U10C4 Thyroid

Question 1

What are the functional units of the thyroid gland?

Answer 1

• The gland is composed of Large number of closed follicles
• Follicles filled with secretory substance colloid
• The major constitute of Colloid is the large glycoproteinThyroglobulin plus iodine, which contains the thyroid hormones
• Thyroid gland secrete hormones: Thyroxine (T4) – 90%, Triiodothyronine (T3) –9%, Calcitonin (Parafollicular cells)
• type 3 deiodinase converts T4 to T3

Question 2

What are the thyroid hormone effects on the body?

Answer 2

Question 3

What is the HPT axis?

Answer 3

1. Hypothalamus secretes TRH through hypothalamic portal vessel it reaches pituitary gland
2. Activates thyotrope cells which secrete TSH
3. TSH binds to receptor on thyroid gland to activate T3 and T4

Question 4

How are thyroid hormones synthesised and secreted?

Answer 4

Oxidation of Iodide:
Iodide (I-) is actively transported into the thyroid follicular cells.
The enzyme thyroid peroxidase (TPO) catalyzes the oxidation of iodide to iodine (I2).
This oxidation reaction is essential for iodine to be incorporated into the thyroid hormones.

Organification of Thyroglobulin:
Thyroid follicular cells synthesize and secrete a glycoprotein called thyroglobulin into the colloid space within the thyroid follicles.
The iodine generated in the oxidation step is then added to specific tyrosine residues within the thyroglobulin molecule.
This process forms monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are iodinated tyrosine residues within thyroglobulin.

Coupling:
Coupling involves the combination of iodinated tyrosine residues to form thyroid hormones.
Monoiodotyrosine (MIT) and diiodotyrosine (DIT) combine to produce either triiodothyronine (T3) or thyroxine (T4) within the thyroglobulin molecule.
For T3, one molecule of MIT combines with one molecule of DIT.
For T4, two molecules of DIT combine.

Question 5

What converts iodide to iodine?

Answer 5

TPO- thyroid peroxidase

Question 6

Hyperthyroidism vs thyrotoxicosis

Answer 6

Hyperthyroidism:overactive thyroid gland. It is specific disorder in which thethyroid gland produces an excess amount of of thyroid hormone

Thyrotoxicosis:Itis a wider medical term that includes any condition in which the body has an excess of thyroid hormones, whether due to hyperthyroidism or other causes.(e.g., ingestion of excess thyroid hormone)

Question 7

What are the causes of hyperthyroidism?

Answer 7

Question 8

Primary vs secondary hyperthyroidism?

Answer 8

Question 9

What are the symptoms of hyperthyroidism?

Answer 9

Question 10

What is Graves’ disease, clinical features, Pathophysiology and treatment?

Answer 10

Graves’disease (Diffuse toxic goiter)
- It is an autoimmune disease of thyroid caused by increased circulating levels of thyroid-stimulating immunoglobulins
- Most common cause of hyperthyroidism in UK (60-80%)
- Occurs any age – peak 20 - 40yrs

Clinical features of Graves’ disease may include:
- Thyroid eye disease/ Graves’ ophthalmopathy/Exophthalmos
- Thyroid acropachy: clubbing or swelling of the digits
- Dermopathy : Thickening of skin lower tibia and oedema of the pretibial portion of the leg (just above the lateral malleolus)
- Presence of thyrotropin receptor antibody in the serum and ophthalmopathy on clinical examination distinguishes Graves disease from other causes of hyperthyroidism

Graves’ ophthalmopathy
●This condition affects up to 50% of patients with Graves’.
●It is more commonly seen in smokers.
●Follows separate time course to thyroid disease

➢Pathophysiology :
TRAb–TSH receptor antibodies binds to TSH receptor antigen → T cell cytokines → fibroblasts GAG deposition.

➢Mnemonic: NO SPECS
- N: No signs or symptoms
- O: Only ocular irritation (dryness, gritty sensation)
- S: Soft tissue involvement (conjunctival oedema or infection)
- P: Proptosis (eye bulging)
- E: Extraocular muscle involvement
- C: Corneal exposure and ulceration
- S: Sight loss (due to compressive optic neuropathy)

Treatment
- Lubrication – artificial tears
- Selenium
- IV Methylprednisolone
- Orbital Radiotherapy
- Surgery

Question 11

What is toxic multinodular goitre?

Answer 11

Plummers disease

• Second most common cause of hyperthyroidism in the UK.
• Middle-aged or elderly
• Long standing goitre
• Iodine deficiency
• Ophthalmopathy extremely rare
• Large nodular goitre - may extend retrosternal
• May be present for many years

Question 12

What is toxic adenoma?

Answer 12

• Patient are youngerthan those with toxic multinodular goiter
• Functioning nodule secreting T3+T4
• Infiltrative ophthalmology never present
• Almost always benign

Question 13

What are the investigations and treatment for hyperthyroidism?

Answer 13

Question 14

What is thyroid storm? Symptoms and risk factors.

Answer 14

• Also known as thyrotoxic crisis, is an acute, life-threatening complication of hyperthyroidism

Symptoms

• CNS manifestation (restlessness, delirium, psychosis, coma)
• Fever (38 degrees or greater)
• Tachycardia (130/min or higher) and atrial fibrillation
• Chronic heart failure (Pulmonary oedema, cardiogenic shock)
• GIT manifestation (Nausea, vomiting, diarrhea)

Risk Factors

• Acute infection
• Recent surgery or RAI
• Withdrawal of Anti-thyroid drugs

Question 15

What is hypothyroidism? Primary vs secondary vs tertiary

Answer 15

Hypothyroidism is a common endocrine condition caused by adeficiency in thyroid hormone

• It has a prevalence of 1-4 per 100 in the UK and is up to 10 times more common in females
• Hypothyroidism can be classified according to which part of the feedback loop is affected, such as:

●Primary hypothyroidismoccurs when the thyroid gland does not release enough thyroid hormones.

●Secondary hypothyroidismoccurs when the pituitary gland does not release enough TSH.

●Tertiary hypothyroidismoccurs when the hypothalamus does not release enough thyrotropin-releasing hormone.

Question 16

What are the causes of hypothyroidism?

Answer 16

Question 17

What are the symptoms of hypothyroidism?

Answer 17

Question 18

What is the treatment of hypothyroidism?

Answer 18

• Replacement of thyroxineis the mainstay of management
• Levothyroxine, a synthetic version of T4, is the main treatment of primary hypothyroidism
• T3 has half short life so not recommended
• The initial dose of levothyroxine is typically 1.6 mcg/kg (to the nearest 25mcg) with a TSH target of 0.4–4.5mU/L
• The dose is titrated up and down by 25 mcg as needed. TSH levels are checked every 2-3 months then yearly once stables

Question 19

What is myoxoedema coma?

Answer 19

• Is arare life-threatening condition in patient with long standingsevere untreated hypothyroidism
• Patients are hypoglycemia, hypothermic, hyponatremia, hypoxia and hypercarbia bradycardic and demonstrate cognitive decline
• IV levothyroxineis the mainstay of management. Electrolyte imbalances and hypothermia should be addressed

Question 20

How is basal metabolic rate controlled?

Answer 20

1. The thyroid hormone regulates the basal metabolic rate of the body.
2. Tetraiodothyronine, often known as thyroxine (T4), and triiodothyronine (T3) are two hormones that the thyroid gland produces.
3. Iodine levels in the body control the synthesis of these hormones.
4. The metabolism of proteins, lipids, and carbohydrates is controlled by thyroid hormones. The thyroid hormones are also important for controlling the balance of water and electrolytes.
5. It does this byincreasing the gene expression of Na+/K+ ATPase in different tissues leading to increased oxygen consumption, respiration rate, and body temperature.

Question 21

What is the Pathophysiology of Graves’ disease?

Answer 21

Question 22

How is graves orbitopathy caused?

Answer 22

Question 23

What are the symptoms of graves?

Answer 23

• Sweating aka hyperidrosis - increased metabolism and sympathetic activation means that the body is producing more heat (evaporation of seat cools the body)
• Weight loss - increased energy demand driven by increased metabolic rate might not be met by the person’s diet, causing unintentional weight loss. Muscle wasting and Gl symptoms can also contribute.
• Emotional lability - rapid mood swings. Increased T3 has an effect on the nervous system and hormones that regulate mood, emotion and behaviour i.e. serotonin and noradrenaline. Psychological impact and stress of being diagnosed can also effect sleep and therefore mood (effect of cortisol).
• Appetite increased - body’s response aims to increase calorific intake to meet demand of metabolic rate.
• Tremor/ tachycardia
• Intolerance of heat/ Irregular menstruation/ Irritability - Thyroid hormones help regulate the menstrual cycle by indirectly influencing the hypothalamic-pituitary-gonadal axis (HPG axis), this balance is disrupted in hyperthyroidism. Also, sex hormone-binding globulin (SHBG) levels are increased, decreasing the amount of free ostrogen in circulation (responsible for thickening of uterine wall)
• Nervousness — activated sympathetic nervous system ‘fight or flight’, as well as sleep disturbances, irritability and stress can contribute to nervousness.
• Goiter and Gi problems (diarrhea) - increased hormone production, autoimmune response and the influence of IRAb on the thyroid gland can cause goiter because thyroid cells undergo hyperplasia. Increased metabolic rate, increased gui motility and impaired absorption of Important nutrients can contribute to Gi symptoms. Sympathetic activation can also inituence the gut as a response to stress
• Muscle weakness - increased muscle protein catabolism and metabolic rate, increased stimulation of muscles in the sympathetic response, fatigue and stress contribute to muscle weakness.

Question 24

Hyper vs hypothyroidism?

Answer 24

Question 25

What are the differential diagnoses for hyperthyroidism?

Answer 25

Question 26

What test results would diagnose graves?

Answer 26

Bloods-
Low TSH
High free T3 and T4

• Radioiodine uptake test. For this test, you take a small, dose of radioactive iodine, called radioiodine, to see how much of it collects in your thyroid gland and where it collects in the gland. If your thyroid gland takes in a high amount of radioiodine, that means your thyroid gland is making too much thyroid hormone. The most likely cause is either Graves’ disease or overactive thyroid nodules. If your thyroid gland takes in a low amount of radioiodine, that means hormones stored in the thyroid gland are leaking into the bloodstream. In that case, it’s likely that you have thyroiditis.
• Thyroid ultrasound. This test uses high-frequency sound waves to make images of the thyroid. Ultrasound may be better at finding thyroid nodules than are other tests. There’s no exposure to radiation with this test, so it can be used for people who are pregnant or breastfeeding, or others who can’t take radioiodine.