lecture 8clau- thyroiditis. thyroid cancer
DESCRIPTION
LECTURE 8TRANSCRIPT
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LECTURE 8
THYROIDITIS THYROID CANCER
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THYROIDITIS
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DEFINITIONInflammatory disorders of thethyroid gland
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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
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SUBACUTE GRANULOMATOUS THYROIDITIS
(DE QUERVAINS)
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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
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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)
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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
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DIFFERENTIAL DIAGNOSISPain:Acute hemorrhage into a thyroid cyst, nodule, or neoplasmInfectious thyroiditisRadiation-induced thyroiditisTrauma-induced thyroiditis
Thyrotoxicosis:Graves diseaseToxic adenomaToxic multinodular goiter
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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
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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.
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CHRONIC THYROIDITIS
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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
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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 .
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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)
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Chronic autoimmune thyroiditis and vitiligo
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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.
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DIFFERENTIAL DIAGNOSISFrom other causes of nontoxic goiter by the presence of antithyroid antibodiesFrom Graves disease by scintigraphyIncreased uptake in GravesDecreased uptake in Hashimoto
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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)
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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
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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
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OTHER FORMS OF THYROIDITIS
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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
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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.
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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.
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THYROID CANCER
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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
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Classification of thyroid tumors histologic and
anatomo-clinical
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Anatomo-clinical classification benign tumors-adenomas: - follicular;- non-follicular;
malignant tumors: - carcinomas: papillary/ folliculary/folliculo-papillary/medulary/undifferentiated/epidermoid; - others : lymphoma /sarcoma/fibrosarcoma/metastasis.
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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.
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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).
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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.
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Thyroid cancer differential diagnosisthyroid adenoma
cysts
localised Hashimotos thyroiditis
peri-thyroid lymphadenopathy
peri-thyroid lipoma
carotidian aneurism
laryngocele.
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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.
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Imaging studies
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1. Ultrasonography May detect: cysts > 2 mm diameter
nodules > 3 mm diameter
cervical adenopathy
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cyst
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Multiple nodules and fibrous tissue
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Benign nodule
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Malignant nodule
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Microcalcifications
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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.
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Gammagraphy
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2. Gammagraphy Neoplasic lesions - cold (usually)
Cold benign lesions - represented by:cystsfocal thyroiditisintraparenchymatous hemorrhage.
Tumors:cold for iodine, could be hot for Tc99.
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3. Conventional cervical X-rayMay reveal calcifications - frequent in :
papillary and
medullary carcinoma
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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.
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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).
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Anatomo-clinical forms Papillary carcinomaFollicular carcinomaMedullary carcinomaAnaplastic carcinomaOccult carcinomaMetastasisOther: Lymphoma, sarcoma, teratoma
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1. Papillary carcinoma
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the most frequent thyroid cancer (30-50%).
50% of cases < 40 yrs of age
Radioiodine uptake - present in 50-75% of cases.
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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.
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Papillary carcinoma lymph nodes metastasis
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2. Follicular carcinoma 25% of thyroid cancer.
maximum incidence - 40-60 years.
may be indistinguishable from: normal thyroid structure or
benign follicular adenoma.
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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.
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3. Anaplastic carcinoma older patients.
the most aggressive form: invading the cervical region and
producing metastasis (frequently).
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Anaplastic carcinoma- cold area
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4. Medullary carcinomadevelops on the C parafollicular cells,
after 40 years of age.
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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
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MEN type II:
IIa: - medullary carcinoma - pheochromocytoma - hyperparathyroidism
IIb: the most aggressive form- medullary carcinoma - bilateral pheochromocytoma- marfanoid phenotype.
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Characteristics: histologic large amounts of amyloid
carcinoembryonic antigen- presence
calcitonin level increase:basal and after stimulation test with:pentagastrin oralcohol.
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Medullary cancerhas a slow evolution,
Produces adenopathy,
does not uptake iodine,
does not respond to external radiotherapy.
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5. Occult thyroid carcinomarepresented by multiple microscopic lesions
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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
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7. Other malignant thyroid tumors primary lymphomas -may associate to Hashimotos thyroiditis;
disseminated lymphomas;
sarcomas - very rare;
malignant teratomas.
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Thyroid lymphoma
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Management of thyroid cancer
- Papillary and follicular carcinomaLobectomy for small (
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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
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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
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Primary thyroid lymphoma:treatmentradiotherapy
chemotherapy
corticotherapy.
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Prognosis in differentiated carcinomas
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Prognosis in medullary carcinoma
Good survival in intrathyroidal small lesionsImpaired survival in cases with extrathyroidal invasion
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Prognosis in anaplastic carcinoma ::
very poor prognosis
almost all are dead within 3 years.