Pediatric Thyroid Disorders

Pediatric Surgery
An interactive discussion about malignant and benign pediatric thyroid disorders between Todd Ponsky, MD and Diana Diesen, MD.

Dr. Diesen is assistant professor of surgery and pediatric surgery fellowship program director at the University of Texas Southwestern Medical Center and is a member of the Children's Health Pediatric Thyroid Center at the Children's Medical Center of Dallas.

Intro track is adapted from "I dunno" by grapes, featuring J Lang, Morusque.
Artist URL: ccmixter.org/files/grapes/16626
License: creativecommons.org/licenses/by/3.0/

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Additional Content

History

  • Focus on risk factors for thyroid lesions and cancers
  • Symptoms of hypothyroidism (fatigue, increased sleepiness, difficulty concentrating, dry hair/skin, constipation) or hyperthyroidism (anxiety, difficulty concentrating, palpitations, oily skin/hair)
  • Difficulty with swallowing or speaking, compressive symptoms
  • Presence of other lumps or bumps?
  • Personal history of thyroid problems, prior malignancies, radiation exposure, alkylating agent exposure (e.g. chemotherapy)
  • Family history of multiple endocrine neoplasia (MEN) syndromes, phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PTHS), familial adenomatous polyposis (FAP) or other adenomatous polyposis coli (APC) gene mutations

Physical exam

  • Nodule location (is it intra- or extrathyroidal?)
  • Fixed or mobile
  • Movement with swallowing
  • Adenopathy
  • Voice changes or hoarseness when speaking
  • For examining an older child, the patient is examined while he/she is sitting and typically examined viewing the patient face-to-face as well as from the the side or from behind.
  • The sternocleidomastoid muscle may need to be manually displaced laterally to palpate the nodule and the thyroid
  • Concerning findings on physical exam include a large nodule which is fixed or any associated adenopathy.
  • Thyroid nodules are less common in adults, but when detected are more likely to be malignant, have extra-thyroid extension, regional lymph node involvement, and distant metastasis.

Laboratory evaluation

  • Thyroid stimulating hormone (TSH) to evaluate for normal thyroid function (euthyroidism).
    • In the presence of a nodule, suppressed TSH will give evidence of a hyperfunctioning nodule (previously called "toxic adenoma”). These patients would likely benefit from nuclear thyroid scintigraphy, whereas those with normal TSH would not.
    • More frequently, TSH is normal. Then ultrasound should be performed with ultrasound-guided fine needle aspiration (FNA) biopsy of the thyroid nodule and any suspicious lymph nodes.

Ultrasound

  • Clinically apparent nodules are at least 1-3 cm in size.
  • Nodule characteristics
    • Suspicious features include hypoechogenicity, irregular margins, hypervascularity, microcalcifications, association with abnormal lymph nodes.
    • Lesions may also be solid, cystic, or a mix of solid and cystic features.
  • Additional nodules
  • Evaluation of adjacent lymph nodes
    • A 1-cm threshold is used for adults, but not children.
    • Suspicious features include loss of hilum, irregularity, hypervascularity

FNA Biopsy

  • Adult guidelines dictate that lesions less than 1-cm not be biopsied.
  • In children, there are no size thresholds and the decision to perform a biopsy is determined by clinical features and ultrasound findings.
  • Anesthesia type (local, MAC, or general) is dependent upon the patient’s age and anticipated overall tolerance of the procedure.
  • Inadequate specimen
    • Occurs in 1-3% of FNA biopsies.
    • Repeat US with FNA in 3-6 months is recommended. Biopsy should not be performed sooner as transient atypia may result from the previous biopsy.

Management of thyroid cysts

  • Small lesions are observed
  • Large lesions are aspirated or resected
  • If the lesion has any solid component, it must be biopsied.

Management of a hyperfunctioning (hot) nodule

  • No indication for biopsy if the nodule is going to already be resected (e.g. if the nodule were symptomatic).
  • If the patient is asymptomatic and does not desire resection, the American Thyroid Association recommends FNA biopsy and ultrasound to rule out suspicious features.

Considerations for benign lesions

  • Size
  • Compressive symptoms
  • Cosmesis
  • Family and patient preference
  • It should be kept in mind that in masses > 4 cm, there is decreased sensitivity of FNA. Thus, benign lesions should still be followed if they are not being resected. Recommendations are for repeat ultrasound with biopsy in 6-12 months, if the mass is enlarging or develops suspicious features.
  • Furthermore, patients with historical risk factors for thyroid malignancy (radiation exposure, family history, etc) may require a more aggressive approach.

Management of papillary thyroid cancer

  • Resect with total or near-total thyroidectomy (leave 1-2% of tissue behind near recurrent laryngeal nerves and/or parathyroid glands)
  • Historically, there was more debate over lobectomy vs thyroidectomy. However, bilateral disease is seen in up to 30% of patients and multi-focal disease is seen in up to 65%, so thyroidectomy is recommended.
  • Patients with thyroidectomy are able to receive radioactive iodine (RA) ablation and are able to have thyroglobulin used as a marker of recurrence, or persistent disease.
  • Tumor, Node, Metastasis (TNM) classification and American Thyroid Association (ATA) pediatric risk level will determine if the patient needs RAI ablation.
    • The intermediate and high risk patients will require RAI ablation.

Lymph node dissection (LND) in papillary carcinoma

  • Performed for clinically palpable nodes or pathologically-confirmed positive nodes.
  • Central and/or lateral LND is performed based on the location of involved nodes.
  • If a lateral node is affected, then central and ipsilateral lateral LND are performed.
  • If a central node is affected, then only a central LND is performed. There is no evidence for performing lateral LND if only central nodes are

Thyroidectomy technique

  • The technique must be adapted to the size of the patient.
  • Incision is made above the sternal notch and below the thyroid cartilage, and it is typically 3-4 cm in length.
  • Divide and elevate the strap muscles.
  • Ligate the middle thyroid vein.
  • Starting with the affected side, reflect the thyroid lobe medially.
  • Ligate the superior pole vessels.
  • Identify and preserve the RLN and parathyroids, then ligate inferior pole vessels.
  • Further reflect the thyroid medially, off the trachea, and ligate the Ligament of Berry.
  • Preoperative US is very sensitive for identification of lymph nodes, thus preventing any surprises.

Tips and tricks

  • Dr. Diesen routinely uses a nerve monitor. Although it does not decrease risk of nerve injury it may be helpful in aiding dissection, particularly in patients with bulky adenopathy.

Post-operative management

  • Same-day discharge for thyroid lobectomy.
  • Total thyroidectomy
    • Overnight observation for monitoring
    • Check PTH and calcium in recovery
    • If PTH is below 10-15, the patient is at elevated risk for hypocalcemia and a calcium supplement, or calcitriol (1,25-dihydroxyvitamin D3), is prophylactically started.
    • Serial calcium is not checked for cases with preservation of parathyroid intraoperatively and normal calcium post-operatively. However, in patients with extensive neck dissection and/or low calcium levels post-op, calcium levels may need to be rechecked in the morning or even every 6 hours.
    • Levothyroxine is started on POD #1 with subsequent TSH monitoring.

Follow up

  • Dr. Diesen uses the TNM system for staging.
  • Low risk patients (disease confined to the thyroid with no nodal spread)
    • Check thyroglobulin levels (goal TSH is 0.5 to 1)
    • Ultrasound at 6-months post-op and then annually for 5 years.
  • RAI Ablation
    • Indicated for patients with intermediate or high ATA pediatric risk level. This entails extensive nodal disease, extrathyroidal extension, and/or distant metastases.
    • These patients also require a 131I or 123I scan to check for residual or distant disease.

Follicular cells on FNA

  • Results of a FNA biopsy can be reported as non-diagnostic, benign, indeterminate, or malignant.
  • A finding of follicular cells is considered indeterminate. Biopsy results showing follicular cells can be divided into follicular lesion of undetermined significance, follicular lesion concerning for neoplasm (aka follicular neoplasm), and suggestive of malignancy with a follicular component.
  • The most recent ATA recommendation is that all of these lesions should be resected. This is different from the adult recommendation because the risk of malignancy is higher in children than in adults.
    • For follicular lesions of undetermined significance, the risk of malignancy is traditionally reported as 5-15%, but is more recently reported as 28%.
    • For follicular neoplasm, the classically reported malignancy rate is 15-30%, but recent data suggests it is closer to 50-60%.
  • If there are no suspicious nodes, lobectomy with removal of the isthmus is recommended.
  • Intraoperative frozen section cannot be used to determine if a follicular carcinoma is present. However, it can demonstrate a papillary carcinoma component.
    • Thus, if the frozen section demonstrates a papillary carcinoma component, then a total thyroidectomy should be performed regardless.

Follicular carcinoma

  • Need to know tumor size and presence of vascular invasion.
  • If a thyroid lobectomy specimen shows significant vascular invasion and/or tumor size > 4 cm, completion thyroidectomy should be performed. Otherwise, the patient may be monitored.

Follicular adenoma

  • If a lobectomy specimen demonstrates follicular adenoma, no additional surgery is required. No further malignancy surveillance is required, but TSH should be monitored because the patient had a lobectomy. Approximately 30% of lobectomy patients will develop hypothyroidism.

Pharmacologic TSH suppression

  • Only performed in patients with papillary carcinoma.
  • TSH levels are adjusted based on ATA pediatric risk level.
  • Low risk patients have a TSH goal of 0.5-1, but for high risk patients the goal is < 0.1.

Medullary carcinoma

  • Need to know if there is family history of thyroid problems, MEN, etc.
  • Patients without significant family history likely have a spontaneous RET mutation.
  • Must ensure there is adequate US of the neck, as these patients are much more likely to have extensive disease.
  • Check calcitonin and CEA levels, as well as RET mutation analysis.
  • If the patient has a RET mutation, then other conditions associated with MEN type 2, such as pheochromocytoma and hyperparathyroidism, should be investigated.
  • Post-op
    • Typically, there is no role for chemotherapy and there is debate over the role of radiation.
    • Measure calcitonin levels as a tumor marker.
      • If normal, perform routine ultrasound every six months for 1 year, then annually.
      • If calcitonin is elevated, but   remains < 150 and there is no evidence of persistent or recurrent MTC on physical exam or US of neck, perform physical exam and US every 6 months with calcitonin and CEA every 3-6 months to determine doubling times
      • If calcitonin > 150, perform CT of the neck and chest, as well as CT or MR of the abdomen (primarily to evaluate for liver metastases). Finally, a bone scan is required in addition to MRI of the pelvis and axial skeleton. If imaging is all negative, continue surveillance ultrasound and serial calcitonin levels. If positive, neck dissection may be indicated (if not previously performed) or systemic therapy (e.g. tyrosine-kinase inhibitor) and/or external beam radiation.

MEN type 2A

  • Characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism
  • MEN type 2a has a lower risk and screening begins at the time of initial presentation for evaluation of medullary thyroid cancer.
  • Patients are divided into high (e.g. 6,34 mutation) and moderate risk based on the type of RET mutation they possess.
    • High risk patients should have a total thyroidectomy by age 5. Surveillance should begin at age 3 with calcitonin, CEA, and US. If calcitonin exceeds 40, the patient should have total thyroidectomy with central neck LND. Screening for pheochromocytoma should begin at age 11 (as malignancy typically develops in the 20’s).
    • Moderate risk patients should have a total thyroidectomy when calcitonin becomes elevated. Screening for pheochromocytoma should begin at age 16 (as malignancy typically develops in the 20’s).
MEN type 2B
  • Characterized by medullary thyroid cancer (which tends to present in infancy), pheochromocytoma, mucosal neuromas, and marfanoid habitus
  • RET proto-oncogene often has 9,18 mutation and has a 50% risk of pheochromocytoma and requires screening to begin at age 11 or time of initial diagnosis.
  • Patients with family history of MEN type 2B should be screened immediately after birth.
  • Those with the 9,18 mutation should have prophylactic thyroidectomy before 1 year of age.
  • De novo mutations (as opposed to inherited) are more likely in MEN type 2B than type 2A.

Grave’s disease

  • Patients are typically referred from endocrinology when symptoms are refractory to medical management.
  • RAI vs surgery
  • In younger children, there is concern for secondary malignancy due to RAI exposure.

Subacute thyroiditis

  • Often presents as a painful, swollen thyroid gland
  • May be caused by viral infection
  • Elevation in thyroid function initially seen, followed by hypothyroidism. Thyroid function returns to normal by 1-2 years.
  • Tend to be self-limiting and require only conservative management.

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