Endocrine Health - Lecture 6 Flashcards
Describe the HPT axis and the role of the various hormones incl.
TRH
TSH
T4
T3
RT3
D1, D2, D3
TRH = Released by the hypothalamus - Stimulates TSH release from the anterior pituitary.
TSH = Stimulates thyroid hormone production. Released by pituitary gland. Activates iodide uptake via the sodium / iodide symporter (SIS).
T4 = AKA thyroxine. Approx. 90% of secreted thyroid hormone. Weak ‘thyroid’ activity — ‘inactive’ form.
T3 = 4 x the ‘strength’ of T4. Increases growth, bone and CNS development, increases BMR, heart rate and activates metabolism. T3 is mostly created in the peripheral tissues around the body where it is needed.
RT3 = Biologically inactive — protects tissues from
excess thyroid hormones.
- Iodothyronine deiodinases are selenoproteins regulating thyroid hormone homeostasis.
- Deiodinase-1 (D1) and deiodinase-2 (D2) convert T4 to T3.
- Deiodinase-3 (D3) coverts T4 to Reverse T3 (RT3).
Name 3 nutrients key for thyroid hormone synthesis and explain how they are involved?
- Tyrosine and iodine: Thyroid peroxidase (TPO) catalyses iodination (a reaction in which iodine is introduced) of tyrosine residues in thyroglobulin to form T4 and T3 (a pro-oxidant process). Takes tyrosine and add iodine to it => thyroglobulin.
- Iron: TPO is haem-dependent (assess iron status).
- Selenium and zinc: Enzyme co-factors and receptor function. Zinc is a co-factor all the way. And selenium key for the conversion of T4 to T3. Selenium also antioxidant function in the thyroid tissue via glutathione.
- Vitamin D: Immune modulation in autoimmune thyroid disorders (AITD) and VDR polymorphism (shown to predispose to AITD).
- Vitamins A, C, E, B2, B3, B6, B12: Support synthesis and function. B vitamins support the energy system and metabolism.
- Copper: A cofactor of deiodinase enzymes.
Give 3 iodine rich foods?
What food is supplemented with iodine in the uk?
Sea vegetables; ocean fish and shellfish such as cod and scallops; eggs and dairy foods (due to the fortification of animal feed) with small amounts in plants depending on the soil.
In the UK the dairy food is supplemented with iodine.
Causes of Iodine deficiency?
- Dietary deficiency (see food sources above).
- Increased risk – low/no dairy/fish, pregnant (iodine requirements increase in pregnancy), vegans.
- High goitrogen intake (e.g., soya, millet peanuts, pine nuts and raw brassicas) — goitrins, thiocyanates and nitriles in foods ↓ iodine uptake and have anti-TPO activity. Goitrogen block iodine receptors – only a pb when raw (too much soy milk, coleslaw, peanuts excess). Not a huge issue in the diet for most people.
What are goitrogen and how do they impact iodine?
High goitrogen intake (e.g., soya, millet peanuts, pine nuts and raw brassicas) — goitrins, thiocyanates and nitriles in foods ↓ iodine uptake and have anti-TPO activity. Goitrogen block iodine receptors – only a pb when raw (too much soy milk, coleslaw, peanuts excess). Not a huge issue in the diet for most people.
Causes of excess iodine
- The Wolff-Chaikoff effect helps reject excess iodine and hormone synthesis. The effect is inhibited in certain individuals leading to induced subclinical or clinical hypothyroidism.
- Consumption of over-iodised salt, animal milk rich in iodine (fortified), iodine-containing dietary supplements.
- Radiocontrast dyes; medications (e.g., amiodarone — used for heart arrythmias and contains iodine).
What symptoms of excess iodine?
Excess iodine can cause hyperthyroidism, hypothyroidism and a goitre (the thyroid gland swells up in the neck because try too hard to create thyroid hormone).
How much T4 and T3 is secreted by the thyroid gland?
What is peripheral conversion?
- The thyroid secretes approx. 80–100 mcg of T4 and 10mcg T3 daily.
- Only 10% of circulating T3 is derived directly from thyroid secretion.
- Remaining 90% is obtained via ‘peripheral conversion’ from T4.
- T4 is converted in peripheral tissues (liver and kidney) to active T3 or inactive reverse T3. The hormones are metabolised by deiodination, sulphation and glucuronidation. Consider detoxification protocols. To get rid of thyroid hormone via the detox pathway.
What is RT3? When does RT3 peripheral conversion occurs?
What pathology can high RT3 present as?
- RT3 — biologically inactive but can bind to T3 receptors, blocking the action of T3. Increase in RT3 = decrease in T3!
- ↑ T4→RT3 increases in:
– Chronic / critical illness — a normal response to ↓ metabolism states — called Low T3 Syndrome.
– High stress (cortisol); zinc, selenium or iron deficiency; liver dysfunction and fasting / significant caloric restriction, advancing age (liver / kidney function), myocardial infarction. - ↑ RT3 can present as hypothyroidism.
Name 4 HTP disruptors?
HPT disruptors: Interfere with HPT axis, thyroid hormone synthesis, secretion, transport, metabolism and function.
* Pesticides: Alter hepatic enzymes, reducing T4 half life. Glyphosate lowers TSH with reduced gene expression for D2, D3 and transporters.
* PCBs (POPs) and bisphenols (e.g., BPA): Affect thyroid hormone receptors.
* Phthalates: Affect synthesis, metabolism and transport.
* Perchlorates (e.g., nitrate fertilisers and food packaging):
Block Na-I symporter, inhibiting iodide uptake.
Can also cause lower levels of T3 in breast milk.
*Halogens = fluoride, chlorine, bromine
Name the 3 halogens disruptors to thyroid functions and where they can be found?
Halogens — disrupt thyroid functioning:
* Fluoride — in toothpaste, tap water and pesticides. Interferes with the sodium iodide symporter (SIS) (= ↓ iodine uptake) and iodothyronine deiodinase (= ↓ T4 to T3 conversion).
The effect seems to be mitigated by adequate iodine status.
* Chlorine — swimming pools, PCBs — ↑ TSH, ↑ thyroid antibodies.
* Bromine — in pesticides, PBDEs (flame retardants used in textiles, farmed fish).
Give 4 tips to avoid HPT disruptors
- Drink filtered water.
- Opt for fluoride-free toothpaste.
- Eat organic.
- Avoid farmed fish.
- Avoid processed foods / beverages.
- Limit time spent in chlorinated pools.
- Avoid plastic packaging.
- Select organic textile products.
- Use natural cleaning products
- Look at detoxification – when in the real world cannot be avoided. How can we help a client detoxify them.
Name 2 medications with effect on thyroid function
- Decrease TSH secretion: Dopamine (L-dopa used in Parkinson’s, antidepressant can increase dopamine levels), glucocorticoids, lithium (anti-psychotic).
- Alter T4 and T3 metabolism: Phenytoin (anti-seizure medication), rifampicin (antibiotic).
- Reduce conversion T4 to T3: Beta-blockers (to interfere with adrenaline receptors because of stress and CVD), amiodarone (NSAIDs).
- Reduce T4 and T3 binding on thyroid receptors: Diuretics, NSAIDs.
- Increase thyroglobulin: Oestrogen (HRT, OCP), tamoxifen (oestrogen blocker in breast cancer).
- Hyperthyroid medications may induce hypothyroidism 10–20 years later in Grave’s disease. If the Dr use strong medication it can cause issues later on in life.
Name 2 medications with effect on thyroid function
- Decrease TSH secretion: Dopamine (L-dopa used in Parkinson’s, antidepressant can increase dopamine levels), glucocorticoids, lithium (anti-psychotic).
- Alter T4 and T3 metabolism: Phenytoin (anti-seizure medication), rifampicin (antibiotic).
- Reduce conversion T4 to T3: Beta-blockers (to interfere with adrenaline receptors because of stress and CVD), amiodarone (NSAIDs).
- Reduce T4 and T3 binding on thyroid receptors: Diuretics, NSAIDs.
- Increase thyroglobulin: Oestrogen (HRT, OCP), tamoxifen (oestrogen blocker in breast cancer).
- Hyperthyroid medications may induce hypothyroidism 10–20 years later in Grave’s disease. If the Dr use strong medication it can cause issues later on in life.
Explain the link between the gut microbiome and thyroid function? Especially in AITD
- Gut dysbiosis negatively affects thyroid function.
- Microbes regulate iodine uptake, degradation, and enterohepatic cycling.
- A healthy gut also help absorption of vitamins and minerals needed for thyroid functions.
- In AITD (autoimmune thyroid condition), low SCFA production (like butyrate important for gut wall integrity as feed gut wall bacteria and help reduce inflammation)is common, as is elevated zonulin (intestinal permeability – gate keeper in the guts that regulates the opening of that gut channels) and elevated serum LPS→ chronic low-grade inflammation. Gut health can help ameliorate the AITD – avoid leaky guts.
- Leaky guts give the immune system a target to attack which increases inflammation in the body and can lead to AI.
What are the Optimal ratios: FT3 / FT4 and T3 / RT3 ?
Optimal ratios:
FT3 / FT4 > 0.33
T3 / RT3 > 6
Thesting interpretation of:
1. High TSH / Normal T4 / Normal T3
2. High TSH / Low T4 / Low-Normal T3
3. Low TSH / Normal T4 / Normal T3
4. Low TSH / High-Normal T4 / High-Normal T3
5. Low TSH / Low T4 / Low T3
- High TSH / Normal T4 / Normal T3 => Subclinical hypothyroidism
- High TSH / Low T4 / Low-Normal T3 => hypothyroidism
- Low TSH / Normal T4 / Normal T3 => subclinical hyperthyroidism
- Low TSH / High-Normal T4 / High-Normal T3 => hyperthyroidism
- Low TSH / Low T4 / Low T3 => Secondary hypothyroidism
What is the optimal level of TSH? total T4 ?
TSH 0.4 - 2.5
T4 70-150
What is an accurate way to measure iodine?
What is an iodine level goal?
What is the level for iodine deficiency? And a severe iodine deficiency?
- Urine iodine test — an accurate way of measuring iodine status.
Iodine goal = A urinary first morning iodine level of:
✓ 100–199 mcg / L in children and adults.
✓ 150–249 mcg / L in pregnant women.
- < 100 mcg / L in children and non-pregnant adults = iodine insufficiency.
- < 20 mcg / L = severe deficiency.
Barnes basal body temperature test? How is it perform? What can it indicate? What are the issues with it?
- The theory is that waking axillary temperature is diagnostic for low thyroid, if < 36.5ºC.
- Useful indicator, but not diagnostic. Take for 7 days upon awakening, before any activity and calculate average.
- Issues: Circadian changes, illness, menstrual changes, sedentary lifestyle, light exposure, alcohol intake can give false readings. Does not correlate with core body temp.
What are physical examinations to asses the health of the thyroid gland?
Thyroid gland enlargement, dry skin, nail beading, thinning eyebrows, hair loss, low blood pressure, bradycardia (< 60 BPM).
What are the 5 classifications of hypothyroidism?
- Primary: Pathological processes are within the thyroid gland. TSH is higher due to low T4 and T3 (e.g., iodine deficiency, autoimmune, viral infections, drug induced, postpartum).
- Secondary: Pathological processes are within the pituitary gland — inadequate TSH to signal the thyroid gland to release more hormones. TSH is low (hypopituitarism).
- Tertiary: Inadequate TRH (hypothalamic disease) – quite rare.
- Peripheral: Insensitivity to thyroid hormones. Normal test results but symptoms – are they insensitive to those hormones? Is the level of thyroid hormone enough to meet their needs?
- Subclinical: TSH is slightly elevated and T4 is normal. T4 to T3 conversion issues, ↑RT3 or thyroid cell receptor resistance.
5 general signs and symptoms of hypothyroidism?
- Fatigue. Long standing fatigue, consistent and persistent throughout the day. Slowdown of the metabolic rate of the mitochondria.
- Weight gain / inability to lose weight – glucose is converted to fat because of the metabolic slow down.
- Heavy or irregular menstrual periods => low fertility, miscarriage, low libido
- Puffy face, swollen eyelids, oedema
- Intolerance to cold, cold extremities
- Joint and muscle pain / weakness
- High cholesterol (usually LDL)
- Dry skin, elbow keratosis, brittle nails
- Hair loss / thinning of hair and eyebrows
- Brain fog / concentration problems
- Depression
- Easy bruising
- Constipation
- Gas / bloating
- Headaches
- Low libido
- Fertility problems
- ↑ miscarriage risk
- Goitre
- Bradycardia
- Carpal tunnel syndrome
What is subclinical hypothyroidism? What diseases is it linked to?
- Elevated TSH levels with normal free T4 levels. Often undetected (up to 10% of the population) and requires naturopathic support.
- Linked to an increased risk of heart failure, coronary artery disease events and infertility. Fertility improves and miscarriage risk reduces when addressed.
- It can cause cognitive impairment, fatigue, and altered mood.
- Higher serum TSH levels (> 10 mU / L) and thyroid autoantibodies, increase the risk of SCH progression to overt hypothyroidism. 25
- Optimal status is a TSH of 2.5 or less. Over 4 increased risk of heart disease later. Over 10 you can get huge problems.
Cause and risk factor of thyroid issues
- Iodine deficiency or iodine excess (in susceptible individuals) — see earlier, including goitrogens. Careful because Iodine excess can be a problem too especially in AI!!
- Women — more common in women, possibly due to increased rates postpartum, during and post menopause. Autoimmunity is also higher in women.
- Increasing age (peak in 4th decade).
- Drug induced: E.g., amiodarone and lithium.
- Congenital (rare) — absence / underdevelopment of thyroid gland and enzymes required for hormone synthesis and iodide transfer.
- A lack of other nutrients (i.e., tyrosine, iron (TPO), selenium, zinc (Deiodinase) enzymes), vitamin D, vitamins C, E, B2, B3, B6, B12, copper). Low protein can lower tyrosine.
- Postpartum thyroiditis — autoimmune thyroiditis which flares as a result of immunologic ‘rebound’ from the relative immunosuppression of pregnancy.
- Chronic stress — inhibits TSH release, ↓ D1
↓ T3, ↓ thyroid hormone receptor sensitivity and ↑ RT3. Also = immunological shift from Th1 to Th2 — predisposing to AITD. - Infection/inflammation – inflammatory conditions or viral infections can = transient hyperthyroidism followed by transient hypothyroidism
- Alcohol — directly suppresses thyroid function, indirectly blunts TRH response. Chronic use can reduce peripheral thyroid hormones.
- Smoking — Cyanide in cigarettes is
converted to thiocyanate during its detoxification, which disrupts iodine absorption. - Post-ablative therapy or surgery — thyroid damage can occur after thyroid or other neck surgery, radioiodine therapy.
- Hereditary link — 23.6% of mothers with children with Hashimoto’s thyroiditis had a history of thyroid dysfunction.
What is Hashimoto Thyroiditis ? How does it look like on blood test? Which virus are often implicated?
Hashimoto’s thyroiditis (HT) = an autoimmune disease that attacks thyroid tissue causing reduced thyroid hormones.
* Female-to-male ratio is at least 10:1.
* ↑ TSH, low FT4, ↑ antithyroid peroxidase (TPO) antibodies.
* Anti-thyroglobulin (anti-Tg) and TSH receptor- blocking antibodies (TBII) may also be present.
* EBV and H. pylori are often implicated.
* Early disease: Individuals often exhibit signs and symptoms with tests revealing hyperthyroidism or normal values due to the intermittent nature of destruction of thyroid cells.
* HT is often diagnosed late.
* Reason: menopause and hormone changes, post-partum, high oestrogen, inflammation.
* A stimulus in the body may start the disease – EPV and H. Pylori both linked (viral or bacterial pathogen)
Hashimoto causes and risk factors ?
- Excess iodine — highly iodinated thyroglobulin is more immunogenic. Makes it more visible to the immune system to target.
- Genetic polymorphisms — VDR, MTHFR (link to AITD).
- HT often co-exists with coeliac disease. Gluten-free diets have been shown to reduce antibody titres.
- Gut dysfunction, gluten and dairy intolerance. GF diet has been shown to reduce antibodies.
- Sleep apnoea and HT may influence each other.
- Heavy metals — mercury, lead, cadmium ↑ TGO antibodies. Metallothioneins (selenocysteine) in the thyroid bind to cadmium and help take them out.
- Triclosan — found in personal care products e.g., toothpastes. Resembles structure of thyroid hormones. Can act as a blocker as well.
- ↑ pro-inflammatory cytokines e.g., IL-6, TNF- α, IL-12, IL-10. Background of someone Hashimoto’s
Hypothyroidism natural approach? Addressing triggers and mediators
- Address triggers and mediators (identify the cause!):
* Optimise micronutrient status — support T4 to T3 conversion (see following slides). Review iodine status (low / excess). Consider nutritive herbs such as nettle (e.g., nettle tea).
* Optimise digestion — e.g., digestive bitters, enzymes, pre and pro biotics etc. Reduce permeability
* Support methylation — folate, B12, B6, B2, choline, betaine, zinc. Consider genetic testing. Folate cycle (methyl folate) that feeds into the NS function via biopterin which helps make tyrosine which is key for Thyroid hormone synthesis. Tyrosine makes dopamine and adrenaline => support NS. Do we have enough tyrosine from the diet and if not, are we borrowing methyl folate from the methyl folate process to synthesised tyrosine. We do need sufficient methyl folate especially If being drained in other areas. We need to be mindful of stress using the tyrosine for adrenaline.
* Remove thyroid disruptors (see previous slides).
* Address possible dysbiosis/SIBO (investigate) — common in HT (see GI health). Importance of SCFA.
* Address stress, support HPA axis (positively influences HPT axis).
See fiche for naturopathic approach to hypothyroidism (4 steps)
Use and dosage of selenium for hypothyroidism
Selenium (Se)
Supplement dosage of selenomethione: 150‒200 mcg / day
- Antioxidant, anti-inflammatory, ↑ T3.
- Selenoenzymes: Glutathione
peroxidases (GPX – key endogenous antioxidant), thioredoxin
reductases (TR – antioxidant at cellular DNA level), deiodinases enzymes and
selenoprotein P (contain selenocyetine – antioxidant in thyroid tissues) play key roles in thyroid function. - Narrow therapeutic range — excessive levels may enhance the effects of iodine deficiency, while proper supplementation may alleviate iodine excess.
- ↓ inflammatory cytokines and thyroid antibodies.
- Use it with other antioxidant such as vitamin A,C and E and Zinc or likely to be as part of a thyroid complex supplement.
Use and dosage of zinc for hypothyroidism
Zinc
Supplement dosage: 15–30 mg / day
- Co-factor of D2 and has a role in TRH synthesis and in converting T4 to T3.
- DNA-binding component of thyroid receptors chelates zinc ions, forming ‘zinc fingers’ which mediate specificity in binding to T3 response elements (TRE) to activate transcription factors.
- Anything we use DNA for zinc is used
- Important in thyroid receptors functions
- Zinc deficiency is associated with enhanced expression of hepatic D1, which ↑ thyroid hormone inactivation.
- Low levels of free T3 and normal T4, but elevated RT3 are associated with mild to moderate zinc deficiency.
Use and dosage of iron for hypothyroidism
Iron – optional one
Supplement dosage: Approx. 10mg maintenance 30 mg/day if deficient check levels before
- TPO is a haem-containing enzyme used in the initial steps of hormone synthesis (adds iodine to thyroglobulin).
- Because people can be iron sufficient, we don’t always add iron into thyroid protocol but you would with zinc and selenium
- Iron-deficiency anaemia decreases: T4 and T3, peripheral conversion of T4 to T3 and hepatic deiodinase.
- Iron-deficiency anaemia blunts the efficacy of iodine supplementation.
- Iron supplementation (correction) has been shown to reduce RT3 and increase T3 and T4 in adolescent girls.
- Big reduction in T4 to T3 reduction in iron deficiency anaemia
- Can reduce iodine utilization, because If TPO is not working iodine levels might be good but the iron is not supporting the TPO, and it is not utilized. If iodine is not working, look into anaemia. Or people not reacting to levothyroxine, could be anaemia.
