1. THYROTOXICOSIS AND OTHER
THYDROID DIEASES
KIZITO FELIX
MANJU BUDIA

2. Thyroid hormone synthesis

3. THYROTOXOCOSIS
• Is a clinical syndrome which results from
exposure of the body tissues to excess
circulating levels of free thyroid hormones.
• Also know as hyperthyroidism.

4. Epidemiology
• It is common disorder with a prevalence of
about 20/1000 females
• Males are affected five times less frequently

5. Aetiology
• Graves diseases (90% of cases)
• Multinodular goitre
• Autonomously functioning solitary thyroid
nodule
• Thyroiditis ie subacute (de quervain’s),post partum
• Iodide induced ie drugs (amiodarone),radiographic
constrast media,iodine prophylaxis programme
• Extra throidal source of thyroid hormone
excess ie factitious hyperthyroidism, struma ovari

6. Aetiology cont…
• TSH induced ie inappropriate TSH secretion by pituitary,chriocarcinoma
and hydatidiform mole
• Follicular carcinoma +_ metastatases

7. Clinical features
• Goitre ie diffuse +_ bruit, nodular
• Gastrointestinal ie weight loss, hyperdefecation,diarrhoea and
steatorrhoea,anorexia,vomiting
• Cardiorespiratory ie palpitation,increased pulse pressure, ankle
oedema in absence of hf,angina ,cardiomyopathy and cardiac failure,dyspnoea on
exertion,exacerbation of asthma
• Neuro muscularie nervousness, irritability,emotional
lability,pshchosis,tremor,hyper reflexia ii sustained clonus,Muscle weakness
,proximal myopathy, bulbar myopathy,periodic paralysis
• Dermatological ie increased sweating, pruritus,palmar erythema,
spidernaevi,onycholysis,alopecia,pigementation,viltigo,digital clubbing,pretibial
myoedema

8. Clinical features….
• Reproductives ie amenorrhoea/ oligmenorrhoea,infertility,
spontaneous abortion, loss of libido ,impotence
• Ocular ie lid retraction,lid lag,grittiness, excessive
lacrimation,chemosis,exopthalmos,corneal ulceration, ophthalmoplegia,
dilopia,papilloedema ,loss of visual acuity
• Other ie heat intolerance,fatigue
,apathy,gynaecomastia,lymphadenopathy,thirst,osteoporosis

9. GRAVES DIASEASE
• It is characterised by presence of diffuse
thyroid enlargement, ophthlmopathy and
rarely pretibial myxedema.
• Occurs at any age but unusual before puberty
• Most commonly affects the 30-50 year old age
group.

10. Pathogensis of GD
• Is a major immunologically mediated form of
hyperthyroidism
• Production of IgG antibodies directed against
the TSH receptor on the thyroid follicular cell
• This stimulate thyroid hormone production
and majority goiter formation
• The antibodies are called thyroid stimulating
immunogloblins or TSH receptor
antibodies(TRAb) can be detected in serum

11. Clinical features of GD
• Goitre
• Opthalmopathy
• Pretibial myxoedema

12. Management of GD
• Antithyroid drugs
 carbimazole
methimazole,
Propythiouracil
• Radioactive iodine
• Beta adrenoceptor antagonist
Propranolol(160mg daily in divided dose)
Nadolol(40-80mg once daily)

13. Management…….
• NB : beta adrenoceptor antagonist will
alleviate but not abolish symptoms of
hyperthrodoism in 24-48 hours, used for a
short term treatment.
• Subtotal throidectomy

14. TOXIC MULTINODULAR GOITRE
• This form of hyperthyroidism is more common
in women.
• Mean age is 60 years
• Thyroid hormones usually slightly elevated
• Cvs features like AF or CF are common
• Treatment with large doses of iodidne 131.

15. Toxic adenoma
• The nodule is a follicular adenoma which
autonomously secretes excess thyroid
hormones
• Nodule is >3cm
• This inhibits endogenous TSH secretion and
atropy of the rest of the gland
• Common in females 40 years above
• Diagnosis by isotope scanning

16. Toxic adenoma…..
• Hyper thyroidism is mild with T3 –
thyrotoxicosis
• Treatment is by hemi thyroidectomy or by
iodine 131

17. Sub acute thyroiditis
• Is virus induced (coxsackie ,mumps or
adenovirus) inflammation of the thyroid gland
which results in release of colloid and its
constituents into circulation.
• Characterized by pain in the thyroid region
radiating to the jaw ,ears worsened by
swallowing ,coughing and movements of the
neck.

18. Sub acute thyroiditis …..
• Palpable thyroid enlarged and tender
• Affect females aged 20-40years
• Thyroid hormones levels are raised for 4-6wks
until a preformed colloid is depleted
• Hyperthyroidism is followed by hypothyroidism,
the normal thyroid functions within 4-6 months
• Management NSAIDS for pain ,propranolol
160mgs,at times prednisolone 40mg daily for 3-
4wks.no need for anti thyroid drugs

19. Hypothyroidism
• Defn
• Hypothyroidism is diminished production of
thyroid hormone leading to clinical
manifestations of thyroid insufficiency
• Iodine deficiency is the most common cause
worldwide
• In areas of iodine sufficiency,
autoimmune(Hashimoto’s thyroiditis) disease and
iatrogenic causes(trmt of hyperthyroidism) are
most common

20. Causes of hypothyroidism
Primary
Autoimmune hypothyroidism: Hashimoto's
thyroiditis, atrophic thyroiditis
Iatrogenic: Treatment, subtotal or total
thyroidectomy, external irradiation of neck for
lymphoma or cancer
Drugs: iodine excess (including iodine-containing
contrast media and amiodarone), lithium, antithyroid
drugs, p-aminosalicylic acid, interferon- and other
cytokines, aminoglutethimide, sunitinib
Congenital hypothyroidism: absent or ectopic
thyroid gland, dyshormonogenesis, TSH-R mutation
Iodine deficiency
Infiltrative disorders: amyloidosis, sarcoidosis,
hemochromatosis, scleroderma, cystinosis, Riedel's
thyroiditis
Overexpression of type 3 deoiodinase in infantile
hemangioma
Transient
Silent thyroiditis, including postpartum
thyroiditis
Subacute thyroiditis
Withdrawal of thyroxine treatment in
individuals with an intact thyroid
After 131I treatment or subtotal thyroidectomy
for Graves' disease
Secondary
Hypopituitarism: tumors, pituitary surgery or
irradiation, infiltrative disorders, Sheehan's
syndrome, trauma, genetic forms of combined
pituitary hormone deficiencies
Isolated TSH deficiency or inactivity
Bexarotene treatment
Hypothalamic disease: tumors, trauma,
infiltrative disorders, idiopathic

21. Symptoms and signs of
hypothyroidism(in adults)
Symptoms
•Tiredness, weakness
•Dry skin
•Feeling cold
•Hair loss
•Difficulty concentrating and poor
memory
•Constipation
•Weight gain with poor appetite
•Dyspnea
•Hoarse voice
•Menorrhagia (later oligomenorrhea or
amenorrhea)
•Paresthesia
•Impaired hearing
Signs
•Dry coarse skin; cool peripheral
extremities
•Puffy face, hands, and feet
(myxedema)
•Diffuse alopecia
•Bradycardia
•Peripheral edema
•Delayed tendon reflex relaxation
•Carpal tunnel syndrome
•Serous cavity effusions

22. Evaluation of hypothyroidism
Measure TSH
Elevated Normal
Measure
Unbound T4
Normal
Mild
hypothyroidism
TPOAb+ or
symptomatic
T4 trmt
TPOAb- or no
symptoms
Annual
followup
Low
Primary
hypothyroidism
TPOAb+
Autoimmune
hypothyroidism
T4 trmt
TPOAb-
Rule out
other
causes of
hypothyroid
ism
Pituitary disease
suspected
No
No further
tests
Yes
Measure unbound T4
Low Normal
Rule out drug
effects, sick
euthyroid
syndrome,
then evaluate
ant. Pituitary
fxn
No further
tests

23. Congenital hypothyroidism
• Hypothyroidism occurs in about 1 in 4000
newborns
• Neonatal hypothyroidism is due to
– thyroid gland dysgenesis(80–85%),
– inborn errors of thyroid hormone synthesis in 10–
15%, and
– TSH-R antibody-mediated in 5% of affected newborns
• The developmental abnormalities are twice as
common in girls
• Mutations are being increasingly identified, but
the vast majority remain idiopathic

24. Congenital hypothyroidism contd..
• Clinical manifestations
– The majority of infants appear normal at birth
– <10% are diagnosed based on clinical features,
o prolonged jaundice,
o feeding problems,
o Hypotonia,
o enlarged tongue,
o delayed bone maturation,
o umbilical hernia
• Permanent neurologic damage if treatment is delayed
• Other congenital malformations, especially cardiac, are
four times more common in congenital hypothyroidism

25. Diagnosis and treatment
• Neonatal screening programs have been established.
These are generally based on measurement of TSH or
T4 levels in heel-prick blood specimens.
• When the diagnosis is confirmed,
– T4 is instituted at a dose of 10–15 g/kg per day, and the
dose is adjusted by close monitoring of TSH levels.
– T4 requirements are relatively great during the first year of
life, and a high circulating T4 level is usually needed to
normalize TSH.
• Early treatment with T4 results in normal IQ levels, but
subtle neurodevelopmental abnormalities may occur in
those with the most severe hypothyroidism at
diagnosis or when treatment is delayed or suboptimal.

26. Autoimmune thyroiditis
• Classification
– Hashimoto’s/Goitrous thyroiditis(goiter)
– Atrophic thyroiditis(reducing residual gland)
• Subclinical vs overt/clinical hypothyroidism
• Prevalence
• Mean annual incidence 4 per 1000 women and 1 per 1000 men.
Subclinical hypothyroidism is found in 6–8% of women (10% over the age
of 60) and 3% of men.
• More common in certain populations, such as Japanese, prob bse of
genetic factors & chronic exposure to a high-iodine diet.
• The mean age at dx is 60 years, and prevalence of overt hypothyroidism
increases with age.
• The annual risk of developing clinical hypothyroidism is about 4% when
subclinical hypothyroidism is associated with positive TPO antibodies.

27. Pathophysiology of autoimmune
thyroiditis
In Hashimoto's,
• Marked lymphocytic
infiltration of the thyroid
with germinal center
formation,
• Atrophy of the thyroid
follicles accompanied by
oxyphil metaplasia, absence
of colloid, and
• Mild to moderate fibrosis.
In atrophic thyroiditis
• Lymphocyte infiltration is
less pronounced,
• Thyroid follicles are almost
completely absent.
• The fibrosis is much more
extensive

28. Pathophysio contd.
• Susceptibility determined by a combination of genetic and
environmental factors, & risk of either autoimmune hypothyroidism
or Graves' disease is increased among siblings.
• HLA-DR polymorphisms are the best documented genetic risk
factors, especially HLA-DR3, -DR4, and -DR5 in Caucasians.
• Both of these genetic associations are shared by other autoimmune
diseases, which may explain the relationship between autoimmune
hypothyroidism and other autoimmune diseases, especially type 1
diabetes mellitus, Addison's disease, pernicious anemia, and
vitiligo.
• Envtal factors poorly defined at present. A high iodine intake may
increase the risk of autoimmune hypothyroidism by immunologic
effects or direct thyroid toxicity.
• There is no convincing evidence for a role of infection except for the
congenital rubella syndrome, in which there is a high frequency of
autoimmune hypothyroidism. Viral thyroiditis does not induce
subsequent autoimmune thyroid disease.

29. Pathophysio contd..
• The lymphocytic infiltrate is composed of activated CD4+ and CD8+ T cells as well
as B cells. Thyroid cell destruction is primarily mediated by the CD8+ cytotoxic T
cells, which destroy their targets. In addition, local T cell production of cytokines,
such as TNF, IL-1, and IFN-gamma, may render thyroid cells more susceptible to
apoptosis mediated by death receptors.
• These cytokines also impair thyroid cell function directly and induce the expression
of other proinflammatory molecules by the thyroid cells themselves, such as
cytokines, HLA class I and class II molecules, adhesion molecules, CD40, and nitric
oxide.
• Antibodies to TPO and Tg are clinically useful markers of thyroid autoimmunity, but
any pathogenic effect is restricted to a secondary role in amplifying an ongoing
autoimmune response.
• Up to 20% of patients have antibodies against the TSH-R, which, in contrast to TSI,
do not stimulate the receptor but prevent the binding of TSH. These TSH-R-
blocking antibodies, therefore, cause hypothyroidism and, especially in Asian
patients, thyroid atrophy. Their transplacental passage may induce transient
neonatal hypothyroidism.

30. Clinical manifestations
• Features of thyroid hormone deficiency.
• May be associated with S&S of other autoimmune diseases, particularly
vitiligo, pernicious anemia, Addison's disease, alopecia areata, and type 1 DM
• Less-common assoc include celiac disease, dermatitis herpetiformis, chronic
active hepatitis, rheumatoid arthritis, SLE, myasthenia gravis, and Sjögren's
syndrome.
• Thyroid-associated ophthalmopathy, which usually occurs in Graves' disease,
occurs in about 5% of patients with autoimmune hypothyroidism.
• Autoimmune hypothyroidism is uncommon in children and usually presents
with slow growth and delayed facial maturation. The appearance of
permanent teeth is also delayed. Myopathy, with muscle swelling, is more
common in children than in adults. In most cases, puberty is delayed, but
precocious puberty sometimes occurs. There may be intellectual impairment
if the onset is before 3 years and the hormone deficiency is severe.

31. Differential diagnosis
• An asymmetric goiter in Hashimoto's thyroiditis
may be confused with
– multinodular goiter or
– thyroid carcinoma, in which thyroid antibodies may
also be present.
– Ultrasound can be used to show the presence of a
solitary lesion or a multinodular goiter rather than the
heterogeneous thyroid enlargement typical of
Hashimoto's thyroiditis.
– FNA biopsy is useful in the investigation of focal
nodules.

32. Others causes of hypothyroidism
• Iatrogenic hypothyroidism is a common cause of
hypothyroidism and can often be detected by
screening before symptoms develop.
• In the first 3–4 months after radioiodine treatment,
transient hypothyroidism may occur due to reversible
radiation damage.
• Low-dose thyroxine treatment can be withdrawn if
recovery occurs.
• Mild hypothyroidism after subtotal thyroidectomy may
also resolve after several months, as the gland remnant
is stimulated by increased TSH levels

33. Other causes contd…
• Iodine deficiency is responsible for endemic goiter and cretinism but is
an uncommon cause of adult hypothyroidism unless the iodine intake
is very low or there are complicating factors, such as the consumption
of thiocyanates in cassava or selenium deficiency.
• Though hypothyroidism due to iodine deficiency can be treated with
thyroxine, public health measures to improve iodine intake should be
advocated to eliminate this problem. Iodized salt or bread or a single
bolus of oral or intramuscular iodized oil have all been used
successfully.
• Paradoxically, chronic iodine excess can also induce goiter and
hypothyroidism. The intracellular events that account for this effect are
unclear, but individuals with autoimmune thyroiditis are especially
susceptible. Iodine excess is responsible for the hypothyroidism that
occurs in up to 13% of patients treated with amiodarone.
• Other drugs, particularly lithium, may also cause hypothyroidism.

34. Other causes contd..
• Secondary hypothyroidism is usually diagnosed in
the context of other anterior pituitary hormone
deficiencies;
– Isolated TSH deficiency is very rare. TSH levels may be
low, normal, or even slightly increased in secondary
hypothyroidism; the latter is due to secretion of
immunoactive but bioinactive forms of TSH. The
diagnosis is confirmed by detecting a low unbound T4
level.
– The goal of treatment is to maintain T4 levels in the
upper half of the reference range, because TSH levels
cannot be used to monitor therapy.

35. Treatment of hypothyroidism
• Clinical hypothyrodism
• If no residual thyroid function, the daily
replacement dose of levothyroxine is usually 1.6
g/kg body weight (typically 100–150 g)
• After trmt of Graves’ disease, lower replacement
dose(75-125microg/d)
• Adult pts < 60 without evidence of heart disease
may be started on 50–100 g levothyroxine (T4)
daily
• Adherence must be ensured and follow-up
measurement of TSH is recommended at annual
intervals

36. Trmt contd
• Subclinical hypothyroidism
• no universally accepted recommendations
• but most recently published guidelines dont
recommend routine treatment when TSH levels are
below 10 mU/L
• Important to confirm that any elevation of TSH is
sustained over a 3-month period before treatment is
given. There is a risk that patients will progress to overt
hypothyroidism, particularly when the TSH level is
elevated and TPO antibodies are present.
• Treatment is by starting with a low dose of
levothyroxine (25–50 g/d) with the goal of normalizing
TSH. If thyroxine is not given, thyroid function should
be evaluated annually.

37. Trmt contd
• Special considerations
• Pregnant women; The dose of levothyroxine may need
to be increased by 50% during pregnancy and returned
to previous levels after delivery.
• Elderly patients may require 20% less thyroxine than
younger patients
• In the elderly, esp pts with known CAD, starting dose of
levothyroxine is 12.5–25 g/d with similar increments
every 2–3 months until TSH is normalized
• Emergency surgery is gen safe in pts with untreated
hypothyroidism, although routine surgery in a
hypothyroid patient should be deferred until euthyroid

38. Myxedema coma
• Clinical manifestations include reduced LOC,
sometimes assoc with seizures, as well as the
other features of hypothyroidism
• Hypothermia can reach 23°C (74°F).
• h/o poor compliance or undiagnosed hypothy
• Almost always occurs in the elderly
• Ppted by factors that impair respiration
• Hypoventilation, leading to hypoxia and
hypercapnia, hypoglycemia and dilutional
hyponatremia contribute to its devt

39. Trmt of myxedema
• Trmt; levothyroxine single IV 500mcg/day or ngt if iv
failed
• Alternatively liothyronine iv or ngt 10-25mcg 8-12
hourly
• Another option is to combine levothyroxine (200 g) and
liothyronine (25 g) as a single, initial IV bolus followed
by daily treatment with levothyroxine (50–100 g/d) and
liothyronine (10 g every 8 h).
• Supportive therapy(correct assoc metabolic disturb,
external warming if temp<30, parenteral
hydrocortisone 50mg every 6 hourly, trmt of ppting
factor, ventilation support, hypertonic saline, glucose

40. Other abnormalities
• Thyroid binding site abnormalities; X-linked
TBG deficiency, TBG levels are elevated by
estrogen, drugs, Mutations in TBG,
TTR(transthyretin), and albumin may increase
the binding affinity for T4 and/or T3 and cause
disorders known as euthyroid
hyperthyroxinemia or familial dysalbuminemic
hyperthyroxinemia