyst. In our series, Four (50%) cases had second ectopic thyroid tissue (thyroglossal duct cyst in two cases, sublingual thyroid in one case and submental swelling in one case) with asymptomatic LT. All of them were symptomatic for neck swelling and three underwent surgery (Sistrunk operation in two cases and transcervical excision of sub-mental swelling in one case). We propose a management algorithim for management of second thyroid anomaly associated with LT based on our experience and review of literature (Fig. 3a–c). The treatment of second anomaly should be planned with inclusion of LT, not in isolation. The treatment of dual ectopics/anomalies depends on the symptoms caused by the neck and tongue masses as well as thyroid hormonal status and general physical condition of the patient. In our cases neck masses were excised to alleviate the concerns of the patient and for cosmetic purpose and the LT were left behind because of the absence of symptoms and to preserve the source of intrinsic thyroid hormone. Asymptomatic second anomaly does not require any active intervention except regular follow. Levothyroxine should be tried in patients with hypothyroidism or with mild symptoms (small cosmetically acceptable neck swelling). Large cosmetically unacceptable neck swelling, suspicion of malignancy and repeated infection are the indication for surgery. Radio-active iodine I131 may be tried in symptomatic patient containing iodine avid ectopic thyroid tissue who denied surgery or are unfit for surgery.

Fig. 3.

Management algorithm for (a). Asymptomatic dual thyroid-anomalies. (b) Patient with dual thyroid-anomalies but symptomatic only for lingual-thyroid. (c) Patient with dual thyroid-anomalies but symptomatic only for second thyroid ectopic/anomaly

Conclusion

Most of LT thyroids are asymptomatic. The children with ectopic thyroid tissue were euthyroid whereas the adults with ectopic thyroids were hypothyroid.LT in are usually asymptomatic in pediatric age.

LT patients with STA are more symptomatic and required more surgical interventions in compare to isolated LT. When appropriate, excision of STA with/without intervention for LT and thyroxin is advocated as the treatment modality of choice in LT patients with STA.

Funding

None.

Declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

The study was approved by our institutional ethics committee.

Informed Consent

Informed consent was obtained from all individual participants included in the study for publication of the data in journals. All author met the criteria for authorship as per ICMJE. The manuscript has been read and approved by all authors for publication.