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Metabolism, Endocrinology and Haemotology > The Thyroid Gland and Dysfunction > Flashcards

The Thyroid Gland and Dysfunction Flashcards

1
Q

Where is the thyroid gland and what does it look like?

A

The thyroid gland lies against and around the front of the larynx and trachea, below the thyroid cartilage (Adam’s apple). He isthmus extends from the 2nd to 3rd rings of the trachea. 2 lobes are joined by the isthmus to make a bow tie shape. The parathyroid and thyroid are distinct glands. It is above the suprasternal notch and some have a pyramidal lobe pointing up. It’s not possible to feel it normally, do exam from behind.

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2
Q

The thyroid gland is the first endocrine gland to develop. When and how? Use the words: diverticulum, thyroglossal duct and hyoid bone.

A

At 3-4 weeks gestation it appears as an epithelial proliferation on the floor of the pharynx at the base of the tongue and takes weeks to migrate to its final position.
It first defends as a diverticulum through the thyroglossal duct and goes down, passing anteriorly to the hyoid bone. It remains connected to the tongue via the thyroglossal duct, which degenerates. The detached thyroid continues descending for 2 weeks.

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3
Q

The thyroid gland is made up of thyroid follicles - what are these, what are they filled with and what do they produce?
(Parathyroid principle cells/chief cells, produce parathyroid hormone)

A

Follicular cells are arranged in spheres called thyroid follicles, which are filled with colloid (thyroglobulin deposit), which is extracellular. Thyroid follicular cells produce thyroid hormone and thyroid parafollicular cells produce calcitonin (for calcium homeostasis).

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4
Q

Thyroid hormones are 2 tyrosines linked together by an iodine at 3/4 positions on the aromatic rings. How are T3 and T4 made?

A

Monoiodotyrosine + Diiodotyrosine –> Triiodothyronine / MIT + DIT –> T3
DIT + DIT –> Tetraiodothyronine / T4 / thyroxine.

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5
Q

What is the purpose of thyroglobulin aka colloid in thyroid follicles?

A

It acts as a scaffold on which thyroid hormones are are formed - some of its tyrosine residues go through ionisation then coupling.

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6
Q

Name the enzyme bound protein that regulates the 3 iodide reactions of oxidation, addition and coupling.

A

Thyroid peroxidase.

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7
Q

Thyroid peroxide catalyses the oxidation reaction if I- –> I. What else does the reaction require?

A

Hydrogen peroxide.

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8
Q

What addition reaction does thyroid peroxidase catalyse?

A

The addition of iodine to to tyrosine acceptor residues on the thyroglobulin protein.

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9
Q

After oxidation and addition of iodine, what is left for thyroid peroxidase to do?

A

Coupling of MIT/DIT to make thyroid hormones within the thyroglobulin protein/colloid.

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10
Q

Dietary iodine is reduced to iodide before ___________, which occurs mainly in the _______ intestine. ___________ hormones and their precursors are the only I containing molecules in the body - the thyroid gland contains ___-____%.

A

Absorption
Small
Thyroid
90-95

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11
Q

What is an ‘iodine trap’ and what is it used for?

A

A Na+/I- symporter on thyroid epithelial cells, which take up iodide from the blood.

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12
Q

Iodine deficiency is a problem in U.K. school girls, name some sources.

A

Iodised salt, grains and dairy products etc.

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13
Q

What happens after production of the thyroid hormones, to get it to the plasma?

A

After pinocytosis, hormone + lysosome –> phagolysosome, which breaks down the thyroglobulin protein to release the thyroid hormone, which enters the plasma and the rest is recycled.

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14
Q

If 90% of the thyroid hormone secreted is T4, why is this percentage not maintained in the plasma?

A

The biological activity of T3 is 4x that of T4. Most T4 is converted into T3 in the liver and the kidneys - 80% of circulating T3 comes from T4

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15
Q

How are the thyroid hormones transported in the blood and why must this be so?

A

They are both bound to thyroxine-binding globulin as they are lipid soluble.

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16
Q

How is thyroid hormone secretion regulated?

A

Negative feedback.
The hypothalamus produces thyrotropin releasing hormone (TRH). The anterior pituitary releases thyroid stimulating hormone (TSH) triggering the thyroid gland to produce T3/4 which act on the target tissues. T3/4 have negative feedback to the anterior pituitary and the hypothalamus.

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17
Q

Thyroid hormones effect virtually every cell in the body and have 2 connected responses, what are they?

A

Effects on cellular differentiation and development and those on metabolic pathways.

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18
Q

TSH is a ____________ hormone made of 2 non-covalently bound subunits (alpha and beta - __ is also in LH and _____ and ___ provides the unique biological activity).

A

Glycoprotein
a
FSH
b

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19
Q

TSH triggers T3/4 release by stimulating what?

A

Iodide uptake and oxidation, thyroglobulin synthesis and iodination, colloid pinocytosis into the cells, proteolysis of thyroglobulin, cell metabolism and growth.

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20
Q

TSH works on thyroid follicular cells by binding to a GPCR - explain this process.

A

GPCR (alpha S then q) couples to 2 proteins - adenylyl cyclase (-> cAMP -> PKA) and phospholipase C (DAG + IP3) which lead to the stimulation of thyroid hormone synthesis and release (ligand, receptor, G protein, effector protein, 2nd messenger, later effector and cellular response).

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21
Q

What are the general actions of the thyroid hormone? (3)

A

Increase basal metabolic rate, stimulation of metabolic pathways and sympathomimetic effects.

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22
Q

Where and how does thyroid hormone increase BMR and heat production?

A

In most tissues (not the brain, spleen or testes), thyroid hormone increases the number and size of mitochondria and synthesises enzymes in the respiratory chain.

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23
Q

How does thyroid hormone stimulate metabolic pathways (generally catabolic more than anabolic)?

A

Lipid metabolism by stimulating lipolysis and beta-oxidation of fatty acids.
Carbohydrates metabolism by stimulating GLUT4 (insulin dependent glucose cell entry) and increasing gluconeogenesis and glycogenolysis.

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24
Q

In what way do thyroid hormones have sympathomimetic effects?

A

The increase the target cell response to catecholamines by increasing the receptor number.

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25
Q

What tissue specific effects does thyroid hormone have?

A

CVS - increases heart response to catecholamines, increasing cardiac output (with positive ionotropy) and causes peripheral vasodilation to carry extra heat to the body’s surface.
Nervous system - is essential for development and adult function, increasing myelination of nerves and neurone development.

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26
Q

Describe thyroid hormone receptors and how they act as hormone-activated transcription factors.

A

Thyroid hormone receptors are nuclear and modulate gene expression. In absence of the hormone, they will bind the DNA usually meaning transcriptional repression and hormone binding triggers a conformational change in the receptor, so it can act as a transcriptional activator.

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27
Q

How does the thyroid hormone enter the cell and what specific effects can this have?

A

The lipid soluble thyroid hormone enters via the thyroid hormone transporter. The receptor is pre-bound to a specific sequence called a hormone response element (HRE) in the promoter region of certain regulated genes. The hormone enters the nucleus, binds and relieves repression e.g. Of PEPCK, Ca2+ATPase, NaKATPase etc.

28
Q

With regards thyroid hormone effects on the cell, what is RXR?

A

RXR is a retinoid X receptor, which forms a diner with the thyroid hormone receptor.

29
Q

Expression of new proteins ____________ the effect of thyroid hormone. Free T3/4 and TSH are in _______molar concentrations in the plasma.

A

Mediates

Picomolar

30
Q

What is Goitre?

A

Enlargement of the thyroid gland, which may accompany hypo or hyperthyroidism (but is not necessarily present), which develops when it is overstimulated.

31
Q

In what condition will there be high blood TSH and low blood T3/4?

A

Hypothyroidism.

32
Q

List some causes of hypothyroidism.

A

Failure of the gland, TRH/TSH insufficiency, inadequate dietary iodine, radioactive iodine, autoimmunity, post-operative, congenital or anti-thyroid drugs.

33
Q

What are the symptoms of hypothyroidism?

A

Obesity, lethargy, intolerance to cold, bradycardia, dry skin, alopecia, hoarse voice, constipation and slow reflexes.

34
Q

What can be the manifestation of hypothyroidism seen in children?

A

Cretinism - dwarfed stature, mental deficiency, poor bone development, slow pulse, weak muscles and GI disturbances.

35
Q

What can be the manifestation of hypothyroidism seen in adults?

A

Myxedema - thick puffy skin, weak muscles, slow speech, mental deterioration and cold intolerance.
Used to describe both sever hypothyroidism and the dermatological symptom that occurs with it (and sometimes hyperthyroidism).

36
Q

What is Hashimoto’s disease and who’s more at risk?

A

Autoimmune destruction of thyroid follicles leading to hypothyroidism. It’s the most common disease of the thyroid. 5x more women get it than men and it may come with or without goitre.

37
Q

How is Hashimoto’s disease treated?

A

Treat with oral thyroid hormone - T4 used as it has a longer half life.

38
Q

Some cases of hyperthyroidism present with goitre and bulging eyes, list some causes.

A

Autoimmunity, toxic multi-nodular goitre, solitary toxic adenoma, excessive T4 (or 3) therapy, drugs, thyroid carcinoma or ectopic thyroid tissue.

39
Q

What are the symptoms of hyperthyroidism?

A

Weight loss, irritability, heat intolerance - sweating with warm hands, tachycardia - often irregular, fatigue/weakness, increased bowel movements and appetite, possible tremor of outstretched hands, hyper-reflexive, breathlessness, loss of libido, sweating and a tremor.

40
Q

What is Grave’s disease?

A

An auto immune production of thyroid stimulating immunoglobulins (TSI), continuously stimulating secretion outside of the normal negative feedback control - increasing BMR, sweating, decreased weight, muscle weakness, heart palpitations with bulging eyes (sometimes).

41
Q

How does Thyroid Scintigraphy work?

A

Technetium-99m is used for isotope scanning of the thyroid with a gamma camera. It has a biologically half life of 1 day, so the radiation exposure is low. It has other uses (like brain imaging).

42
Q

How is hyperthyroidism treated?

A

Anti-thyroid drugs.
Carbimazole is used the most in the U.K.; it is a prodrug that is converted into Methimazole, which prevents thyroid oxidase from iodinating and coupling tyrosines on thyroglobulin.

43
Q

Why does the thyroid gland move up on swallowing? The feature is important when diagnosing neck lumps.

A

The pretracheal fascia attaches the thyroid gland (the gland is invested in it), to the trachea and larynx.

44
Q

To view the thyroid, Technetium may be given IV or idioms swallowed, but what other method is commonly employed?

A

Thyroid ultrasound.

45
Q

What is the Foramen Caecum and how is it related to a lingual thyroid?

A

The Foramen Caecum of the tongue is where the thyroid originates and a part may stay there - a lingual thyroid (enlarges with high TSH in hypothyroidism).

46
Q

How is a thyroglossal duct cyst formed and how may it be spotted?

A

The thyroglossal duct normally disappears but remnants of the epithelium may remain and form a thyroglossal duct cyst (fluid filled bag) - usually near or within the body of the thyroid and forms a swelling in the anterior neck - always on the midline! The skin is drawn in and it moves up on tongue protrusion.

47
Q

Metabolic thyroid disease is where it’s over or under functioning. It is very rare for a pituitary adenoma (benign tumour of glandular epithelium) to cause thyrotoxicosis, what is it?

A

Thyrotoxicosis is too much thyroid-like activity, not the same as hyperthyroidism, which is overactivity of the gland.

48
Q

Because it’s very rare for a pituitary adenoma to produce TSH and lead to thyrotoxicosis and pituitary failure rarely presents with isolated hypothyroidism, what is the main cause (98%) of metabolic thyroid disease?

A

A primary abnormality in the gland itself.

49
Q

As the pituitary gland is rarely involved causatively with metabolic thyroid disease, what does this mean about a potential marker?

A

TSH levels can be used as a screening test (negative feedback), e.g. TSH is raised in hypothyroidism where free T4 is decreased.
T4 is in picomolar concentrations and like TSH, has a wide range, as does TRH, so all 3 are constantly responding to the environment.

50
Q

What type of diseases often affect endocrine glands e.g. The islets of Langerhans in type 1 diabetes?

A

Autoimmune.

51
Q

Goitre refers to a thyroid swelling, describe some different types and say who’s likely to get it?

A

It may be diffuse, multinodular or single nodular. In the U.K. It’s 7% of females and 1% males. Physiological goitre (with normal heroic function) may occur at Menarche, pregnancy and menopause.

52
Q

What is the commonest cause of goitre globally and what type is it? Explain.

A

Iodine deficiency (I deficient areas are mostly mountainous) leads to reduced thyroxine levels, so increased TSH and general thyroid enlargement, usually nodular in severe cases, there will be hypothyroidism.

53
Q

What is the commonest cause of goitre in the U.K.?

A

Multinodular goitre (aka Colloid goitre), the aetiology of which is unknown, that is accompanied by normal thyroid function (after years, few people will get hyperthyroidism - toxic multinodular goitre.

54
Q

When is iodine deficiency a particular concern?

A

Pregnancy - of the mother is deficient (+hypothyroid) then so will the foetus. The child will have: mental retardation, abnormal gait, deaf-mutism, short stature, goitre and hypothyroidism - Cretinism.

55
Q

What is retrosternal multinodular goitre?

A

Where the thyroid gland enlarges inferiorly in the super mediastinum, which may cause tracheal compression and so inspiratory stridor.

56
Q

The symptoms of hypothyroidism are logical, with everything slowed down, as the thyroid regulates metabolic rate (constipation, cold intolerance etc), with puffy eyes and flaky skin. What is another symptom, that doesn’t fit with the slowing down concept?

A

Menorrhagia (menstrual periods with abnormally long or heavy bleeding).

57
Q

What signs might a patient spot if they have hypothyroidism?

A

There may be none obvious, but they could include weight gain, coarse/brittle hair, loss of the outer third of the eyebrows, pallor (peaches and cream), bradycardia, hyporeflexia and myxoedema - non-pitting (mucopolysaccharides deposited around the eyes, hands and feet). Ascites/pericardial effusion are uncommon.

58
Q

List some causes of hypothyroidism (aka myxoedema)?

A

Severe iodine deficiency, post surgical removal of the thyroid (with inadequate thyroxine replacement), autoimmune destruction of the thyroid (Hashimoto’s).

59
Q

What is Hashimoto’s disease, who gets it, how is it treated and what type of goitre may it produce?

A

It is 10x commoner in women. There are antibodies to thyroglobulin and thyroid peroxidase in the blood. It may be associated with a small, diffuse goitre early on from inflammation, or none at all, with it shrinking from the beginning. Treat with oral thyroxine (not destroyed by gastric acid) and adjust the dose to normalise the TSH.

60
Q

What is hyperthyroidism?

A

Thyrotoxicosis causes by overproduction of thyroxine by the thyroid gland.

61
Q

Thyrotoxicosis symptoms are fairly logical: palpitations, proximal muscle weakness, , weight loss despite an increased appetite, warm sweaty hands and amenorrhea. List some signs.

A

Fine hand tremor, tachycardia - atrial fibrillation, bounding pulse, lid lag, staring eyes (see White above pupil when look down) - the levator palpebrae superioris muscle is 10% smooth muscle supplied by the SNS, which may be overstimulated.

62
Q

List some causes of hypothyroidism.

A

Toxic multi-nodular goitre, toxic adenoma, Grave’s disease.

63
Q

Explain Grave’s disease and its consequences.

A

Autoimmune disease with circulating thyroid stimulating immunoglobulin (TSI) and stimulates the TSH receptor –> thyrotoxicosis symptoms + exopthalamos (bulging eyes) and possible pretibial myxoedema.

64
Q

How is toxic adenoma a cause of hyperthyroidism?

A

A single adenoma develops in the thyroid and makes thyroxine autonomously (low TSH levels suppress the rest of the gland).

65
Q

Other than the prodrug carbimazole that converts into methimazole (prevents prevents thyroid peroxidase coupling and iodinating, reducing T4), what can treat hyperthyroidism?

A

Surgical excision - thyroidectomy, or an ablative dose of radioactive iodine.

66
Q

Why is thyroid cancer not a huge worry?

A

Less than 1% of nodules in the thyroid are malignant and they account for less than 1% of U.K. cancers. They don’t cause metabolic disturbances, just present with a nodule and have an excellent cure rate (97%)/prognosis.

67
Q

Name:
A metabolic dysfunction of the thyroid that may not produce goitre.
3 conditions that may result in goitre, but do not count as a metabolic dysfunction.
3/4 disorders considered metabolic dysfunctions of the thyroid and also may result in goitre.

A

Hashimoto’s disease.
Thyroid cancer (rare), multi-nodular goitre (U.K.), iodine deficiency (global).
Some Hashimoto’s disease, Grave’s disease, toxic multi-nodular goitre, toxic adenoma.

Metabolism, Endocrinology and Haemotology (12 decks)

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