Understanding Hypothyroidism

Hypothyroidism Overview

• Clinical hypothyroidism affects one in 300 people in the United States
• It's more prevalent among female and older patients

Thyroid Hormones

• T4 and T3 are key thyroid hormones
• T2 increases the metabolic rate of the muscles and fat tissue.

Signs and Symptoms of Low Thyroid Production

• Earliest signs and symptoms can occur years before labs show abnormalities
• Depression and weight gain are common
• Constipation and headaches, including migraines, may occur.
• Nails may become brittle, ridged, striated, and thickened
• Skin may become rough and dry
• Menstrual irregularities and fluid retention can be experienced
• Poor circulation and elbow keratosis can manifest
• Speech can slow, and nails may break easily
• Anxiety, panic attacks, decreased memory, and inability to concentrate are possible
• Muscle and joint pain can also occur
• Reduced heart rate and slow movements might be observed
• Morning stiffness and a puffy face may be evident
• Swollen eyelids, decreased sexual interest, and cold intolerance are symptoms
• Cold hands and feet can be experienced
• Swollen legs, feet, hands, and abdomen can occur
• Insomnia and fatigue might develop
• Low body temperature and a horse or husky voice are possible
• Low blood pressure, muscle weakness, and agitation/irritability could be present
• Sparse, coarse, dry hair and a dull facial expression may appear
• Yellowish discoloration of the skin and inability to convert beta carotene into vitamin A may be noted
• Muscle cramps and drooping eyelids can occur
• Carpel tunnel syndrome can develop
• Sleep apnea and endometriosis may be related
• The immune system can be compromised
• Hypercholesterolemia and infertility can be signs
• PMS (premenstrual syndrome) and hyperinsulinemia may be observed
• Fibrocystic breast disease, nutritional imbalances, and paresthesias are possible
• Myxedema can occur
• Down-turned mouth and acne may appear
• Allergies and painful menstrual cycles may be experienced
• There may be a tendency to develop allergies
• "Fat pads" above the clavicles
• Hair loss can occur in the front and back of the head
• Loss of the outer third of the eyebrows is a sign ("Queen Anne's sign" or "sign of Hertoghe").
• Vision can worsen, leading to poor night vision
• Eyelashes or general hair loss may become thin, sparse, or fall out
• Dry, scaly, itchy ear canals
• Excess cerumen (earwax) formation is associated
• Iron deficiency anemia and B12 deficiency are possible
• Tinnitus and delayed DTRs may develop
• Bipolar disorders, schizoid or affective psychoses, and miscarriage can relate
• Low amplitude theta and delta waves on EEG are observed
• Dizziness/vertigo and CHF (congestive heart failure) can manifest
• CAD/MI (coronary artery disease/myocardial infarction) and decreased cardiac output are possible
• Arrhythmias and increased risk of developing asthma can occur
• Hypertension and mild elevation of liver enzymes may be present
• Arthralgias/joint stiffness and menorrhagia (heavy menstrual bleeding) can manifest
• Hypoglycemia and shortness of breath can occur
• Erectile dysfunction, recurrent miscarriage, nocturia (frequent nighttime urination), and easy bruising are symptoms
• Impaired kidney function is also noted

Osteoporosis and Remodeling

• Bone structure may become abnormally thick or weakened in individuals with osteoporosis.
• With thyroid replacement, bones remodel to become stronger and thinner.
• This remodeling process takes approximately 6–12 months.

Hypothyroidism and Adrenal Dysfunction

• Adrenal dysfunction and primary or secondary hypothyroidism can occur together.
• Individuals with positive thyroid antibodies often have positive adrenal cortex antibodies.
• Cortisol levels might increase to compensate for low T3 levels.

Factors That Cause Decreased Production of T4

• Deficiencies in zinc and copper
• Vitamin deficiencies include A, B2, B3, B6, and C

Conversion of T4 to T3

• Production of 5'deiodinase is required
• It has three types of this enzymes
• Type I is found in the thyroid liver and kidney and plays an important role in T3 production
• Type II is found in the pituitary, hypothalamus, and brown fat which converts T4 to T3
• Type III catalyzes deiodination of the inner ring of T4 and T3, inactivating them.

Elements That Affect 5'deiodinase Production

• Selenium Deficiency
• Stress
• Cadmium, mercury, or lead toxicity
• Starvation
• High Carbohydrate Diet
• Elevated Cortisol
• Chronic Illness
• Decreased Kidney or liver function
• Inflammation: Proinflammatory cytokines inhibit human type I 5'deiodinase expression and function in HepG2 hepatocarcinoma cells.

Factors Causing Inability to Convert T4 to T3

• Nutrient deficiencies: Iodine, Iron, Selenium, Zinc and Vitamins A, B2, B6, B12
• Certain medications include Beta blockers, birth control pills, estradiol, lithium, phenytoin, theophylline, and chemotherapy
• Glucocorticoids, Interleukin-6, and Clomipramine

Dietary Factors

• Too many cruciferous vegetables, low protein, low fat, or low Carbohydrate diet.
• Excessive alcohol use and walnuts
• Soy may interfere with T4 to T3 conversion.

Other factors

• Aging and Excess alpha-lipoic acid
• Diabetes and Fluoride
• Lead and Mercury
• Pesticides and Radiation
• Surgery and Copper excess
• Calcium excess and Dioxins and PCB
• Inadequate production DHEA,Cortisol
• Phthalates (chemicals added to plastics)
• Stress

Factors Associated with Low T3 or Increased Reverse T3

• Elevated levels of IL-6, TNF-alpha and IFN-2
• Prolonged Illness and Diabetes
• Infections like COVID-19
• Increased E, NE and Free radicals
• Aging and Toxic mental exposure
• Fasting and Stress

Factors That Increase the Conversion of T4 to T3

• Selenium, Potassium, Iodine and Iron
• Zinc and High protein diet
• Ashwagandha

Increase T4 to T3

• Vitamins A, B2, E and Growth hormone
• Portes, E., et al., "Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children," Clin Endocrinol 2000; 53(2):183-89.
• Jorgensen, J., et al., "Effects of growth hormone on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism," Jour Clin Endocrinol Metab 1989; 69(6):1127-32.
• Testosterone: Decreases the concentration of TBG
• Deyssig, R., et al., "Ingestion of androgenic-anabolic steroids induces mild thyroidal impairment in male body builders," Jour Clin Endocrinol Metab 1993; 76(4):1069-71.
• Insulin and Glucagon
• Melatonin and Tyrosine
• Estrogen-over dosage

Lab Studies to Evaluate Thyroid Function

• TSH, Free T4, and Free T3
• Reverse T3 and Thyroid antibodies

Thyroid Antibodies

• Antithyroglobulin antibody
• Antimicrosomal antibody
• Antithyroperoxidase (anti-TPO) antibody

Other Lab Studies to Evaluate Thyroid Function

• Thyroid Binding Globulin:
  • Stores the thyroid hormone which is produced in the liver
  • Thyroid binding globulin is affected by the liver, illness and medications
  • Estrogens can increase Thyroid Binding Globulin levels
• thyrotropin-releasing hormone (TRH) also called thyrotropin-releasing factor (TRF):
  • Releases TSH
  • Stimulates the the release of prolactin from the pituitary gland
  • Produced by the hypothalamus

Hashimoto's Thyroiditis Overview

• This is also called the chronic lymphocytic thyroiditis or autoimmune thyroiditis.
• AITDs (Autoimmune thyroid diseases) have been estimated to be 5-10 times more common in women than in men
• AITDs are characterized pathologically by infiltration of the thyroid with sensitized T lymphocytes and serologically by circulating thyroid autoantibodies
• Determining the presence of elevated anti-thyroid antibody titers including anti-thyroglobulin antibodies (TgAb), anti-microsomal/thyroid peroxidase antibodies (TPOAb), and TSH receptor antibodies (TSHRAb) is key is diagnosing AITDs
• Around 75% of people have elevated anti-thyroid antibody titers, with present antibodies generally persisting
• Positive TPOAb tests were significantly associated with hypothyroidism, tests for TgAb were positive in 10.4% and TPOAb in 11.3%
• Progression to overt hypothyroidism is predicted with elevated TPOAb titers
• Those with elevated TPOAb titers have 4.3% per year, without elevated TPOAb titers have 2.6% per year
• increased frequency of other autoimmune disorders such as type 1 diabetes, pernicious anemia, primary adrenal failure, myasthenia gravis, celiac disease, rheumatoid arthritis, systemic lupus erythematosus, and rarely thyroid lymphoma is seen in people with Hashimoto's thyroiditis

Medical Trial in Hashimoto's Patients

• Medical Trial placed patients with Hashimoto's thyroiditis on a gluten-free diet that were not on any medications for hypothyroidism resulted in a gluten-free diet reducing thyroid antibody titers.
• Treatment of Hashimoto's Thyroiditis includes stopping gluten, fixing the gut, starting LDN and Medication if needed

LDN Overview

• There have been some novel and significant findings on the off-label usage of naltrexone in recent years
• Within a specific dosage window, LDN can act as an immunomodulator in multiple autoimmune diseases and malignant tumors as well as alleviate the symptoms of some mental disorders.
• The results of increasing studies indicate that LDN exerts its immunoregulatory activity by binding to opioid receptors in or on immune cells and tumor cells which can make it a promising immunomodulatory agent in the therapy for cancer and many immune-related diseases
• Possible Short-Term Side includes Insomnia (most common), vivid dreams, fatigue, loss of appetite, nausea, hair thinning, mood swings, and mild disorientation
• Possible Long-Term Side Effects includ Possible liver and kidney toxicity, Possible tolerance to the beneficial rebound effect and other unknown sequelae

LDN CONTRAINDICATIONS

• Acute hepatitis and Liver failure

LDN DOSAGE

• Start: 1.5 mg capsule qhs x 7 days
• Next stage: Two 1.5 mg capsules qhs x 7 days
• Third stage: Three 1.5 mg capsules qhs x 7 days
• Ending Stage: Then 4.5 mg thereafter compounded as a single capsule
• Patients with Hashimoto's thyroiditis are frequently iron deficient so always measure Ferratin and TIBC levels and replace iron if needed
• For optimal thyroid Function make sure the thyroidis levels are normal

Factors for Diagnosing Hashimoto's

• Lower vitamin D status has been found in Hashimoto's thyroiditis patients than in controls, and inverse relationships of serum vitamin D with TPO/Tg antibodies has been reported
• Autoimmune disease processes include vitamin D receptor dysfunction that results in low vitamin D levels
• It is Vital to Measure vitamin D levels and replace according to lab results and in areas of iodine deficiency/excess, and in regions of low selenium intake a supplement of 50-100 µg/day of selenium may be needed and also always measure selenium levels and replace if needed.

Basal Body Temperature

• Take temperature under the arm for 10 minutes for 3 days before arising. If the patient is cycling, then take the temperature during the menstrual cycle.

Treatment factors

• Is soy intake a problem?
• Detoxification, medication, and nutrition

All of these toxins affect thyroid function.

• PCBs, Dioxins,DDT, HCB (hexachlorobenzene), Phthalates, Heavy metals-lead, arsenic, mercury

Thyroid Treatment

• T4 must be converted to T3 to be utilized by the cells.
• The conversion takes place in the liver and kidneys.
• T3 is five times stronger than T4
• T4 has never been proven to be effective for treating the symptoms of hypothyroidism in any long-term study.
• Intracellular thyroid hormone receptors have a high affinity for T3.
• 90% of the thyroid hormone molecules that bind with the receptors are T3 and 10% are T4.

Considerations For Those metabolize thyroid

• If a patient can't metabolize thyroid is not able to metabolize thyroid (convert T4 to T3, then T3 to T2, and T2 to T1) then they will not be as healthy
• Compounded thyroid answers this issue.

Replacing Thyroid hormone

• Needs both T4 and T3
• Need T3 an T4 alone
• Desiccated thyroid (both T3 and T4) Compounded thyroid replacement (both T3 and T4)

Function of T3

• Has direct effects on the mitochondria.
• Has direct effects on the heart. Synthroid, Levothyroid, Levoxyl and Eltroxin are all immediate release and contain lactose which can interfere with thyroid absorption that varies from 48-80%
• T3 (Liothyronine Sodium): Cytomel, Triostat (injection) and Liothyronine sodium (generic) are all immediate release
• Desiccated Thyroid Hormone: Armour (porcine) and Liotrix are immediate release

Factors for consideration for Desiccated Thyroid

• Factors for Desiccated Thyroid that are all immediate release: Armour (porcine) (ratio: T4 4 to T3 1), Thyroid USP (ratio: T4 4.2 to T3 1), Thyroid Strong (ratio: T4 3.1 to T3 1), Thyrar (bovine), S-P-T (pork thyroid suspended in soybean oil) and Liotrix (ratio: T4 4 to T3 1)
• Factors for Consideration for Compounded Thyroid Replacement -Is not USP -can be any ratio of T4 to T3. -Can also ass selenium, chromium, zinc and iodine/iodide to thecompound Lab results not better but patients felt better when both T3 and T4 were replaced. Optimal TSH Level ( TSH, 0.3-5.5 (N) (want below 2.0), FT3 2.3-4.3(Ν) ( 3.5-4.3), rT3 (optimal) 90-350 pg/ml (N) (want 50-150) Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH with one study on postmenopausal women.

Personalized Thyroid Replacement CONT.

• Recent studies have shown that it is now time for personalized thyroid replacement to be prescribed and highlighted newest research suggests mechanisms for the inadequacies of L- thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms, understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.
• High normal or elevated reverse T3 is indicative of reduced thyroid transport that can result in celluar transport Cellular levels of thyroid are not detected well by serum T4 levels since serum T4 is transported into the cell and the lower the cellular level of T4 the higher the serum level.
• This is due to mitochondrial dysfunction.
• Any disease process associated with mitochondrial dysfunction may be associated with high normal or elevated reverse T3.

Factors to reduce High rT3

• Excess rT3 (stored thyroid hormone) will further inhibit conversion from T4 to T3.
• if rT3 is elevated the patient will have symptoms of hypothyroidism, even if labs are normal.
• To reduce the adverse effects always give T3 to to produce Thyroid hormones

Other actions to take to reduce High rT3

• The need to reduce/eliminate stress, support GH, treat underlying mitochondrial problem and selenium and iodine deficiency and any inflammation

Conditions for consideration during thyroid treatments

• A patient should always be revaluated for detoxification and treatment to ensure safety and health
• Those patients that don't respond well need to ensure cellular uptakes and should get measured to determine

Treatment of patient concerns:

Agents That Lower Absorption/ Elevate and Excretion of Thyroid include Ferrous sulfate, Sucralfate, Bile acid sequestrants and Lactose Other Agents lowering agents: Calcium carbonate and Aluminum hydroxide Other Medications That Alter Thyroid Function include Haloperidol, Lithium- blocks iodine transport with one being Amiodarone.

Other medication that alter the Oral Contraceptives

• Metoclopramide, Cimetidine and Clomiphene
• Dilantin (phenytoin), Tegretol (carbamazepine) and Phenobarbital Tamoxifen is also used for more than one year with Rifampinand Ritonavir and Sertraline increase the clearance
• About 70% of the T4 secreted daily is deiodinated to yield T3 + rT3 in equal parts. 80% of circulating T3 comes from peripheral monodeionization of T4 at the thyrosyl ring
• Occurs in the liver, kidney, and other tissues and Circulating rT3 is made the same way

Treatments for hypothyroidism

Therefor study 89 patients with hypothyroidism treated with T4 previously, compared to group of people with low thyroid function that were untreated and seen to need their function improved to change

• Those patients reported their improvements with with desiccated thyroid but before make sure that the adrenal glands are healthy before replacing, wait until two months after the patient has had an acute and need a healthy gut to do absorption Check for:SR thyroid absorption, adequate magnesium level, and exposure to mold Therapeutic Actions of Iodine are Antibacterial, Anticancer, Antiparasitic, Antiviral and Mucolytic agent
• lodine helps the body provide the minerals and helps with growth so to support that provide 150 and 1,100 micrograms
• If you use thyroid replacement hormone without first correcting (or simultaneously correcting) the iodine deficit you will exacerbate the body's deficit of iodine.

Treatment

• Relationship Between Hypothyroidism& Breast Cancer and Breast Cancer from areas like Japan are shown to need approximately 5mg in a 50 kg woman • Best to supplement both since different
• Both Lugol's solution (metallic taste) and Iodoral (tablet) will ensure health
• Take 3 to 6 months of iodine supplementation before iodine saturation is reached
• about 1/3 of patients being treated for hypothyroidism will need to lower their dose of thyroid hormone when an iodine deficiency is corrected
• Up to 72% of the world's population is affected by an iodine deficiency disorder and the ground depletes over time
• Causes of lodone Deficiency include Diets without ocean fish or sea vegetables such as seaweed, Inadequate use of iodized salt, Diet high in pasta and breads that contain bromide, Fluoride use and Vegan and vegetarian diets and medications such as Sucralose along with Atrovent Inhaler

Tissues That Use Iodine

• Are thyroid, Breast, Prostate, Kidneys, Spleen liver, Blood and intestines always measure

What happens if your missing levels

• If you use thyroid replacement hormone without first correcting (or simultaneously correcting) the iodine deficit you will exacerbate the body's deficit of iodine. Always review with patients and measure

Treatments vs Iodine

• It is best to supplement both since different tissues concentrate different forms of iodine such a Lugol's solution (metallic taste) and Iodoral (tablet)
• Iodine deficiency effects from not supplementing includes the thyroid activity compensating for low iodine intake and and results is thyroid stimulation results in goiter and hyperthyroidism
• Over Treatment leads to associated thyroiditis. which is why it is important to measure iodine levels It is shown that higher content results in an increasing cancer rate

Thyroid Function and

• Ferritin requires over 100 ng/ml
• If the patient is in the cycle always suggested 130

Soy

• Controversial as a diet rich in it may inhibit function
• Study of 37 adults who ate a high soy diet for 3 months revealed that almost 12 had low thyroid function so it usually resolved stopping

Selenium

• Study of a normal critically ill of both TT3 and FT4 and was improved Selenium

Zinc

Helps with thyroid homorme Study also included patients wit zinc levels improving

• Patients with Hashimoto require TSH that helps
• In most cases thyroid improves the treatment -This shows the importance of helping to support balance for all patients
• The right mix will result optimal thyroid function and that should be the goal The need for that mitochondria working and transmission
• Diseases to associate for reference include ADHD, Cardiac Vascular disease, CFS and Fibo
• Studies do show is related to more genetic issue with function as result and need for both treatment

To Note

• All patients as shown do need a great mix and testing can be difficult If the TSH is to low increases risk

Thyroid Hormone and Memory

• When looking at function review TSH and Ft4. It could improve attention and be the source

Replacing treatment and thyroid

• With study it is revealed that SIBO and are related in ascending order are immunosuppression, impairment of intestinal clearance and levothyroxine use
• For the patient over age help and manage to make sure the levels don't lower and keep them alive

Conclusion

Optimal thyroid function requires adequate nutritional intake, toxin avoidance, hormonal balance, and appropriate medication usage. Many factors influence optimal thyroid replacement, emphasizing accurate measurement techniques. Most patients benefit from replacing both T3 and T4 for optimized thyroid function.