Surgical management of the thyroid nodules

Introduction
Thyroid nodules are a relatively common and problematic pathology because of the risk of dysfunction and malignancy. They are more common in women and in areas with iodine deficiency. Anamnesis is rarely helpful in differentiating benign and malignant nodules. Reports of the risk of malignancy in palpable thyroid nodules vary in the literature between 10% and 14 % (1-3). The majority of thyroid nodules are follicular adenomas, which are benign tumors that may occur singly or in multiples and may mimic normal thyroid function, trapping iodide and producing thyroid hormones. Other common benign nodules include colloid adenomas or cysts (4).
The objective of this paper is to evaluate the thyroid nodules and their management, including the clinically inapparent nodules (incidentaloma), especially when the risk of cancer is high, considering that the ultrasonographic discovery of incidentaloma grows the medical expenses and the patient’s psychological stress (5,6).

Material and methods
We retrospectively evaluated 40 patients treated in our clinic for a subsequent nodular thyroid pathology during a period of 5 years.
The laboratory evaluation was made in different medical places. The evaluation included in each case a determination of serum TSH, T3 and T4 levels and in some cases serum calcitonin level. A cervical ultrasonography was performed for each patient. Fine needle aspiration technique was performed under ultrasonographic guidance (3 biopsies for every nodule greater than 1 cm). We excluded from this study the surgical management for the hyperparathyroidism and the Basedow disease.
We established 3 major indications for surgery concerning a thyroid nodule: mechanical complications (the compression of the aerodigestive tract), hyperthyroidism( unique nodules or multinodular goiter) and the risk of cancer. The last group was made of asymptomatic patients having a thyroid nodule and we evaluated the risk of thyroid cancer among them.
There are 2 major indications for surgery:
A. Compulsory surgical approach
There are 3 criteria that lead to this type of surgery:
- Laboratory tests: serum calcitonin levels higher than 10 pg/mL are current in the medullary thyroid carcinoma and in the C-cell hyperplasia.
- Histology: a “suspicious” or “malignant” categorized nodule after the FNAB.
- Clinical aspects: a hard nodule (risk of cancer) or a suspicious cervical lymphadenopathy.
B. Optional surgery approach
In this case there aren’t any elements to suggest a compulsory surgical approach and thus we have 2 possibilities:
- performed as a surgeon’s option if there are elements of predictive malignancy (for example a male immuno-depressed person, presenting a 20 mm hypoechoic thyroid nodule);
- performed as a patient’s option when there is little or no sign of malignancy.
The predictive elements of malignancy are: the patient’s concurrent diseases (other that the thyroid nodule), the patient’s age (under 25 years old and older than 60), male patients, immunodepression, antecedents of cervical radiation therapy, antecedents of thyroid cancer in the family, the size of the nodule (greater than 3 cm), ultrasonographic data - the presence of a full, hypoechoic nodule with poorly defined margins and the presence of pinpoint calcifications (7-9) (Fig. 1,2).
Our study presents a detailed description of the clinical, biological, ultrasonographic and histological characteristics of the surgically-removed thyroid nodules, the epidemiology of the population having thyroid cancer and the analysis of the predictive malignancy factors.

Statistic Analysis
In this study we analysed the correlation between the final diagnosis of thyroid cancer and each one of the quality variables (sex, antecedents, clinical and ultrasonographic characteristics and the FNAB).We also emphasized on the relationship between the final diagnosis of thyroid cancer and the quantity variables ( patient’s age, the ultrasonographic size of the nodule).

Results
There were 40 patients included in this 5-year retrospective study (2004-2008), of which 33 were women and 7 men. The histological examination of the surgically-removed thyroid nodules found the evidence of malignancy in 7 cases - 5 women and 2 men, with a rate of cancer of 17,5% in the studied population, which is superior to that found in the French ENT Society report from 1995 (7,56%) (10).
The indications for the surgical management of the thyroid nodule, taking into consideration our experience and the ANDEM recommendations (11-13) (each one not excluding the others) were:
- mechanical complications: 5 patients (12,5%);
- hyperthyroidism: 7 patients (17,5%);
- suspicious or cancer-risk nodules (unique nodule or multinodular goiter, with one or more suspicious nodules): 30 patients( 75%).
Of the 5 patients having at least one malignant lesion, the diagnosis was made by analysing the most suspicious nodule in 4 of them, while in the fifth patient the discovery was by chance. The data of this patient was introduced in the ‘benign’ section of the group because the nodule was benign, the cancerous cells being discovered in other part of the surgical specimen.
One asymptomatic patient presenting high calcitonin levels had a papillary thyroid carcinoma discovered by chance.
Of the seven thyroid cancers discovered, 3 were papillary thyroid carcinoma, of which 2 on a suspicious nodule and 1 discovered on the surgical specimen after the ablation; 2 were follicular carcinoma, both on suspicious nodules; 1 was a medullary thyroid carcinoma and 1- an anaplastic carcinoma.
A cytological exam after the FNAB was performed in 30 patients, the non-conclusive results being excluded from the final evaluation. For the sensibility and the specificity of the test, we included in the evaluation only the malignant and suspicious results after the FNAB.
The results were as follows: sensibility 92,9%, specificity 49,5%, (positive predictive value 35,1%, negative predictive value 95,9%). False-negative results rate was 4,1% and the false-positive results rate was 64,9%.
The rate of cancer in front of a positive FNAB( malignant or suspicious- medullary and papillary carcinoma) was 35,1%. The rate of cancer in front of a negative FNAB was 4,1%.

Discussion
Thyroid nodules’ evaluation represents a challenge for the clinician because he must be able to identify those nodules representing cases of carcinoma that require surgical intervention. The optimal clinical management of nodular thyroid disease is somewhat controversial.
Based upon our experience we suggest the following algorithm for the diagnosis and management of thyroid nodules (Fig. 3)
Analysis of ultrasonographic risk factors: there were evaluated 3 major risk factors predictive for thyroid cancer: hypoechogenity, poorly defined nodular margins and the presence of small calcifications in the nodule. These factors were studied in 39 cases, because in the remaining case the cervical lymphadenopathy was the point of departure, the final histological analysis showing a 7 mm papillary thyroid carcinoma. The size of the nodules was not among the criteria used for differentiating the benign from the malignant nodules. The average was 25,5 mm for the benign nodules and 23,2 mm for the malignant ones. A size superior to 30,0 mm wasn’t more frequently found in the benign nodules compared to the malignant ones.
The correlation between the frequence of the thyroid cancer found in the surgical specimens and the number of ultrasonographic risk factors present at the preoperative evaluation: the multi-variable analysis of ultrasonographic criteria allowed the evaluation of every factor’s contribution to the characterization of malignant nodules and led to the conclusion that only hypoechogenity and the small nodular calcifications are predictive for thyroid cancer.
The presence of small, pinpoint calcifications in the nodules at the ultrasonographic evaluation was 5 times more frequent among the malignant nodules than in the benign ones therefore representing an important predictive risk factor for cancer.

Conclusion
We evaluated the risk of cancer of the thyroid nodules upon the clinical findings and the laboratory investigations, FNAB and HRUS. Nowadays FNAB is the most precise and effective investigation and can be performed sistematically. HRUS can remain an important tool for assisting in surgical decision even though it is operator-depending.
The new immunohistochemical and genetic techniques will be in the near future the reference-tests for the nodules diagnosis.

References
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