S3C9 (2.0) Flashcards

1
Q

What is the thyroid?

A

A butterfly-shaped, unpaired endocrine gland composed of two lobes

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2
Q

Where is the thyroid?

A

Located anteriorly in lower part of neck
C5-T1
Surrounded by pretracheal fascia

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3
Q

What are the anterior relations to the thyroid?

A

Strap muscles (sternohyoid, sternothyroid, thyrohyoid, and omohyoid muscles)

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4
Q

What are the posterior medial relations to the thyroid?

A

Trachea
Oesophagus
Recurrent laryngeal nerve
External branch of superior laryngeal nerve

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5
Q

What are the posterior lateral relations to the thyroid?

A

Parathyroid glands
Cricoid cartilage
Lower thyroid cartilage
Carotid sheath - internal jugular vein, vagus nerve, and common carotid artery

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6
Q

What is the function of the thyroid?

A

Produce thyroid hormones that are essential for regulation metabolism and growth

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7
Q

What connects the two lobes of the thyroid?

A

Isthmus

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8
Q

What encapsulates the thyroid?

A

Pretracheal fascia - false/surgical capsule

Internal capsule - inner connective tissue covering that cannot be separated from the gland (true capsule)

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9
Q

What does the internal capsule around the thyroid form?

A

Septae, dividing the gland into lobes and lobules

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10
Q

What supplies the superior and anterior part of the thyroid?

A

Superior thyroid artery (from external carotid)

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11
Q

What supplies the posterior and inferior part of the thyroid?

A

Inferior thyroid artery (the thyrocervical trunk - branch of subclavian artery)

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12
Q

What does the thyroid ima artery supply?

A

Anterior surface of isthmus
Present in 10% of people
from the brachiocephalic trunk of the arch of aorta

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13
Q

What is the venous drainage of the thyroid?

A

Superior and Middle thyroid vein - drains into IJV

Inferior thyroid vein - drain into r/l brachiocephalic veins

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14
Q

What nodes are involved in lymphatic drainage of the thyroid?

A

Paratracheal nodes

Deep cervical nodes

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15
Q

What nerve provides the parasympathetic innervation for the thyroid?

A

Vagus

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16
Q

What provides the sympathetic innervation for the thyroid?

A

Superior, middle, and inferior cervical ganglia of the sympathetic trunk

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17
Q

What are thyroid follicles?

A

Small functional units
Spherical, vesicular components of the thyroid gland lined with epithelium
Follicular lumen filled with colloid

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18
Q

What are the two types of cells forming epithelium of thyroid follicles?

A

Thyroid epithelial cells

C cells

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19
Q

What fills the interfollicular spaces in the thyroid?

A
Reticular connective tissue
Fenestrated capillaries - facilitate the release of hormones into the blood
Lymphatic vessels
Adipocytes
Sympathetic nerves
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20
Q

How are thyroid epithelial cell arranged?

A

Basophilic cuboidal epithelium

Arranged in spherical follicles surrounding colloid

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21
Q

What receptors are found on the surface of thyroid epithelial cells?

A

TSH receptors

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22
Q

What is the function of thyroid epithelial cells?

A

Take up amino acids and iodine on basolateral side from blood
Synthesise, secrete and store thyroid peroxidase and thyroglobulin

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23
Q

What is thyroglobulin?

A

A protein made in the thyroid gland that is a precursor to thyroid hormone.

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24
Q

What is thyroid peroxidase?

A

An enzyme in the thyroid gland which catalyses the addition of iodine onto thyroglobulin to make thyroxine (T4) or triiodothyronine (T3)

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25
Q

How are C Cells arranged?

A

Large pale staining cells between thyrocytes

Found along the basement membrane of thyroid epithelium, which surrounds follicles and has no direct contact with lumen

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26
Q

How are C Cells activated?

A

Calcium-sensing receptors (CaSR) on surface
High extracellular calcium activates G-protein-coupled second-messenger (IP3 and DAG)
Increase of intracellular Ca2+ levels which increases calcitonin release

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27
Q

What is the function of C Cells?

A

Hormone production and storage in granules
Procalcitonin → proteolytic cleavage of N- and C-terminal peptide → calcitonin
Also secretes several neuroendocrine peptides in smaller quantities such as serotonin, somatostatin, dopamine, TRH, and motilin

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28
Q

What is the function of calcitonin?

A

Lowers calcium in serum

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29
Q

What is the function of calcitonin in bones?

A

Increase osteoclast activity

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30
Q

What is the function of calcitonin in kidneys?

A

Increases excretion of calcium and phosphate

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31
Q

What is the function of calcitonin in the intestine?

A

Lowers calcium absorption

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32
Q

What is the process of thyroid hormone synthesis?

A
  1. Thyroglobulin, an iodine-free hormone precursor, is stored in the follicular lumen.
  2. Iodide is actively taken up by thyrocytes and transported into the follicular lumen.
  3. Here, thyroid peroxidase catalyses the iodination of tyrosine residues of thyroglobulin, creating precursors monoiodotyrosine (MIT) and diiodotyrosine (DIT) and eventually the thyroid hormones.
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33
Q

How is T3/T4 released from the follicular lumen?

A

The iodinated thyroglobulin must be taken up again by thyrocytes, where it is broken down by lysosomes, thus releasing attached T4 and T3.
T4 and T3 are then transported out of the thyrocyte into the blood

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34
Q

What are the transport proteins involved in transporting thyroid hormone?

A

Primarily thyroxine-binding globulin (TBG)
Transthyretin: transports thyroxine and retinol
Albumin

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35
Q

How is thyroid hormone degraded?

A

Degraded in liver

sulfation/glucuronidation (biotransformation) → excretion via bile

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36
Q

What is the effect of thyroid hormone on the heart?

A
Increased cardiac beta-receptors
Increased heart rate
Increase stroke volume
Increase cardiac output
Increased contractility
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37
Q

What is the effect of thyroid hormone on the lungs?

A

Stimulation of the respiratory centre

Increase oxygenation due to increased lung perfusion

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38
Q

What is the effect of thyroid hormone on skeletal muscle?

A

Increased development of type 2 muscle fibres

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39
Q

What is the effect of thyroid hormone on metabolism?

A

Increased metabolic rate due to increased expression of Na+/K+ ATPase in many tissues

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40
Q

What is the effect of thyroid hormone on growth during childhood?

A

stimulation of bone growth
induction of chrondrocytes, osteoblasts and osteoclasts
promotion of synthesis and secretion of growth hormone

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41
Q

What is the parathyroid gland?

A

Four, oval-shaped endocrine glands embedded in the posterior surface of the thyroid gland

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42
Q

Where are the two superior parathyroid glands located?

A

Near the superior pole of the thyroid gland at the junction of cricoid and thyroid cartilages

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43
Q

Where are the two inferior parathyroid glands located?

A

Located in the area between the inferior poles of the thyroid lobes and the superior mediastinum

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44
Q

What is the function of the parathyroid glands?

A

Secretion of parathyroid hormone (PTH) in response to low calcium serum levels

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45
Q

What is the vasculature of the parathyroid gland?

A

Arterial supply: inferior thyroid arteries
Venous drainage: thyroid plexus of veins
Lymphatic drainage: deep cervical nodes, paratracheal nodes

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46
Q

What innervated the parathyroid gland?

A

Thyroid branches of the cervical ganglia

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47
Q

What different cells are found in the parathyroid gland?

A
Adipocytes (∼ 50%)
Parathyroid cells (parathyroid chief cells)
Oxyphil cells: red/pink cytoplasm; function not clear
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48
Q

What are parathyroid cells?

A

Polygonal, hormone-secreting cells with round nucleus
Produce and secrete PTH
Have calcium-sensing receptors (CaSR), which detect changes in calcium concentration and modulate PTH secretion

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49
Q

What are the adrenal glands?

A

Two endocrine glands that produce steroid hormones and adrenaline

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50
Q

What is the approximate size of the adrenal gland?

A

Height and thickness ~5cm and width 1-2cm

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51
Q

Where are the adrenal glands located?

A

Primary retroperitoneal organs
Each gland is located superior to the upper pole
Enclosed by the renal fascia and adipose capsule of the kidney

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52
Q

Whats the function of the adrenal gland?

A

Adrenal cortex: outer layer produces steroid hormones

Adrenal medulla: inner part produces catecholamines

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53
Q

What is the arterial blood supply to the adrenal glands?

A

Superior suprarenal artery (from the inferior phrenic artery)
Medial suprarenal artery (from the abdominal aorta)
Inferior suprarenal artery (from the renal artery)

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54
Q

What is the venous drainage from the adrenal glands?

A

Right suprarenal vein into the inferior cava vein

Left suprarenal vein into the left renal vein

55
Q

What is the lymph drainage from the adrenal glands?

A

Left - aortic lymph nodes

Right - caval lymph nodes

56
Q

What is the innervation of the adrenal gland?

A

Sympathetic - major and minor splanchnic nerves from coeliac ganglion
Parasympathetic - vagal nerve

57
Q

What are the layers of the adrenal cortex?

A

Zona glomerulosa
Zona fasciculata
Zona reticularis

58
Q

What is the structure of the zona glomerulosa?

A

Cells arranged in oval clusters surrounded by connective tissue from the fibrous capsule

59
Q

What is the function of the zona glomerulosa?

A

Mineralocorticoid synthesis - regulates of renal sodium and water reabsorption and potassium excretion

60
Q

What is the structure of the zona fasciculata?

A

Cells arranged in straight columns that are separated by small fibrous septa
Steroid synthesizing cells contain many lipid droplets that contain the cholesteryl ester for steroid production

61
Q

What is the function of the zona fasciculata?

A

Glucocorticoid synthesis - metabolism: mobilise energy reserves

62
Q

What is the structure of the zona reticularis?

A

Small cells arranged in an irregular netlike formation surrounded by connective tissue and capillaries

63
Q

What is the function of the zona reticularis?

A

Androgen synthesis -precursor for oestrogen and testosterone

64
Q

What is the structure of the adrenal medulla?

A

Large chromaffin cells with many secretory granules (catecholamine storage)

65
Q

What is the function of the adrenal medulla?

A

Synthesis of catecholamines

66
Q

What is the hypothalamic-pituitary gland-adrenal cortex feedback mechanism?

A

corticotropin-releasing hormone (CRH) → increased secretion of adrenocorticotropic hormone (ACTH) in the pituitary gland → increased secretion of glucocorticoids in the adrenal cortex

67
Q

What does the presence of TSH receptor autoantibodies and/or Thyroid peroxidase antibodies suggest?

A

An autoimmune thyroid disorder such as Graves or Hashimoto’s

68
Q

What does the presence of thyroglobulin antibody indicate?

A

Thyroid cancer

69
Q

What is BMI?

A

The body mass index (BMI) is a measure that uses your height and weight to work out if your weight is healthy.

70
Q

What are the BMI ranges?

A

below 18.5 – you’re in the underweight range
between 18.5 and 24.9 – you’re in the healthy weight range
between 25 and 29.9 – you’re in the overweight range
between 30 and 39.9 – you’re in the obese range

71
Q

What is the BMI formula?

A

The formula is BMI = kg/m2 where kg is a person’s weight in kilograms and m2 is their height in metres squared.

72
Q

Explain the fight/flight response pathway.

A

Hypothalamus activates the sympathetic nervous system. This activates smooth muscles and the adrenal medulla to release noradrenaline and adrenaline into the bloodstream.
At the same time, the hypothalamus stimulates the anterior pituitary gland to release corticosteriod releasing factor.
The pituitary gland the secretes ACTH, which arrives at the adrenal cortex to release ~30 hormones

73
Q

What happens if there is a prolonged threat?

in regards to fight/flight

A

If threat continues, the hypothalamic-pituitary-adrenal axis activates.
Keeps the sympathetic nervous system active
Releases cortisol

74
Q

What percentage of people have a long term anxiety problem in England?

A

17.6%

75
Q

What is the recovery rate for someone with anxiety in England?

A

51%

76
Q

Describe the Hypothalamus-Anterior pituitary-thyroid axis

A

The hypothalamus secretes TRH.
This stimulates the A Pituitary to secrete TSH
This activates the thyroid to produce T4 and T3.
T3 inhibits both the anterior pituitary and the hypothalamus secretions

77
Q

What is T4 broken down into?

A

Reverse T3

78
Q

What is T3 broken down into?

A

T2

79
Q

How much of each thyroid hormone is secreted?

A

80% T4

20% T3

80
Q

How much of T4 is metabolised into T3?

A

40%

81
Q

When treating someone, why do you give them T4 supplements instead of T3?

A

T4 lasts longer in body
T3 half-life is 1-3 days
T4 half-life is 5-7 days

82
Q

What is the action of T3?

A

T3 binds to the Thyroid receptor attached to the retinoid X receptor
This affects gene expression
Meaning slow acting

83
Q

Describe the epidemiology of hyperthyroidism

A
1% of the general population 
Sex women:men 7:1
Ages:
	Graves disease: 20–30 years
	Toxic adenoma: 30–50 years
	Incidence of toxic multinodular goitre: peak incidence > 80 years of age
84
Q

What are the different ways hyperthyroidism can occur?

A

Hyperfunctioning thyroid gland - overproduction of thyroid hormones
Destruction of the thyroid gland - release of preformed thyroid hormones secondary to inflammation/destruction
Exogenous hyperthyroidism - excessive intake of thyroid hormones
Exctopic hormone production

85
Q

What are examples of hyperfunctioning hyperthyroidism?

A

Graves disease (60%-80% of cases)
Toxic multinodular goitre (15-20% of cases)
Toxic adenoma (3-5% of cases)
TSH-producing pituitary adenoma
β-hCG mediated hyperthyroidism - pregnancy 2.5%
Hashitoxicosis

86
Q

What are the signs of fetal hyperthyroidism?

A

> 160bpm fetal
Goitre
Advanced neonatal bone age
craniosynotosis

87
Q

What can happen when pregnant with Graves?

A
Spontaneous abortion
Premature labour
Small birth weight
	Congestive cardiac failure
Pre-eclampsia
1% generate fetal hyperthyroidism - placental crossing of TSHR stimulation Abs
88
Q

What are the effects of hyperthyroidism?

A

Generalised hypermetabolic state - increased substrate consumption
Hyperstimulation of the sympathetic nervous system
Cardiac effects - caused by a direct effect of thyroid hormones on the cardiac myocytes and the hyperadrenergic state.

89
Q

What are the Basic clinical features of hyperthyroidism?

A
Heat intolerance, excessive sweating Weight loss despite increased appetite
Hyperdefecation 
Weakness, fatigue
Hyperreflexia
Eye issues
Diffuse, smooth, nontender goiter
90
Q

What are the eye-related symptoms of hyperthyroidism?

A

Lid-lag - Sclera visible above the cornea when looking down
Lid retraction - Sclera visible above the cornea when looking straight ahead
Graves opthlmopathy

91
Q

What causes lid lag?

A

An adrenergic overactivity resulting in a spasm in the smooth muscle portion of the levator palpebrae superioris

92
Q

What are the cardiovascular symptoms of hyperthyroidism?

A

Tachycardia:
Palpitations, irregular pulse (due to atrial fibrillation/ectopic beats)
Hypertension with a widened pulse pressure
Cardiac failure

93
Q

What are the musculoskeletal symptoms of hyperthyroidism?

A

Fine tremor of the outstretched fingers
Myopathy with muscle weakness, particularly in patients > 40 years of age
Osteoporosis , fractures (in the elderly)

94
Q

What are the Endocrinological symptoms of hyperthyroidism?

A

Women: Oligo/amenorrhoea and anovulatory infertility
Men: Gynecomastia, decreased libido, erectile dysfunction

95
Q

What are the Neuropsychiatric symptoms of hyperthyroidism?

A
Anxiety
Agitation
Depression
Insomnia
Emotional instability
96
Q

Why use a thyroid ultrasonography?

A

Thyroid ultrasonography is particularly useful in evaluating hyperthyroidism in pregnant women since scintigraphy is contraindicated in this group of patients.

97
Q

What is a thyroid scintigraphy?

A

A nuclear medicine imaging technique, which demonstrates the structure and function of thyroid tissue based on its selective uptake of radioactive iodine (RAI)

98
Q

When would you use a thyroid scintigraphy?

A

Patients in whom the aetiology is uncertain or if physical examination suggest nodular thyroid disease
Identification of ectopic thyroid tissue
Evaluation of thyroglossal cyst

99
Q

When wouldn’t you use a thyroid scintigraphy?

A

Pregnant or breast-feeding

100
Q

What can be given to treat the symptoms of hyperthyroidism?

A

Beta-blockers offer immediate control of symptoms - Improve tachycardia, hypertension, tremor and neuropsychiatric symptoms
Propranolol decreases peripheral conversion of T4 to T3 by inhibiting the 5’-monodeiodinase enzyme

101
Q

What different definitive therapies can be used to treat hyperthyroidism?

A

Anti-thyroid drugs
Radioactive iodine ablation
Surgery

102
Q

What are the indications of anti-thyroid drugs?

A

Patients with high likelihood of remission
Active Graves ophthalmopathy
Children ≤ 5 years
Pregnancy
Thyroid storm
Patients who need rapid disease control
Patients with an inability to follow radiation safety regulations

103
Q

What is the permanent remission rate after 1-2 years of treatment?

A

20-75%

104
Q

What is the drug of choice for hyperthyroidism when the patient is pregnant or in a thyroid storm?

A

Propylthiouracil

105
Q

What is radioactive iodine ablation?

A

The destruction of thyroid tissue using radioactive iodine (iodine 131) through a sodium/iodine symporter

106
Q

What are the indications for using RAIA?

A

High surgical risk; limited life-expectancy
Liver disease
Major adverse reaction to ATDs
Previous operations or radiation of the neck
Patients with congestive heart failure, right heart failure, pulmonary hypertension, or periodic hypokalemic paralysis

107
Q

When shouldn’t you treat hyperthyroidism with RAIA?

A

Pregnant/breastfeeding
Children <5
Thyroid malignancy
Moderate to severe Grave ophthalmopathy

108
Q

How does RAIA work?

A

Single oral dose of 131 Iodine
Isotope uptake by thyroid gland
Emission of β-radiation that slowly destroys the thyroid tissue

109
Q

What are the indications for thyroid surgery?

A

Large goiters (≥ 80 g) or obstructive symptoms
Confirmed or suspected thyroid malignancy
Moderate to severe active Graves ophthalmopathy
Women planning to become pregnant in the next < 6 months

110
Q

What are the contraindications for surgery?

A

Severe comorbidities that influence surgical risk

1st and 3rd trimester of pregnancy

111
Q

What is a thyroid storm?

A

Thyrotoxic crisis

An acute exacerbation of hyperthyroidism, resulting in a life threatening hypermetabolic state

112
Q

What is the aetiology of a thyroid storm?

A

A sudden surge in thyroid hormones

Stress-related catecholamine surge - worsened the pre-existing hyperadrenergic state of hyperthyroidism

113
Q

What are the clinical features of a thyroid storm?

A
Hyperpyrexia w/ profuse sweating
Tachycardia
Hypertension
AF
Congestive cardiac failure
Severe nausea
Vomiting
Diarrhoea
Possibly jaundice
Severe agitation and anxiety
Delirium and psychoses
Seizures 
Coma
Low/ undetectable TSH
Elevated free T3/T4
114
Q

What are the immediate treatments available for thyroid storm?

A

IV dextrose solutions are preferred to meet the high metabolic demand
Treatment of hyperthermia: ice packs, cooling blankets, and antipyretics (e.g., acetaminophen)

115
Q

What is the epidemiology of Graves disease?

A

~30 cases per 100,000 people per year
8:1 w:f
20-40 years

116
Q

What are the genetic predispositions linked with Graves?

A

50% of patients have family history of autoimmune disorders

Associated with HLA-DR3 and HLA-B8 alleles

117
Q

What cells mediate graves?

A

B and T lymphocyte mediated

118
Q

What infectious agents can trigger Graves?

A

Yersinia enterocolitica and Borrelia burgdorferi - shown to trigger antigen mimicry for homologies between their protein constituents and thyroid autoantigens

119
Q

How does pregnancy increase the risk of Graves?

A

Thyroid overstimulation by high levels of hCG and TRAb during the first trimester

120
Q

How does the second trimester of pregnancy decrease the risk of Graves?

A

Progesterone-induced immunosuppression.

121
Q

Why does the risk of Graves increase postpartum?

A

A drop in progesterone level which leads to the rebound of the immune system that can trigger autoimmunity

122
Q

What is the pathophysiology of Graves?

A

B and T cell-mediated autoimmunity
Production of stimulating immunoglobulin G (IgG) against TSH-receptor (TRAb; type II hypersensitivity reaction)
↑ thyroid function and growth

123
Q

How does Thyroid-associated ophthalmopathy occur in Graves?

A

activated B and T cells infiltrate retro-orbital space targeting orbital fibroblasts
Cytokine release (e.g. TNF-α, IFN-γ) → local inflammatory response
Fibroblast proliferation and differentiation to adipocytes
Production of hyaluronic acid and GAGs and increased amount of adipocytes
Increase in the volume of intraorbital fat and muscle tissues

124
Q

How does pretibial myxoedema occur?

A

dermal fibroblast stimulation and deposition of glycosaminoglycans in connective tissue

125
Q

What are the histological features of an overactive thyroid?

A

Diffuse hyperplasia of thyroid follicles
Hyperplastic and hypertrophic follicular cells
Colloid reabsorption with peripheral scalloping
Irregular stromal lymphocytic infiltration

126
Q

How many newborns have congenital hypothyroidism a year?

A

1/2000-1/4000

127
Q

What is the cause of primary hypothyroidism?

A

Insufficient thyroid hormone production

128
Q

What is the cause of secondary hypothyroidism?

A

Pituitary disorders - thyroid stimulating deficiency

129
Q

What is the cause of secondary hypothyroidism?

A

Hypothalamic disorders -

Thyrotropin-releasing hormone deficiency

130
Q

What are the effects of hypothyroidism?

A

Generalised decrease of the basal metabolic rate
myxoedema - increased deposition of glycosaminoglycans
Hyperprolactinemia - stimulated by TRH

131
Q

What are the symptoms of a decreased metabolic rate?

A
Fatigue, bradykinesia
Cold intolerance
Cold, dry skin, and hair loss
Weight gain (despite poor appetite)
Constipation
Myopathy , myalgia, stiffness, cramps, delayed tendon reflex relaxation, entrapment syndromes (e.g., carpal tunnel syndrome)
132
Q

What are the symptoms linked to myxoedema?

A
Doughy skin texture, puffy appearance
Myxedematous heart disease (dilated cardiomyopathy, bradycardia, dyspnoea)
Myxoedema coma 
Hoarse voice, clumsy speech
Pretibial and periorbital oedema
133
Q

What are the symptoms of hyperprolactinemia?

A

Abnormal menstrual cycle (esp. secondary amenorrhea or menorrhagia)
Galactorrhoea
Decreased libido, erectile dysfunction, delayed ejaculation and infertility in men