Continuing Education Activity

The thyroid gland is the first endocrine gland that develops during fetal embryology, which starts between the third and fourth gestational weeks. The primary origin of the thyroid gland is the endoderm, which gives rise to the median (the significant portion of each lateral lobe, isthmus, and thyroglossal duct with pyramidal lobe), and the two lateral anlages which contain c-cells, solid nests cells, and portions of the lateral thyroid. Failure of the thyroid to descend from the thyroid anlage region to its final location in front of the trachea is called an ectopic thyroid. This activity reviews the ectopic thyroid gland's pathophysiology and highlights the interprofessional team's role in its management.

Objectives:

• Identify the locations of an ectopic thyroid gland.
• Assess the presentation of a patient with an ectopic thyroid gland.
• Evaluate the treatment options for ectopic thyroid.
• Communicate strategies to optimize care coordination among interprofessional team members to improve outcomes for patients affected by ectopic thyroid.

Introduction

The thyroid gland is the first endocrine gland that develops during fetal embryology, which starts between the third and fourth gestational weeks. The primary origin of the thyroid gland is the endoderm, which gives rise to the median (the significant portion of each lateral lobe, isthmus, and thyroglossal duct with pyramidal lobe), and the 2 lateral anlages, which contain c-cells, solid nest cells, and portions of the lateral thyroid.[1]  Failure of the thyroid to descend from the thyroid anlage region to its final location in front of the trachea is called an ectopic thyroid (see Image. Ectopic Thyroid). Ectopic thyroid can present anywhere from the foramen caecum at the base of the tongue to the mediastinum.[2] Dr. Hickman described the first ectopic thyroid in a newborn who died after 16 hours of life due to severe respiratory distress and suffocation. Eventually, the cause turned out to be due to ectopic lingual thyroid.[3] The ectopic thyroid is classified under the category of congenital hypothyroidism, and it is 1 of the top causes of thyroid dysgenesis.[4]

Etiology

Most of the causes are multifactorial and associated with the embryological process. Recently, genetic research has demonstrated that the gene transcription factors TITF-1(Nkx2-1), Foxe1(TITF-2), and PAX-8 are essential for thyroid maturation and differentiation. Mutation in these genes may share a connection with abnormal migration of the thyroid.[4] The category of the genes listed below may contribute to the process of ectopic as well as the unusual morphology of the thyroid.[5][6]

• Thyroid ectopy: Genes:  1- NKX2-5 (Ectopy, no cardiac alterations) 2- FOXE1 (Bamforth-Lazarus syndrome)
• Thyroid hypoplasia: Genes: 1- NKX2-1 (Choreoathetosis, hypothyroidism, and pulmonary alterations) 2- TSHR (Resistance to TSH)  3- PAX8 (Hypothyroidism)
• Athyreosis: Genes: 1- FOXE1 (Bamforth-Lazarus syndrome)2- NKX2-5 (Athyreosis, no cardiac alterations)  3- PAX8 (Hypothyroidism)

Epidemiology

The prevalence of ectopic thyroid gland is 1 case for every 100000 to 300000 healthy individuals, but it reportedly occurs in 1 of 4000 to 8000 patients who have thyroid disease.[7] The ectopic thyroid can present at any age, with most cases identified during the neonatal period through newborn screening. Still, some cases are delayed up to the fourth through the sixth decade when the ectopic thyroid tissue transforms into abnormal tissue pathology and presents with symptomatic manifestations. In other cases, the ectopic thyroid gland enlarges during periods of stress and is then identified during imaging. Both males and females are equally affected.

Pathophysiology

The most common thyroid location in ectopic cases is the Lingual thyroid. Incomplete migration can lead to a high cervical thyroid, and excessive movement can lead to a superior mediastinal or even paracardiac location. Studies have shown that more than 70% of lingual thyroid cases correlate with the absence of normal cervical thyroid.[8] This percentage is significant because not all cases are single ectopic thyroid tissue. Studies are reporting cases of dual and triple ectopic thyroids.[9][10] The other possible locations of ectopic thyroid are:

• The head and neck include the trachea, submandibular and lateral cervical regions, palatine tonsils, carotid bifurcation, eye iris, and pituitary gland.
• Axilla
• Heart and ascending aorta
• Lymphoid tissue: thymus
• Gastrointestinal system: esophagus, duodenum, gallbladder, stomach bed, pancreas, mesentery of the small intestine, porta hepatis
• Adrenal gland
• Reproductive system: ovary, fallopian tube, uterus, and vagina

History and Physical

Ectopic lingual thyroid is usually asymptomatic (47%) but may lead to some of the local symptoms, such as dysphagia, dysphonia with stomatolalia, and upper airway obstruction.[4] Other clinical manifestations of definitive clinical hypothyroidism (like fatigue, cold intolerance, constipation, dry skin, weight gain, puffy face, hoarseness, and muscle weakness) are present in 70% of all reported cases.[11][12] Hyperthyroidism is a rare association with lingual thyroid, with few cases reported.[13] The local neck examination is essential to rule out other neck masses. The physical examination of the thyroid is not sensitive enough to identify the cause of congenital hypothyroidism; the ectopic thyroid could be missed during physical examination even by expert endocrinologists.

Evaluation

Newborn screening is the recommendation since many studies suggest that "almost all individuals with ectopic thyroid are hypothyroid." Thus, a biochemical thyroid profile may be necessary at birth. Many centers are now routinely obtaining a thyroid profile in all newborns[14][15][4]

• Serial thyroid function tests (TSH, T3, total T4, free T4, and thyroglobulin are mandatory in the screening and diagnosis of the ectopic thyroid - the majority of the cases provide evidence of hypothyroidism, while some patients may be euthyroid
• The etiological diagnosis is established by thyroid scintigraphy
• MRI and CT scan also can be used as modalities to determine the exact location of ectopic thyroid
• High-resolution ultrasound scanning could help as an initial assessment, especially in patients presenting with neck masses
• If the case is highly suspicious for malignancy, then tissue biopsy for histology or fine needle aspiration cytology should be performed

Treatment / Management

The quick identification of congenital hypothyroidism and further prevention of unwanted intellectual disability by early starting appropriate treatment is paramount.[16] Life-long thyroxin replacement therapy and regular follow-up are optimal for such patients.[17][18] The indications for surgical removal of the ectopic thyroid include the following: malignancy, bleeding or ulceration of the gland, uncontrolled hyperthyroidism, and severe local/respiratory symptoms. Some lingual thyroids are visible in the neck, and females prefer surgical removal for cosmetic reasons.[15][19][20][21]

Differential Diagnosis

The differential diagnosis for ectopic thyroid include the following:

• Thyroglossal cyst

The differentiation between the lingual ectopic thyroid and thyroglossal duct cyst is by performing thyroid scintigraphy; usually, thyroglossal duct cysts remain unidentified because they do not typically contain sufficient functioning thyroid tissue.[22]

• Other neck masses are included in the differential diagnosis of ectopic thyroid

Complications

Fortunately, the studies have estimated the risk of developing malignancy from ectopic tissue is less than 1%.[23] Benign neoplasms and thyroiditis are also infrequent complications. If the patient is symptomatic and kept without treatment, they are more likely to develop complications of hypothyroidism.

Consultations

For any child who is experiencing frequent high TSH with normal other thyroid function with or without symptoms, especially respiratory or dysphagia symptoms, always consider ectopic thyroid and consult the endocrinologist to evaluate the case.

Pearls and Other Issues

Bringing attention to ectopic thyroid is extremely important because it may be the only thyroid tissue or may be causing upper airway symptoms. Also, one should always consider malignancy.

Enhancing Healthcare Team Outcomes

The management of an ectopic thyroid is done by an interprofessional team that includes an endocrinologist, an ENT surgeon, a pediatric surgeon, and a pediatrician. It is crucial to rule out the presence of other functioning thyroid tissue before considering surgical removal. For most patients, removal of the ectopic thyroid tissue has little morbidity, but if it is the only thyroid tissue, the patient needs lifelong thyroid hormone supplementation.[24]

Review Questions

• Access free multiple choice questions on this topic.
• Click here for a simplified version.
• Comment on this article.

References

1.

Johansson E, Andersson L, Örnros J, Carlsson T, Ingeson-Carlsson C, Liang S, Dahlberg J, Jansson S, Parrillo L, Zoppoli P, Barila GO, Altschuler DL, Padula D, Lickert H, Fagman H, Nilsson M. Revising the embryonic origin of thyroid C cells in mice and humans. Development. 2015 Oct 15;142(20):3519-28. [PMC free article: PMC4631767] [PubMed: 26395490]

2.

Siddique M, Bashir H. 99mTc Sodium Pertechnetate Uptake in Ectopic Mediastinal Thyroid Tissue on Hybrid Thyroid Scintigraphy. Clin Nucl Med. 2018 Nov;43(11):820-822. [PubMed: 30015662]

3.

Kumar Choudhury B, Kaimal Saikia U, Sarma D, Saikia M, Dutta Choudhury S, Barua S, Dewri S. Dual ectopic thyroid with normally located thyroid: a case report. J Thyroid Res. 2011;2011:159703. [PMC free article: PMC3134180] [PubMed: 21765986]

4.

Ibrahim NA, Fadeyibi IO. Ectopic thyroid: etiology, pathology and management. Hormones (Athens). 2011 Oct-Dec;10(4):261-9. [PubMed: 22281882]

5.

Nettore IC, Cacace V, De Fusco C, Colao A, Macchia PE. The molecular causes of thyroid dysgenesis: a systematic review. J Endocrinol Invest. 2013 Sep;36(8):654-64. [PubMed: 23698639]

6.

Abu-Khudir R, Paquette J, Lefort A, Libert F, Chanoine JP, Vassart G, Deladoëy J. Transcriptome, methylome and genomic variations analysis of ectopic thyroid glands. PLoS One. 2010 Oct 15;5(10):e13420. [PMC free article: PMC2955549] [PubMed: 20976176]

7.

Kim MS, Kong YH, Lee DY. A Case of Subclinical Hypothyroidism with Lingual and Right Pretracheal Ectopic Thyroid. J Clin Res Pediatr Endocrinol. 2015 Jun;7(2):148-50. [PMC free article: PMC4563188] [PubMed: 26316439]

8.

Fisher DA, Klein AH. Thyroid development and disorders of thyroid function in the newborn. N Engl J Med. 1981 Mar 19;304(12):702-12. [PubMed: 6258072]

9.

Passah A, Arora S, Damle NA, Sharma R. Triple Ectopic Thyroid on Pertechnetate Scintigraphy. Indian J Endocrinol Metab. 2018 Sep-Oct;22(5):712-713. [PMC free article: PMC6166550] [PubMed: 30294586]

10.

Matta-Coelho C, Donato S, Carvalho M, Vilar H. Dual ectopic thyroid gland. BMJ Case Rep. 2018 Oct 02;2018 [PMC free article: PMC6169627] [PubMed: 30279251]

11.

Amani Mel A, Benabadji N, Benzian Z, Amani S. Ectopic lingual thyroid. Indian J Nucl Med. 2012 Apr;27(2):124-6. [PMC free article: PMC3665141] [PubMed: 23723588]

12.

Singhal P, Sharma KR, Singhal A. Lingual thyroid in children. J Indian Soc Pedod Prev Dent. 2011 Jul-Sep;29(3):270-2. [PubMed: 21985888]

13.

Abdallah-Matta MP, Dubarry PH, Pessey JJ, Caron P. Lingual thyroid and hyperthyroidism: a new case and review of the literature. J Endocrinol Invest. 2002 Mar;25(3):264-7. [PubMed: 11936471]

14.

Jaruratanasirikul S, Piriyaphan J, Saengkaew T, Janjindamai W, Sriplung H. The etiologies and incidences of congenital hypothyroidism before and after neonatal TSH screening program implementation: a study in southern Thailand. J Pediatr Endocrinol Metab. 2018 Jun 27;31(6):609-617. [PubMed: 29750647]

15.

Elprana D, Manni JJ, Smals AG. Lingual thyroid. Case report and review of the literature. ORL J Otorhinolaryngol Relat Spec. 1984;46(3):147-52. [PubMed: 6728436]

16.

Agrawal P, Philip R, Saran S, Gutch M, Razi MS, Agroiya P, Gupta K. Congenital hypothyroidism. Indian J Endocrinol Metab. 2015 Mar-Apr;19(2):221-7. [PMC free article: PMC4319261] [PubMed: 25729683]

17.

Touati G, Léger J, Toublanc JE, Farriaux JP, Stuckens C, Ponte C, David M, Rochiccioli P, Porquet D, Czernichow P. A thyroxine dosage of 8 micrograms/kg per day is appropriate for the initial treatment of the majority of infants with congenital hypothyroidism. Eur J Pediatr. 1997 Feb;156(2):94-8. [PubMed: 9039509]

18.

Turri-Zanoni M, Battaglia P, Castelnuovo P. Thyroglossal Duct Cyst at the Base of Tongue: The Emerging Role of Transoral Endoscopic-Assisted Surgery. J Craniofac Surg. 2018 Mar;29(2):469-470. [PubMed: 29023300]

19.

Naik K. Redefining anatomy in a case of midline subhyoid ectopic thyroid. Indian J Surg. 2014 Aug;76(4):333-5. [PMC free article: PMC4175677] [PubMed: 25278663]

20.

Jakibchuk K, Ali S, Samantray J. Recurrence of Graves' disease in ectopic thyroid tissue. BMJ Case Rep. 2018 Jan 23;2018 [PMC free article: PMC5786967] [PubMed: 29367360]

21.

Sturniolo G, Vermiglio F, Moleti M. Thyroid cancer in lingual thyroid and thyroglossal duct cyst. Endocrinol Diabetes Nutr. 2017 Jan;64(1):40-43. [PubMed: 27825535]

22.

Lianos G, Bali C, Tatsis V, Anastasiadi Z, Lianou E, Papathanasiou V, Messinis T. Ectopic thyroid carcinoma. Case report. G Chir. 2013 Apr;34(4):114-6. [PMC free article: PMC3915575] [PubMed: 23660162]

23.

Leung AKC, Leung AAC. Evaluation and management of the child with hypothyroidism. World J Pediatr. 2019 Apr;15(2):124-134. [PubMed: 30734891]

Disclosure: Sami Alanazi declares no relevant financial relationships with ineligible companies.

Disclosure: Faten Limaiem declares no relevant financial relationships with ineligible companies.