Hyperthyroidism

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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

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  • 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

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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.

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  • 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

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  • 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

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Antithyroglobulin antibody fluorescence dye

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

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  • 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:

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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

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Nodular goiter with papillary carcinoma

Secondary cystic & haemorrhagic areas

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*Variable sized colloid filled follicles

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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)

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  • 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

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image  Hot nodule

Ultrasound

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  • 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

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