THYROID GLAND AND HORMONES
Thyroid anatomy
Gross anatomy Microscopic anatomy
Largest purest endocrine gland Composed of hollow spherical follicles formed by
Located in the anterior region of the throat below the specialised epithelial cells
larynx Lumen of follicle contains amber coloured sticky/viscous
Bi-lobal gland with each lobe flanking the trachea material called colloid
Lobes are connected by an isthmus Follicles are separated by and held together by a soft
Highly vascularised and innervated connective tissue matrix
Dispersed throughout the follicular cells and protruding
into the connective tissue are parafollicular cells
(epithelial)
Follicular cells: thyroid hormone synthesis
Parafollicular cells – calcitonin synthesis (function not
clear)
Parathyroid gland
Secretes parathyroid hormone (PTH) targets kidney and intestine to inc blood Ca+
See s2c8 arthritis and s2c10 osteoporosis
Thyroid hormones (T4, T3)
Imp regulators of overall basal metabolic rate
o Regulate body’s consumption of O2 and energy expenditure
o Inc metabolic activity (breakdown of ATP) = inc heat prod peripheral vasodilation
Sympathomimetic effect
o Inc target cell responsiveness to catecholamines (Adrenaline, Noradrenaline)
o Permit proliferation of catecholamine target-cell receptors
Inc rate and force of contraction inc cardiac output
Stim GH secretion, inc hepatic IGF-1 prod, promote effects of GH & IGF-1 on new structural proteins and on bone
growth
TSH
Released from ant pituitary most imp regulator of
thyroid hormone secretion
Also maintains structural integrity of the thyroid gland
Absence of TSH thyroid atrophies
Excess TSH thyroid hypertrophy & hyperplasia
TRH
Turns on TSH secretion
Negative feedback
thyroid hormone in turns off TSH secretion
achieves day-to-day regulation
Hypothalamus mediates long-term regulation
Thyroid disorders causes: Causes of goiters: excessive stim of thyroid gland by TSH or
Autoimmune (eg. Graves’ disease) TSI
Infection (eg. post viral inflammation) Idiopathic (most)
Medications (eg. lithium, amiodarone) Puberty or pregnancy
Nutritional excess or deficiencies (eg. iodine) Thyroiditis
Tumours, Trauma Iodine deficiency or excess
Pregnancy Inborn errors of thyroid hormone synthesis
Thyroid hormone synthesis:
1. Tyrosine-containing Tg produced within the thyroid follicular cells by the endoplasmic reticulum–Golgi complex is
transported by exocytosis into the colloid.
2. Iodide is carried by secondary active transport from the blood into the colloid by symporters in the basolateral membrane of
the follicular cells.
3. Iodide exits the cell through a luminal channel to enter the colloid.
4. Catalyzed by TPO, iodide is simultaneously oxidized to iodine (Io) and attached to tyrosine within the Tg molecule to yield
MIT. Attachment of two iodines to tyrosine yields DIT.
5. Coupling of one MIT and one DIT yields T3. Coupling of two DITs yields T4.
6. On appropriate stimulation, the thyroid follicular cells engulf a portion of Tg-containing colloid by phagocytosis.
7. Lysosomes attack the engulfed vesicle and split the iodinated products from Tg.
8. T3 and T4 diffuse into the blood (secretion).
9. MIT and DIT are deiodinated, and the freed iodide is recycled for synthesizing more hormone.
Thyroid diseases
Investigations:
Thyroid function tests: Blood (sera) – TSH, Free T4, Free T3. Additional tests:
Imaging – US, Nuclear scan
Histopathology – Fine needle aspirate, Biopsy
Bloods:
o TSH receptor Ab (thyroid stimulating immunoglobulin) – Graves
o Anti-thyroid peroxidase (Ab-TPO Ab), Anti-thyroglobulin Ab – Hashimoto
o Thyroglobulin
General principles:
If TSH low check Free T4 & T3 & If TSH low check Free T4
THYROTOXICOSIS: Elevated T3/T4 w/ low TSH (clinical if S/S are present)
S/S (thyrotoxicosis specific) = Lid retraction and lid lag (specific to any type of thyrotoxicosis)
S/S (Graves’ disease specific) = Chemosis, External ophthalmoplegia, proptosis/exophthalmos
In pregnancy
Graves’ disease
HCG-mediated (HCG levels are very high during pregnancy and drop completely after birth)
o gestational transient thyrotoxicosis – goes away after delivery
o hyperemesis gravidarum – severe persistent nausea and vomiting)
Hyperthyroidism: inflammatory state Thyroiditis
↑ syn of T4 & T3 Release of pre-formed T4, T3
Graves disease, toxic nodule Infection: viral
Revolve with treatment Spontaneous resolution w/ time (may become hypothyroid
Non-tender thyroid May be tender (De Quervain thyroiditis
Thyroid bruit present No thyroid bruits
↑ Uptake on nuclear scan Reduced or no uptake on nuclear scan
THYROID STORM
Pathogenesis Severe life-threatening symptoms (hyperpyrexia, cardiovascular dysfunction, altered mentation) in a pt. with
biochemical evidence of hyperthyroidism.
S/S (main only) Fever, altered mentation/CNS effects, precipitant history – thyroid or non-thyroidal surgery, trauma, infection,
acute iodine lead or parturition
Treatment Beta blockers – control S/S of increased adrenergic tone
Thionamide – block new hormone synthesis
Iodine solution – block release of thyroid hormone
Glucocorticoids – reduce T4 to T3 conversion, promote vamotor stability, possible dec autoimmune process in
Grave’s doease and treat assoc adrenal insufficiency
Bile acid sequestrants – dec enterohepatic recycling of thyroid hormones
HYPOTHYROIDISM
Pathogenesis Not enough thyroid hormone (T3, T4) produced by thyroid follicular cells.
Clinical autoimmune thyroiditis (Hashimoto’s).
Chronic lymphocytic thyroiditis caused by an autoimmune disorder involving chronic inflammation of the
thyroid. May be associated to some thyroid lymphoma and carcinomas.
Often hypothyroid but may have transient hyperthyroidism in initial stages:
o Types: Post-partum thyroiditis or Sub-acute thyroiditis
Aetiology Primary failure of the thyroid gland
Secondary deficiency of TSH, TRH or both
Inadequate dietary supply of iodine
Others: Hashimoto’s thyroiditis (autoimmune destruction), congenital defects, hyperthyroidism treatment, blockage by
meds such as lithium
S/S General S/S:
Decreased BMR Poor tolerance for cold, tendency to gain weight, weakness
↓ SNS stim slow/weak pulse and slow mental responsiveness
Main characteristic S/S:
Iodine deficiency or excess (Wolff-Chaikoff effect)
Myxoedema – puffy appearance from oedema
Hashimoto’s S/S: Low T3 & T4 w/ elevated TSH + Autoantibodies
Histology Hashimoto’s:
Hurtle cells – pink cells filled w/ mitochondria and some metabolic blockade in them
Thyroid enlarges w/ dense mononuclear cell infiltrates – lymphocytes, plasma cells
Destruction of thyroid follicles (atrophy) visible
Investigations Thyroid peroxidase (TPO) antibodies – involved in destructive process assoc w/ hypothyroidism in
Hashimoto’s and atrophic thyroiditis. Precede thyroid dysfucntion & may be cytotoxic.
Others: Thyroidectomy, RAI, External neck irradiation
Treatment Anti-thyroid (CBZ, PTU)
Lithium
Amiodarone
For iodine deficiency – dietary changes to inc iodine intake
Consequences Cretinism – dwarfism and mental retardation
HYPERTHYROIDISM
Pathogenesis Elevated levels of T3 & T4, but TSH can be low due to:
Graves’s disease – an autoimmune disease in which thyroid stimulating immunoglobulin (TSI) , an antibody mimic
TSH is produced. TSI bind TSH receptors & effects thyroid follicular cells similar to TSH but is not subject to
negative control overproduction of T3, T4 & suppression of TSH.
Excess TSH or TRH
Hypersecreting thyroid tumour
Hyperfunctional multinodular goiter
S/S General S/S:
Elevated BMR Excessive perspiration, low tolerance for heat, weight loss, peripheral vasodilation
↑ SNS activity tachycardia, palpitations, inc. mental alertness, anxiety, muscle tremors, irritability
↑ SNS stim of ocular muscles wide staring gaze and lid lag
Hypermotility malabsorption and steatorrhea
Main characteristic of Graves’ disease:
Exophthalmos – protrusion of one or both eyes due to antibodies related to proliferation of retro-orbital structures
incl. retroorbital fat & connective tissue
Hyperthyroid w/ diffuse toxic goitre
Dermopathy – localised lesion of the skin due to deposition of hyaluronic acid
Histology Colloid scalloping
Colloid no longer fills the follicle
Scalloping is an artefact due to lack of fixation on the slide as the abnormal architecture of cells does not stick to
the formaldehyde slide
Lymphoid infiltrates present but not as high as Hashimoto’s
Infolding of follicular structures
Thyroid is enlarged due to diffuse hypertrophy and hyperplasia of follicular cells
form finger-like projections into centre of the follicle (called pseudopapilli)
Investigations Thyroidectomy, RAI, External neck irradiation
Treatment Anti-thyroid (CBZ, PTU)
Lithium
Amiodarone
THYROID MASSES
Can be diffuse or nodular
Causes: most are benign, but can are:
Related to hyperplasia
Benign neoplasm
Malignant
Related to destructive inflammatory disease (eg. Hashimoto, Riedel (IgG4 disease that causes destruction and fibrosis along with
Hashimoto’s thyroiditis).
Diagnostic measure: use assays (T3, T4, TSH, autoantibodies), ultrasound, FNA, scans radioiodine (rare), biopsy
THYROID NEOPLASIA
Can be benign or malignant
Classification of malignant thyroid neoplasia:
Papillary carcinoma
- Well differentiated w/ different histological types
- Incidence: Common (85% of cases, can present at any age)
- Mutations – two forms of chromosomal translocation and one form of point mutation
o Tumour is assoc w/ activation of MAP kinase pathway (a common carcinogenic pathway) due to rearrangement of the RET
proto-oncogene or activating mutations involving BRAF.
o 1/5th of pts have chromosomal translocations involving RET protooncogene (encoding a tyrosine kinase receptor involved in
development of neuroendocrine cells) located on chr 10q11
- Histology: Lesions may be solitary or multiple, and can infiltrate into the adjacent parenchyma; presence of branching
papillae covered by well-differentiated epithelial cells w/ finely dispersed chromatin (makes them look clear/empty.
Follicular carcinoma
- More malignant (aggressive) than papillary carcinoma; 5-15% of cases
- Risk factors: Peak onset b/w 40-60yrs; more common in females (3:1 ratio), rarely due to radiation exposure
- Histology: invasion into vascular structures or capsules, uniform cells forming small follicles
- Prognosis: directly related to tumour size (<1cm is good), overall cure rate is high but decreases w/ age
Anaplastic carcinoma
- Aggressive tumour that is almost always fatal (very poor prognosis) – Less than 1 year survival
- Incidence: Rare (<5% of cases)
- Risk factors: More common in elderly (mean age 65yrs)
- Half of all pts have pre-existing papillary or follicular carcinoma ∴ usually present w/ large mass
- Histology: poorly differentiated, rapidly growing cells. Tumour expands and metastases rapidly.
Medullary carcinoma
- Derived from calcitonin-producing neuroendocrine cells
- Incidence: Rare (<5% of cases)
- Risk factors: Sporadic in most cases (70%), rest are familial causes Polygonal spindle shaped cells
- Histology: nests of polygonal/spindle-shaped cells w/ amyloid deposits (from large calcitonin conc)
- Prognosis poor but screening affected families beneficial
- Metastasis to lymph nodes poorer prognosis
PARATHYROID PATHOLOGY
- Normal parathyroid glands are small, w. overall dimensions 5x3x1 mm and weight <50mg.
- Most parathyroid diseases identified in patients w/ hypercalcemia
- Include: parathyroid hyperplasia, parathyroid adenoma (PA), atypical PA, and parathyroid carcinoma (PC)
Hyperparathyroidism
- May stem from primary abnormality of the glands or secondary to renal failure
- Involves high calcium conc.
- Risk factors: Not common but more prevalent in people over 50. Women also more likely than men.
- Causes: Most are benign, sometimes parathyroid hyperplasia, rarely parathyroid carcinoma
- Imaging: 99mTc – sestamibi scintigraphy
- Histology: nodule – expansile, absence of adipose tissue, no infiltration, all cells have same morphology
