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 fails 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 pathophysiology of ectopic thyroid gland and highlights the role of the interprofessional team in its management.

Objectives:

• Describe the locations of an ectopic thyroid gland.
• Recall the presentation of a patient with an ectopic thyroid gland.
• Summarize the treatment options for ectopic thyroid.
• Explore 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 two lateral anlages which contain c-cells, solid nests cells and portions of the lateral thyroid.[1]  Failure of the thyroid fails to descend from the thyroid anlage region to its final location in front of the trachea is called an ectopic thyroid. Ectopic thyroid can present at any position 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 to be due to ectopic lingual thyroid.[3] The ectopic thyroid is classified under the category of congenital hypothyroidism, and it is one of the top causes of thyroid dysgenesis.[4]

Etiology

The majority of the causes are multifactorial associated with the embryological process, and recently the 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 be contributing 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 one case for every 100000 to 300000 of healthy individuals, but it reportedly occurs in one 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, but some cases are delayed up to the fourth through the sixth decade when the ectopic thyroid tissue transforms to 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 the 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 to know 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:

• In the head and neck: the trachea, submandibular, lateral cervical regions, palatine tonsils, carotid bifurcation, iris of the eye 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, muscle weakness) are present in 70% of all reported cases.[11][12] Hyperthyroidism is a very 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 for identifying 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 diagnosing of the ectopic thyroid - the majority of the cases will 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 (FNAC) should be performed

Treatment / Management

The quick identification of congenital hypothyroidism and further preventing unwanted intellectual disability by early starting appropriate treatment is paramount.[16] Life long thyroxin replacement therapy and regular follow-up are an optimum choice 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

• 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 with an interprofessional team that includes an endocrinologist, ENT surgeon, 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 will need life long thyroid hormone supplementation.[24] (Level V)