thyroid dysfunction - josh gitalis · thyroid metabolism hypothalamus sends trh pituitary releases...
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Thyroid Dysfunction
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Pathologies
• Hypothyroidism
• Hyperthyroidism
• Autoimmune thyroid (Hashimoto’s and Grave’s)
• Thyroid cancer
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Definitions
• Thyrotropin releasing hormone (TRH): hormone made by hypothalamus
• Thyroid Stimulating Hormone (TSH): hormone made by pituitary
• Thyroxine (T4): hormone made by thyroid
• Triiodothyronine (T3): active thyroid hormone
• Thyroid peroxidase (TPO): enzyme that makes thyroid hormone
• Thyroglobulin: protein that joins iodine to make T4
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Metabolism
T3
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid MetabolismHypothalamus
sends TRH
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid MetabolismHypothalamus
sends TRH
Pituitary releases TSH
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid MetabolismHypothalamus
sends TRH
Pituitary releases TSH
TSH stims TPO
93% is T4
7% is T3✓
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid MetabolismHypothalamus
sends TRH
Pituitary releases TSH
TSH stims TPO
93% is T4
7% is T3
60% converted to T3 in liver
✓
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid MetabolismHypothalamus
sends TRH
Pituitary releases TSH
TSH stims TPO
93% is T4
7% is T3
60% converted to T3 in liver
20% goes to reverse T3 (inactive)
✓
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid MetabolismHypothalamus
sends TRH
Pituitary releases TSH
TSH stims TPO
93% is T4
7% is T3
60% converted to T3 in liver
20% goes to reverse T3 (inactive)
20% converted to active T3 in GI
✓✓
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid MetabolismHypothalamus
sends TRH
Pituitary releases TSH
TSH stims TPO
93% is T4
7% is T3
60% converted to T3 in liver
20% goes to reverse T3 (inactive)
20% converted to active T3 in GI
Remaining T4 to T3 in tissues
✓
✓
✓
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Statistics (US)
• 27 million with thyroid disease
• 13 million undiagnosed
• 14 million Hashimotos
• 80% are women
American Association of Clinical Endocrinologists (AACE)
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
The thyroid is the ‘sentinel’ gland for the environment.
Dr. Jeffrey Bland
Advanced Clinical Focus:Hormones and Endocrinology
Loss of Thyroid Function
• No thyroid gland
• Autoimmune
• Postpartum thyroiditis
• Medications
• Toxins
• Stress
• Nutritional deficiencies or excesses
• Thyroid hormone resistance
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Symptoms (Most Common)
• Fatigue
• Weight gain
• Depression
• Constipation
• Hypersensitivity to cold water
• Poor circulation
• Muscle cramps
• ↓ Immunity
• Slow wound healing
• Excessive sleep
• Hypochlorhydria
• Itchy, dry skin
• Dry, brittle hair
• Hair loss
• ↓ Body temp
• Edema (esp. face)
• Lost of outer 1/3 of eye brow
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Others Signs Indicating Thyroid Issues
• Heart palpitations
• Inward trembling
• Increased pulse rate
• Feeling nervous
• Insomnia
• Night sweats
• Difficulty gaining weight
Advanced Clinical Focus:Hormones and Endocrinology
Top 10 Symptoms: Hypothyroidism
1. Fatigue
2. Weight gain
3. Feeling cold
4. Dry hair and skin
5. Hair loss
6. Menstrual irregularities
7. Edema
8. Muscle aches and joint pain
9. Constipation
10. Depression
Advanced Clinical Focus:Hormones and Endocrinology
Hypothyroid
Shilomo, Melmed, Kenneth S. Polonsky, et .al. Williams Textbook of Endocrinology, 12th Ed. Elsevier Saunders: Philadelphia, PA. 2011.
Hypothyroidism can affect all organ systems. These manifestations are largely independent of the underlying disorder but are a function of the degree of hormone deficiency.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Assessing Thyroid Function
• Symptomatology (questionnaire)
• Basal temperature test
• Blood work
• Ultrasound
• Biopsy
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Questionnaire
Advanced Clinical Focus:Hormones and Endocrinology
Simple Test
• Basal Temperature Test
• Easy, non-invasive
• Monitor progress
• Not well validated
• Not diagnostic
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Hypothyroidism
• Primary: ↑TSH, ↓FT4
• Secondary: ↓TSH, ↓ FT4
• Subclinical: ↑TSH, normal FT4
• Hashimoto’s thyroiditis: antibodies present
Dx
Advanced Clinical Focus:Hormones and Endocrinology
Dx
Hyperthyroidism
• ↓TSH, ↑FT4
• Subclinical: ↓TSH, normal FT4, high FT3
• Grave’s disease: antibodies present
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid: Lab Testing
• Standard of care = TSH
• Is this enough?
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Example of TSH Unreliability
• Patient with Hashimoto's getting no treatment
TSHJanuary 4.5February 0.08
March 2.3April 3.8May 8.7June 7.4July 1.6
Advanced Clinical Focus:Hormones and Endocrinology
• Can TSH reflect variations in target cell sensitivity?
• Can TSH reflect peripheral T4 to T3 conversion?
• Can TSH reflect cellular transport problems where there is faulty transport into the mitochondria?
• Can TSH reflect displacement of thyroid hormones from cellular receptors by RT3?
TSH Considerations…
Advanced Clinical Focus:Hormones and Endocrinology
What Does TSH Test?
• TSH indicates pituitary production
• Genetic and environmental factors can effect TSH secretion
• Pituitary hormone levels alone are not sufficient to measure the function of the gland they regulate
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
European Thyroid Association
• “…pituitary TSH secretion may not reflect what happens in other target tissues, and therefore serum TSH alone may not be a good marker for the adequacy of thyroid hormone replacement.”
Wiersinga W.M., L. Duntas. V. Fadeyev. et al. ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism.. European Thyroid Journal 2012 . Vol 1 No. 12 2012
Advanced Clinical Focus:Hormones and Endocrinology
TSH Range
Normal
0.0-0.39 mU/L
Hyperthyroid/ Grave’s
5.5+ mU/L
Hypothyroid/ Hashimotos
1-2 mU/LSymptoms Symptoms
• Standard of care for thyroid monitoring
0.4-5.5 mU/L
Advanced Clinical Focus:Hormones and Endocrinology
National Academy of Clinical Biochemistry (NACB)
• New guideline suggested in 2002
• TSH may be too wide
• People in this range = borderline thyroid disease
0.0-0.39 mU/L
1-2 mU/L
5.5+ mU/L
Normal
Symptoms Symptoms
Hyperthyroid/ Grave’s
Hypothyroid/ Hashimotos
0.4-5.5 mU/L
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
American College of Clinical Endocrinologists
• Clinicians should consider treatment for patients who “test outside the boundaries of a narrower margin based on a target TSH level of 0.3-3.04 mU/L.”
• “ The AACE believes the new range will result in proper diagnosis for millions of Americans who suffer from a mild thyroid disorder, but have gone untreated until now.”
ACCE Press release January 2003
TSH is normal but my patient is not well.
Advanced Clinical Focus:Hormones and Endocrinology
TSH Conclusion
• “Normal” is too wide
• Optimal should be 0.4-2.0 mU/L
Vanderpump M.P.J., W.M.G. Tunbridge, J.M. French, et al. The incidence of thyroid disorders in the community; a twenty year follow up of the Whickham survey. Clinical Endocrinology 1995; 43(1):55-68
Following an optimal range, is probably a much better approach.
Advanced Clinical Focus:Hormones and Endocrinology
What to Measure
• TSH
• Free-T4
• Free-T3
• Thyroid antibodies
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
“Bound” is Unavailable
Thyroid Hormone
1% Free
Free T3 Free T4
99% Bound
Advanced Clinical Focus:Hormones and Endocrinology
Why Test for T3?All had normal TSH
Medication No Meds
Gullo D, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One. 2011; 6(8):e22552.
15.2% below normal for Free-T3
29.6% below normal FT3/FT4
Advanced Clinical Focus:Hormones and Endocrinology
Why Test for T3?
Gullo D, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One. 2011; 6(8):e22552.
“…a subset of patients…do not reach a serum FT3/FT4 ratio within the reference range…These patients, therefore, live in chronic condition of abnormal thyroid hormone availability for the peripheral tissues, even if the administered levothyroxine dose is able to maintain the serum TSH within the normal range.”
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Why Test for T3?
Gullo D, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One. 2011; 6(8):e22552.
The insufficient T3 peripheral production cannot be appropriately corrected by increasing levothyroxine because T4 inhibits the conversion, and furthers the problem.
Advanced Clinical Focus:Hormones and Endocrinology
European Thyroid Association
• “Theoretically, thyroid hormone replacement therapy should aim not only at normalization of serum TSH but also at normalization of serum free T4, free T3 and FT4:FT3.”
Wiersinga W.M., L. Duntas, V. Fadeyev , et. al. ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. European Thyroid Journal 2012. Vol 1 No. 12 2012
Advanced Clinical Focus:Hormones and Endocrinology
Reverse T3Hypothalamus send
TRH
Pituitary releases TSH
TSH stims TPO
93% is T4
7% is T3
60% converted to T3 in liver
20% goes to reverse T3 (inactive)
20% converted to active T3 in GI
Remaining T4 to T3 in tissues
✓
✓
✓
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
20% goes to reverse T3 (inactive)
✓ ✗
Reverse T3
Advanced Clinical Focus:Hormones and Endocrinology
Reverse T3
• Converting T4 to T3 is optional
• The body determines whether it will convert T4 to T3 or RT3
Advanced Clinical Focus:Hormones and Endocrinology
Reverse T3: Contributing Factors
• Stress
• Trauma
• Low-calorie diet
• Inflammation
• Toxins
• Infections
• Liver/Kidney dysfunction
• Certain medications
Kelly GS. Peripheral metabolism of thyroid hormones: a review. Altern Med Rev. Aug 2000; 5(4):306-33.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Function of RT3
• Discovered in 1975 and found incapable of increasing metabolism
• RT3 considered “functionless”
• RT3 useful when a slower metabolism is advantageous: life-threatening illness, injury, or starvation
• Example: RT3 lets a person live longer without food and water
Advanced Clinical Focus:Hormones and Endocrinology
What Slows T4 to T3 Conversion
• Certain medications
• Se deficiency
• Protein deficiency, high carb diet
• Chronic illness
• Compromised liver/kidney
• Cd, Hg, Pb, herbicides, pesticides
• Stress (cortisol)
• Excess estrogen
• RT3
T4 T3-
Advanced Clinical Focus:Hormones and Endocrinology
Autoimmune Thyroid
• Most common AI disease
• It is not a metabolic issue
• This is an immune issue
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Autoimmune Thyroid Known to Follow
• Radiation exposure
• Bacterial and viral infection
• Toxic exposure
• Other AI diseases
• Pregnancy
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Antibodies
• TPO antibodies
• Anti-TG antibodies
• Should be negative
Advanced Clinical Focus:Hormones and Endocrinology
Autoimmune Disease
Genetics
Nat Clin Prac Gastro & Hep, Sept 2005, Vol2;No.9
Gut PermeabilityEnvironmental Trigger
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Leaky Gut Syndrome
“The autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier function.”
Genes Environment
You
“Phenotype”Nat Clin Prac Gastro & Hep, Sept 2005, Vol2;No.9
Advanced Clinical Focus:Hormones and Endocrinology
Estrogen and Thyroid
• Estrogen can trigger Hashimoto’s
• Can cause Hashimoto’s after pregnancy
• Perimenopause also common due to fluctuations
• Thyroid symptoms can mimic PM symptoms
Amino N, Hidaka Y, Takano T, et al. Possible Induction of Graves disease in painless thyroiditis by gonasotropin-releasing hormone analogues. Thyroid 2003;13(8):815-8 Risk of subclinical hypothyroidism in pregnancy women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metal 1994;79(1):197-204Massoudi MS, Milan EN, Orchard TJ, et al. Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women. Ann Epidemiol 1995:5(3):229-33
Advanced Clinical Focus:Hormones and Endocrinology
Reference Ranges
Source: The Gitalis System
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Other Nutrients to Consider
• Selenium
• Zinc
• Iron
• Iodine
• Vitamin D and A
• Celiac screen
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid Function
T4/T3
RT3 T3
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
+
Factors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
+
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
-
Factors that increase conversion of T4 to T3: • Selenium • Zinc
++Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
JoshGitalis.com
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Selenium
• Two enzymes involved in thyroid hormone synthesis are selenoproteins
• Thyroid contains one of the highest Se concentrations of any tissue
Zimmermann MB, Köhrle J. The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid. Oct 2002;12(10):867-78. Dickson RC and RH Tomlinson. Selenium in blood and human tissues. Clin Chim Acta 1967;16:311-321.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
↑TSH, Ab
↓Selenium
• Selenium inversely correlated with TSH
• Selenium inversely correlated with TPO antibodies
Thyroid and Selenium
Tong YJ et al. An epidemiological study on the relationship between selenium and thyroid function in areas with different iodine intake. Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2036-9.
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Selenium
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Zinc
• Zn deficiency lowered thyroid hormones by 30%
• Zn supplements normalized thyroid hormones
Kralik A, et al. Influence of zinc and selenium deficiency on parameters relating to thyroid hormone metabolism. Horm Metab Res. May 1996; 28(5):223-6. Nishiyama S, et al. Zinc supplementation alters thyroid hormone metabolism in disabled patients with zinc deficiency. J Am Coll Nutr. Feb 1994;13(1):62-7. Taneja SK & R. Mandal. Beneficial effect of modified egg on serum T3, T4 and dyslipidaemia following dietary Zn-supplementation in Wistar rat. Indian J Exp Biol. March 2008;46(3):171-9.
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Iron
• 15.7% of women with subclinical hypothyroidism were iron deficient compared to only 9.8% in the control group
Duntas LH, et al. Incidence of sideropenia and effects of iron repletion treatment in women with subclinical hypothyroidism. Exp Clin Endocrinol Diabetes. 1999;107(6):356-60. Cinemre H, et al. Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study. J Clin Endocrinol Metab. Jan 2009; 94(1):151-6.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Iron
• Iron deficiency imparts thyroid hormone synthesis by reducing activity of thyroid peroxidase
• Iron supplementation normalizes thyroid hormones
Zimmermann MB, Köhrle J. The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid. Oct 2002; 12(10):867-78. Eftekhari MH, Eshraghian MR, Mozaffari-Khosravi H et al, Effect of iron repletion and correction of iron deficiency on thyroid function in iron-deficient Iranian adolescent girls. Pak J Biol Sci. 2007 Jan 5;10(2):255-60.
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
Advanced Clinical Focus:Hormones and Endocrinology
• Diets both low and high in iodine associated with hypothyroidism
• High intake of iodine increases risk of Hashimoto’s
• “For the person with Hashimoto’s, supplementing with iodine is like throwing gasoline onto a fire.” - Datis Kharrazian
• Iodine supplementation prevents and treats Hashimoto’s and other thyroid disorder. - David Brownstein
Thyroid and Iodine
Laurberg P, et al. Environmental iodine intake affects the type of nonmalignant thyroid disease. Thyroid. May 2001; 11(5):457-69. Duarte GC, et al. Excessive iodine intake and ultrasonographic thyroid abnormalities in schoolchildren. J Pediatr Endocrinol Metab. April 2009; 22(4):327-34.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Vitamin A
• Vitamin A deficiency results in poor thyroid hormone signalling
Feart C, et al. Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells. Eur J Endocrinol. Mar 2005; 152(3):449-58.
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Vitamin D
• Vitamin D deficiency significantly higher in those with autoimmune thyroid disease (72%) versus healthy individuals (30.6%)
Kivity S, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. May 2011; 8(3):243-7.
Advanced Clinical Focus:Hormones and Endocrinology
Vitamin D Deficiency Causes
• Indoor/sedentary lifestyle
• Skin pigment
• Aging
• Sunscreen
• Latitude
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Basic Supplementation
• Selenium: 200-400 mcg
• Zinc: 15-30 mg
• Iron: 15-20 mg (confirm deficiency)
• Iodine: 150 mcg
• Vitamin D: 2000 iu
• Vitamin A: 2000 iu
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Toxins
• 150 industrial chemicals have been shown to result in reduction of TSH and/or T4
Howdeshell KL. A model of the development of the brain as a construct of the thyroid system. Environ Health Perspect. Jun 2002;110 Suppl 3:337-48.
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Toxins
Alternative Medicine Review. Thorne Research, Inc. 4 November 2009; Volume 14.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Toxins
Alternative Medicine Review. Thorne Research, Inc. 4 November 2009; Volume 14.
Advanced Clinical Focus:Hormones and Endocrinology
Halogens
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Toxins • Infections • Certain medications • Low calories • Inflammation • Liver/Kidney dysfunction
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Iodine Forms
Iodine Iodide Both
Breasts Prostate Stomach
Thyroid Skin
Kidneys Spleen Liver
Blood Salivary glands
Intestines
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Gluten
• Studies confirm link between gluten and Hashimoto’s
• “Cellular mimicry”
Eur J endocrinol 1994 Feb; 103(2):137-40 Hepatogastroenterology 2003 Dec;50 Eur J Gasteroenterol Hepatol 1999 Aug;11(8):939-40 Clin Endocrinol (Oxf) 2003 Sep;59(3):396-401 Dig Dis Sci. 2001 Dec;46(12):2631-5 Physical Res 2003;52(1):79-88
=
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid and Gluten
• Removing gluten is a critical step in any thyroid protocol
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Non-Celiac Gluten Sensitivity (NCGS)
“Increased intestinal permeability after gliadin exposure occurs in all individuals.”
Nutrients 2015, 7, 1565-1576.
Advanced Clinical Focus:Hormones and Endocrinology
Factors that Affect Thyroid FunctionFactors that contribute to proper production of T4/T3: • Iron • Iodine • Zinc • Selenium • Iron • Vitamin E, B2, B3, B6, C, D • Tyrosine
Factors that increase conversion of T4 to RT3: • Stress • Trauma • Low calories • Inflammation • Toxins • Infections • Liver/Kidney dysfunction • Certain medications
Factors that inhibit proper production of T4/T3: • Stress • Trauma • Toxins • Infections • Certain medications • Radiation • Fluoride • Hg, Cd, Pb • Pesticides • Autoimmune (celiac)
Factors that increase conversion of T4 to T3: • Selenium • Zinc
Factors that improve cellular sensitivity to thyroid hormones: • Vitamin A • Zinc • Exercise
T4/T3
RT3 T3
-
+
+
+
+
Advanced Clinical Focus:Hormones and Endocrinology
Thyroid Summary
• Assess function
• Support proper hormone production:
• Essential nutrients
• Stress management
• Decrease toxins
• Address infection
• Decrease inflammation
• Heal the gut
• Remove gluten
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Female Specific
Advanced Clinical Focus:Hormones and Endocrinology
Female Concerns
• PMS
• Low libido
• Fibroids
• Endometriosis
• PCOS
• Menopause
Advanced Clinical Focus:Hormones and Endocrinology
Healthy Menstrual Cycle
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Healthy Menstrual Cycle
• Flow 3-6 days
• Raspberry, wine, or currant red in colour
• Flow is like a jellied fluid
• 30-125 ml
• None to mild cramping not requiring meds
• Post-ovulatory 12-16 days
• Cycle 26-35 days
• Premenstrual symptoms mild or non-existent
Source: Justisse Method
Advanced Clinical Focus:Hormones and Endocrinology
Menstrual Cycle
Advanced Clinical Focus:Hormones and Endocrinology
PMS: What is it?
• Recurrent signs and symptoms that develop during the 7-14 days prior to menstruation
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
PMS: What is it?
• Diagnostic criteria:
• Emotional:
• Depression
• Angry outbursts
• Irritability
• Anxiety
• Confusion
• Social withdrawal
• Physical:
• Breast tenderness
• Bloating
• Headache
• Swelling of extremities
Advanced Clinical Focus:Hormones and Endocrinology
PMS Causes
• Stress
• Hormone imbalance
• Poor diet
• Nutrient deficiency
Advanced Clinical Focus:Hormones and Endocrinology
PMS and Hormones
• No consistent pattern in all women
• Often associated with estrogen dominance
• May also result from:
• Hypothyroidism
• ↑ prolactin
• ↑ FSH
• ↑ Aldosterone
• Lower levels of neurotransmitters (i.e. serotonin)
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Helpful Treatments for PMS
• Exercise
• Stress management
• Whole foods diet
• Detox support
• Magnesium: 400-800 mg
• Calcium: 800-1200 mg
• Zinc: 30-50 mg
• Vitamin B6: 50-200 mg
• Vitex: 20-40 mg
Advanced Clinical Focus:Hormones and Endocrinology
Chaste Tree Berry (Vitex)
• One of the top remedies for PMS
• Effective in moderate to severe PMS after 3 cycles
Dante et al., J Psychosom Obstet Gynaecol. 2011Mar;32(1):42-51 Freeman, Expert Opin Pharmacother. 2010 Dec;11(17):2879-89 Ma et al., Gynecol Endocrinol. 2010 Aug;26(8):612-6
Advanced Clinical Focus:Hormones and Endocrinology
Chaste Tree Berry (Vitex)
• Reduces prolactin
• Improves Est:Proges
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Chaste Tree Berry (Vitex)
• Can mimic estrogen
• Proceed with caution:
• Fibroids
• Endometriosis
• Breast cancer (or high risk)
J trig. Food Chem. 2001, 49, 2472-2479
Advanced Clinical Focus:Hormones and Endocrinology
Chaste Tree Berry (Vitex)
• 1-5 ml/day (1:5 tincture)
• 1-4 ml/day (1:2 extract)
• 500 mg BID
Mills Simon, Bone Kerry. Principles and Practice of Phytotherapy. Churchill Livingstone. 2009
Advanced Clinical Focus:Hormones and Endocrinology
Cimicifuga Racemosa Black cohosh
• Used since the 1950s
• Does not activate estrogen receptors
• Anti-estrogenic effects
• Can treat hot flashes
• Activity against breast cancer
Menopause: The Journal of the North American Menopause Society. Vol 9, No. 2, pp. 145-150
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Cimicifuga Racemosa Black cohosh
• 3.5-7 ml/day (1:5 tincture)
• 1.5-3 ml/day (1:2 extract)
• 40-200 mg/day
Mills Simon, Bone Kerry. Principles and Practice of Phytotherapy. Churchill Livingstone. 2009
Advanced Clinical Focus:Hormones and Endocrinology
Birth Control Pill
Before age 20
More than 5 yrs before age 35= 3x Risk of Breast Cancer
Advanced Clinical Focus:Hormones and Endocrinology
Birth Control Pill
• ↑ed risk cervical cancer
• ↑ed risk heart attack
• Yeast overgrowth
• Mask underlying issues (PCOS, endometriosis, fibroids)
• Nutrient depletions: B2, B6, B12, F.A., Vitamin C, Zn, Mg
• Immature reproductive system
• Increased risk of DVT
• Possible contributor to autism1,2
1. Medical Hypothesis. December 2014 Volume 83, Issue 6, Pages 718–725 2. Medical Hypothesis. December 2015 Volume 85, Issue 6, Pages 1006–1011
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Birth Control Pill Discontinuation
• 3-6 months for body to heal
• Length of time it takes depends on:
1. Type of hormonal contraceptive used
2. Length of time on drug
3. Age of drug introduction
4. How healthy cycle was before drug
5. Basic health and nutritional statusSource: Justisse Method
Advanced Clinical Focus:Hormones and Endocrinology
Endocrine Disrupting Chemicals
• Bisphenol A
• Phthalates
• Pesticides
• Persistent organic pollutants
Gore AC, et.al. Executive Summary to EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews 36: 09, 2015 doi: 10.1210/er.2015-1093
Advanced Clinical Focus:Hormones and Endocrinology
• Obesity
• Diabetes
• Female reproduction
• Male reproduction
• Cancers
• Thyroid disease
• Neurodevelopment
Endocrine Disrupting Chemicals
Gore AC, et.al. Executive Summary to EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews 36: 09, 2015 doi: 10.1210/er.2015-1093
Executive Summary to EDC-2: The EndocrineSociety’s Second Scientific Statement onEndocrine-Disrupting Chemicals
A. C. Gore, V. A. Chappell, S. E. Fenton, J. A. Flaws, A. Nadal, G. S. Prins, J. Toppari,and R. T. Zoeller
Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734;Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences,National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences(J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM(A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology andPhysiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612;Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku,Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003
This Executive Summary to the Endocrine Society’s second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full ScientificStatement represents a comprehensive review of the literature on seven topics for which there is strong mech-anistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity anddiabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thy-roid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides,persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxinswere emphasized because these chemicals had the greatest depth and breadth of available information. TheStatement also included thorough coverage of studies of developmental exposures to EDCs, especially in thefetus and infant, because these are critical life stages during which perturbations of hormones can increase theprobability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over thepast 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, includingnonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will proveuseful to researchers, physicians, and other healthcare providers in translating the science of endocrine dis-ruption to improved public health. (Endocrine Reviews 36: 593–602, 2015)
Introduction
In 2008, The Endocrine Society convened a group of ex-perts to review the state of the science on endocrino-
logical effects of environmental endocrine-disruptingchemicals (EDCs), leading to the landmark ScientificStatement on EDCs published in 2009, called hereafter“EDC-1” (1). EDCs are the hundreds or more “exogenouschemical(s), or mixtures of chemicals, that interfere withany aspect of hormone action” (2). In the subsequent 5years, the field has moved forward substantially. Fourlines of research have particularly influenced our knowl-edge about EDCs: 1) studies describing the consequencesof EDC exposure on development and physiology (mainly
conducted in rodent models, but with some notable ex-ceptions in sheep and nonhuman primates); 2) reports in-vestigating the mechanistic underpinnings of these disor-ders (gene expression and epigenetic changes induced incell and tissue culture, together with molecular and cellu-lar work conducted in endocrine tissues of EDC-exposedanimals); 3) work documenting associations betweenbody burdens of certain EDCs with disease propensity inhumans (mainly epidemiological work); and 4) investiga-tions of humans with known occupational or acute expo-sures to a particular chemical or group of chemicals withEDC activity. In 2015, there is far more conclusive evi-dence about whether, when, and how EDCs perturb en-
ISSN Print 0163-769X ISSN Online 1945-7189Printed in USACopyright © 2015 by the Endocrine SocietyReceived August 27, 2015. Accepted September 2, 2015.First Published Online September 28, 2015
Abbreviations: BPA, bisphenol A; DOHaD, developmental origins of health and disease;EDC, endocrine-disrupting chemical; ER, estrogen receptor; PBDE, polybrominated diethylether; PCB, polychlorinated biphenyl; PPAR, peroxisome proliferative-activated receptor.
R E V I E W
doi: 10.1210/er.2015-1093 Endocrine Reviews, December 2015, 36(6):593–602 press.endocrine.org/journal/edrv 593
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 11 December 2015. at 09:58 For personal use only. No other uses without permission. . All rights reserved.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
• Common in household products: food storage, water bottles, health and beauty products, household products
• The BPA substitute BPS also an endocrine-disruptor
• Long-lived chemicals have life-time body burden
• Short-lived may induce permanent changes
• Transgenerational effects now observed
Gore AC, et.al. Executive Summary to EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews 36: 09, 2015 doi: 10.1210/er.2015-1093
Endocrine Disrupting Chemicals
Advanced Clinical Focus:Hormones and Endocrinology
Chemicals
• By the time a women leaves her home, she has applied 126 different chemicals in 12 different products to her face and hair
ewg.org
Advanced Clinical Focus:Hormones and Endocrinology
Libido
• Always a downstream effect of other factors:
• Adrenals
• Thyroid
• Sex hormones
• Stress
• Sleep
• Relationship
• Mind
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Female Hormonal Pathologies
• Fibroids
• Endometriosis
• PCOS
Advanced Clinical Focus:Hormones and Endocrinology
Fibroids and Endometriosis
• Similar etiology
• It’s more than estrogen dominance
Evans, JM. Fibroids and endometriosis. In Textbook of Functional Medicine (Ch. 32, Clinical Approaches to Hormonal and Neuroendocrine Imbalances). Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005. pp. 635-638.
Advanced Clinical Focus:Hormones and Endocrinology
Estrogen Influence
• Not seen prior to puberty
• Enlarge during pregnancy
• Regress at menopause
✗ ↑ ↓
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Inflammation Increases Estrogen
• PG2 stimulates aromatase
Bulun SE, et al., Regulation of aromatase expression in breast cancer tissue. Ann N Y Acad Sci. 2009 Feb;1155:121-31
Advanced Clinical Focus:Hormones and Endocrinology
Aromatization
Aromatase
Advanced Clinical Focus:Hormones and Endocrinology
Decrease Estrogen Formation
• Aromatase inhibitors:
• Dietary fiber and lignins (i.e. flax seed)
• Soy (genistein daidzein)
• Resveratrol (grapes)
• Grape seed extract (proanthocyanidins)
• White button mushrooms
Wang et al., J Steroid Biochem Molec Biol 1994;50:205-12. Eng et al., Ann N Y Acad Sci. 2002 Jun;963:239-46. Kijima et al., Cancer Res. 2006; 66:5960.
Eng et al., Cancer Res. 2003; 63:8516. Grube et al., J. Nutr. 2001; 131:3288. Balunas et al., Phytochem. Lett. 2008.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Estrogen Dominance
• Relatively small amounts (nanograms) of estrogen compared to larger amounts (micrograms) of other steroid hormones have powerful effects
• Regulation of estrogen is potentially much more important
Textbook of Functional Medicine. Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005.
Advanced Clinical Focus:Hormones and Endocrinology
↑Estrogen
↓Progest.
Estrogen Dominance Symptoms
• Breast tenderness
• Fibrocystic changes
• Heavy periods
• Fat distribution on hips and thighs
• Anxiety/Depression
• Fibroid growth
• Endometriosis
• Dysmenorrhea
• Cervical dysplasia
Textbook of Functional Medicine (Ch. 32, Clinical Approaches to Hormonal and Neuroendocrine Imbalances). Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005. pp. 623-6248.
Advanced Clinical Focus:Hormones and Endocrinology
↑Estrogen
↓Progest.
Lack or Progesterone
• Spotting
• Anxiety
• Infrequent ovulation
• Peri-menopause
• Hormone replacement
Textbook of Functional Medicine (Ch. 32, Clinical Approaches to Hormonal and Neuroendocrine Imbalances). Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005. pp. 623-6248.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Estrogen Detoxification and Elimination
• Support liver detoxification
• Promote elimination
• Prevent recirculation
Advanced Clinical Focus:Hormones and Endocrinology
Food and Hormones
• Chemicals can have a hormonal effect
• Full fat dairy from pregnant cows contain lots of estrogen
• Inflammatory foods can increase estrogen
Advanced Clinical Focus:Hormones and Endocrinology
Therapeutic Foods
• Raspberries
• Pomegranate
• Mung beans
• Cruciferous veg.
• Fermented Soy
• Flax
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Nutrients Supporting Detoxification
• Indole-3-Carbinol (I3C): 200mg BID
• Calcium D-Glucarate: 500 mg BID
• Sulforaphane: 1.1-5.5 mg/day
• Curcumin: 500 mg TID (depends on form)
• Rosemary extract: 200-300 mg/day
• Green tea extract: 50mg TID
• Milk thistle extract: 70-210 mg TID
• N-Acetyl-Cysteine: 1 gram TID
Advanced Clinical Focus:Hormones and Endocrinology
Vitamin D
Lower vitamin D levels resulted in higher risk of fibroids. Check vitamin D!
Advanced Clinical Focus:Hormones and Endocrinology
Fibroids and Endometriosis
Estrogen
Inflammation
Insulin
Fat
+
++ +
++
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Stress and Endometriosis
“Endometriosis is an inflammatory disease, and stress and poor quality of
life may cause inflammation…”
Advanced Clinical Focus:Hormones and Endocrinology
PCOS
• Affects 5-10% of women of childbearing age
• Symptoms:
• Irregular menstrual cycles
• Hirsutism
• Acne
• Male pattern baldness (in women)
• Lack of ovulation
Advanced Clinical Focus:Hormones and Endocrinology
Polycystic Ovarian Syndrome (PCOS)
↑ Stress
↑ Cortisol
↑ Blood Sugar
↑ Insulin
↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen
Virilization Amenorrhea
Insulin Resistance
Obesity Metabolic Syndrome
Basin S, Fisher CE, Swerdcloff RS. Follicle stimulating hormone and luteinizing hormone. In: Memed S (ed). The pituitary. 2nd ed. Malden, MASS: Blackwell Publishing 2002; 216-278
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Polycystic Ovarian Syndrome (PCOS)
↑ Stress
↑ Cortisol
↑ Blood Sugar
↑ Insulin
↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen
Virilization Amenorrhea
Insulin Resistance
Obesity Metabolic Syndrome
Basin S, Fisher CE, Swerdcloff RS. Follicle stimulating hormone and luteinizing hormone. In: Memed S (ed). The pituitary. 2nd ed. Malden, MASS: Blackwell Publishing 2002; 216-278
Stress management
Advanced Clinical Focus:Hormones and Endocrinology
Polycystic Ovarian Syndrome (PCOS)
↑ Stress
↑ Cortisol
↑ Blood Sugar
↑ Insulin
↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen
Virilization Amenorrhea
Insulin Resistance
Obesity Metabolic Syndrome
Basin S, Fisher CE, Swerdcloff RS. Follicle stimulating hormone and luteinizing hormone. In: Memed S (ed). The pituitary. 2nd ed. Malden, MASS: Blackwell Publishing 2002; 216-278
Blood sugar regulation
Advanced Clinical Focus:Hormones and Endocrinology
Polycystic Ovarian Syndrome (PCOS)
↑ Stress
↑ Cortisol
↑ Blood Sugar
↑ Insulin
↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen
Virilization Amenorrhea
Insulin Resistance
Obesity Metabolic Syndrome
Basin S, Fisher CE, Swerdcloff RS. Follicle stimulating hormone and luteinizing hormone. In: Memed S (ed). The pituitary. 2nd ed. Malden, MASS: Blackwell Publishing 2002; 216-278
Decrease androgen production
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Multi-Factorial Treatment
• Decrease inflammation
• Improve estrogen metabolism
• Production
• Detoxification and elimination
• Check vitamin D
• Decrease BMI
• Improve insulin sensitivity
• Stress management
Diet Functional Foods
SupplementsLifestyle
Menopause
Advanced Clinical Focus:Hormones and Endocrinology
Menopause
• Permanent cessation of menstruation
• Avg age: 51
• Ovaries stop making hormones
• Adrenals and adipose tissue take over
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Menopause Symptoms
• Hot flashes
• Headaches
• Atrophic vaginitis
• Freq. UTIs
• Cold hands/feet
• Forgetfulness
• Inability to concentrate
Advanced Clinical Focus:Hormones and Endocrinology
Menopause and Exercise
• Women who spent 3.5 hours per week exercising had no hot flashes
Hammar M, Berg G, Lingren R. Does physical exercise influence the frequency of post-menopausal hot flushes? Acta Obstetrica et Gynecologica Scandinavica 1990;69:409-412
Advanced Clinical Focus:Hormones and Endocrinology
Menopause and Soy
• ↓s hot flashes
• Slow bone loss
• ↓s cholesterol
• ↓s blood pressure
• ↓s risk of breast cancer Dose = 2/3 cup
Dalais FS, Rice GE, Dahlqvist ML, et al. Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1998;1(2):124-129
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
• Key factor: ability to convert isoflavones into equol
• Healthy microbiome essential
Menopause and Soy
Advanced Clinical Focus:Hormones and Endocrinology
Microbiome and Hormones
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 2011, p. 1494–1503 Vol. 55, No. 40066-4804/11/$12.00 doi:10.1128/AAC.01664-10Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Effect of Antibiotic Treatment on the Intestinal Metabolome!
L. Caetano M. Antunes,1 Jun Han,2 Rosana B. R. Ferreira,1 Petra Lolic,1,3
Christoph H. Borchers,2 and B. Brett Finlay1,3*Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada1; University of
Victoria Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia V8Z 7X8, Canada2; andDepartment of Microbiology and Immunology, The University of British Columbia,
Vancouver, British Columbia V6T 1Z3, Canada3
Received 1 December 2010/Returned for modification 8 January 2011/Accepted 21 January 2011
The importance of the mammalian intestinal microbiota to human health has been intensely studied over thepast few years. It is now clear that the interactions between human hosts and their associated microbialcommunities need to be characterized in molecular detail if we are to truly understand human physiology.Additionally, the study of such host-microbe interactions is likely to provide us with new strategies tomanipulate these complex systems to maintain or restore homeostasis in order to prevent or cure pathologicalstates. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between theintestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and hasa profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected.Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid,and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficialmicrobes on some of these pathways will be instrumental in understanding the interplay between the host andits complex resident microbiota and may aid in the design of new therapeutic strategies that target theseinteractions.
The human body is colonized by a complex community ofmicrobes termed microbiota or microbiome (9, 17, 18, 24).Virtually every surface of the human body that is exposed tothe environment has its own microbial assemblage, with dif-ferent microbial species and distinct functions associated withthem. The intestinal tract is by far the most heavily colonizedbody site; it has been estimated that the human gut harborssome 1014 microbial cells (14, 22, 32). This microbial consor-tium is critical for human health and has been implicated in thedevelopment of the immune system, energy homeostasis, andprotection against pathogens, among other processes (18, 24).Conversely, imbalances in the intestinal microbiota have alsobeen associated with many pathological processes, includinginflammatory bowel disease, diabetes, asthma, obesity, autism,and others (18, 24).
The use of antibiotics is known to have significant effects onthe intestinal microbiota. The acquisition and spread of anti-biotic resistance genes between and within bacterial commu-nities due to antibiotic use have also been studied thoroughly(12). This has caused an increased awareness of the impor-tance of a more responsible use of antibiotics. However, it isonly recently that studies began to reveal details of the impactof these drugs on intestinal microbial communities. For in-stance, it is now well established that antibiotic treatment in-creases susceptibility to enteric infections (10, 23, 25); some ofthe members of the microbiota involved in this process arecurrently under investigation. Although these studies are in-
dispensable to our understanding of the effects of antibiotics inthe human body and the importance of the intestinal microbi-ota for human health, the mechanisms involved in these inter-actions remain mostly unknown.
Much of what we have learned about the intestinal micro-biota comes from high-throughput sequencing studies of theintestinal metagenome, which address only the microbial com-position of the samples but do not define the metabolic func-tions involved (3, 34). Recently, metabolomics has been estab-lished as a new technology whose aim is to study the complexlexicon of small molecules present in any given biological sam-ple, or the metabolome (6, 8, 19, 31). In order to expand ourunderstanding of the importance of the intestinal microbiotaas well as the disturbances elicited by antibiotic treatment, wehave used metabolomics to obtain a snapshot of the chemicalcomposition of the intestinal environment before and afterantibiotic treatment. By using Fourier transform ion cyclotronresonance mass spectrometry with direct infusion (DI-FT-ICR-MS) (6), we determined that a single, high dose of theantibiotic streptomycin can have a profound impact on thelevels of the majority of the compounds detected. Predictivemapping of these compounds to corresponding metabolicpathways showed that many crucial host metabolic functionsare disturbed. Among some of the pathways affected are thoseinvolved in sugar, amino acid, fatty acid, bile acid, steroid, andeicosanoid metabolism. Additionally, we show that clinicallyrelevant antibiotic doses can also disrupt host eicosanoid me-tabolism. Our results show that the microbiota has effects onpreviously unidentified host functions. Additionally, the criticalfunctions of all pathways affected suggest that the impact ofantibiotics on mammalian physiology extends far beyond thedevelopment of microbial drug resistance.
* Corresponding author. Mailing address: The University of BritishColumbia, 301-2185 East Mall, Vancouver, BC V6T 1Z4, Canada.Phone: (604) 822-2210. Fax: (604) 822-9830. E-mail: [email protected].
! Published ahead of print on 31 January 2011.
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Of the many metabolic pathways affected by antibiotic treatment, the metabolism of steroid hormones was the most profoundly impacted.
Advanced Clinical Focus:Hormones and Endocrinology
Menopause and Flax Seeds
• Contain lignans: matairesinol, secoisolariciresinol
• Estrogen-modulating effect
• 2 tbsp BID decreases hot flashes by 50% within 6 weeks
Haggans CJ, Hutshins AM, Olson BA, et al. Effect of flax-seed consumption on urinary estrogen metabolites in post-menopausal women. Nutrition and Cancer 1999;33(2):188-195 Pruthi SL et al. Pilot evaluation of flaxseed for the management of hot flashes. Journal of the Society for Integrative Oncology 2007;5(3):106-112
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Cimicifuga Racemosa Black cohosh
• Selective estrogen receptor-modifying activity
• Most prescribed natural treatment
• As good as estrogen replacement without the risks
Wattle W. Seilova-Wuttke D, Gorkow C. The Cimifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind study: effects on menopause symptoms and bone markers. Maturitas 2003;44:S67-S77
Advanced Clinical Focus:Hormones and Endocrinology
Other Nutrients That Can be Helpful
• Fish oil: 1000 mg/day
• Vitamin C: 500-1000 mg/day
• Vitamin E: 200-400 iu/day
• Black Cohosh: see above
• Maca: 3.5 grams/day
• Red Clover: 40-80 mg/day
• Dong Quai: 1-2 g TID
• Estrovera: 1 tablet/day
Male Specific
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Male Concerns
• Andropause
• Erectile dysfunction
• Prostate enlargement (benign prostate hyperplasia)
• Prostate cancer
Advanced Clinical Focus:Hormones and Endocrinology
Does Andropause Exist?
Advanced Clinical Focus:Hormones and Endocrinology
Testosterone Decline
http://www.londonendocrinecentre.co.uk/Androgen-Deficiency.html
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Prevalence of Low T In Other Conditions
• Obesity 52%
• Diabetes 50%
• AIDS/HIV 30%
• Hypertension 42%
• Hyperlipidemia 40%
• Erectile dysfunction 19%Daniel HW. J Pain. 2002: 3:377-384 Mulligan T, et al., Int J Clin Pract. 2006; 60: 762-769 Grinspoon S, et al., Ann Intern Med. 1998; 129:18-26 Dobs AS. Bailliere Clini Endocrin Metabol. 1998
Advanced Clinical Focus:Hormones and Endocrinology
Catch 22
Low testosterone
Obesity
Chen RY, et al., Diabetes Obes Metab. 2006 Jul;8(4):429-35.
Advanced Clinical Focus:Hormones and Endocrinology
Obese Teens and Testosterone
• Obese males 14-20 = 50% less testosterone
• Increases risk of impotence and infertility
Testosterone
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Testosterone and Longevity
• Mortality levels 88% higher in men with low testosterone
Shores MM, et al., Arch Intern Med. 2006 Aug 14; 166(15):1660-5.
Advanced Clinical Focus:Hormones and Endocrinology
Influence of Testosterone
Bone marrow •RBC production
Male sex organs •Sperm production •Prostate growth •Erectile dysfunction
Muscle •Muscle mass and
strength
Brain •Libido •Positive feelings •Cognition and memory
Skin • Growth of facial and body hair
• Supports collagen
Bone •Bone density
Advanced Clinical Focus:Hormones and Endocrinology
Erectile Dysfunction
• Inability to maintain erection
• Prevalence:
• <59 = 12%
• 60-69 = 22%
• >69 = 30%
• Atherosclerosis cause of ED in 50% over 50
Hatzimouratidis K. Epidemiology of male sexual dysfunction. American Journal of Men’s Helath 2007 Jun;1(2):103-125
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Erectile Dysfunction Causes
• 90% Organic
• Vascular insufficiency
• Drugs
• Alcohol/tobacco
• Endocrine disorders
• 10% Psychological
Advanced Clinical Focus:Hormones and Endocrinology
• Plays a critical role in erections
• Causes vasodilation
• Nutrients that increase:
• L-arginine
• L-citrulline
Nitric Oxide
Advanced Clinical Focus:Hormones and Endocrinology
Selenium and Prostate
• Selenium decreases PSA
• 200 mg/day
Zhang W, et al., Nutr Res. 2011 Feb 12.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Maca and Prostate
• Red maca reduces prostate size in rats
• Increase sperm production, motility, and semen volume
• 4:1 extract 525 mg TID
Forsch Komplementmed. 2009 Dec;16(6):373-80. Epub 2009 Dec 16.
Advanced Clinical Focus:Hormones and Endocrinology
Pygeum Africanum and Prostate
• “Pygeum Africanum extract administration improved all the urinary parameters we investigated; prostatic echography relieved reduction of peri-urethral edema.”
• 300 mg BID-TID
Arch Ital Urol Nefrol Androl. 1991 Sep;63(3):341-5.
Advanced Clinical Focus:Hormones and Endocrinology
Urtica Dioica (Nettle) and Prostate
• Decreases prostate size
• Beneficial for benign prostate hyperplasia
• 1000 mg BID-QID
J Herb Pharmacother. 2005;5(4):1-11.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Saw Palmetto and Prostate
• “The evidence suggests that serenoa repens provides mild to moderate improvement in urinary symptoms and flow measures. Serenoa repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events.”
• 300-600 mg BID
Cochrane Database Syst Rev. 2002;(3):CD001423. Cochrane Database Syst Rev. 2009;(2):CD001423.
Advanced Clinical Focus:Hormones and Endocrinology
Zinc for Sexual Health
• Multiple studies on Zn for infertility and low testosterone
• 37 infertile men given 60 mg of Zn for 45-50 days
• Testosterone in 22 patients significantly increase and sperm count went from 8 to 20 million
Tikkiwal M, et al. Ind J Phys Pharm 1987 Jan-Mar; 31(1):30-34. Takihara H, et al. Urology 1987 Jun; 29(6): 638-641. Netter A, et al. Arch Androl 1981; 7(11): 69-73.
Advanced Clinical Focus:Hormones and Endocrinology
Exercise and Testosterone
• Strength training, high-intensity cycling increase testosterone
Izquierdo M, et al. J App Physiol 2001; 90(4): 1497-1507. J Strength Cond Res. 2011 Jan;25(1):23-31. Kraemer WJ, et al. J App Physiol 1999 Sep; 87(3): 982-92.
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Addressing Male Hormone Imbalance
• Decrease aromatase activity
• Prevent the cortisol steal
• Improve BMI, and muscle
• Eliminate xenoestrogens
• Avoid toxins
• Low GI/GL diet
• Exercise
• Supplements
Diet Functional Foods
SupplementsLifestyle
Advanced Clinical Focus:Hormones and Endocrinology
Summary
• The endocrine system autocorrects when the root cause is addressed
• Address blood sugar first, then adrenals, then thyroid, then sex hormones
• Give at least 2-3 months to begin to see changes
Advanced Clinical Focus:Hormones and Endocrinology
Summary
Diet Functional Foods
SupplementsLifestyle
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
Current
EvidencePatient’sStory
Advanced Clinical Focus:Hormones and Endocrinology
Personalized
Advanced Clinical Focus:Hormones and Endocrinology
“Knowledge is not power, until it’s applied.”
Dale Carnegie
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved
Advanced Clinical Focus:Hormones and Endocrinology
evidence-based clinical nutrition and integrative healthcare
Thank you!
Copyright © 2015 ● Josh Gitalis Ba(H), RNCP/ROHP, CNP ● All Rights Reserved