Week 7 - Thyroid Functions and Thyroid Disease Therapeutics Flashcards
What is the thyroid gland
- Secretes hormones:
- Thyroxine (T4) and T3
- both are iodinated hormones which maintain growth (cell proliferation) + development of tissues
- T4 = tetra-iodothyronine / thyroxine
- T3 = tri-iodothyronine- Calcitonin
- Regulates metabolism (increases body heat)
How is thyroid hormones synthesised
ATE ICE
ATE ICE
A - Active transport of iodine and sodium into follicular cells
T - Thyroglobulin (protein) formed in follicular ribosome
E - Exocytosis of thyroglobulin (leavesribosome + goes into follicular lumen) causes iodination
I - Iodination of thyroglobulin (iodine binds to thyroglobulin forming either mono-iodotyrosine (MIT) or di-iodotyrosine (DIT) )
C - Coupling of MIT and DIT = T3 AND DIT and DIT = T4
E - Endocytosis iodinated thyroglobulin goes back into follicular cell + thyroglobulin is removed and recycled
- free T3 and T4 is released into bloodstream
What does thyroid gland do in relation to T3, T4. and TSH
Synthesises T3 and T4
- We produce more T4 BUT T3 is MORE POTENT
- as T3 has higher affinity for thyroid receptor
- T4 (prohormone) can be converted into to T3 at target tissue by enzy,e
- T4 has a longer t1/2 than T3 = stays in body longer
- T4 and T3 are transported to target cells via binding to proteins (albumin + thyroxine-binding globulin)
- ONLY UNBOUND / free T3 and T4 is active
How does Negative Feedback Mechanism Work
- Hypothalamus releases thyrotropin releasing hormone (TRH)
- TRH stimulates anterior pituitary gland = release of thyroid stimulating hormones (TSH)
- TSH stimulates follicular cells in thyroid, stimulating production of T3 and T4
- When levels of T3 and T4 are high negative feedback occurs
- T3 and T4 acts on hypothalamus + anterior pituitary = ↓ production TRH and TSH
What are the causes of hypothyroidism
Lack of thyroid i.e. TSH, T3, T4
- Failure of the thyroid gland (95% cause)
- can be drug induced, iodine deficiency - Hypothalamus disease = ↓ TRH
- anterior pituitary disease = ↓ TSH
- Insensitivity to thyroid horme
What are the symptoms of hypothyroidism
- Fatigue
- Dry skin
- Weight gain but have increased apetite
- Puffy face
- Depresion
- Cosnitpation
- Muscle pain + weakness
How can you interpret biochemical results - Diagnosics for hypothyroidism
Primary hypothyroidism = ↓ T4 but ↑ TSH
- TSH is trying to compensate for low T4 but thyroid gland isn’t working
Subclinical hypothyroidism = T4 and T3 is within range but have ↑ (elevated) TSH
Decide if patient requires treatment by looking at TSH levels:
- if <10 = self limiting
- if >10 may have to consider treatment
How is primary hypothyroidism treated
Inc. monitoring, side effects
1st line = LEVOTHYROXINE (T4 replacement)
- once daily for life, 1hr before breakfast
- <65 with no heart disease = 1.6mcg/kg/day
- >65 = 25-50mcg titrated appropriately
MONITORING:
- TSH every 3 months until stable, then check TSH annualy
- in pregancy need to increase dose due to presence of more binding globulins
Other treatment:
1. Liothyronine (synthetic T3)
- only used if not recting well to levothyroxine
What are the causes of hyperthyroidism
↑ synthesis + secretion of thyroid hormone (too much)
- Grave’s disease (75% cases)
- autoimmune condition resulting in ↑ producting of thyroid receptor antibodies which act like TSH o TSH receptors - Thyroid nodules (20%)
- nodules which over produce T3 and T4 - Thyroiditis
- inflammation of thyroid gland = damages thyroid tissue = all stored hormone (T3/T4) leaks out - Drug induced
What are the symptoms of hyperthyroidism
- Warm, moist skin
- Thirst
- Weight loss but no increased apetite
- Tremor
- Insominia due to agitation
- Agitation + anxiety
- Palipitations
How can you interpret biochemical results - Diagnosics for hyperthyroidism
Primary hyperthyrodism = ↑ T4 and ↓ TSH
- have ↓ TSH due to negative feedback (have high amount os T3 and T4)
Subclinical hyperthyroidism = T4 within range but ↓ TSH
How is hyperthyroidism treated
Inc. monitoring, side effects
1st line - Carbimazole (anti-thyroid drug)
- 15-40mg until until thyroid levels within range THEN reduce to 5-15mg daily
- Reduce dose gradually then STOP (not for life)
MONITORING (before commence treatment):
- FBC (full blood count)
- LFT (liver function test)
MHRA WARNING for carbimazole
- Pancreatitis: if occurs stop medication immediately + DO NOT restart treatment
- CAN NOT give if PREGNANT (can cause cognetial malformation)
- Bone marrow supression = ↓ WBC = ↑ infection risk (with PTU too)
- Hepatoxicity (with PTU too)
OTHER TREATMENT:
1. PTU (Propylthiouracil)
- given if pregnant or breastfeeding
- history of pancreatitis
- can’t take carbimazole
- reduces production of T3/T4 and Inhibits conversion of T4 into T3
- DOSE: 200-400mg divided dose, reduce to 50-100mg
- Radioactive iodine
- 1st line for graves disease (unless pregnant, planning pregnancy, cancer)
- damages DNA = thyroid cell death = ↓ thyroid function (BUT causes lifelong hypothyroidism) - Surgery
- causes lifelong hypothyroidism
What 2 regimes can be used for anti-thyroid drugs
- Titration - block
- adjust dose regularly based on free T4 levels
- titrate dose to lowest possible which maintains thyroid levels in range
- Block and replace
- block synthesis of thyroid hormone + monitor T4 levels
- add levothyroxine to get T4 levels in range
What monitoring is required for anti-thyroid treatment
- TSH and free T4 / T3 levels every 6 weeks until in range
- AFTER in range monitor TSH every 8 weeks, then 3 months until stop treatment
- don’t need to monitor FBC, LFTs (only before starting carbimazole or if suspcious of liver damage, immune system being affected)
Patient Counselling
- report any unsual signgs, jaundice, fever, yellow eyes
- could be liver damage
- Adjust food intake to prevent unwanted weight gain
- Monitoring required
