Test: Thyroid - 1 - NEET PG MCQ

• Lingual
• Cervical
• Thoracic

Radioactive Iodine (I₁₃₁) therapy is a potent method for administering significant radiation doses to thyroid tissue. It primarily emits beta radiation (90%), which penetrates only 0.5 mm of the tissue, thereby enabling therapeutic effects on the thyroid while safeguarding adjacent structures, especially the parathyroids.

Mechanism of Action

• I₁₃₁ releases beta particles and X-rays.
• Beta rays are employed for their damaging effects on thyroid cells.
• X-rays are beneficial for tracer studies.

Indications in Carcinoma

However, there are certain contraindications for I₁₃₁ therapy:

• Distant metastasis at the time of diagnosis.
• Childhood.
• Incomplete tumour resection.
• Pregnancy.
• Patients with a high risk of mortality or recurrence.
• Lactation.

Carcinoma of the thyroid can be classified into different types based on their spread:

• Papillary carcinoma: spreads via lymphatic pathways
• Follicular carcinoma: spreads through the bloodstream
• Medullary carcinoma: spreads through both lymphatic and hematogenous routes
• Anaplastic carcinoma: spreads through direct invasion

The most common sites of metastasis for each type of thyroid carcinoma are as follows:

• Papillary carcinoma: lungs
• Follicular carcinoma: bones
• Medullary carcinoma: liver
• Anaplastic carcinoma: lungs

Pulsating secondaries are observed in:

• Follicular carcinoma of the thyroid
• Renal cell carcinoma (RCC)

Bone metastasis in thyroid carcinoma includes:

• Follicular carcinoma: osteolytic metastasis (pulsating secondaries in flat bones)
• Medullary carcinoma: osteoblastic metastasis

• It cannot differentiate between follicular adenoma and follicular carcinoma.
• It cannot distinguish Hurthle cell adenoma from Hurthle cell carcinoma.
• It is ineffective in cases of Reidel’s thyroiditis (biopsy is recommended).
• FNAC is less dependable for individuals with a history of head and neck irradiation or a family history of thyroid cancer, as there is a greater chance of multifocal lesions and hidden cancer.

• Oncogenes and Tumour-Suppressor Genes Involved in Thyroid Tumourigenesis

• Oncogenes
• RET^Q - Membrane receptor exhibiting tyrosine kinase activity; linked to sporadic and familial MTC, PTC (RET/PTC rearrangements).
• MET^Q - Functions similarly; overexpressed in PTC.
• TRK1 - Also functions similarly; activated in certain PTC cases.
• TSH-R - Associated with heterotrimeric G protein; linked to hyperfunctioning adenoma.
• Gs (gsp) - A signal transduction molecule (GTP binding); implicated in hyperfunctioning adenoma and follicular adenoma.
• Ras^Q - A signal transduction protein; involved in follicular adenoma and carcinoma, PTC.
• PAX8/PPAR¹ - An oncoprotein; associated with follicular adenoma and follicular carcinoma.
• B-Raf (BRAF)^Q - A signal transduction protein; connected to PTC, tall cell, poorly differentiated, and anaplastic types.
• Tumour Suppressors
• p53^Q - A cell cycle regulator that halts cells in G1 and induces apoptosis; found in de-differentiated PTC, FTC, and anaplastic cancers.
• p16^Q - A cell cycle regulator that inhibits cyclin-dependent kinase; observed in thyroid cancer cell lines.
• PTEN^Q - A protein tyrosine phosphatase; linked to follicular adenoma and carcinoma.

Follicular carcinoma of the thyroid (FTC) represents 10% of thyroid cancers and is more prevalent in areas where iodine is deficient. It occurs more frequently in women, with an average age of diagnosis around 50 years. The genes associated with FTC include:

• p53
• PTEN
• Ras
• PAX8/PPAR¹

Pathology: Typically, it presents as a solitary lesion encapsulated by a capsule. Histologically, follicles can be observed, although the lumen may lack colloid. Malignancy is characterised by the presence of capsular and vascular invasion. During surgery, tumour infiltration and invasion, as well as tumour thrombus within the middle thyroid or jugular veins, may be evident.

Clinical Features: It usually manifests as solitary thyroid nodules, sometimes accompanied by a history of rapid size increase, along with long-standing goitre. Pain is rare unless there has been bleeding into the nodule. Cervical lymphadenopathy is infrequent at initial presentation, occurring in about 5% of cases. Preoperative clinical diagnosis of cancer is challenging unless distant metastases are evident. Larger follicular tumours (greater than 4 cm) in older men have a higher likelihood of being malignant. The most common site of metastasis is bone, characterised by osteolytic metastasis with pulsating secondaries in flat bones.

Diagnosis: Fine-needle aspiration cytology (FNAC) cannot effectively differentiate benign follicular lesions from follicular carcinomas. Intraoperative frozen-section examination is typically not beneficial, though it should be conducted if capsular or vascular invasion is suspected, or if adjacent lymphadenopathy is present.

Treatment: For follicular lesions, a hemithyroidectomy is performed, as 80% of these patients will have benign adenomas. In cases of thyroid cancer, total thyroidectomy is indicated, particularly in older patients with follicular lesions over 4 cm due to an increased risk of cancer (50%). Prophylactic nodal dissection is unnecessary, as nodal involvement is rare.

Prognosis: The cumulative mortality rate is 15% at 10 years and 30% at 20 years. The most critical prognostic factors include age and the presence of distant metastasis. A poor long-term prognosis is associated with:

• Age over 50 years
• Tumour size greater than 4 cm
• Higher tumour grade
• Significant vascular invasion
• Extrathyroidal invasion
• Distant metastases

Hürthle Cell Carcinoma accounts for about 3% of all thyroid cancers. It is regarded as a subtype of follicular thyroid cancer.

• Hürthle cell tumours are different from follicular carcinomas in several ways:
• They are more frequently multifocal and bilateral (approximately 30%).
• They typically do not uptake RAI (around 5%).
• They have a higher likelihood of metastasising to local lymph nodes (25%) and distant locations.
• They are associated with a greater mortality rate (roughly 20% at 10 years).

Pathology is marked by vascular or capsular invasion, and diagnosis cannot be made through FNAC. The tumours consist of sheets of eosinophilic cells filled with mitochondria, originating from the oxyphilic cells of the thyroid gland.

Treatment for unilateral Hürthle cell adenomas involves hemithyroidectomy. For invasive Hürthle cell neoplasms, total thyroidectomy along with routine central neck node removal is recommended, and modified radical neck dissection (MRND) is performed when lateral neck nodes are palpable. Retinoic acid and PPAR agonists have demonstrated some effectiveness in treating these tumours in vitro.

Medullary Carcinoma of the thyroid is a neuroendocrine carcinoma that originates from parafollicular ‘C’ cells of the thyroid. The parafollicular ‘C’ cells are derived from the ultimobranchial bodies and are responsible for secreting calcitonin. These ‘C’ cells are primarily located superolaterally in the thyroid lobes, where most Medullary Thyroid Carcinomas (MTC) typically develop.

• Approximately 75-80% of MTCs arise sporadically.
• The spread of the disease occurs via both lymphatic and haematogenous routes.
• The liver is a common site for metastasis.

Medullary Carcinoma of the thyroid is classified as follows:

• Sporadic cases make up 80%.
• Familial cases account for 20% (including Non-MEN setting, MEN-2A, and MEN-2B).

The carcinoma usually originates in one lobe and is often observed in individuals during their sixth decade of life. A mutation in the RET proto-oncogene is associated with this condition. MTC can be multicentric and bilateral, occurring at a younger age and is linked to C-cell hyperplasia, also associated with a RET proto-oncogene mutation.

Clinical features: Medullary carcinoma should be suspected if there are elevated levels of serum calcitonin and carcinoembryonic antigen (CEA). The involvement of cervical lymph nodes is common at the time of diagnosis, with both lymph node and blood-borne metastases occurring early. Patients may present with diarrhoea and histological examination may reveal amyloid deposits in the stroma. In a familial context, the presence of pheochromocytoma, hyperparathyroidism, or thyroid cancer should prompt further investigation, as the discovery of medullary carcinoma thyroid necessitates family surveillance.

Diagnosis: This condition is diagnosed through fine needle aspiration cytology (FNAC). The use of I-131 scans is ineffective since MTC is independent of thyroid-stimulating hormone (TSH). The primary tumour marker, calcitonin, is elevated in nearly all MTC cases, and increased levels of calcitonin in MTC are not associated with hypocalcemia.

Treatment: Total thyroidectomy combined with central lymph node dissection is recommended, along with ipsilateral modified radical neck dissection if the tumour exceeds 1 cm. If lymph nodes are positive on the ipsilateral side, a bilateral modified radical neck dissection should be performed.

Follow-up: After surgical resection, the calcitonin levels typically decrease, but may rise again in cases of recurrence, making it useful for follow-up monitoring.

Prognosis: MTC is generally associated with a poor prognosis.

Treatment for medullary carcinoma, thyroid pheochromocytoma should begin with surgery. These tumours are predominantly (>50%) bilateral. A total thyroidectomy is the preferred treatment for patients with MTC due to the high likelihood of multicentricity, a more aggressive progression, and the ineffectiveness of 131I therapy. The central compartment nodes are often involved early in the disease, so a bilateral central neck node dissection should be routinely conducted.

• For patients with palpable cervical nodes or affected central neck nodes, whether ipsilateral or bilateral, modified radical neck dissection is advised.
• The necessity of prophylactic lateral neck dissection is debated.
• Nonetheless, in patients with tumours larger than 1 cm, ipsilateral prophylactic modified radical neck dissection is recommended since over 60% of these patients exhibit nodal metastases.
• If the ipsilateral nodes are positive, a contralateral node dissection should be undertaken.
• In cases of locally recurrent or metastatic disease, tumour debulking is suggested not only to relieve symptoms like flushing and diarrhoea but also to lower the risk of mortality from recurrent central neck or mediastinal disease.
• External beam radiotherapy remains controversial but is advised for patients with unresectable residual or recurrent tumours.
• No effective chemotherapy regimen is available.
• Radiofrequency ablation performed laparoscopically shows promise in the palliative care of liver metastases larger than 1.5 cm.

In patients experiencing hypercalcaemia at the time of thyroidectomy, only visibly enlarged parathyroid glands should be excised. The remaining parathyroid glands ought to be preserved and marked in individuals with normocalcaemia, as merely about 20% of patients with MEN2A develop hyperparathyroidism. If a normal parathyroid cannot be maintained on a vascular pedicle, it should be removed, biopsied to ensure it is indeed a parathyroid, and subsequently autotransplanted to the forearm of the non-dominant arm. A total thyroidectomy is warranted in RET mutation carriers once the mutation is confirmed. This procedure should be carried out before the age of 5 years in MEN2A patients and before the age of 1 year in MEN2B patients.

• In children who are RET-positive and calcitonin-negative with normal ultrasound findings, central neck dissection can be avoided.
• However, when calcitonin levels are elevated or the ultrasound indicates possible thyroid cancer, a prophylactic central neck dissection is warranted.

The I¹³¹ scan is ineffective because MTC is TSH independent, meaning MTC does not absorb radioiodine (I¹³¹).

Radioactive iodine is utilised to eliminate remaining thyroid tissue (thyroid ablation) in well-differentiated thyroid cancer.

• For MEN-2A, prior to the age of 5 years.
• For MEN-2B, before 1 year of age.

• Elevated calcitonin levels.
• Ultrasound suggesting thyroid cancer greater than 5 mm.
• Presence of lymph node metastasis.