LECTURE 8clau- Thyroiditis. Thyroid Cancer

LECTURE 8

THYROIDITIS THYROID CANCER

THYROIDITIS

DEFINITIONInflammatory disorders of thethyroid gland

ClassificationAmerican Thyroid Association : 1. Acute/subacute thyroiditis:A. SuppurativeB. Subacute (non-supurative)a) Granulomatous thyroiditis (De Quervains)b) Limphocytic subacute thyroiditis (painless)

2. Chronic thyroiditis:A. Chronic lymphocytic thyroiditis (Hashimotos)B. Fibroinvasive thyroiditis (Riedels)C. Chronic suppurative thyroiditis (tuberculosis,siphillis)D. Chronic non-suppurative thyroiditis

SUBACUTE GRANULOMATOUS THYROIDITIS

(DE QUERVAINS)

Etiopathogenesis most likely due to viral infectionViral particles NOT identified within the thyroid episodes often follow upper respiratory infectionsassociated with falling postconvalescent viral titers of various viruses (influenza, adenovirus, mumps, and coxsackievirus)Histologic features:Destruction of the thyroid parenchymaLarge phagocytic cells Giant cells

CLINICAL FEATURESFeverMalaiseSoreness in the neck (which may extend up to the angle of the jaw, or toward the ear lobes)Simptoms of hyperthyroidism may occur:PalpitationsAgitationSweatOn physical examination the gland is tender (the patient objects to pressure upon it)No evidence of abscesses formation (no redness, no local heat)Clinical signs of toxicity (Tachycardia, tremor)

LABORATORY FINDINGSESR is markedly elevated (as high as 100mm/1h);Initially: Thyrotoxicosis profile (elevated T3, T4, low TSH, low RAIU)Thyroid autoantibodies usually not detectableAs the disease progresses: T3, T4 will drop, TSH rises, symptoms of hypothyroidism occurRAIU will rise later, reflecting recovery of the gland after the insult

DIFFERENTIAL DIAGNOSISPain:Acute hemorrhage into a thyroid cyst, nodule, or neoplasmInfectious thyroiditisRadiation-induced thyroiditisTrauma-induced thyroiditis

Thyrotoxicosis:Graves diseaseToxic adenomaToxic multinodular goiter

TREATMENTMost cases: symptomatic treatment (acetaminophen 500mg every 6 hours)If pain and fever are disabling short course of NSAID or glucocorticoid therapy (Prednisone, 20-30mg initially, with gradually diminishing dosage for 3-4 weeks) may be necessary Levothyroxine is indicated during hypothyroid phaseIn 5-10% of cases permanent hypothyroidism may occur and long-life thyroxine therapy is required

COURSE & PROGNOSISSubacute thyroiditis usualy resolves completely and spontaneously over weeks/months.Occasionally: the disease starts to resolve, then suddenly get worse;Rarely: the course may extend over several years, with repeated episodes of inflammatory disease and remission.

CHRONIC THYROIDITIS

Hashimotos thyroiditisThe most common cause of hypothyroidism and goiter in the USAThe major cause of goiter in children and young adultsThe major cause of idiopathic myxedema (the end stage of Hashimotos thyroiditis)Riedels thyroiditis is considered a variant of Hashimotos thyroiditis, characterized by extensive fibrosis outside the gland; the thyroid body is enlarged, with a stony consistence

ETIOLOGY & PATHOGENESISautoimmune disease Tg-AbTPO-AbTSH-receptor-blocking Ab (TRAb-block) found in patients with atrophic thyroiditis

1-4 % of the general population (F:M=9:1).

Familial character, may be associated with other autoimmune diseases (pernicious anemia, vitiligo, miasthenia gravis, adrenal insufficiency, hypoparathyroidism)

peak of incidence: during puberty and menopause.

Histologic features: heavy infiltation of lymphocytes destruction of normal thyroidal architecture; lymphoid follicles and germinal centers may be formed;

Destruction of the gland fall in the serum T4 and T3 and rise in TSH .

SYMPTOMS AND SIGNSGoiter in an euthyroid patient / in a patient with mild hypothyroidismmild, diffuse, firm tendency to lobulation;polinodular (some cases)

Atrophic thyroid glandNo painOcular changes may occurSigns of other autoimmune disease (eg vitiligo)

Chronic autoimmune thyroiditis and vitiligo

LABORATORY FINDINGSHigh titer of thyroid autoantibodiesCirculating T3, T4 may be normal or low;normal/elevated TSHEpisodes of transient thyrotoxicosis may occur: elevated T3, T4, inhibited TSHRAIU: normal/ lowScintigramm: inhomogenous uptakeNegative inflammatory tests (ESR, fibrinogen are normal);FNAB: large infiltration of lymphocytes and Hurtle cellsUltrasound examination reveals hypoechogeneicity with pseudomicronodular pattern.

DIFFERENTIAL DIAGNOSISFrom other causes of nontoxic goiter by the presence of antithyroid antibodiesFrom Graves disease by scintigraphyIncreased uptake in GravesDecreased uptake in Hashimoto

COMPLICATIONSHypothyroidism : becomes permanent in 15% of casesLymphoma of the thyroid gland (rapid growth of the thyroid despite thyroxine therapy)Hashimotos thyroiditis may coexist with differentiated carcinoma of the thyroid (thyroid mass that fails to regress when maximum tolerated dose of T4 is given)

TREATMENTpositive thyroid antibody test does not require therapyIn patients with goiter and/or hypothyroidism thyroxine therapyLarge goiter surgeryDuring transient thyrotoxicosis Prednisone 30-40mg/dayIf ophthalmopathy is present Treat as if Graves disease is present

COURSE & PROGNOSISWithout therapy goiter/hypothyroidism myxedema

Transient thyrotoxicosis (with low RAIU and white scintiscan)

Because Hashimotos thyroiditis may be a part of multiple autoimmune diseases monitor for other autoimmune diseases

OTHER FORMS OF THYROIDITIS

Acute abscesses

very rare disease (between 1900-1985 only 253 cases) local pain, tenderness, swellingwarmth and redness of the overlying skin needle aspiration will confirm bacterial infection, identifying the germtreatment: antibiotics, incision, drainage

Lymphocytic subacute thyroiditis (painless)autoimmune disease

represents 5-20% of the hyperthyroidism cases

affecting predominately women

concerning all groups of age

frequently occurs postpartum

frequently relapses.hyperthyroidism phenomena without:infiltrative ophthalmopathypretibial myxedema mild intensity and transient character; the thyroid gland:normal or slightly enlarged, painless, firm consistency.Differential diagnosis

Gravesdisease;

Subacute granulocytic thyroiditis (De Quervains);

Chronic lymphocytic thyroiditis (Hashimotos);

Thyrotoxicosis factitia.

Chronic fibrous thyroiditis (Riedl)rare disease - fibrous proliferative process :goiter - hard consistency andExtended fibrosis (mediastinum, retroperitoneum) clinical features : dyspnea, dysphagia, disphoniatreatment surgery followed by replacement therapy (levo-thyroxine);Tamoxiphene seems to be benefic in limiting fibrosisprognosis - poor.

THYROID CANCER

most frequent endocrine neoplasia in the general population:

0.1-3.7/100 000 in men;

0.4-9.6/100 000 in women.

incidence of occult (unknown) cancer 1-30 % based on necroptic studies

Classification of thyroid tumors histologic and

anatomo-clinical

Anatomo-clinical classification benign tumors-adenomas: - follicular;- non-follicular;

malignant tumors: - carcinomas: papillary/ folliculary/folliculo-papillary/medulary/undifferentiated/epidermoid; - others : lymphoma /sarcoma/fibrosarcoma/metastasis.

Clinical manifestations Non-specific at the beginning

Diagnostic suspicion is represented by rapid enlargement of a:

single thyroid nodule

Dominant nodule in a polynodular goiter.

Thyroid nodule intrathyroid process, combined with

influence of extrathyroid factors:variations of iodine intake;

cervical irradiation;

heredity; association to autoimmune thyroid diseases (e.g. association of Hashimotos thyroiditis to thyroid lymphoma).

Clinical suspicion of malignity

intensemoderate MEN syndrome in familyRapid tumoral growth Very hard noduleFixation on surrounding structuresVocal cords paralysisLocal lymphadenopathyPresence of metastasisage under 20 or age over 60history of cervical irradiationmale genderuncertain fixation on surrounding tissuesdiameter more than 3-4 cm.

Thyroid cancer differential diagnosisthyroid adenoma

cysts

localised Hashimotos thyroiditis

peri-thyroid lymphadenopathy

peri-thyroid lipoma

carotidian aneurism

laryngocele.

Laboratory tests Not of great value:Normal thyroid hormone level is the rule.There are not specific tumoral markers,excepting calcitonin (marker for medullary carcinoma).serum thyroglobulin - useful only to appreciate tumoral relapse after surgery.Carcinoembryonic antigen - present in 20% of cases of medular carcinoma.

Imaging studies

1. Ultrasonography May detect: cysts > 2 mm diameter

nodules > 3 mm diameter

cervical adenopathy

cyst

Multiple nodules and fibrous tissue

Benign nodule

Malignant nodule

Microcalcifications

2. Gammagraphy Using Iodine123 and Technetium 99

Thyroid nodules: hypofunctional or cold

isofunctional or warm

hyperfunctional or hot.Cannot efficiently evaluate nodules < 1 cm diameter.

Gammagraphy

2. Gammagraphy Neoplasic lesions - cold (usually)

Cold benign lesions - represented by:cystsfocal thyroiditisintraparenchymatous hemorrhage.

Tumors:cold for iodine, could be hot for Tc99.

3. Conventional cervical X-rayMay reveal calcifications - frequent in :

papillary and

medullary carcinoma

4. Fine needle aspiration biopsy Best method to differentiateBenign from

Malignant nodulesAspiration sample is expressed onto a clean slide,

stained with Giemsas / Papanicolaus stain and

cytologically examined.

For small / deep nodules: ultrasound guidance

Useful method:

to evacuate the liquid content of a cyst

to introduce sclerogenic substancesinto the cyst.

Results interpretation limits:

follicular carcinoma - similitude with follicular adenoma

autoimmune thyroiditis - similar to anaplasic carcinoma

previous ATD therapy leads to histological changes (follicular carcinoma-like aspect).

Anatomo-clinical forms Papillary carcinomaFollicular carcinomaMedullary carcinomaAnaplastic carcinomaOccult carcinomaMetastasisOther: Lymphoma, sarcoma, teratoma

1. Papillary carcinoma

the most frequent thyroid cancer (30-50%).

50% of cases < 40 yrs of age

Radioiodine uptake - present in 50-75% of cases.

Metastasis:ganglionar - even if the primary tumour is not palpable ( high lymphophilia) hematogenic dissemination - late, sometimes after years of evolution. rarely a cause of death (even if lung metastasis are present).

cause of death - conversion to anaplastic carcinoma.

Papillary carcinoma lymph nodes metastasis

2. Follicular carcinoma 25% of thyroid cancer.

maximum incidence - 40-60 years.

may be indistinguishable from: normal thyroid structure or

benign follicular adenoma.

blood vessels invasion with distant metastasis to: bone or lung.Radioiodine - present in about 75 % of cases.These 2 forms of cancer may associate, resulting different clinical profiles.

3. Anaplastic carcinoma older patients.

the most aggressive form: invading the cervical region and

producing metastasis (frequently).

Anaplastic carcinoma- cold area

4. Medullary carcinomadevelops on the C parafollicular cells,

after 40 years of age.

Medullary carcinomaSporadic (80 % of cases):frequent at 50-60 years of age;

Familial:within MEN (Multiple Endocrine Neoplasia) type II

non MEN- the less aggressive

MEN type II:

IIa: - medullary carcinoma - pheochromocytoma - hyperparathyroidism

IIb: the most aggressive form- medullary carcinoma - bilateral pheochromocytoma- marfanoid phenotype.

Characteristics: histologic large amounts of amyloid

carcinoembryonic antigen- presence

calcitonin level increase:basal and after stimulation test with:pentagastrin oralcohol.

Medullary cancerhas a slow evolution,

Produces adenopathy,

does not uptake iodine,

does not respond to external radiotherapy.

5. Occult thyroid carcinomarepresented by multiple microscopic lesions

6. Secondary cancer (thyroid metastasis)represents 2-4 % of thyroid cancer.

cancers that may produce metastasis in the thyroid gland are :mammary,pulmonary, renal, malignant melanoma

7. Other malignant thyroid tumors primary lymphomas -may associate to Hashimotos thyroiditis;

disseminated lymphomas;

sarcomas - very rare;

malignant teratomas.

Thyroid lymphoma

Management of thyroid cancer

Medullary carcinomaTotal thyroidectomy followed by thyroxine therapyThe marker for recurrent cancer is serum calcitonin or serum carcinoembryonic antigen (CEA)If elevated serum calcitonin persists after total thyroidectomy MRI of the neck/chest, selective venous catheterization and sampling for serum calcitonin are necessaryNo radioactive iodine therapy; chemotherapy is not effective

Anaplastic carcinoma Does not fix radioactive iodine external radiotherapy (cobaltotherapy)chemotherapy (Doxorubicin 75mg/sqm, every 3 weeks)

the results are transient.Prognosis is very poor

Primary thyroid lymphoma:treatmentradiotherapy

chemotherapy

corticotherapy.

Prognosis in differentiated carcinomas

Prognosis in medullary carcinoma

Good survival in intrathyroidal small lesionsImpaired survival in cases with extrathyroidal invasion

Prognosis in anaplastic carcinoma ::

very poor prognosis

almost all are dead within 3 years.