Disorders of thyroid

Hyperthyroidism

Clinical features:

• Increased BMR
  • Heat intolerance
  • Weight loss
  • Increased appetite
• Peripheral vasodilation
  • increase heat loss
  • increase blood flow
  • skin soft, warm & flushed
• Increase cardiac output
  • tachycardia
  • palpitations, arrhythmias
  • cardiomegaly
  • congestive cardiac failure
  • cardiomyopathy
• Overactivity of sympathetic nervous system
  • tremor
  • hyperactive
  • anxiety
  • inability to concentrate
  • insomnia
  • proximal muscle weakness due to muscle mass loss
• Ocular changes
  • staring gaze
  • lid lag
    • sympathetic nervous system overstimulation of levator palpebrae superiosis
• Hyperstimulation of gut
  • hypermotility
  • malabsorption
  • diarrheoa
• Bone resorption
  • osteoporosis
  • risk of fracturss
• Hepatomegaly
  • fatty deposits in liver
• Hair loss
• Oligomenorrhea
• Thyroid storm (abrupt onset of severe thyrotoxicosis)
  • Febrile
  • Increase heart rate (in response to fever)
  • Emergency (death from cardiac arrhythmias

Apathetic hyperthyroidism

• seen in elderly
• age & other co-morbidities blunt effects of excess thyroid hormone
  • effects not clearly seen eventhough hyperthyroid
• diagnosed when seen for unexplained weight loss/ worsening cardiovascular disease

Cause/aetiology

Primary

• Thyrotoxicosis (High T3,T4)
  • most common
• Diffuse hyperplasia
  • Grave’s disease (85%)
• Hyperfunctional multinodular goiter
• Multifunctional adenoma of the thyroid
• Other:
  • Subacute granulomatous thyroiditis
  • Subacute lymphocytic thyroiditis
  • Struma ovarii

Secondary

• TSH-secreting pituitary adenoma

Epidemiology

• 2% of female population
• More female than male
• 30-40 years old
• Genetic factors
  • HLA-B8 & DRw3 – Caucasians
  • HLA-Bw36 – Japanese
  • HLA-Bw46 – Chinese

Graves’ disease/diffuse toxic goiter

Also known as Parry’s / Basedow’s disease

• Females
• 20-40 y.o
• Autoimmune
• Autoantibody to TSH receptor (LATS/TSI)

Triad of clinical features:

• Hyperthyroidism with diffuse goiter
• Infiltrative Ophthalmopathy (exophthalmus)
• Infiltrative Dermopathy (Pretibial myxoedema)

Microscopic:

• Diffuse hyperplasia
• Papillary folds
• Scalloped
• pale scanty colloid

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Hypothyroidism

Types

• Primary hypothyroidims
• Secondary hypothyroidism
• Tertiery hypothyroidism

Causes/ Aetilogy

Primary

• Developmental
  • dysgenesis
  • TSH receptor mutations
• Post ablative
  • surgery
  • radioiodine therapy
  • external radiation
• Autoimmune
• Iodine deficiency
• Drugs
• Lithium, p-amino salicylic acid
• Dyshormonogenetic goitre (congenital biosynthesis defect)

Secondary pituitary failure

Tertiary hypothalamic failure

Clinical features

Signs

• Coarse & brittle hair
• Hair loss
• Jaundice, Pallor
• Dull facial expression
• Periorbital puffiness
• Macroglossia (large tongue)
• Goitre
• Hoarseness
• Decrease systolic BP, Increase diastolic BP
• Bradycardia
• Pericardial effusion
• Non-pitting oedema (myxoedema)

Symptoms

• Fatigue
• Lethargy
• Weight gain
• Decreased appetite
• Constipation
• Cold intolerance
• Dry skin
• Muscle pain
• Join pain
• Weakness
• Depression
• Mental impairment (fetal developmnet)
• impaired fertility
• Menstrual disturbance
• Less perspiration
• Paraesthesia
• Blurred vision

Epidemiology

• 15/1000 in females
• 1/1000 in males
• Peak in 50-60 years old
• White females

Cretinism (infancy/childhood/congenital)

• No/Low iodine diet
• 1/4000 newborns
• Absense of thyroid hormone during first 2 years
  • brain development & linear growth
• If treatment started while epiphyseal plates are still open & undamaged, growth will resume.

• Impaired CNS & bone growth
  • Epiphyseal plate are still open, but severely damaged
• Mental retardation
• Short stature
• Coarse facial features
• Protruding tongue
• Umbilical hernia
• thick dry skin
• saddle nose
• Primary teeth still present
  • secondary teeth not yet erupted

Myxoedema

Myxoedema is a condition where upon applied pressure, the oedema is non-pitting. The skin and subcutaneous tissue is thickened, due to the accumulation of hyaluronic acid & chondroitin sulfate in the dermis. Thyroid hormones is important in the synthesis & catabolism of mucopo
lysaccharides & collagen by dermal fibroblasts.

Myxoedema coma:

Undiagnosed/ untreated hypothyroid patients subjected to stress (cold, surgery, infection)

• altered mental status
• hypothermia
• bradycardia
• hyponatremia
• cardiomegaly, pericardial effusion & ascites

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THYROIDITIS

Hashimoto Thyroiditis

• Common cause of non-endemic goitre
• Females
• 45-65 years old
• Autoimmune (HLA-DR5, DR3)
  • T-cell mediated
  • Antibodies directed to various thyroid antigens
    • antithyroid peroxidase (anti-TPO)
    • antithyroglobulin (anti-TG)
• Initially hyperthyroid, then become hypothyroid
• high risk of B cell lymphoma
• Detected by special staining (immunohistochemistry)
  • antithyroglobulin antibody

Antithyroglobulin antibody fluorescence dye

• firm diffuse enlargment
  • intact capsule
• Small follicles
• lymphoid follicles
• Hurthle cells (eosinophilic epithelial cells)

• Oxyphilic cells (of follicular epithelium)
• Anisokaryosis
• Irregular cytoplasm
• Background of blood
• Lymphocytic infiltration with germinal center formation
• Extensive fibrosis
• atrophy of follicular epithelium
• squamous metaplasia

*Get images for these features

Granulomatous Thyroiditis

Also known as Subacute granulomatous thyroiditis (SAGT) / DeQuervain GT.

• It is a viral/post viral syndrome
• Genetic association: HLA B35
• Hyperthyrodisim in initial phase (3-6 weeks) but low iodine intake
• increased T3 & T4
• Suppressed TSH secretion (not stimulated by TSH)
• Hypothyroidism in late phase
• Heals with return of normal thyroid function

Clinical features:

• **PAINFUL goiter
• both lobes & radiates to the neck
• Dysphagia & hoarseness
• fever
• fatigue
• myalgia

Gross:

• unilaterally/bilaterally enlarged
• firm & rubbery
• yellow white
• adherent to surrounding areas (due to inflammation)

Microscopic:

Note the fibrosis

• **Patchy inflammation
• Microabscesses
• **Granulomas
• Chronic inflammation with
• lymphocytes
• histiocytes
• plasma cells
• multinucleated giant cells
• Extensive fibrosis

Other types of thyroiditis

Subacute lymphocytic thyroiditis

• Silent/painless
• Post partum
• middle aged
• similar to Hashimoto’s but no Hurthle cells

Riedel’s thyroiditis

• hard fixed mass
• extensive fibrosis

Palpation thyroiditis

• Due to vigorous clinical palpation
• leading to follicular disruption + inflammation

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GOITER

Non-Neoplastic

• Common
• *multiple/diffuse
• Hyperplasia – MNG
• Inflammation
• Infections
• Cysts

Neoplastic

• Uncommon
• *Solitary nodule
• Young males
• *Hot nodules are benign!
• Follicular adenoma
• Carcinoma

Diffuse & multinodular goiter

When there are repeated diffuse attacks, the goiter can progess to be multinodular.

Types

• endemic/non-endemic types (sporadic)
• sporadic: rare, females, young
• toxic/non toxic types

Stages

• Hyperplastic stage
• Colloid stage

Goitrogens

Certain food can cause goiter (on top of not having enough iodine in the daily uptake)

• Cassava & cabbage
• contain thiocyanate which blocks iodide transport
• It will block the organification (therefore not T4, T3 formed, just excessive thyroglobulin)

Gross

• Mass effect
• dysphagia
• airway obstruction

It can be

• hyperplasia
• fibrosis
• cystic
• necrosis

Plummer syndrome: toxic nodule develops causing hyperthyroidism (hyperfunctioning nodule), but it is rare

Nodular goiter

Nodular goiter with papillary carcinoma

Secondary cystic & haemorrhagic areas

*Variable sized colloid filled follicles

With papillary formations protruding towards the center of a cystically dilated follicle. ?

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Data interpretations for thyroid disorders

Antibodies

• Antithyroid Microsomal
• measured by Antithyroid peroxidase assay
  (anti TPO antibodies)
• Antithyroglobulin
• Thyroid stimulating immunoglobulin (TSI)
• also known as Long acting thyroid stimulator (LAPS)

Radioactive Iodine Scan (RI scan)

• Cold nodules:
• nodules that do not take up RI
• may be malignant (10%)
• Hot nodules:
• nodules that take up most of the iodine at the expense of the rest of the gland
• can be overactive and cause hyperthyroidism
• Warm nodules/functioning nodules:
• nodules that take up the same amount of iodine as the rest of the gland

  Hot nodule

Ultrasound

• highly sensitive
• useful for helping delineate discrete nodules not palpable during examination
• used to guide FNAC (fine needle aspiration) of nodules larger than 1cm
• determine whether nodule is cystic/solid
• may be used to serially determine size of thyroid nodules

FNA Cytology (FNAC)

• cells & fluides are removed from the thyroid gland
• to determine benign/malignant
• Fluid:
• reddish-brown colour
• due to altered blood on the broken down thyroid tissue within a tumour
• clear yellow
• congenital cyst
• occasionally pus is found
• thyroid abscess

Nuclear scintigraphy

• useful in differetial diagnosis of thyrotoxicosis from the amount of thyroid uptake
• thyroiditis
• TNG
• diffuse TNG
• Radioactive iodine-131 ablation of the thyroid gland may be considered if thyroid uptake value is elevated.
• performed with iodine-123 / technetium-99m
• shorter half life
• lower radiation exposure
• determine presence of substernal extension of the thyroid gland
• may contain toxic nodule

CT, MRI

CT Scan

• establish patency of the trachea
• tracheal deviation
• compression of any structures due to goiter
• Side effect: CT scan with iodinated contrast may induce thyrotoxicosis in individuals with non-toxic multinodular goiter
• by supplying an iodine load (Jod-Basedow effect)
• Thyrotoxicosis is self limited & goes away by it’s own

Functional examinations

• measure uptake of iodine into thyroid gland
• use iodine isotopes
• used to identify nodular thyroid disease
• Hot (hyperfunction) or Cold (hypofunction)
• Determine cause for hyperthyroid state
• Graves
• thyroiditis
• Determine dose of radioiodine for treatment

Erythrocyte sedimentation rate

• to confirm subacute (viral) granulomatous thyroiditis
• when felt tenderness on thyroid palpation

Lab

Hypothyroid

• High TSH
• Low T3,T4
• Other
• Low erythropoietin
• Vit B12 deficiency
• Hyponatremia
• Hypoglycemia
• Increased cardiac enzyme

Elevated thyroid microsomal antibodies: Hashimoto’s thyroiditis