Patologia tiroidea

Le neoformazioni benigne e maligne della tiroide e delle paratiroidi

ANATOMY AND PHYSIOLOGY

The thyroid is an endocrinal gland that is positioned in the middle region of the neck, in front of the trachea and above the suprasternal notch. It consists in two symmetrical lobes that are united by an isthmus; it is often accompanied by an embryonic residual of the thyroglossal duct, which is called the pyramidal lobe (the Lalouette or Morgagni Pyramid).
The hormones produced by the thyroid gland are thyroxin (T4) and triiodothyronine (T3), the production of both being iodine-dependent. The gland captures iodine with an active transport mechanism that is regulated by TSH (thyroid stimulating hormone), which in turn is produced by the hypophyseal gland. The gland then incorporates the iodine in thyroglobulin. Enzymes (protease and peptidase) then transform the thyroglobulin into thyroid hormones (T3 and T4).
Thyroid hormones perform very important metabolic functions with regard to blood sugars (which potentially induce hyperglycaemia), fats (lipolytic substances) and, at low doses, proteins (protein synthesis).

BENIGN THYROID PATHOLOGY

Benign thyroid pathology can be the exclusive domain of medical therapy, and particularly of endocrinology, but it can also require surgery. Of the benign forms that require surgery, benign nodular pathology and benign diffuse pathology stand out.
From a functional point of view, each form can be associated with hypothyroidism, euthyroidism and hyperthyroidism – in other words, with both normal and altered thyroid functioning; alterations can be the result of defect and/or excess.

HYPOTHYROIDISM

This disorder derives from impairment of the thyroid gland function. Symptoms manifest, slowly and progressively, as a slowing down of physical activity, fatigability, tiredness, somnolence, a reduction in memory, intolerance of cold, weight increase and constipation. Grave cases can be affected by myxoedema (an increase in the liquid content of cutaneous tissues) and bradycardia; extreme cases can progress to myxoedema-induced coma.
Diagnosis of hypothyroidism is confirmed by a reduction in thyroid hormones and increased TSH. A useful precaution is that of dosing antithyroglobulin antibodies (anti-TGH) and anti-thyroid peroxidase (anti-TPO) so as to exclude the possibility of autoimmune defects as the basis of glandular suffering.

HYPERTHYROIDISM

This disorder is characterised by an excessive concentration of circulating thyroid hormones.
The symptoms and clinical signs of hypothyroidism are tachycardia, trembling hands, irritability, insomnia, hypersensitivity to heat, increased appetite, loss of weight, diarrhoea, menstrual disturbances (amenorrhea) amd alterations in cutaneous annexes (hair loss and brittle nails).
Diagnosis of hyperthyroidism is confirmed by an increase in thyroid hormones with suppressed TSH. In hyperthyroidism secondary to hyper secretion of TSH, as in pituitary adenoma, TSH values increase.

BENIGN NODULAR PATHOLOGY

Thyroid nodules are defined as zones in which glandular consistency differs from that of the surrounding glandular material. Differential consistency enables diagnosis by palpation and echography.
This pathology is extremely common and its victims usually remain asymptomatic; diagnostic attention is typically triggered when glandular function alters (decompensated hyperfunctioning nodules) or when nodular zones become particularly large.
One prominent class of benign modular forms is that of the adenomas, whose characteristics lead to a distinction between papillary and follicular forms. Within this class, Plummer’s toxic adenoma (Plummer’s disease) merits particular attention. Hyperfunctional and functionally autonomous, it is a clinically evident form of hyperthyroidism. Clinical data, functional analysis and instrumental examination (echography and scintigraphy) enable accurate diagnosis and framing of this modular disorder. Treatment is initially medical (antithyroid and betablocking drugs) and aimed at correcting hyperthyroidism, and subsequently surgical (total thyroidectomy).

DIFFUSE PATHOLOGY GOITER OR STRUMA

The world’s commonest thyroid pathology is goiter. It presents as a dimensional increase in the gland and it derives principally from a lack of iodine. It mainly affects women and is endemic in certain geographical areas. The thyroid hosts hypertrophy and total or partial hyperplasia of the glandular material. Depending on circumstances, goiter manifests in various forms, from diffuse goiter to focal nodular goiter and diffuse multinodular goiter. In the initial phases, the only symptom is that of an increase in the size of the thyroid. In the most serious cases, the gland displaces the trachea and the oesophagus and thus causes symptoms of respiratory (dyspnea) and digestive (dysphagia) compression. In functional terms, the goiter can maintain a state of euthyroidism, or hyperthyroidism or hypothyroidism.
Therapy is usually medical, but switches to surgery when such treatment is resisted or when the goiter’s dimension is large enough to determine compressive symptoms or aesthetic damage.

BASEDOW DISEASE

This form of hyperthyroidism is caused by autoimmune factors. Specifically, the involvement of immunoglobulin stimulates homogeneous enlargement of the gland. This condition is associated with a form of ophthalmopathy that is characterised by exophthalmos (bulging eyes) and periorbital oedema.
Initial therapy is medical, but if pharmacology proves to be insufficient, recourse is taken to surgery (total thyroidectomy) or to radio-iodine with iodine isotope therapy (iodine isotope l131).

THYROIDITIS

The principal forms of chronic phlogosis (inflammatory processes) in the thyroid are Hashimoto’s chronic thyroiditis and Riedel’s thyroiditis. The aetiology of Hashimoto’s chronic thyroiditis is autoimmune; it starts slowly and leads to an increase in gland volume, accompanied by progressive evolution towards sclerosis in glandular tissue, and by hypofunction (hypothyroidism). Medical treatment avails of immunosuppressors, but above all of hormone substitution therapy as ways to achieve functional rebalancing.
Riedel’s thyroiditis distinguishes itself from Hashimoto’s by hosting a process that replaces normal thyroid parenchyma with fibrotic tissues. This confers the gland with a wooden consistency, which in turn stimulates substantial adhesion and compression phenomena on the trachea and the oesophagus.

MALIGN THYROID TUMOUR PATHOLOGY

The principal forms of chronic phlogosis (inflammatory processes) in the thyroid are Hashimoto’s chronic thyroiditis and Riedel’s thyroiditis. The aetiology of Hashimoto’s chronic thyroiditis is autoimmune; it starts slowly and leads to an increase in gland volume, accompanied by progressive evolution towards sclerosis in glandular tissue, and by hypofunction (hypothyroidism). Medical treatment avails of immunosuppressors, but above all of hormone substitution therapy as ways to achieve functional rebalancing.
Riedel’s thyroiditis distinguishes itself from Hashimoto’s by hosting a process that replaces normal thyroid parenchyma with fibrotic tissues. This confers the gland with a wooden consistency, which in turn stimulates substantial adhesion and compression phenomena on the trachea and the oesophagus.

PAPILLARY THYROID CARCINOMA (PTC)

This is the commonest variant of differentiated malign thyroid neoplasia. It is normally capsulated, or partially capsulated, and it comprises calcified or cystic areas with haemorrhagic content; these features are recognised and assessed under routine diagnostic echography.
Histology enables recognition of several variants: follicular (well capsulated), sclerosing (with diffuse lymphatic involvement) and tall-cell; a fourth variant is composed of highly aggressive column-shaped cells.
About 30% of PTC cases present cervical lymphatic invasion, but in 95% of such cases diagnosis demonstrates that the disease is confined to a cervical level and is free of distant metastases.

FOLLICULAR THYROID CARCINOMA (FTC)

This is an epithelial neoplasia with follicular differentiation and absence of the typical histological characteristics of papillary carcinoma. One variant within this carcinoma class features Hurtle cells with a predominant oncocytic component.
Follicular carcinoma is correlated to a chronic lack of iodine and it arises later in the life-cycle than does papillary carcinoma. Compared to PTC, FTC rarely presents with cervical lymph node diffusion (4-6%, while pulmonary and skeletal distant metastases are more frequent (5-20 %).

MEDULLARY THYROID CARCINOMA (MTC)

MTC originates from the C parafollicular cells of the thyroid. These cells produce a hormone, calcitonin, that controls the metabolism of calcium.
This neoplasia determines high serum concentrations of calcitonin, lymphatic diffusion via cervical lymph nodes and hematogenous diffusion with possible skeletal, hepatic and pulmonary metastasis.
MTC can present sporadically or, in 20% of cases, it can be associated with other endocrinal forms of familial neoplasia; these forms are defined as multiple endocrine neoplasia (MEN) syndromes. MEN syndromes associated specifically with MTC are defined as MEN 2A and MEN 2B.

ANAPLASTIC THYROID CARCINOMA (ATC)

ATC accounts for 5% of malign thyroid neoplasia cases and usually appears beyond the sixth decade of life.
It is highly malignant, its local and regional invasion is rapid and it metastasizes at distance.

DIAGNOSIS

Correct diagnosis of a thyroid pathology requires close collaboration between the exponents of various specialities (ENT, endocrinology, echography, anatomic pathology, medical laboratory). Diagnosis comprises Level I and Level II analysis

BLOOD CHEMISTRY ANALYSIS

Thyroid function is analysed by measurement of TSH (thyroid-stimulating hormone) and of thyroid hormones in the fT3 and fT4 free circulating fractions.
The measurement of calcitonin is indispensable for diagnosis of medullary thyroid carcinoma. Diagnosis of an autoimmune pathology benefits from measurement of antithyreoglobulin antibodies (TGAb) and anti thyroid peroxidase (TPOAb).
Other useful tests for the assessment of thyroid disorders are those that measure calcium, phosphorus and PTH (parathyroid hormone) levels.

INSTRUMENTAL INVESTIGATION THYROID ECHOGRAPHY

Thyroid echography plays an important role in diagnosis because of the simplicity of its execution, its repeatability and its non-invasiveness. It enables determination of the site, volume and lobar symmetry, the presence and characteristics of glandular nodules, and the presence of suspected laterocervical lymph nodes.
Ecocolour doppler examination yields information on the intensity of gland vascularisation and hence on the possible presence of malign nodular content.

NECK CT e MRI

In cases of neoplastic illness or of endothoracic retrosternal goiter, these examinations serve to analyse the relationships between the thyroid and the adjacent organs and vascular structures. Regarding CT, iodine based contrast medium should be avoided when a neoplastic pathology is suspected, so as not to preclude the option of radioactive iodine treatment/ radioiodine treatment.

THYROID SCINTIGRAPHY

This technology enables discrimination between “hot” and “cold” nodules. Under scintigraphy, “hot” nodules are hyperfunctional; they account for 5% of thyroid nodules and run a very low risk of malignancy.
The “cold” nodules (which have high glucose uptake) and the “warm” nodules (which have normal glucose uptake) are at greater risk of malignancy (c. 10%).

FIBEROPTIC LARHYNGOSCOPY

This examination enables assessment of vocal cord mobility. Said mobility is informative in the context of malign thyroid neoplasia because of the latter’s ability to infiltrate the nerve that controls vocal cord movements (the inferior laryngeal nerve or recurrent nerve). Additionally, this information is mandatory prior to thyroid surgery, which could cause iatrogenic damage to the nerve in question.

CYTOMORPHOLOGIC ASSESSMENT

Cyst aspiration is performed by means of a fine needle (Fine Needle Aspiration Biopsy, FNAB) and is
monitored by echography.
This procedure is highly accurate and is appropriate for all nodules that have a diameter greater than 1 cm under echography, or that are clinically suspect. When nodular diameter is below 1cm, cyst aspiration should in any case be applied to subjects who have a family history of thyroid carcinoma, and/or whose nodules bear dubious echographic signs (micro calcifications, vascularisation) and/or who have previously undergone irradiation.

SURGERY

All forms of malign tumour pathology, whether suspected or confirmed, require surgical treatment.
Endocrinologists and surgeons alike need to bear this requirement in mind. If surgery is favoured, the choice must be clearly explained, in terms of characteristics, advantages and consequences, to the patient.
The clinical situations that militate in favour of surgery are

  • rapid nodular volume growth
  • evolution from the neck to the thorax of cervicomediastinal goiter
  • tracheal deviation and/or tracheal compression
  • toxic goiter, i.e., thyroid hyperfunction – toxic adenoma (Plummer’s adenoma)
  • disturbances deriving from dysphagia – cervical aesthetic imperfections deriving from increased glandular dimensions.

In contrast, all malign thyroid tumours must undergo surgery, when and where possible. On the basis of histological type and of the possible presence of suspect lymphatic glands, good practice for these tumours is removal of regional lymph nodes. This extension of lymph node surgery conforms to exact codification and belongs to a type of procedure known as neck lymph node dissection. Less frequently, for advanced stage tumours, surgery also addresses bordering anatomic structures. These radical tumour extensions are normally predicted by pre-operative assessment (disease stadiation) and are described to and discussed with the patient prior to admission to surgery.
Currently, there are two alternatives for the surgical removal of thyroid pathologies: total thyroidectomy and partial thyroidectomy (lobectomy and removal of the isthmus). In both cases, the operation requires a small horizontal incision in a neck skinfold. Use of optic fibre endoscopy, a routine procedure in ENT, enables a considerable reduction in the length of the incision; this “mini-invasive” procedure is known by the acronym MIVAT (mini-invasive video assisted thyroidectomy). The advisability of this specific approach (which does not modify the thyroid material to be removed) can be discussed whenever appropriate by the surgeon and the patient. In any case, the operation consists in: the identification and preservation of the recurrent laryngeal nerve and of the parathyroid glands (which are responsible for blood calcium concentration); the removal either of the entire gland or of a single thyroid lobe; the placement of two small drainage tubes; and stitching that, by its hidden position within the previously mentioned neck skinfold, pays particular attention to aesthetic appearance.
Identification and preservation of the recurrent laryngeal nerves and of the parathyroid glands requires the surgeon to have considerable experience and to be able to sustain meticulous attention. Monolateral damage to the recurrent laryngeal nerve, as previously mentioned, provokes paralysis of the given side of the mouth and, possibly, voice disturbances (dysphonia); if the damage is bilateral, the risk (albeit very remote) is that of closure of the respiratory space and hence of tracheotomy.
Preservation of the parathyroid glands is indispensable to the maintenance of appropriate homeostasis in the organism’s calcium levels. In the immediate post-operative period, the patient undergoes calcium checks to ascertain whether or not the preserved glands function correctly.
Occasionally, although the parathyroid glandular tissue has been preserved, post-operative hypocalcaemia occurs as the result of surgery-related ischemic damage. This scenario requires a therapy of orally administered calcium that continues until the affected glands have resumed normal functioning.
Discharge depends on when the drainage tubes are removed, but normally occurs 2-3 days after the operation.
When surgery involves complete removal of the thyroid (total thyroidectomy), hormonal substitution therapy (Levotiroxina) is necessary. Daily dosage is established with the help of an endocrinology expert.