Thyroid Flashcards
What three hormones does the thyroid secrete?
What hormone does the parathyroid secrete?
Thyroid - Thyroxine (T4) - Tri-iodothyronine (T3) - Calcitonin Parathyroid - Parathyroid hormone
The thyroid sits at what vertebral and tracheal level?
5th cervical- 1st thoracic vertebrae
2-4th tracheal rings
What is the nervous innervation of the thyroid?
Autonomic:
Parasympathetic from vagus nerve
Sympathetic from superior, middle and inferior ganglia of the sympathetic trunk
What is the arterial blood supply to the thyroid?
Superior and inferior thyroid arteries (branch of external carotid) +/- Thyroidea ima (a smaller vessel which is sometimes present)
What is the Berry ligament?
Aka posterior suspensory ligament - attaches the posteromedial aspect of the thyroid gland
Outline the basic histology of the thyroid
Organized into larger circular strutures called follicles
The cells which line the follicles are called follicular cells
In the centre of each follicle is colloid which contains tyrosine
Parafollicular C cells are found in the space between follicles - these are neuroendocrine cells important in the production of calcitonin
What is the main fuel for the thyroid gland?
Iodine
Through what process are hormones secreted from colloid into follicular cells?
Pinocytosis
What is the significance of thyroglobulin?
What is MIT and DIT?
What are the two types of thyroglobulin?
What is the chemical structure of T3 and T4?
Iodine attaches to tyrosine residues on thyroglobulin to form MIT and DIT MIT = monoiodotyrosine unit DIT = di-iodotyrosine unit Two types of thyroglobulin, according to the number of iodine attachments: - Mono - Dio T3 = MIT + DIT T4 = DIT + DIT
Of the total thyroid hormone secreted, what % do T3 and T4 make up?
Which thyroid hormones is more potent?
Which is converted to which, and where does this occur?
T4 - thyroxine ~90% of thyroid hormones secreted
T3 - triiodothyronine ~10% of thyroid hormones secreted
T3 - ~ 4 times more potent than T4 -> T3 is a very active thyroid hormone when it comes to tissue action
T4 - converted to T3 by liver & kidney
Which thyroid hormone is more biologically active?
T3
Are thyroid hormones hydrophilic or phobic?
They are hydrophobic/lipophilic – need to be bound to plasma proteins within the blood stream.
What are the three thyroid binding plasma proteins?
- Thyroxine binding globulin (TBG ~70%)
- Thyroxine binding prealbumin (TBPA ~20%)
- Albumin (~5%)
Is the bound or unbound thyroid hormone the biologically active one?
Which of these does metabolic state correlate with?
Which is measured at Ninewells?
Unbound thyroid hormone is biologically active
Metabolic state correlates more closely with the amount of free than with the total concentration in the plasma.
Free T4 and free T3 are measured
Increased thyroid binding globulin level
- What causes this?
- What effect does this have on T4?
INCREASE TOTAL T4 but not free T4
- Pregnancy
- Newborn state
- Liver problems
Decreased thyroid binding globulin level
- What causes this?
- What effect does this have on T4?
DECREASE TOTAL T4 but not fT4
- Androgens
- Large doses of glucocorticoids, Cushings S.
- Active acromegaly
- Severe systemic illness
- Chronic liver disease
- Nephrotic syndrome
Which systems does thyroxine act on?
CNS URT Gynaecology Musculoskeletal Dermatology Cardiovascular Gastrointestinal
What do thyroid hormones do to metabolic rate?
Give three ways in which they do this
Thyroid hormones ↑ basal metabolic rate
- Increase number & size of mitochondria
- Increase oxygen use and rates of ATP hydrolysis
- Increase synthesis of respiratory chain enzymes
What effects do thyroid hormones have on:
- CHO metabolism?
- Lipid metabolism?
- Protein metabolism?
Carbohydrate metabolism - increase insulin-dependent glucose uptake into cells
Lipid metabolism
- Mobilise fats from adipose tissue
- Increase fatty acid oxidation in tissues
Protein metabolism
- ↑ protein synthesis
Give three effects that thyroid hormone has on growth
- Growth hormone releasing hormone (GHRH) production & secretion requires thyroid hormones
- Glucocorticoid-induced GHRH release also dependent on thyroid hormones (permissive action)
- GH/somatomedins require presence of thyroid hormone for activity (permissive action).
What effect does thyroid hormone have on development of the foetus?
Clinical relevance?
Myelinogenesis & axonal growth require thyroid hormones
Expectant mothers with hypothyroid need treatment to increase their levels of thyroid hormone in order to prevent foetal abnormalities
What is thyroid hormone’s sympathonimetric action?
Clinical relevance?
Thyroid hormones increase responsiveness to adrenaline & sympathetic NS neurotransmitter, noradrenaline, by increasing numbers of receptors.
Cardiovascular responsiveness also increased due to this effect – increased force and rate of contraction of heart.
Pharmacology note - need to use beta-blocker e.g. PROPRANOLOL to treat symptoms in initial stages on therapy for hyperthyroidism.
How are thyroid hormones regulated?
Thyrotrophin releasing hormone (TRH) produced from hypothalamus, stimulates thyroid stimulating hormone (TSH) release from anterior pituitary.
TSH = major stimulant to release of T3 and T4 from thyroid gland.
T3 and T4 exert negative feedback control of release of TRH and TSH.
There is potential for further conversion of T3 and T4 within the periphery.
Feedback of T3 back to the pituitary and hypothalamus to complete the negative feedback loop.
What are delodinase enzymes?
What are the three types and their functions?
Subfamily of 3 enzymes (type 1, 2 and 3) important in the activation and deactivation of thyroid hormone
D2 – activates T4 >T3 in tissues.
Type I (D1) is commonly found in the liver and kidney. Type II (D2) is found in the heart and skeletal muscle, CNS, fat, thyroid, and pituitary this is the main one concerned in the interplay between T4 and T3. Type III (D3) found in fetal tissue and placenta and brain (except pituitary).
What will the values of TSH and T3/T4 be in:
- Primary hyperthyroidism
- Primary hypothyroidism
Why do these levels occur?
Primary hyperthyroidism - TSH low - T3/T4 high Primary hypothyroidism - TSH high - T3/4 - low Feedback effect on pituitary gland – this is why TSH is low in hyperthyroidism-> it’s trying to limit the production of T3 and T4. Same concept in hypothyroidism – pituitary is trying to produce more TSH.
What are the most probably causes of:
- Secondary hyperthyroidism
- Secondary hypothyroidism
Hyper - cancer
Hypo - pituitary gland failure
What will the values of TSH and T3/T4 be in:
- Secondary hyperthyroidism
- Secondary hypothyroidism
Why do these levels occur?
Hyperthyroidism - TSH high - T3/T4 high Hypothyroidism - TSH low - T4/T4 high
What will be the values of TSH, T3 and T4 in primary subclinical hypothyroidism?
TSH - high
fT4 normal
fT3 normal
What should you look out for in fT3 in hypothyroid bloods?
In both primary and secondary hypothyroidism, fT3 can be normal
What two things can be called myxedema?
Either refers to severe hypothyroidism e.g. Myxoedema coma
OR
Accumulation of hydrophilic mucopolysaccharides in the ground substance of the dermis and other tissues → doughy induration of the skin classical seen in the shins = PRETIBIAL MYXOEDEMA. This is seen in GRAVES disease (i.e. thyrotoxicosis)
Which drug is a common cause of hypothyroidism?
Amiodarone
Give five causes of Goitrous hypothyroidism
- Chronic thyroiditis (Hashimoto’s thyroiditis aka chronic thyroditis)
- Hereditary biosynthetic defects
- Maternally transmitted (antithyroid agents, iodides)
- Iodine deficiency
- Drug induced (amiodarone, lithium, IL-2, IFN-α, iodides, aminosalicylic acid)
Give four causes of non-goitrous hypothyrodism
- Congenital developmental defect
- Atrophic thyroiditis
- Post-ablative (radioiodine, surgery)
- Postradiation (e.g. for lymphoma)
Give four causes of hypothalamic hypothyroidism
Give four causes of pituitary hypothyroidism
Hypothalamic - Congenital - Infection: encephalitis - Infiltration: sarcoidoisis - Malignancy e.g. craniopharyngioma Pituitary - Panhypopituitarism : trauma – infection – infiltration - neoplasm - Histiocytosis - Pituitary metastatic deposits e.g. breast and lung) - Isolated TSH deficiency
What is the most common cause of hypothyroidism in the western world?
What does this cause?
What is significant in the history of the patient?
Which antibodies are found?
What is seen on microscopy?
Autoimmune hypothyroidism aka Hashimotos thyroiditis
Autoimmune destruction of thyroid gland resulting in reduced thyroid hormone production.
Family history of thyroid/ autoimmune disease – tends to run in families, probably to do with HLA subtypes.
Presence of Thyroid Peroxidase Antibodies (in blood)
T-cell infiltrate and inflammation on microscopy
Describe the typical natural history of hypothyroid disease?
Where in this does subclinical hypothyroidism lie?
Quite gradual onset – often takes several years before a person becomes fully hypothyroid.
Then go through a period of mild thyroid failure – T4/T3 levels start to drop (still within normal range), whilst TSH increases.
Subclinical hypothyroidism – thyroid is just managing to produce enough hormone, but is requiring a lot more pituitary stimulation to do this – can this on the graph where the T3 and T4 levels are in normal range, but TSH is high.
Name seven systems that hypothyroid can affect
CNS URT Gynaecology MSK Dermatology Cardiovascular GI
How does hypothyroidism affect the following systems in a patient? Skin/hair? Thermogenesis? Fluid retention? Cardiac? Gynae?
Hair/skin - Coarse, sparse hair - Dull expressionless face - Pale cool skin that feels doughy to touch - Vitiligo may be present Thermogenesis – cold intolerance Fluid retention – pitting oedema. Cardiac - Reduced heart rate - Cardiac dilatation - Pericardial effusion - Worsening of heart failure Gynae - Menorrhagia - Later oligo or amenorrhoea - Hyperprolactinaemia
How does hypothyroidism affect the following systems in a patient? Metabolic? GI? Resp? CNS?
Metabolic - Hyperlipidaemia - Decreased appetite - Weight gain GI - constipation Respiratory - Deep hoarse voice - Macroglossia - Obstructive sleep apnoea Neurology/CNS - Decreased intellectual and motor activities - Depression, psychosis, neuro-psychiatruc - Muscle stiffness, cramps - Prolongation of the tendon jerks - Carpal Tunnel Syndrome
What will the following bloods be like
- Size of blood cells
- CK
- Cholesterol
- Na
- Prolactin
- Macrocytosis (large blood cells, causing raised MCV) is typical – rule out a concurrent vitamin B12 deficiency
- Elevated creatinine kinase
- ↑ LDL cholesterol
- Hyponatraemia – reduced renal tubular water loss - less commonly due to co-existing cortisol deficiency
- Hyperprolactinaemia - ↑TRH leads to ↑ prolactin secretion
What are the three thyroid antibodies that we look at?
Anti-TPO
Anti-thyroglobulin
TSH receptor
What % of patient have the following antibodies: - Anti-TPO - Anti-thyroglobulin - TSH receptor In: - Graves disease - Autoimmune hypothyroidism
Graves disease
- Anti-TPO 75%
- Anti-thyroglobulin 40%
- TSH receptor 70-100%
Autoimmune hypothyroidism
- Anti-TPO 95%
- Anti-thyroglobulin 60%
- TSH receptor 15%
How should you restore the metabolic rate in hypothyroid patients?
What happens if you don’t do this?
Normal metabolic rate should be restored gradually, particularly in the elderly – can damage cardiac system if you suddenly replace thyroid hormone. Should do this over a matter of months.
Rapid restoration of metabolic rate may precipitate cardiac arrhythmias.
