Thyroid

Thyroid Developmental Abnormalities Thyroglossal Duct Cyst and Sinus  Most common congenital cervical anomaly.  Obliterates during 5th week of gestation and disappears by 8th week.  Persist in whole, or in part.  80% are found in juxtaposition to the hyoid bone.  Asymptomatic, may become infected by oral bacteria.  Result from infection of the cyst 2⁰ to spontaneous or surgical drainage of cyst, minor inflammation of the surrounding skin.  Pseudostratified ciliated columnar epithelium and squamous epithelium w/ heterotopic thyroid tissue in 20%. Dx:  Observation 1-2 cm, smooth, well-defined midline neck mass that moves upward w/ protrusion of the tongue.  Routine thyroid imaging is not necessary.  Thyroid scintigraphy and ultrasound to document the presence of normal thyroid tissue in the neck. Treatment:  Sistrunk Operation  - en bloc cystectomy plus excision of the central hyoid bone to minimize recurrence.  1% cyst contain papillary (85%) CA, others- squamous; Hΰrthle cell, and anaplastic CA.  Lingual Thyroid  Failure of the median thyroid anlage to descend normally and may be the only thyroid tissue present.  Develops hypothyroidism (70% ).  Intervention becomes necessary for obstructive symptoms.

Tx:  Medical- Exogenous Thyroid Hormones to suppress TSH- RAI ablation.  Surgical Excision- rare; if required should be preceded by an evaluation of normal thyroid tissue in the neck to avoid inadvertent hypothyroidism.  Ectopic Thyroid  Anywhere in the central neck compartment.  Thyroid tissue situated lateral to the carotid sheath and jugular vein, always represent metastatic thyroid CA in lymph nodes and not remnants of lateral anlage failed to fuse with the main thyroid.  Thyroid Anatomy  BLOOD SUPPLY 3 Arteries: 1. SUPERIOR THYROID ARTERIES ( Paired)  from- IPSILATERAL EXTERNAL CAROTID ARTERIES and divided into anterior the posterior branches at apices of the thyroid lobes. 2. INFERIOR THYROID ARTERIES ( Paired )  from- thyrocervical trunk shortly after their origin from the subclavian arteries.  associated with-RLN, necessitating identification before arterial branches can be ligated. 3. THYROID IMA ARTERY  directly from the aorta or innominate in 1-4% to enter the ISTHMUS or replacing a missing inferior thyroid artery.  VENOUS DRAINAGE 1. SUPERIOR THYROID VEIN  Run w/ STA bilaterally, drains directly to IJV. 2. MIDDLE VEIN  Least consistent;drains directly to IJV.

3. INFERIOR THYROID VEIN

 Form a plexus,w/c drains into the brachiocephalic veins.  NERVES 1. LEFT RECURRENT LARYNGEAL NERVE  from the VAGUS NERVE where it crosses the aortic arch, loops around ligamentum arteriosum and ascends medially in the neck w/in the tracheoesophageal groove. 2. RIGHT REECURRENT LARYNGEAL NERVE  from VAGUS NERVE at its crossing w/ the right SUBCLAVIAN ARTERY.  Passes posterior to the artery before ascending in the neck.  Right RLN- non recurrent in 0.5-1%.  Non-recurrent Left RLN is rare, reported in SITUS,INVERSUS and R SIDED AORTA ARCH.  RLN’s terminate by entering the larynx posterior to the cricothyroid muscle.  RLN’s innervate all the intrinsic muscle,except the cricothyroid muscles,w/c are innervated by the EXTERNAL LARYNGEAL NERVE. INJURY TO RLN’s Injury to one RLN 

Paralysis of ipsilateral vocal cord.

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Normal but weak voice- paramedian position.

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Hoarseness and ineffective cough-abducted position.

Injury to Bilateral RLN 

airway obstruction, or loss of voice.

3.SUPERIOR LARYNGEAL NERVE  from vagus nerve.  2 branches A. INTERNAL BRANCH Sensory to the supraglottic larynx ; injury may result in aspiration B.EXTERNAL BRANCH

Innervate the cricothyroid muscle. Also called “Amelita Galla Curci” or “ high note” nerve Injury-inability to tense the IPSILATERAL VOCAL CORD leading to difficulty “ hitting the high notes”, projecting the voice, and voice fatigue during prolonged speech.  SYMPATHETIC INNERVATION  From fibers of superior and middle cervical sympathetic GANGLIA.  Enter the gland with the blood vessels.  Vasomotor in action. PARASYMPATHETIC INNERVATION  From vagus nerve and reach the gland via branches of the laryngeal nerves.  THYROID CANCER  Clinical history and PE- cornerstone of appropriate Mx. Pertinent Historical Factors Predicting Malignancy include: 1.Hx of H and N irradiation 2.Total body irradiation for bone marrow transplantation. 3.Exposure to fallout 4.Family Hx of thyroid CA 5.Rapid growth or hoarseness 6.Children, men, adults› 60 y/o  Pertinent PE suggestive of CA.  Pertinent P.E. suggestive of Cancer:  Gritty texture of thyroid nodule, CLAD, vocal cord paralysis, fixation of nodule to surrounding tissues.  MALIGNANT THYROID DISEASE  Most common endocrine malignancy, 95% of all endocrine CA’s  Accounts for ‹1% of all malignancy

( 2% of women ) ( 0.5 of men )  Most present w/ a palpable swelling in the neck.  MOLECULAR GENETICS of THYROID TUMORIGENESIS Ret Proto- Oncogene  Plays a significant role in thyroid cancer.  Located at Chromosome 10, encodes receptor tyrosine kinase  Germline mutations predispose to men 2A,men 2B and familial medullary thyroid cancer.  Tyrosine kinase domain fusion implicated in PTC’s  RET/ PTC3 is ass’od w/ a solid type of papillary thyroid cancer that presents at higher stage and to be more aggressive. RAS ONCOGENES  Identified in 40% of thyroid follicular adenomas and CA’s. TSH-R MUTATIONS  80% of toxic adenomas, in hyperfunctioning modules of MCAG, rarely in thyroid CA’s. P53 MUTATIONS  Common in undifferentiated thyroid CA’s and thyroid cancer cell line  PAPILLARY CARCINOMA  80% of all malignancies in iodine-sufficient areas.  Familial - 5%  Predominant thyroid CA in children and individuals exposed to external radiation ( 90%)  More often to women 2:1 F.M ratio  Age 30-40 years  Most are euthyroid  Slowly growing painless mass  Lymph nodes metastases are common,esp.in children and young adults.

Dx:  FNA Biopsy of the thyroid mass or lymph node  Common sites of metastases- LUNGS,BONE,LIVER and BRAIN.  PATHOLOGY  Grossly – hard, whitish, remain flat on cut section. -macroscopic calcification, necrosis, cyst.  Histo-papillary projections, mixed pattern of papillary & follicular structures. - cells are cuboidal w/ pale, abundant cytoplasm “growing” crowded nuclei & intranuclear cytoplasmic inclusions( Orphan Annie Nuclei ), w/c allows Dx by FN AB. Psammoma Bodies -microscopic calcified deposits representing clumps of slough cells. -multifocal in 85%,asso’d w/ the risk of cervical nodal metastases. -rarely invade adjacent structures. Variants: -Tall cell, insular, columnar, diffuse sclerosis, clear cell, trabecular, poorly differentiated ( 1% ). -asso’d w/ worse prognosis.

 Classification of Low versus High Risk Using the Risk Patients Using the AGES System  Prognosis- In general, excellent prognosis w/ >95% 10 year survival rate AGES Scoring System- age,histologic grade, extrathyriodal invasion & metastases & tumor size to predict the risk of dying from papillary CA. Low Risk Patients  young, well-differentiated tumors no metastases, small primary lesions.

High Risk  older, poorly differentiated tumors,local invasion,distant metastases, large 1° lesion.

 MACIS Scale-distant metastases age of presentation, completeness of original surgical resection, extrathyriodal invasion & size of original lesion. -postoperative system  AMES System-differentiated thyroid tumors into low & high risk groups. -age ( men 4 cm ) in older men are more likely to be malignant PATHOLOGY  Tendency to spread by hematogenous route.  Solitary lesions, surrounded by a capsule  Malignancy is defined by the presence of CAPSULAR & VASCULAR INVASION. SURGICAL TREATMENT  FNAB of follicular lesions- Thyroid lobectomy - 80% will have benign adenomas.  Follicular lesion >4 cm- total thyroidectomy (50% risk of malignancy )  Intraop Frozen Section- not helpful but should but should be performed, or when adjacent lymphademopathy is present.  Total thyroidectomy should be performed when thyroid CA is diagnosed.  A Dx of frankly invasive CA necessitates completion of total thyroidectomy 1° so that can be used to detect & ablate metastases disease. PROGNOSIS  Cumulative Mortality-15% at 10 yrs., 30% at 20 yrs.  Poor long term in prognosis in: >50 yrs.old at presentation,>4 cm higher tumor grade, mark vascular invasion, extrathyroid invasion & distant metastases.  Overall Survival: 43%-95% at 10 yrs. Mx:  Similar to follicular neoplasm  Unilateral Lobectomy & Isthmusectomy  Invasive on Intraop Frozen Section- Total thyroidectomy, central neck node removal, & MRND when lateral neck nodes are palpable. HURTHLE CELL CARCINOMA  3% of all thyroid malignancies

 peak incidence 50-60 yrs.  Subtype of follicular thyroid cancer  Vascular or capsular invasion, therefore, cannot be diagnosed by FNAB  Sheets of eosinophilic cells packed w/ mitochondria, w/c derived from oxyphilic cells of thyroid glands  Multifocal & bilateral ( 30%), usually do not take up RAI (5%), more likely to metastasize to local nodes (25%) & distant sites.  w/ higher MR (20% at 10 yrs.)  10 yrs survival 70%  POSTOPERATIVE Mx of DIFFERENTIATED of THYROID CA Treatment Thyroid hormone  Replacement Thx after total or near total thyroidectomy  Suppresses TSH & reduces the growth stimulus for any residual thyroid cancer cells.  TSH suppression reduces tumour recurrence rates particularly in young pts.  Thyroxine w/ circulating TSH of 0.1 μU/L in low risk pts, or 2 ng/ml is highly suggestive of metastatic.  95% of pts. w/ persistent or recurrent thyroid CA of follicular cell origin well have Tg>2 ng/ml  Tg and anti Tg antibody levels should be measured initially at 6 months & then annually if the pt.is clinically disease free.  High risk patients should have US of neck & CT or MRI scan of the neck & mediastinum for early detection of any persistent or recurrent disease.

 Radioiodine Therapy  Postop RAI therapy reduces recurrence & provides a small improvement in survival, even low risk pts.  Screening w/ RAI is more sensitive than CXR or CT scanning for detecting metastases.  Metastatic differentiated thyroid CA can detected & treated by ¹³¹ I is 75% of pts.  RAI effectively treats > 70% of lung metastases that are detected by RAI scan w/ normal CXR.  Success rates drop to < 10% w/ pulm macrometastases.  Pts. Should be receive T₃ during this time period to decrease the period of hypothyroidism  T₃ has s shorter half-life than T₄ ( 1 day vs. 1 week), needs to be discontinued for 2 weeks to allow TSH levels to rise prior to treatment.  Low-iodine diet is also recommended during this 2 week period. OTHER IMAGING  If RAI scan are negative but Tg levels remain elevated , other imaging studies such as neck US, MRI scan, & FDG.PET scan may be considered. External Beam Radiotherapy and Chemotherapy  EBR occasionally required to control unresectable, locally invasive or recurrent disease & to treat metastases in support bones to ↓ the risk of of fractures.  EBR also is of value for tx & control of pain from bony metastases when there is minimal or no RAIµ.  Single and multidrug ChemoThx has been used w/ little success in disseminated thyroid cancer.  MEDULLARY CARCINOMA  57% of thyroid malignancies  from Parafollicular or C-cells of thyroid w/c are derived from the ultimobranchial bodies.  C- cells are concentrated superolaterally in the thyroid lobes,where MTC usually develop.  C-cells secrete Calcitonin w/c lower serum calcium levels

 most occur sporadically (75%)  25% have inherited syndromes-Familial  Medullary thyroid CA,men 2A,men 2B  Germline mutations in the RET proto-oncogene. S/SX  Neck mass  Palpable cervical lymphadenopathy- 15 to 20%  Local pain or aching  Local invasion MODE OF METASTASES  Blood borne  Liver, bone ( osteoblastic) and lung MTC’s secrete the ff. Hormones:  Calcitonin  CEA  Calcitonin Gene related peptide (CGRP)  Histaminadases  PGE₂ and F2 alpha  Serotonin  Cushing’s syndrome-2 to 4% due to ectopic ACTH production. PATHOLOGY  Unilateral (80%)  Multicentric -asso’d w/ C-cell hyperplasia  Bilateral (90%)  Familial :C-cell hyperplasia w/c is considered a premalignant lesion.

 Infiltrating neoplastic cells separated by collagen and amyloid cells may be polygonal or spindle shaped.  Amyloid is a diagnostic finding but immunohistochemistry for calcitonin is more commonly used as a diagnostic tumor marker.  Stain positively for CEA and CGRP. DIAGNOSIS  Hx, P.E and ↑CEA, ↑Calcitonin,↑Ca++  FNAC of thyroid mass  Attention to family Hx is impt.:25% of MTC have familial disease.  MTC should be screened for RET point mutations, pheochromocytoma.  Coexisting pheochromocytoma to avoid precipitating a hypertensive crisis and death.  Calcitonin and CEA are used to identify points w/ persistent or recurrent MTC.  Calcitonin is a more sensitive tumor marker but CEA is a better predictor of prognosis. TREATMENT  If pts has a pheochromocytoma, this must be operated on first. These tumor rare generally (>50% ) bilateral  Total thyroidectomy is the treatment of choice.  Central compartment nodes are frequently involved early so bilateral central neck node dissection should be routinely performed.  MRND-if with palpable cervical nodes laterally  Tumors >1.5 cm should undergo ipsilateral prophylactic MRND bec >60% have nodal metastases  30% have contralateral nodal metastases TX of Local Recurrence or Metastases 

Tumor Debulking is advice to ameliorate symptoms of flushing.

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Ext. Beam Radiotherapy

 Controversial

 For unresectable residual or recurrent tumor  No effective chemotherapy regimen.  Tx of liver metastases-Radiofrequency ablation (RFA) done laparoscopically or palliative Tx of liver met >1.5 cm  Tyrosine kinase inhibitors-for tumor that express C-kit.  Tx of hyper CA++ at the time SX -Only the enlarge parathyroid gland should be removed.  Total thyroidectomy is indicated in RET mutation carriers once mutation is confirmed  Sx should be performed before age 6 years in MEN 2A, prior to age 1 in MEN 2B pts.  Central neck dissection can be avoided in children who are RET positive, calcitonin negative w/ normal US.  If calcitonin is ↑’d or US suggest thyroid CA, a prophylactic central neck dissection is indicated. POSTOPERATIVE FOLLOW UP and PROGNOSIS  Prognosis is related to disease  10 yrs.survival rate-80%,if w/ positive lymph nodes-45%  Survival is best with: 1. Non-men familial MTC 2. Men 2A 3. Sporadic  If men with 2B-35%  Worse if tumor stain poorly for calcitonin and heterogeneous distribution  Performing prophylactic Sx but also renders most patients calcitonin free.  ANAPLASTIC THYROID CARCINOMA  1% of all thyroid CAs  Affects more women  Majority present in 7th and 8th decades of life.

 Long standing neck mass which rapidly enlarge , painful.  Dyspnea,dysphagia,dysphonia  Tumor is large,fixed to surrounding structures or may be ulcerated. Dx:  Confirmed by FNAB (Giant and multinucleated cells)  Incisional biopsy  Isthmusectomy is performed to alleviate tracheal compression. PATHOLOGY  Gross – firm,whitish  Histo – sheet of cells, marked heterogeneity spindle shaped, polygonal or large multinucleated cells.  Arise from well differentiated tumors. Tx:  One of the most aggressive thyroid malignancies  Surviving 6 months beyond diagnosis  All forms of Tx have been disappointing  Combined radiation, chemo Tx in an adjacent setting in point w/ resectable dose may improve survival.  Tracheostomy- alleviate airway obstruction  LYMPHOMA  1-2 % of thyroid malignancies,1 cm in size are considered clinically significant and require further evaluation.  Evaluate regardless of the size if: 1. Personal Hx of thyroid lobectomy fore CA 2. Family Hx of thyroid CA 3.Hx of head and neck irradiation 4. Nodule w/ suspicious sonographic findings.

 Evaluations begin w/ a thorough Hx and PE.  Pertinent historical features that should ↑ suspicion for malignancy. 1. Age 60 yrs.

2. Male sex 3.Hx of head and neck irradiation 4.Total body irradiation for bone marrow transplantation.  Risk of malignancy is 2X higher in pts. Younger than 20 yrs. 5.FHx of MTC men type 2, familial PTC, familial polyposis coli, cowden’s disease, gardner’s syndrome.  Hx- onset of hoarness, dysphagea, dyspnea, rate of growth of nodule  Slow but progressive ↑ in nodule size over a period of weeks to month is worrisome of malignancy  Rapid ↑ in size should raise concern for anaplastic CA or a 1⁰ lymphoma.  Neck pain  Solitary nodule + hyperthyroidism  P.E alone detects only 40% of nodule that are >1.5 cm  Size, shape, consistency, location and inability, tracheal displacement, CLAD and substernal extension Pemberton’s sign  Pt.w/ a large nodule that extends substernally  Refers to facial plethora, neck vein distention, difficulty breathing from a narrowing of the thoracic inlet that occurs when the pt. Elevates his arms above their heads. Suggestive of malignancy if: 1. Firm or hard nodule 2. Fixation of nodule to surrounding tissues 3. Ipsilateral cervical lymphadenopathy 4. Paralyzed vocal cord by laryngoscopy  Laboratory Evaluation  The only lab test that must be performed routinely in the evaluation of a pt. w/ a thyroid nodule is a 3rd generation TSH level  If TSH is low-request free T₃ and free T₄

 Incidence of malignancy in hyperfxn’g nodule=1%  If (+)of MTC or men2 , a basal serum calcitonin level shld. Be obtained.  Baseline level of calcitonin >100pg/ml are highly suggestive of MTC. 1.FNAB- the diagnostic procedure of choice in the evaluation of thyroid nodules. 2.High resolution ultrasound  Detects nodule as small as 2mm Sonographic features that can be associated w/malignancy. 1.Indistinct or irregular margins 2.Intranodular calcification 3. Hypoechogenecity 4.Nodule that is taller than it is wide 5. ↑’d intranodular vascular markings 6.Suspicious lymph nodes  The presence or absence of these sonographic findings cannot reliably distinguish benign from malignant lesions. →all pts.w/ a nodule ≥1 cm shld be evaluated w/ FNAB. 3.Iodine ¹²³ thyroid scintigraphy Selected indications in patients w/a dominant thyroid nodule. 1.Low TSH before performing FNAB (10% CA) 2.FNAB consistent w/a follicular neoplasm and low serum TSH level (20-30% incidence CA) 3.Persistently non diagnostic FNAB and a low serum TSH level ( 10 % incidence CA)  hyperfxn’g nodules almost never represent malignant lesion (1%).  Isofunctioning and hypofunctioning nodules=5 to 10% risk of malignancy.  Bec.>80% of nodules are hypofxn’g and only 5-10% are malignant, the predictive value of thyroid scintigrahpy for the presence of malignancy is low Management  Simple thyroid cysts resolve w/ aspiration-75%

1.After >3 aspirations 2.>4 cm cyst 3.Complex cyst w/ solid component (when FNAB is used in the complex nodules, the solid portion shld.be sampled, bec.the latter have a higher incidence of CA 15%)  If colloid nodule is Dxd by FNAB, pt.shld be observed w/ serial US and Tg.  Controversial -TX: L- thyroxine suppression sufficient to maintain a serum TSH level bet. 0.1 and 0.5µU/ml (50% response)  Do not caused marked TSH suppression- risk of osteoporosis and arrythmias Indications of Thyroidectomy 1. Nodule enlarges on TSH suppression 2. Compressive symptoms 3. Cosmetic reason 4. Hx of previous irradiation 5. Family Hx of thyroid CA 6. Recurrent cysts w/ persistent nondiagnostic FNAB >3 aspiration. 

Hyperthyroidism

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Hyperthyroidism

Diffuse Toxic Goiter ( Grave’s Disease )  most common cause of hyperthyroidism in North America (60-80%)  An autoimmune disease  Strong familial predisposition  Female preponderance (5:1)  Peak incidence: 40-60 yrs  Char’c: 

1)Thyrotoxicosis

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2) Diffuse Goiter

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3) Extrathyroidal conditions

 Extrathyroidal s/sx’s:  Ophthalmopathy,dermopathy(pretibial myxedema),thyroid acropathy,gynecomastia Etiology, Pathogenesis:  Exact etiology of initiation of autoimmune process is unknown.  Poss. Triggers: Postpartum state, Iodine excess, Lithium thx,bacterial & viral infxns  Genetics: HLA haplotypes-HLA-B8 ,HLA-DR3 & HLADQ1*501  Protective :HLA-DR B1*0701 *Sensitized T-helper lymphocytes stimulate B lymphocytes,w/c produce antibodies directed vs. thyroid hormone receptor.  TSI’s or antibodies that stimulate TSH-R & TSH-binding inhibiting Ig’s or Ab’s  Thyroid stimulating Ab’s stimulate thyrocytes to grow & synthesize excess thyroid hormone (Hallmark of Grave’s Disease).  Pathology  Grossly: Thyroid is diffusely & smoothly enlarged ; ↑’d vascularity  Histo: hyperplastic gland, columnar epithelium with minimal colloid Clinical features:  Divided into:  I.Hyperthyroidism –heat intolerance,↑’d sweating & thirst, weight loss,palpitationfatigue,emotional lability,hyperkinesis,tremors,diarrhea,amenorrhea.↓ fertility,miscarriages,rapid growth w/ early bone maturation in children,atrial fib,CHF P.E:  Wt. loss,facial flushing,warm moist skin,darkening of skin,↑ HR,cutaneous vasodilatation  Widening of pulse pressure & rapid falloff in transmitted pulse wave (collapsing pulse)  Fine tremor,muscle wasting,prox’l muscle group weakness  Hyperactive tendon reflexes

 Thyroid diffusely enlarged including pyramidal lobe,± bruit or thrill  Loud venous hum in supraclavicular space. II.Those specific to G.D.  Ophthalmopathy -50%  Dermopathy -1-2% -deposition of Glycosaminoglycans leading to thickened skin in pretibial region & dorsum of foot.  Lid Lag ( von Graefe’s sign)  Dalrymple’s sign –spasm of upper eyelid revealing the sclera above the corneo-scleral limbus.  Prominent stare due to cathecholamine excess  Periorbital edema,conjunctival swelling & congestion (chemosis),proptosis,limitation of upward & lateral gaze(fr. involvement of Inferior & Medial Rectus m.)’keratitis,blindness due to Optic n. involvement Etiology of Grave’s Ophthalmopathy;  Unknown  Orbital fibroblasts & muscles are thought to share a common antigen,the TSH-R  Inflammation caused by cytokines released from sensitized killer T lymphocytes & cytotoxic antibodies.  Gynecomastia in young men  Thyroid Acropathy-rare;subperiosteal bone formation & swelling in metacarpals.  Onycholysis-separation of fingernails from their beds.  Diagnostic Tests  Dx: ↓ TSH ,± ↑ FT4 or T3  If eye signs are present,other tests are gen’lly not needed.  In the absence of eye signs,123 I uptake and Scan should be performed. An elevated uptake,with diffusely enlarged gland confirms the Dx of Graves Disease.  If T4 is normal,request FT3-elevated in Early G.D. or Plummer’s dse(T3 Toxicosis)

 Anti Tg & anti TPO antibodies : ↑ in 75% but not specific  ↑ TSH-R or Thyroid-stimulating antibodies (TSA) are Diagnostic of G.D.;↑’d in 90%.  MRI scan of orbits-useful in Grave’s ophthalmopathy.  Treatment of Grave’s Disease 3 TX Modalities:  1) Antithyroid drugs  2) Thyroid Ablation with Radioactive 131 Iodine  3) Thyroidectomy  Antithyroid Drugs  Gen’lly given in preparation for RAI ablation or surgery  1) Propylthiouracil (PTU, 100-300 mg TID)  2) Methimazole (10-30 mg TID,then OD )  -methimazole is asso’d with Congenital aplasia; longer half-life  Both drugs reduced thyroid hormone production by inhibiting the organic binding of Iodine & coupling of iodotyrosine.  PTU also inhibits the peripheral conversion of T4 to T3, making it useful for tx of Thyroid storm.  PTU-lower risk of transplacental transfer; preferred in pregnant & breastfeeding women. Side effects: 

-reversible granulocytopenia, skin rashes, fever, peripheral neuritis, polyarteritis, vasculitis,agranulocytosis,aplastic anemia

Tx of Agranulocytosis:  -admit ; D/C drug, Broad spectrum antibiotics.postponed Sx until granulocyte count reaches 1000 cells/m3.  Most pts have improved symptoms in 2 weeks & become Euthyroid in about 6 weeks.  Outcome of Antithyroid Drugs  High relapse rate when drugs are discontinued.

 40-80% develop recurrent disease after a 1-2 yr course.  Treatment with curative intent is reserved for pts. With: 

1) Small,nontoxic goiter < 40 gm

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2) Mildly elevated thyroid hormone

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3) Rapid decrease in gland size

 3) Propanolol  Most commonly prescribed med.  Dose: 20-40 mg QID OD  Alleviates catecholamine response of thyrotoxicosis  Added effect of ↓’g peripheral conversion of T4 to T3.  Radioactive Iodine Therapy (131 I )  mainstay of tx of G.D. in North America Advantages:  1) Avoidance of Sx & its concomittant risks  2) Reduced overall Tx costs  3) Ease of Tx  Antithyroid drugs are given until pt. is euthyroid & then D/C’d to maximize drug uptake.  Pt. become Euthyroid w/in 2 months  Only 50% are Euthyroid 6 months after Tx.  After 1 yr.,about 2.5% of pts. Develop hypothyroidism each yr.  Disadvantages of RAI:  1) Progression of Grave’s ophthalmopathy 

-(33% after RAI vs. 16% after Sx )

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- more common in smokers

 2) Small ↑’d risk of nodular goiter,thyroid Ca,hypoparathyroidism (HPT)

 3) Unexplained ↑’d in overall cardiovascular MR’s.  Indications for RAI Tx:  1) Older pts. With small or moderate-sized goiters.  2) Relapsed after medical or Sx Tx.  3) Antithyroid drugs or Sx are contraindicated. Absolute CI:  1) Women who are pregnant or breastfeeding. Relative CI:  1) Young pts.(esp children n adolescents)  2) Those w/ thyroid nodules.  3) Those w/ ophthalmopathy.  Surgical Treatment of Grave’s Disease: Indications:  1)when RAI is contraindicated.  2)Have confirmed cancer or suspicious thyroid nodules  3)Young  4)Pregnant or desire to conceive soon after Tx.  5)Have had severe reactions to antithyroid meds.  6)Have large goiters causing compressive symptoms.  7)Reluctant to undergo RAI therapy.  Relative Indications for Thyroidectomy:  1) Smokers  2) Moderate to severe Grave’s ophthalmopathy.  3) Those desiring rapid control of hyperthyroidism.  4) Poor compliance to antithyroid meds.

Goal of Surgery:  Complete & permanent control of disease w/ minimal morbidity.  Pts. Should be rendered euthyroid before Sx with antithyroid drugs that should be continued up to the day of Sx. Lugol’s Iodide sol’n or Saturated K+ Iodide  -given beginning 7-10 days preop’ly (3 gtts BID) to reduce vascularity of the glands & to ↓ risk of precipitating thyroid storm.  Iodide inhibits release of thyroid hormone.  Surgery  Total or Near Total Thyroidectomy  Remnants of 40 %) rate of hypothyroidism  Recurrent thyrotoxicosis is managed by RAI Thx.  Toxic Multinodular Goiter  Older ; insidious onset  Prior Hx of nontoxic multinodular goiter  Over several yrs,enough thyroid nodules become autonomous to cause hyperthyroidism.  Hyperthyroidism may only become apparent when pts are placed on low dose of thyroid hormone suppression for the goiter.  May present w/ T3 Toxicosis or Atrial fibrillation or CHF.  Can be precipitated by Iodide-containing drugs:  -Contrast media & antiarrhythmic agent AMIODARONE (Jodbasedow Hyperthyroidism )  Extrathyroidal manifestations are absent. DIAGNOSTIC STUDIES  ↓ TSH ; ↑ FT4 or T3  ↑ RAI uptake

 Treatment of Toxic Multinodular Goiter  Adequate control of hyperthyroidism  SUBTOTAL Thyroidectomy –standard procedure  Remnant is not crucial;pts.  Require thyroid hormone suppresion to prevent recurrence  Hartley-Dunhill procedure-preferred over a bilateral subtotal thyroidectomy  TOTAL Thyroidectomy-done if no normal thyroid tissue is present.  RAI Thx-reserved for elderly w/ poor operative risks w/ no airway compromise from goiter.  TOXIC ADENOMA (PLUMMER’S DISEASE )  Hyperthyroidism from a single autonomous hyperfunctioning nodule.  Younger pts with recent growth of a long standing nodule.  Somatic mutations in TSH-R gene & G-protein stimulating gene (GSP)  Most have attained nodule size of at least 3 cm before hyperthyroidism occurs.  P.E:  Solitary thyroid nodule without palpable thyroid tissue on contralateral side.  RAI scan: “Hot “ nodule  Rarely malignant  Mx:  Smaller nodules- Tx w/ antithyroid meds & RAI  LOBECTOMY & Isthmusectomy- preferred tx for young pts & those w/ larger nodules. Thyroid Storm

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 Hyperthyroidism w/ fever,CNS agitation or depression,CVS dysfxn,delirium,seizures,coma,vomiting,diarrhea,jaundice that maybe pptd by: -Acute illness(Infection, Stroke, DKA ) -Surgery

-Trauma - Amiodarone - RAI Tx MR due to heart failure,arrhytmia or hyperthermia: 30% even with Tx. Mx: -admit to ICU ; 1)Identify & treat the precipitating cause. 2)Betablocker (Propanolol) -↓ peripheral T4 to T3 conversion & ↓ hyperthyroid symptoms  3) O2 supplementation  4) Hemodynamic support  5) Antipyretics  6) Lugol’s Iodine or Sodium Ipodate (I.V.) -↓ Iodine update & thyroid hormone secretion.  7) PTU -blocks formation of new thyroid hormone -↓ peripheral conversion of T4 to T3  8) Corticosteroid ( Dexamethasone) -prevent adrenal exhaustion & block hepatic thyroid hormone conversion. 

HYPOTHYROIDISM

 Clinical Features Cretinism  hypothyroidism in Neonate  Neurologic impairment & mental retardation  Failure of thyroid gland dev’t or function in utero  Facie similar to Down’s Syndrome

 Dwarfism  Failure to thrive Mx:  Immediate testing & Tx w/ T4 at birth to lessen neurologic & intellectual deficits.  Hypothyroidism in Childhood or Adolescence  Delayed dev’t  Abd’l distention, umbilical hernia, rectal prolapse Hypothyroidism in Adults  Non specific s/sx’s  Tiredness,weight gain. Cold intolerance,constipation,menorrhagia  MYXEDEMA  Severe hypothyroidism in adult  char’c facial features due to deposition of glycosaminoglycans in subcutaneous tissues.  facial & periorbital puffiness  rough,dry skin w/ yellowish hue due to ↓ conversion of carotene to Vitamin A.  dry, brittle hair  hair loss  char’c loss of outer 2/3rd of eyebrows  enlarged tongue  slowed speech & mentation  abd’l pain,distention & constipation  impaired libido & fertility