2. Objectives
⢠To give an overview of thyroid disorders
⢠To discuss approach to management of some of them
3. Outline
⢠Introduction
⢠Brief Anatomy
⢠Functions
⢠Regulation of hormone production
⢠Classification of disorders
⢠Hyperthyroidism
⢠Hypothyroidism
⢠Goitres ânon functional
4. Introduction
⢠Thyroid disorders are common in endocrinology
⢠These disorders affect most of the systems of the body
⢠Complications are usually difficult to manage
8. The thyroid gland
⢠2 lobes connected in the middle by an isthmus
⢠Produces thyroxine (T4) & triidothyronine (T3)
⢠T4 secreted > than T3 ; T3 more biologically potent
⢠Most T3 derived from extrathyroidal conversion of T4
9. Functions of the thyroid gland
Thyroid hormones play critical role in:
⢠Cell differentiation during development
⢠maintaining thermogenesis
⢠metabolic homeostasis
13. Thyrotoxicosis
⢠results from exposure of body tissues to excess circulating levels of thyroid
hormones
⢠Several disorders cause Thyrotoxicosis
⢠Hyperthyroidism: a subset of thyrotoxicosis
⢠accounts for major aetiologies of thyrotoxicosis in which there is excess synthesis
& secretion of thyroid hormone by the thyroid gland
16. Thyrotoxicosis contd
⢠Thyrotoxicosis with high RAIU indicates de novo synthesis of hormone
⢠Thyrotoxicosis with low RAIU indicates either:
⢠Inflammation & destruction of thyroid tissue with release of preformed
hormone into the circulation
or
⢠extrathyroidal source of thyroid hormone
18. Graves disease
⢠Most common cause of thyrotoxicosis (50- 80%)
⢠Autoimmune disorder resulting from TSH receptor antibodies (a.k.a. thyroid-
stimulating immunoglobulins), which activate receptor & stimulate thyroid gland
growth & thyroid hormone synthesis
⢠Characterized by a variety of circulating antibodies to thyroid components
including:
⢠TSH-R-stimulating Ab â specific for Graves disease
⢠anti-thyroid peroxidase (anti-TPO)
⢠antithyroglobulin (anti-TG) antibodies
19. Graves disease
⢠TSH-R-Ab is directed toward epitopes of the TSH receptor & acts as a
TSH-receptor agonist
⢠Similar to TSH, TSH-R-Ab binds to the TSH receptor on the thyroid
follicular cells to activate thyroid hormone synthesis, release &
thyroid growth
20. Graves disease
Consists of
⢠Hyperthyroidism
⢠Goiter
⢠Ophthalmopathy
⢠& occasionally a dermopathy (pretibial or localized myxedema)
21. Graves disease
⢠Peak incidence: 20-40yrs
⢠Prevalence varies among populations - areas of high iodine intake ass
with â prevalence of Gravesâ
⢠Female:Male ratio reported as ~ 5-10:1
⢠Combination of genetic & environmental factors â â susceptibility to
Gravesâ disease
22. Graves disease: Precipitating factors
⢠Genetic susceptibility
⢠Abundant epidemiologic evidence in support
⢠Stress:
⢠Often hx of psychological stress before onset of dx. Suppression of
stress followed by immunologic hyperactivity â disease in
genetically susceptible
⢠Pregnancy: a time of immune suppression, with rebound post partum
23. Precipitating & Predisposing factors
⢠Sex steroids
⢠estrogen enhances immunologic activity
⢠Smoking
⢠Drugs: Iodine & iodine containing drugs may ppt disease in
susceptible individual
⢠may also damage thyroid cell directly & release thyroid antigens to
immune system
⢠Interferon ι treatment of patients with hepatitis C infection
⢠Infections:
⢠Possible infections of the thyroid gland could initiate class II
molecule expression
24. Graves disease continued
⢠Usually thyroid gland palpable with diffusely enlarged smooth goitre,
initially soft
⢠May become progressively firmer
⢠Nodular Graves (Marine-Lenart syndrome)
⢠Graves disease in association with thyroid nodules reportedly increases risk of
thyroid carcinoma
25. Symptoms in thyrotoxicosis
⢠Tremors
⢠Heat intolerance
⢠Hyperkinesis
⢠Irritability, nervousness
⢠Jitteriness
⢠increased sweating
⢠Increased appetite
⢠Palpitations
⢠Eye symptoms (staring
gaze, increased
protrusion, pain, redness)
⢠Diarrhea /
Hyperdefaecation
⢠Weight loss despite good
or ď appetite
⢠Dyspnoea on exertion
⢠Itching
⢠Muscle weakness/wasting
â˘may manifest as
exercise intolerance or
difficulty climbing stairs
⢠Menstrual irregularities
⢠Reduced libido/ED
26. Signs may include:
General /skin
⢠Fine tremor
⢠Evidence of weight loss
⢠Warm, moist skin
⢠Fine silky hair ¹ alopecia
⢠Hyperhidrosis
⢠Sweaty palms
⢠Palmar erythema
⢠Onycholysis
27. Signs in thyrotoxicosis
Eye signs
⢠Lid lag, Lid retraction
⢠Exophthalmos (Graves disease)
⢠Cranial nerve palsy
⢠Goitre
⢠Thyroid bruit
31. Other findings in thyrotoxicosis
⢠Osseous-osteoporosis
⢠Reproductive - gynecomastia, sub-fertility
⢠Hematopoietic- normochromic, normocytic anemia, lymphocytosis,
lymphadenopathy, thymus enlargement, splenomegaly
⢠Neurologic: Choreoathetosis
⢠Others: Syncope, Delirium, stupor, coma, vomiting, (in severe cases)
32. Thyroid eye disease
⢠Clinically evident in 20-25 %
⢠More may have evidence on USS, CT, MRI (enlarged retro-ocular
muscles)
⢠appears before, concurrently or after treatment in Graves
⢠most patients with ophthalmopathy have evidence of thyroid disease,
but absent in ~ 10% of patients
â˘âEuthyroid gravesâ
⢠Ophthalmopathy may occur in chronic autoimmune thyroiditis
(Hashimoto's) & may have TSHR receptor Ab (blocking )
34. Thyroid eye disease
⢠Look out for: redness, congestion, periorbital oedema conjunctival
injection & oedema, proptosis, ophthalmoplegia
⢠Failure of lid apposition promotes drying & ulceration of cornea
⢠Objective measurement of degree of proptosis using an hertelâs
exophthalmometer
⢠measurement of distance b/w lateral angle of bony orbit &
imaginary line tangent to most anterior part of cornea
⢠upper limit of normal: 20 mm in whites; 22 mm in blacks
⢠Visual acuity, visual fields & color vision
35.
36. Thyroid eye disease
⢠N âNo signs or symptoms 0
⢠O â only symptoms 1
⢠S â soft tissue involvement 2
⢠P â proptosis 3
⢠E â Extraocular muscle involvement 4
⢠C- corneal involvement 5
⢠S â sight loss 6
37. Pretibial myxoedema
⢠Accumulation of fluid & mucopolysaccharides in pretibial region
⢠Mild
⢠Severe
⢠Incapacitating
May appear as:
⢠Non pitting oedema
⢠Nodular
⢠Plaques
40. Toxic multinodular goitre
⢠Orbitopathy, pretibial myxedema, acropachy not observed
⢠TSH-R antibodies absent
⢠Size of thyroid gland variable with a dominant nodule or multiple
irregular, variably sized nodules typically present
⢠Neck USS should help delineate discrete unpalpable nodules
41. Thyroiditis
Causes include:
⢠Direct chemical toxicity with inflammation (amiodarone)
⢠Radiation thyroiditis, from external radiation or after radioiodine
therapy
⢠Palpation thyroiditis e.g occurring during parathyroid surgery
42. Diff diagnosis of thyrotoxicosis
⢠Single nodule raises possibility of an autonomously functioning thyroid adenoma
⢠Painful, tender thyroid in subacute granulomatous thyroiditis
⢠Subacute lymphocytic (usually painless) thyroiditis may have no, minimal, or
modest thyroid enlargement
⢠Absence of any thyroid enlargement: consider exogenous thyroid hormone ingestion
or ectopic thyroid tissue
43. Investigation of thyroid function
⢠Sensitive TSH assay
⢠3rd gen assays:10 fold greater functional sensitivity than 2nd gen
⢠Assay of circulating thyroid hormones
⢠Total (protein bound)
⢠Free T4/T3
44. Assessment of thyroid function
⢠Thyroid autoantibody tests
⢠Thyroid imaging - of value in assessment of thyroid size & differential
diagnosis â Ultrasound scan; CT; MRI
⢠Nuclear scintigraphy: Radionuclide imaging
⢠evaluate functional activity of thyroid -hot or cold
⢠determine location & size of functional thyroid tissue (& to
localize ectopic thyroid tissue)
⢠Fine needle aspiration cytology
⢠differentiating benign from malignant disease
45. Biochemical diagnosis of Hyperthyroidism
⢠Overt: except for lab error, all patients with low/undetectable serum
TSH & high free T4 & T3 concentrations have hyperthyroidism
⢠In some pts, only serum T3 or serum T4 is elevated
⢠T3 toxicosis â Low serum TSH; high free T3; normal free T4
⢠Tends to occur early in course of hyperthyroidism
⢠T4 toxicosis â Low serum TSH, high free T4, normal T3
⢠Pattern in pts with hyperthyroidism & non thyroidal illness
⢠May occur in persons with amiodarone induced thyrotoxicosis
46. Biochemical diagnosis of Hyperthyroidism
⢠TSH-induced hyperthyroidism: Very rare cause of hyperthyroidism,
due to:
TSH-secreting pituitary adenoma
or
partial resistance to feedback effect of thyroid hormones on TSH
secretion
defects in the T3-nuclear receptor
Normal or high serum TSH despite high free T4 & T3 concn
47. Radioactive I uptake & thyroid scanning
Radionuclide scans provide information
⢠shape, size of thyroid gland, distribution of tracer activity within gland
⢠limited role in differentiating benign from malignant nodule
⢠Thyroid gland selectively transports radioisotopes allowing for thyroid
imaging & quantification of radioactive tracer uptake
⢠useful to differentiate causes of thyrotoxicosis particularly when
used in conjunction with imaging
⢠Graves: usually diffuse uptake
⢠Toxic nodular goiter usually patchy uptake, with areas of
increased & decreased uptake
48.
49. Nuclear scintigraphy
Cold nodule: nonfunctioning thyroid nodule/lump
⢠doesn't concentrate radioactive isotopes in thyroid scan
⢠Higher incidence of malignancy
Hot nodule: nodular region of thyroid gland
⢠takes up large amounts of radioactive iodine relative to rest of thyroid gland,
visualized as "hot spot"
⢠majority of hot nodules function autonomously
⢠Much lower malignancy potential
50.
51. Treatment of hyperthyroidism
B-blockers
⢠relieves many of the symptoms (particularly palpitations, tremor,
anxiety)
⢠Atenolol â advantage of single daily dose & ď˘-1 selectivity
⢠Propanolol also reduces T4 to T3 conversion
⢠Contraindicated in asthma; caution in patients with heart
failure
Antithyroid drugs: Carbimazole, Methimazole, Propyl thiouracil
inhibit thyroid hormone biosynthesis & secretion
52. Thionamide therapy in Hyperthyroidism
⢠Aim: to restore euthyroid state as soon as possible, so as to achieve
lasting remission in patients with Grave's disease or to prepare
patients treatment with radioactive iodine or surgery
⢠Duration of treatment with drugs:â 12 to 24 months if ablation not
intended
⢠Reports of permanent remission after discontinuing drugs is achieved
- 15-80%
53. Side effects of Thionamides
⢠Rash
⢠Nausea
⢠Epigastric distress
⢠Agranulocytosis*
⢠Hepatitis
⢠Lupus like syndrome
⢠Vasculitis
⢠Polyarthritis
54. Other Medications
Iodides, Ipodate (iodinated radio contrast agent)
⢠Inhibit thyroid hormone synthesis and secretion
⢠Useful in lowering T3 & T4
⢠Can be used to quickly prepare patients for surgery, when there is
insufficient time to give thionamides
⢠Useful in combination treatment of thyroid storm
55. Radioactive iodine (I 131)
⢠Treatment of choice in patients with toxic nodular goitre
⢠1st line for patients with Gravesâ disease in US
⢠Increasingly used as first-line therapy for adults
⢠Contraindicated in children, during pregnancy & breast feeding
⢠Pregnancy contraindicated for 6-12 months after therapy
⢠Fixed or individualized doses
56. Radioactive iodine (I 131)
⢠Stop thionamides 3-5 days before RAI, to avoid impairing uptake;
restart few days later
⢠May aggravate uncontrolled hyperthyroidism
⢠Small but definite risk of development or worsening of
ophthalmopathy, esp if smoker or high T3 before therapy
⢠(Tx with prednisolone reported to prevent worsening)
⢠Toxic nodules require higher doses
⢠side effect â hypothyroidism, radiation thyroiditis
⢠life-long follow-up of thyroid function required
57. Thyroidectomy
⢠Those with very large goiters
⢠Where there is possibility of malignancy
⢠Severe or advancing ophthalmopathy
⢠Patient who relapses after medical therapy
⢠Pregnant patient on drugs whose disease is hard to control
⢠Those with severe reactions to antithyroid drugs
⢠Patients who have refused I 131 therapy
⢠Woman wishing to achieve a pregnancy in near future
58. Treatment of other causes
Self-limiting causes of thyrotoxicosis: subacute thyroiditis, iodine-
induced, exogenous administration of T4
⢠Treat symptomatically
⢠Therapy: beta-blockers for symptomatic control and
antiinflammatory drugs such as aspirin, or nonsteroidal
antiinflammatory drugs, or, in severe cases, prednisone
⢠Ipodate also useful: blocks conversion of T4 to T3 & reduces the
tissue effects of thyroid hormones
⢠Thionamides have no role in treatment, since new hormone is
not being synthesized
61. Hypothyroidism
⢠Diagnosis relies heavily on lab tests
â˘many of the clinical manifestations non-specific
⢠Clinical presentation highly variable
â˘depends on age of onset and duration & severity of disease
â˘Presentation in adults varies from asymptomatic elevation in TSH
concentration to myxedema coma
64. Transient hypothyroidism
⢠Sub acute lymphocytic thyroiditis
⢠Sub acute granulomatous
⢠Postpartum thyroiditis
⢠After 131I treatment or subtotal thyroidectomy for Gravesâ disease
65. Chronic Autoimmune thyroiditis
⢠Commonest cause of hypothyroidism in iodine-sufficient areas of the
world
⢠Commoner in older women
⢠cellular & antibody-mediated destruction of thyroid tissue
⢠Goitrous
⢠Atrophic
⢠differ in extent of lymphocytic infiltration, fibrosis, & follicular
cell hyperplasia of thyroid, but not in pathophysiology
66. Chronic Autoimmune thyroiditis
Hashimotoâs
⢠Marked lymphocytic infiltration
CD4+, CD8+ & B cells
Atrophic
⢠More fibrosis, less lymphocytic
infiltration
⢠Represents end stage of Hashimoto
thyroiditis
67. Chronic autoimmune (Hashimoto's) thyroiditis
Role for genetic susceptibility
⢠more likely to have personal or family history of autoimmune
diseases
⢠Association with Turners syndrome
No well-defined environmental risk factors for chronic autoimmune
thyroiditis
⢠evidence linking a high iodine intake with this disorder
⢠serum antithyroid antibody concentrations increase after
dietary iodine intake is increased in endemic goiter regions
⢠Reports of association between cigarette smoking & risk of
hypothyroidism in pts with autoimmune thyroid disease
68. Hypothyroidism
Symptoms in adults often non-specific:
⢠Fatigue
⢠Cold intolerance
⢠Weight gain
⢠Constipation
⢠Myalgia
⢠Menstrual irregularities
⢠Slow movement and speech
69.
70. Hypothyroidism
Older children may present on account of:
⢠Short stature due to linear growth retardation
⢠Retarded secondary sexual characteristics
⢠Delayed onset of puberty
⢠Poor school performance
71. Hypothyroidism
⢠Delayed relaxation of deep tendon reflexes
⢠Bradycardia
⢠Coarse hair and skin, puffy facies, loss of eyebrows, enlargement of
the tongue, voice hoarseness
⢠Overt muscle weakness
72. Other clinical features
⢠Entrapment neuropathy of median nerve
⢠producing paresthesia & weakness of hands
⢠Obstructive sleep apnoea
⢠Cardiomegaly: dilation of the heart; pericardial effusion
⢠Neuropsychiatric manifestations
⢠Adynamic ileus leading to mega colon & functional intestinal
obstruction
73. Investigations
⢠Primary hypothyroidsm â low or normal serum FT4 with elevated
TSH
⢠Secondary hypothyroidsm â low serum FT4 with low or
inappropriately normal TSH
⢠Subclinical hypothyroidsm â normal serum T4 & elevated serum
TSH (no symptoms or signs usually)
74. Investigation
⢠Raised TSH, normal free T4 or T3
⢠Recovery phase of non thyroidal illness
⢠Intermittent thyroxine therapy in hypothyroidism
⢠Interfering antibodies
⢠Drugs-cholestyramine, sertraline
⢠Congenital
⢠TSH receptor defects
⢠TSH resistance syndromes
75. Investigations
⢠Hyperlipidaemia â occurs with increased frequency in hypothyroidism
⢠Hyponatraemia â often resulting from inappropriate ADH secretion
⢠Elevated muscle enzymes (CPK, AST. LDH)
⢠Anaemia normochronic, normocytic
⢠E.C.G. changes- bradycardia, low amplitude QRS complexes, evidence
of ischaemic heart disease
⢠Thyroid autoantibodies (antithyroglobulin antibody, thyroid
peroxidase antibody)
77. Treatment
⢠If no residual thyroid function, daily replacement of levothyroxine
@~1.6Âľg/kg( 1-2 Âľg/kg per day)
⢠Elderly (> 50-60) years & no evidence of heart disease, stat 50 ¾g
daily
⢠Those who have history of CHD initiate at 25 ¾g /day
⢠dose can be increased by 25 mcg/day every 3 to 6 wks until replacement
is complete
⢠Gradual increase, as rapid increase in dose may tax coronary or cardiac
reserve
78. Treatment
⢠Therapeutic goal: alleviation of clinical syndrome & normalization of
TSH in primary hypothyroidism
⢠After initiation of T4 therapy, reevaluate
⢠Serum T4 & TSH measured in 3 to 6 wks (depending upon patient's
symptoms) & dose adjusted accordingly
⢠process of increasing dose of Levothyroxine should continue,
based upon periodic measurements of serum TSH (& free T4 if
therapeutic goals have not been achieved)
79. Treatment
⢠Once desired T4 dose is established, annual evaluation
⢠Changing requirements
⢠Altered absorption
⢠Compliance issues
⢠Monitor for signs of overtreatment
⢠Life long therapy in majority
⢠Surgical therapy for huge goiters with compressive symptoms
â˘Subclinical hypothyroidism: Treat if there is goitre, suggestive
symptoms, low T3, drugs which may potentiate, uncertain follow
up, ďcholesterol
80. Thyroid cancer
⢠95% of thyroid cancer presents as nodule or lump in thyroid gland
⢠Thyroid cancer may coexist with thyrotoxicosis
⢠Graves disease in association with thyroid nodules reportedly â risk of
thyroid carcinoma
â˘
81. ⢠Cold nodules frequent in hyperthyroid patients in endemic iodine-deficient
regions
⢠3.8% in GD; 6.4% Toxic multinodular goitre; 12% in thyroid adenoma
⢠Older patients (>/=50 years) & cold nodules:- significant risk factors for
malignancy in patients with hyperthyroidism
Giles SY et al: Surgery 2008;144: 1028-36
83. Thyroid cancer
Surgery is primary mode of therapy for patients with differentiated thyroid
cancer
⢠For most patients with papillary or follicular carcinoma:
⢠Total thyroidectomy followed by I131 ablation
Levothyroxine TSH suppression
⢠Diff thyroid cancers contain TSH receptors &TSH stimulates their growth
⢠Reduced recurrence & cancer specific mortality rates
84. Thyroid cancer
Follow-up
⢠long-term with physical examinations, biochemical testing (including
serum thyroglobulin measurements), radioiodine imaging, ultrasound