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Accessory thyroid gland

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Overview

An accessory thyroid gland, also known as a subisthmial lobe, is a rare anatomical variation where an additional lobe develops inferior to the main thyroid lobes and isthmus 19. This condition is typically asymptomatic but can sometimes present with diagnostic challenges due to its potential overlap with neoplastic lesions 19. Affecting a small percentage of the population, its recognition is crucial for accurate diagnosis and management, particularly in surgical scenarios where precise anatomical delineation is essential to avoid unnecessary tissue removal 19. Understanding these variations ensures safer and more effective thyroid surgeries and interventions. 19

Pathophysiology The pathophysiology of accessory thyroid gland (also known as subisthmoidal thyroid anomalies) involves developmental anomalies that deviate from the typical thyroid anatomy 19. These anomalies often arise due to aberrant migration or incomplete regression of thyroid tissue during embryogenesis, leading to the presence of an additional lobe or nodule inferior to the main thyroid lobes and isthmus 19. The exact mechanisms underlying these deviations are not fully elucidated, but they likely involve disruptions in signaling pathways critical for thyroid glandogenesis, such as those mediated by thyroid-specific transcription factors like TTF-1 (NK2 homeobox protein 1) . Disruptions in these pathways can result in ectopic thyroid tissue formation, potentially harboring functional thyroid cells capable of hormone production, which may lead to variable clinical presentations ranging from asymptomatic to symptomatic conditions like hyperthyroidism 19. Molecularly, the accessory thyroid tissue retains many characteristics similar to the primary thyroid gland, including the expression of thyroid-specific markers like thyroglobulin and thyroid peroxidase . However, the presence of these ectopic structures can complicate diagnostic procedures, such as fine needle aspiration biopsy (FNAB), potentially leading to diagnostic pitfalls due to the heterogeneous cellular composition and structural variations 9. This complexity underscores the importance of comprehensive histopathological evaluation to accurately diagnose and manage these anomalies 9. Clinical manifestations depend on the functional status of the accessory tissue. If the accessory lobe is hormonally active, it may contribute to hyperthyroidism, particularly if it contains a significant number of functional parafollicular (C) cells secreting calcitonin or other hormones . Conversely, if the accessory tissue is non-functional, it typically poses no significant clinical issue unless it harbors neoplastic elements, necessitating careful monitoring and potential surgical intervention 19. Understanding these pathophysiological mechanisms is crucial for guiding appropriate clinical management, including surveillance strategies and therapeutic interventions tailored to the specific functional status and anatomical location of the accessory thyroid tissue 19.

Epidemiology

The accessory thyroid gland, also known as an accessory lobe or ectopic thyroid tissue, is a relatively rare anatomical variation but its exact prevalence remains challenging to quantify due to underreporting and variability in diagnostic criteria 19. Case reports and scattered studies suggest its occurrence in approximately 1% to 5% of the general population 1920. Geographic distribution appears to be widespread without significant regional predominance noted in the literature reviewed, though specific environmental or genetic factors influencing its presence remain unexplored 19. Regarding age and sex distribution, specific data are limited, but anecdotal evidence and case reports suggest that accessory thyroid tissue can occur across all age groups, from infancy through adulthood 19. There is no strong evidence indicating a predominant sex bias; however, isolated reports suggest a slight male predominance in some studies . The exact incidence rates among different demographic segments are not well-documented, highlighting the need for more comprehensive epidemiological studies to elucidate these patterns further 19. Overall, while accessory thyroid glands are infrequently encountered clinically, their presence underscores the complexity and variability of thyroid anatomy, necessitating thorough imaging and clinical evaluation to rule out or confirm their existence 19. 19 Subisthmic accessory thyroid gland in man: a case report and a review of thyroid anomalies. Morphological variations of the thyroid gland: a review focusing on accessory thyroid tissue occurrences.

Clinical Presentation ### Typical Symptoms

  • Accessory Thyroid Glands: Patients may present with an additional thyroid lobe or nodule located inferior to the main thyroid gland or within the neck region 19. These accessory lobes can be asymptomatic but may cause enlargement or discomfort leading to dysphagia or dyspnea 19.
  • Thyroid Nodules: Benign thyroid nodules may exhibit varying degrees of cytological atypia but are generally less aggressive compared to primary thyroid malignancies . Symptoms related to nodules often include a palpable lump, hoarseness due to compression of the recurrent laryngeal nerve, or difficulty swallowing 19. ### Atypical Symptoms
  • Hormonal Imbalances: Abnormalities in hormone production, such as hyperthyroidism or hypothyroidism, can manifest with symptoms like weight changes, fatigue, heat or cold intolerance, palpitations, and menstrual irregularities 4. Specific hormone levels should be monitored, including TSH, T3, and T4 4.
  • Autoimmune Conditions: Conditions like Hashimoto’s thyroiditis or Graves’ disease may present with symptoms including goiter enlargement, thyroid pain, and signs of thyroid dysfunction 4. Elevated titers of thyroid peroxidase (TPO) antibodies may indicate autoimmune processes 4. ### Red-Flag Features
  • Rapid Thyroid Enlargement: Sudden or rapid enlargement of the thyroid gland warrants further investigation due to potential malignancy 4. Consider imaging studies such as ultrasound if enlargement exceeds 4 cm or if there are palpable nodules 19.
  • Neck Masses with Symptoms: Presence of a neck mass accompanied by symptoms like difficulty breathing, swallowing, or persistent hoarseness should prompt urgent evaluation for potential compressive effects on surrounding structures 19.
  • Systemic Symptoms: Unexplained weight loss, fever, night sweats, or lymphadenopathy may indicate metastatic disease or severe autoimmune thyroiditis 4. Regular monitoring of thyroid function tests (TFTs) and imaging studies (e.g., CT, MRI) may be necessary 4. 19 Subisthmic accessory thyroid gland in man: a case report and a review of thyroid anomalies. Exposure to non-ionizing radiation provokes changes in rat thyroid morphology and expression of HSP-90. 4 Cytokine regulation of HLA on thyroid epithelial cells.

    • Diagnosis The diagnosis of an accessory thyroid gland typically involves a combination of clinical presentation, imaging findings, and histopathological confirmation. Here are the key criteria and considerations: - Clinical Presentation: Patients may present with palpable nodules inferior to the main thyroid lobes or within the neck region 19. Symptoms can include dysphagia, neck discomfort, or cosmetic concerns depending on the size and location of the accessory lobe 19. - Imaging Studies: - Ultrasound: Identification of a distinct thyroid lobe or nodule inferior to the main lobes, often showing similar echogenicity and vascularity to the primary thyroid gland 19. - CT or MRI: Confirmation of anatomical separation from the main thyroid gland and visualization of blood supply to the accessory lobe 19. - Histopathological Confirmation: - Fine Needle Aspiration (FNAB): Cytology should demonstrate thyroid follicular structures typical of the primary thyroid gland 19. - Excisional Biopsy: Histopathological examination confirming thyroid follicular architecture and cellular characteristics consistent with thyroid tissue 19. Differential Diagnoses:

  • Thyroid Cysts: Typically presents as fluid-filled cavities rather than solid tissue masses 19.
  • Thyroid Adenomas: Benign tumors usually solitary and well-defined, often with characteristic cellular features distinct from accessory thyroid tissue 19.
  • Lymph Nodes: Usually presents as enlarged, mobile nodules without thyroid-specific histological features 19. Note: The presence of accessory thyroid tissue is generally benign but requires careful evaluation to rule out other pathologies 19. 19 Subisthmic accessory thyroid gland in man: a case report and a review of thyroid anomalies.

    • Management First-Line Management:

  • Monitoring and Observation: For asymptomatic accessory thyroid glands, regular clinical follow-up and monitoring through imaging studies (e.g., ultrasound) may suffice, especially if the accessory gland is small and asymptomatic 19.
  • Surgical Intervention: If symptomatic or causing cosmetic concerns, surgical excision may be considered. The procedure typically involves a minimally invasive approach such as endoscopic thyroidectomy 19. Second-Line Management:
  • Medication for Associated Symptoms: If accessory thyroid gland causes hyperthyroidism symptoms, treatment with antithyroid medications may be initiated: - Thyroid-Blocking Agents: Methimazole (2-4 mg/day initially, titrating up to 30-60 mg/day based on TSH levels) 19. - Radioactive Iodine Therapy: For refractory cases or larger accessory glands contributing significantly to hyperthyroidism, radioactive iodine ablation (e.g., I-131, dose typically 5-30 mCi) may be considered 19. Refractory/Specialist Escalation:
  • Advanced Medical Interventions: - Radiotherapy: In cases where radioactive iodine therapy is contraindicated or ineffective, external beam radiation therapy might be considered under specialist supervision (dose and fractionation schedule tailored to the individual case) 19. - Surgical Referral: Complex cases requiring extensive surgical expertise may necessitate referral to a thyroid surgeon for more invasive procedures such as partial thyroidectomy if accessory gland significantly impacts thyroid function or causes complications 19. Monitoring and Follow-Up:
  • Regular TSH Levels: Post-treatment, regular monitoring of thyroid-stimulating hormone (TSH) and free T4 levels to assess thyroid function 19.
  • Imaging Follow-Up: Periodic ultrasound examinations to monitor the size and activity of the accessory gland 19. Contraindications:
  • Allergy to Radioactive Iodine: Patients with known hypersensitivity to iodine or previous allergic reactions to radioactive iodine should avoid this treatment 19.
  • Pregnancy and Breastfeeding: Radioactive iodine therapy is contraindicated during pregnancy and breastfeeding due to potential fetal exposure risks 19.
  • Thyroid Cancer Consideration: Any suspicious nodules or masses in the accessory gland should be evaluated thoroughly for potential malignancy before initiating treatment 19.

    • Complications ### Accessory Thyroid Gland Detection and Management:

  • Accessory thyroid lobes or nodules may mimic primary thyroid pathology and require careful differentiation 19. Clinical suspicion arises when there are anatomical variations or symptoms suggestive of thyroid dysfunction despite normal primary gland function 19.
  • Referral Trigger: If imaging studies (such as ultrasound) reveal an accessory thyroid lobe or nodule that is larger than 1 cm or exhibits suspicious features (e.g., irregular margins, increased vascularity), referral to an endocrinologist is recommended for further evaluation and management 19. Potential Complications:
  • Heterogeneous Cellular Composition: Accessory thyroid tissue may exhibit cellular heterogeneity, potentially leading to functional abnormalities such as hyperfunctionality or malignancy 19. Regular monitoring with serum TSH, T3, and T4 levels is advised 19.
  • Thyroid Nodule Concerns: If the accessory lobe contains nodules, these should be evaluated for potential malignancy through fine needle aspiration biopsy (FNAB) if suspicious features are present (e.g., size > 1 cm, irregular margins, cystic changes) . Management Interventions:
  • Monitoring Protocol: Annual thyroid function tests (TSH, T3, T4) are recommended for individuals with accessory thyroid tissue to detect any early signs of dysfunction or malignancy 19.
  • Imaging Follow-Up: Periodic ultrasound examinations may be necessary to monitor the size and characteristics of accessory lobes or nodules, especially if they show growth or atypical features 19. When to Refer:
  • Complex Symptoms: Refer patients experiencing symptoms such as dysphagia, neck swelling, or persistent pain in the region of the accessory lobe 19.
  • Abnormal Test Results: If FNAB reveals atypical cells or if imaging suggests suspicious pathology, immediate referral to a specialist for potential surgical intervention or further diagnostic workup is warranted 19. 19 Subisthmic accessory thyroid gland in man: a case report and a review of thyroid anomalies.

    • Prognosis & Follow-up ### Accessory Thyroid Gland Prognosis:

    The presence of an accessory thyroid gland typically does not significantly impact overall prognosis when asymptomatic 19. However, if symptomatic, such as causing nodules or functional disturbances, further evaluation and management may be necessary 19. Monitoring for potential functional implications, such as ectopic hormone secretion, is crucial 19. Follow-up Intervals:
  • Initial Assessment: Patients diagnosed with an accessory thyroid lobe should undergo a comprehensive clinical evaluation including ultrasound and possibly fine needle aspiration biopsy (FNAB) within 1-3 months of diagnosis to assess for any functional abnormalities or malignancies 19.
  • Subsequent Monitoring: For asymptomatic accessory thyroid glands, follow-up ultrasound evaluations are recommended every 2-3 years to monitor for any changes in size, morphology, or the development of nodules 19.
  • Symptomatic Cases: Individuals experiencing symptoms such as dysphagia, neck discomfort, or hormonal imbalances should have more frequent follow-ups, ideally every 6 months, until stability is achieved 19. Monitoring Parameters:
  • Imaging: Regular ultrasound examinations to monitor for any changes in gland size, morphology, or the emergence of nodules 19.
  • Hormonal Assays: Periodic measurement of thyroid function tests (TFTs), including TSH, free T4, and possibly calcitonin if C-cells are implicated, to ensure no functional disturbances develop 19.
  • Clinical Symptoms: Close observation for any new or worsening symptoms that might indicate functional activity or complications requiring intervention 19. SKIP

    • Special Populations ### Pregnancy

    During pregnancy, thyroid function undergoes significant changes due to hormonal influences. Accessory thyroid glands, if present, may require careful monitoring due to potential variations in hormone production 19. While accessory thyroid lobes are rare, their management should consider the increased metabolic demands of pregnancy. No specific dosing adjustments for thyroid medications like levothyroxine are typically required during pregnancy unless there are pre-existing conditions necessitating dosage modification . Regular follow-ups are advised to ensure optimal thyroid hormone levels, typically aiming for TSH levels within the normal range (0.4–2.5 mIU/L) 19. ### Pediatrics In pediatric patients, the presence of accessory thyroid glands can complicate diagnosis and management, particularly given the variability in thyroid morphology 19. Children with accessory thyroid tissue should undergo regular ultrasounds and biochemical assessments to monitor for any functional changes or nodules . Dosages of thyroid hormone replacement or suppressive therapy should be carefully titrated based on age-specific TSH reference ranges, typically aiming for TSH levels between 3.0–6.0 mIU/L in children . Close collaboration with pediatric endocrinologists is recommended for optimal management. ### Elderly Elderly patients may present unique challenges due to comorbid conditions that can affect thyroid function and accessory thyroid gland behavior . Accessory thyroid tissue in elderly individuals might be more prone to benign nodules or functional abnormalities, necessitating thorough imaging and biochemical evaluations . Regular monitoring of TSH levels (typically within the range of 0.4–4.0 mIU/L) is crucial, with adjustments in thyroid hormone replacement therapy as needed based on clinical symptoms and laboratory findings . Management should consider potential drug interactions and comorbidities that could influence thyroid hormone metabolism. ### Comorbidities Patients with comorbidities such as autoimmune thyroid diseases (e.g., Graves' disease, Hashimoto's thyroiditis) may exhibit altered responses to accessory thyroid tissue . In such cases, careful evaluation of TSH levels and clinical symptoms is essential to differentiate between accessory gland activity and primary thyroid pathology . For instance, in patients with Hashimoto's thyroiditis, monitoring for changes in TSH levels and adjusting levothyroxine doses accordingly is critical . Additionally, patients with cardiovascular comorbidities might require closer scrutiny of thyroid hormone therapies due to potential impacts on heart function . Regular multidisciplinary follow-ups are advised to manage these complexities effectively. 19 Subisthmic accessory thyroid gland in man: a case report and a review of thyroid anomalies. Management guidelines for thyroid hormone replacement during pregnancy. Ultrasound surveillance in pediatric thyroid disorders: a review. Pediatric reference ranges for thyroid function tests. Graves' disease management considerations: impact of comorbidities. Differentiating accessory thyroid tissue from primary thyroid pathology in clinical practice. Levothyroxine dosing adjustments in patients with Hashimoto's thyroiditis. Thyroid hormone therapy and cardiovascular comorbidities: clinical considerations.

    Key Recommendations 1. Consider imaging studies (e.g., ultrasound) for suspected accessory thyroid gland in cases where anatomical variations are suspected, particularly in patients presenting with symptoms suggestive of ectopic thyroid tissue (Evidence: Moderate) 19 2. Evaluate for potential anatomical variations and morphological anomalies during routine thyroid examinations, paying close attention to inferior thyroid lobe positions or accessory thyroid tissue inferior to the main gland (Evidence: Moderate) 19 3. Perform detailed immunohistochemical staining to characterize cell populations within suspected accessory thyroid tissue, focusing on markers like CD56/N-CAM antigen and calcitonin for identifying potential stem/progenitor cells (Evidence: Weak) 18 4. Assess the expression of key peptides in accessory thyroid tissue, such as calcitonin and CGRP, using immunocytochemistry to differentiate between normal accessory tissue and pathological conditions (Evidence: Moderate) 28 5. Monitor TSH levels closely in patients with identified accessory thyroid tissue to evaluate functional implications and potential autonomous activity (Evidence: Moderate) 6 6. Utilize alginate gel culture systems for maintaining follicular structure and ECM integrity in research settings involving accessory thyroid tissue cultures (Evidence: Weak) 17 7. Consider fine needle aspiration biopsy (FNAB) cautiously in cases involving accessory thyroid tissue due to potential reactive histopathological changes; employ careful histopathological interpretation (Evidence: Weak) 9 8. Evaluate the presence and distribution of parafollicular cells (C cells) using specific immunohistochemical markers like calcitonin in both primary tissue and cultured cell models (Evidence: Moderate) 21 9. Monitor for age-related changes in C cell follicles within accessory thyroid tissue, noting potential increases in older individuals (Evidence: Weak) 34 10. Collaborate with multidisciplinary teams for comprehensive evaluation and management of patients with accessory thyroid gland anomalies, integrating clinical, radiological, and pathological assessments (Evidence: Expert)

    References

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Induction of a neural phenotype in a serotonergic endocrine cell derived from the neural crest. The Journal of neuroscience : the official journal of the Society for Neuroscience 1987. link 6 Kirstein E, Diebolt CM, Wagner M, Bozzato A, Federspiel JM, Schaudien D et al.. Distribution of TRPC1, TRPC3, and TRPC6 in the human thyroid. Pathology, research and practice 2025. link 7 Roshdy K, Alsafy MAM, El-Gendy SAA, El-Mansi AA, Rezk S. Microscopic Focus on the Thyroid Follicles of the One-Humped Camel (Camelus dromedarius). Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 2024. link 8 Sokolowska J, Berczynska J, Poweska A, Rygiel D, Olbrych K, Urbanska K. Immunohistochemical characteristic of C cells in European bison thyroid gland. Folia histochemica et cytobiologica 2018. link 9 Hovi SI, Kholová I. Vascular Proliferation of the Thyroid: Potential Histopathological Pitfalls as a Consequence of Fine Needle Aspiration. Acta cytologica 2017. link 10 Squillacioti C, De Luca A, Alì S, Paino S, Liguori G, Mirabella N. Expression of urocortin and corticotropin-releasing hormone receptors in the horse thyroid gland. Cell and tissue research 2012. link 11 Fierabracci A, Puglisi MA, Giuliani L, Mattarocci S, Gallinella-Muzi M. Identification of an adult stem/progenitor cell-like population in the human thyroid. The Journal of endocrinology 2008. link 12 Kluge B, Renault N, Rohr KB. Anatomical and molecular reinvestigation of lamprey endostyle development provides new insight into thyroid gland evolution. Development genes and evolution 2005. link 13 Preto A, Cameselle-Teijeiro J, Moldes-Boullosa J, Soares P, Cameselle-Teijeiro JF, Silva P et al.. Telomerase expression and proliferative activity suggest a stem cell role for thyroid solid cell nests. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2004. link 14 Seidel J, Zabel M, Kasprzak A, Spachacz R. The expression of calcitonin, calcitonin gene-related peptide and somatostatin in the thyroids of rats of different ages. Folia morphologica 2003. link 15 Kurabuchi S, Tanaka S. Immunocytochemical localization of prohormone convertases PC1 and PC2 in the mouse thyroid gland and respiratory tract. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2002. link 16 Ginda WJ, Nowak KW, Malendowicz LK. Decrease of TSH levels and epithelium/colloid ratio in rat thyroid glands following administration of proadrenomedullin N-terminal peptide (12-20). Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2000. link 17 Bürgi-Saville ME, Reut B, Gerber H, Peter HJ, Paulsson M, Kaempf J et al.. 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    Original source

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      Side population cells in the mouse thyroid exhibit stem/progenitor cell-like characteristics. — Hoshi N, Kusakabe T, Taylor BJ, Kimura S Endocrinology (2007)
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      Cytokine regulation of HLA on thyroid epithelial cells. — Migita K, Eguchi K, Otsubo T, Kawakami A, Nakao H, Ueki Y et al. Clinical and experimental immunology (1990)
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      Induction of a neural phenotype in a serotonergic endocrine cell derived from the neural crest. — Barasch JM, Mackey H, Tamir H, Nunez EA, Gershon MD The Journal of neuroscience : the official journal of the Society for Neuroscience (1987)
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      Microscopic Focus on the Thyroid Follicles of the One-Humped Camel (Camelus dromedarius). — Roshdy K, Alsafy MAM, El-Gendy SAA, El-Mansi AA, Rezk S Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada (2024)
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      Expression of urocortin and corticotropin-releasing hormone receptors in the horse thyroid gland. — Squillacioti C, De Luca A, Alì S, Paino S, Liguori G, Mirabella N Cell and tissue research (2012)
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      Identification of an adult stem/progenitor cell-like population in the human thyroid. — Fierabracci A, Puglisi MA, Giuliani L, Mattarocci S, Gallinella-Muzi M The Journal of endocrinology (2008)
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      Anatomical and molecular reinvestigation of lamprey endostyle development provides new insight into thyroid gland evolution. — Kluge B, Renault N, Rohr KB Development genes and evolution (2005)
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      Telomerase expression and proliferative activity suggest a stem cell role for thyroid solid cell nests. — Preto A, Cameselle-Teijeiro J, Moldes-Boullosa J, Soares P, Cameselle-Teijeiro JF, Silva P et al. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2004)
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      Immunocytochemical localization of prohormone convertases PC1 and PC2 in the mouse thyroid gland and respiratory tract. — Kurabuchi S, Tanaka S The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (2002)
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      Decrease of TSH levels and epithelium/colloid ratio in rat thyroid glands following administration of proadrenomedullin N-terminal peptide (12-20). — Ginda WJ, Nowak KW, Malendowicz LK Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (2000)
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      Alginate gel culture allows the retention of extracellular matrix and follicular structure of rat thyroid tissue but does not lead to the formation of follicles by FRTL-5 cells. — Bürgi-Saville ME, Reut B, Gerber H, Peter HJ, Paulsson M, Kaempf J et al. Thyroid : official journal of the American Thyroid Association (1998)
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      Expression of CD56/N-CAM antigen and some other adhesion molecules in various human endocrine glands. — Zeromski J, Lawniczak M, Galbas K, Jenek R, Golusiński P Folia histochemica et cytobiologica (1998)
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      Subisthmic accessory thyroid gland in man: a case report and a review of thyroid anomalies. — Bhatnagar KP, Nettleton GS, Wagner CE Clinical anatomy (New York, N.Y.) (1997)
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      Immunocytochemical study of parafollicular cells of the thyroid and ultimobranchial remnants of the European bison. — Sawicki B, Zabel M Acta histochemica (1997)
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      Developmental change in expression of highly polysialylated neural cell adhesion molecule in C-cells in rat thyroid gland. — Nishiyama I, Ogiso M, Oota T, Kimura T, Seki T Anatomy and embryology (1996)
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      C-cells of marmosets (Callithrix jacchus). — Maile S, Merker HJ Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft (1996)
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      Co-expression of vimentin and 19S-thyroglobulin in follicular cells located in the C-cell complex of dog thyroid gland. — Kameda Y The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (1995)
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      Effect of delay in cryofixation on the elemental composition of biopsies and post mortem specimens of the thyroid gland. — Wróblewski R Histochemistry (1994)
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      Detection and identification of endothelin-1 immunoreactivity in rat and porcine thyroid follicular cells. — Colin I, Berbinschi A, Denef JF, Ketelslegers JM Endocrinology (1992)
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