Thyroid

Question 1

Hypothalamus-Pituitary-Thyroid (H-P-T) axis

Answer 1

Thyrotropin-releasing hormone (TRH) stimulates thyroid-stimulating hormone (TSH) release; TSH stimulates thyroid hormone release — T4 (around 90%) and T3

Question 2

Iodothyronine deiodinases

Answer 2

Iodothyronine deiodinases are selenopr regulating thyroid hormone homeostasis.

‒ Deiodinase-1 (D1) and deiodinase-2 (D2) covert T4 to T3.

‒ Deiodinase-3 (D3) coverts T4 to Reverse T3 (RT3)

Question 3

TRH

Answer 3

Stimulates TSH release from the anterior pituitary

Question 4

TSH

Answer 4

Stimulates thyroid hormone production.

Activates iodide uptake via the sodium / iodide symporter (SIS).

Question 5

Triiodothyronine (T3)

Answer 5

4 x the ‘strength’ of T4. Increases growth, bone and CNS development, increases BMR, heart rate and activates metabolism.

Question 6

Tetraiodothyronine (T4)

Answer 6

AKA thyroxine. Approx. 90% of secreted thyroid hormone. Weak ‘thyroid’ activity — ‘inactive’ form

Question 7

Reverse T3 (RT3)

Answer 7

Biologically inactive — protects tissues from excess thyroid hormones

Question 8

SIS

Answer 8

SIS = a transmembrane glycoprotein needed for the active transport of iodine into thyroid follicular cells

Question 9

SIS

Answer 9

SIS = a transmembrane glycoprotein needed for the active transport of iodine into thyroid follicular cells

Question 10

Thyroid hormone synthesis: Nutritional status

Answer 10

• Tyrosine and iodine: Thyroid peroxidase (TPO) catalyses iodination of tyrosine residues in thyroglobulin to form T4 and T3 (a pro-oxidant process). iodination = a reaction in which iodine is introduced
• Iron: TPO is haem-dependent (assess iron status).
• Selenium and zinc: Enzyme co-factors and receptor function.
• 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.
• Copper: A cofactor of deiodinase enzymes.

Question 11

Iodine rich foods

Answer 11

• 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

Question 12

Iodine rich foods

Answer 12

• 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

Question 13

Iodine deficiency — causes

Answer 13

• Dietary deficiency.
• Increased risk – low/no dairy/fish, pregnant, 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

Question 14

Excess iodine — causes:

Answer 14

• 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)

Question 15

T3 and T4:

Answer 15

• 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.
• T4 is highly bound (99.98%), 0.02% circulates freely.
• T3 is slightly less protein bound (99.8%), 0.2% as free fraction

T4 is converted to T3 (D1 and D2) or RT3 (D3 enzyme). * 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

Question 16

HPT disruptors

Answer 16

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. (Patrick, 2009; Oliveira et

Can also cause lower levels of T3 in breast milk.

Halogens — disrupt thyroid functioning:

• Fluoride — in toothpaste, tap water and pesticides. Interferes

with the sodium iodide symporter (= ↓ iodine uptake) and iodothyronine deiodinase (= ↓ T4 to T3 conversion).

– In a study, a widely-fluoridated area was almost

twice as likely to report high hypothyroidism

prevalence in comparison to a non-fluoridated area.

The effect seems to be mitigated by adequate iodine status.

• Chlorine — swimming pools, PCBs — ↑ TSH, ↑ thyroid antibodies.
• Bromine — in pesticides, PBDEs (flame retardants, farmed fish)

Question 17

To avoid HPT disruptors

Answer 17

• 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

Question 18

Medications — often exert effects on thyroid function

Answer 18

Medications — often exert effects on thyroid function:

• Decrease TSH secretion: Dopamine, glucocorticoids, lithium.
• Alter T4 and T3 metabolism: Phenytoin, rifampicin.
• Reduce T4 to T3: Beta-blockers, amiodarone.
• Reduce T4 and T3 binding: Diuretics, NSAIDs.
• Increase thyroglobulin: Oestrogen, tamoxifen.
• Hyperthyroid medications may induce hypothyroidism 10–20 years later in Grave’s disease.

Question 19

Gut microbiome and thyroid

Answer 19

• Gut dysbiosis negatively affects thyroid function.
• Microbes regulate iodine uptake, degradation, and enterohepatic cycling.
• In AITD, low SCFA (short chain fatty acid) production is common, as is elevated zonulin (intestinal permeability) and elevated serum LPS → chronic low-grade inflammation

Question 20

Conventional medicine diagnostic

Answer 20

Question 21

Thyroid Investigations interpretation

Answer 21

Question 22

Comprehensive thyroid function testing

Question 23

Measuring iodine

Answer 23

Measuring iodine — urine iodine test:

• Iodine goal = A urinary first morning iodine level of:

✓ 100–199 mcg / L in children and adults. What do you make of

✓ 150–249 mcg / L in pregnant women. you this result? address How this? would

• < 100 mcg / L in children and non-pregnant adults = iodine insufficiency.
• < 20 mcg / L = severe deficiency

Question 24

Barnes basal body temperature test

Answer 24

Barnes basal body temperature test:

• The theory is that waking axillary temperature is diagnostic for low thyroid, if < 36.5º C.
• 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

Question 25

Physical Thyroid examination

Answer 25

Physical examination:

• Thyroid gland enlargement, dry skin, nail beading, thinning eyebrows, hair loss, low blood pressure, bradycardia (< 60 BPM)