TBL3 Thyroid Flashcards
The adenohypophyseal thyrotrophs synthesise and secrete _______ in response to hypothalamic ________.
Adenohypophyseal thyrotrophs secrete TSH/thyrotrophin in response to hypothalamic TRH.
Thyrotrophin/TSH act on ________ cells to secrete _______.
TSH acts on thyroid follicular epithelial cells to stimulate production of T3 and T4.
Thyroid follicles are lined by _________ with a central cavity known as the _____.
Stroma between the follicles contain capillaries and ________.
Thyroid follicles lined by follicular epithelial cells with central cavity known as the colloid.
Stroma between follicles contain capillaries and parafollicular cells.
Parafollicular cells (in the stroma between follicles of thyroid) secrete ________.
calcitonin - responsible for decreasing calcium levels
A ___________ embryological remnant of the thyroid descent and may sometimes be present extending superiorly from the isthmus.
Pyramidal lobe
Thyroid is supplied by the (arteries).
Superior and inferior thyroid arteries
Blood is drained from the thyroid by _______.
superior, middle and inferior thyroid veins that eventually drain into internal jugular vein and brachiocephalic veins.
The __________ nerve runs closely posteriorly to the thyroid gland.
left recurrent laryngeal nerve
voice hoarseness, supplies the vocal cord
The parathyroid glands lie ________ to the thyroid.
posterior
The thyroid gland originates from a midline outpouching of the ____________ from the base of the tongue.
ventral pharyngeal wall
Thyroxine synthesis from the _______:
- TSH from the _________ binds to TSH receptor present on the (apical/basolateral) membrane.
- ________ is activated to pump sodium and iodide ions from the blood into the cells.
- Transcription and translation of ________ is also stimulated, and it is released into the colloid.
- Apically-bound __________ (enzyme) is activated, catalysing the iodination to form reactive iodide in the presence of ____.
Reactive iodide immediately binds to ____. - MIT or DIT is formed. ______ occurs, forming T3 and T4.
- TSH binds to TSH receptor present on the basolateral membrane.
- Sodium-iodide symporter (NIS) is activated, pumping sodium and iodide ions from the blood into the cells.
- Transcription and translation of thyroglobulin (TG) is stimulated, and it is released into the colloid.
- Apically-bound thyroid peroxidase (TPO) is activated, catalysing iodination to form reactive iodide in the presence of H2O2. Reactive iodide immediately binds to TG, causing the iodination of tyrosine residues.
- MIT or DIT is formed. Coupling reaction occurs, forming T3 and T4.
To release T3 and T4,
_________ migrate to the apical membrane and pinocytose T3 and T4 into the thyroid follicular cells, before being ________ into the blood circulation.
Lysosomes migrate to apical membrane and pinocyose thyroxine hormones back into the thyroid follicular cells. T3 and T4 are then exocytosed into the general circulation.
3 types of plasma proteins dynamically bound to T3/T4 (iodothyronines):
- Thyronine-binding globulin (TBG)
- Albumin
- Prealbumin/transthyretin
Why is T3 more bioactive than T4?
Only the unbound/free iodothyronine molecules that are not bound to plasma proteins are bioactive. There is a greater percentage (0.5%) of T3 unbound compared to 0.05% of T4.
T4 is deiodionated in most of its target tissues by _______ to a more bioactive T3 molecule.
Occasionally, T4 can also be deiodinated at a different position to produce a biologically inactive ______ molecule => target tissues can control the biological activity of iodothyronines.
deiodinases
deiodinated at a different position to produce a biologically inactive reverseT3 (rT3) molecule
Main actions of iodothyronine
- Increase basal metabolic rate
- increase fat, carbohydrate and protein metabolism
- work with catecholamines
- interact with other endocrine systems e.g. oestrogen
- affects CNS
- increase Vit A synthesis
Iodothyronines are important for normal growth and development due to its role in increasing metabolism. Therefore, any lack of foetal growth and development due to lack of thyroxine hormones may cause _______ where there is abnormal physical and mental growth.
cretinism
In hypothyroidism, the deficiency in _________ synthesis causes accumulation of keratins in the blood and yellow discoloration of the skin.
vit A (because iodothyronines stimulate the synthesis of vitamin A)
Iodothyronine receptors are found ________.
iodothyronine receptors are found intracellularly in the nucleus or the cytoplasm
(while they are amino acid hormones they act like steroid hormones)
What is the main mechanism of action by t3/t4 hormones?
T3/T4 hormones bind to INTRACELLULAR receptors and increase protein synthesis/upregulate transcription of certain gene products that may have effects on metabolic activity.
Control of T3/T4 hormone production
- TRH (hypothalamus), TSH (pituitary gland) => stimulatory
- Sympathetic innervation to the follicular cells and vasculature
- Wolf-Chaikoff effect: infusion of inorganic iodide has an inhibitory effect
- Interaction with other endocrine systems (e.g. oestrogen stimulates thyrotrophin production)
What is the Wolf-Chaikoff effect?
infusion of inorganic iodide that has an inhibitory effect on the production of iodothyronines
______ refers to the complete absence of thyroid due to developmental problems.
Agenesis
Failure of the thyroid gland to descend to the trachea may cause incomplete descent, lingual thyroid.
-
Developmental problems can also lead to a ________, which is a segment of duct that persists and presents as a lump later.
thyroglossal cyst (ectopic thyroid)
_________ is the remnant of the embryological descent of thyroid gland that extends superiorly from the isthmus.
This can form from the lower end of the __________ that failed to degenerate.
Pyramidal lobe
Lower end of thyroglossal duct (connects the tongue to thyroid gland during development) that fails to degenerate —> pyrimidal lobe
Level of thyroid gland
C5-T1 (deep to the strap muscles of the neck)
The thyroid gland is invested within the ________ fascia. It overlies the ______ tracheal cartilages.
pre-tracheal
(thyroid gland lies anteriorly to the larynx and trachea)
overlies the 2nd and 3rd tracheal cartilages
Lateral lobes of thyroid are attached to the trachea via _______.
Berry’s ligament
moves upwards upon swallowing
Superior thyroid artery is a branch of the _________ and supplies the superior pole of the thyroid lobes.
It is accompanied by the _________ nerve.
Superior thyroid artery:
- branch of external carotid artery (that arise from the common carotid artery of the aortic arch)
- supplies superior aspect
- accompanies the external laryngeal branch of the superior laryngeal nerve
Inferior thyroid artery arises from the __________ of the _______ artery. It supplies the posterior aspect of the gland and is closely related to the (nerve).
Inferior thyroid artery:
- arises from the thyrocervical trunk of the subclavian artery
- supplies posterior aspect of thyroid lobe
- related to recurrent laryngeal nerve
The thyroid gland drains lymphatically into the central compartment of the neck at level __ lymph nodes.
Boundaries of the central compartment of neck:
Superior -
Inferior -
Lateral -
Level VI lymph nodes
Central compartment of neck:
Superior - Hyoid bone
Inferior - brachiocephalic artery
Lateral 0 common carotid arteries
Thyroid gland is supplied by the autonomic nerves.
Sympathetic -
Parasympathetic -
Sympathetic - superior, middle and inferior cervical sympathetic ganglia
Parasympathetic - vagus nerve
Any damage to the recurrent laryngeal nerve causes hoarseness of voice/vocal cord paralysis as the __________ is supplied by the nerve.
cricoarytenoid muscles
- abduct the vocal cord
Parathyroid glands are located ______ to the thyroid gland.
posteriorly
Superior parathyroid glands are usually located (above/below) the inferior thyroid artery, (anterior/posterior) to the recurrent laryngeal nerve.
Superior parathyroid glands:
- above the inferior thyroid artery
- posterior to the recurrent laryngeal nerve
Parathyroid glands are supplied by _______ artery.
inferior thyroid artery
- branch of thyrocervical trunk of subclavian artery
Pharyngeal arches are made of ______.
Pharyngeal cleft =>
Pharyngeal pouch =>
(CAP) Cleft —> ectoderm Arch —> mesoderm Pouch —> endoderm (From external to internal)
Parathyroid glands develop from the ___________.
dorsal parts of the 3rd and 4th pharyngeal pouches (endoderm)
3rd - inferior
4th - superior
The ventral part of the 3rd pharyngeal pouch develops into __________, whereas the ventral part of the 4th pharyngeal pouch develops into __________.
ventral part of 3rd pharyngeal pouch - thymus
ventral part of 4th pharyngeal pouch - ultimobranchial body (gives rise to parafollicular cells of thyroid)
The functional unit of the thyroid gland is
thyroid follicle - composed of a single layer of cuboidal epithelial cells with a central cavity inside
Central cavity of each thyroid follicle contains
thyroglobulin that is secreted by the cuboidal follicular epithelial cells (in which it combines with iodine to form iodinated thyroglobulin)
__________ cells are located in the stroma outside the follicle of the thyroid.
Parafollicular cells - secrete calcitonin involved in the regulation of calcium
The follicular epithelial cells may vary in shape:
________: normal activity
________: inactive
________: highly active
Cuboidal: normal activity
Flattened: Inactive
Columnar: Highly active
Follicular epithelial cells have _______-located rough ERs, with closely associated mitochondria and Golgi apparatuses.
basally-located
Secretes thyroxine hormones into the bloodstream
Actions of PTH:
- (BONES) Act on osteoclasts to increase bone resorption and break down bone matrix to increase blood calcium
- (KIDNEYS DCT) Act on kidneys to increase calcium reabsorption at nephrons and inhibit phosphate reabsorption from the glomerular filtrate
- Act on kidneys to stimulate 1a-hydroxylase activity to increase production of calcitriol
There are 2 main cell types in the parathyroid gland arranged in cords and nests with capillary network in between.
Chief cells
- secrete PTH
Oxyphil cells
Appearance of chief cells
- small round cells
- central round dark nuclei and pale pink cytoplasm
Appearance of oxyphil cells
- larger cells
- abundant pink cytoplasm
Primary hyperparathyroidism
Parathyroid glands produce excessive PTH
- most commonly due to parathyroid adenoma
- causes hypercalcemia
Secondary hyperparathyroidism
Secondary response to chronic renal failure resulting in persistently low calcium levels (constantly losing calcium in the urine)
- Feedback mechanism due to hypocalcemia —> stimulates PTH causing hyperparathyroidism
- parathyroids become enlarged (chief cell hyperplasia)
Tertiary hyperparathyroidism
Hyperplastic glands of secondary hyperparathyroidism stops responding to calcium levels
=> autonomous secretion of excessive PTH
Binding of TSH to the TSH receptor on thyroid follicular epithelial cells results in activation and conformational change, allowing it to associate with __________.
Gs protein
- leading to the activation of adenylyl cyclase
- increase in intracellular cAMP levels
- stimulates thyroid hormone synthesis and release
(tSh —> gS)
_________ is a hypermetabolic state caused by elevated circulating levels of free T3 and T4.
Thyrotoxicosis
- Graves’ disease
- Toxic multinodular goiter
- Toxic adenoma of thyroid
Why are ocular changes often present in hyperthyroidism?
Sympathetic overstimulation of superior tarsal muscle (Muller’s muscle), which functions to raise the upper eyelid.
*Fullblown thyroid opthalmopathy associated with proptosis is a feature seen only in Graves’.
The single most useful screening test for hyperthyroidism is
measurement of serum TSH
Diagnosis of hyperthyroidism can be confirmed by
measuring TSH and free thyroxine hormone
measurement of radioactive iodine uptake can be useful in determining etiology
________ refers to hypothyroidism developing in infancy or early childhood.
Cretinism
Clinical features:
- impaired development of the skeletal system and CNS
- mental retardation
Hypothyroidism in older children and adults results in a condition known as ______.
myxedema
__________ encompasses a diverse group of disorders characterised by some form of thyroid inflammation.
Thyroiditis
___________ is an autoimmune disease characterised by an immune response to thyroid autoantigens, leading to progressive depletion of thyroid epithelial cells associated with lymphocytic infiltrates and fibrosis. This leads to hypothyroidism.
Hashimoto thyroiditis
The most significant gene associated with Hashimoto thyroiditis
CTLA-4 gene
Microscopic features of Hashimoto
- Thyroid gland symmetrically enlarged
- Widespread infiltration of parenchyma by mononuclear inflammatory infiltrate
- Presence of Hurthle cells (oxyphil cells)
Hashimoto thyroiditis patients have a higher risk of developing (cancer).
B-cell non-Hodgkin lymphoma
______________ is caused by a viral infection or an inflammatory process triggered by viral infections, not autoimmune.
Subacute granulomatous thyroiditis
______________ is also known as silent thyroiditis and is most likely autoimmune in nature.
Subacute lymphocytic thyroiditis
_________ is the most common cause of endogenous hyperthyroidism. It is an autoimmune condition that is caused by autoantibodies against the TSH receptor that stimulate follicular epithelial cells to secrete thyroid hormones. It is characterised by a triad of manifestations:
Graves disease
- Thyrotoxicosis caused by hyper-functional thyroid
- Ophthalmopathy
- Dermopathy (pretibial myxedema)
A genetic susceptibility to Graves disease is associated with the presence of _______.
HLA-DR3
3 types of auto-antibodies present in Graves disease:
- Thyroid-stimulating immunoglobulin (TSI)
- Thyroid growth-stimulating immunoglobulin
- TSH-binding inhibitor immunoglobulin
______ refers to the enlargement of the thyroid that results from the impaired synthesis of thyroid hormones.
Goiter
Impaired thyroxine synthesis leads to a compensatory rise in TSH levels, driving hyperplasia and hypertrophy of thyroid follicular cells.
___________, also known as toxic multinodular goiter, is a thyroid condition that is characterised by marked enlargement of the thyroid gland (Goiter) and overproduction of the thyroid hormone.
Plummer syndrome
__________ are benign neoplasms derived from the follicular epithelium that produce thyroid hormones, causing thyrotoxicosis.
Toxic adenomas
The hallmark of all follicular adenomas is ___________.
the presence of an intact well-formed capsule encircling the tumor
A goiter can cause Horner’s Syndrome.
How?
Horner’s syndrome refers to interruption of sympathetic nerve supply to the eye (causing ptosis and miosis).
A goiter (enlarged thyroid gland) can compress on the sympathetic superior cervical ganglion.
