2. OUTLINE
– Embryology and anatomy of the thyroid
– Physiology of the thyroid
– Investigations of thyroid diseases
– Causes of Hyperthyroidism
– Thyroid Cancers
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4. STEPS OF THYROID HORMONE SYNTHESIS
• Involves:
– Iodide trapping
– Oxidation of iodide to iodine and iodination of tyrosine residues on
thyroglobulins (Tg)
– Coupling of iodothyronines to form T4 , T3 or rT3
– Hydrolysis to release free iodothyronines (T3 and T4) and mono- and
diiodotyrosines
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5. TESTS OF THYROID FUNCTION
• Serum thyroid hormones:
– Serum TSH
– Thyroxine (T4) and tri-iodothyronine (T3)
– Thyroid autoantibodies
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11. THYROID ENLARGEMENT
• The normal thyroid gland is impalpable
• Goiter- generalized enlargement of the thyroid gland
• Solitary (isolated) nodule -a discrete swelling in one lobe with no palpable abnormality
elsewhere
• Dominant nodules- discrete swellings with evidence of abnormality elsewhere in the
gland
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15. • Deficiency in circulating levels of thyroid hormone
– Cretinism (fetal or infantile hypothyroidism)
• Dx:
• A hoarse cry
• Macroglossia and
• Umbilical hernia in a neonate
• Features of thyroid failure
• RX: thyroxine within a few days of birth
• Adult hypothyroidism
• Myxoedema -severe thyroid failure
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17. CLINICAL FEATURES
• The symptoms are:
• tiredness
• mental lethargy
• cold intolerance
• weight gain
• constipation
• menstrual disturbance
• carpal tunnel syndrome
• The signs of thyroid deficiency are:
• bradycardia
• cold extremities
• dry skin and hair
• periorbital puffiness
• hoarse voice
• bradykinesis, slow movements
• delayed relaxation phase of ankle
jerks
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18. INVESTIGATION AND Rx
• Thyroid function tests:
–low T4 and T3
–high TSH (except in the rare event of pituitary failure)
–High serum levels of TPO antibodies are characteristic of
autoimmune disease
•Rx:
–Oral thyroxine (0.10–0.20 mg) as a single daily dose is curative
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20. DEFINITION
• Thyrotoxicosis
– the state of thyroid hormone excess
• Hyperthyroidism
– is the result of excessive thyroid function
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26. • An Autoimmune disease
• 60-80% of thyrotoxicosis
• Age = 20-50 yrs
• M:F = 1:5
• Exact cause not known(
environment & genetics)
• Possible triggers:
– Postpartum period( 3х ↑ risk)
– Stress
– Smoking
– Excess Iodine intake
– Bact. / viral infection
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27. WHAT CAUSES THE
HYPERTHYROIDISM?
• Sensitized T-helper cells stimulate B-lymphocytes produce Abs
– TSI, TS Ab stimulate TSH receptor
– Abs against TH receptor
– TPO Abs
• The coexisting thyroiditis can also affect thyroid function
• In the long term, spontaneous autoimmune hypothyroidism may develop in upto 15% of
Graves' patients.
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28. CLINICAL FEATURES
• Signs and symptoms
– General SSx common to thyrotoxicosis by other causes
– SSx Specific to Graves’ disease
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30. CONT…
• There is increased tissue sensitivity to catecholamines in hyperthyroidism with an
increase in either the number of β-adrenoceptors or the second messenger response to
their stimulation
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32. GRAVES’ OPHTALMOPATHY
• Also called thyroid-associated ophthalmopathy as it occurs in the absence of Graves'
disease in 10% of patients
• Unilateral signs are found in up to 10% of patients
• The earliest manifestations are usually a sensation of grittiness, eye discomfort, and
excess tearing
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33. GRAVES’ OPHTHALMOPATHY
• Proptosis – in 1/3 of patients
• may cause corneal exposure and
damage in severe cases
• Periorbital edema,
• Scleral injection,
• Chemosis
• Diplopia – in 5-10%, with severe
muscle swelling
Papilledema, peripheral field defects,
and, if left untreated, permanent loss
of vision 2⁰ to compression of the
optic nerve at the apex of the orbit
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34. "NO SPECS" SCORING SCHEME
To gauge the extent and activity of the orbital change
0 = No signs or symptoms
1 = Only signs (lid retraction or lag), no symptoms
2 = Soft tissue involvement (periorbital edema)
3 = Proptosis (>22 mm)
4 = Extraocular muscle involvement (diplopia)
5 = Corneal involvement
6 = Sight loss
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36. THYROID DERMOPATHY
• In <5% of patients with Graves' disease
• Almost always in the presence of moderate or severe
ophthalmopathy
• Typical lesion - noninflamed, indurated plaque with a deep pink or
purple color & "orange-skin" appearance.
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37. CONT…
• Most frequent over the anterior and lateral aspects of
the lower leg (pretibial myxedema)
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38. THYROID ACROPACHY
• A form of clubbing found in <1% of patients with
Graves' disease
• Strongly associated with thyroid dermopathy
• without coincident skin and orbital involvement –
search for other causes of clubbing
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39. LABORATORY FINDINGS
• ↓TSH , ± ↑Free T3 & T4
– 2-5% - only T3 ↑(T3 toxicosis) – in borderline iodine intake, & early
Graves’ ds
– T4 toxicosis – in excess iodine intake
• ¹²³I scan – homogenously enlarged gland with increased uptake , confirms
Dx
• Positive TPO or TSH-R Abs – in 75%
• TSH-R Abs & TSI diagnostic - in 90%
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40. • A normal TSH excludes Graves' disease as a cause of
diffuse goiter
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41. TREATMENT
• Reducing thyroid hormone synthesis
–Antithyroid drugs
• Reducing the amount of thyroid tissue
–Radioiodine (131I) treatment
–Thyroidectomy
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43. CONT…
• TSH is low
• T4 – normal or minimally increased
• T3 – often elevated to a greater degree than T4
• Thyroid scan shows heterogeneous uptake
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44. TREATMENT
• Antithyroid drugs, often in combination with beta blockers
– Often stimulates the growth of the goiter
–Spontaneous remission does not occur
– rendered euthyroid before operation
• Surgery provides definitive treatment of underlying thyrotoxicosis as well as goiter
• RAI - reserved for elderly, larger doses needed
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46. • Thyrotoxicosis is usually mild
• A thyroid scan - definitive diagnostic test,
– Focal uptake in the hyper functioning nodule
– Diminished uptake in the remainder of the gland (activity of the
normal thyroid is suppressed)
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47. TREATMENT
• Radioiodine ablation is usually the treatment of choice – for small nodules
• Surgical resection is also effective and is usually limited to enucleation of the
adenoma or lobectomy
• Medical therapy using antithyroid drugs and beta blockers can normalize
thyroid function
• Ethanol injection under ultrasound guidance
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49. Is life-threatening exacerbation of hyperthyroidism, accompanied by
• Fever
• Cardiac failure & arrhythmia
• Delirium
• Seizures
• Coma
• Vomiting
• Diarrhea
• Jaundice
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50. PRECIPITATING FACTORS
• Acute illness (e.g., stroke, infection, trauma, diabetic ketoacidosis),
• Surgery (especially on the thyroid) & Trauma
• Radioiodine treatment of a patient with partially treated or untreated
hyperthyroidism
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51. MANAGEMENT
• Aim of treatment:
– Intensive monitoring and supportive care
– Treatment of the precipitating cause
– Reduce thyroid hormone synthesis
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52. HOW?
• O₂ supplementation
• Hemodynamic support
• Antipyretic & antibiotics
• Large doses of PTU (600 mg loading dose and 200–300 mg every 6 h)
• Saturated solution of potassium iodide (5 drops every 6 h), or ipodate or iopanoic acid
(0.5 mg every 12 h)
• Propranolol = 40–60 mg orally every 4 h
• Dexamethasone, 2 mg every 6 h
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54. • Most common malignancy of the endocrine system
• Incidence of thyroid cancer (~9/100,000 per year) increases with age, plateauing after
about age 50
• M:F = 1:2
• history of childhood head or neck irradiation – a risk factor
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55. PROGNOSTIC FACTORS
• Age (<20) or in older persons (>45) is associated with a worse prognosis
• Male sex is associated with a worse prognosis
• Histologic type – anaplastic ca has very poor prognosis & poor response to therapy
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56. CLASSIFICATION
• Neoplasms can arise in each of the cell types that populate the gland
– Thyroid follicular cells –
Papillary thyroid ca
Follicular thyroid ca
Hurthle cell ca
– Calcitonin-producing C cells – Medullary thyroid ca
– Lymphocytes - lymphomas
– Stromal and vascular elements
– Metastases from other sites
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58. PTC
• Accounts for 80% of all thyroid malignancies in iodine-sufficient areas
• >95% 10-year survival rate
• The predominant thyroid cancer in children and individuals exposed to external radiation.
• F : M = 2:1
• Mean age - 30 to 40 years
• Most are euthyroid
• slow-growing painless mass in the neck
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58
59. PTC
• Dysphagia, dyspnea, and dysphonia -locally advanced invasive disease
• Lymph node metastases are common, especially in children and young adults, and may
be the presenting complaint.
• "Lateral aberrant thyroid" almost always denotes a cervical lymph node that has been
invaded by metastatic cancer
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60. PTC
• Macroscopic findings- calcification, necrosis, cystic change
• Histologic variants – papillary, follicular, mixed
• Microscopic features
• Orphan Annie nuclei
• Psammoma bodies
• Multifocality is common – in 85%, ↑risk of cervical nodal metastasis
• Microcarcinoma - ≤ 1cm, no invasion
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61. FTC
• 10% of thyroid cancers
• Common in iodine-deficient areas
• F : M = 3:1
• Mean age = 50 yrs
• Usu. - solitary thyroid nodules, long-standing goiter
• cervical LAP is uncommon
• In <1% of cases – SSx of thyrotoxicosis
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62. • FNAC is unable to distinguish benign follicular lesions from follicular
carcinomas
• preoperative clinical diagnosis of cancer is difficult unless
distant metastases are present
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63. MANAGEMENT
• All well-differentiated thyroid cancers should be surgically excised
• 131I ablation is necessary to eliminate remaining normal thyroid tissue and to treat
residual tumor cells.
• Patients should be placed on a low-iodine diet
• Levothyroxine suppression of TSH is a mainstay of thyroid cancer treatment
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64. FOLLOW-UP
• Tg measurement - measurable levels indicate incomplete ablation or recurrent
cancer
• Whole-body scan should be performed about 6 months after thyroid ablation
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65. ANAPLASTIC THYROID CANCER
• Poorly differentiated and aggressive cancer
• Prognosis is poor, most die within 6 months of diagnosis
• Uptake of radioiodine is usually negligible
• Chemotherapy has been attempted , but it is usually ineffective
• External beam radiation therapy can be attempted and continued if tumors
are responsive
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66. MEDULLARY THYROID CARCINOMA
• Serum Calcitonin - a sensitive marker of MTC
• Serum CEA
• The management - primarily surgical
• Do not take up radioiodine
• External radiation treatment and chemotherapy may provide palliation in patients
with advanced disease
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67. THYROID LYMPHOMA
• Often arises in the background of Hashimoto's thyroiditis
• Rapidly expanding thyroid mass
• Diffuse large-cell lymphoma is the most common type in the thyroid
• Often highly sensitive to external radiation
• Surgical resection should be avoided as initial therapy because it may spread disease
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122. Retrosternal Goiter
-It is prolongation of the lower pole of the thyroid behind
the sternum into the superior mediastinum, with blood supply
from inferior thyroid artery branch
-Clinical features: from pressure effect
1. Dyspnoea & cough
2. Dysphagia
3. Prominent veins occur at the root
of the neck
- Rx surgery indicated
Macroglossia is the medical term for an unusually large tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties in speaking, eating, swallowing and sleeping.Macroglossia is uncommon, and usually occurs in children. There are many causes
Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel. The main symptoms are pain, numbness, and tingling, in the thumb, index finger, middle finger, and the thumb side of the ring fingers. Symptoms typically start gradually and during night ...
The recommended average daily intake of iodine is 150 g/d for adults, 90–120 g/d for children, and 200 g/d for pregnant women. Urinary iodine is >10 g/dL in iodine-sufficient populations.
Hyperthyroidism in adolescents is associated with rapid growth but
normal adult height. It is almost always caused by Graves disease and is much more common in girls.
Amiodarone inhibits extrathyroidal conversion of T4 to T3 in all patients. Thus, patients with amiodarone-induced hyperthyroidism may also have T4-hyperthyroidism
Has strong familial predisposition, 20 -30 % familial predisposition
rarely begins before adolescence
Exophthalmos, periorbital and conjunctival edema, limitation of eye movement, and infiltrative dermopathy (pretibial myxedema) Systolic hypertension and tachycardia are common in hyperthyroidism; however, diastolic pressure is not usually elevated.
There is infiltration of the extraocular muscles by activated T cells; the release of cytokines such as IFN-, TNF, and IL-1 results in fibroblast activation and increased synthesis of glycosaminoglycans that trap water, thereby leading to characteristic muscle swelling, Late in the disease, there is irreversible fibrosis of the muscles.Increased fat is an additional cause of retrobulbar tissue expansion
Orbital fibroblasts may be particularly sensitive to cytokines, perhaps explaining the anatomic localization of the immune response
Diplopia - typically but not exclusively when the patient looks up and laterally
Most serious manifestation is compression of the optic nerve at the apex of the orbit -> papiledema
the NO SPECS scheme is inadequate to describe the eye disease fully, and patients do not necessarily progress from one class to another
Carbimazole and methimazole (the chief metaboliteof carbimazole) (t1/2, 6h) and propylthiouracil (t1/2 2 h) are commonly used, but t1/2 matters little since the drugs accumulate in the thyroid and act there for 30-40 h; thus a single daily dose suffices.
Propylthiouracil differs from other members of the group in that it also inhibits peripheral conversion of T4 to T3, but only at the high doses used in treatment of thyroid storm
enlarged gastric bubble and a dilated proximal duodenum
usually precipitated by acute illness (e.g., stroke, infection, trauma, diabetic ketoacidosis), surgery (especially on the thyroid), or radioiodine treatment of a patient with partially treated or untreated hyperthyroidism.
As most tumors are still TSH-responsive, levothyroxine suppression of TSH is a mainstay of thyroid cancer treatment
For patients at low risk of recurrence, TSH should be suppressed into the low but detectable range (0.1–0.5 IU/L
