Deghas

1
THYROID DYSFUNCTION

• Deghas
• lecture

2
(No Transcript)
3
Thyroid Hormone Control
4
TSH

• THS regulation- TRH ?, T3,T4 ?
• TSH ? synthesis of T3,T4
• TSH ? thyroid gland growth

5
FUNKCE ŠTÍTNÉ ŽLÁZY
6
T3 RECEPTOR
7
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

8
THYROID HORMONE FUNCTION

• Body growth (? gene expression GH)
• Maturation of CNS
• Adrenergic effect ? ß-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)

9
GOITER
10
TYPES OF GOITER

• ACCORDING TO FUNCTION
• Euthyroid
• Hypothyroid
• Hyperthyroid
• ACCORDING TO STRUCTURE
• Diffuse (colloid)
• Nodular

11
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

12
LABORATORY FINDINGS

• PRIMARY HYPOTHYROIDISM
• ? TSH, ?fT3,fT4
• SECONDARY HYPOTHYROIDISM
• ?TSH, ? fT3,fT4
• TERTIARY HYPOTHYROIDISM
• ?TRH, ?TSH, ? fT3,fT4
• HYPOTHYROIDISM ?cholesterol is typical

13
72-year old woman with hypothyroidism
14
Cretenism
15
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. Riedels goiter)

16
HYPOTHYROIDISM

• SECONDARY HYPOTHYROIDISM origin in the
  pituitary
• Craniopharyngioma, chromophobe adenoma, teratoma
• TERTIARY HYPOTHYROIDISM
  origin in the hypothalamus
• Extremely rare

17
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)

18
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

19
DIFF. DG.

• OTHER CAUSES OF HYPOTHYROIDISM
• Low T3/T4 syndrome
  ?fT3,fT4, ? rT3,
  clinically
  irrelevant
  no thyroxin supplementation
  needed

20
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

21
THYROIDECTOMY

• INDICATIONS for thyroidectomy
• Graves disease
• Toxic adenoma, toxic multinodular goiter
• Thyroid carcinoma

22
I131 THERAPY

• Graves disease
• Thyroid carcinoma

23
EXTERNAL RADIATION ( gt 25 Gy)

• Hodgkins lymphoma neck lymphadenopythy
• Malginant tumors of the head and neck
• Nuclear catastrophy

24
DRUGS

• Lithium
• Amiodarone
• Phenytoin
• Carbamazepine
• Ethonamide (anti-TBC)
• Overdose with thyreostatic drugs
• Methimazole
• Propylthiouracil
• TPO inhibitors sunitinib, sorafenib, imatinib

25
INFILTRATIVE DISEASE (less common)

• Riedels fibrotic goiter
• Hemochromatosis
• Sclerodermia
• Leukemias
• Amyloidosis

26
Riedels goiter

• Synonym Riedels 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

27
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)

28
THYROID ULTRASOUND
29
(No Transcript)
30
SEVERE HYPOTHYRODISM-MYXEDEMA

• EMERGENCY (result of prolonged and severe
  hypothyroidism)
• Triggered by infection, trauma, surgery, cold
• Weakness, impaired conciousness to COMA
• Hypothermia
• Hypotension
• Hypoventilation
• Hypoglycemia
• Hyponatremia
• Edema, swollen tongue

31
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

32
(No Transcript)
33
HYPERTHYROIDISMNEUROPSYCHIATRIC SYMPTOMS

• Restlessness
• Irritability
• Insomnia
• Anxiety
• Emotional lability
• Personality changes
• Psychosis
• Hyperactive deep tendon reflexes

34
HYPERTHYROIDISMCARDIOVASCULAR SYMPTOMS

• ? cardiac output (tachycardia, ? periph.
  resistance)
• ? SBP, ?DBP
• Atrial fibrillation (in 20-30 )
• Congestive heart failure
• Cardiomyopathy
• Mitral valve prolapse, mitral regurgitation

35
HYPERTHYROIDISMGASTROINTESTINAL 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

36
HYPERTHYROIDISMMETABOLIC SYMPTOMS

• Weight loss
• ? total cholesterol, ?HDL cholesterol
• Hyperglycemia (insulin action antagonism)
• ?cortisol

37
HYPERTHYROIDISMMUSCLE SYMPTOMS

• Adynamia
• Muscle weakness (esp. thigh muscles)

38
HYPERTHYROIDISMBONE 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

39
HYPERTHYROIDISMGENITOURINARY 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

40
HYPERTHYROIDISMLUNG SYMPTOMS

• Dyspnea
• ? O2 consumption, ? CO2 production
• Respiratory muscle weakness
• Trachea stenosis by enlarged goiter

41
HYPERTHYROIDISM SKIN SYMPTOMS

• Sweating
• Warm, moist, fine skin
• Fine hair
• Fine nails, onycholysis
• Hyperpigmentation
• Vitiligo
• Alopecia areata

42
HYPERTHYROIDISM HEMATOLOGY SYMPTOMS

• ?erytrocyte volume (MEV)
• Normocytic normochromic anemia (due to increased
  plasma volume)
• ?ferritin
• autoimmune hematologic diseases (pernicious
  anemia, idiopatic trombocytopenic purpuraITP)
• Risk of thrombosis (?fibrinogen, ?v. Willebrand
  f., ?thrombocyte aggregation)

43
(No Transcript)
44
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

45
GRAVES DISEASE

• Autoimmune disease
• Genetic background-HLA-DQA10501
• Viral infection as trigger ?
• Production of TSH-receptor antibodies
  TSI (thyroid stimulating antibodies)
• In GD sometimes initially hypothyroid period

46
GRAVES' DISEASE DIAGNOSIS

• CLINICAL SYMPTOMS OF HYPERTHYROIDISM
• GRAVES' ORBITOPATHY
• LAB TESTS
• ? TSH, ?fT3,fT4
• TSI (gt 95)
• Anti TPO (70)

47
HYPERTHYROIDISM GRAVES' ORBITOPATHY

• 25 patients with Graves disease
• Correlation of orbitopathy with the severity of
  hypothyroidism
• Deposition of collagen and glycosaminoglycans in
  the muscles, enlargement of the retroorbital
  space
• Exophtalmos
• Upper eyelid retraction
• Von Greafes sign (lid lag on infraduction)
• Kochs sign (bulbus lag on supraduction)
• Lagophtalmos

48
GRAVES ORBITOPATHY
49
GRAVES ORBITOPATHY
50
GRAVES' DISEASETHERAPY

• 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)

51
DIFF.DG.

• OTHER CAUSES OF HYPERTHYROIDISM
• Vegetative instability
• Psychosis
• High fever
• Cocaine, Amphetamine
• Tachycardia of different origin

52
THYROTOXIC CRISIS

• Etiology spontaneously in
• Graves disease
• autonomic adenomas (nodes)
• iodine agents
• thyroxin overdose
• inefficient thyrostatic therapy

53
THYROTOXIC CRISISSTAGES

• Stage I Tachycardia gt 150, AF, Fever gt 41,
  sweating, psychomotoric agitation, diarrhea,
  vomiting, adynamia
• Stage II somnolence, psychotic symptoms
• Stage III coma w/wo adrenal failure, shock

54
THYROTOXIC CRISISTHERAPY

• 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

55
THYREOTOXIC CRISISTHERAPY

• IN SEVERE CASES (e.g. iodine induced)
• PLASMAPHERESIS
• SUBTOTAL THYROIDECTOMY

56
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-hypothyroidi
  c, painful thyroid,
• Lab tests ?ESR, ?CRP, normal leukocytes
• Therapy mostly spontaneous healing, NSA,
  rednisolon are optional

57
MULTINODULAR GOITERAUTONOMOUS ADEMOMA

• DIAGNOSIS 131I accumulation on thyroid scan, US
• CLINICAL SYMPTOMS of hyperthyroidism
• THERAPY thyreostatics, radioactive iodine

58
MULTINODULAR GOITER
59
ULTRASOUND OF A THYROID NODULE
60
THYROID SCAN normal accumulation
61
THYROID ADENOMA