MEZINÁRODNÍ CENTRUM KLINICKÉHO VÝZKUMU „TVOŘÍME BUDOUCNOST MEDICÍNY“ Thyroid gland, salivary glands ENT Clinic of Masaryk university, Brno Faculty St. Ann Hospital Head: Ass.prof. Gál Břetislav, MD, Ph.D. Pekařská 53, Brno , 656 91 Anatomy ▪ 2.-4.trach. ring, C5-Th1; butterfly shape, lobus dexter, sinister, isthmus, lobus pyramidalis 50% ▪ Nervus laryngeus recurrens (innervation of laryngeal muscle) et superior (m. cricothyreoideus) ▪ Blood suply: ATS (ACE/ACC), ATI (TTC), a.thyreoidea ima (aorta/ABC); VTS (VF), VTM (VJI), VTI (v. brachiocephalica) ANATOMY Physiology of thyroid gland The largest purely endocrine gland producing thyroidal hormones – iodized amino acids. ▪ Thyrocytes – creates follicles. The thyroid secretes several hormones, collectively called thyroid hormones. The main hormone is thyroxine, also called T4. Thyroid hormones act throughout the body, influencing metabolism, growth and development, and body temperature. During infancy and childhood, adequate thyroid hormone is crucial for brain development. ▪ Parafollicular cells: hormone calcitonin – calcium metabolism Diagnosis ▪ History of disease, clinical evaluation – aspection, palpation ▪ WHO goiter classification: I palpable, invisible II palpable, visible III visible from distance ▪ Functional endocrinologic evaluation – TSH, T3, T4, Tg, calcium, (calcitonin) Diagnosis - ultrasound ▪ Ultrasound – gold standard both in early diagnosis and in follow up ▪ reproducible, non invasive evaluation ▪ goiter (man >22ml, women > 18ml) ▪ The smallest lesion for detection ≥2mm Ultrasound guided fine needle aspiratory cytology (FNAC), Bethesda classification cytology from nodule > 1cm, Bethesda classification I-VI Ultrasound guided fine needle aspiratory cytology (FNAC) ▪ uncertain category III, IV, - FNAC is not helpful in decision about therapy ▪ FNAC – possible repeat in 3 months, follow up of nodules ▪ In future – detection of mutations BRAF, NRAS, HRAS, KRAS, RET/PTC1, RET/PTC3 a PAX8/PPARγ Diagnosis ▪ CT (without contrast medium, possible delay of radio iodium in 3 months), magnetic resonance – in retrosternal spread, primary retrosternal goiter, lymphadenopathy) ▪ Scintigraphy – tumors accumulated 131I, residual tissue, recurrence of disease, primary hyper parathyreosis ▪ PET/CT ▪ Fibro endoscopy – laryngo-tracheoscopy Disease of thyroid gland ENDOCRINOLOGY – diagnosis and conservative treatment ENT, surgery – surgical treatment According to function: ▪ Hyperfunction(thyrotoxicosis) ▪ Hypofunction ▪ Diseases with eufunction According to morphology: ▪ Congenital diseases ▪ inflammations, diffuse hyperplasia ▪ tumors: – benign – malignant Congenital developmental diseases ▪ Agenesis ▪ Accessory / ectopic gland – Lingual, thoracic goiter ▪ Persist. dct. thyroglossal ▪ Medial cervical cyst and fistula ▪ Ectopic parathyroid glands Inflammatory diseases Type Etiology Clinical features Therapy Acute thyroiditis • Bacterial • Viral • Specific (actinomycosis, tbc) Pain, fever, swelling, redness of overlying skin Antibiotics, corticosteroids In Abscess: surgery Subacute thyroiditis (de Quervain) Paramyxovirus infection, genetic predisposition Pain, fever, recurrences, sometimes hypofunction, In connection with viruses' Antibiotics, non-steroidal anti-inflammatory drugs, corticosteroids in severe cases Chronic lymphocytic autoimmune Hashimoto Autoimmune disease Hard, often asymmetrical thyroid swelling, infiltration of surrounding tissue Medical treatment with thyroid hormone Total thyroidectomy to reduce compression syndrome Chronic fibrous thyroiditis (Riedel) Not known compression syndrome hypofunction Medical treatment with thyroid hormone Total thyroidectomy to reduce compression syndrome Disesases with hyperfunction of thyroid gland Thyrotoxicosis (Graves-Basedow disease – autoimmune disease) Toxic adenoma (independent adenoma) ▪ Symptoms-hyperactivity, muscle adynamia, tachycardia, higher perspire, ev. exophthalmia (endocrine orbitopathy) ▪ Diagnosis – higher level of thyroidal hormones, high level of antibodies against TSH ▪ Therapy – medical, if no effective – total thyroidectomy or hemithyroidectomy Benign tumors of thyroid gland ▪ eufunction, hypo-, hyperfunction ▪ diffuse/nodal ▪ benign/malignant ▪ primary/ secondary retrosternal goiter ▪ compression syndrome Benign tumors of thyroid gland Cysts, adenomas, diffuse, autoimmune disease Nodules - solitary, multiple ▪ incidence growing with age>50 let, female : male 6:1 ▪ diagnosis – laboratory tests, ultrasound, (CT), cytology ▪ Significant for diagnosis – increase of nodule 2-4mm/ year Thyroid carcinoma (TC) thyroid malignancy ▪ Well differentiated TC (WDTC) – papillary (PTC) 70-80% – follicular (FTC) 10-20% ▪ Medullary (MTC) parafollicularcells 5% ▪ Anaplastic not differentiated 1% increasing incidence of PTC, incidence of other stabile Risk factors of thyroidal malignancy ▪ Ionization radiation, radiotherapy (especially in childhood) ▪ smoking ▪ Low income of iodine, high TSH ▪ thyroid antagonists in food ▪ Positive congenital history Well differentiated TC (WDTC) ▪ prognostic factors WDTC MACIS – M distant metastasis – A age – C completness of surgery – I invasion to neighborhood – S size of tumor ▪ M0 <45 let, negative resection margins, intracapsular growth < 1cm Papillary thyroid cancer Follicular thyroid cancer Neck metastasis without prognostic influence Neck metastasis worsening prognosis ~35 year Older patients intrathyroid., lymphatic, hematogenous spread lymphatic, hematogenous spread utilize 131I utilize 131I WDTC – primary surgical treatment ▪ Total thyroidectomy, 1, 2 stages surgery ▪ cervical lymphadenectomy in cN+ (lymphatic nodule +) ▪ adjuvant 131 I on case of risk factors ▪ Follow up (TSH, Tg, ultrasound, scintigraphy) ▪ hormonal substitution MTC medullary cancer ▪ sporadic 70-80%, hereditary (autosomal dominant) syndroms MEN2A, MEN2B (pheochromocytoma, neurofibroma, parathyroid adenomas); marker: calcitonin ▪ aggressive, early neck metastases, ipsi- (50%), kontralaterální (25%), distant metastases more radical treatment: ▪ total thyroidectomy ▪ prophylactic neck lymphadenectomy (central/lateral region) ▪ adjuvant actinotherapy (external irradiation) (not utilize 131I) ▪ prognosis – 75% ▪ Genetic evaluation of family members, ev. TTE Anaplastic cancer ▪ Poor prognosis, survival < 1 year, patients > 60-70 year ▪ Quickly growing neck mass , dyspnea, recurrent nerve palsy, compression syndrome ▪ Therapy - palliative actinotherapy, symptomatic treatment, tracheostomy Other thyroid malignancy Very rare tumor: lymphoma (very frequently in terrain of Hashimoto thyroiditis), sarcoma. Secondary tumor: lung, breast, uterus, renal cancer Thyroid malignancy Histologic type Histology Clinical features Therapy Well differentiated cancer (papillary and follicular adenocarcinoma Thyrocytes Papillary Follicular Proof of thyroglobulin Solid tumor with fibrotic capsule Metastasis on the neck, to the lung and bones Total thyroidectomy+- neck dissection, radio-iodine or external RT, hormonal suppression and substitution Medullar thyroid carcinoma (C-cell carcinoma) C-cells (parafollicular) Amyloid Proof of calcitonin Early hematogenic and lymphogenic metastases Tendency to rapid growth, Higher level of calcitonin , metastasis to the lung, bones and liver Total thyroidectomy+ neck dissection, external RT, hormonal suppression and substitution Anaplastic thyroid carcinoma Atypical cells similar sometimes to sarcomas rapid growth, hard solid tumor, infiltration of surroinding tissue, distant metastasis Palliative external RT, surgery, chemotherapy - or symptomatic treatment Malignant lymphoma Non-Hodgkin from B- lymphocytes rapid growth, neck lump, enlarged lymph-nodes external RT, chemotherapy Indication to surgery ▪ Suspicion of malignancy, confirmed malignancy – ultrasound, FNAC ▪ compression syndrome (discomfort, pressure in the neck, dysphagia, disorder of swallowing, hoarseness, dyspnea) ▪ Thyrotoxicosis resistant to medical treatment Extent of surgery ▪ hemithyroidectomy (second lobe without suspicious nodules , benign cytology) ▪ total thyroidectomy (malignancy, Bethesda (IV) V, VI), compression syndrome ▪ therapeutic neck dissection – Well differentiated TC ▪ prophylactic neck dissection – medullar carcinoma ▪ MIVAT miniinvasive video-assisted thyreoidectomy Total thyroidectomy ▪ cca 2 hours, stay in hospital until 5.-7. day, 3 weeks rekonvalescence, hormonal substitution – months; lázeňská léčba; lymfodrenáže total thyroidectomy total thyroidectomy Lateral approach – widely used as the most safe Identification of NLR in tracheoesophageal groove,/ in the place of crossing with ATI/ below inferior Para thyroidal body / Wang method Neuromonitoring ▪ Non invasive method ▪ bipolar probe, electric impulse, recording electrode ▪ Outcome of stimulation: biphasic amplitude, with characteristic latency Neuromonitoring Risk of thyroidectomy N. recurrens paresis – nerve contused / interrupted (neuropraxia, axonotmesis, neurotmesis); micro suture in case of interruption, end to end, ansa n. XII – higher tonus of vocal cord – unilateral (hoarse voice)/ bilateral (acute dyspnea, cave tracheostomy!) – temporary / permanent > 1 year – voice rehabilitation – days to months Unilateral n. recurrens paresis ▪ hoarseness, faint, dyspneic voice ▪ corticotherapy, B12, speech(-language) therapy ▪ Surgery treatment of permanent unilateral paresis medialization of vocal cord (fat injection) Bilateral n. recurrens paresis ▪ Inspiratory dyspnea and stridor ▪ laryngoscopy , tracheostomy, corticoids, B 12, speech(-language) therapy ▪ Surgery after 1 year – lateralization Bilateral n. recurrens paresis- arytenoidectomy Paresis N.Laryngeus superior ▪ sensitive innervation of aditus laryngis ▪ motoric innervation m.cricothyreoideus (tensor of vocal cord) ▪ symptoms: lower voice efficiency, inability raise one's voice, aspiration (in both sided injury) ▪ prevention – ligation branches of ATS closely to thyroid gland capsule ▪ Frequent spontaneous recovery ▪ speech(-language) therapy, Hypocalcemia after surgery ▪ Ca < 2,00 mmol/l without clinical symptoms, Ca < 2,10 mmol/l with clinical symptoms, in two following sampling ▪ hypo- parathyrosis, frequently perceived negatively ▪ temporary / permanent > 6 months ▪ damage of blood supply of parathyroid body/ his removal ▪ auto transplantation of parathyroid body Hypocalcemia – symptoms, diagnosis ▪ paresthesia sup. and inf. extremities, around mouth, convulsions ▪ The Chvostek sign - the twitching of muscles innervated by the facial nerve (CNVII), Trousseau's Sign - is characterized spasming of wrist and hand muscles due to neuromuscular irritation following brachial artery occlusion ▪ anxiety, lability, depression in chronic cases ▪ development some hours after surgery, the lowest level 3.-5.den ▪ Calcium sampling 1st, (2nd), 4th day Hypocalcemia – therapy ▪ asymptomatic hypocalcemia above 2 mmol/l without substitution – 2-2,1 mmol/l: 1-2g calcium/d p.o. – 1,86-2 mmol/l: 1-2g calcium/d , 0,25 mcg/d AlphaD3 – < 1,86 mmol/l: 3g calcium/d , 1mcg AlphaD3, Mg 250mg/d – in spams calcium and magnesium parenterally ▪ dismission in > 1,9mmol/l and growing tendency Complication after surgery ▪ bleeding - life threatening, open suture, evacuation of hematoma, revision under general anesthesia ▪ laryngeal edema ▪ cosmetic defect – keloid, atrophy, fixation of scar to trachea Salivary glands ▪ Serous: gl. Parotis (dct. Stenoni), Ebner´s lingual glands ▪ Mixed: gl. Submandibullaris (dct. Whartoni), gl. Sublingualis ▪ small salivary glands – on oral cavity mucosa membrane Function: Moistening of mucosa membrane, mouthful wrapping, ferment ptyalin Parotid gland ▪ Strictly serous tubo-alveolar salivary gland ▪ Ramification of facial nerve (CN VII): Pes anserinus nervi facialis: – rr. temporales – rr. zygomatici – rr. buccales – r. marginalis mandibulae – r. colli ▪ Duct - dct. Stenoni Salivary glands inflammations Acute ▪ acute bacterial sialadenitis parotid gland/submandibular gland. Ascendent infection, bad hygiene of oral cavity, diabetes mellitus, dehydration. – Painful swelling, include skin, pus discharge from duct – Antibiotic treatment; in abscess – incision ▪ acute viral (mumps) – paramixoviridae family (parotitis), affection of testes, CNS,CN VIII - deafness – analgesics, antiphlogistic, Chronic chronic recurrent parotitis – congenital duct ectasia, with „milk“ saliva. In acute exacerbation AB, massage, hygiene of oral cavity Chronic sclerosing sialadenitis of the submandibular Gland („Küttner tumor“) fibrous changes, enlargement of the gland, diff dg: cave tumor. Therapy: surgery, the gland is removed. Myoepithelial sialadenitis (Sjögren Syndrome), Benign lymphoepithelial lesion ▪ autoimmune disease ▪ Lesion of other exocrine glands, rheumatic disease ▪ Bilateral enlargement of parotid gland, sometimes submandibular gland, xerostomia, „sicca syndrome“ (affecting upper respiratory mucosa), xerophthalmia ▪ Treatment: corticosteroids, immunosuppressive drugs ▪ In terrain diseased parenchyma - malignant lymphoma 40x frequently – removal and histological evaluation! Sialoadenosis ▪ Non inflammatory gland parenchyma hyperplasia and hypertrophia, various etiology, for inst.: antihypertensive drugs, beta sympathomimetics ▪ endocrine sialoadenosis – in diabetes (Charvat sign), pregnancy ▪ Non painful enlargement of glands without greater clinical trouble Mixtumor parotis Advanced cancer of submanbulary salivary gland Tumors of salivary glands ▪ All ages ▪ children – 95% vasoformative lesions ▪ Maximum of incidence 4. - 6. decennium ▪ Highly malignant 6. - 8. decennium Tumors of salivary glands epidemiology ▪ 1% of human tumors, 3-4% HNSCC ▪ Incidence 1 on 100 000 inhabitants • parotis 80% • submandibular 10% • small glands 8-9% • sublingual 1% Parotid pleomorph adenoma side left Mixtumor parotis Diagnosis • History of disease - time, change in growth speed, hydration, infectious contact?, pain, comorbidities, surgery • Palpation - consistence, fixation, pain • Ultrasonography, duplex ultrasonography • FNAB (fine needle aspiration biopsy) • CT, MRI, CT sialography • Facial nerve function • Sialography • Scintigraphy • Cryotome intraoperative evaluation • Definitive histologic evaluation Positive clinical finding ultrasonography tumor normal inflammation parasialomy, lymphnodes ultrasound check after some time dg. punctio / surgery CT, MRI Sialography, MR / CT sialography Diagnosis FNAB (fine needle aspiration biopsy) Histologic classification of salivary gland tumors and their incidence Benign tumors Epithelial (adenomas) Pleomorphic adenoma 50 % Cystic adenolymphoma 30 % Other adenomas 10 % Mesenchymal 5 % Other 5 % Malignant tumors Epithelial (carcinomas) Adenoid cystic carcinoma 20 % Acinic cell adenocarcinoma 15 % Mucoepidermoid carcinoma 15 % Malignancy in Pleomorphic adenoma 15 % Other carcinomas 15 % Malignant lymphomas 15 % Other 5 % Therapy ▪ Surgery – Surgery of parotid gland – Extirpation of submandibular gland, small salivary glands – Possible complication – facial paresis, syndrome Frey (auriculotempoal syndrome) caused by aberrant growth of parasymphatic fibers nerve auriculotemporalis into skin sweat gland. redness, sweat (perspiration), burning sensation in the skin parotid region. ▪ Radiotherapy Surgery of parotid gland ▪ Extracapsular extirpation – removal of limited tumor with surrounding tissue ▪ Conservative superficial parotidectomy – removal of the whole superficial lobe in the level of ramification CN VII ▪ Conservative total parotidectomy – removal of the tumor mass in both lobes, preservation of ramification CN VII ▪ Semi radical parotidectomy – superficial, subtotal or total parotidectomy, sacrificed ramification CN VII infiltrated by tumor ▪ Total radical parotidectomy – removal of the whole gland include CN VII ramification Conservative total parotidectomy Schwanom n. VII Schwanom n. VII Schwannoma of CN VII Schwanom n. VII