Endocrinology - Thyroid Flashcards
At what vertebral level is the thyroid gland located?
The thyroid gland is located roughly at the level of C5/C6 cervical vertebrae. Remember that the bifurcation of the common carotid occurs at C4.
Describe the structure of the thyroid gland. How many lobes does it have?
The thyroid gland is composed of:
1) the isthmus - overlying the 2nd and 3rd rings of the trachea
2) the lateral lobes - each extending from the side of the thyroid cartilage downwards to the 6th tracheal ring
3) an inconsistent pyramidal lobe projecting upwards from the isthmus, usually on the left side, which represents a remnant of embryological descent of the thyroid
What structure encloses the thyroid gland?
The gland itself is enclosed by the pre-tracheal fascia, which is in turn covered by strap muscles and overlapped by the sternocleidomastoids.
When the thyroid enlarges, the strap muscles stretch and adhere to the gland so that, at operation, they often appear to be thin layers of fascia.
What are the important anatomic relations of the thyroid?
On the deep aspect of the thyroid is the larynx and trachea, with the pharynx and oesophagus behind and the carotid sheath on either side.
What two nerves lie in close relationship to the thyroid gland?
In the groove between the oesophagus and the trachea lies the recurrent laryngeal nerve and deep to the upper pole lies the external branch of the superior laryngeal nerve passing to the cricothyroid muscle.
What blood vessel supplies the thyroid gland?
Three arteries supply and three veins drain the thyroid gland.
Arteries:
1) Superior thyroid artery - arises from the external carotid and passes to the upper pole
2) Inferior thyroid artery - arises from the thyrocervical trunk of the 1st part of the subclavian artery and passes behind the carotid sheath to the back of the gland
3) Thyroidea ima artery - is inconsistent, and when present it arises from the aortic arch or the brachiocephalic artery
Veins:
1) Superior thyroid vein - drains the upper pole into the inferior jugular vein
2) Middle thyroid vein - drains from the lateral side of the gland to the inferior jugular vein
3) Inferior thyroid veins - often several - drain the lower pole to the brachiocephalic veins
From which structure does the thyroid develop from?
The thyroid develops from a bud which pushes out the floor of the pharynx. This outgrowth then descends to its final position in the neck. It normally loses all connection with its origin which is marked however, by the foramen caecum at the junction of the middle and posterior thirds of the tongue and by the inconsistent pyramidal lobe of the thyroid.
What is meant by the following terms:
a) lingual thyroid
b) thyroglossal cyst
c) retrosternal goitre
a) The development of the thyroid accounts for the rare or part of the thyroid remaining as a swelling at the base of the tongue base (called a lingual thyroid) and for the much more commoner occurrence of a b) thyroglossal cyst along the pathway of descent.
c) Descent of the thyroid may go beyond the normal position in the neck down into the superior mediastinum (retrosternal goitre)
What structure is usually also removed when a thryoglossal cyst is removed?
The cyst (or sinus) can be dissected from the midline of the neck along the front of the hyoid (in such intimate contact with it that the centre of the hyoid bone must be excised during the dissection) then backwards through the muscles of the tongue to the foramen caecum.
Do thyroid malignancies invade or compress?
Benign enlargement of the thyroid may displace any of the important surrounding structures. The trachea and oesophagus may be narrowed causing difficulty swallowing and breathing. The carotids may be displaced posteriorly.
A thyroid carcinoma usually invades rather than displaces - eroding into trachea or oesphagus, surrounding the carotid sheath and occasionally causing severe haemorrhage therefrom. The recurrent laryngeal nerve and the cervical sympathetic chain may be involved, producing changes in the voice and Horner’s syndrome respectively.
Where to thyroid goitres tend to spread? Why is this?
The thyroid gland is enclosed in the pre-tracheal fascia which is much thicker in front that behind. An enlarging gland therefore tends to push backwards, burying itself around the sides and even at the back of the trachea and oesophagus. Because of the attachments of its fascial compartments, a large goitre will also extend downwards into the superior mediastinum (“plunging goitre”).
How is a thyroidectomy carried out? Where are strap muscles divided if a large goitre needs removal?
Thyroidectomy is carried out through a transverse “collar” incision, two fingers breadth above the suprasternal notch. This lies in the line of the natural skin folds of the neck. Skin flaps are reflected together with platysma, and the investing fascia opened longitudinally between the strap muscles and between the anterior jugular veins.
If a large goitre requires removal then the strap muscles are divided. This is carried out at their upper extremity because there nerve supply (the ansa hypoglossi) enters the lower part of the muscles and is henced preserved.
The pre-tracheal fascia is then divided exposing the thyroid gland. The thyroid is then mobilised and its vessels ligated seriatim. Both the recurrent and superior laryngeal nerves are at risk during the procedure and must be avoided.
What hormone stimulates thyroid hormone production?
Thyroid stimulating hormone (TSH) released by the thyrotrophs of the anterior pituitary stimulated all steps in the synthesis of thyroid hormone.
What is thyroglobulin?
This is a molecule synthesised from tyrosine in follicular cells of the thyroid, packaged in secretory vesicles and extruded into the follicular lumen. This is the first step in thyroid hormone synthesis.
What ion is required for thyroid hormone synthesis?
Iodide (I-) is required for thyroid hormone synthesis. It is transported into follicular cells by the iodide-sodium cotransporter and located on the basal surface of the follicular cells.
It actively transports I- into the thyroid follicular cells for subsequent incorporation into thyroid hormones.
What inhibits the iodide-sodium cotransporter?
Thiocyanate and perchlorate anions inhibit this pump.
What happens to iodide ions before they can be used to produce thyroid hormones?
Iodide ions need to be oxidised into iodine (I2). This is catalysed by the peroxidase enzyme in the follicular cell membrane. Iodine is the reactive form, which will be “organified” by combination with tyrosine on thryoglobulin.
The same peroxidase enzyme catalyses the remaining organification and coupling reactions involved in the synthesis of thyroid hormones.
What inhibits the peroxidase enzyme?
Propylthiouracil inhibits the peroxidase enzyme which is used therapeutically to reduce thyroid hormone synthesis in the treatment of hyperthyroidism.
What is organification and where does it occur?
Organification is the joining of iodine with tyrosine on thyroglobulin. It occurs at the junction of the follicular lumen where tyrosine residues of thyroglobulin react with I2 to form monoiodotyrosine (MIT) and diiodotyrosine (DIT).
What is the Wolff-Chaikoff effect?
High levels of serum iodide inhibit organification and therefore inhibit the synthesis of thyroid hormone.
How is MIT and DIT coupled together to produce thyroid hormone?
While MIT and DIT are attached to thyroglobulin 2 coupling reactions occur:
- when 2 molecules of DIT combine thyroxin (T4) is formed
- when one molecule of DIT combines with one molecule of MIT, triiodothyronine (T3) is formed
More T4 is synthesised than T3 even though T3 is the most active form.
Iodinated thyroglobulin is stored in the follicular lumen until the thyroid gland is stimulated to secrete thyroid hormone.
What happens when the thyroid gland is stimulated by TSH?
Stimulation leads to iodinated thyroglobulin being taken back into the follicular cells by endocytosis. Lysosomal enzymes then digest thyroglobulin releasing T3 and T4 into the circulation.
What is thyroid deiodinase?
Leftover MIT and DIT are deiodinated by thyroid deiodinase. The I2 that is released is reutilised to synthesise more thyroid hormone Therefore, deficiency of thyroid deiodinase mimics iodine deficiency.
How are thyroid hormones transported in the bloodstream? What can affect the levels of transport proteins?
In the circulation, most of the T3 and T4 is bound to thyroxine binding globulin (TBG). In hepatic failure, TBG levels decrease leading to a decrease in TOTAL thyroid hormone levels but normal levels of free hormone.
In pregnancy, TBG levels increase leading to an increase in total thyroid hormone levels but not levels of free hormone.
What is reverse T3 (rT3)?
In peripheral tissues, T3 is converted into T4 (the more active form) by 5’ iodinase or into rT3 by the liver.
T3 is MORE biologically active than T4. rT3 is inactive.
What regulates thyroid hormone production?
The HPT axis controls thyroid hormone secretion. TRH is secreted by the hypothalamus and stimulates secretion of TSH by anterior pituitary. TSH increases both synthesis and secretion of thyroid hormones by follicular cells via an adenylate cyclase - cAMP mechanism. Chronic elevation of TSH causes hypertrophy of the thyroid gland.
T3 down regulates TRH receptors in the anterior pituitary and therefore inhibits TSH secretion.
What are thyroid stimulating globulins?
These are components of IgG fraction of plasma proteins and are antibodies to TSH receptors on the thyroid gland. These bind to TSH receptors and like TSH, stimulate the thyroid gland to secrete T3 and T4.
These antibodies circulate in high concentrations in patients with Graves disease which is characterised by high levels of circulating thyroid hormones and accordingly low concentrations of TSH (because of negative feedback on the anterior pituitary).
How do thyroid hormones affect growth?
Attainment of adult stature requires thyroid hormones.
Thyroid hormones act synergistically with growth hormone and somatomedins to promote bone formation.
Thyroid hormones stimulate bone maturation as a result of ossification and fusion of the growth plates. In thyroid hormone deficiency, the bone age is less than the chronologic age.
What is the affect of thyroid hormone on the adult CNS?
Hyperthyroidism causes hyperexcitability and irritability.
Hypothyroidism causes listlessness, slowed speech, somnolence, impaired memory and decreased mental capacity.
How does thyroid hormone affect the perinatal CNS?
Maturation of the CNS requires thyroid hormone in the perinatal period. Thyroid hormone deficiency causes irreversible mental retardation. Because there is only a brief perinatal period where thyroid supplementation is helpful, screening for neonatal hypothyroidism is mandatory.
What is the effect of thyroid hormone on the autonomic nervous system?
Thyroid hormone has many of the same actions as the sympathetic nervous system because it upregulates beta 1 adrenoceptors in the heart. Therefore, a useful adjunct for treating hyperthyroidism is treatment with beta blockers.
How does thyroid hormone affect basal metabolic rate?
Oxygen consumption and basal metabolic rate are increased by thyroid hormone in all tissues EXCEPT the brain, gonads, and spleen. The resulting increase in heat production underlies the role of thyroid hormone in temperature regulation.
Thyroid hormone also increases the activity of the Na+/K+ ATPase and consequently increases oxygen consumption of this pump.
What is the effect of thyroid hormone on the cardio-respiratory system?
Effects of thyroid function on cardiac output and ventilation are to ensure increased oxygen supply to tissues.
Heart rate and stroke volume are increased. These effects combine to produce increased cardiac output. Excess thyroid hormone can cause high output cardiac failure.
Ventilation rate is increased.
What are the metabolic effects of thyroid hormone?
Overall metabolism is increased to meet the demand for substrate associated with the increased rate of oxygen consumption:
- glucose absorption from the GIT is increased
- glycogenolysis, gluconeogenesis, and glucose oxidation are increased
- lipolysis is increased
- protein synthesis and degradation are increased (the overall effect of thyroid hormone is catabolic)
What TFT is more useful, total T4 and T3 or free T4 and T3?
Free concentrations are more useful as total amounts are affected by TBG. Total T4 and T3 are increased when TBG is increased and visa versa.
TBG is increased in pregnancy, oestrogen therapy and hepatitis.
TBG is decreased in nephrotic syndrome and malnutrition, drugs (androgens, corticosteroids, phenytoin) chronic liver disease and acromegaly.
What basic TFTs would suggest hyperthyroidism?
Ask for T3, T4 and TSH. In hyperthyroidism, all will have reduced TSH (except for the rare phenomena of a TSH secreting pituitary adenoma). Most have a raised T4 but only 1% have raised T3.
