13.1 - Thyroid Gland Dysfunction

Question 1

Basic anatomy of the thyroid

Answer 1

• 2 lobes joined by isthmus
• Bow tie shape
• Lies against and around front larynx and trachea
• Below thyroid cartilage and above cricoid cartilage
• Located near C7 of spine

Question 2

Thyroid embryology

Answer 2

• First endocrine gland to develop
• At 3-4 weeks gestation, appears as an epithelial proliferation in base of tongue
• Takes several weeks to migrate to final position
• First descends as diverticulum through thyroglossal duct and migrates downwards
• During migration it remains connected to tongue by thyroglossal duct, which subsequently degenerates
• If migration doesn’t occur as normal, thyroid gland will be located in a different place

Question 3

Normal stimulation of production of thyroid hormones (recap)

Answer 3

Low blood levels of thyroid hormone detected by hypothalamus → hypothalamus releases TRH into the hypophyseal portal system → stimulates anterior pituitary to produce more TSH → stimulates thyroid gland → more T3 + T4 produced

Question 4

What is hypothyroidism and primary/secondary (brief)

Answer 4

• Endocrine condition where too little thyroid hormones are produced
• Two main causes of hypothyroidism: primary and secondary (in more detail on sep cards)
• primary is where the thyroid gland is the problem ☞ not making enough T3 + T4
• secondary aka central hypothyroidism where the body doesn’t produce enough TSH
• Both types result in decreased thyroid hormone and reduced BMR

Question 5

Primary hypothyroidism (causes + features, symptoms on different card)

Answer 5

Thyroid gland problem, where it’s not making enough thyroid hormone. Increased TSH due to negative feedback. Causes include:

iodine deficiency as follicular cells don’t have enough iodine to produce T3 + T4. This is most common in countries that don’t fortify foods with iodine

hashimoto’s thyroiditis (autoimmune disorder) where T-cells and autoantibodies infiltrate the thyroid → thyroid responds to autoimmune damage by hypertrophy + hyperplasia (causes goitre) → this compensation is short lived → eventually autoantibodies cause so much follicular cell damage → destroy thyroid function altogether

treatment for hyperthyroidism ie surgery (removes thyroid tissue) or radioiodine therapy (damages too many follicular cells)

congenital hypothyroidism newborn’s thyroid gland not working properly (gland can be absent, underdeveloped, in wrong location or defective). Either sporadic (at random) or inherited gene cause.

Question 6

Secondary hypothyroidism

Answer 6

aka ‘central hypothyroidism where body doesn’t produce enough TSH. Two main causes:
- Damage to hypothalamus ie from tumours or trauma, decreasing TRH production
- Tumor in anterior pituitary: compresses gland → prevents TRH production

Question 7

Symptoms of hypothyroidism (congenital on different card)

Answer 7

• myxedema (swelling in soft tissues and skin, eg eyes and tongue). Due to increased TSH (due to negative feedback trying to stimulate the gland) → stimulates fibroblasts in skin and soft tissues → start depositing glycosaminoglycans in the interstitium
• goiter mainly in hashimoto’s thyroiditis (due to the initial hyperplasia + hypertrophy)
• weight gain despite decreased appetite (due to decreased BMR)
• sensitivity to cold as body is producing less heat
• bradycardia, mental slowness, constipation, lethargy due to decreased effects of thyroid hormone on sympathetic NS
• Other general symptoms: obesity, dry skin, alopecia, hoarse voice, constipation and slow reflexes

Question 8

Symptoms of congenital hypothyroidism

Answer 8

mainly due to decreased BMR ie excessive sleeping, however if it goes on undetected long enough, can cause:
- Mental retardation
- Intellectual disabilities
- Delayed physical growth
- Shortened height
- Poor bone development
- Slow pulse
- Muscle weaknesses
- GI disturbances
= cretinism

Question 9

How is diagnosis of hypothyroidism made (and how to differentiate between primary and secondary causes)

Answer 9

• Will have decreased T3 + T4
• Elevated TSH if primary
• Normal or decreased TSH if secondary
• In congenital hypothyroidism, screening programme in all newborns in NHS

Question 10

What is the main treatment for hypothyroidism

Answer 10

Hormone replacement therapy using thyroid hormones (most commonly synthetic T4)

Question 11

What is myxedema coma

Answer 11

• Severe and life-threatening hypothyroidism
• Complication in poorly managed cases of hypothyroidism who undergo stress, eg serious infection or surgery
• All normal symptoms of hypothyroidism are elevated eg:
  ☞ severe bradycardia
  ☞ altered consciousness
  ☞ confusion
  ☞ hypothermia

Question 12

What is hyperthyroidism (in general, causes and symptoms on separate card)

Answer 12

• Condition where excess thyroid hormones
• Aka thyrotoxicosis
• Can happen in a few different ways (causes on separate card)
• All of causes result in too much thyroid hormone
• Leads to a hypermetabolic state

Question 13

Causes of hyperthyroidism

Answer 13

graves disease in more detail on another card. Primary cause. Autoimmune disorder → B cells produce antibodies against thyroid proteins → autoantibodies can stimulate FSH → results in growth of thyroid gland + stimulates follicular cells to produce more thyroid hormones

toxic nodular goiter where one or more follicles start generating lots of THs. This could be due to a mutated TSH receptor that keeps the follicular cells inappropriately active. Primary cause

hyperfunctioning thyroid adenoma where follicular cells start proliferating. Forms a benign tumour and makes excess thyroid hormones. primary cause

inflammation or trauma to thyroid causes a large release of pre-formed thyroid hormones. Primary cause

Jod-Basedow syndrome ie iodine – induced thyrotoxicosis. Occurs after an iodine deficient person receives a large dose of iodine. primary cause

neonatal hyperthyroidism occurs in newborns who have mothers with Grave’s Disease → thyroid stimulating immunoglobulins crosses the placenta → received by baby → causes baby to generate too much THs. primary cause

pituitary tumor where a TSH secreting tumor in anterior pituitary → healthy thyroid starts generating too much thyroid hormone. secondary cause

Question 14

General symptoms of hyperthyroidism

Answer 14

• weight loss despite decreased appetite due to increased BMR
• heat intolerance as body producing excess heat
• tachycardia, sweating, hyperactivity, anxiety, insomnia due to the effect of THs on sympathetic NS
• exophthalmos ie eye bulging due to sympathetic over-stimulation of muscles controlling eye movement
  ☞ longer term risk of developing congestive heart failure and osteoporosis

Question 15

Mechanism of Grave’s Disease

Answer 15

B cells produce antibodies against thyroid proteins → produces thyroid-stimulating immunoglobulin (TSI) → binds to TSH receptors on thyroid follicle cells, imitating TSH → greater production of T3 + T4

Additionally, TSI can also stimulate thyroid hypertrophy + hyperplasia → more follicular cells → goitre

Question 16

Diagnosis of hypothyroidism

Answer 16

Blood test would show elevated T3 + T4, but very low TSH
- This is because excessive thyroid hormone are causing negative feedback to the anterior pituitary
- Therefore very low / supressed TSH levels

☞ additional tests would include radioiodine scans and iodine uptake measurements

Note: in Grave’s Disease, TSI is outside of the normal negative feedback loop, the stimulation of the thyroid gland isn’t due to TSH but is due to TSI

to diagnose Grave’s Disease there will be the presence of thyroid stimulating antibodies

an increased or normal TSH (with increased T3 + T4) would suggest a pituitary tumour

Question 17

What is the triad of symptoms for Grave’s disease

Answer 17

hyperthyroidism
Due to TSI stimulating TSH receptor. Leads to symptoms like goiter, weight loss (despite increased appetite), heat intolerance, tachycardia, sweating, hyperactivity, anxiety and insomnia

ophthalmopathy
Can cause exophthalmos in some cases (bulging of the eyeball)
- Due to build up of glycosaminoglycans (as fibroblasts get stimulated and produce these in soft tissues, skin and eyes)
- This causes swelling and inflammation around eyes
- Weakens muscles that control eye movement and upper eyelid movement
- Can damage cornea over time, as the eyes are at greater risk of drying out

dermopathy
- Can cause pretibial myxedema in some cases
- Build up of glycosaminoglycans
- Leads to non-pitting oedema and thickening of the skin
- Usually occurs over the shins

Question 18

Treatment for hyperthyroidism

Answer 18

• Will vary depending on the cause
• beta-blockers to treat immediate symptoms
• anti-thyroid drugs to block TH production and release
• radioiodine therapy to partially destroy thyroid function
• surgery required in some cases to remove the thyroid
• note that these may cause hypothyroidism

Question 19

What is a thyroid storm

Answer 19

• Life threatening complication of hyperthyroidism
• Occurs when someone stops treatment, has surgery or an infection
• Body is in severe state of hypermetabolism
• Symptoms are an exaggeration of hyperthyroidism (ie high fever, arrythmia and excessive sweating)

Question 20

Clinical investigations for thyroid

Answer 20

• Physical examination however can only feel it if it is englarged
• ultrasound but will need specialist radiologist
• radio-isotope scan where radioactive iodine is injected, and can see areas of thyroid activity with this, to see if there are toxic nodules of hyperthyroidism or supressed activity
• x-ray and CT scan to see masses (or deviated windpipe can suggest that there is a huge swelling of the thyroid)

Question 21

Different types of goitre (and possible causes)

Answer 21

• diffuse ie due to auto-immune thyroid disease or thyroiditis
• nodular can be multinodular or solitary nodule (look for red flag symptoms)
• fibrotic ie riedel’s thyroiditis (very rare)
• iodine deficiency (much more common)

Question 22

Thyroid cancer features and differential diagnosis

Answer 22

• Red flag symptoms include very young or very old patient, rapid enlargement of lump in neck, hoarse voice, dysphagia
• May have a family history of thyroid cancer
• On examination, may have hard irregular thyroid mass that is fixed to the surrounding structures
• differential diagnosis is a thyroglossal cyst, but this moves up when sticking the tongue out

Question 23

Investigation of suspected thyroid cancer

Answer 23

• Carry out thyroid ultrasound
• Fine needle aspiration to test tissue
• CT scan of thorax and mediastinum
  ☞ if suggests cancer, surgical removal and this will often give good prognosis