2 Physiology Seretion of thyroid hormones – T3, T4, calcitonine Iodine: 100 microgrames; 30% absorbed in digestive tractCapture in thyroid gland – oxidation (peroxidaze) – transportation in coloid (thyroglobuline) – iodisation of thirozine – MIT, DIT –T3, T4 – blood stream
3 Thyroid hormones Increase O2 consumption and metabolism Proteic metabolism: increase catabolism and anabolism (groth and development)Lipid metabolism: mobilization of lipids from fatty tissue and stimulates oxidation at cellular level.Glucidic metabolism: hyperglicemia (sinergistic with adrenaline - β-receptori), diabetes: newly developed or worseningEssential for the normal brain development (stimulated myelin production and neuronal ramifications) idiotism.Excess of T3 and T4 – thyrotoxicosis
4 Hyper Hypo Protidic metabolism Catabolism – loss of weight and muscular tissuePozitiv nitrogen balance but with anabolismLipidic metabolismLow cholesterol and TGHigh cholesterol- ateroscolerosisGucidic metabolismHyperglicemiaLow intestinal absorbtionH2O electolitesEdemaWater retention and depolimerization of MPZ = mixedemaBasal metabolismIncrease = heat productionDecereasedCardiovascularHyperkinesiaDeceresed cardiac output (mixedematous infiltration of myocardial muscle)Nervous systemHyperexcited, nervousness, insomniaApatie, lentor, comaDigestivDiharreaConstipation
5 GOITER ANY increase of volume Associated with : Benign Malignant NormalHyper-functionHypo- function
6 Goiter structural changes in thyroid gland generated by the incapacity to inssure a normal plasmatic level of thyroid hormonesA. Familial goiter – geneti factors, many mambers on the same familyB. Endemic goiter – a significant number of cases in the same arrea – low iodine in the environmentC. Sporadic – not always a clear cause.
7 Iodine deficit in thyroid gland Deficit in synthesis or hormon excretion (normal iodine or excess of iodine)Increased hormonal needsLack of iodine in waterLack of intakeAbnormal absorbtionExcessive loss (diarrhea, breast feeding)Blocked transmembrane transport of Iodine (perclorate, thyocianate intoxication)Genetic factors (under evaluation)Iatrogenic (long term iodine, AINS, corticoids, synthetic antithyroid drugs)Endoscrine diseases (acromegaly)MenopausePuberty/Pregnancy/Stress
17 Abnormal positions Ectopic goiter Intrathoracic goiter: abnormal thyroid tissue developed in the thorax – vasculature from thoracic cavityLateral cervical goiter: abnormal thiroid tissue developed in the lateral cervical areaLingual – defect in migration of tissues in emriogenesis: the thyroid gland is stuck at the level of foramen cecumIntratracheal goiter: first segments: produces obstructionIntraesophageal goiter: rarity ~ esophageal tumorOvarina goiter: abnormal thyroid tissue in the ovary (disembrioplastic/metastasis)Cervical-mediastinal goiter: cervical origin but aspirated in the upper part of thoracic cavity: feeding vessels are normal from cervical sources.
18 Treatment L-THYROXINE IODINE THERAPY RADIO-IODINE THERAPY SURGERY 50% reduction in volume in 30% of casesIODINE THERAPYRADIO-IODINE THERAPY50-60% reduction in ~1-1.5 ySURGERYTiroidectomy subtotal/total + L-Thyroxine
19 Surgical treatment – WHEN? Failure of other modalitiesMultinodular goiter or cold nodules on scintigrafyGoiter with lesions which are most probably irreversible: fibrosis, recurrent cysts)Complicated goiter: hyperthyroidism, inflammation, intracystic bleeding, compression syndromeEsthetic indications
20 THYROTOXICOSISHypermetabolic condition characterised by increased levels of FT3 and/or FT4HyperthyroidismSubacute thyroiditisExogenous administration of thyroid hormones
21 HYPERTHYROIDISMExcess synthesis and discharge of hormones in the circulationGraves 50-60%Autoimune conditionMultinodular goiter 15-20%Long lasting goiterToxic adenoma 3-5%
22 PATHOGENY Graves Disease Ig G acting aginst Thyroid gland , including effect against TSH receptor in a stimulatory fashion: activation of cAMP = increase the volume of the gland, vascular pattern and hypersecretion of thyroid hormones.LATS - Long Acting Thyroid StimulatorTSI - Thyroid Stimulating ImmunoglobulinsNodular Goiter associated with hyperthyroidism:Nodules producing high levels of hormone secretionToxic adenoma:Thyroid nodule completely independent (bening in majority of cases) without feed back inhibition = administration of T3/T4 does not produce suppression.
23 HYPERTHYROIDISM Neurological problems Fine tremour Exophthalmia Neurovegetative imbalance:Excessive sweeteningLow level feverThyroid hypertrophyHyperthyroidism syndrome depending on T3/T4 levels
24 HYPERTHYROIDISM Skin Warm, fine, moist, intense dermographism Nails Thin, fragileInfiltrative demopathyPretibial mixedemaThyrotoxic myopathyLoss of muscular massHypotoniaMuscular painFatigueAll systems are affectedCardiovascularRespiratorDigestivGenital
25 HIPERTHYROIDISM LAB SCINTIGRAPHY Increased RIC Imaging the gland Low TSHHigh FT3, FT4TSI, LATSSCINTIGRAPHYIncreased RICImaging the glandUltrasoundCTRMNFNA
26 TREATMENT Iodine – Lugol solution Corticosteroizii Symptomatic treatment:Beta-blockersSedativesInhibitors of hormone synthesis- synthetic antithyroid drugs (propiltiouracil, methimazol, carbimazol)Block the oxidation of iodine with sequential block in iodothyrozine synthesisProduces a secondary goiter development due to rises in TSHNormal thyroid hormone levels in weeksMajor side effects: Agranulocitosis, liver toxicity, LES, alopecia, nefrotic syndrome, poliarthritis, poliradiculonevritis.Iodine – Lugol solutionReduce the volume and vascular pattern of the thyroid gland. Effect is maximal in 10 days, maintained 2-3 weeks, then the gland escapes suppresion.Preopertaive or in thyrotoxicosis associated with syntehetic antithyroid drugs.CorticosteroiziiLower T secretionInhance urinary lossPrevent and treat thyrotoxicosis cresc ioduriaRADIOACTIV IODINEThyroid tissue destruction – aiming to transform all patients in hypothyroid patients.
27 TREATMENT SURGERY THYROIDECTOMY: subtotal, quasitotal, total Correct preoperative preparation – normal thyroid hormone levels + sedationPostoperative complicationsHemorrhageThyrotoxic crisesRecurrent nerve palsyHypoparathyroidism
28 THYROTOXIC CRISIS – major emergency Acute augmentation of hyperthyroid statusMay develop in the first hours postoperative, more often after incomplete preparationStage I : tachicardia >130/minute, hiperthermia, massive sweating, dehydration, intense tremour.Stage II: adds desorientation, stupor and somnolence.Stage III: comaTreatment:Large doses of synthetic antithyroid drugsMineral iodine (KCl or Lugol)Symptomatic treatment: corticoids and beta-blockersLower body temperature – refrigerationIntensive care: O2, ionic balance
32 CLINICAL EXAMINATION Anamnesis Clinical examination Sudden onset Local inflammatory signsFever high ( ), chills and tachicardiaAnterior cervical painPressure sensationRadiating: mandible, earIntensifies with swallowingAntalgic positionDysphagiaDyspnoeaDysphoniaIrritative coughingClinical examinationT gland enlarged (whoe or part) and very painfulAll inflammatory signs in the anterior cervical area (skin)Abscess formation can produce fluctuence.Inflammatory LN in the latero-cervical area
33 LAB EVALUATION High WBC with % PMN Vey high ESR Thyroid scintigram: a cold difuse area (no iodine capture)US: hypoecoic i the begining, transsonic if absecess is formed.Blood cultures – isolation of bacteriaRIC may be normal/lower then normal.In cases of abscess: puncture and culture of pathogenic germ
34 TREATMENTPrognostic: very good if rapidly diagnosed and treatment is adequateComplications without proper treatment:Septic: local (mediastinitis, fistula formation – skin, esophagus, trachea), or metastatic.Mechanic: large abscess behaves like a tumorVascular: thrombosis of adjacent veinsEndocrine: very unusual
35 TREATMENT - early Medical Surgical Antibiotics: empirical + cultures NSAIDAntialgic medicationSurgicalAbscess – drainagePartial thyroidectomy +/-
37 PATHOGENY 5% of all T pathology F>M 20 – 40y Ethiology unknownKnown:Viral (urlian, influenza)Bacteria (streptococcus, entorobacteriacea)Genetic predispositionPathogeni: destruction of folicular epithelium:Immediate release of thryoid hormonesLowers capacity to produce hormones in time
38 Pathological changes Macroscopic Mycroscopic T is increased in size (2-3x), harder, yelowishMycroscopicMultifocal granulomatous inflammatory reaction, limfocityc and plasma cells infiltration + interstitial
39 DIAGNOSTIC Past medical history: Anamnesis Clinical evaluation 50% cases2-6 weeks before respiratory infection, rhinopharinx, sometimes easy to forget about.Anamnesis+/- Sudden onsetFever (High), chills, malaiseCervical pain aggravated by swallowing, cough and head movements.Clinical evaluationT gland enlarged, asymetrical, ferm and painful.No palpable LNSigns of moderate hyperthyroidism in 20% of cases
40 LAB EVALUATION High WBC – lymphocites High ESR High T3 – T4, thyroglobulin in early stages of inflammation, while TSH and RIC are diminished.Increses levels of antyT antibody ~3 weeks after onset.US – diffuse hypoechigenityScintigram – inhomogeneous fixation with cold areas, but will become normal with healingGigantic multinuclear cells on FAC
41 DIAGNOSTIC Acute thyroiditis Hashimoto Graves Carcinoma POZITIV Pain Local and general inflammatory signsVery low RICCytologyantyT antibodyDifferentialAcute thyroiditisHashimotoGravesCarcinoma
42 PROGRESSION Self healing condition Transform in chronic inflammation 1-3 monthsNo sequelsTransform in chronic inflammationRiedel/ HashimotoHipothiroidism - 10%Recurrent condition – very rare
43 TREATMENT NSAID/ CORTICOSTEROIDS Hormonal – hyper or hypo function Surgical – an exceptionLobectomy, thyroidectomyWhen a nodular hypertrophy persists
45 PATHOGENY The most common type of inflammatory disease of T gland The most common cause of hypothyroidismF>B; 40-50yCAUSEAutoimmune aggression: ATB against Thyroglubuline, Mycrosomes.
46 Histology MACRO MICRO Hypertrophy with accentuated lobulation Ferm, pale, grey, reduced vascular pattern.MICROLymphocytic infiltration– even formation of germinative centersFollicular epithelium destruction – large oxiphilic cells Askenazy cells (diagnostic)Fibrosis
47 PRESENTATION GOITER Past medical history: Other autoimmune diseases (LES, rheumatoid arthritis, dermatomiositis)GOITERInsidious onsetNot very largeDifuse, asymmetrical, no signs of compressionThyroid function can be high, normal or lowFatigue
48 LAB WORK Nonspecific inflammatory reaction (normal WBC, increased ESR) ImmunologyAntimicrosomal antibodies 100%Antithyroglobulin antibodie 90% iThyroid functionInitial: hyperfunction without increased production (RIC increased, basal metabolism increased)Late: hypofunctiondue to destruction of parenchime (RIC bellow normal, decresed basal metabolism)
53 PATHOGENYChronic inflammation with fibrotic transformation of T gland and surrounding tissueCan be associated with other fibrotic diseases:Retroperitoneal fibrosisMediastinal fibrosisParotid gland fibrosis, salivary/lacrimal gland fibrosisSclerosing cholangitisHLA-DR3 – genetic determinationAntimicrosomal antibodies : autoimmune mechanismMycroscopy: fibrosis + lymphocytic infiltrationUnknown causeFinal stage of any autoimmune thyroiditis.
54 PATHOLOGY One lobe or whole gland Fibrotic, white tissue Fibrosis extends outside T gland: there are no cleavage plans and structures can not be identified
55 CLINICAL PRESENTATION Females: 30-60y ageAnamnesissigns of diffuse hypertrophy + compression of adjacent organsClinical examinationwood-hard consistencyTenderT gland fixed to all plansT gland does not invade skinHormonal status: normal (most cases) or hypo
56 LAB WORK Slight inflammatory response Normal or low T hormones Sometimes: low levels of antyThyroid antibodiesUS: hypoechoic + invasion in adjacent structuresScintigram: inhomogenous fixation with areas with non-fixation of iodine
57 DIAGNOSTIC Pozitiv: pathologic examination Differential COMPLICATIONS cancerHashimotoDeQuervainCOMPLICATIONSCompressionProgressionVery slow: years until compression is significant
58 TREATMENT Hormonal Surgical Replacement for hypothyroidism May reduce progression to fibrosisSurgicalThyroidectomyLimited excision for decompression
60 MOST COMMON ENDOCRINE CANCER 1% OF ALL CANCERSOccurs mainly in patients yearsAnnual incidence new cases/106Annual mortality ~4/106Most carcinomas – favorable prognosisNecroptic incedence much higher and with significant variations:USA ~1.8%; Honolulu~15%; Hiroshima 25%
61 RISK FACTORSIodine supplements increase the incidence of papillary carcinoma (<T, well differentiated, overall increases survival)External irradiationin human the only proven carcinogenic factor for thyroid carcinomachildren with neck irradiation develop papillary carcinoma
62 RISK FACTORS 1986 Cernobil effect- steady increase (Pacini 1997) Peak 3x in ;~80% children <14 years of age
64 PATHOLOGY essential in classification Papillary carcinoma 80%from follicular cellsusually well differentiatedbut very frequently multifocalmixed forms are includedslow growing – excellent prognosisSpreading: tends to spread locally into lymph nodes and adjacent structures
65 PATHOLOGYInvasion in the local lymph nodes is not associated with a worse prognosisPoor prognosis:Male gender>50 yearsLess differentiatedMetastases: lungs, rarely to bonesTumors larger then 4 cmLocal invasion or distant metastases
66 PATHOLOGY Follicular carcinoma 10% from follicular cells HIGHER FREQUENCY IN IODINE DEFICIENT AREASfrom follicular cellsusually well differentiatedslow growing – good prognosisclosely resemble folicular adenomascapsular and/or vascular invasion is defining the malignant statustends to take up radioactive iodine.10% chance of being multifocal.
67 PATHOLOGYSpreading: tends to spread through the blood stream making it more difficult to control and also grows into adjacent structures.Metastaseslung and boneusually concentrate iodinePoor prognosis associated with:Age >45 yearsLocal extracapsular invasionDistant metastases
68 PATHOLOGY Hürthle Cell carcinoma 3.6% composed of "modified follicular cells"very similar to follicular carcinoma25% chance of being multifocaldoes not tend to take up radioactive iodinehas a prognosis similar to that of follicular carcinoma.
69 PATHOLOGY Medullary carcinoma 2.7% from the parafollicular C cells There are two typesGenetic disposition – AD MUTATIONS- represents about 20% of all patients with medullary carcinomaUSUALLY PRESENT IN BOTH LOBESSporadic – occurs randomly and represents 80% of medullary carcinomaUSUALLY PRESENTS UNILATERAL
70 PATHOLOGY - CMTWorse prognosis compared with previous forms: 50% survive at 10 yearsOccult tumors discovered in families at risk – 95% cure rateDetection by screening for calcitonin basal and/or pentagastrin infusion testTUMOR PRESUMED – 95% cureTUMOR PALPABLE – 17% cureSPREADING: blood born metastases and lymphnodes
71 PATHOLOGY Anaplastic carcinoma 1.7% develops from follicular cellspoorly differentiatedaggressive and rapidly growing.poor prognosis <2 yearsSpreading: rapidly in the adjacent structures and also sends blood born metastasis – STAGE IVOthers rare tumors that may develop in the thyroid gland areLymphomaSarcoma – originating in the connective tissueCarcinosarcoma - composed of both malignant thyroid cells and connective tissueMetastatic tumors
72 SIGNIFICANT MICROSCOPIC FEATURES Differentiation levelCapsular or vascular invasion (in follicular and Hürthle cell carcinomas invasion is needed to prove the tumor malignantRegional lymph node involvement4. Invasion of adjacent structures (extracapsular invasion)
73 DIAGNOSTIC clinical examination Evaluation of the neck NODULEAssesment of nodulesFirmnessMobilityMultipleEvaluation of typical metastatic sitesCervical nodesBonesLungs
75 DIAGNOSTIC anatomical test Scintiscan:Evaluate the capacity to concentrate iodineCold nodules – 15-20% are malignantEssential in postoperative follow-upEstimate the remnant thyroid tissueDiagnose iodine concentrating metastatic tumorWBS - Diagnose bone metastases
76 DIAGNOSTIC anatomical test CAT scan and chest X-RayLung metastasesRestrosternal goiters
77 FUNCTIONAL EVALUATION Is mostly used in the follow-upThyroglobuline>5ng/ml after total thyroidectomy>10ng/ml after total thyroidectomyCalcitonine (Pg-CT)marker for the diagnosis of MTC in high risk populations (nodule + CT(+) the most significant association)Marker for postoperative follow-up
78 CYTOLOGIC DIAGNOSISFine needle aspiration cytology – most important study in evaluating thyroid nodulesCore biopsy – larger sample but higher riskHISTOLOGIC DIAGNOSISPreoperative diagnosis of most thyroid cancersHelp to plan the extent of surgical resectionSelection of cases which will not benefit from surgical management
85 SURGICAL TREATMENT FOLLICULAR CARCINOMA Dg. suspected on FNB and CONFIRMED on frozen sectionTotal/near total thyroidectomyTotal thyroidectomymakes metastases visible5-10% recur in residual tissue
86 SURGICAL TREATMENT ANAPLASTIC TUMORS Old age patients– usually is of no benefitMiddle age – total thyoidectomy may be tried, but little benefitIstmusectomy – pressure on the trachea (similar results with radiotherapy)1 year survival rate ~0
87 SURGICAL TREATMENT MEDULLARY CARCINOMA Total thyroidectomyFrequent multicentric (both forms)Lymphadenectomy in the primary drainage area – essential. 75% of cases demonstrate MTS in nodes from the central compartmentNodes in the secondary drainage area should be sampled - if involved RADICAL NECK DISSECTIONPheocromocytoma and parathyroid tumors should be checked and solved prior to total thyroidectomy
88 COMPLICATIONS recurrent laryngeal nerve damage 2-8% permanent hypoparathyroidism 1-3% ; 5-10% in difficult resectionshematoma formationwound infectionkeloid formation in the scarairway compromise (anaplastic carcinoma)
93 Disorders of the Parathyroid Glands Maintenance of calcium, phosphate and magnesium homeostasis is under the influence of two polypeptide hormones;* parathyroid hormone(PTH)* calcitonin (CT),* sterol hormone, 1,25 dihydroxy cholecalciferol (1,25 (OH)2D3.
94 Parathyroid GlandsThese hormones regulate the flow of minerals in and out of the extracellular fluid compartments through their actions on intestine, kidneys, and bones.
95 Normal functionThe PTH acts directly on the bones and kidneys and indirectly on the intestine through its effect on the synthesis of 1,25 (OH)2D3.Its production is regulated by the concentration of serum ionized calcium.Lowering of the serum calcium levels will induce an increased rate of parathyroid hormone secretion
96 Normal functionCalcitonin is released by the “C” cells (parafollicular cells in the thyroid gland)Secretion in response to small increases in plasma ionic calcium. It acts on the kidney and bones to restore the level of calciumPTH and calcitonin are antagonistic
97 Disorders of the Parathyroid Function Primary HyperparathyroidismExcessive PTH from one/more glands which are hyperfunctional.HyperCa that fails to inhibit in normal feed-back loop.Cause? – possible genetic (multiple adenomas are frequent) . Carcinoma<1%
98 Clinical FeaturesKidneys: renal stones or nephrocalcinosis (diffuse deposition of CaPO4.Skeleton: osteitis fibrosa cysticaMassive subperiostal resorbtion of boneBone cysts and brown tumors of long bonesOther: muscle weakness, easy fatigability, peptic ulcer disease, pancreatitis, hypertension, gout and pseudogout as well as anemia and depression90% cases diagnosed before that on screening for calcium
99 Diagnosis hypercalcaemia in more than one serum measuremen elevated immunoreactive PTH is characteristic (iPTH)
100 LAB Work Serum phosphate is usually low but may be normal. Hypercalcaemia is commonalkaline phosphatase (of bone origin)- highurinary hydroxyproline concentrations are commonly elevated when the bones are involved.Negative glucocoticoid supression test (supression indicates no adenoma)
101 RADIOLOGYsubperiosteal bone resorption usually on the radial surfacy of the distal phalanx with distal phalangeal tuftingcysts formation and generalized osteopenia.
102 Pre-operative localization of the abnormal parathyroid gland(s): UltrasonographyMRICTThallium 201 – Tehcnichum99m scan (subtraction study)
103 Treatment Very often “biochemical” hyperPTH. Resection of the parathyroid lesion is curative with recurrences observed mainly in the multiple glandular disease.Tumor31/2 of all hyperplastic tissueMedical management of hypercalcemiaGlucocorticoids - DiuresisMithramycin - CalcitoninBisphosphonates - PhosphatesEstrogen
104 Secondary hyperparathyroidism chronic stimulation of the parathyroid glands by a chronic decrease in the ionic calcium level in the blood
105 Major causes Dietary deficiency of vitamin D or calcium Decreased intestinal absorption of vitamin D or calcium due to primary small bowel disease, short bowel syndrome, and post-gastrectomy syndrome.Drugs that cause rickets or osteomalacia such as phenytoin, phenobarbital, cholestyramine, and laxative.
106 Major causes of chronic hypocalcemia States of tissue resistance to vitamin DExcessive intake of inorganic phosphate compundsPsudohypoparathyroidismSevere hypomagnesemiaChronic renal failure
107 HypoparathyroidismDeficient secretion of PTH which manifests itself biochemically by hypocalcemia, hyperphospatemia diminished or absent circulating iPTH and clinically the symptoms of neuromuscular hyperactivity.
108 Surgical hypoparathyroidism – the commonest Causes:Surgical hypoparathyroidism – the commonestIdiopathic hypoparathyroidismGeneticAutoimmuneFunctional (associated with hypoMg – PTH can not be released in this condition)
109 Clinical features Neuromuscular: Cardiovascular Cataract Dental problemsMalabsorbtionParesthesiaTetanyHyperventilationAdrenergic symptomsConvulsionSigns of latent tetanyProlonged QT interval in the ECGResistance to digitalisHypotensionRefractory heart failure
110 Diagnosis In the absence of renal failure hypocalcaemia with hyperphosphataemia is virtually diagnostic of hypoparathyroidism.Undetectable serum iPTH confirms the diagnosis or it can be detectable if the assay is very sensitive.
111 TREATMENT Prevention – surgical trauma Oral calcium with pharmacological doses of vitamin D or its potent analogues.Phosphate restriction in diet may also be useful with or without aluminum hydroxide gel to lower serum phosphate level.