HYPER AND

HYPOTHYROIDISM
-

Dr. Raluca-Alexandra Trifanescu

THYROID- ANATOMY
THYROID- ANATOMY and
ULTRASOUND
THYROID – OPTIC MICROSCOPY

Thyroid follicles with

colloid
Thyroid follicular cell
 Iodine and thyroid hormones

-  iodine: 66% of T4 and 58% of T3

-  intrathyroid iodine: 5-10 mg
-  iodine concentration thyroid: serum= 30:1 (NIS, active
transporter)
-  recommended iodine intake: 150 µg/day in adults, 200
µg/day in pregnant women
Thyroid hormone synthesis
Thyroid hormone secretion
Nuclear receptor of thyroid hormones
Regulation of thyroid secretion
Pituitary-thyroid axis
Deiodinases (type 1,2,3)
 Carbimazole
Ioine excess: KI/NaI, Lugol Imidazole Deriv.
solution, iopanoic acid Methimazole
Thiourea deriv. PTU

Iodine

Thyroid ablation: 131I, after Williams, 2003

thyoidectomy
TSH receptor
 Normal thyroid function

Secretion: T4, T3 Free T4

Tissue effect TSH

 Normal thyroid function

Thyroid secretion Tissues

T4:T3= 14:1 in men Brain- T4:T3= 1,17:1
T4:T3= 6:1 in mice Heart- T4:T3= 2,25:1

Daily thyroid secretion rate :

101 µg T4 + 6 µg T3
T4 à T3 = 20 µg T3
Pilo A, Am J Physiol, 1990; 258:E715

Escobar-Morreale HF, Endocrinology, 1996; 137(6):2490

Thyroid function
 Adult hypothyroidism
-  Definition -  Mechanisms
-  Classification -  Pathology
-  Clinics -  Physiopathology
-  Lab -  Evolution
-  Diagnosis -  Complications
-  Differential diagnosis -  Treatment
– Causes
-  Prognosis
 ADULT HYPOTHYOIDISM

Definition: deficient thyroidal production of thyroid

hormones

MYXEDEMA
Definition: severe hypothyroidism with acumulation
of glycosaminoglycans (GAG)
 Classification of hypothyroidism
depending on etiology
PRIMARY: SECONDARY:
-  after thyroid surgery
-  after radioiodine - panhypopituitarism
- TSH deficit
-  congenital defects (aplasia, - Hypothalamic causes
hypoplasia)
-  atrophic thyroiditis after
radioterapy for lymphoma
- 
- chronic autoimmune thyroiditis
(Hashimoto)
-  subacute thyroiditis/postpartum
thyroiditis
-  iodine deficiency
-  drugs: amiodarone, lithium, TKI
- congenital defects in thyroid
hormone biosynthesis
 Classification of hypothyroidism
depending on presence of goiter

Without goiter: With goiter:

-  chronic autoimmune thyroiditis
- after thyroid surgery
(Hashimoto)
-  after radioiodine
-  subacute thyroiditis/postpartum
-  congenital defects (aplasia,
thyroiditis
hypoplasia)
-  atrophic thyroiditis after -  iodine deficiency
radioterapy for lymphoma
-  drugs: amiodarone, lithium, TKI
- panhypopituitarism

- TSH deficit

- Hypothalamic causes
 Clinical presentation
-  asthenia
-  constipation
-  cold intolerance
-  carpal tunnel syndrome
-  oligo/amenorrhoea
-  memory deficit
-  dry skin
-  voice modification
-  obstructive sleep apnea
 Signs
-  thick, dry, cool skin, pale skin/ carotenodermia
-  low pulse rate (bradycardia), diastolic
hypertension
-  pleural effusion
-  pericardial effusion
-  ascites
-  bradypsychia
-  bradykinesia
-  coarse voice
Hypothyroidism
Hypothyroidism
 Lab
Thyroid function tests

Disease TSH FT4 T3

Primary
hypothyroidism
Secondary
/ Normal
hypothyroidism
Diagnostic algorithm
 Lab
Antithyroid antibodies

Anti
Disease ATPO TRAb
Tgl

Autoimmune
majorit majorit 10-20% (blocant)
hypothyroidism
Hashimoto Thyroiditis
Ultrasound aspect
 Lab
Additional investigations

-  anemia (Biermer)
-  dyslipidemia (hypercholesterolemia,
hypertriglyceridemia)
-  ECG: bradycardia, low voltage QRS complexes ±
ischemic features
-  increased CPK, TGO, TGP
-  severe primary hypothyroidism: increased PRL
-  X rays: cardiomegaly, pleural effusion
-  cardiac ultrasound: pericardial effusion
 Diagnosis

1. Clinical symtoms and signs

2.  increased TSH, decreased FT4, T3
3. ± increased TPO, antiTgl Abs
4.  ± personal history of ablative thyrapy,
goiter from childhood
 Differential diagnosis
Of hypothyroidism
q  nephrotic syndrome
q  heart failure
q  cirrhosis

Of etiology: TSH, TPO Abs, ultrasound

q  primary
q  secondary
 Etiology
Genetic predisposition: HLA DR3, DR5, Dqx7,
DRw53, DR9 (autoimmune)
Enzyme defects: TPO
Tg, NIS, Pendrine defects
Development deffects: aplasia, hypoplasia
Association of hypothyroidism with other
autoimmune diseases
SD. SCHMIDT

v  Hashimoto thyroiditis
v  Addison disease
v  ± hypoparathyroidism
v  ± type 1 DM
v  ± premature ovarian faillure ±
rare: candidiasis
 Complications

-  myxedema coma
-  dyslipidemia, atherosclerosis
-  depression, encephalopathy
 Myxedema coma

Ø  hypotermia
Ø  altered mental status, stupor
Ø  hypoventilation
Ø  mortality 80%
 Myxedema coma
Precipitating factors
-  infecţions
-  cold exposeure
-  heart failure
-  stroke
-  acute myocardial infarction
-  digestive bleeding
-  drugs
 Myxedema coma
Laboratory test

1.  Respiratory acidosis

2.  hypoxemia, hypercapnia
3.  hyponatremia: up to 80%
4.  hypoglycemia
5.  increased CPK, LDH, ALT, AST
 Treatment
Objectives

1. Normalization of tissue levels of thyroid

hormones
2. Prevention and treatment of complications
 Treatment principles

•  levothyroxine/ levothyroxine + T3
•  gradual increase of doses in elderly people,
patients with coronary heart disese (risk of
arrhytmias, angina)
•  monitoring: clinically + TSH
•  TSH: measurement at 6-8 weeks after
dosage change
•  secondary hypothyroidism: FT4 monitoring
 Methods

Drugs:
Levothyroxine 1.6- 1.7 µg/kg/day (50-200 µg/day)
 Treatment of myxedema coma

•  inpatient in ITU
•  O2, assisted ventilation if necessary
•  fluids
•  Correction of hyponatremia if present
•  Levothyroxine (300 – 500 µg in i.v. bolus) thereafter 50 – 100 µg/day
•  liothyronine (T3) i.v. 10 µg every 4 hours or 25 µg every 8 hours
(caution at arrhytmias)
•  iv. glucocorticoids (Hydrocortisone hemisuccinate 50-100 mg every 6
hours)
•  Correction of anemia or other causes
•  Correction of hypothermia
 Congenital hypothyroidism

Early diagnosis permits prevention of mental retardation

in children.

INCIDENCE:
1: 4000 new borns
 Classification of congenital
hypothyroidism
1. Primary congenital hypothyroidism
Ø  without goiter
Ø  with goiter

2. Secondary congenital hypothyroidism

3. Resistence to thyroid hormones

(Refetoff syndrome)
 Clinical features

-  normal height at birth, weight at birth could be increased

-  lethargy, hypotonia, dry, cool skin, hypothermia,

macroglosia, prolonged neonatal jaundice, umbilical hernia,
etc

-  Growth failure

-  Mental retardation
 Lab

- TSH >20 mUI/L, T4 < 6,5 µg/dl (screening)

-  icreased bilirubinemia
-  hyponatremia
-  delayed bone age
-  athyroglobulinemia (thyroid agenesia)
-  thyroid ultrasonography
- Presence or absence of eutopin thyroid tissue
-  sublingual thyroid gland
- Technetium 99m sau 123I (not 131I) thyroid scintigraphy:
 Neonatal screening

-  „dry spot” measurement of TSH (day 3-5 after birth)

-  Children with high TSH levels are re-called for

venous sampling as soon as possible
 Defects in thyroid hormones
transport Target cell
Blood
T4 T4
Type 2
deiodinase
T3
T3
R
T Coactivator
X T s
R
T3 T3 R R
MCT8 TRE Target genes

Gene
expression

Cytoplasm Nucleus

R T Heterodimer receptor
Thyoid hormone transporter (affinity X R
for T3 >T4) retinoid X- receptor-
R thyroid hormones
 Treatment
Principles
- as soon as possible
- we treat both overt and subclinical hypothyroidism
- we treat both permanent and transient hypothyroidism

Objectives:
- normal mental development and normal growth
- normalization of TSH and FT4

Methods: orally levothyroxine

- 10-15 µg/kg day (37.5-50 µg/day).
 Treatment monitoring

-  TSH, FT4 every 2,4 weeks initially, thereafter monthly in the

first year, every 2-3 months between 1-3 years, thereafter every
3-12 months

-  Normal TSH and FT4

-  To avoid overdosage (attention deficits, etc).

Thyroiditis Classification

Hipotiroidism
 Subacute thyroiditis

Ø  most frequent in women

Ø  after an infection
Ø  fever
Ø  increase in thyroid volume
Ø  spontaneous and palpatory painfull thyroid
gland
Ø  ± transient signs of thyrotoxicosis
 Lab
•  Increased ESR (100 mm/hour)
•  functio lesa à decrease RAIU (radioiodine
uptake)
•  increased T3, T4 à normal à decreased
•  Decreased TSH à normal à increased
 Thyroid function test during
subacute thyroiditis
Transient Hypothyroidism Recovery
thyrotoxicosis
18 Euthyroidism 20

16 18

14 16
14
12
12
10
10
8
8
6
6
4 4
2 2
0 0
3 6 9 12
1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4

0
T4 (µg/dl) TSH (mUI/l)
Time (months
 Differential diagnosis

Ø Thyroid cysts
Ø  other forms of thyroiditis (drugs, etc)/
thyrotoxicosis
Ø Thyroid cancer

Etiology
- viral
Course of subacute thyroiditis
 Treatment
Principles: we do not treat thyrotoxicosis
Methods:
- non steroidal antiinflammatory drugs 6-10
weeks à ESR decrease
- glucocorticoids: Prednisone 30-40 mg/day
x 10 days à gradual decrease of doses
- β blockers, sedatives
Chronic autoimmune thyroiditis
(Hashimoto)

Ø The most frequent chronic thyroiditis

Ø Prevalence:3%
Ø Women:men= 8:1
Ø High levels of antithyroid antibodies
 Chronic autoimmune thyroiditis
(Hashimoto)

Ø  diffuse or nodular goiter

Ø  some forms with thyroid atrophy
Ø  ± subclinical/overt hypothyroidism signs
Ø  rare thyrotoxicosis (Hashitoxicosis)
Chronic autoimmune thyroiditis
(Hashimoto)
Ultrasonography aspect
 Lab
•  Increased antiTPO, antiTGL antibodies
•  + increased TSH
 Treatment

•  LT4 50-200 µg/day if

hypothyroidism is present
 Thyrotoxicosis

Definition: thyroid hormones excess at tissue levels

Hyperthyroidism

Definition: thyrotoxicosis due to increased thyroid

function
 Thyrotoxicosis classification

With Without
hyperthyroidism hyperthyroidism

-  subacute thyroiditis
-  Graves disease -  post partum thyroiditis
-  toxic multinodular goiter -  drugs iduced thyroiditis
-  solitary toxic adenoma (Plummer -  factitia thyrotoxicosis
syndrome)
-  struma ovarii (ovarian teratoma
-  TSH secreting pituitary adenoma with functional thyroid tissue)
- Metastatic follicular carcinoma
 Clinical features
Symptoms

-  weight loss despite increased apetit

-  tachycardia
-  dyspnea
-  asthenia, fatigability
-  heat intolerance, excessive sweating
-  iritability
-  insomnia
 Clinical features
Signs
-  tachycardia, atrial fibrillation
-  tremor
-  wet skin
-  myopathy
-  heart failure
-  hypokalemic periodic palsy (in Asian men)
-  psyhosis
Lab
 Lab
Thyroid function tests

Disease TSH FT4/TT4 FT3/TT3

Primary hyperthyroidism

T3 toxicosis normal
Subclinical
normal normal
hyperthyroidism
Secondary
hyperthyroidism (TSH
/ normal
secreting pituitary
adenoma)
Thyroid hormones
/ normal
resistance
 Lab
Thyroid autoantibodies

ATPO Anti Tgl TRAb (stimulating)

Graves
70-80% 30-50% 70-100%
disease
Radioiodine uptake (RAIU)
 Thyroid scintigraphy

RAIU Aspect
Graves disease Diffuse enlargement
Toxic multinodular Cold and warm
goiter thyroid nodules
Subacute thyroiditis No image
Solitary warm
nodule, the rest of
Toxic adenoma / normal
the thyroid is not
visible
Factitia No image
thyrotoxicosis
 Thyroid ultrasound

Increased vascularization at Doppler ultrasound

 Additional investigations

-  anemia
-  neutropenia
-  increased hypercalcemia, hypercalciurie
-  increased SHBG
-  TGO, TGP
-  K+, CK
 COMPLICATIONS

-  thyrotoxic crisis
-  periodic hypokalemic palsy
-  heart failure with increased cardiac
output
-  cachexia
 Thyrotoxic crisis
Clinical presentation

Ø  fever
Ø  agitaţion, delir or stupor
Ø  jaundice, vomiting
Ø  dehydration
Ø  arrhythmias with high heart rate
Ø  heart failure
Ø  collapse
 Thyrotoxic crisis
Precipitating factors

-  infections
-  iodine overload (constrast media agents,
amiodarone)
-  surgery (thyroidectomy)
-  stroke
-  acute myocardial infarction
-  pulmonary embolism
-  trauma
-  diabetic cetoacidosis
 Principles of treatment

•  it is not an etiological treatment

•  pathogenic treatment: glucocorticoids (in

Graves ophthalmopathy)

•  do not administer antithyroid drugs (ATD) in

thyrotoxicosis without hyperthyroidism
 Principles of treatment

•  to restore normal thyroid function, avoiding hypothyroidism

•  prevention and treatment of Graves ophthalmopathy is
important
•  in patients with autoimmune hyperthyroidism – remissions
and relapses – long term follow-up is needed.
 Hyperthyroidism treatment
Methods

1.  To avoid stress, iodine excess

2. Drugs: Antithyroid drugs (ATD)
3. Radioiodine (131I)
4. Surgery: subtotal thyroidectomy
5. + adjuvant therapy (beta blockers, iodine,
lithium, sedatives)
 Treatment strategy

Patient
•  Age
•  Gender: M/F, desire to conceive
•  Associated diseases
•  Patient’s preference

Disease:
•  Severity of the disease
•  Presence/absence of evolutive GO
•  Presence/absence of complications
•  Goiter’s size
 Antithyroid drugs (ATD)

Methimazole (Thyrozol)

•  Initially dose 15-30 mg/day (5-10 mg every 8-12 hours x

3-4 weeks)
•  gradual decrease of doses: 10 à 2.5 mg/day
•  treatment duration: 18-24 months
•  remission rates (Graves disease): 30-50%
•  Side effects: agranulocytosis (<1%), rash, allergies,
hepatotoxicity, fever
•  Monitoring: FT4, whole blood count, TGO, TGP
•  Combined therapy: ATD 20 mg/day + Levothyroxine
 Thyroid storm – Treatment

•  O2, fluids
•  PTU: 600 mg initially, thereafter 200-300 mg/6 h; Thyrozol 80
mg/day
•  KI solution 5 drops/6 h– 1 h after ATD
•  Propranolol 40-60 mg/4 h or 2 mg i.v./4 h
•  Dexamethasone 2mg/6 h
•  +/- Lithium Carbonate 600 mg initially, thereafter 300 mg/8 h
(measurement of lithemia!)
•  Phenobarbital
•  Decrease of body temperature
•  Dialysis, hemodialysis/ peritoneal dialysis/ plasmapheresis
 Graves disease (GD)
Definition
Hyperthyroidism with autoimmune pathogeny,
associating:
Ø  diffuse goiter
Ø  ± exophthalmic syndrome
Ø  ± pretibial mixedema

Prevalence: 2% in women, 0.2% in men

à the most frequent form of hyperthyroidism both in iodine repleated
and iodine deficient areas

Harrison, Principles of Internal Medicine

Forbes, Clinical Medicine ,1997
Ophthalmopathy in Graves disease

Williams, Textbook of Endocrinology

 Graves Ophthalmopaty (GO)
Clinical features

-  proptosis (> 16 mm)

-  excessive lacrimation
-  photophobia
-  diplopia
-  pain at eye movements, retroorbital
pains
 Graves Ophthalmopaty (GO)
CLINICAL ACTIVITY SCORE MOURITS
Add 1 point for each finding
• Symptoms
– Pain or pressure in a periorbital or retroorbital distribution
– Pain with upward, downward, or lateral eye movement
• Signs
– Swelling of the eyelids
– Redness of the eyelids
– Conjunctival injection
– Chemosis
– Inflammation of the caruncle or plica
• Changes
– Increase in measured proptosis > 2 mm over 1-3 months
– Decrease in eye movement limit of > 8º over 1-3 months
– Decrease in visual acuity (2 Snellen chart lines) over 1-3 months
.
 Graves Ophthalmopaty (GO)
CLINICAL ACTIVITY SCORE MOURITS

Clinical Activity Score

• Score > 4
– Positive predictive value 80%
– Negative predictive value 64%

Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag
R. Br J Ophthalmol. 1989 Aug;73(8):639-44.
 Basic NOSPECS Classification

• N = No symptoms or signs
• O = Only signs
• S = Soft tissue involvement
• P = Proptosis
• E = Extraocular muscle involvement
• C = Corneal involvement
• S = Sight loss due to optic nerve
compression
 Thyroid ultrasound

LS

LD

Doppler sonography: increased vascularization

 Thyroid scintigraphy

Enlarged thyroid, increased radioioidine uptake

(RAIU)
 Orbitary MRI

Coronal Transverse

muscles’ hypertrophy
 Diagnosis

1. Hyperthyroidism with diffuse goiter ±

exophthalmic syndrome
2.  suppressed TSH, increased FT4, T3
3.  TRAb-70-100%
4.  increased TPO, AntiTgl Abs
5.  ± ultrasound, scintigraphy: diffuse
goiter
 Differential diagnosis
Of hyperthyroidism
q  anxiety
q  pheochromocytoma
q  neoplasia

Of etiological form: ultrasound, scintigraphy, TPO

Abs, TRAb
q  toxic multinodular goiter
q  toxic adenoma
q  subacute thyroiditis
 Etiology
Unknown
Genetic predisposition: HLA DR3, DQA1* 0501

Pathogeny

Autoimmune
Graves disease and autoimmune disorders

v  type 1 DM
v  Addison disease
v  vitiligo
v  pernicious anemia
v  alopecia areata
v  miastenia gravis
v  celiac disease
v  etc
 Graves disease pathogeny
Genetic predispozition: HLA

- Increased TH Ly, decreased TS Ly à Plasmocytes à

TRAb à stimulation of TSH receptor à
hyperthyroidism
Pathogeny of Graves ophthalmopathy

Retroorbitar fibroblast

TSH-R
 Pathology

Active follicles with tall cells and reduced colloid, lymphocytes

 Evolution

•  complications: atrial fibrillation, heart

failure, cachexia

•  Duration of hyperthyroidism: cca. 2 years

•  Duration of active GO: 5 years à fibrosis
 Graves disease

Adjuvant therapy (beta blockers)

ATD 18-24 months 131I: 5-15 mCi

Remission Relapse Major side

(30-50%) (50-70%) effects

or

Periodical ATD
follow-up Surgery
or
 Graves disease

ATD

Side effects

Minor Major (<1%)

• Rash/allergy • Agranulocitosis
• Fever •  Jaundice/hepatitis
• Arthralgia •  Lupus-like syndrome

CONTINUE ATD
Change the drug MMI to Immediately ATD withdrawal
PTU
Antihistamine drugs 131I or Surgery
 Surgery in Graves disease
Relapse after ATD
withdrawal
Big goiter
Pregnancy (T II)
Patient’s preference
Normal thyroid
function on ATD

Solution KI 3 drops x 3/day, 7-14 days before surgery

SUBTOTAL THYROIDECTOMY

Success rate: 98% Complications à Hypothyroidism

Recurrence rate: 2-5% Hypoparathyroidism, lesions of recurrent
larynx nerve, bleeding <4%
 Treatment of Graves orbitopathy

1.  To avoid powerful light, wind

2. Refrain for smoking
3.  Sunglasses
4.  Artificial tears and ointments, Nocturnal eye taping
5. Drugs: glucocorticoid (oral, iv)
3. Orbital Radiotherapy: HVR (20 Gy/eye, in 10 sessions, 2 Gy/
session)

4. Surgery: orbital decompression, Rehabilitative Surgery

(squint surgery, eyelid surgery)
Ophthalmopathy evolution depending on
hyperthyroidism treatment
 Glucocorticoids in GO

- Prednisone 1 mg/kgc/day
- “pulse therapy”
Methylprednisolone 500 mg/week x 6 weeks
250 mg/week x 6 weeks
- SINERGISTIC effect with radiotherapy
 TOXIC MULTINODULAR GOITER

- elderly patients
- originating from iodine deficient areas
- sometimes after iodine overload
- “apathetic hyperthyroidism”
Toxic multinodular goiter
 Thyroid scintigraphy
Toxic multinodular goiter
 Treatment

1.  Normalization of thyroid function (ATD)

2.  Radical therapy

Surgery 131 I
-  large goiter -  small-medium goiter
-  younger patients -  elderly patients
-  suspicion of malignancy -  patients with increased
surgical risk
-  patients preference
 Toxic adenoma
PLUMMER SYNDROME

Definition: A toxic adenoma is a monoclonal,

autonomously functioning thyroid nodule (AFTN) that
produces supraphysiological amounts of T4 and/or T3
resulting in suppression of serum TSH. The function of
the surrounding normal thyroid tissue is often, but not
always, suppressed.
 Toxic adenoma
Clinical presentation

ü  signs and symptoms of

thyrotoxicosis
ü  and/or a thyroid nodule.
 Thyroid scintigraphy
Toxic thyroid adenoma (PLUMMER syndrome)
 Etiology
- Activating mutation of TSH receptor
 Toxic adenoma treatment

1.  Antithyroid drugs if overt or subclinical

hyperthyroidism
2.  Surgery (hemithyroidectomy)
3.  Radioiodine treatment