Transcript hyperthyroidism[1]

Hyperthyroidism
Defintion
 THYROTOXICOSIS
 Increased
thyroid hormone levels with
biological effects on tissues and systems
 HYPERTIROIDISM
 Hyperfunction
of thyroid gland
History

Have described different forms of
hyperthyroidism
Parry (1786),
 Flajani (1808),
 Graves (1835),
 Basedow (1840),
 Moebius (1886),
 Plummer (1913 – adenomul toxic),
 Adams, Purves, Mc Kenzie (1956 – long-acting thyroid
stimulator immunoglobulins – LATS)

Thyrotropic axe
TRH
piytuitary
II-
I2
TSH
MIT
T
T44
fT
fT44
T4
DIT
T
T33
fT
fT33
T3
thyroglobulin
II--
TBG
HYPERTIROIDISM
Etiolology : incidence
Autonomic
- >40 ani
- b=f
other (< 1%)
Graves disease
- < 40 ani
- f / b = 10 / 1
HYPERTIROIDISM
Most frequent forms
Basedow-Graves disease
Toxic adenoma Plummer
Toxic multinodular goiter
TSH
TSH
TSH
T4
T4
T4
Hypertiroidism – etiology
A. tirotoxicosis with hyperthyroidism
1. Thyroid stimulation

TSI

Graves disease
 TSH
 thyrotropinoma
Resistance to thryoid hormone
action
 Refetoff syndromes
Human Chorionc Gonadotropin
 Trophoblastic tumors
 hiperemesis gravidarum




3. Iodine induced

2. Autonomous thyroid function



Toxic adenoma
Toxic multinodular goiter
Non-autoimmune difuse
hyperthyroidism(familiala,
sporadic?)
Thyroid carcinoma follicular
struma ovarii
Jod-Basedow
 Iodine contrast media, amiodarone (thyroid excess and autonomous
thyroid function)
Hypertiroidism - etiology
B. Thyrotoxicosis without hyperfunction of the thyroid
gland
4. Distruction
 thyroiditis
 subacute de Quervain thyroiditis
 Silent thyroiditis
 Drug induced (amiodarone, interferon-alfa)
 Irradiation,
5. External intake
 Iatrogenic
 Factitia
 foods (« hamburger thyrotoxicosis »)
HYPERTIROIDISM / THYROTOXICOSIS
signs and symptoms

Simptoms due to increased number of cathecolamine
receptors




Simptoms due to metabolic actons of thyroid hormones







palpitation (tachicardia, atrial fibrilation)
Increasd perspiration
tremor , hiperreflexia, eyelids retraction
Weight loss with increased appetite , decreased fat and muscle
mass
termofobia
Warm skin, fine, moist; onicholisis
Muscle weakness,
osteoporosis
Menstrual problems in women and gynecomastia in men
Simptoms induced by thyrpid hormone effects on central
nervous system

Nervousness , irritability, psychological labillity,
Clinical signs
33
35
54
65
70
75
82
85
88
89
89
91
99
0
25
50
75
100
frequent stool
pretibial oedema
ophtalmopathy
increased appetite
weakness
Dyspnea
tachicardia82
weight loss
astenia
Palpitatii
termofobia
Hipersudatie
nervousness
Clinical symptoms
10
gynecomastia
10
10
splenomegaly
71
77
eye symptoms
97
Tremor
97
skin manifestations
fibrilation
thyroid trill
100
goiter
100
tachicardia
0
20
40
60
80
100
Hypertiroidism - simptoms
SIGNS
CAUSE
Thyroid
Diffuse goiter
Uninodular goiter
Multinodular goiter
Non-palpable thyroid
Painfull thyroid
Graves’ disease, autoimmune thyroiditis
with thyrotoxicosis
Thyroid autonomy
Thyroid autonomy
Exogenous thyroid hormones
Subacute thyroiditis
Associated signs
Ophtalmopaty
Pretibial mixoedema
Acropachy
Graves’ disease
Graves’ disease
Graves disease
Cardio-vascular signs and symptoms
signs



Tachicardis, continous,
nocturnal

+ effort associated dyspnea

Systolic Hypertension
Increased cardiac output

 FC

 peripheral resistance

 miocardial contractility
Cardiotireosis

Atrial fibrilation : 10%





Congestive hearth failure



Rarely < 40 ani
Corrected by euthyroid state
Anticoagulant treatment
Embolic risk (8%)
Fibrilation,
Aged patients
Worsening coronary hearth disease
Neuro muscular signs
Nervosness, irritability,
 Emotional disturbance
 Disturbance of
attention and mood.



Pseudo psychotic forms
Tremor
Muscle weakness
 Rapid reflexes,
 Amiotrophy (pseudo
miopathic forms)
 Hypokaliemic
periodic paralysis

Digestive signs

Tranzit accelerat
(motor)


pseudodiaree = poli
exoneratie
Anomalii hepatice

Icter, citoliza,
hipocolesterolemie
Genital
abnormalities
men
 gynecomastia (40%)
 Erectile dysfunction
 infertility
women
 Menstrual
abnormalities
 disovulation
Bone abnormalities
Skin problems
Decreased BMD :
distruction>formation
 Spontaneous fractures
 Hypercalcemia,
hypercalciuria
  alkaline phosphatase
and osteocalcin


pruritus
 Localized edema
 Alopecia
Metabolic abnormalities
Hypocholesterolemia
 Hyperglicemie,
worsening of diabetes
mellitus

Positive diagnosis
Clincal signs and symptoms
 TSH: suppressed (excepton TSH-secreting pituitary adenoma)
  FT4 and/or FT3
 Etiologic diagnosis


history




pregnancy
Painfull thyroid
drugs
Clinical signs


goiter
Extrathyroidal signs
TSH receptor stimulating immunoglobulins (TRAb)
 Scintigraphy
 Urinary iodine

HYPERTIROIDISM
Peripheral metabolism
Parameter
Hypertiroidism
Hypotiroidism
Basal metabolic rate


Cholesterole


SHBG


Osteocalcin


OH-proline


Pyridinoline


< 240 ms
> 360 ms


Deep tendon reflex
Qkd interval
HYPERTIROIDISM / TIROTOXICOSIS
Paraclinical diagnosis
TSH, fT4
TSH↓, fT4↑
Hyipertiroidism
T3 tirotoxicosis
fT3↑
Exoftalmie +
Exophtalmos -
TS-Ab +
Ultrasound
Scintigram I123
TS-Ab
hypoechoic
TS-Ab +
Graves’s disease
Multiplee hot nodules
TS-Ab -
TSH↓, fT4=
TSH ↑, fT4↑
fT3
TSH adenoma
Syndrome Refetoff
fT3↓
Euthyroid sick syndrome
Critical diseases
Dopamine,
Hypoechoic thyroid
TS-Ab -
Subacute thyroiditis
Toxic adenoma
Hashimoto’s thyroiditis
Toxic multinodular goiter
Jod-Basedow
Tirotoxicosis factitia
Struma ovarii (rarely)
HYPERTIROIDIS / THIROTOXICOSIS
Imagery: Graves’disease
Thyroid ultrasound
HYPERTIROIDISM / THYROTOXICOSIS
Imagery : toxic adenoma
Thyroid ultrasound
Scintigram
HYPERTIROIDISM / THYROTOXICOSIS
tests: toxic adenoma
TSH
Studer Wyss
T4
PTU
HYPERTIROIDISM / THYROTOXICOSIS
tests: toxic adenoma
TSH
Studer Wyss
PTU
Querido
TSH
TSH
T4
HYPERTIROIDISM / THYROTOXICOSIS
tests: toxic adenoma
fT4
TSH
Studer Wyss
PTU
Querido
TSH
Werner
fT4
T4
HYPERTIROIDISM / THYROTOXICOSIS
Complications

Hearth


atrial fibrilation resistant to treatment
hyperkinetic hearth failure
Infertility / amenorrhea
 Osteoporosis (postmenopausal)
 Thyrotoxic periodic paralysis





flaccid paralysis and hypokalemia
asian men
reversible on treatment
Apathetic hyperthyroidism

Aging patients
Thyrotoxic crisis (thyrotoxic storm)
 Etiology

determinant factors
Undertreated thyrotoxicosis
 Recently developed untreated hyperthyroidism

 Precipitating
factors
 medical
infecţions
Diabetic ketoacidosis
Lung embolism
Labor or pregnancy
Premature stopping treatment
I131 treatment

surgery
Thyrotoxic crisis
severe signs and symptoms of thyrotoxicosis
severe hipermetabolism

fever

over >38oC (til 41-42oC)
Neuro-psychological

symptoms
“thyrotoxic encephalopathy" -
cardio-vascular
symptoms
tachicardia - >140/min,
 arhitmias (atrial fibrillation )
 Hearth failure (left, global)
 Variations of arterial blood pressure

gastro-intestinal
symptoms
Mimikin acute abdomena
 Jaundice (index of severity)

Graves disease

Most frequent cause of hyperthyroidism

Prevalence 1%



19/1000 ♀
1,6/1000 ♂ (Sex ratio 7 / 10)
Incidence 2 - 3 cases / year /1000 ♀
Young female patient, psychological trauma
 Autoimmune, familial


Asociated with other autoimune diseases:


tip 1DM, adrenal insufficiency, vitiligo, miastenia gravis
Stimulating immunoglobulins
perspiration
flushes
< 40 years
Lymp node enlargement
amiotrophie
dispnea
Gynecomastia in ♂
Weigh loss
nervosness, emotional instability
exophtalmos
goiter (± thrill)
Hot, mois skin
palpitations,
tachicardia, low
response
apetit to
 digytalis 
diarheea
tremor
acropachia
oligo/amenorrea
Local mixedoema
Muscle weakness,
fatigability
Graves’ disease
goiter
Graves’
disease
Graves’ disease
GOITER
 Difuse
 Elastic
 Homogenous
 painless
 Vascular (thrill)
Graves exophtalmos
Graves ophtamopathy







Eyelid edema, periorbital edema, proptosis
Increase tears production
Incomplete close eyelids during night
Fotofobia,
Eye disconfort, pruritus, “alergy
Painfull eyes, associated or not with eye mouvments
Dyplopia
 Intermitent: when patinets is tired
 Inconstant
 Constant: when reading
Graves ophtalmopathy NOSPECS
Class
Definition
0
No phisical signs and symptoms
1
Only signs, no symptoms
(upper lid retraction, stare, proptosis to 22 cm)
2
Soft tissue involvement (symtpoms and signs)
3
Proptosis > 22 cm
4
Extraocular muscle involvement
5
Corneal involvement
6
Sight loss (optic nerve involvement)
Severity of Graves ophtalmopathy
Degree
Signs and symptoms
EUGOGO
(European Group on Graves’ Orbitopathy)
Mild
1.
2.
3.
4.
Minimal or moderate edema
Proptosis <25 mm
Diplopia: absent or intermitent
No optic nerve envolvement
Moderate
Important edeme
1. And/or proptosis >25 mm
2. And/or inconstant dyplopia
3. And/or corneal point lesions
4. No optic nerve involvement
Severe
Constant dyplopia
1. And/or optic nerve involvement
Clinical Activity Score (CAS)
1.
2.
3.
4.
5.
6.
7.
Spontaneous retroocular pain
Pain at eye mouvments
Eyelid erithema
Corneal increased vascularity
Chemosis
Edema of caruncula
Eyelid edema
 Every item has 1 point. Active
ophtalmopathy: >3 poins
Graves’ ophtalmopathy
Eyelid retraction
Graves’ ophtalmopathy
 Eyelid
edema
Graves’ ophtalmopathy
 Superioar
eyelid edema
Graves’ ophtalmopathy
Eyelid edema
Graves’ ophtalmopathy
Enlarged eyelid opening
Graves’ ophtalmopathy
 Corneal
involvment
Graves’ ophtalmopathy
Corneal and conjunctival problems
Graves’ ophtalmopathy
 Exophtalmos
Graves’ ophtalmopathy
 Exophtalmos
Graves’ ophtalmopathy
Ophtalmoplegia
Graves’ ophtalmopathy
Graves’ ophtalmopathy
CT of orbotal area
 Pretibial
mixoedema
 Nodous
eritema
Acropachy
Toxic adenoma (Plummer)

Isolated thyroid
nodule


autonomous
Extranodular
parenchima is not
functioning
Evolutia
adenomuui
toxic
1
2
3
4
5
Autonomous functioning tissue
TSH
Normal
secretion
1
2
3
4
Normal secretion
Autonomous secretion
5
TSH level
Toxic multinodular goiter
 Hearth
signs and symptoms are
dominant
 10
- 15 % of atrial fibrillation in aged
patients is associated with TMG
 Hearth failure
 Compressive
goiter
Subacute thyroiditis




Neck pain
Tirotoxicosis
Post viral
Trifase evolution




Hipoechogenicity



hyperthyroidism
hypothyroidism
euthyroidism
inhomogenous
Pseudo nodular
Absence of iodine uptake
and “white scintigram”
hipertiroidism
eutiroidism
hipotiroidism
HYPERTHIROIDISM / THYROTOXICOSIS
Age-related characteristics
Newborns
• neonatal Graves disease (goiter exophtalmos, thyrotoxicosis)
• temporarly
• permanent
• familial non-autoimmune thyrotoxicosis
Children
• Graves disease
• increased growth rate
Aging patients
•Toxic adenoma / TMNG / Graves
• clinical signs are less obvious
• suspected when
• it is an unexpected weight loss
• atrial fibrilation and hearth failure unresponssive to
digitalis
Amiodarona si tiroida
O
I
C

Celular :



I
se opune intrarii tiroxinei
si fixarii T3 de receptorii nucleari
 TSH us in prima saptamina fara hipotiroidie
Tiroida:



C 4 H9
C 2 H5
Hipofiza tireotropa :


O
O CH2 CH2 N
C 2 H5
acumulare de iod - efect Wolf Chaikoff
citotoxicitate foliculaira
Periferic :

 conversie T4 in T3 (inhiba 5’ deiodaza)
 manifestari tirotoxice putin marcate
amiodarona
Amiodarone –induced hyperthyroidism
Type I : hyperfunctional
(previous thyroid
autoimmunity)
Type II : distructive
(previous normal thyroid)
women 1/2
men 2/3
N, 
Scintigram positive
absente
Scintigram absent
IL6
Normal
 and  Tg
Ultrasound
volume
Normal volume
Hypervascularity
(grad 1-3)
Hipoechoic, hipovascular
(grad 0)
Classic treatment
ATS 6-9 month
KCLO4 Potasium perclorate
Glucocorticoids
Prognosis
Sponaneous regression (3-6
month)
Prolonged hyperthyroidism
Spontaneous regression (36 month)
Transitory hypothyroidism
Affected individuals
123I
uptake
Echodoppler
Thyrotoxicosis treatment
AIM: to decrease thyroid hormones to normal levels
 Distruction of thyroid
1.


surgery
Radio iodine
 Inhibition


of thyroid hormone synthesis (ATD)
Antithyroid drugs
Glucocorticoids adjuvant therapy
Decreases conversion of T4 to T3
3. inhibition
2.




ATD
glucorticoids (high doses)
propranolol
iodine
 Reduction


of receptor coupling
-blokers
plasmaferesis
Antithyroid drugs
Imidazole derivatives (methimasole)
H
H
N
N
S
NH
S
N
Inhibit TPO
COOC2H5
carbimasole
Thyourheea derivatives (thiouracile)
H
H
N
CH3-CH2-CH2
S
N
NH
NH
O
S
O
propilthiouracile
Inhibits TPO
Inhibits type
1deiodinase
Treatment of hypothyroidism ATD

2 possibilities
Continous high dosage and association ofthryoid drugs
when hypothyroidism occurs
 Decreasing dosage to the minimal dosage that
maintans an euthyroid state


Graves disease
Young women
 1,5 years at least
 Monitoring the resullts TS-Ab
 < 50%cure


in toxic adenoma /GMNT

Only a temporary solution
Antithyroid drugs
 Dosage
 Adults

10-20 mg x 2 po initially
Dosage will be decreased to ½ doza when patient
becomes euthyroid
 Children:
initial;y

15-20 mg/m2 divided in 2 doses
Later: minomal efficient dose
Treatment of hyperthyroidism
other possibilities
 Litium



inhibits TPO
high toxicity
 Stable
Iodine
solution
 1 g iodne
 2 g KI
 20 ml distilated water
 Preoperative for surgery
 3 × 20 picături pe zi, 1014 zile
Nodule necrosis with
alcohol


toxic adenoma
Potassium perclorate
amiodarone induced
 thyrotoxicosis

 Lugol

Antiimflamatory drugs
subacute thyroiditis
 Type II amiodarone
induced

radioactive iodine: Graves disease
80-100 mCi/g
131I
x
thyroid
wight (g)
100
x
RIU 123I (24 h)
Radioactive iodine: toxic adenoma
TSH
I*
T
4
Surgery

Graves disease
tyroidectomy (near) total
 indications



GMNT


Increased thyroid nodule
tyroidectomy (near)total
adenomul toxic

lobectomy

Complications
hypothyroidism
 hypoparathyroidisme (35%)
 laringeal nerve paralisis
 hemorrhage during
surgery

GRAVES
OPHTALMOPATHY

Total thyroidectomy or ATD

+ terapie prednisone !


10 mg x 4 – 7d
Form of ophtalmopathy?

recente –immunosupressive




prednisone 25 mg x 4, 7-14 d
metilprednisolone 250 iv, repeated at 3 days (pulse)
Polyclonal immunoglobulins
old (GAG infiltration, fibrosis)




Retroorbitar irradiation
enlargement of the orbitis
surgery on orbital muscles
other plastic surgery procedures
Tratamentul exoftalmiei basedowiene
Decompresie orbitara
Inainte
Dupa tratament
Graves ophtalmopathy
Orbital decompression
Before
After treatment
Thyreotoxic crisis
Objectives
I. Inhibition of thyroid hormone synthesis and
liberation
II.Decreased action of thyroid hormones on target
tissues
Reduction of thyroid hormone concentration
 Conversion inhibition of T4 into T3
 Adrenergic blokade

III.Treatament of systemic symptoms
fever
 dehydration
 supportive

IV.Treatament of precipitating factors
Thyrotoxic crisis
Inhibiton of hormone synthesis
 Antithyroid drugs (ATD)
 Large doses, per os
 Propiltiouracile (PTU) - 1200 - 1500 mg/d (200-250mg la 4h);
 Methimasole (MMI) - 120 mg/d (20 mg la 4h);
Inhibition of TH liberation
 Iodine-containing compaunds
 Lugol
sol; saturate solution of KI (SSKI) -p.o., 5 drops every 6h;
 Contrast media (inhibition of conversion of T 4 into T3):
Criza tireotoxica
Inhibition
II. Reduction of TH action on target tissues
of peripheral conversion T4 to T3
propilthyouracil;
Adrenergic
ipodate, iopanoate; propranolol; glucocorticoids
blokade:
betablokers
- propranolol – most used:
iv, large doses
 short-action blokers (labetalol, esmolol);

reserpine,
utile
guanetidine:
în contraindicaţiile -blocantelor;
Removal
of thryoid hormone excess
plasmapheresis;
dialysis
Thyrotoxic crisis
Treatment od systemic
symptoms
 fever
Coated
with cold sheets
drugs
paracetamole
Dihydration
 heath failure
 glucocorticods

IV. Treatment of
precipitating factors