Endocrine System Flashcards
List three selenoproteins involved in thyroid hormone homestasis and give their functions.
- Deiodinase-1 (D1) and deiodinase-2 (D2) covert T4 to T3.
- Deiodinase-3 (D3) coverts T4 to Reverse T3 (RT3).
What are the functions of the following hormones: 1. TRH 2. TSH 3. T3 4. T4 5. Reverse T3
- TRH: Stimulates TSH release from the anterior pituitary.
- TSH: Stimulates thyroid hormone production. Activates iodide uptake via the sodium / iodide symporter (SIS).
- T3: 4 x the ‘strength’ of T4. Increases growth, bone and CNS development, increases BMR, heart rate and activates metabolism.
- T4: AKA thyroxine. Approx. 90% of secreted thyroid hormone. Weak ‘thyroid’ activity — ‘inactive’ form.
- Reverse T3: Biologically inactive — protects tissues from excess thyroid hormones.
List four essential minerals and the role they play in thyroid hormone synthesis.
- Iodine: Along with tyrosine, used to form T4 and T3, catalysed by TPO.
- Iron: TPO is haem-dependent.
- Selenium & zinc: Are enzyme co-factors and important for thyroid receptor function.
- Copper: A cofactor of deiodinase enzymes.
Which vitamins support the synthesis and function of thyroid hormones?
Vitamins A, C, E, B2, B3, B6, B12
List four food sources rich in iodine.
- Sea vegetables
- ocean fish and shellfish (ie. cod, scallops)
- eggs
- dairy foods (due to the fortification of animal feed)
Which of the following promotes iodine disorders? a) Low iodine intake b) Excess iodine intake c) Both
c) Both
List two possible causes of excess iodine and the conditions this could lead to.
- An inhibited Wolff-Chaikoff effect (helps reject excess iodine and hormone synthesis)
- Over-consumption of iodised salt, iodine fortified milk and iodine-containing dietary supplements.
- Radiocontrast dyes / medications (e.g., amiodarone — used for heart arrythmias and contains iodine).
Excess iodine can cause hyperthyroidism, hypothyroidism and a goitre.
How much T4 and T3 is secreted by the thyroid daily?
The thyroid secretes approx. 80–100 mcg of T4 and 10mcg T3 daily.
Where is most T3 in the body obtained from?
Only 10% of circulating T3 is derived directly from thyroid secretion. The remaining 90% is obtained via conversion from T4 in peripheral tissues (liver and kidney) to active T3 or inactive reverse T3.
Explain why elevated Reverse T3 (RT3) levels can be problematic.
RT3 is biologically inactive but can bind to T3 receptors, blocking the action of T3. An increase in RT3 = decrease in T3.
↑ RT3 can present as hypothyroidism.
Give examples of four types of HPT disruptors that can interfere with the 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: (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).
What advice can be given 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.
Give an example of a medication that often exert the following effects on thyroid function: a) Decrease TSH secretion b) Alter T4 and T3 metabolism c) Reduce T4 to T3 conversion d) Reduce T4 and T3 binding e) Increase thyroglobulin
a) Dopamine, glucocorticoids, lithium.
b) Phenytoin, rifampicin.
c) Beta-blockers, amiodarone.
d) Diuretics, NSAIDs.
e) Oestrogen, tamoxifen.
What condition could result from the long-term use of hyperthyroid medication?
Hyperthyroid medications may induce hypothyroidism 10–20 years later in Grave’s disease.
How is the gut microbiome related to the thyroid?
Gut dysbiosis negatively affects thyroid function. Microbes regulate iodine uptake, degradation, and enterohepatic cycling.
Which gut markers are typically out of range in auto-immune thyroid disease (AITD)?
In AITD, low SCFA production is common, as is elevated zonulin (intestinal permeability) and elevated serum LPS, leading to chronic low-grade inflammation.
What are the optimal ranges for the following thyroid tests: 1. TSH 2. Free T4 3. Total T4 4. Free T3
- TSH: 0.4 to 2.5
- Free T4: 12.8 to 19.5 pmol/L
- Total T4: 70 to 150
- Free T3: 3.2 to 4.5 pmol/L
How might you interpret the following test results: a) High TSH; Normal T4; Normal T3 b) High TSH; Low T4; Low/Normal T3 c) Low TSH; High/normal T4; High/normal T3
a) Subclinical hypothyroidism
b) Hypothyroidism
c) Hyperthyroidism
What is the optimum level of iodine as measured in the first morning urine for adults, children and pregnant women?
Iodine goal = A urinary first morning iodine level of:
- 100–199 mcg / L in children and adults.
- 150–249 mcg / L in pregnant women.
Which level of urinary iodine is considered as severe deficiency?
< 20 mcg / L = severe deficiency.
Which at home test can be recommended to give an indication of thyroid status?
The Barnes basal body temperature test The theory is that waking axillary temperature is diagnostic for low thyroid, if < 36.5 degrees C.
How would the following SNPs impact thyroid function: - VDR - BC01 - GPX
- VDR: Vitamin D is a co-factor required for T3 to function correctly.
- BC01: Retinol is a co-factor required for T3 to function correctly.
- GPX: A SNP in the gene that codes for glutathione can increase oxidative stress which can disrupt the HPT axis.
How would you classify the following presentations of hypothyroidism: a) TSH is slightly elevated and T4 is normal. T4 to T3 conversion issues, ↑ RT3 or thyroid cell receptor resistance. b) 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).
a) Subclinical
b) Primary
List 10 general signs and symptoms of hypothyroidism.
- Fatigue.
- Weight gain / inability to lose weight
- Heavy or irregular menstrual periods
- 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 hair & 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 the optimal level for TSH?
2.5 or less
List 5 common causes / risk factors for hypothyroidism
- Iodine: deficiency or excess (in susceptible individuals) — see earlier, including goitrogens.
- Women: more common in women, poss. due to ↑ rates postpartum, during and post menopause. Autoimmunity is also higher in women.
- Increasing age: peaks in 4th decade.
- Drug induced: E.g., amiodarone and lithium.
- Congenital: absence / underdevelopment of thyroid gland and enzymes required for hormone synthesis and iodide transfer.
- Nutrient deficiencies: i.e., tyrosine, iron, selenium, zinc, vit D, vits C, E, B2, B3, B6, B12, copper.
- Postpartum thyroiditis: autoimmune thyroiditis flaring as a result of immunologic ‘rebound’ from the relative immuno-suppression 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.
Define: Hashimoto’s thyroiditis
Hashimoto’s thyroiditis (HT) is an autoimmune disease that attacks thyroid tissue causing reduced thyroid hormones.
Which viruses are often implicated in the pathogenesis of Hashimoto’s thyroiditis?
EBV and H. pylori
What condition is suggested by the following laboratory markers: * ↑ TSH * low FT4 * ↑ antithyroid peroxidase (TPO) antibodies. * Anti-thyroglobulin (anti-Tg) antibodies * TSH receptor- blocking antibodies (TBII).
Hashimoto’s Thyroiditis
List 5 Hashimoto’s thyroiditis causes and risk factors
- Excess iodine — highly iodinated thyroglobulin is more immunogenic.
- Genetic polymorphisms — VDR, MTHFR (link to AITD).
- HT often co-exists with coeliac disease. Gluten-free diets have been shown to reduce antibody titres.
- Sleep apnoea and HT may influence each other.
- Heavy metals — mercury, lead, cadmium ↑ TGO antibodies. Metallothioneins (selenocysteine) in the thyroid bind to cadmium.
- Triclosan — found in personal care products e.g., toothpastes. Resembles structure of thyroid hormones.
- ↑ pro-inflammatory cytokines e.g., IL-6, TNF- α, IL-12, IL-10
What is the first line allopathic treatment for hypothyroidism and why might this fail?
Levothyroxine (synthetic T4). Doses range from 25 to 200 mcg daily.
Medication failure is often due to conversion problems e.g., nutrient deficiencies — where nutrition is key.
What important absorption and interaction factors needs to be kept in mind when considering Levothyroxine?
- Due to many interactions, take levothyroxine on an empty stomach in the morning. Food / drinks / other drugs taken 1 hour or more later.
- Drug absorption is affected by factors such as coeliac disease, atrophic gastritis, coffee and PPI use.
List 5 common triggers and mediators in the development of thyroid disorders
- Pathogens
- Increased intestinal permeability
- Blood glucose imbalance
- SNPs
- H-P-A axis imbalance
- TH1-Th2 imbalance
- Micronutrient insufficiencies
- Environmental toxins
- Inflammation
- Iodine status
- Radiation
- Medications
- Goitrogens
- Food sensitivities
- Surgery
Briefly outline the Naturopathic approach to hypothyroidism
1. Address triggers and mediators (identify the cause!):
* Optimise micronutrient status.
* Optimise digestion.
* Support methylation.
* Remove thyroid disruptors.
* Address possible dysbiosis/SIBO.
* Address stress, support HPA axis.
* Assess for coeliac disease.
* Identify food intolerances.
* Increase exercise.
* Identify and manage sleep disorders.
2. Reduce inflammation and IR:
* Optimise omega-3:6 ratio.
* Balance blood sugar and improve insulin sensitivity.
* ↑ antioxidant sources to ↓ oxidative stress.
3. Reduce goitrogenic compounds in food:
* Pre-soaking, steaming or boiling reduces goitrogens.
4. Balance T-cell functioning (Th1 / Th2 / Th17 / T-reg cell balance):
* Address increased intestinal permeability.
* Support butyrate producing commensal bacteria.
* Support SIgA levels.
How can methylation be supported in the client with hypothyroidism?
Optimise levels of folate, B12, B6, B2, choline, betaine, zinc. (Consider genetic testing).
How can detoxification and elimination be supported in the client with hypothyroidism?
Increase:
- B vitamins,
- ↑ glutathione (NAC, milk thistle, resveratrol, etc.),
- flavonoids.
How can detoxification and elimination be supported in the client with hypothyroidism?
Increase:
- B vitamins,
- ↑ glutathione (NAC, milk thistle, resveratrol, etc.),
- flavonoids,
- fibre,
- carotenoids,
- chlorophyll (green juice).
What steps can be taken to optimise omega-3:6 ratio?
Avoid trans fats, sugar, alcohol, high GL foods, smoking, limit arachidonic acid (Hs-CRP < 1).
What steps can be taken to address increased intestinal permeability and why is this important?
Integrity of the intestinal mucosa is critical for immune tolerance, T-reg cells (maintain tolerance).
Increase food containing or supplement with: glutamine (10 g BID), aloe vera, zinc carnosine, vit A, D, EPA and DHA (3–4 g), curcumin.
How can SIgA levels be supported?
Probiotics including S. boulardii, zinc, A, D, omega-3, colostrum.
For immune tolerance and reduced food reactions
List three minerals which you could consider to supplement in hypothyroidism with reasoning and dosage.
Selenium (Se)
It is an antioxidant, anti-inflammatory, ↑ T3
Selenomethione dosage: 150‒200 mcg / day
Zinc
D2 co-factor and has a role in TRH synthesis. Deficiency = enhanced expression of hepatic D1 (↑ thyroid hormone inactivation - ↑RT3.
Dosage: 15–30 mg / day
Iron
TPO is haem-dependent.
Iron-deficiency anaemia (IDA) decreases: T4 and T3, peripheral conversion of T4 to T3 and hepatic deiodinase. IDA blunts the efficacy of iodine supplementation.
Supplement dosage: Approx. 10mg maintenance; 30 mg/day if deficient. (NB: Check levels before)
Iodine
Decreases response of the thyroid to TSH, but at high concentrations, inhibits thyroid hormone secretion.
*Supplement dosage: 150–400 mcg – baseline to optimal dose.
(DO NOT use in AITD, hyperthyroid or thyroxine use).
Which amino acid is a precursor to thyroglobulin and at what dosage could a supplement be recommended?
Tyrosine
Dosage: 200 - 500 mg
Avoid high doses long term and with thyroxine use.
Why would you consider a Vitamin A supplement for a client with hypothyroidism and at which dosage?
- Vitamin A deficiency increases TSH.
- Supplementation can reduce TSH and increase T3.
- Deficiency reduces iodine uptake in thyroid.
- Via its role in retinoic acid receptors (RAR), vitamin A modulates thyroid hormone receptor function.
- Insufficiency could be due to low intake or BC01 SNPs.
Supplement dosage: 2000 IU
What is the significance of vitamin D and hypothyroidism?
- Vitamin D has an immune-modulatory role (T-reg cells).
- Deficiency is significantly higher in those with AITDs.
- Levels inversely correlated with thyroid antibodies.
- Supplementation found to be beneficial even in those with ‘normal’ levels.
- Aim for vitamin D levels of 100–150 nmol / L.
List two herbs that can be considered for hypothyroidism.
- Nigella sativa (1 g / day) — reduces TSH, TPO antibodies and increases T3 in those with Hashimoto’s. Antioxidant and immunomodulatory.
- Ashwagandha (Withania somnifera) — shown to significantly improve TSH, T4 and T3 levels in hypothyroidism (immunomodulator, aids conversion of T4 to T3).
- Guggul (Commiphora wightii) — enhances iodine uptake and TPO.
Define ‘hyperthyroidism’ and list two subtypes.
Hyperthyroidism is increased levels of thyroid hormones.
This is sub-divided into:
1. Thyrotoxicosis (increased synthesis of thyroid hormones).
2. Thyroiditis (release of stored hormones due to thyroid damage.)
What is the main cause of thyrotoxicosis?
Grave’s disease (80%).
List 4 signs/symptoms of hyperthyroidism.
-
Skin / appendages:
Thinning or loss of hair. Warm, moist skin. Sweating and heat intolerance. -
Nervous system:
Irritability, nervousness, insomnia, anxiety. Lid retraction. Psychosis. -
Musculoskeletal:
Muscle weakness, fine motor tremor. -
Gastrointestinal:
Weight loss despite increased appetite. Thirst and diarrhoea. -
Cardiovascular:
Tachycardia, palpitations and shortness of breath on exertion. Atrial fibrillation (AF), heart failure and worsening angina. -
Reproductive:
Menstrual irregularities. -
Face / neck:
Goitre and Grave’s orbitopathy.
What is Grave’s disease?
Grave’s disease (GD) is B and T-lymphocyte-mediated autoimmune hyperthyroidism.
Which diagnostic marker is raised in 75% of patients with Grave’s disease?
TPO antibodies.
What are two characteristic signs / symptoms of Grave’s disease?
Grave’s orbitopathy (in 25%): Antibody-mediated inflammation of orbital contents. Often asymmetrical and characterised by:
* Photophobia:
Excess eye watering, red, swollen eyes / eyelids.
* Eyelid retraction:
Visible sclera. Deterioration in visual acuity.
* Exophthalmos:
eyeball protrusion. Lid lag. Double vision.
Grave’s dermopathy: Painless rash — appears thick lumpy and red like ‘orange peel’ (lower legs, top of feet).
List 5 causes and risk factors of hyperthyroidism.
- Family history of thyroid disorders (esp. maternal relatives). Maternal TRABs cross the placenta — neonatal thyrotoxicosis.
- Stress (e.g., emotional shock).
- Inflammation / oxidative stress.
- Excess iodine intake — overstimulating thyroid hormone production.
- Dysbiosis and intestinal permeability. Propionate-producing bacteroides promote Treg / Th17 imbalance and GD. Levels of prevotella are often significantly higher in GD patients.
- Food allergy / intolerances
- Heavy metals — e.g., mercury, cadmium.
- Smoking (cadmium) — risk for GD. 3-fold risk of developing orbitopathy. More severe disease.
- Other AI conditions — GD is associated with Type 1 diabetes, Coeliac disease and pernicious anaemia.
- Infections — Yersinia enterocolitica, Borrelia burgdorferi, hepatitis C (strong correlation).
- Vitamin D, selenium, CoQ10 deficiency
Hyperthyroidism usually presents with low _ _ _, high _ _ _ and _ _ _ (sometimes T4 is normal).
Hyperthyroidism usually presents with low TSH, high FT3 and FT4 (sometimes T4 is normal).
What is a T3 / T4 ratio > 20 or FT3 / FT4 ratio > 0.3 suggestive of?
Grave’s disease.
What is the presence of abnormal IgG (TRAbs) suggestive of?
Grave’s disease
Also TPO antibodies (TPOAbs)
Which inflammatory markers are usually raised in thyroiditis?
ESR and CRP.
What does the following diagnostic picture suggest? ‘Low but detectable’ TSH of 0.1 to 0.4 mIU / L. T3 / T4 are usually normal
Subclinical hyperthyroidism.
Briefly outline the aims of a naturopathic approach to hyperthyroidism.
- Address micronutrient insufficiencies and ↓ oxidative stress
- Inhibit thyroid hormone synthesis
- Reduce inflammation and insulin resistance
- Support the nervous system and address stress
- Assess and address gut health and pathogen load
- Support thyroid hormone clearance.
What can be suggested to support glutathione to reduce oxidative stress for a client with hyperthyroidism?
Glutathione support — NAC, milk thistle, resveratrol, selenium. Selenium supplementation (200 mcg) slows eye disease (GD).
Which foods should be avoided and included in order to help inhibit thyroid hormone synthesis in hyperthyroidism?
Avoid: Iodine-containing foods such as sea vegetables, ocean- and shellfish and iodated table salt.
Include: goitrogen-containing foods such as raw kale and cabbage.
Which two liver pathways can be supported in order to enhance thyroid hormone clearance?
The sulphation and glucuronidation pathways.
List four compounds and/or nutrients that can be used to support the following pathways: a) Sulphation b) Glucuronidation
a) Sulphation:
- Glucosinolates (from brassicas)
- Vit E, A
- Selenium (induces SULT enzymes)
- Sulphur-containing foods (onions, garlic)
- Methionine, Vit B12, folate (to support methylation)
- NAC, taurine
b) Glucuronidation:
- Quercetin, luteolin and chrysin rich foods (honey, propolis, broccoli, peppers, celery, parsley, rosemary, onions).
- Magnesium and green tea.
- β-glucuronidase inhibitors: milk thistle, strawberry, reishi, probiotics, citrus, watercress, brassicas, turmeric.
Why would you consider Carnitine in a hyperthyroid nutritional protocol and at what dosage?
- Carnitine peripherally antagonises thyroid hormones (inhibiting nuclear entry of T3 and T4).
- Can prevent or reverse muscle weakness.
- Can prevent the possible lethal outcome of a ‘thyroid storm’ (a medical emergency more common in severe Grave’s disease; high T3, progressive tachycardia to circulatory collapse).
- ↑ T3 / T4 = ↑ metabolism = ↑ carnitine turnover and urinary loss – deprives tissues of L-carnitine, ↓ conc. in skeletal muscle may contribute to myopathy.
Dosage: 2,000 to 4,000 mg daily
Why should hyperthyroid clients specifically focus on including nutrient dense foods such as nuts, seeds, avocado, olives, coconut, high vegetables, legumes and other protein rich foods?
To counteract weight loss. Faster metabolism brought about by hyperthyroidism increases the need for calories.
What is the reasoning behind a B-vitamin complex recommendation in hyperthyroidism?
Increased metabolism leads to higher B vitamin requirement.
How is vitamin D supportive in hyperthyroidism?
- Vitamin D plays a key role in innate and adaptive immunity.
- May slow disease progression. Low levels found in hyperthyroid patients.
- Low status exacerbates accelerated bone turnover, low BMD and ↑ risk of fracture (seen in untreated cases).
- Test and optimise levels or use 2000 IU daily whilst waiting for test results.
Which herbs can be used to support the client with hyperthyroidism?
- Passionflower and valerian — anxiolytics with calming effects on the nervous system (‘nervines’ — GABA inducing). Can help to control the symptoms of an overactive thyroid.
- Ashwagandha — adaptogen to increase resistance to stress. Although avoid herbs that are too energetically stimulating.
- Bugleweed (Lycopus virginicus) tincture — regarded as a thyroxine antagonist. Used to manage mild hyperthyroidism by decreasing T4.
- Motherwort (Leonurus cardiaca) — Helps reduce cardiac signs / symptoms. Avoid in pregnancy, breastfeeding, diagnosed CNS and cardiac pathologies.
- Lemon balm (Melissa officinalis) — blocks thyroid hormone activity.
