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.
How should you treat young patients with hypothyroidism?
What about elderly patients with a history of IHD?
Start thyroxine at 50-100 μg daily.
In the elderly with a history of IHD: start thryroxine (T4) at 25-50 μg daily, adjusted every 4 weeks according to response
When should you check TSH in any patient on thyroxine?
Check TSH 2 months after any dose change
Once stabilised, TSH should be checked on every 12 – 18 months
Why are patients treated with T4 and not T3?
No benefit of combined T4 and T3 therapy
T3 effects develop within a few hours and disappear within 24-48 hours of discontinuation
How can TSH be utilized in:
- Primary hypothyroidism
- Secondary hypothyroidism
Primary - TSH is an index of therapeutic success and potential toxicity
Secondary - TSH is not a useful index of therapeutic success – it will remain low if T4 therapy is commenced; T4 is used to monitor treatment
Myxodema coma - Who does this typically affect? - Mortality rate? - ECG? - Which type of respiratory failure? What is also present in 10% of patients?
Typically affects elderly women with long standing but frequently unrecognized or untreated hypothyroidism
Mortality up to 60% despite early diagnosis and treatment
Findings
- ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval
- Type 2 respiratory failure: hypoxia, hypercarbia, respiratory acidosis
Co-existing adrenal failure is present in 10% of patients
How do you treat myxedema coma?
- Intensive care
- Passively rewarm: aim for a slow rise in body temperature
- Cardiac monitoring for arrhythmias
- Monitor blood pressure, CVP, oxygenation, urine output, blood glucose levels
- Fluids/ fluid restrict/ electrolyte balance
- Broad Spectrum Antibiotics
- Thyroxine cautious (hydrocortisone)
How does hyperthyroidism affect the following systems?
- Cardiac?
- Sympathetic?
- CNS?
- GI?
- Thermogenesis?
Cardiac - Palpatations/ Atrial Fibrillation - Cardiac Failure (rare) Sympathetic - Tremor - Sweating CNS - Anxiety, Nervousness, Irritability, Sleep Disturbance GI - Frequent, loose bowel movements Thermogenesis - intolerance to heat.
How does hyperthyroidism affect the following systems?
- Eyes?
- Hair and skin?
- Reproductive?
- MSK?
- Metabolism?
Vision – depends on the cause of hypothyroidism
- Lid Retraction (all hyperthyroidism)
- Double vision
- Eyes that bulge out, or “protrude” (in patients with Graves’ disease)
Hair and skin
- Brittle hair, thinning hair
- Rapid fingernail growth
Reproductive - menstrual cycle changes, including lighter bleeding and less frequent periods.
Muscles - muscle weakness, especially in the thighs and upper arms.
Metabolism - weight loss despite increased appetite.
Give some common causes of hyperthyroidism in relation to:
- Autoimmune
- Nodular thyroid
- Thyroiditis
Auto-immune – Graves disease. Nodular thyroid - Multi-nodular goitre - Toxic nodule (adenoma) Thyroiditis (inflammation) - Subacute - Post-partum
Give two rare causes of hyperthyroidism
Iodine
- Medication – Amiodarone, Thyroxine
- Supplements – Kelp
Medication – lithium, Amiodarone, Thyroxine
Graves disease
- Lifetime risk?
- Age group?
- Men or women?
- Other associations?
Lifetime Risk of 2% (women), 1% (men) Younger (20-50yrs) Females > Male Other - Genetic/ FH - High Iodine intake - Smoking - ?Viral trigger
What three tests can you do for Graves disease?
- Thyroid hormone levels
- Antibodies
- Other invesigation
High T3/ T4, low TSH Antibody positive (TRAbs) SMOOTH SYMETRICAL GOITRE (Scintigraphy- high uptake/ Ultrasound)
Describe the natural history of Graves disease
At 18 months 50% will have ‘burnt out’,50% will relapse.
Once patients get it, there tends to be an up and down affect.
By about 18 months, patient may have resolved, however the other 50% still require treatment.
Gradually reduce dose of drugs at about 12 months – 50% will relapse, so consider going back onto drugs, or other treatments.
What are the main treatment principles in Graves disease?
- Lubricants
- Decompression Surgery
- Radiotherapy
- Corrective Surgery
- Stop Smoking
What is the second most common cause of an over active thyroid? Who gets it? Character of onset? What might the gland feel like? Three tests?
Nodular thyroid disease (Multinodular Goitre/ Dominant Nodule(Toxic Adenoma)) Older Patients More Insidious Onset Gland may feel nodular Tests - High T3/ T4, low TSH - Antibody negative (TRAbs) - ASSYMETRICAL GOITRE - (Scintigraphy- high uptake/ Ultrasound) – shown opposite
Thyroid storm What is this the opposite of? What is this? Which systems might collapse? Temperature? Reflexes? What might it be associated with? Treatment?
This is the opposite of myxedema coma. Severe Hyperthyroidism Respiratory and Cardiac Collapse Hyperthermia Exaggerated reflexes May be associated underlying infection Tx: Lugols Iodine, glucocorticoids, PTU, B-blockers, fluids, monitoring.
Which two drugs are given to treat hyperthyroidism?
How should you dose Graves?
Which drug can you give to control symptoms?
- Carbimazole – risk of very low blood cell drop -> if they develop a bad fever and sore throat, then should get their blood count checked for WBCs
- Propylthiouracil (preferred in pregnancy)
In Graves- start at high dose, reduce dose over 12-18 months then stop. (50% relapse risk).
Symptoms Tx (Sympathomimetic) -> beta-Blockers (propranolol).
Radio-iodine
Who gets this?
What is this?
Essentially a radioactive capsule of iodine – patients swallow this, absorbed by gut, into blood stream, into thyroid gland. While it’s in the thyroid gland, the radioactivity destroys the thyroid gland. They are most radioactive during the first couple of weeks – should avoid close contact with young children or pregnant women.
What is the most common type of thyroiditis?
Male or female?
Age group?
What might trigger it and what might it be associated with?
Natural history?
Sub-acute thyroiditis/ De Quervians
Females> Males
Age 20-50
May be viral triggered
May be associated with sore throat/fever/ other viral symptoms
Initially have an overactive thyroid, then underactive, then back to normal, occurring over about 6 months.
What are the levels of the following in De Quervians
- T4
- TSH
- Scintigraphy scan
T4- high in early stage, low in late, then normal
TSH- low in early stage, high in late, then normal
Scintigraphy Scan- LOW UPTAKE
Briefly describe the embryology of the thyroid
Give three abnormalities that can occur here
Develops from evangination of the pharyngeal epithelium. It then descends from the foramen caecum to its normal location along thyroglossal duct.
Abnormalities
• Failure of descent – lingual thyroid
• Excessive descent – retrosternal locations in mediastinum
• Thyroglossal duct cyst
What is found in the centre of each thyroid follicle?
Each follicle is surrounded by flat to cuboidal follicular epithelial cells. Within the centre of each follicle is dense amorphic pink material containing thyroglobulin.
How do C cells show on histology?
What is their function and what does this do?
These are slightly larger cells with a clearer cytoplasm which secrete calcitonin. This results in lower serum Ca levels but in practice is of little clinical significance.
Briefly describe the stages involved between TSH being released and secretion of T4 and T3
TSH binds to the TSH receptor on the surface of thyroid epithelial cells.
G proteins activate with conversion of GTP to GDP and production of cAMP.
cAMP increases production and release of T3 and T4.
What is the main cause of thyroid disease?
What are the two ends of the spectrum?
Autoimmune
Hypofunction - Hashimoto’s thyroiditis
Hyperfunction - Grave’s disease
Name three anti TSH receptor antibodies
1 Thyroid stimulating immunoglobulin - relatively specific (unlike peroxisome and thyroglobulin abs)
- Thyroid growth stimulating immunoglobulin
- TSH binding inhibitor immunoglobulins - may explain episodes of hypofunction
What will you see on histology of Graves disease?
Small follicles with scalloped edge
Abrupt follicles
Inflammatory infiltrate
Which HLA antigents is Hashimotos thyroiditis associated with?
HLA – DR3 and DR5
Polymorphisms in which two immune regulated genes are associated with Hashimotos thyroiditis?
CTLA-4 - Negative regulator of T cell responses - Polymorphisms with reduced protein level / function increase risk of auto-immune disease PTPN-22 - Inhibits T cell function
Which two anti-thyroid antibodies are found in Hashiotos thyroiditis?
When bound what do these cause?
Anti-thyroglobulin and anti-peroxidase
When bound cause antibody dependent cell mediated cytotoxicity
What is a diffuse goitre?
Who gets it?
Give two possible causes
What are the typical values of T3/4 and TSH?
A goitre where all of the thyroid is uniformly bigger - should feel smooth to touch
Sporadic – F > M, puberty and young adults
- Ingestion of substances limiting T3/T4 production
- Inborn errors of metabolism (dyshormonogenesis)
Usually euthyroid – present with mass effects.
T3 / T4 normal but TSH high or upper limit of normal.
Multinodular goitre - What does this start as? - What should be in your differential? - What will you see on histology? What are the mass effects of this?
Evolution from long standing simple goitre - get recurrent hyperplasia and involution
- Thyroid neoplasm
Rupture of follicles, haemorrhage, scarring, calcification.
Mass effects
- Cosmetic
- Airway obstruction, dysphagia, compress vessels
Thyroid adenoma
- What does it look like?
- What encapsulates it?
- What is it composed of?
- What might it progress to?
- What can it be difficult to distinguish from?
- What can it secrete?
Discrete solitary mass, usually an incidental swelling.
Encapsulated by a surrounding collagen cuff.
Composed of neoplastic thyroid follicles i.e. Follicular Adenoma.
Rarely it will enlarge to the point where you will see it and it may cause dysphagia.
Can be difficult to distinguish from
- Dominant nodule in multinodular goitre
- Follicular carcinoma
Can secrete thyroid hormones – thyrotoxicosis -> TSH independent.
Thyroid carcinomas
Male or female?
Commonest age group?
Environmental associations?
Female Predominance (except childhood & elderly)
Predominantly occur in early adulthood
Environmental associations
- Ionising radiation (papillary carcinoma)
- Iodine deficiency (follicular carcinoma)
Papillary carcinoma
- What does it look like?
- What can it sometimes present with?
- Histology?
Usually solitary nodule in thyroid
- Can be multifocal
- Often cystic
- May be calcified
Sometimes present with lymph node metastasis -> compare with follicular carcinoma.
Histology – clear nuclei which are crowded and overlapped.
Follicular carcinoma
- What does it look like?
- How/where does it spread?
Usually single nodule
- slowly enlarging, painless, non-functional
Rarely lymphatic spread but propensity for haematogenous spread -> bone, lungs, liver
Medullary thyroid carcinoma
- What is this derived from?
- Histology?
- What does it deposit?
- Which two hormones might it produce in paraneoplastic syndrome?
Derived from C-Cells (neuroendocrine) -> can secrete calcitonin.
Composed of spindle or polygonal cells arranged in nests, trabeculae or follicles.
Associated Amyloid deposition (amyloid represents deposition of an abnormally folded protein – in this case calcitonin.
Paraneoplastic syndrome
• Diarrhoea (VIP production)
• Cushings (ACTH production)
Anaplastic caricinoma
- What are these?
- Who gets them?
- What might be in the history?
- Natural history?
These are undifferentiated and aggressive tumours
Usually older patients
May occur in people with a history of differentiated thyroid cancer
Rapid growth and involvement of neck structures and death
What are the five classifications of thyroid cytology?
What should you note with this re follicular lesions?
Thy 1 – insufficient/uninterpretable Thy 2 – benign Thy 3 – atypia probably benign/equivocal Thy 4 – atypia suspicious of malignancy Thy 5 – malignant Typical nuclear features of papillary lesions can be identified but follicular lesions can be difficult to interpret as the relationship to capsule is not assessed. Follicular lesions are graded as Thy 3.
What almost always causes hypoparathyroidism?
Almost always a result of small adenomas (85 - 95%). Hyperplasia is responsible for 5 - 10% and carcinoma for about 1%.
Give some symptoms of hyperparathyroidism related to the following systems:
- Bones
- Kidneys
- GI
- CNS
- Neuromuscular
- CVS
Bone disease - pain, fracture, osteoporosis or osteitis fibrosa cystica.
Nephrolithiasis - renal stones and complications.
GI complications - constipation, nausea, peptic ulcer disease, pancreatitis, gall stones.
CNS - depression, lethargy, seizures.
Neuro-muscular - weakness and fatigue.
CVS - calcification of aortic and mitral valves.
What are the four main types of thyroid cancer?
Papillary 76%
Follicular 17%
Medullary 3%
Anaplastic 2%
Differentiated thyroid cancer
- What is this?
- What does “differentiated” mean?
- What is this cancer dependent on?
- What do they take up and secrete?
Umbrella term - this refers to Papillary and Follicular variants.
The word differentiated is crucial – makes reference to two things
1. Differentiate to a pathologist – look like normal thyroid cells
2. Functional capacity – vast majority take up iodine and secrete thyroglobulin
Differentiated thyroid cancer is TSH driven/dependent.
Most take up Iodine and secrete Thyroglobulin
Epidemiology of differentiated thyroid cancer
- Children?
- Female?
- Male?
- Afro-americans?
- Exposure to radiation?
- Uncommon in childhood
- In females, rates increase from 15-40 then plateau
- In males, steady increase with age
- Lower incidence in Afro-Americans
- Strong association with exposure to radiation
No association with diet, other proven malignancies, family history, smoking or other lifestyle factors.
How does DTC commonly present?
How does it rarely present?
Common distant metastases?
Majority present with palpable nodules i.e. a palpable lumen the neck – mostly in the thyroid. Can be a chance finding in thyroidectomy.
Small percentage are chance findings on histological section of thyroidectomy tissue.
Approximately 5% present with local or disseminated metastases (local = cervical lymphadenopathy).
Common distant metastases – pathological fractures of long bones, especially the femur.
What is the commonest histological type of DTC?
- How does it spread?
- Which thyroid condition is it associated with?
- General prognosis?
Papillary thyroid cancer
Tends to spread via lymphatics
Can also get haematogenous spread to lungs, bone, liver and brain
Associated with Hashimoto’s thyroiditis (weak association)
Prognosis generally very good with 10 year mortality < 5%
What is the 2nd commonest histological type of DTC?
- Where is incidence higher?
- How does it spread?
- General prognosis?
Incidence slightly higher in regions of relative iodine deficiency
Tend to spread haematogenously
Lymphatic spread and therefore lymph node enlargement relatively rare.
Prognosis similar to that of papillary cancer
What is the main difference between papillary and follicular thyroid cancer?
Mode of spread:
- Papillary tends to by lymphatic
- Follicular tends to be haematogenous
NB - there is a big overlap
What is the most common investigation for DTC?
What other investigations can you do?
What should you do if there is vocal cord palsy?
Ultrasound guided FNA of the lesion
- Can involve excision biopsy of lymph node
- No role for isotope thyroid scan
- No role for CT / MRI
- If vocal cord palsy suspected clinically, for pre-operative laryngoscopy – important for surgery
Give 6 clinical indicators of malignancy in DTC
- New thyroid nodule age <20 or >50
- Male
- Nodule increasing in size
- Lesion > 4cm in diameter
- History of head and neck irradiation
- Vocal cord palsy
What are the three surgical options for DTC?
- Thyroid lobectomy with isthmusectomy – half of the thyroid gland is removed along with the isthmus; leaves one half of the thyroid in situ - Dr hates this one with a passion
- Sub-total thyroidectomy – leave about 5-10% of the gland in place
- Total thyroidectomy
Which system is used for risk stratification post op in DTC?
How does it categorize patients?
AMES: A- Age M- Metastases E- Extent of primary tumour S- Size of primary tumour AMES aims to optimize the treatment to each individual patient. Patients are either given high or low risk.
Who tends to get an AMES low risk?
What is the prognosis?
How are these patients treated?
Younger patients (men <40, women <50) with no evidence of metastases.
Older patients with intrathyroidal papillary lesion or minimally invasive follicular lesion and primary tumour < 5cm and no distant metastases.
20 year survival for AMES low risk group is claimed to be 99%.
Majority of these patients will have surgery and not be put forward for radioactive treatment.
AMES high risk
- Who gets this?
- 20 year survival?
This is all patients with distant metastases.
Extrathyroidal disease in patients with papillary cancer.
Significant capsular invasion with follicular carcinoma.
Primary tumour > 5cm in older patients.
20 year survival in AMES high risk is 61%.
Thyroid Lobectomy with Isthmusectomy
- How commonly is this done?
- What do you run the risk of?
- Who gets this?
This is now relatively uncommon, and both patients and surgeons don’t like it.
You run the risk of leaving some cancer in the other half of the thyroid.
- Papillary microcarcinoma ( < 1cm diameter)
- Minimally invasive follicular carcinoma with capsular invasion only
- Patients in AMES low risk group
Lymph node surgery in DTC
- What does lymph node spread depend upon?
- Practical problem?
- Treatment for a patient with macroscopic lymph node disease?
- Treatment for a patient with papillary tumour?
- Treatment for a patient with follicular tumour?
Lymph node spread at diagnosis depends on histology - papillary 35-60%, follicular 20%.
Within the cervical region there are 50-60 lymph nodes and if you tried to take them all out it would take all day. The surgeon is selective and only removes some.
Patients with macrosopic lymph node disease should undergo nodal clearance.
Current practice in Tayside is for central compartment clearance and lateral lymph node sampling for papillary tumours -> if there are any enlarged in the lateral compartment, they will be removed as well.
Role in follicular cancer unclear, but current practice is to perform central lymph node clearance.
What should postoperative care of a patient with DTC involve?
- Calcium checked within 24 hours
- Calcium replacement initiated if corrected Calcium falls below 2 mmol/l
- Intravenous calcium for calcium levels below 1.8 mmol/l or if symptomatic
- Patient discharged on T3 or T4
Whole body iodine scanning
- Who is this performed in?
- How recent must this have been?
- Which drugs have to be changed in anticipation?
- What do you want to be high? Why?
Used in patients who have undergone sub-total or total thyroidectomy
Usually performed 3-6 months post-op
T4 (thyroxine supplements) stopped 4 weeks prior to scan
T3 (if they’re on T3 instead of thyroxine) stopped 2 weeks prior to scan
You want the TSH levels to be high – either remove thyroxine or give them TSH
- rhTSH is far better as no need to stop T3/T4
- TSH should be greater than 20 for best results
Basically trying to make the cancer cells hungry for iodine
How do you elevate TSH in anticipation of whole body iodine scanning?
Two IM injections
Describe what happens on each day of the week that a patient receives whole body iodine scanning
rhTSH injections Monday/Tuesday
2-4 mCi (75-150 MBq) I-131 administered as capsule on Wednesday
Patient returns for imaging on Friday
Results of scan inform treatment decision
Where is iodine usually taken up into (useful to know for whole body iodine scanning)
Salivary glands
Gastric mucosa
Bladder
Thyroid remnant ablation
- How is the patient prepared?
- What capsule do you give the patient?
- What are the side effects of this?
- When are they admitted and discharged?
- How do patients manage their thyroid hormone level after this?
Injection of TSH will have worn off now, so you need to elevate the TSH again to excite the cancer cells
- Pre-treated with rhTSH as before
2 or3 GBq capsule of I-131 administered – roughly 250x the dose used for the scan
Few side effects - sialadenitis, sore throat
Admitted on the Wednesday – have to stay until the radiation has fallen below a certain number, usually about 48 hour stay
Normally, after completion of TRA and scans, patients maintained on T4
Basically use thyroxine to suppress the TSH -> improves prognosis if they have a suppressed TSH in the long term. The risk of recurrence is significantly less.
Post thyroid remnant ablation
- What can be used as a tumour marker?
- Why
- What should you do for patients who have antibodies to this?
- Why does this make lobectomy annoying?
Thyroglobulin
Thyroglobulin is produced by only thyroid cells and thyroid cancer cells. If a patient has been treated surgically and with radioactive iodine, their thyroglobulin level should be 0. If it is detectable, then there are still active cancer cells somewhere in their body.
Some patients have antibodies to thyroglobulin -> you have to do whole body scans every 6 months for these patients.
If the patient still has half of the thyroid still in place, that half continues to produce thyroglobulin -> makes interpretation of a thyroglobulin result almost impossible.
What are the long term effects of TRA?
Doubles the risk of leukaemia, but still a very small risk.
No convincing evidence of increase in incidence of other solid tumours.
No evidence of infertility or subsequent genetic abnormalities in children.
NB – don’t give this to pregnant women.
How is recurrent DTC detected?
When is it most likely to come back?
Can be detected clinically, by rising Tg, or by imaging. Usually detected by routine bloods of thyroglobulin.
Most likely to come back within two years of treatment – radioactive iodine destroys most but not all of the cancer cells. This manifests itself with a raise of thyroglobulin level.
If you get to two years with a negative thyroglobulin, then you can relax a little.
NB – you can get raised thyroglobulin with only a very little number of cells – this won’t show up on scan, but you should still retreat the patient.
