THYROID

DISORDERS
Dr. Ananta Aryal
MBBS, MD
Lecturer , Internal Medicine , KMC
Contents
Anatomy and physiology
Regulation of thyroid hormone synthesis
Normal characteristics of thyroid hormones
Significance of unbound thyroid hormones
Approach to hyperthyroidism
Approach to hypothyroidism
Thyroid gland
Anatomy
The thyroid gland consists of two lobes that are
connected by an isthmus.

It is located anterior to the trachea between the

cricoid cartilage and the suprasternal notch
Anatomy
The normal thyroid is 12–20 g in weight, highly
vascular, and soft in consistency

The Thyroid gland consists of numerous spherical

follicles composed of thyroid follicular cells

The C cells (parafollicular ) are interspersed

throughout the thyroid gland
Physiology of thyroid gland
 Characteristics of circulating T4 and T3
Hormone Property T4 T3
   
Serum concentrations    
  Total hormone 8 g/dL 0.14 g/dL
  Fraction of total hormone 0.02% 0.3%
in the free form
  Free (unbound) hormone 21 x 10-12 M  6 x 10-12 M 
   
Serum half-life 7d 0.75 d
Fraction directly from the 100% 20%
thyroid
Production rate, including 90 g/d 32 g/d
peripheral conversion
Intracellular hormone 20% 70%
fraction
Relative metabolic potency 0.3 1
Receptor binding 10-10 M  10-11 M
 
WHY TO MEASURE UNBOUND T3 T4
T4 and T3 are highly protein-bound

Illness, medications, genetic factors can influence

protein binding
Total thyroid hormone levels are
elevated when TBG is increased due to estrogens
(pregnancy, oral contraceptives, hormone therapy,
tamoxifen), and

decreased when TBG binding is reduced (androgens,

nephrotic syndrome).

Genetic disorders and acute illness can also cause

abnormalities in thyroid hormone binding proteins.
Drugs [phenytoin, carbamazepine, salicylates, and
NSAIDs can interfere with thyroid hormone binding

Unbound thyroid hormone levels are normal and the

patient is euthyroid in all of these circumstances
Hyperthyroidism
A state of excessive thyroid function( synthesis and
release )

Thyrotoxicosis: the state of thyroid hormone

excess(irrespective of source)

It is a multi system disease with elevated levels of FT4

or FT3 or both
Causes of hyperthyroidism
1. Graves Disease – Diffuse Toxic Goiter
2. Plummer’s Disease – Toxic MNG
3. Toxic phase of Sub Acute Thyroiditis - SAT
4. Toxic Single Adenoma
5. Pituitary Tumours – excess TSH
6. Molar pregnancy & Choriocarcinoma (↑↑ βHCG)
7. Metastatic thyroid cancers (functioning)
8. Struma Ovarii (Dermoid and Ovarian tumours)
9. Thyrotoxicosis Factitia: Amiodarone, SSRIs
Clinical Features
1. Those that occur with any type of thyrotoxicosis

2. Those that are specific to Graves disease

3. Non specific changes of hyper metabolism

Common Symptoms
1. Nervousness
2. Anxiety
3. Increased perspiration
4. Heat intolerance
5. Tremor
6. Hyperactivity
7. Palpitations
8. Weight loss despite increased appetite
9. Reduction in menstrual flow or oligo-menorrhea
Common Signs
1. Hyperactivity, Hyper kinesis
2. Sinus tachycardia or atrial arrhythmia, AF, CHF
3. Systolic hypertension, wide pulse pressure
4. Warm, moist, soft and smooth skin- warm
handshake
5. Palmar erythema, Onycholysis
6. Lid lag and stare (sympathetic over activity)
7. Fine tremor of out stretched hands – format's sign
8. Large muscle weakness, Diarrhea, Gynecomastia
Specific to Graves Disease
1. Diffuse painless and firm enlargement of thyroid gland
2. Thyroid bruit is audible with the bell of stethoscope
3. Ophthalmopathy – Eye manifestations – 50% of cases
 Sand in eyes, periorbital edema, conjunctival edema
(chemosis), poor lid closure, extraocular muscle
dysfunction, diplopia, pain on eye movements and
proptosis.
4. Dermoacropathy – Skin/limb manifestations – 20% of cases
 Deposition of glycosaminoglycans in the dermis of the lower
leg – non pitting edema, associated with erythema and
thickening of the skin, without pain or pruritus - called
(pretibial myxedema)
Extrathyroidal manifestations of Graves' disease

Ophthalmopathy
Dermopathy
Immunologically mediated activation of fibroblasts
in the extraocular muscles and skin, with accumulation of
glycosaminoglycans, leading to the trapping of water and
edema. Later, fibrosis becomes prominent .The fibroblast
activation is caused by cytokines derived from locally
infiltrating T cells and macrophages
Eye signs in hyperthyroidism
Von Graefe’s sign – lid lag
Joffroy’s sign – absence of wrinkling of forehead on
looking up
Stellwag’s sign - decreased frequency of blinking
Dalrymple’s sign – lid retraction exposing the upper
sclera (staring appearance of the eyes, caused by a
widened palpebral fissure )
Mobius sign – absence of convergence
Non specific changes
1. Hyperglycemia (endogenous sugar production ),
Glycosuria
2. Osteoporosis and hypercalcemia
3. ↓ LDL and Total Cholesterols
4. Atrial fibrillation, LVH, ↑ LV EF
5. Hyper dynamic circulatory state
6. High output heart failure
7. H/o excess Iodine, amiodarone, contrast dyes
Diagnosis
1. Typical clinical presentation
2. Markedly suppressed TSH (<0.05 µIU/mL)
3. Elevated FT4 and FT3 (Markedly in Graves)
4. Thyroid antibodies – by Elisa – anti-TPO,
5. ECG to demonstrate cardiac manifestations
6. Nuclear Scintigraphy to differentiate the causes
 PATTERNS OF THYROID
FUNCTION TEST RESULTS
TSH T4 T3 INTERPRETATIO
N
Low RAISED RAISED PRIMARY
THYROTOXICOSI
S
low NORMAL RAISED PRIMARY T3 -
TOXICOSIS

low NORMAL NORMAL SUBCLINICAL

THYROTOXICOSI
S
low LOW LOW SECONDARY
HYPOTHYROIDIS
M (i.e. PITUTARY
OR
HYPOTHALAMIC
DISEASE) 0R
TRANSIENT
THYROIDITIS IN
EVOLUTION
 Management of
Hyperthyroidism
EVALUATION OF THYROTOXICOSIS
Source-Harrison’s principles of internal medicine,20th edition,
Laboratory findings
 Serum T3 and T4 are elevated

 TSH – Suppressed except in cases of pituitary inappropriate secretion of thyrotropin

 TSH-R Ab – High in 75% of cases

 ESR – Increased in subacute thyroiditis

 Thyroid RAI uptake and scan- Usually performed on patients with an established
diagnosis of thyrotoxicosis
 High RAI uptake – Grave’s disease and toxic nodular goiter
 Low RAI uptake – Subacute thyroiditis

 Others – Hypercalcemia, increased ALP, anemia

Imaging
Only in severe cases or in euthyroid exophthalmos

MRI of the orbits – Method of choice to visualize Grave’s

ophthalmopathy affecting extraocular muscles

CT scanning and USG scan

Grave’s disease
Propranolol
 Symptomatic relief

 Relieves the tachycardia, tremor, diaphoresis, and anxiety

 Initial treatment of choice for thyroid storm

 20 – 40 mg four times daily,

Grave’s disease
Thiourea drugs
 Methimazole
 Carbimazole
 Propylthiouracil

 For young patients with mild thyrotoxicosis, small goiters, or fear of

isotopes.
 Lower chance of posttreatment hypothyroidism
 Usually given for 12-24 months
 Recurrence rate after discontinuation – about 50%
 Side effects- agranulocytosis, usually in the first 60 days of
therapy,
pruritus, allergic dermatitis, nausea, and dyspepsia

 Drug of choice during breast feeding and pregnancy –

Propylthiouracil
Dose 300-600 mg daily in four divided doses
Grave’s disease
Iodinated contrast agents
 Effective temporary treatment
 Iopanoic acid or ipodate sodium
 Inhibit peripheral 5’-monodeiodination of T4, thereby block its conversion
to active T3

Radioactive iodine(131I)
 Excellent method of destroying overactive thyroid tissue
 Should not be given during pregnancy
 Posttreatment hypothyroidism several years after therapy
Grave’s disease
Thyroid surgery
 Pregnant women whose thyrotoxicosis is not controlled with low doses of
thioureas

 Women who desire to become pregnant in the very near future

 Children with grave’s disease

 Nodular goiter when there is suspicion of malignancy

Complications:
 Damage of recurrent laryngeal nerve palsy

 Hypoparathyroidism
Toxic Solitary Thyroid Nodule
 Propranolol – symptomatic

 Definitive
 Surgery – age < 40years

 RAI - age > 40years

Toxic Multinodular Goiter
 Older age

 RAI is preferred

 Surgery – for pressure symptoms or cosmetic indications

Subacute Thyroiditis
 Propranolol

 Iodinated contrast agents

 Subsides spontaneously within weeks to months

 Thioureas are ineffective – hormone production is low

 RAI is ineffective thyroid’s iodine uptake is low

 Pain – aspirin or other NSAIDS

Hypothyroidism
Hypothyroidism
Clinical syndrome that result from cellular
responses to a deficiency of thyroid hormones
or rarely, from cellular unresponsiveness to
normal or high level of thyroid hormone.
Iodine deficiency is the most common cause
worldwide.
Autoimmune disease (Hashimoto's
thyroiditis) and iatrogenic causes (treatment of
hyperthyroidism) are common in areas of iodine
sufficiency
 Prevalence

• Annual incidence of autoimmune hypothyroidism

4/1000 women and 1/1000 men

•Mean age at diagnosis-60 yrs , prevalence increases with

age

•Subclinical hypothyroidism;6-8% women(10% over age

60yrs) and 3% in men
Causes of Hypothyroidism

1.Primary
Congenital
Agenesis
Ectopic thyroid remnant

Defect of hormone synthesis

Iodine def.
Dyshormonogenesis
Antithyroid drugs,lithium,
Amiodarone ,interferon
Autoimmune
Atrophic thyroiditis
Hasimoto’s thyroiditis
Postpartum thyroiditis

Infective
Post-subacute thyroiditis
Post surgery
Post irradiation
Radioactive iodine therapy
External neck irradiation

Infiltrative tumour
2. SECONDARY
Hypopituitarism
Isolated TSH deficiency

3. Others
Peripheral resistance to thyroid hormone(Refetoff
syndrome)
Symptoms of Hypothyroidism

 Tiredness

 Fatiguability

 Cold intolerance

 Constipation

 Paresthesias
Symptoms contd.

Difficulty in concentrating
Poor memory
Dyspnea
Hoarse voice
Joint stiffness and muscle cramps
Menstrual disturbances-menorrhagia.
Weight gain with poor appetite
Impaired hearing
 Signs of Hypothyroidism

• Dry coarse skin, cool peripheral extremities

• Puffy face, hand and feets
• Diffuse alopecia
• Bradycardia
• Peripheral edema
• Delayed tendon reflex relaxation
• Carpel tunnel syndrome
• Serous cavity effusions
 Secondary Hypothyroidism

• Headache

• Visual disturbances

• Amenorrhea
 Myxedema coma
•defined as severe hypothyroidism leading to slowing of
function in multiple organs
•medical emergency with a high mortality rate
•Pathogenesis not clear

•Proposed
Alveolar hypoventilation-CO2 retention
and narcosis , dilutional hyponatremia

• Reduced level of consciousness, seizure with other features

of hypothyroidism
Myxedema madness-delusional psychosis with
paranoid, manic and depressive features.

Hashimoto’s encephalopathy-
steroid responsive syndrome with TPO
antibodies, myoclonus and slow wave
activity in EEG.
 Diagnosis of Hypothyroidism

In Primary Hypothyroidism
TSH is high.
Free thyroid hormone are depressed.

In Secondary Hypothyroidism
Both TSH and free thyroid hormones are low.
 Antibodies
•Anti thyroid peroxidase [ anti microsomal] antibodies
•Anti thyroglobulin antibodies.
•Anti bodies against T3 and T4 in auto immune
hypothyroid disease.
•In primary hypothyroidism;
up to 12 % pt do have anti gastric parietal cell
antibodies.
these pts. Can develop pernicious anemia.
•In primary hypothyroidism , additional imaging or
serologic testing is unnecessary if gland is normal on
exam.

•In secondary hypothyroidism, further laboratory testing

and imaging to rule out microadenoma.

• Evidence of decreased levels of more than one pituitary

hormone is indicative of a panhypopituitary problem.
•Other tests
•FNA biopsy
•CPK(increase)
•Cholesterol/triglyceride(increase)
•Hb(decrease-normocytic or macrocytic anemia)
EVALUATION OF HYPOTHYROIDISM
Harrison’s principles of internal medicine,20h edition
Source-
 PATTERNS OF THYROID
FUNCTION TEST RESULTS
TSH T4 T3 INTERPRETATIO
N
NORMAL LOW LOW SECONDARY
HYPOTHYROIDIS
M
ELEVATED LOW LOW PRIMARY
>20 mU/L HYPOTHYROIDIS
M
MILDLY NORMAL NORMAL SUBCLINICAL
ELEVATED HYPOTHYROIDIS
5 – 10 mU/L M
ELEVATED NORMAL NORMAL ARTEFACT –
20 - 500 mU/L ENDOGENOUS
IgG Ab WHICH
INTERFERE
WITH TSH ASSAY
ELEVATED HIGH HIGH HIGH T4 DOSE
SECONDARY
THYROTOXICOSIS -
TSH SECRETING
PITUTARY TUMOUR
THYROID HORMONE
RESISTANCE
Management of
Hypothyroidism
EVALUATION OF HYPOTHYROIDISM
Harrison’s principles of internal medicine,20h edition
Source-
Treatment
Clinical hypothyroidism
Hormone replacement therapy
Levothyroxine 1.6 microgram /kg body wt/day (usually 100 to 150
microgram)
Starting dose
Adult patients under 60 without heart disease
50 microgram daily
Dose adjustment – TSH levels
Treatment
Goal
Normal TSH level, ideally in the lower half of the reference range

Repeat TSH
After 2 months of starting treatment

Clinical effects very slow

Relief of symptoms until 3-6 months after normal TSH level
Increased requirement
Interferance with T4
absorption
clearance
 Estrogen
Malabsorption,eg.Celiac
therapy disease, small bowel surgery
 Rifampicin,
Cholestyramine,
 Amiodarone,
Ferrous sulphate,
 Carbamazepine
Calcium supplement,
 Phenytoin
Aluminium hydroxide
Special situations
Pregnancy
Women with a history or high risk of hypothyroidism
 Euthyroid prior to conception and during early pregnancy

Maternal hypothyroidism
 Poor fetal neural development

TFT
 Once pregnancy is confirmed
 At the beginning of second and third trimesters
Special situations
Elderly

 Less requirement

 Starting dose – 12.5 to 25 micrograms/d

Thank you