Transcript GRAVES` DISEASE

THYROID DYSFUNCTION
DEGHAS
LECTURE
Thyroid Hormone Control
TSH
 THS regulation- TRH , T3,T4 
 TSH  synthesis of T3,T4
 TSH  thyroid gland growth
FUNKCE ŠTÍTNÉ ŽLÁZY
T3 RECEPTOR
THYROID HORMONES
 Most of the T4 nda T3 in plasma bound to TBG
 Only free hormones are active !
 The fT3 has 8 x higher activity than the fT4
 20% of the T3 comes directly from the thyroid
 80 % of the T3 se formed in tissues (esp. liver and
kidney) from T4 by 5’-deiodase
 Identic amount of rT3 formed by 5-deiodase
THYROID HORMONE FUNCTION
 Body growth ( gene expression GH)
 Maturation of CNS
 Adrenergic effect–  β-1 receptor response to
catecholamines
  basal metabolic rate ( cytochromes of the
respiratory chain, cytochromoxidase
and Na+-K+-ATPase)
 mobilize energy stores and catabolism
(lipolysis, glycogenolysis, gluconeogenesis)
GOITER
TYPES OF GOITER
ACCORDING TO FUNCTION:
 Euthyroid
 Hypothyroid
 Hyperthyroid
ACCORDING TO STRUCTURE:
 Diffuse (colloid)
 Nodular
HYPOTHYROIDISM-SYMPTOMS
 Fatigue, somnolence, muscle weakness, letargy, depression
 Bradypsychia, memory and concentration problems
 Bradycardia, decreased DBP
 Cold intolerance
 Constipation
 Body weight gain
 Diminished deep tendon reflexes
 Eybrow loss, dry skin, decreased sweating
 Pericardial and pleural effusions
 Forearm edema
 Hoarseness
LABORATORY FINDINGS:
PRIMARY HYPOTHYROIDISM:
  TSH, fT3,fT4
SECONDARY HYPOTHYROIDISM:
 TSH,  fT3,fT4
TERTIARY HYPOTHYROIDISM:
 TRH, TSH,  fT3,fT4
HYPOTHYROIDISM: cholesterol is typical
72-year old woman with hypothyroidism
Cretenism
HYPOTHYROIDISM-CAUSES
PRIMARY HYPOTHYROIDISM (origin in the thyroid):
Chronic lymphocytic thyroiditis – CLT (Hashimoto)
Thyroidectomy
Radiation therapy or nuclear catastrophy
Lack or excess of iodine
Drugs (methimazol, sunitinib, carbamazepin, amiodaron,)
Infiltrative dieseases (e.g. Riedel’s goiter)
HYPOTHYROIDISM
SECONDARY HYPOTHYROIDISM – origin in the pituitary
Craniopharyngioma, chromophobe adenoma, teratoma
TERTIARY HYPOTHYROIDISM –
origin in the hypothalamus
Extremely rare
CLT (HASHIMOTO)
 The most common cause of hypothyroidism !
 Women 30-50 y!
 9 x higher incidence in women than in men
 Positive PA/FA for autoim.dis., HLA-DR3, -DR4, -DR5,
often vitiligo or alopecia
 Hepatitis C history
 Often as part of the “polyglandular syndrom”
 Autoimmun. inflam.-cellular and humoral resonse
(cytotoxic T cells, auto-antibodies: anti TPO, anti TGB,
anti TSH-R)
CLT - DIAGNOSIS
 SYMPTOMS – initially unapparent (sometimes
hyperthyroid )
 Most of the cases dg. as advanced disease, when
hypothyroidism is clinically present
 LAB TESTS:  TSH, fT3,fT4
 Anti TPO (95%), anti TGB (70%), anti TSH-R
 US: non-homogenic, hypoechogenic, often
diminished thyroid
 FNAC: lymphocytic thyreoiditis, later fibrosis
DIFF. DG.
 OTHER CAUSES OF HYPOTHYROIDISM
 Low T3/T4 syndrome
fT3,fT4,  rT3,
clinically irrelevant
no thyroxin supplementation needed
CLT - THERAPY
 L-thyroxin replacement
 25, 50, 75, 100, 150 μg tablets
 Avarage replacement dose 1.6 μg/kg/ PO daily
 Goal: TSH 0.5 – 2.0 mIU/l
THYROIDECTOMY
INDICATIONS for thyroidectomy:
Graves’ disease
Toxic adenoma, toxic multinodular goiter
Thyroid carcinoma
I131 THERAPY
 Graves’ disease
 Thyroid carcinoma
EXTERNAL RADIATION ( > 25 Gy)
 Hodgkin’s lymphoma– neck lymphadenopythy
 Malginant tumors of the head and neck
 Nuclear catastrophy
DRUGS
 Lithium
 Amiodarone
 Phenytoin
 Carbamazepine
 Ethonamide (anti-TBC)
Overdose with thyreostatic drugs:
 Methimazole
 Propylthiouracil
 TPO inhibitors: sunitinib, sorafenib, imatinib
INFILTRATIVE DISEASE (less common)
 Riedel’s fibrotic goiter
 Hemochromatosis
 Sclerodermia
 Leukemias
 Amyloidosis
Riedel’s goiter
 Synonym: Riedel’s thyroiditis
 Extremely rare
 Etiology: unknown
 Slowly growing goiter-extremely solid consistency
 Painless
 Fibrotic inflammation w. lymphocytic infiltration
 Dif.dg.: tumor !
 Possible destruction of the parathyroid glands
 Retrosternal expansion: stridor, dysphagia
DIAGNOSIS OF HYPOTHYROIDISM
 TSH, fT3, fT4
 Ultrasound
 Fine Needle Aspiration Cytology (FNAC)
 Antibody titre measurement (anti TPO, anti TGB,
anti R-TSH)
 Scintigraphy (I131 accumulation)
THYROID ULTRASOUND
SEVERE HYPOTHYRODISM-MYXEDEMA
 EMERGENCY (result of prolonged and severe
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hypothyroidism)
Triggered by: infection, trauma, surgery, cold
Weakness, impaired conciousness to COMA
Hypothermia
Hypotension
Hypoventilation
Hypoglycemia
Hyponatremia
 Edema, swollen tongue
THERAPY OF MYXEDEMA
 INTENSIVE CARE UNIT
 Support of vital functions, ventilation support
 Glucocorticoids
 Glucose infusion
 Sodium supplementation
 L-thyroxin 100-200 μg IV initially
 Slow rewarming in hypothermia
HYPERTHYROIDISM
NEUROPSYCHIATRIC SYMPTOMS
 Restlessness
 Irritability
 Insomnia
 Anxiety
 Emotional lability
 Personality changes
 Psychosis
 Hyperactive deep tendon reflexes
HYPERTHYROIDISM
CARDIOVASCULAR SYMPTOMS
  cardiac output (tachycardia,  periph. resistance)
SBP, DBP
 Atrial fibrillation (in 20-30 %)
 Congestive heart failure
 Cardiomyopathy
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 Mitral valve prolapse, mitral regurgitation
HYPERTHYROIDISM
GASTROINTESTINAL SYMPTOMS
 Increased peristaltics
 Malabsorption
 Hyperphagia in young patients
 Loss of appetite in older patients
 Vomiting
 Dysphagia due to enlarged goiter
 Liver enzyme elevation, esp. ALP, rarely steatosis
HYPERTHYROIDISM
METABOLIC SYMPTOMS
 Weight loss
  total cholesterol, HDL cholesterol
 Hyperglycemia (insulin action antagonism)
 cortisol
HYPERTHYROIDISM
MUSCLE SYMPTOMS
 Adynamia
 Muscle weakness (esp. thigh muscles)
HYPERTHYROIDISM
BONE SYMPTOMS
 Bone resorption
 Porosity of the cortical bone, thinner trabecular bone
 ALP, osteocalcin (higher bone turnover)
 Hypercalcemia leading to PTH suppression
 conversion of D2 to D3
 Ca2+ resorption from the gut
 Ca2+ renal elimination
 OSTEOPOROSIS in chronic hyperthyroidism
HYPERTHYROIDISM
GENITOURINARY SYMPTOMS
 Polyuria, polydypsia
  SHBG
 MEN: total but free testosteron: gynecomastia,
loss of libido, erectile dysfunction, impaired
spermatogenesis
 WOMEN: total, but free estradiol:
oligo-, amenorrhea, infertility
HYPERTHYROIDISM
LUNG SYMPTOMS
 Dyspnea
  O2 consumption,  CO2 production
 Respiratory muscle weakness
 Trachea stenosis by enlarged goiter
HYPERTHYROIDISM – SKIN SYMPTOMS
 Sweating
 Warm, moist, fine skin
 Fine hair
 Fine nails, onycholysis
 Hyperpigmentation
 Vitiligo
 Alopecia areata
HYPERTHYROIDISM
HEMATOLOGY SYMPTOMS
 erytrocyte volume (MEV)
 Normocytic normochromic anemia (due to
increased plasma volume)
 ferritin
 autoimmune hematologic diseases (pernicious
anemia, idiopatic trombocytopenic purpura=ITP)
 Risk of thrombosis (fibrinogen, v. Willebrand f.,
thrombocyte aggregation)
HYPERTHYROIDISM-ETIOLOGY
 GRAVES' DISEASE (60-80 % of hyperthyroidism)
 Toxic multinodular goiter (15-20%)
 Thyroid adenoma (single thyroid nodule 3-5%)
 Subacute de Quervain thyroiditis
 Drugs: thyroxin excess (hyperthyreosis factitia),
amiodarone, iodine (contrast agents)
 Second. hyperthyroidism (pituitary adenoma)-rare
GRAVES’ DISEASE
 Autoimmune disease
 Genetic background-HLA-DQA1*0501
 Viral infection as trigger ?
 Production of TSH-receptor antibodies =
= TSI (thyroid stimulating antibodies)
 In GD sometimes initially hypothyroid period
GRAVES' DISEASE
DIAGNOSIS
 CLINICAL SYMPTOMS OF HYPERTHYROIDISM
 GRAVES' ORBITOPATHY
LAB TESTS:
  TSH, fT3,fT4
 TSI (> 95%)
 Anti TPO (70%)
HYPERTHYROIDISM – GRAVES'
ORBITOPATHY
 25 % patients with Graves’ disease
 Correlation of orbitopathy with the severity of
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hypothyroidism
Deposition of collagen and glycosaminoglycans in
the muscles, enlargement of the retroorbital space
Exophtalmos
Upper eyelid retraction
Von Greafe’s sign (lid lag on infraduction)
Koch’s sign (bulbus lag on supraduction)
Lagophtalmos
GRAVES’ ORBITOPATHY
GRAVES’ ORBITOPATHY
GRAVES' DISEASE
THERAPY
 Beta blockers
 Thyrostatic drugs-blocking MJT and DJT synthesis
(methimazole, thiamazole, propylthiouracil)
 Radiactive iodine 131I (dos 200-2000 MBq)thyreostatics before and after the procedure recom.
EUTHYROIDISM RESTORED AFTER SEV.MONTHS
 Subtotal thyroidectomy (after sev.months) if large
goiter, thyreotoxic crisis)
DIFF.DG.
 OTHER CAUSES OF HYPERTHYROIDISM
 Vegetative instability
 Psychosis
 High fever
 Cocaine, Amphetamine
 Tachycardia of different origin
THYROTOXIC CRISIS
Etiology: spontaneously in
 Graves disease
 autonomic adenomas (nodes)
 iodine agents
 thyroxin overdose
 inefficient thyrostatic therapy
THYROTOXIC CRISIS
STAGES
 Stage I: Tachycardia > 150, AF, Fever > 41°,
sweating, psychomotoric agitation, diarrhea,
vomiting, adynamia
 Stage II: + somnolence, psychotic symptoms
 Stage III: coma w/wo adrenal failure, shock
THYROTOXIC CRISIS
THERAPY
EMERGENCY-INTENSIVE CARE UNIT
 Thiamazol 80 mg IV every 8 hours
 Beta-blockers
 Corticosteroids
 Fluid: 3-4 Liters IV/D
 Calorie intake: 3000 kcal/D
 Lowering body temperature (ice)
 Sedation
 Thromboembolic prophylaxis
THYREOTOXIC CRISIS
THERAPY
IN SEVERE CASES (e.g. iodine induced):
 PLASMAPHERESIS
 SUBTOTAL THYROIDECTOMY
SUBACUTE de QUERVAIN'S THYROIDITIS
 Rare cause of hyperthyroidism
 Incidence 5 x higher in women than men
 Etiology: probably viral infection, often after
respiratory infection
 Clinical signs: hyperthyroidic-euthyr-hypothyroidic,
painful thyroid,
 Lab tests: ESR, CRP, normal leukocytes
 Therapy: mostly spontaneous healing, NSA,
rednisolon are optional
MULTINODULAR GOITER
AUTONOMOUS ADEMOMA
 DIAGNOSIS: 131I accumulation on thyroid scan, US
 CLINICAL SYMPTOMS of hyperthyroidism
 THERAPY: thyreostatics, radioactive iodine
MULTINODULAR GOITER
ULTRASOUND OF A THYROID NODULE
THYROID SCAN – normal accumulation
THYROID ADENOMA