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HYPO- AND
HYPERTHYROIDISM
Esztella Mikolás MD
Semmelweis University
2nd Department of Medicine
Anatomy
https://healthjade.com
Histology
http://www.proteinatlas.org
Thyroxin synthesis and excretion
Production is regulated by TSH (thyroid-stimulating hormone) level and iodine supply
Häggström, Mikael (2014).
"Medical gallery of Mikael
Häggström 2014". WikiJournal of
Medicine 1 (2). DOI:10.15347/wj
m/2014.008. ISSN 2002-4436
Regulation of thyroid hormone secretion
Hypothalamic-pituitary-thyroid axis
From the collection of Dr Sheikh-Ali
Physiological effects
thyroid hormone receptors (nuclear):
TR-alpha 1: widely expressed (heart, skeletal muscles, bone)
TR-alpha 2: antagonistic
TR-beta 1: brain, liver, kidney
TR-beta 2: pituitary gland, hypothalamus
increase basal metabolic rate and thermogenesis
stimulate water- and electrolyte transport
accelerate the substrate-turnover, the amino acid and lipidmetabolism
potentiate the effect of catecholamine compounds
regulate growth and neurological development
TSH - thyroid
stimulating
hormone
normal range: 0.45-4.12 mU/l
depends on age, iodine supply, BMI, pregnancy, ethnicity, test method, etc.
www.synthroidpro.com
T3 and T4
Biologically active portion:
FT4 (free T4) ~0,015%
FT3 (free T3)~0,33%
normal range:
FT4: 12-22 pmol/l
FT3: 2.5-6.5 pmol/l
T3 is 2-10-fold more potent
Binding proteins: thyroxine binding protein,
transthyretin, albumin
http://www.anaesthetist.com
Conversion
Deiodinase 1:
expressed mainly in liver and kidney, with lesser expression in the thyroid
Produces small amount of circulating T3 (approx. 24%)
Preserves iodide by removing iodine from inactive metabolites of T3 and T4 in the liver and
kidney
Deiodinase 2:
central nervous system, pituitary gland, thyroid, heart,
brown adipose tissue, and skeletal muscle
T4=>T3 conversion (approx 60%)
Deiodinase 3:
brain and skin
T4=>T2
T4=>rT3
Pol et al, DOI: 10.1007/s10741-008-9133-7
HYPOTHYROIDISM
Definition and frequency
subclinical hypothyroidism: elevated TSH, normal FT4
prevalence: 4-10%
manifest hypothyroidism: elevated TSH, low FT4
prevalence: 0,2-1%
secondary hypothyroidism: elevated/normal/low TSH,low/normal FT4
Clinical symptoms
general: fatigue, headache, cold intolerance, weight gain, anemia
cardiac: pericardial fluid, heart contractility and pulse rate decrease,
but hypertension (peripheral resistance increases)
metabolic: dyslipidemia, hyponatremia
GI tract: constipation, dysphagia
skin: pale, cold, atrophic, myxedema, hair loss, weak, fragile nails
neurological: ataxia, dementia, cognitive dysfunction, hypo-areflexia
respiratory system: hypoventilation, sleep apnea
reproductive system: amenorrhea, decrease of sex drive, infertility,
hyperprolactinemia
musculoskeletal: elevation of creatin-kinase, myopathy, myalgia,
rhabdomyolysis
Etiology
primary hypothyroidism (99%):
autoimmune thyroiditis
iatrogenic (radioiodine
treatment, surgery,
amiodarone)
congenital
iodine insufficiency
malignancy
transient (Wolff-Chaikoff effect,
thyroiditis, thyreostatic
treatment, Li-carbonate, IF-
alpha, IL-2)
secondary hypothyroidism:
pituitary
tertiary hypothyroidism:
hypothalamic origin
thyroid hormone
resistance
http://wikiwel.com/wikihealing//images/d/df/Hypothyroidism.jpg
Diagnostic protocol
aspecific symptoms (elderly!)
history: previous irradiation, thyreostatic treatment,
amiodarone, surgery
TSH, if out of normal range FT4
thyroid specific antibodies
neck ultrasonography
www.med-ed.virginia.edu
Treatment I.
Main goals (ATA 2014):
to provide resolution of the patients' symptoms and
hypothyroid signs, including biological and physiologic
markers of hypothyroidism
to achieve normalization of serum thyrotropin with
improvement in thyroid hormone concentrations
to avoid overtreatment (iatrogenic thyrotoxicosis), especially
in the elderly.
Treatment II.
When to treat:
manifest hypothyroidism
subclinical hypothyroidism:
TSH>10 mU/l
goiter
ischemic heart disease
pregnancy
aTPO positivity
older than 70, TSH>8 mU/l + any of above
symptomatic disease
Treatment III.
levothyroxine (L-T4): 1.6-1.8 µg/kg (75-150 µg)
T1/2 : 7-8 days => orally once daily
absorbed only at low pH value => 30 min before meal
start with lower dose, especially in elderly and/or in case of
cardiac disease (25-50 µg)
first TSH control after 4 weeks
TSH control 6 weeks after every dose adjustments
if stable - yearly
Pregnancy
placental deiodinase => ~45% higher L-T4 dose needed
trimester specific target values:
1st: 0.1-2.5 mU/l
2nd: 0.2-3.0 mU/l
3rd: 0.3-3.0 mU/l
subclinical cases have to be treated
closer TSH control
screening in case of aTPO or aTG positivity, autoimmune history,
goiter, any relevant symptoms present, positive family history,
radioiodine therapy, surgery, miscarriage
routine screening?
Elderly I.
Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism Martin I. Surks, and Joseph G. Hollowell J Clin Endocrinol Metab DOI:
http://dx.doi.org/10.1210/jc.2007-1499
Elderly II.
sensitivity of feedback mechanism decrease with age
alteration of biological activity of TSH
decrease of thyroidal sensitivity to TSH
apathetic hyperthyroidism
Thyroiditis
acute
infective thyroiditis
radiation-induced thyroiditis
palpation-induced thyroiditis
subacute
de Quervain thyroiditis
painless thyroiditis
drug induced (amiodarone, alpha-interferon, IL-2)
chronic
Hashimoto-thyroiditis
infective thyroiditis (immunodeficiency)
De Quervain thyroiditis
(subacute granulomatosis thyroiditis)
etiology: viral infection (?)
female:male=5:1
clinical signs: myalgia, fatigue, thyroid is painful, swollen
laboratory markers: high sedimentation rate, elevated CRP,elevated TG level, moderate leucocytosis
low 24 hour radioiodine uptake
hyper-, eu-, hypothyroidism, euthyroidism
therapy: NSAID, corticosteroids, propranolol
recovery in 3-6 months
short term relapse ~20%, long term relapse ~4%
Hashimoto thyroiditis
organ-specific autoimmune disease => 90% follicular destruction => chronichypothyroidism
female: male=10:1
prevalence: 2-7% (female)
histology: infiltration of lymphocytes, Hürtle-Askanazy cells, follicular destruction, fibrosis(FGF-23)
aTPO and aTG positivity >95%
laboratory markers: sedimentation, CRP mildly elevated
radioiodine uptake: „salt and pepper” pattern
clinical signs: mild thyroid enlargement, sensitivity, transitional hyperthyroidism,permanent hypothyroidism, rare endocrine orbitopathy
therapy: levothyroxine substitution (50-200 µg)
TSH target: 2.5 mU/l
prednisolon in acute phase if necessary
Normal
Hashimoto-thyroiditis De-Quervain-thyroiditishttp://www.ultrasoundcases.info
Congenital hypothyroidism
hypothyroidism is present at birth
incidence:
primary form: 1:3000-5000
secondary form: 1: 10 000
more frequent in girls and twins
in Hungary screened since 1984
only 1/3 of the world is screened!
Orphanet Journal of Rare Diseases20105:17
https://doi.org/10.1186/1750-1172-5-17
HYPERTHYROIDISM
Definition
subclinical hyperthyroidism: low TSH (0.1 mU/l>), normal FT4
manifest hyperthyroidism: low TSH (0.1 mU/l>), high FT4
prevalence: ~0.75%
secondary hyperthyroidism: elevated/normal TSH, elevated
FT4
Clinical symptoms general: weakness, fatigue, high body temperature, hot
intolerance, weight loss with good appetite, resting tremor
skin: warm, wet skin, intense sweating
cardiac: tachycardia, systolic blood pressure elevation, lower
diastolic pressure, positive inotropic effect
metabolic: high metabolic rate
GI tract: diarrhea
neurological: tremor, hyperactivity
respiratory system: hyperventilation
reproductive system: irregular period, amenorrhea,
sex hormone binding protein
musculoskeletal: muscle weakness
Etiology
Thyroid hormone overproduction
TSH-receptor stimulation
Graves-Basedow-disease
mola hydatiosa
choriocarcinoma
TSH overproduction
TSH-producing pituitary adenoma
thyroid hormone resistance
Thyroid autonomy
toxic adenoma
toxic multinodular struma
Unregulated hormone excretion
subacute
Hashimoto
silent (painless) thyroiditis
postpartum
iodine induced
Extra thyroidal hormone production
DTC
struma ovarii
Factitious hyperthyroidism
Diagnosis I.
Anamnesis and physical examination
Laboratory markers:
low TSH, elevated FT4 and FT3 levels
TSH can remain low for months after treatment
FT4 and FT3 indicate severity better
„grey zone TSH” 0.1-0.3 µU/l => repeat test 1-3 months later
Diagnosis II.
Radiology:
ultrasonography (hypervascularisation, nodules)
99mTc gamma scan
low uptake => thyroiditis
high uptake => Graves-Basedow disease
focal high uptake => toxic adenoma
Graves-Basedow disease
incidence: 5-10/100 000
20-40 year-old female patients
TSH-receptor stimulating IgG antibody (TSHR-Ab) in half of all cases
genetic predisposition: HLA-A1, -B8, DR3
physical signs: thyroid can be enlarged, look for signs of EOP or
pretibial myxedema
Graves-Basedow disease -> Thyroid inferno pattern
(increased vascularity and arteriovenous shunting)www.radiopaedia.org
Gamma scan
Treatment I.
Thyreostatic treatment – thionamides
thiamazol (methimazol)
20-60 mg/die => dose reduction
continue for at least one year in euthyreotic state
TSH in every 6-8 weeks
propylthiouracil (PTU)
150-400 mg/die => dose reduction
carbimazol
Side effects
agranulocytosis 1:1000 => radioiodine or surgery
ANCA positive vasculitis
fulminant hepatitis (PTU)
Treatment II.
Radioiodine (RI) treatment
131I-isotope orally – dose: 70 Gy
expected to be effective in 2-6 months
in case of severe, active EOP RI is contraindicated!
preventive corticosteroid for 6-12 weeks in risk groups (smokers, EOP in
history, 35-55-year-old females)
Subtotal thyroidectomy - indications
Basedow-Graves disease + cold thyroid nodule
RI not possible
size reduction needed
Endocrine orbitopathy I.
inflammation of the orbital tissue and ocular muscles
10-30% present in Basedow-Graves disease
TSH-R is expressed on orbital fibroblasts => lymphocyte and macrophage
activation => increase of glycosaminoglycan and sulphated
mucopolysaccharide formation
edema, thickening of orbital muscles, exophthalmos
smoking increases risk by 70%!
diagnosis: MRI T1 - muscle thickening
ATA classification
clinical activity score
Endocrine orbitopathy II.
treatment indications: loss of sight, subluxation of eyeball, change in color
sight, cornea blurriness, progressive exophthalmos, papillary edema,permanently visible cornea
treatment:
euthyreosis
avoidance of smoking
immunosuppression – corticosteroid (per os or iv)
pentoxyphyllin
selenium
retrobulbar irradiation (contraindicated in diabetes mellitus)
surgical decompression
antalgic treatment
Toxic adenoma (TA)
hot nodules on gamma camera
malignancy is extremely rare
compensated TA: normal thyroid tissue function decreases
decompensated TA: normal thyroid tissue is completely suppressed
subclinical cases have to be treated
therapy: RI 300 Gy
radio ablation
laser ablation
surgery
www.memorangapp.com
Toxic multinodular goiter
mainly in older age
can be contrast- or drug induced
therapy: RI 150 Gy (contraindication: significant trachea compr.)
surgery
Kamal A.S. Al-Shoumer, Hossein Gharibentokey.com
THYROID EMERGENCIES
Thyreotoxicosis (thyroid storm)
potentially life threatening condition
provoking factors: RI treatment, surgery, trauma, myocardial infarction, iodine
exposition
symptoms: fever, sweat, flush, tachycardy, cardiac failure, vomiting, diarrhea, loss
of conciousness, coma
FT3 and FT4 is increased but not extreme
Treatment
thyreostatic treatment (thiamazole 80 mg per day/ PTU 250 mg/6 hours)
iodine compounds (Lugol iodine or potassium iodine)
glucocorticoids
beta-blockers
sedatives
Myxedema coma
multi organ failure
more common in elderly
symptoms: severe myxedema, hypotension, bradycardia, low body temperature,
hypoventillation (CO2-retention), SIADH, convulsion, coma
treatment: iv 500 µg levothyroxine (or 25-50 µg T3 every 12 hours)
100 µg levothyroxine per day
5-10 mg/hour hydrocortisone
hyperosmolar fluids only
THANK YOU FOR YOUR ATTENTION!