A Case of Goitre – What You Must Know?

CME INDIA Presentation by (Prof) Prabhat Agrawal, PG Dept. of Medicine, SN Medical College, Agra, MD, MAMS, FRCP (Edin.), FRCP (Glas.), FICP, FIACM FRSSDI, PG Diploma of Diabetes (London).

Based on presentation at APICON-2022, Jaipur.

Defining Goitre

• Goiter is defined as an enlarged thyroid gland. It may or may not be associated with overt hypothyroidism or hyperthyroidism.
• They become palpable on reaching diameter >1 cm.

How much Prevalent?

• In an adult nonpregnant population, the Framingham survey revealed a 4.6% prevalence of goiter with a strong female predominance.
• Using ultrasonography as the screening method, the prevalence of goiter in an unselected adult population has been reported to be as high as 30% to 50%.

What it could be?

Clinical Presentation

• Most growths are asymptomatic and are incidentally picked up on imaging.
• In majority of cases Free T4, TSH is normal.
• Goitre develops over years and if large enough may cause compressive symptoms.

What factors suggest Benign Diagnosis?

Factors Suggesting a Malignant Diagnosis

Laboratory Evaluation

• Serum TSH.
• ↓T4 ↑TSH Hypothyroidism – Hashimoto, Endemic goiter.
• ↑T4 ↓ TSH Hyperthyroidism – Grave, Toxic nodule, Viral Thyroiditis, Thyroid carcinoma with metastasis.
• Euthyroid – Benign / malignant tumor.
• Other investigations including S. Thyroglobulin, TPO Antibodies and S. Calcitonin are not routinely recommended.

Thyroid Imaging-USG

• Clinical Utility of Neck Ultrasound:
• Nodules: number and characteristics of each nodule: diameters, shape, echogenicity, composition, limits, presence of calcifications, vascularization
• Vascularity and type of halo around nodule
• Follow-up: numbers and diameters of nodules
• Guidance for fine-needle aspiration biopsy

Factors Favoring Malignant Diagnosis in USG

MRI

• Recurrent neoplasms in the thyroid bed or regional lymph nodes can be detected with MRI.

External Scintigraphy

• The thyroid normally demonstrates symmetric uniform uptake in the two lobes.
• The most important use of scintigraphic imaging thyroid tissue is in defining areas of increased or decreased function (hot or cold areas, respectively).

Thyroid Scan

FNAC

• FNA of thyroid nodule has eclipsed all other diagnostic modalities and has emerged as the most preferred test with overall sensitivity and specificity exceeding 90%.
• FNA is considered the gold standard test for evaluating thyroid nodules.
• FNA is recommended at a size cutoff of 1cm (lower size cutoffs for nodules with suspicious USG patterns).
• As per 2015 ATA guidelines do not recommend FNA for any nodule <1 cm unless metastatic cervical lymph nodes are present.

Core Biopsy

• Core biopsy is useful as an adjunct to FNAB in the setting of a prior nondiagnostic or indeterminate FNAB.
• The diagnostic yield of combined FNAB–core biopsy is 87%, compared with 47% for FNAB.

Non-Toxic Multinodular Goiter

• Nontoxic MNG occurs in up to 12% of adults.
• These are mostly asymptomatic and euthyroid.
• Radioiodine is used for treatment as it achieves 40-50% reduction in goiter size.
• When there is acute compression, steroid treatment or surgery is required.
• T4 suppression is rarely effective as it increases the risk of thyrotoxicosis

Toxic Multinodular Goiter (Joffroy Disease)

• It is more common in elderly and present with atrial fibrillation (AF), palpitations, tremors and weight loss.
• The major difference between toxic and nontoxic MNG lies in the presence of functional autonomy in the former.
• The clinical presentation tends to include subclinical or mild overt hyperthyroidism.
• Thyroid scan demonstrates heterogenous uptake and ultrasonography should be used to assess the areas of decreased uptake.
• Surgery is definitive treatment.

Hyperfunctioning Solitary Nodule

• Most patients have acquired somatic, activating mutations in the TSH-R.
• Mild thyrotoxicosis usually results and usually detected when a nodule is >3 cm.
• Thyroid scan is definitive diagnostic test.
• Radioiodine ablation is usually the treatment of choice.
• Anti-thyroid drugs and beta blockers can normalize the thyroid function but it is not an optimal long-term treatment.

Hashimoto’s Thyroiditis

Thyroid Cyst

• Generally seen in age group of 20-40 yrs. and more in females.
• Constitutes about 30% of clinically diagnosed solitary nodule.
• Usually formed as a result of colloid degeneration or involution of follicular adenoma.
• FNAC is diagnostic as well as therapeutic as it resolves the cyst but re accumulation is frequent.

Follicular Adenoma

• Generally, they involute & chances of malignancy are infrequent
• TSH suppression with levothyroxine decrease the size of 30% nodule & may prevent growth.
• If nodule size does not decrease after 6-12 months of suppressive therapy, then treatment is discontinued.
• FNAC can’t rule out malignancy as it may not see the capsule.
• If there is increase in size or symptoms, then plan for repeat FNAC and if FNAC is inconclusive then proceed for surgical excision & biopsy.

Papillary Thyroid Carcinoma

• Commonest malignancy of thyroid.
• It is multifocal & tends to invades locally.
• Spread by lymphatics but can metastasize hematogenously as well.
• In India, coexistent tubercular lymphadenopathy may be there which would not take up radioiodine on scan.
• FNAC of L.N. is needed to exclude associated tubercular lymphadenopathy.

Follicular Carcinoma

• More common in iodine deficient region.
• It is difficult to differentiate between benign & malignant follicular neoplasm by FNAC because capsule can’t be seen.
• FTC tend to spread by hematogenous route to bone, lungs & CNS.
• Patient of follicular carcinoma present at later stage; hence, mortality rate is high.

Management

• Surgery- near total thyroidectomy is preferable in almost all patients.
• Thyroxin- As most tumors are TSH responsive so thyroxin is given in doses of 0.1-0.2 mg daily.to suppress endogenous TSH production.
• Radioiodine- If metastasis take up radioiodine they may be detected by scanning and treated by larger doses of radioiodine.
• Thyroglobulin- measurement of serum thyroglobulin is of value in the follow up and detection of metastasis in patient who have undergone surgery.

Anaplastic Thyroid Carcinoma

• As it is undifferentiated uptake of radioiodine is negligible.
• It has very poor prognosis and most of the patients die within 6 months of diagnosis.
• Can often be picked off by PET scan.
• Chemotherapy with anthracycline and paclitaxel has been attempted but it is usually ineffective.
• External beam radiation therapy can be attempted and continued if tumors are responsive.

Medullary Thyroid Carcinoma

• Can be sporadic or familial, there are three familial forms of MTC – MEN 2A, MEN 2B & familial MTC.
• Elevated serum calcitonin is a marker of residual or recurrent diseases.
• It is reasonable to test all patient with MTC for RET mutation.
• Treatment is primary surgical.
• External radiotherapy & chemotherapy provide palliation in patient with advanced disease.

Thyroid Lymphoma

• Usually arise in the background of Hashimoto’s thyroiditis and it presents as rapidly expanding thyroid mass.
• These tumors are highly sensitive to external radiation.
• Surgical resections should be avoided as initial therapy for fear of spread.

Subacute Thyroiditis

• Sometimes presents as solitary thyroid nodule.
• Painful thyroid swelling, fever and raised ESR.
• Clinical course consists of initial thyrotoxic phase followed by hypothyroid phase and the patient becomes euthyroid within a span of 1-2 years.
• Thyrotoxic phase of thyroiditis can be differentiated from Graves by RAIU, low in thyroiditis and high in Graves. Hypothyroid phase of thyroiditis can be differentiated from Hashimoto’s by FNAC and TPO antibody.
• NSAID, steroid and B-blocker are the mainstay of treatment.
• If the patient is hyperthyroid anti thyroid drug can be used.

Final Points

• Malignancy is a potential risk (about 5%) in thyroid nodule and one should not underestimate the value of early diagnosis as various forms of malignant neoplasm carry a favorable prognosis.
• If FNAC leaves any doubt or does not coincide with U/S or clinical evaluation, go for excisional biopsy.
• It is constructive, therefore, to review the diagnostic approach and to reassure patients at subsequent steps.

References:

1. https://www.racgp.org.au/afp/2012/august/goitre
2. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer
   Keith C. Bible, et al., Thyroid.Mar 2021.337-386.http://doi.org/10.1089/thy.2020.0944
3. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. doi:10.1089/thy.2015.0020
4. https://www.seep.es/images/site/enlaces/ACCE_thyroid_nodule_2010.pdf

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