Thyroid Disorders  Pitfall of Diagnosis & Management

Thyroid Disorders Pitfall of Diagnosis & Management

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Description: What Is the Thyroid? A small butterfly - shaped gland (~20 gm in an adult) located in the neck in front of the trachea. Producing thyroid hormones (T4 and T3), chemicals that travel through the blood to every part of the body. Thyroid hormones tell the body how many calories we burn, how warm we feel, and how much we weigh.

Mechanism of Thyroid Hormones Action at the Cell Level: Binds to high affinity T3 nuclear receptor complex, which stimulates the formation of mRNA sequences and subsequently brings about new protein synthesis. Binds to receptors for T3 at the mitochondrial level; stimulation of oxygen consumption and increase in BMR. Enhance sympathetic activities.

 
Author: KW Lo MD (Senior) | Visits: 619 | Page Views: 1269
Domain:  Medicine Category: Therapy 
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Contents:
Thyroid Disorders –
Pitfall of Diagnosis &
Management
Dr. KW Lo

Division of Endocrinology & Diabetes
HK Sanatorium & Hospital

What Is the Thyroid
A small butterfly-shaped gland (~20 gm in
an adult) located in the neck in front of the
trachea
Producing thyroid hormones (T4 and T3),
chemicals that travel through the blood to
every part of the body
Thyroid hormones tell the body how many
calories we burn, how warm we feel, and
how much we weigh

Mechanism of Thyroid Hormones
Action at the Cell Level
Binds to high affinity T3 nuclear receptor
complex, which stimulates the formation
of mRNA sequences and subsequently
brings about new protein synthesis
Binds to receptors for T3 at the
mitochondrial level; stimulation of oxygen
consumption and increase in BMR
Enhance sympathetic activities

Physiological Effects of
Thyroid Hormones (1)
Skin & connective tissue: important in the
integrity of the collagen, essential for normal
hair growth
Respiratory: regulation of ventilation, affect
respiratory muscle function
CVS: affect cardiac contractility, velocity of
muscle shortening and the rate of isometric
tension development
Neuromuscular: required for normal brain
morphology and histogenesis, and deficiency in
neonatal life results in irreversible brain damage

Physiological Effects of
Thyroid Hormones (2)
GI and Kidney: affect the motility of the GI tract;
inability to clear free water if no thyroid hormones
Endocrine: affect growth and sexual development,
control menstrual regularities and fertility, affect
metabolism of steroid hormones in the liver
Intermediary metabolism: stimulate lipolysis,
enhance hepatic gluconeogenesis, stimulate protein
synthesis and breakdown, increase bone turn over
Erythropoiesis: enhance red cell formation

Production of T41 T31 and rT3. The principal thyroid gland secretion is
T41 85% of which is monodeiodinated by peripheral tissues to T3 and
rT3. Under normal conditions only small amounts of T3 and rT3 are
derived from thyroidal secretion, a discovery that has led to the
concept of T4 as a prohormone. In nonthyroidal illness peripheral
conversion of T4 to rT3 is enhanced leading to a reduction in serum T3
concentration (“sick euthyroid”). The physiological significance of this
shift in T4 metabolism is not well understood.

Serum Proteins that Transport
Thyroid Hormones*
Proteins

T4 Bound (%)

Thyroxine-binding globulin (TBG)

75

Thyroxine-binding prealbumin (TBPA)

20

Albumin

5

*The amount of free and metabolically active hormone is extremely small,
accounting for about 0.03% of circulating T4 and 0.3% of circulating T3

Thyroid Function Tests: The modern assay of TSH

Diagram of principles involved in immunoradiometric assay for
thyroid-stimulating hormone (TSH: thyrotropin). Assay
monoclonal antibody linked to a solid phase
support.(Photograph courtesy of Boots-Celltech Diagnostic,
Limited, Product Information, Slough, United Kingdom.)

Proposed strategy for investigation of thyroid function in patients
with suspected thyroid disease. FT3 = free triiodothyronine; fT4
= free thyroxine; IRMA = immunoradiometric assay; TSH =
thyrotropin. (From Caldwell G, Kellett HA, Gow SM. Beckett GJ,
Sweeting VM, Seth J, Toft AD: A new strategy for thyroid function
testing. Laneet 1:1117-1119, 1985. By permission.)

Interpretation of TSH and FT4 Results

4
FT

Normal

High

High
(pmmol/l)

Low
•Hyperthyroidism

•Euthyroid

sick syndrome
•T4 autoantibodies
•Thyroid hormone
resistance syndrome
•TSH-secreting pituitary

•Thyroid

hormone
resistance syndrome
•TSH-secreting pitutary
adenoma

Norm
al

•Subclinical

hyperthyroidism
•T3 thyrotoxicosis
•Pregnancy (first trimester)
•Drugs (eg. Glucocorticoids,
dopamine, amiodarone)

•Euthyroidism

•Subclinical

Low

•Central

•Central

•Primary

hypothyroidism

hypothyroidism
•Euthyroid sick syndrome
(more severe, uncommon)

TSH (0.3-4.0) mIU/l

(compensated)
hypothyroidism

hypothyroidism

Causes of an undetectable/suppressed TSH
•Thyrotoxicosis
•Transient hyperthyroxinemic state
•Hypopituitarism / central hypothyroidism
•Euthyroid patients in the first trimester of pregnancy
•Exophthalmic Graves’ disease
•Nodular goitre
•Early weeks and months following treatment of hyperthyroidism
•Nonthyroidal medical illness
•Psychiatric illness, e.g. Depressive disorders, schizophrenia
•Medications such as corticosteroids, dopamine
•Exogenous thyroxine

Prevalence of Thyroglobulin
Autoantibody (TGAb) and Thyroid
Peroxidase Autoantibody (TPOAb)
TGAb

TPOAb

Graves’ disease

67%

87%

Hashimoto’s thyroiditis

90-100%

90-100%

Non-organ specific auto-immune
disease
Normal controls

35%

50%

10-18%

10-18%

Assessment of Thyroid
Anatomy and Structure
1.

2.

3.

4.

5.

X-Ray of the thoracic inlet – trachea
compression and distortion, retrosternal
extension
Ultrasound – size, texture, nodules, retro-orbital
changes
Isotope scan (I 131) / (Tc 99M) – size, shape,
position, activity, nodules
CT scan / MRI of orbit – infiltrative
ophthalmopathy
Percutaneous biopsy – fine needle aspiration
(FNA) cytology, trucut biopsy

Thyroid disease

Medical:
•Hyperthyroidism
(Thyrotoxicosis)
•Hypothyroidism
•Thyroiditis

Surgical:
•Goitre
•Nodules
•Cancer

Common Symptoms and
Signs of Hyperthyroidism
Symptoms
Palpitations
Heat intolerance
Nervousness
Insomnia
Breathlessness
Increases bowel
movements
Light or absent
menstrual periods
Fatigue

Signs
Fast heart rate
Trembling hands
Weight loss
Muscle weakness
Warm moist skin
Hair loss
Staring gaze
Enlarged thyroid gland

Clinical Features of Hyperthyroidism (the most common features are in italic)
General

Heat intolerance, sweating
Weight loss despite increased appetite

Fatigue
Lymphadenopathy*
Lymphadenopathy*
Cardiovascular

Palpitations, dyspnoea
Sinus tachycardia, atrial fibrillation
tachycardia,
Systolic hypertension, collapsing pulse, flow murmurs
Cardiac failure
Neuromuscular
Tremor, choreoathetosis
Muscle weakness, proximal myopathy
Periodic paralysis
Myasthenia gravis*
Neuropsychiatric
Nervousness, agitation
Depression, insomnia
Emotional lability, poor concentration
lability,
Psychosis
Gastrointestinal
Increased frequency and softening of bowel motions
Vomiting
Splenomegaly*
Splenomegaly*

Ocular (5.3.2)
Lid retraction, lid lag
Stare and photophobia*
Increased lacrimation and grittiness of eyes*
Periorbital puffiness*
Chemosis (conjunctival oedema)*
oedema)*
Proptosis, corneal ulceration*
Proptosis,
Ophthalmoplegia, diplopia*
Ophthalmoplegia, diplopia*
Papilloedema, loss of visual acuity*
Papilloedema,
Reproductive
Oligo-amenorrhoea
OligoInfertility
Impotence
Gynaecomastia
Dermatological
Pruritus
Palmar erythema
Ankle oedema
Thinning of hair, alopecia
Brittle nails, onycholysis
Finger clubbing (acropachy)*
(acropachy)*
Pretibial myxoedema (Figure 5.3.3)
Goitre
Diffuse with / without bruit*
Nodular

Causes of Hyperthyroidism
Normal / High RAIU

Low RAIU

Graves’ disease

Subacute thyroiditis

Toxic multinodular goitre

Painless(silent)thyroiditis

Solitary toxic nodule

Postpartum thyroiditis

Choriocarcinoma or hydatiform
mole

Factitious hyperthyroidism

Hyperemesis gravidarum
(gestational hyperthyroidism)
TSH – secreting pituitary
adenoma
Pituitary selective thyroid
hormone resistance syndrome

Iodine-induced hyperthyroidism
(Jod-Basedow)
Struma ovarii

RAIU = radioactive iodine uptake

Metastatic functioning thyroid
carcinoma

A Case of Hyperthyroidism due
to Graves’ Disease
F/33, housewife
c/o weight loss of 10 lbs in 2 months despite
good appetite, heat intolerance, increased
sweating, palpitation and bad temper
Pulse 100/min, sweaty palm, hand tremor,
stare look, diffuse goitre with bruit
TSH < 0.01 mIU/l, FT4 = 60.6 pmol/l, TgAb
1/400, TPOAb 1/1600, USS showed a diffuse
goitre

Thyroid Eye Signs
Lid retraction, lid lag (sympathetic overtone)
Periorbital puffiness
Chemosis
Proptosis, corneal ulceration
Ophthalmoplegia
Optic nerve compression

Selection of Antithyroid Treatment for Common Forms of
Hyperthyroidism
Antithyroid drugs
(thionamide) (ATD)

Radioiodine (RAI)

Subtotal thyroidectomy (SX)

Strongly
indicated

•Thyrotoxic

crises or severe
•Preparation for RAI/SX
•Pregnancy
•Young Graves’ disease

after SX
•Thyrotoxic heart disease
after stabilization
•Hyperthyroidism with
concomitant disease or
complication

Not
recommended

•As

long-term treatment in
toxic nodules or toxic
multinodular goitre
•For relapse of Graves’
disease after first course of
ATD or after SX
•Large vascular and/or
nodular goitre
•Poor drug compliance

•“young”

patients (arbitrary •Relapse after first operation
limit < 20 years)
•Patients relying on their voice
for their profession
•Large compressing and/or
retrosternal goitre
•Unstable significant Graves’
ophthalmopathy

Contraindicated

•Known

•Pregnancy

fatal allergy to
thionamides (blood
dyscrasia, hepatotoxicity,
see text)

•Relapse

•Thyrotoxic

•Large

and/or nodular goitre
with pressure symptoms
•Rapidly growing goitre with
suspicion of cancer

•Thyrotoxicosis

crises

not yet
controlled by drugs

Example of ATD Regimen:
•One course of ATD varies from 9 months to 2 years,
average 12 – 18 months.
•e.g. medications by titration method:
(carbimazole [CBZ] 10mg = propylthiouracil [PTU] 100mg)
Dosage

Duration/FU

CBZ 10 – 15 mg tds / 15 mg 4 – 6 wks
bd
10mg bd
8 – 10 wks
15mg OD

10 – 12 wks

10 mg OD

10 – 12 wks

5 mg OD

10 – 12 wks

Side Effects of ATD
Side effects
Skin rash, pruritus,
arthralgias

Action
Try other alternative ATD

Agranulocytosis

Stop and never ATD again,
may need admission

Cholestatic hepatitis

Stop and evaluate, ? Try
other ATD

•It’s a good practice to mention and warn patients about these
possible side effects (severs toxic reaction is extremely rare
from our own experiences) when first starting ATD. Any
doubt, check CBP, LFT
•PTU to be preferred during pregnancy

WBC & Thyrotoxicosis
Graves’ thyrotoxicosis may have low
WBC & platelet at presentation
0.5 to 1.0 % may develop
agranulocytosis after ATD, usually
abrupt presentation, routine CBP
surveillance not indicated
Routine warning to patients
Recovery within 1 week, may be
shortened with G-CSF

Liver Derangement &
Thyrotoxicosis
Related directly to the state of thyrotoxicosis –
mild ↑ ALT, ↑Alk PO4 (bone)
Thyrotoxic heart disease with CHF and
congested liver
Idiosyncratic reaction to thionamides antithyroid
medications
Aetiologically related to the underlying Graves’
disease – autoimmune hepatitis, primary biliary
cirrhosis

Radioiodine TherapyFacts (1)
Nearly for all causes of hyperthyroidism
Safely be given to patients of all age gp but
is less often given to children 6 weeks before monitor
Caution in patients with IHD or elderly, start
at low dose
If suspect adrenal insufficiency or
hypopituitarism, must replace steroids
before thyroxine

Thyroid enlargement
(Goitre)
•Diffuse or nodular
•Single nodule or multinodular
•Cystic or solid
•Benign or malignant
•Any pressure effects

•Simple euthyroid
•Hyperthyroid
•Hypothyroid
•?Autoimmunity

•Neck palpation
•Thyroid scintiscan
•Ultrasound
•FNA

•Examination
•TFTs
•TGAb & TPOAb

Etiology of Simple Goiter
1. Iodine deficiency
2. Iodine excess
3. Goitrogenic agents
a. Drugs
b. Food stuffs
4. Dyshormonogenesis
5. Autoimmunizing thyroiditis
6. Ionizing radiation

Nomenclature of thyroiditis according to the
American Thyroid Association (WERNER 1969)
American Thyroid Association Synonyms
Subacute or acute
nonsuppurative thyroiditis
Chronic lymphocytic thyroiditis

Chronic invasive fibrous
thyroiditis
Acute suppurative thyroiditis
Chronic nonsuppurative
thyroiditis due to specific
infection (tuberculosis, syphilis)

Granulomatous thyroiditis
Giant cell thyroiditis
De Quervain’s thyroiditis
Hashimolo’s thyroiditis
Struma lymphomatosa
Autoimmune thyroiditis
Riedel’s thyroiditis

De Quervain’s thyroiditis
Spontaneously remitting inflammatory
disease of the thyroid gland
Believed to be viral in aetiology

Incidence : not an uncommon disease,

Woolner et al collected 162 cases over 5
years, approximate one-eighth the
incidence of Graves’ disease and 50 times
more frequently than Riedel’s thyroiditis

De Quervain’s thyroiditis
Clinical features:
Pain and tenderness in thyroid
region
Malaise , fatigue with fever (PUO)
Typically gradual onset over 1 to 2
weeks , continues with fluctuating
intensity for 3 to 6 weeks

De Quervain’s thyroiditis
Approximately one half of the patient
present in first week with symptoms of
thyrotoxicosis
Hoffman HS (US) and Harefuah (Israel)
reported 2 cases presented as PUO similar
to our local experiences
Demonstrated association with HLA-B35
and B67 by Ohsako (Japan) in 1995

De Quervain’s thyroiditis
Diagnosis : clinical, with striking
elevation in ESR , mild leucocytosis
and high serum T4, T3 level
Low thyroidal RAIU
Birchall , Chow and Metreweli in
1990 demonstrated the ultrasonic
features and striking volume
change after treatment of 2 cases
of De Quervain’s thyroiditis in HK

De Quervain’s thyroiditis
Treatment :

some patients do
not need treatment, most of them need
NSAID as analgesic, if this fails : 1 short
course steroid for 3-6 weeks

Prognosis :

90% with complete
and spontaneous recovery and return to
normal thyroid function. Litaka (Japan)
evaluated 3344 patients, at least recur
in 2% of patients and exhibited
relatively mild clinical manifestation

Other topics of interest
Pregnancy related thyroid disorders
– Hyper & Hypothyroidism
– Postpartum thyroiditis

Thyrotoxic heart disease
Thyrotoxic periodic paralysis
Thyroid Disorders in the Elderly