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New Technologies and Treatments

Thyroid Cancers : new methods for diagnosis, follow up and treatments
Drs G. Andry, E. Willemse, A. Digonnet, M. Quiriny, M. Lemort, D. Larsimont, P. Flamen

 

Recently, progress have been made in the well-differentiated thyroid cancers ( they account for approximately 84 % of all thyroid cancers) to substitute the weaning off thyroid hormone life treatment. These weaning processes were very unpleasant as patients were tired, hypothyroid and were not able to attend their professional occupations and familial tasks for 2 to 3 weeks or more.

Currently, it has been revealed that a rh TSH injection (recombinant human TSH), on the basis of two 0.9 mg-intramuscular injections for 2 days running and 48 hours previous to the whole-body Iodine 131 scintigraphy, allows to avoid these weaning process and proved to be more beneficial for the patient and has a similar sensitivity to detection.

On the other hand, by systematically measuring serum thyroglobulin and thyroid antithyroglobulin antibodies, the patient’s follow up is improved.

Finally, the development of Spiral CT pulmonary scintigraphy without contrast dye allows the early detection of pulmonary micronodules and to complete, if necessary, with a iodine scintigraphy after a rh TSH injection.

 

We must remind that most of patients with well-differentiated thyroid tumors are young (the average age : 40 to 45 years) and that a mere surgical treatment combined with thyroid hormone administration is sufficient with an excellent prognosis without any other treatment modality.

Our approach to the disease will depend much on the age of the patient, the histological characteristics of the tumor and its extent at diagnosis.

Finally, computerized systems allow the merger of scintigraphy-recorded and CT-scan-recorded images, giving a very complete anatomical view from thyroid tumors but also from parathyroid adenomas as a cause of primary hyperparathyroidism (parathyroid adenoma or hyperplasia), which is easily curable by a mere little invasive surgery.

 

Medullary thyroid cancer constitutes about 10% of all thyroid malignancies. This cancer arises in C cells (originating from the neural crest), not in follicular cells. These tumors secrete a 32-amino acid peptide : calcitonin (also termed hCT : for human Calcetonin). Another tumor marker although non-specific and with a low reproducibility is CEA (carcinoembryonic antigen). The symptoms are quite characteristic : diarrhea, facial erythema episodes, «café-au-lait» cutaneous spots (light brownish cutaneous frechels), etcetera…

These tumors may be induced by sporadic mutations or may be inheritable(family history of cancer) ( RET proto-oncogene transmissible mutation). Thanks to research conducted in the field of Molecular Biology, it is possible to identify among family members those who present the mutation and are likely to transmit or to develop the disease.

In the same way, patients having relatives carrier of other mutations in the RET proto oncogene and belonging to Type 2 Multiple Endocrine Neoplasia (MENIIa), can be diagnosed.

Patients suffering this mutation present both adrenal tumors (pheochromocytoma) and medullary thyroid cancer and sometimes parathyroid adenoma with hyperparathyroidism. The symptoms consist of sick feeling, hypertension, renal lithiasis, gastric duodenal ulcers, pancreatitis, sometimes asthenia and depression.

A simple serologic test allow the detection of hypercalcemia and high level of parathormone in peripheral blood sample as well as a 24-hour urine measurement for catecholamines or the performance of more simple methods such as an abdominal echography (adrenal glands). The MENIIb is characterized by mucosal neuromas (appear about the lips and tongue), and conjuntivae syndrome often associated with marfanoid habitus (with joint/ ligamentous hyperlaxity).

 

It is very important to proceed to the required investigations and especially to test the level of catecholamines in urine and to perform an echography in patients affected by medullary thyroid tumors because pheochromocytoma must be detected prior to any surgery. The objective is to remove the pheochromocytoma first with the required precautions for narcosis in order to suppress any risk of malign hypertensive episodes during the induction phase of anaesthesia. While the thyroid or parathyroid will be operated at a second stage, thyroidectomy with lymph node dissection, especially of the central compartment (tracheo-esophageal groove, along the current nerves and anterosuperior mediastinum) is performed.

If some lymph nodes are suspicious in the lateral compartment of the neck (previously detected by echography or Pet-scan), a dissection of lateral neck compartments or the jugulo-carotid regions will be performed.

Indeed PET scan has been proved to be extremely important in the follow-up of patients with medullary thyroid cancer : between 30 and 40 % out of those patients, despite a well-conducted surgery , show a persistence or reappearance of supranormal serum calcitonin ( and possibly of CEA), and until now, it was almost impossible to find the tumor foci responsible for these secretions.

Usually were performed Tc-DMSA scintigraphy or iodine 131-MIBG scintigraphy, scanners and magnetic resonance and even sometimes catheterization during which blood samples are drawn from the cervical area for the determination of local calcitonin gradients with regard to peripheral calcitonin. These exams had low sensitivity. Consequently, patients couldn’t be adequately diagnosed and treated. Moreover, catheterization is an invasive procedure and salvagesurgery revealed uneffective in most cases. To the contrary, the new methods in imagery and more specifically the Pet-scan have been proven to be effective.

 

According to recent research, Pet-scan is much more sensitive for the identification of neoplastic foci/lesions than resonance or CT-scan. Pet-scan combined with resonance are of course even more performant in the localization of remaining hot spots, being it in the neck, in the supraclavicular space or in the mediastinum.

(Réf. Szakall&al, J Nucl.Med, 43 (1), 2002).

According to other recent studies, Pet-scan has a sensitivity of 78% for the detection of occult medullary thyroid tumor compared to 33% for Tc-DMSA.

(Réf Dhiel&al, J Nucl Med, 20 (11), 2001).

Most of the authors agree on saying that the Pet-scan (18 Fluorine fluorodeoxyglucose positron emission tomography) is a very sensitive and effective mean for the detection of occult medullary cancer foci/lesions.

 

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Person in charge : Pr Andry Guy

Updating/Checking of this page : 02/2011