Thyroid disorders

1. Thyroid disorders
Dr Arinola Esan FMCP,FWACP,FACE
Consultant Endocrinologist
University College Hospital, Ibadan

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 –non 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

5. The thyroid gland

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

10. Regulation of thyroid hormone

11. Classification
• With goitre or without goitre
• Hyper or hypofunctioning
• Benign or malignant

12. Thyrotoxicosis or hyperthyroidism

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

14. Causes of thyrotoxicosis

15. Causes of thyrotoxicosis

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

17. Graves disease

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 – 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 ↑ prevalence of Graves’
• Female:Male ratio reported as ~ 5-10:1
• Combination of genetic & environmental factors → ↑ susceptibility to
Graves’ 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 → 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 α 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  appetite
• Dyspnoea on exertion
• Itching
• Muscle weakness/wasting
•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 ± 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

28. Signs in thyrotoxicosis
Cardiovascular
• Tachycardia
• Atrial fibrillation
• High output heart failure
• Systolic hypertension
• Pretibial myxedema (Graves disease)

29. Signs
Neurological
• Restlessness
• Other mental state changes
• Irritability, anxiety, emotional lability, depression, other psychiatric
reactions
• Proximal myopathy
• Hyperreflexia

30. Other findings in thyrotoxicosis
• Skin - hyperpigmentation, acropachy, urticaria, vitiligo
• CVS-premature atrial contractions
• GIT - hepatomegaly, LFT abnormalities, jaundice
• Metabolic-serum calcium & alkaline phosphatase, hypercalciuria,
glucose intolerance
• Neuromuscular-periodic paralysis(Asian males, sudden flaccid
paralysis of muscles, occ hypo K+), muscle atrophy

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
•“Euthyroid graves”
• Ophthalmopathy may occur in chronic autoimmune thyroiditis
(Hashimoto's) & may have TSHR receptor Ab (blocking )

33. Thyroid eye disease

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 hertel’s
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

36. Thyroid eye disease
• N –No signs or symptoms 0
• O – only symptoms 1
• S – soft tissue involvement 2
• P – proptosis 3
• E – Extraocular muscle involvement 4
• C- corneal involvement 5
• S – sight loss 6

37. Pretibial myxoedema
• Accumulation of fluid & mucopolysaccharides in pretibial region
• Mild
• Severe
• Incapacitating
May appear as:
• Non pitting oedema
• Nodular
• Plaques

38. Pre-tibial myxoedema

39. Graves disease – some associations
• Addisons disease
• DM
• Vitiligo
• Myasthenia gravis
• SLE
• RA
• Scleroderma
• Thymic hyperplasia
• ITP
• Dermatitis herepetiformis
• Pernicious anaemia
• Albright syndrome
• Cutaneous pigmentation
• Precocious puberty
• Polyostotic fibrous dysplasia

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 – 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 – Low serum TSH; high free T3; normal free T4
• Tends to occur early in course of hyperthyroidism
• T4 toxicosis – 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

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

51. Treatment of hyperthyroidism
B-blockers
• relieves many of the symptoms (particularly palpitations, tremor,
anxiety)
• Atenolol – advantage of single daily dose & -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:– 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 Graves’ 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 – 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

59. Hypothyroidism

60. Hypothyroidism
Clinical syndrome resulting from a deficiency of thyroid hormone →
to generalised slowing of metabolic process

61. Hypothyroidism
• Diagnosis relies heavily on lab tests
•many of the clinical manifestations non-specific
• Clinical presentation highly variable
•depends on age of onset and duration & severity of disease
•Presentation in adults varies from asymptomatic elevation in TSH
concentration to myxedema coma

62. Hypothyroidism
Classified as:
• Primary
• Secondary
• Tertiary
• Peripheral resistance to action of thyroid hormone
OR
• Goitrous
• Non- Goitrous

63. Primary Hypothyroidism: Causes
• Chronic autoimmune thyroiditis
• Iodine deficiency & iodine excess
• Post irradiation (I131, external irradiation)
• Post ablative
• Drug induced: Thionamides, lithium, amiodarone, IF-
• Infiltrative diseases: Sarcoidosis, haemochromatosis, amyloidosis,
• Congenital thyroid agenesis, dysgenesis or biosynthetic defects

64. Transient hypothyroidism
• Sub acute lymphocytic thyroiditis
• Sub acute granulomatous
• Postpartum thyroiditis
• After 131I treatment or subtotal thyroidectomy for Graves’ 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
Hashimoto’s
• 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

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 – low or normal serum FT4 with elevated
TSH
• Secondary hypothyroidsm – low serum FT4 with low or
inappropriately normal TSH
• Subclinical hypothyroidsm – 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 – occurs with increased frequency in hypothyroidism
• Hyponatraemia – 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)

76. Investigations contd
• Imaging studies of sellar and suprasellar region
• Evaluate for other hormone deficiencies

77. Treatment
• If no residual thyroid function, daily replacement of levothyroxine
@~1.6µg/kg( 1-2 µg/kg per day)
• Elderly (> 50-60) years & no evidence of heart disease, stat 50 µg
daily
• Those who have history of CHD initiate at 25 µg /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
•Subclinical hypothyroidism: Treat if there is goitre, suggestive
symptoms, low T3, drugs which may potentiate, uncertain follow
up, cholesterol

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 ↑ risk of
thyroid carcinoma
•

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

82. Thyroid cancer
• Differentiated
• Papillary carcinomas
• Follicular carcinomas
• Undifferentiated
• Anaplastic
• Others
• Medullary thyroid cancer
• Lymphomas
• Sarcomas
• Metastases
Pathogenesis
• Radiation
• TSH & growth factors
• Oncogenes & tumour suppression
genes
• Approach to patients with thyroid
nodules

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

85. Thank you for your attention