Thyroid Flashcards
Parafollicular cells
Occasional scattered C cells
- Slightly larger cells with clearer cytoplasm
- Secrete calcitonin
- Lower serum Ca but in practise is of little significance
Causes of Hyperthyroidism
Graves disease Hyperfunctioning nodules/tumours Thyroiditis TSH secreting pituitary adenoma (rare) Ectopic production (struma ovarii) Factitious (exogenous intake)
Struma ovarii
Literally a goitre of the ovary, containing thyroid tissue
Palpation thyroiditis
Palpation thyroiditis refers to the development of thyroid inflammation due to mechanical damage to thyroid follicles. This can occur by vigorous repeated palpation (as with thyroid examination) or surgical manipulation (as can occur with radical neck dissection)
Subacute lymphocytic thyroiditis
Subacute lymphocytic thyroiditis features a small goiter without tenderness. This condition tends to have a phase of hyperthyroidism followed by a return to a euthyroid state, and then a phase of hypothyroidism, followed again by a return to the euthyroid state. The time span of each phase can vary; however, each phase usually lasts 2-3 months
Can be diagnosed by radioactive iodine uptake test
During hyperthyroid period, uptake is suppressed. During hypothyroid it is incresased
de Quervains Thyroiditis
Hyperthyroid
Hypothyroid
Euthyroid
Distinguishing between subacute thyroiditis and Graves disease
The clinical presentation during the hyperthyroid phase can mimic those of Diffuse Toxic Goiter or Graves’ disease. In such cases, a radionuclide thyroid uptake and scan can be helpful, since subacute thyroiditis will result in decreased isotope uptake, while Graves’ disease will generally result in increased uptake. Distinguishing between these two types of disease is important, since Graves’ disease and Diffuse Toxic Goiter can be treated with radioiodine therapy, but subacute thyroiditis is usually self-limited and is not treated with radioiodine.
Riedel’s Thyroiditis
Riedel’s thyroiditis is characterized by a replacement of the normal thyroid parenchyma by a dense fibrosis
Who does Grave’s disease tend to affect?
F:M 10:1
Age 20-40
When might you see antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin?
Grave’s Disease
Anti-TSH receptor antibodies
Thyroid stimulating immunoglobulin
Relatively specific (unlike peroxisome and thyroglobulin abs)
Thyroid growth stimulating immunoglobulin
TSH binding inhibitor immunoglobulins
May explain episodes of hypofunction
Triad of features of Grave’s disease
Hyperthyroidism with diffuse enlargement of the thyroid
Eye changes (exophthalmos)
Pretibial myxoedema
Why do you get eye changes in hyperthyroidism?
The eye changes result from fibroblasts etc expressing TSH receptors
Hashimoto’s Thyroiditis
Affects middle aged women
Associated with other AI disease
Associated with HLA – DR3 and DR5
Causes of hypothyroidism
Hashimoto’s Thyroiditis
Iodine deficiency, drugs, post therapy (surgery, 131 I, irradiation)
Congenital abnormalities
Inborn errors of metabolism
Which has a longer half life, T3 or T4?
T4.
T4 is also the major form of thyroid hormone in the blood
People most likely to develop Hashimoto’s thyroiditis?
F:M 10-20:1
Ages 45-60
Gene Polymorphisms associated with Hashimoto’s Thyroiditis?
CTLA-4
PTPN-22
What may preceded hashimoto’s thyroiditis?
Hashitoxicosis
What does hashimotos thyroiditis put you at a greater risk of?
Other autoimmune diseasea
Increased risk of developing B cell non- Hodgkin’s lymphoma in affected gland
What are goitre’s often caused by?
Lack of iodind
Diffuse Goitre
Endemic - >10% population affected
Sporadic – F > M, puberty and young adults
Ingestion of substances limiting T3/T4 production
Inborn errors of metabolism (dyshormonogenesis)
Most cases – cause unknown
Usually euthyroid – present with mass effects
T3 / T4 normal but TSH high or upper limit of normal
In children dyshormonogenesis may cause cretinis
T3/T4 and TSH levels in diffuse goitre?
T3/T4 levels normal
TSH high or upper limit of normal
Multi-nodular goitre differential diagnosis?
Thyroid neoplasm
Multi-nodular goitre
Evolution from long standing simple goitre
Recurrent hyperplasia and involution
Enlargement can be impressive
DDx thyroid neoplasm
Variation of response of follicular cells to external stimuli
Mutations of TSH signaling pathway.
Rupture of follicles, haemorrhage, scarring, calcification
Mass effects
Cosmetic
Airway obstruction, dysphagia, compress vessels
May develop autonomous nodule – hyperthyroid
10% after 10 years
Low risk of malignancy (<5% but not 0)
What does the thyroid produce?
Tri-iodothyronine
Thyroxine
Calcitonin
What cells secrete calcitonin?
Parafollicular C cells
Structure of the thyroid gland tissue
Follicular cells
Colloid – tyrosine-containing thyroglobulin filled spheres enclosed by follicular cells
Parafollicular cells
What do the follicular cells make?
T3, T4 and thyroglobulin
Which organs can convert T4 into T3?
The liver and the kidney
What type of receptors does T3 bind to?
Nuclear receptors
Are T3 and T4 lipophilic? And if so what do they bind to?
Yeah
thyroxine binding globulin (TBG ~70%)
thyroxine binding prealbumin (TBPA ~20%)
Albumin (~5%)
Plasma protein which binds the most T3 and T3
Thyroxine binding globulin (70%)
What is TTR?
Transthyretin, a T4 carrier
Phenytoin
Anti-epileptic
Can cause decrease in TBG
Clofibrate
Cholesterol lowering drug
Can cause increased TBG
Thryoid hormone effects on carbohydrate metabolism
Increases blood glucose due to stimulation of gluconeogenesis and glycogenolysis
Thyroid hormone effects on protein metabolism
Increases protein synthesis
Thyroid hormone effects on lipid metabolism
Mobilises fats from adipose tissue
Increases fatty acid oxidation in tissues
Thyroid hormone and growth
- Thyroid hormone needed for production and secretion of growth hormone releasing hormone (GHRH)
- Thyroid hormone needed for glucocorticoid stimulated release of GHRH
- Growth hormone/somatomedins require thyroid hormone for activity (permissive action)
Thyroid hormone and foetal/neonatal brain development
Thyroid hormone needed for myelinogenesis and axonal growth
Thyroid hormone and normal CNS activity
Hypothyroidism - slow intellectual functions
Hyperthyroidism – nervousness, hyperkinesis & emotional lability
Thyroid hormone Sympathomimetic action
Permissive Sympathomimetic action
- 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
Thyroid hormone regulation:
- Low temperature
- Stress
- Circadian rhythm
- Low temperatures - In babies and young children, exposure to cold environments stimulates TRH release which stimulates TSH release and so increases T3 &T4 release from thyroid
- Stress – inhibits TRH & TSH release
- Circadian rhythm – thyroid hormones highest late at night, lowest am
Thyroid stimulating immunoglobulin
Hyperthyroidism - Grave’s disease
Autoimmune disease – Thyroid stimulating immunoglobulin (TSI) acts like TSH but unchecked by T3 & T4
Which 2 hormones can lead to insulin resistance in mothers?
Human placental lactogen
Progesterones
(insulin resistance may lead to raised blood glucose if predisposed and then gestational diabetes.)
Which trimester does gestational diabetes develop?
Third trimester
In which trimester does the baby begin to make its own insulin?
Third trimester (it is a major growth factor)
How much folic acid would you give to mothers with gestational diabetes?
5mg
If a woman has gestational diabetes, what test should you carry out SIX WEEKS AFTER BIRTH to ensure resolution
Glucose tolerance test ;)
You should also do an annual fasting glucose
hCG levels in hyperemesis gravidarum?
hCG HIGH
50-60% have abnormal TSH/fT4
What hormone increases TBG?
Oestrogen
Where is T4 converted to T3?
Liver and kidneys
Why do thyroxine hormones bind to protein and which proteins do they bind to?
T3 &T4 are hydrophobic/ lipophillic - so bind to plasma proteins
thyroxine binding globulin (TBG ~70%)
thyroxine binding prealbumin (TBPA ~20%)
Albumin (~5%)
Which hormones are required for production and secretion of GHRH?
Thyroid hormones
Glucocorticoid-induced GHRH release also dependent on which hormones?
Thyroid hormones
Myelinogenesis & axonal growth of the foetal and neonatal brain require which hormones?
Myelinogenesis & axonal growth
Thyroid hormones and effect on responsiveness to adrenaline and noradrenaline?
And effect on the heart?
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
Thyroid hormone regulation and stress?
inhibits TRH & TSH release
Low temperatures and thyroid regulation?
In babies and young children, exposure to cold environments stimulates TRH release which stimulates TSH release and so increases T3 &T4 release from thyroid
Primary or secondary thyroid dysfunction is associated with goitre?
Primary (gland) failure – may be associated
with enlarged thyroid (goitre)
Secondary to TRH or TSH (no goitre)
Lack of iodine in diet (may be associated with goitre
In adults – Myxoedema – puffy face, hands & feet
Babies - Cretinism – dwarfism & limited mental functioning due to deficiency of thyroid hormones present at birth
Hypothyroidism
Thyroid stimulating immunoglobulin?
Autoimmune disease – Thyroid stimulating immunoglobulin (TSI) acts like TSH but unchecked by T3 & T4
Exophthalmos – bulging eyes due to water retaining carbohydrate build up behind eyes
Goitre –enlarged thyroid gland
