yes Flashcards
thyroid, adrenals, pituitary
State layers of adrenal cortex and hormones produced in each
GFR - glomerulosa, fasiculata, reticulata,
SSS - salt (aldosterone), sugar (cortisol), sex (androgens)
How do steroid hormones work?
- usually bound to protein e.g. albumin in blood
- enters cell through membrane
- displaces heat shock protein (HSP) from hormone receptor to and binds to receptor to form hormone receptor complex
- complex enters nucleus and activates specific hormone response element (a short sequence of DNA within the promoter of a gene that is able to bind to a specific hormone receptor complex and therefore regulate transcription)
- more protein is made
- delayed response takes at least 4 hours but effects can last for days
How does the insulin receptor work
insulin dimer binds to receptor causing phosphorylation on its own and also through protein kinase b (pKb), which phosphorylates other things leading to glucose 4 transporter being transposed to membrane and thus decreasing glucose levels as it transports glucose into cells
How do you assess hormone levels
Radioimmunoassay
ELISA - enzyme linked immunosorbant assay
What joins to lobes of thyroid
isthmus
When is thyroid naturally enlarged?
adolescence, pregnancy, lactation and later portion of menstrual cycle
Describe blood supply of thyroid
From superior and inferior thyroid arteries
Very high perfusion rate: 4-6ml
What do parathyroids secrete and what does it do?
secrete PTH - parathyroid hormone which increases Ca2+ levels in blood (opposing effects of calcitonin secreted by thyroid’s c-cells which lower it)
State functions of thyroid hormones
- neural development in foetus
- growth in young child
- controls BASAL METABOLIC RATE i.e. digestion + metabolism
- heat generation (from digestion)
- increased gut motility
- concentrates iodine for incorporation into thyroid hormones
- contains 60-65% of body iodine concentration
- increased protein synthesis
- increased ATP turnover
- increased O2 consumption (from increased erythropoetin)
- increased number of adrenoceptors on various tissues - catecholamines more sensitive
- B receptor expression also increased (B1 on heart - increased cardiac muscle contractility)
- increased bone turnover
- increased cholesterol degradation
- increased metabolic turnover of hormones and drugs (might have to increase dosage in hyperthyroidism)
Distinguish between TRH, TSH, T3, T4, THR, thyroxine, thyroglobulin, thyrotrophs, reverse T3 (rT3), tyrosine residues, TPO (thyroid peroxidase) and TBG
TRH - thyroid releasing hormone (from hypothalamus to anterior pituitary)
TSH - thyroid stimulating hormone (from anterior pituitary to thyroid)
Thyroxine is the main hormone produced by thyroid gland, it’s free form is T4 which is made from two diiodotyrosine (DIT) molecules, it is (35%) converted to it’s more potent (x10) active form T3 in the periphery tissues cells by removing one of the iodines. T3 can then go into nucleus and bind to thyroid hormone receptor (THR). That PLUS retinoid acid forms complex that recognises sequence in DNA switching on gene transcription
T3 also provides negative feedback on TSH and TRH.
rT3 is an isomer of T3 but inactive - created by removing a different iodine from T4 (45% converted). rT3 levels can be raised in certain diseases.
Thyroglobulin is the pre-thyroxine form made of 100-129 tyrosine residues and stored in colloid of follicular cells of thyroid (though only 15-20 resides can act as substrates for iodine). Iodine is added to colloid by enzyme pendrin and attached to thyroglobulin by enzyme thyroid peroxidase (TPO). Then it is taken back out of colloid into phagosomes and lysosomes that breaks it into T3 and T4. Mainly T4 produced - higher half life.
TBG - thyroid binding globulin is what most T3 and T4 bind to in serum. Barely any of it is free in blood. Also bound to albumin and TBPA - thyroid binding pre-albumin/transthyretin
how does TSH work?
stimulated by TRH from hypothalamus
released by anterior pituitary
g-coupled protein receptor. increasing levels of cAMP which up regulates iodine pumping (co-transporter is Na into cell) thyroglobulin synthesis, iodination, endocytosis, and proteolysis; thyroid peroxidase activity; and hormone release
(in primary hypothyroidism - TRH is in v high levels and can also cause early puberty in men and hyperprolactinaemia as it affects those receptors as well)
What is myxoedema? How is it treated?
Severe hypothyroidism caused by dietary iodine deficiency (less than 50micrograms/day) leading to non-toxic goitres (enlargement of glands due to excess TSH production). Treated with iodine supplements.
What happens in excess intake of iodine in diet? What foods have a lot of iodine?
Can get goitrogens –> suppression of hormone secretion. Foods include kelp, cabbage, cassava and some local drinking waters.
Describe causes of primary hypothyroidism and investigations to diagnose them
- Hashimoto’s thyroiditis (affects 3% of population) - autoimmune disease where antibodies attach thyroglobulin, TPO, and follicular cells of thyroid. Thyroid enlarged.
Can check antibodies but 12% have TPO Abs very common - not diagnostic but a risk factor. - Atrophic thyroiditis - shrunken thyroid.
- Radiotherapy/surgery for hyperthyroidism
- Failure of delivery of thyroid hormones in foetus - called cretinism (neural deficit)
- Could simply be non-thyroidal illness - secondary drop to other illness when acutely unwell (not primary hypothyroidism)
Describe symptoms and signs of hypothyroidism
- increased body weight
- cold intolerance
- constipation
- slow reflexes
- bradycardic
- hypercholesterol
- drowsier
- decreased reflexes
- decreased sympathetic effects
- dry skin (less glycoaminoglycans made)
- hoarse voice
- slower movements
- periorbital puffiness
Describe treatments for hypothyroidism
HRT
Give synthetic T4 levothyroxine 75-125 micrograms/day or 1.6micrograms per kg
In severe cases give synthetic T3 liothyronine - shorter half-life but rapid response
Describe causes and investigations for hyperthyroidism
- Grave’s disease - autoimmune disease where antibodies constantly stimulate TSH receptor on thyroid
- Toxic thyroid nodules (have high uptake activity and produces a lot of thyroids)
RARER: - Unregulated TSH excess from pituitary tumour
- HCG mediated hyperthyroidism
- Excess thyroid hormone medication
- Thyroiditis (there are several kinds)
Do TFTs should have low TSH and high T4/T3. Test for receptor antibody in Grave’s/ Also consider uptake scan to differentiate 1 and 2 (1 will take up a lot , but if only taken up in concentrated areas it’s 2) or ultrasound.
Describe signs and symptoms of hyperthyroidism
- Nervousness/anxiety/mood or behavioural changes
- sweating
- heat intolerance
- palpitations/tachycardia
- fatigue (from anxiety)
- restlessness
- weight loss
- tremors
- thyroid bruits
- eye signs (muscles push eyes forward)
- ^ lid lag - eyes follow movement but eyelids stay retracted
- diarrhoea
- rare: AF
Descrive treatments for hyperthyroidism
First line: carbimazole and propylthiouracil (both inhibit TPO and the latter also prevents peripheral conversion of T4 to T3) - taken for 6-12 months
Also given beta blockers for heart symptoms e.g. propanolol.
If medication doesn’t work:
- Radioiodine - oral solution taken up into follicular gland cells and irradiates them. Give more than estimated because hypothyroid easier to deal with than hyper. AVOID in thyroid eye disease
- Surgery - partial to total thyroidectomy, might take more than necessary. Blood loss also a big risk + damage to larynx and nerves (give large doses of iodine LUGOL’s solution to suppress hormone production before surgery to reduce vascularity of thyroid gland)
How do you assess and manage thyroid nodules? What must you exclude?
Take TFTs, check for antibodies, do an ultrasound and fine needle aspiration/core biopsy.
90% of nodules in thyroid are benign but must exclude thyroid cancer.
If all investigations are benign no treatment necessary, consider scan for cosmetic purposes.
If malignancy is suspected either lobectomy or total thyroidectomy. q
