10. CONGENITAL HYPOTHYROIDISM PREVALENCE
• 1 in 4000 newborns
• Can be
• Transient - if the mother has TSH-R blocking antibodies
• Permanent- majority
• Causes
• 80-85% cases - Thyroid gland dysgenesis
• 10-15% cases- Inborn errors of Thyroid hormone synthesis
• 5% cases- TSH-R antibody mediated
• Gene Mutations include:
• PROP-1, PIT-1, TSH-receptor, TSH beta, Thyroid Peroxidase,
Thyroglobulin, Pendrin
11. Clinical manifestation
• Majority- appear normal at birth
• Few cases are diagnosed on the basis of clinical features &
biochemical screening
• Clinical Features include:
• Prolonged jaundice
• Feeding problems
• Hyotonia
• Enlarged tongue, Umblical hernia
• Delayed bone maturation
• Complications:
• Congenital malformations (Cardiac)
• Permanent neurological damage
12. DIAGNOSIS & TREATMENT
• Neonatal Screening programs
• Measurement of TSH or T4
• Heel prick blood sample
• Treatment dose: T4 10-15 ug/kg per day
• Early treatment- normal IQ levels
13. AUTOIMMUNE HYPOTHYROIDISM
• Classification:
• Hashimoto’s or Goitrous Thyroiditis
• Atrophic Thyroiditis
• Prevalence
• 4 per 1000 women, 1 per 1000 men
• Mean age ~ 60 years
• Subclinical hypothyroidism prevalence
• 6-8% women
• 3% men
14. PATHOGENESIS
GENETIC ENVIRONMENTAL
• HLA-DR3, DR4 and DR5
• CTLA-4
• Association with Down’s Syndrome
• Association with Turner’s Syndrome
• Other asso. autoimmune diseases
• High iodine intake
• Low selenium intake
• Decreased exposure to microbes in childhood
• Smoking cessation
• Alcohol- protective
HASHIMOTO’S THYROIDITIS ATROPHIC THYROIDITIS
• Marked lymphocytic infiltration
• Germinal center formation
• Atrophy of thyroid follicles,
oxyphil metaplasia
• Absence of colloid
• Mild to moderate fibrosis
• Extensive fibrosis
• Lymphocyte infiltration- Less
• Thyroid follicles- completely
absent
• Usually the end stage of
Hashimoto’s
15. ANTIBODIES CYTOKINES
• 20% Patients- TSH-R antibody- Blocking type
• Responsible for transient neonatal
hypohyroidism
• TBII assays
• Anti TPO
• Anti Tg
• Lymphocytic infiltrate- T cells & B cells
• CD8+ cytotoxic T cells
• TNF, IL-1, IGN gamma
16. Clinical manifestation
• Onset-usually insidious
• Hashimoto’s- Goitre rather than other features
• Irregular & firm in consistency
• Atrophic thyroiditis or late stages of Hashimoto’s- Present with
symptoms & signs of Hypothyroidism
20. Other causes
• Iatrogenic
• Radioiodine treatment
• Subtotal Thyroidectomy
• Iodine Deficiency
• Endemic goitre & cretinism
• Uncommon in adults
• Public health measures avoid this condition
• Iodine excess
• Chronic excess can induce goitre & hypothyroidism
• Amiodarne, Lithium
• Secondary Hypothyroidism
• Ant pituiary hormone deficiencies
• TSH levels can be low, normal or even slightly increased
21. TREATMENT - CLINICAL HYPOTHYROIDISM
• Dose of Levothyroxine (T4) ?
• Ideal time of taking?
• Goal of treatment?
• TSH monitoring?
• Symptom relief?
• Risk of overtreatment?
• Issues with adherence?
• Don’t feel any difference after missing few doses
• If misses single dose?
• Increased requirements?
24. SPECIAL CONSIDERATIONS
• Pregnancy
• Thyroid function should be monitored
• Before conception- therapy to target TSH in normal range
• TFT
• Every 4 weeks in first half of pregnancy
• every 6-8 weks after 20 weeks
• Levothyroxine dose is increased by 45%
• After delivery dose- Pre pregnancy levels
• Elderly
• Require 20% less dose than younger specially cardiac patients
• Starting dose 12.5 to 2 ug/day
• Gradual increments in 2-3 months
• Surgery?
26. Subclinical hypothyroidism
• Overview
• Subclinical hypothyroidism is defined as an increased
serum TSH in the presence of normal serum T4.
• Prevalent in Women and Elderly
36. Clinical manifestation
• Features common to Thyrotoxicosis
• Specific for Graves’ Disease
• Clinical presentation depends upon:
• Severity
• Duration
• Age
• Individual responsiveness to excess thyroid hormone
• Apathetic Thyrotoxicosis?
37.
38. Specific for graves disease
Gland is diffusely enlarged, 2-3 times
normal size, consistency is firm, thrill or
bruit can be heard at the inferolateral
borders of the gland.
Opthalmopathy Dermopathy Acrophathy
• Thyroid asso. ophthalmopathy
• 75% cases- Onset 1 yr before or after
the onset of Graves
• Euthyroid ophthalmopathy
• 10% patients- Unilateral
• Earliest symptoms-Gritty sensation,
eye discomfort, excess tearing
• Severe cases- Corneal damage,
periorbital
edema, scleral injecion, chemosis,
Diplopia(5%)
• Most serious manifestation- Optic
nerve compression
• <5% patients
• Always occurs in presence
of moderate to severe
ophthalmopathy
• Most frequent location?
• Non inflames, indurated
plaque, deep pink to
purple, Orange skin
appearance
• <5% patients
• Always occurs in
presence of moderate to
severe ophthalmopathy
• Most frequent location?
• Non inflames, indurated
plaque, deep pink to
purple, Orange skin
appearance
39.
40. Laboratory evaluation
• TSH level is suppressed, total & free T3, T4 are increased
• T3 toxicosis?
• T4 toxicosis?
• Associated abnormalities:
• Elevation of Bilirubin
• Liver enzymes
• Ferritin
• Microcytic anemia
• Thrombocytopenia
41.
42. Clinical course
• Clinical features worsen without treatment
• Mortality 10-30% without treatment
• 15% patients- Develop Hypothyroidism 10-15 years later
• Ophthalmopathy
• Worsens over initial 3-6 months-->Plateau phase 12-18 months ->
Improves spontaneously
• Radioiodine treatment- worsens ophthalmopathy
• Dermopathy
• appears after 1-2 years
• may improve spontaneously
44. ANTITHYROID DRUGS (THIONAMIDES
• Used for 1-2 years prior to definitive therapy (surgery or radioablation)
• Indications:
• Pregnancy
• Children & Adolescent
• Severe Graves’ disease with eye changes
• MOA: Inhibit TPO enzyme & iodination & organification
45. METHIMAZOLE CARBIMEZOLE PTU
Free T4
•1-1.5 times ULN
•1.5-2 times ULN
•2-3 times ULN
Tapering
• Additinal
immunosuppressive action
• Dose- 20-60 mg-->5-15 mg
• Total duration- 18-24
months
• Adverse effects-
Rashes,Urticaria, Fever,
Athralgia, Agranulocytosis,
hepatotoxicity, aplasia cutis
(neonates
• Preferred during first
trimester of pregnacy
(donot cross placenta)
• Additionally inhibits
peripheral T4->T3
conversion
• Dose- 100 mg TDS->50 mg
TDS
ADVANTAGES DISADVANTAGES
No surgical scar, Chances of
injury,Hypothyroidism if induced is reversible,
Can be used in children and young.
Prolonged treatment, High relapse, impractical in
huubnhacmooUppaedhryaatyive patient
46. Radioiodine ablation
• Definite therapy in non-pregnant patients
• Strictly avoided in smokers & those with moderate - severe
ophthalmopathy
• Indications
1. Patients >40 years of age
2. Young individuals who are sterilized
3. Young patients with short life span
• I131 capule -> emits gamma radiation -> ablation of thyroid
gland within 6-18 weeks
• Dose- 185-555 MBq
• Complications- Hypothyroidism, Infertlity, Secondary cancers
47. Surgery
• Subtotal Thyroidectomy
• Indications
• Severe hyperthyroidism in children
• Pregnant women who cannot tolerate thionamides
• Large goitre with severe ophthalmopathy or pressure symptoms
• Who require quick normalization of thyroid function
• Preparation: Propanolol, Methimazole, Potassium Iodide
• Complications
• Hypothyroidism
• Hypoparathyroidism
• Hypocalcemia
• RLN damage
48. ADJUNCTIVE THERAPIES
• Oral Radio-contrast Agents: Sodium Ipodate, Iopanoic acid
• Iodine elixirs: 10 drops of SSKI
• Glucocorticoids
• Cholestyramine: 4 gm four times a day
• Potassium perchlorate
• Lithium
• Calcium: for skeletal health 1 gm per day
49. Treatment for graves
disease
• Reversal of Hyperthyroidism
• Smoking cessation
• Local measures: Eyes shades, artificial tears
& lubricants
Drugs
• Selenium - Antioxidant
• Glucocorticoids - Anti inflammatory
• Teprotumumab - IGF-1 receptor inhibitor
• Mycophenolate moetil
• Tocilizumab - Anti IL6
• Rituximab - Anti CD 20
Surgery
• Orbital decompression
• Fat decompression
• Bilateral lateral tarsorrhaphy
• resection of Muller’s muscle
Treatment of dermopathy
• Usually asymptomatic- Treatment is not
necessary
• Indications: Pruritus, Local discomfort,
Unsightly appearance, progression of
lesions
Non Pharmacological
• Avoid tobacco
• Reduce weight
• Normalize thyroid function
Pharmacological
• Topical Fluocinolon acetonide
• Intralesional Triamcinolone acetate
• Pentoxiphylline
50. ACUTE THYRODITIS SUBACUTE THYRODITIS CHRONIC
THYRODITIS
DEF Suppurative infxn of
thyroid gland
Infiltrative DZ of thyroid
gland
Infiltrative DZ of the
thyroid gland
ETIO Bacterial/fungal Viral/ TPO A/B Autoimmune/TPO
A/B
GOIT Small, tender asymmetric Small, exquisitely tender Firm, hard, with
variable sizes
CLIN Febrile illness with LAP,
dysphagia and erythema
around the gland
Fever, +/- hypo/hyperthyroid
signs /symptoms
Local compressive
symptoms,
Hashimoto
Dx Elevated WBC AND ESR,
FNA shows PMN
infiltration, gram stain and
Cx
TFT, FNA to R/O bleeding
into cyst or CA
Open Bx
Rx ABX • ASPRIN( 600MG Q4-6HR)
• PREDNISOLONE(14-40MG)
• PHASE Tx
Surgical
decompression,
tamoxifen
51.
52. Phase Tx
• Thyrotoxicosis improve spontaneously but may be
ameliorated by β-adrenergic blockers; antithyroid drugs play
no role in treatment of the thyrotoxic phase.
• Levothyroxine replacement may be needed if the
hypothyroid phase is prolonged, but doses should be low
enough (50–100 μg daily) to allow TSH-mediated
recovery.
53. Amiodarone induced thyroditis
• Amiodarone (iodine in sheeps clothing) contains 39% iodine
by weight.
Pathophysiology Clinical manifestation
• Acute/transient suppression of thyroid
function
• Hypothyroidism in pts susceptible to inhibitory
effects of high iodine load.
• Thyrotoxicosis(Jod-basedow effect, in
MNG,Graves or thyroiditis)
• Hypothyroidism
• Thyrotoxicosis
Diagnosis & Treatment
• Color-flow U/S is used to differentiate type 1 AIT from type 2
AIT.
• D/C if possible
• Potassium percholorate (200mg Q6hrs), R/F of
agranulocytosis.
• GC have modest effect on type 2 AIT
• Lithium has some benefit
• Near total thyroidectomy is the most effective long-term sol’n if
it can be performed safely.
55. DIFFUSE NON-TOXIC (SIMPLE) GOITER
Etiopathogenesis Clinical manifestations & DX
• Iodine deficiency(MCC)
• Environmental goitrogens(e.g cassava
roots)
• Inherited defects in thyroid hormone
synthesis.
• Mostly ASX
• P/E diffuse, nontender, soft symmetrically
enlarged.
• Substernal goiter(blocks thoracic inlet,
pemberton’s sign)
• CT/MRI if obstructive features present in
substernal goiter
• TFT’s
Treatment
• Iodine replacement induces variable regression.
• Surgery is indicated if compression of trachea or thoracic inlet
occurs.
• Cosmetic surgery
56. Nontoxic MNG
Etiopathogenesis Clinical manifestations & DX
• Occurs in up to 12% of adults
• Females > Males
• MC in areas of iron defeciency, but
also occurs in areas of iron excess.
• Polyclonal/ monoclonal
hypercellular/hyerplastic regions to
cystic areas of hemmorhage may be
seen.
• Extensive fibrosis
• ASX & euthyroid
• Compressive SX( rare)
• SX if extremely large and fibrotic.
• Pain suggests hemorrhage into nodule
or suggest malignancy
• Hoarseness, also suggests
malignancy
57. Diagnosis Treatment
• P/E thyroid architecture is distorted
and multiple nodules ov varying size
are present.
• Pamberton’s sign could be positive
• TSH (usually normal)
• Tracheal deviationand airway
compromise (>70% of tracheal
diameter), inspiratory stridor.
• PFT to assess respiratory function.
• CT/MRI
• Barium swallow may reveal extent of
tracheal compression.
• U/S for which nodules to be Bx
• Conservative management
• Avoid contrast agents, iodine containing
substances (Jod-Basedow effect)
• Radioiodine ablation(3.7MBq per gram
tissue, enganced by rTSH 0.1 IM)
• GC along with surgery in acute
compression
• Surgery remains the definitve Tx
58.
59. Toxic MNG
Pathogenesis and Diagnosis Clinical manifestations
• Autonomous toxic nodules are present.
• Molecular bases for autonomy is unknown.
• TSH is low, T4 level is normal or minimally
increased, T3 is elevated often to greater
degree than T4.
• Thyroid scan shows heterogenous uptake
• U/S for cold nodules, then FNA may be
indicated based on sonographic pattern.
• Surgery if CA on cytology
• Subclical/ overt hyperthyroidism
• AFIB, palpitation, tachycardia, nervousness,
tremor, and weight loss in elderly.
Treatment
• Antithyroid drugs elderly/paliative)
• Radioiodine is the Tx of choice
• Surgery is definitive Tx
• Tx hypothyroidism afterwards.
60. Toxic adenoma
Pathogenesis & clinical manifestation Diagnosis
• Acquired, somatic mutation in TSH-R
pathway leading to enhanced thyroid
follicular cell proliferation and function.
• Mild thyrotoxicosis, only detected
when nodule >3cm
• Subnormal TSH level
• P/E presence of nodule, absence of
graves specific signs,
• Thyroid scan is definitive (increased
uptake by the toxic adenoma)
Treatment
• Radioiodine ablation is the Tx of choice (large doses
are used)
• Surgical resection(lobectomy)
• Antithyroid drugs and BB for short term.
• U/S guidance, repeated percutaneous radiofreaquency
thermal ablation.
• Hypothyroidism occurs in <10%
63. Thyroid cancer
• Most common malignancy in endocrine system.
• Malignant tumors derived from the follicular epithelium
are classified according to histologic features.
– Differentiated tumors, such as papillary thyroid cancer (PTC) or
follicular thyroid cancer (FTC), are often curable, and the
prognosis is good for patients identified with early-stage disease.
– In contrast, anaplastic thyroid cancer (ATC) is aggressive,
responds poorly to treatment, and is associated with a bleak
prognosis.
64.
65.
66.
67. Papillary Follicular Anapalastic Medullary
• Well
differentiated
• MC(80-85%)
• FNA(orphan
annie eye
appearance)
• Can infiltrate
adjacent
structures of the
neck
• Spreads
lymphatically
• Have excellent
prognosis
• Tx
• TSH
suppression
• Radioiodine
• Well
differentiated
• Accounts for 5%
of thyroid CA
• Difficult to DX by
FNA
• Dx by capsular
and/or vascular
invasion
• Spreads
hematogenously
• Poor prgnosis if
hematogenously
spread.
• Tx
• TSH
suppression
• radioiodine
• Poorly
differentiated
aggressive
cancer.
• Poor
prognosis(pts die
with in 6 months
of Dx)
• Chemotherapy is
ineffective.
• External beam
therapy
• Immune
checkpoint
inhibition therapy
may beneficial
(recent data)
• Sporadic or
familial
• Associated with
MEN
• More aggressive
when associated
with MEN 2B
• Elevated serum
calcitonin
provides a
marker for
residual or
recurrent DZ
• Tx is surgical
