Perioperative management - Total thyroidectomy for benign multinodular goiter on both sides.

Bilateral multinodular goiter with

• Compression symptoms
  
  
  • Pressure sensation in the neck
  • Swallowing difficulties
  • Shortness of breath or a globus sensation
  • Tracheal or esophageal displacement or narrowing in CT/MRI
  • Retrosternal growth (extension behind the sternum)
  • Superior vena cava syndrome
     
• disturbing cosmetics
• autonomous adenoma
• suspected malignant nodule

Note: For benign nodular goiter, subtotal resection was long considered the standard procedure, leaving a "thumb-sized" remnant of thyroid tissue with safe distance to the recurrent laryngeal nerve and parathyroid glands in situ. However, subtotal resections had high recurrence rates of up to 40%, leading to a paradigm shift towards more radical resection.

For definitive cure of both nodular goiter and Graves' disease, (near) total thyroidectomy is often required, as the entire thyroid tissue is affected by the disease.

Graves' Disease

not a first-line therapy!

• In case of high risk of recurrence and persistence: Great-Score 4/5
  
  Note: The GREAT Score for Graves' Disease (not to be confused with the same-named score for thyroid carcinoma!) is a predictive scoring system used to assess the risk of recurrence or chance of remission after drug therapy (antithyroid drugs) in Graves' Disease.LINK to Great Score
   
• In case of endocrine orbitopathy
• Desire for children
• Side effects from antithyroid drugs

Further indications for total thyroidectomy:

• Medically uncontrollable dysfunction (e.g., severe iodine-induced hyperthyroidism, history of thyrotoxic crisis)
• Hashimoto's thyroiditis with pronounced systemic symptoms
  
  With high TPO antibody titers, which are the decisive trigger for the systemic disease. Significant improvement of symptoms by removing the trigger

Thyroid carcinoma

Papillary and follicular thyroid carcinoma T1a to T4

• A thyroidectomy for papillary thyroid carcinoma is necessary or advisable when there is a high risk of multifocal, aggressive, or metastatic tumor biology, or when complete follow-up (e.g., via thyroglobulin) or radioiodine therapy is desired.
• Follicular thyroid carcinoma (FTC) is a thyroid malignancy arising from follicular cells that do not show the characteristic nuclear criteria of papillary thyroid carcinoma. The tumors are usually encapsulated and, unlike adenomas, show invasive growth in the form of complete capsular breakthrough. In minimally invasive FTC without or with only minor evidence of angioinvasion and a size ≤4 cm, a primary or secondary total thyroidectomy is not required.
• Clinically, prognostically, and therapeutically, tumors with a high risk of multifocal, aggressive, or metastatic tumor biology must be distinguished.Advantages of a thyroidectomy include complete histopathology, possibility of radioiodine therapy, thyroglobulin monitoring, and better prognosis assessment.
• Advantages of a hemithyroidectomy include a risk of hypoparathyroidism < 1% compared to 10.8% permanent with thyroidectomy, remaining thyroid with its own function, better quality of life in the early postoperative phase, lower overall disease costs. Disadvantage is demanding sonographic follow-up by specialists, possibly higher rate of secondary interventions.
• In follicular thyroid carcinoma, a distinction is made between a minimally invasive form with and without angioinvasion and a widely invasive tumor. A special form is the oncocytic carcinoma (Hürthle cell carcinoma), a variant with often more aggressive course.
• In differentiated thyroid carcinomas, primary or secondary total thyroidectomy is also recommended in the presence of distant metastasis, especially to enable postoperative radioiodine therapy.
• In a T4a tumor extending beyond the organ capsule, a cervicovisceral resection should generally be considered.
  LINK TNM

Poorly differentiated thyroid carcinoma (PDTC)

• First defined as a distinct entity by the WHO in 2004, prognostically standing between differentiated and undifferentiated carcinomas. Even with distant metastasis, complete tumor resection with total thyroidectomy and postoperative radioiodine therapy should be performed. However, radioiodine uptake is often limited.

Undifferentiated (anaplastic) carcinomas (UTC) (T4a N0/1 M0/1)

• If resectable, thyroidectomy as radical tumor resection in bilateral involvement plus multimodal therapy

Medullary thyroid carcinoma (with central compartment resection in pathological calcitonin levels)

• Medullary thyroid carcinoma (MTC) accounts for about 5% of all thyroid carcinomas and is characterized by some peculiarities: The much more common differentiated thyroid carcinomas (DTC) originate from the thyroid hormone-producing cells themselves and therefore take up iodine. In contrast, MTC derives from the calcitonin-producing C-cells. These are located between the cavity structures of the thyroid tissue and do not take up iodine. Thus, the possibility of classical radioiodine therapy is eliminated.
• MTC secretes calcitonin (Ctn) and carcinoembryonic antigen (CEA). It can only be cured by surgery. It occurs sporadically in about 75% and hereditarily in about 25%, usually as part of multiple endocrine neoplasia type 2 (MEN2) in association with pheochromocytomas and/or primary hyperparathyroidism. In suspected MEN2, appropriate diagnostics (plasma, urine metanephrines, serum calcium, parathyroid hormone) should be performed before surgery to exclude or confirm pheochromocytoma or hyperparathyroidism.
• In biochemically confirmed MTC (in women from 30 pg/ml, in men from 60 pg/ml calcitonin), total thyroidectomy is recommended, as 10% of sporadic MTCs also occur multifocally (bilaterally).
• Thyroidectomy should be supplemented by central and possibly lateral cervical lymph node dissection, as early local/regional metastasis can occur, and even micro-MTCs (≤10mm) can be associated with lymph node metastases (exception: absence of desmoplasia in frozen section). At the latest, with a basal Ctn >200pg/ml, contralateral lateral lymph node dissection should also be performed.
• In suspected MTC as part of MEN2, a germline analysis of the RET gene should be performed, and the molecular genetic proof of an activating pathogenic germline variant of the RET gene is evidence of an MEN2 syndrome. All affected individuals with MTC should receive genetic counseling.
• Post-operative incidental finding after non-total thyroidectomy: no re-operation if calcitonin is below the detection limit.

Lymph node dissection

• In nodal-positive thyroid carcinomas, total thyroidectomy with dissection of the first lymph node station in the so-called central compartment is the procedure of choice.
• Prophylactic lymph node dissection is generally not routinely recommended for PTC, but only in cases of higher risk or clinical/intraoperative suspicion. The decision is made individually and should be made in an interdisciplinary tumor board or according to guidelines.
• The central compartment includes the anatomical space between the carotids on both sides as lateral boundaries, the hyoid bone cranially, and the brachiocephalic vein caudally.
• The organ-related components of the central neck area are the two thyroid lobes, the short straight neck muscles (sternohyoid, sternothyroid), and the central lymph nodes (pre- and paratracheal, prelaryngeal).

• Manifest hyperthyroidism: Before elective thyroid surgery, the patient must be euthyroid to minimize the risk of a thyrotoxic crisis.LINK Hyperthyroidism
   
• Cardiopulmonary risk assessment
   
• General anesthesia intolerance
   
• Coagulation disorder or use of anticoagulants
   
• Guidelines recommend an individual benefit-risk analysis before elective surgeries: If the operative bleeding risk clearly outweighs the potential cardiovascular benefit, aspirin therapy should be interrupted.
   
• In cases of higher-grade anticoagulation such as P2Y₁₂-ADP receptor antagonists (e.g., Clopidogrel), NOACs (e.g., Xarelto), or vitamin K antagonists (e.g., Falithrom or Marcumar), a therapeutic concept should be developed in an interdisciplinary consultation regarding the indication for anticoagulation, the possibility of bridging with heparin, and the operative bleeding risk.
   
• An asymptomatic nodular goiter and a scintigraphically hypofunctioning (“cold”) nodule without suspicion of malignancy are not indications for surgery.

Medical History

• local symptoms of thyroid enlargement, nodule growth (cervical pressure or globus sensation, swallowing difficulties, and dyspnea, especially under exertion)
   
• voice changes/hoarseness, recurrent laryngeal nerve paralysis
   
• symptoms of hyperthyroidism
   
• medications (iodine-containing preparations, antithyroid drugs)
   
• family medical history
   
• previous radiation in the neck area: A confirmed etiological factor for the development of differentiated thyroid carcinoma is exposure to ionizing radiation, which is why patients with thyroid nodules should be specifically asked about previous radiation to the head-neck region.
   
• Pre-existing cervical spine problems (head reclination during positioning!)

Physical Examination

• palpation (size, consistency of thyroid lobes, nodules, swallowing mobility, palpable lymph nodes)
   
• endocrine ophthalmopathy
   
• superior vena cava syndrome
   
• Stages of Thyroid Enlargement:
• Ia palpable goiter, not visible even with head reclination
  Ib goiter visible only with head reclination
  II goiter visible with normal head posture
  III goiter with local congestion and compression signs

Vocal Cord Function Test

• A preoperative ENT laryngoscopy to assess vocal cord mobility is essential.
   
• It can detect pre-existing damage to the recurrent laryngeal nerve, e.g., after previous surgery or in malignancy.
   
• It allows for a situation-adapted surgical strategy.
   
• It is the basis of perioperative quality assurance
   
• Pre- and postoperative laryngoscopy and intraoperative neuromonitoring form the basis of perioperative quality assurance and are an inseparable diagnostic unit. Neuromonitoring is not usable without knowledge of clinical laryngeal function! LINK to PDF IONM

Laboratory Tests

• usual preoperative laboratory parameters depending on underlying disease, coagulation, calcium, PTH
   
• TSH, thyroid hormones: fT3, fT4
  The most important in-vitro parameter is TSH, whose pathological change indicates a long-standing thyroid dysfunction. Note: A low concentration suggests hyperthyroidism, while a high concentration suggests hypothyroidism. In these cases, additional determination of thyroid hormones (fT3 and fT4) is mandatory; if TSH is normal and clinical euthyroidism is present, it can be omitted.
   
• Thyroid antibodies for the diagnosis of immunothyropathy and thyroiditis
  
  
  • Antibodies against TSH receptor (TRAK) should be determined if a clear distinction between Graves' disease and non-immunogenic hyperthyroidism is not possible based on clinical examination and imaging.
     
  • Antibodies against thyroid peroxidase (anti-TPO) are determined when autoimmune thyroid disease is suspected; they are elevated in 95% of patients with Hashimoto's thyroiditis (autoimmune thyroiditis) and in 70% of patients with Graves' disease.
     
  • Antibodies against thyroglobulin (anti-TG) are less specific and are additionally determined when autoimmune thyroiditis is suspected, especially if anti-TPO is negative.
     
•  Determination of basal calcitonin level
  
  Calcitonin is a highly specific tumor marker for medullary thyroid carcinoma (MTC). German guidelines recommend a one-time determination before any thyroid surgery to detect C-cell changes at an early stage. The level of basal calcitonin provides insights into the stage of the disease and helps plan the extent of resection.
  A threshold of ≥ 30 pg/ml Ctn for women and ≥ 60 pg/ml for men indicates a high probability of MTC, justifying further treatment steps.
  Lymph node metastases in the lateral lymph node compartment seem to occur only at a calcitonin level above 85/100 pg/ml and simultaneous detection of desmoplasia. Otherwise, lateral lymph node dissection can be omitted. 25% of tumors are familial, e.g., lead tumor in MEN 2a. Therefore, molecular genetic clarification is always recommended in suspected MTC.
  
  Note: Smoking, proton pump inhibitors, renal insufficiency, and chronic alcohol consumption can lead to slightly to moderately elevated calcitonin levels (control under abstinence if necessary).

Ultrasound with TI-RADS Classification (Thyroid Imaging Reporting and Data System)

Preoperative neck ultrasound plays a significant role in surgical planning. It is the basic examination method for assessing thyroid morphology.

The standardization of thyroid nodule findings allows for an assessment of dignity or risk stratification of nodules, as required by guidelines.

Thyroid nodular findings are described in detail under documentation of the following criteria:

• Size (specify diameter in all 3 planes)
• Echogenicity (hypoechoic, isoechoic, hyperechoic, anechoic, and complex echo)
• cystic components
• micro or macrocalcifications
• presence of a hypoechoic halo (halo sign)
• margin definition (sharp versus blurred)
• configuration (asymmetric, "taller than wide")
• vascularization

The following sonographic criteria are associated with a significantly increased likelihood of malignancy:

• Hypoechogenicity
• blurred margins
• non-oval shape
• "Taller-than-wide" shape: The nodule is more pronounced in depth than in width in the axial section.
• Presence of microcalcifications
  LINK TIRADS

Note:
Ultrasound can also assess the relationship to neighboring structures, lymph node status, and possible retrosternal spread.

Thyroid Scintigraphy

Scintigraphy with the tracer 99m-Technetium pertechnetate (Tc-99m) has a discrimination limit of about 1cm for lesions that are either more, equally, or less storing than the surrounding tissue and are thus described as scintigraphically warm/hot (with simultaneous suppression of surrounding tissue), indifferent, or cold.

Notes:

• The scintigram, together with ultrasound, is the basic examination method in the evaluation of thyroid nodules.
• Autonomous areas that are no longer subject to regulatory control by TSH can be unmasked by suppression scintigraphy (with orally administered thyroxine).
• Even with a normal TSH level, functionally autonomous nodules may be present. These should not be biopsied.
• Scintigraphically cold nodules that are sonographically anechoic correspond to cysts and are considered benign.
• Non-anechoic cold nodules require further evaluation

Optional Preoperative Diagnostics

Magnetic Resonance Imaging/Native Computed Tomography

• In retrosternal goiter, to assess the extent of the retrosternal portion, facilitating preoperative planning of a potentially necessary thoracic surgical access route (sternotomy).
   
• in cases of pronounced local compression symptoms
   
• in cases of organ-overlapping growth
  
  Note 1: These two examinations have no role in the initial assessment of thyroid nodules.
  
  Note 2: In differentiated thyroid carcinoma (DTC), MRI should be preferred to avoid contrast exposure.
  Computed tomography has the disadvantage that contrast enhancement with contrast medium must be avoided, partly due to the risk of iodine-induced hyperthyroidism, and partly to avoid iodine contamination in preparation for radioiodine therapy. After exogenous iodine intake, iodine receptors are blocked for an extended period, making radioiodine therapy and thyroid scintigraphy impossible.

PET-CT

• Molecular whole-body imaging in advanced tumors for recurrence and metastasis diagnostics with functional tracers such as dopamine (18F-DOPA), somatostatin analogs (68Ga-DOTATOC) in MTC, and fluorodeoxyglucose (18F-FDG) in PDTC, which often does not store radioiodine.

Scintigraphy with ⁹⁹ᵐTc-MIBI with Washout Index as a Semi-Quantitative Method

For assessing the dignity of thyroid nodules, sestamibi scintigraphy is used clinically off-label. Off-label use must be disclosed. MIBI scintigraphy should only be used for scintigraphically hypofunctional nodules from 1cm in size and suspicious sonomorphology (TIRADS 4 and 5) and detection of a follicular neoplasm (Bethesda 3/4).

Imaging with ⁹⁹ᵐTc-MIBI can be particularly used when fine-needle aspiration is indicated but not possible or has not yielded a conclusive result.

The predictive negative predictive value with rapid washout is good, follow-up controls are required.

Fine Needle Aspiration Cytology

Based on clinical, sonographic, and scintigraphic criteria, risk nodules are identified, which are then further clarified by fine needle aspiration. Because multinodular thyroid changes are common in Germany, it is advisable to limit the need for aspiration to non-autonomous nodule areas >1 cm – depending on sonographic features.
Fine needle aspiration (FNA) of a suspicious thyroid nodule serves to assess the risk of malignancy. It is particularly indicated when non-surgical treatment of the lesion is considered.

In the following scenarios, an indication for aspiration of thyroid nodules may arise:

• Patients with clinical signs of thyroid carcinoma, when the cytological diagnosis is important for surgical planning.
   
• Nodules depending on size from EU-TIRADS classification class 3: class 3 (> 2 cm), class 4 (> 1.5 cm), class 5 (> 1 cm)
   
• Nodules of any size with extracapsular growth or unclear cervical lymph nodes (here, the lymph node should also be aspirated if necessary).
   
• Nodules of any size in patients with a history of neck radiation without evidence of autonomy
   
• First-degree relatives of a patient with papillary or medullary thyroid carcinoma or multiple endocrine neoplasia type 2

Notes:

• In MTC, Ctn determination is superior to cytology. Due to the special importance of calcitonin screening, FNA is generally not required for the preoperative diagnosis of MTC. The assessment of a desmoplastic stromal reaction in histology is no longer reliably possible after FNA, so FNA should not be performed if Ctn is elevated.
• Explicitly refrain from aspiration in nodules that correspond to scintigraphically focal autonomies, as well as in nodules that do not exhibit any sonographic criteria suspicious for malignancy. 
• Cytologically, many tumor entities can be diagnosed with high accuracy. Follicular neoplasia requires histological clarification.
• The indication for surgery is based on cytology in cases of follicular neoplasia, detection of specific mutations, or other indications or evidence of malignancy.
• Detection of benign findings in FNA can avoid unnecessary surgeries. Detection of malignant cells significantly influences the surgical strategy (hemithyroidectomy versus thyroidectomy, extent of lymph node dissection).
• In encapsulated follicular tumors, differentiation between follicular adenoma and carcinoma is not possible with FNA. Similarly, FNA cannot distinguish between a non-invasive encapsulated follicular variant of a papillary thyroid tumor (NIFTP) and a papillary thyroid carcinoma. Molecular pathological additional investigations can increase the sensitivity and specificity of FNA but are not yet routinely used.
• The most common papillary carcinoma, accounting for over 80% of all differentiated thyroid carcinomas, can be diagnosed with high reliability.

Cytopathological Evaluation of FNA

The Bethesda classification is a 6-grade system designed exclusively for thyroid aspiration and is largely evidence-based. The advantage of this system lies in the clear assignment of malignancy probability in the individual groups. Furthermore, this classification allows for international comparability due to its international use.

LINK Bethesda Classification

In suspected transmural infiltration, additionally panendoscopy, tracheoscopy, and esophagoscopy

Euthyroid

• no special preparation

Hypothyroidism

Information on preoperative treatment of hypothyroidism can be found at:
LINKHypothyroidism

Hyperthyroidism
Every patient with hyperthyroidism undergoing elective thyroid surgery should have a stable euthyroid metabolic state before the operation.

• The safest method is the administration of an antithyroid drug for several weeks.
  
• In cases of manifest hyperthyroidism, additionally block iodine with short-term administration of high-dose iodide (Plummer's) 5 - 10 days preoperatively to inhibit hormone release from the thyroid, reduce thyroid perfusion (lower bleeding risk), and prevent a thyrotoxic crisis during surgery. Always after initiating medical thyrostatic therapy, otherwise risk of iodine-induced hyperthyroidism.
  
• In mild forms of hyperthyroidism, a few days of treatment with beta-blockers may be sufficient.

Information on preoperative treatment of hyperthyroidism can be found at:
LINKHyperthyroidism

Increased cardiopulmonary risk

• Assessment of surgical risk through further diagnostics (stress ECG, heart echo, coronary angiography, lung function)

Fine needle aspiration/ intraoperative frozen section

• One-stage primary surgery requires preoperative fine needle aspiration cytology and/or the possibility of intraoperative frozen section diagnosis.
  
• The intraoperative frozen section cannot reliably predict the malignancy of encapsulated tumors. The diagnosis of a PTC in the frozen section is possible if pronounced papillary structures and typical cell nuclei are visible – however, it is often uncertain, especially in small or atypical tumors. The frozen section can guide the surgical strategy but does not replace the final diagnosis in the paraffin section.
  
• The metastatic potential/lymph node metastasis potential in MTC can be assessed intraoperatively histopathologically by the extent of intratumoral desmoplasia (desmoplastic stromal reaction) and the breach of the thyroid capsule. MTC without desmoplasia do not show lymph node metastases.

Increased cardiopulmonary risk

• Assessment of surgical risk through further diagnostics (stress ECG, heart echo, coronary angiography, lung function test)

Anticoagulants

• should be discontinued 7 days before surgery, if necessary, bridging.

• Bleeding/Postoperative bleeding/Hematomas
• Wound infection/Wound healing disorder
• Thromboembolism
• Position-related cervical spine complaints
• Vocal cord paralysis/Dysphonia
• Dysphagia
• Hypocalcemia requiring substitution and follow-up checks
• Permanent hypoparathyroidism
• Thyroid hormone substitution
• Need for radioiodine therapy under exogenous or endogenous TSH stimulation
• Tumor follow-up

For large goiters extending into the mediastinum and before reoperation, rare complications should also be mentioned:

• Injuries to the sympathetic nervous system (Horner's syndrome)
• Injuries to the trachea or neck vessels
• Injury to the esophagus, pleura with tension pneumothorax, thoracic duct with chyle fistula