LET S TALK TESTING! *Why am I stressed, tired, fat, sick, moody, anxious and more?

Transcription

1 LET S TALK TESTING! *Why am I stressed, tired, fat, sick, moody, anxious and more? By: Carrie Jones, ND, MPH Medical Director Precision Analytical, Inc. Lecture in conjunction and sponsored by:

2 Medical Disclaimer: The medical information in this lecture is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This lecture contains general information about medical conditions and treatments. The information is not advice, and should not be treated as such. This information is not intended to be patient education, does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment. The medical information in this lecture is provided as is without any representations or warranties, express or implied. Precision Analytical, Inc (DUTCH) makes no representations or warranties in relation to the medical information on this website.

3 Objectives 1. Understand what the adrenals do 2. Understand cortisol s main jobs 3. Differentiate between anabolic and catabolic patients 4. Understand Adrenal related hormones 5. Understand 5a-Reductase and its impact on your patients 6. Learn 11bHSD1 vs 11bHSD2 7. Debunk Adrenal Fatigue and why 8. Review diagnosable Adrenal conditions 9. Understand different testing forms focusing on DUTCH testing 10. Learn comprehensive treatment options for patients 11. Review estrogen metabolism

4 Reality in the United States In 2014, NPR did a survey where they questioned 2,500 adults across the country. 49% said they had a stressful EVENT in the past year. Poor health was listed as the number 1 reason. The Anxiety and Depression Association of America states 40 million suffer from anxiety disorders and 75% have their first episode of anxiety by age 22yo. In 2013, the Work Stress Survey conducted by Harris Interactive on behalf of Everest College found 83% of 1,019 Americans polled are stressed out by work increasing workloads and poor pay were the biggest stressors. In 2012, Diabetes.org reported 29.1 million Americans have diabetes (9.3% of the population) they feel 20.1 million are undiagnosed. In 2014, the CDC stated they feel 40% of Americans (or 2 out of every 5 Americans) will develop diabetes at some point in their adult life. The CDC states 36% of Americans are obese. That s over 1/3 of Americans. The NIH feels 23.5 million Americans have autoimmune conditions while the American Autoimmune Related Diseases Association feels it s more like 50 million. NIH estimates annual direct health care costs for autoimmune Disease to be in the range of $100 billion/yr

5 Reality in Canada: You re not exempt! A 2010 report says 1 in 4 Canadians are clinically obese. The direct costs of addressing these obesity related issues is $6 billion CAD/year Statistics Canada state over 1 in 4 (27%) workers report being highly stressed 6 in 10 workers reported WORK as their primary stressor The remainder sited financial, family and health as major causes of stress Mental health problems are due to cost $20 billion CAD/year The Canadian Diabetes Association states 11 million Canadians have diabetes or pre-diabetes (population of Canada: 36 million)

6 Stress Definition: State in which homeostasis is actually threatened or perceived to be so from: 1. emotional, physical, psychological, environmental, chemical stressors 2. actual, anticipated and/or imagined stress Stress is cumulative!

7

8 Back to the basics: What do the Adrenal Glands do?

9 Zona fasiculata Cortex Makes cortisol Cortisol not stored for immediate release (estimated takes about 10 min for release to occur compared to norepi/epi) Normal ½ life with a healthy liver is 1-2 hours (depending on research) Bound by cortisol binding globulin/transcortin (mostly) and albumin 75% circulating cortisol bound to CBG, 20+% bound to albumin 78% cortisone bound to CBG Free cortisol is <5% circulating but is active form.

10 Zona Glomerulosa cortex Makes Aldosterone Salt/water balance 17% aldosterone bound to CBG, 47% bound to albumin, 36% free Controlled mostly by angiotensin II and partly by ACTH

11 Zona reticularis cortex Makes Sex Hormones: In women: all DHEAs, 80% of the DHEA, 50% of androstenedione 25% of testosterone in women In Men: all DHEAs 80% DHEA <10% androstenedione <5% testosterone

12 Adrenal Medulla Makes Catecholamines: Norepi and Epi Tyrosine phenylalanine dopamine norepi via stimulation of PNMT enzyme by cortisol epi These are pre-stored, ready to be released immediately when triggered by acetylcholine Half-life of a few minutes Broken down by deamination/mao and methylation/comt

13 *Take Home* The principle hormones are cortisol and DHEA (regulated by the HPA axis) and the catecholamines (norepi and epi) regulated by the systemic and adrenomedullary sympathetic nervous system.

14 What is the fight or flight response? The problem when stress occurs, the HPA axis RUNS to the adrenals instead of going to the neocortex for logical processing = *Freak out*

15 What is the (simplified) stress response?

16 What is the fight or flight response? Initiation of the response sensory nerve cells pass the perception of a threat, or stress, from the environment (internal or external) to the hypothalamus in the brain. Neurosecretory cells in the hypothalamus transmit a signal to the pituitary gland inciting cells there to release a chemical messenger into the blood stream (CRH ACTH) Simultaneously, the hypothalamus transmits a nerve signal down the spinal cord. Both the chemical messenger and nerve impulse travel to the same destination = the adrenals Norepi and epi dumped immediately Cholesterol pulled into the mitochondria for cortisol to be made

17 Wait what? Cholesterol pulled into the mitochondria for cortisol to be made (what about the pregnenolone steal?)

18 What is the fight or flight response? Continuation of response cortisol and norepi/epi are released into the blood stream where they continue the signaling cascade in several cell types, resulting in an increase in blood pressure, increase in blood sugar levels (gluconeo/glycogeno), and suppression of the immune system as well as: Acceleration of heart and lung action Paling or flushing, or alternating between both Inhibition of stomach and upper intestinal action (digestion slows down or stops) General effect on the sphincters of the body Constriction of blood vessels in many parts of the body Liberation of nutrients (particularly fats and glucose) for muscular action Dilation of blood vessels for muscles Inhibition of lacrimal gland (responsible for tear production) and salivation Dilation of pupils Relaxation of bladder Inhibition of erection/loss of libido Auditory exclusion (loss of hearing) Tunnel vision (loss of peripheral vision) Acceleration of instantaneous reflexes Shaking

19 Fight or flight: Energy to run : 1. When epi binds to receptors on liver cells gluconeogenesis. 2. Cortisol sets fatty acids free glycogenolysis. Now your glucose in the blood stream is much higher.

20 What is the fight or flight response? Long term: consistently in fight/flight mode, the cortisol and epi/norepi production starts to fail, the brain downregulates, receptor sensitivity occurs and the para-sympathetic nervous system is continuously downregulated.

21 What are the long term consequences? more GI issues, anxiety/panic, sleep disturbance, sexual problems, fatigue, damage to the mitochondria, killing off of the neurons in the hippocampus (memory and creativity) and more!

22 Who has the patient who comes in reporting fatigue, digestive issues, infertility, no libido, thirsty all the time, frequent urination, and increased anxiety? Maybe she has bad hot flashes when she s stressed? Perhaps he s not motivated anymore, can t lose weight or get an erection?

23 Chronic stress can lead to a rut in which the wiring of our neural networks keeps us repeating the same dysfunctional behavior and hoping for a different outcome Power Up Your Brain (David Perlmutter MD, Alberto Villoldo Ph.D.)

24 Let s talk emotions and thoughts:

25 Emotions and thoughts continued Neural networks are plastic Thinking something over and over, do a particular activity over and over = reinforce the neural network to correlate with those thoughts/activity/skills (good or bad) Repetitive thoughts/activities once use to serve us (good or bad) get stuck in a rut and become habit but it can give us false beliefs about the world, acquaintances, friends or even family These beliefs become subconscious leading to self-sabotage Trauma is not what actually happened but how you stored it as the story in your mind. Power Up Your Brain

26 To Sum up: It all starts with the brain s decision to kick off the cascade Hypothalamus CRH pituitary ACTH adrenal glands cortisol formation Norepi and epi are released immediately as they are pre-formed

27 So if it s the brain s decision, why do we blame the adrenals?

28 Reality check: It s very complicated and systemically involved!

29 What are cortisol s primary jobs? 1. Blood sugar balance gluco cortico steroid for a reason. Gluconeogenesis and glycogenolysis 2. Wake/sleep center 3. Anti-inflammatory to a point Influences both innate and acquired immunity Can influence a Th1 to Th2 switch Proinflammatory cytokines stimulate the stress system

30 Anabolic versus Catabolic people *Helpful to know if someone is cortisol dominant or not.

31 Anabolic Processes that build up create complex materials from simpler substances. Hormones: Growth hormone IGF-I and other insulin like growth factors Insulin healthy response, not IR Testosterone Estrogen Push anabolic through: Amino acid mineral chelates (creatine magnesium chelate) Ecdysterone rich herbal extracts Rhaponticum and Suma Epimedium (Icariin) improves testosterone to cortisol ratio Whey protein Testosterone, DHEA HIIT and intermittent fasting raise GH Strength training to build muscle Sleep need 7-9 hours/night for hypothalamus

32 Catabolic Processes that break things down break down large molecules into smaller ones, release energy as ATP Hormones: Norepinephrine Cortisol Glucagon made by pancreas to break down glycogen in liver Adrenalin/Epinephrine Cytokines Push Catabolic through: Aging Stress Cardio exercise steady state burns lots of calories doesn t accumulate muscle mass (running, cycling, swimming, crosscountry skiing)

33 Catabolic people have higher Cortisol to DHEA/Testosterone 1) Due to aging, high stress and people s belief in steady state cardio, the catabolic process is only increased over time. 2) If catabolism is producing more energy than anabolism requires there will be excess energy. The human body stores this excess energy in fat or glycogen (glycogen stored as carbohydrate in liver, and some in muscles)

34 Let s review other hormones:

35 WHICH MODEL IS CORRECT? Cholesterol Cholesterol Pregnenolone Circulating Hormone Pregnenolone In Mitochondria of Adrenal Gland Progesterone Progesterone Cortisol Cortisol Adrenal gland makes cortisol from circulating pregnenolone or progesterone (ie. supplementing) Cholesterol is converted to pregnenolone, then progesterone, and finally cortisol all within the mitochondria of the adrenal gland

36 What does Pregnenolone do? Synthesized from cholesterol in the MITOCHONDRIA Depending on ACTH, FSH or LH it makes Progesterone 17a-hydroxypregnenolone 17,20 Lyase DHEA Neurosteroid in the brain Neuroprotective, improve myelination, improve cognition Allopregnenolone (in particular) = agonist at GABAa receptor and modulates NMDA receptor

37 What does DHEA do? 80% DHEA made in the adrenals, 100% of DHEA-s made in the adrenals DHEA DHEAs via the SULT2A1 gene, sulfotransferase enzyme in the endoplasmic reticularis DHEAs is the sulfate ester of DHEA o Reversibly catalyzed in adrenals, liver and intestines (DHEA-s DHEA) o DHEA supplementation converted to DHEAs in liver and intestines o DHEAs has no diurnal pattern like cortisol, DHEA (no s) is highest in the morning

38 DHEA, Stress and the Brain Function as anabolic counter-regulatory hormone to cortisol Weak partial agonist at androgen receptor DHEA can be made in the brain as a neurosteroid to protect CNS tissues from high cortisol

39 DHEA Increased by: 1. Supplementation 2. Stress 3. Insulin 4. PCOS 5. Alcohol 6. Meds ADD meds Xanax Wellbutrin Decreased by: 1. Age 2. HPA axis dysfunction 3. inflammation (inflammation lowers sulfation) 4. SULT2A1 problems 5. Sulphur deficiency 6. glucocorticosteroids 7. opioid pain medications

40 What about when DHEA/Testosterone cause symptoms? Look at the 5a-Reductase activity!

41 What is 5a-Reductase? The enzyme that converts androgens to the more potent alpha pathway. Hormones Androsterone 5a-DHT

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43 How do you lower 5a-Reductase? Lower stress Lower inflammation Balance blood sugar/insulin Saw palmetto Zinc Stinging nettles Pygeum Reishi mushroom Medications: Advodart(men) Metformin Spironolactone

44 What does Melatonin do? Not an adrenal hormone but highly involved Made in the pineal gland in response to darkness Comes from serotonin via stimulation of MSH MSH: melanocyte stimulating hormone

45 Melatonin continued Helps the circadian rhythm Helps with timing and release of female reproductive system Strong anti-oxidant often used in cancer treatment in integrative practices Low melatonin can cause insulin resistance The action of melatonin also regulates the expression of transporter glucose type 4 (GLUT 4) or triggers phosphorylation of the insulin receptor

46 Melatonin continued Raises Melatonin: Supplementation, stress(mildly), 5HTP, SAMe, tryptophan, Luvox/fluvoxamine (SSRI), Birth control pills, cherries, walnuts, mustard, corn, rice, ginger, peanuts, barley, oats, asparagus, and tomatoes. Suppresses or causes decreased Melatonin: cortisol, Caffeine, tobacco, alcohol, blue-light exposure at night (ie. phones), mutations in snps AANAT and ASMT, Fluoxetine in particular (prozac), calcium channel blockers (amlodipine, verapamil, diltiazem, nifedipine), Beta Blockers (atenolol, metoprolol, propranolol), NSAIDS (aspirin, ibuprofen/advil, motrin, alleve)

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48 Does Adrenal Fatigue Exist?

49 Raise your hand if all of your patients have self-diagnosed adrenal fatigue?

50 Adrenal Fatigue? How do you know?

51 History lesson 101: Hans Selye and the General Adaptation syndrome in the late 1930 s until his death in 1982: indicating that people when through phases: Phase 1, Phase 2 and Phase 3 Adrenal Fatigue He was the first to show the existence of biological stress Turns out in the 1950 s until his death he was a paid consultant for the tobacco industry working on pro-smoking campaigns and research funded by the tobacco industry. You have to look at both cortisol production (total) coupled with free cortisol While the symptoms are absolutely real, the adrenal glands do not burn out In essence they do not go through menopause and shut down like the ovaries do It s the brain s job to communicate down to the adrenal glands Lots of factors influence this: nutrient depletion, stress, inflammation, thyroid issues, infection, lifestyle factors, sleep, medications, Traumatic brain injury etc. Better qualified as HPA axis dysfunction than adrenal fatigue = look at the entire HPA axis.

52 What are the main diagnosable adrenal conditions?

53 Medical Adrenal Conditions: Congential Adrenal Hyperplasia (CAH): Inherited form of adrenal hyperplasia due to mutations in the 21-hydroxylase enzyme Causes low cortisol, elevated ACTH, elevated 17 hydroxyprogesterone and low aldosterone Cushing s: Disease: produces too much cortisol due to a tumor Syndrome: excessive long-term exposure to glucocorticoids like prednisone 70% are due to pituitary adenomas but can be due to ectopic ACTH-tumor in the lung or adrenal gland Addison s Disease: From immune mediated destruction of the adrenocortical cells predominantly Th1

54 Let s talk testing beyond diagnosable conditions

55 Because the stress response is so complex, having as comprehensive of testing as possible is helpful. It goes beyond Stage I, II and III Adrenal Fatigue

56 What are my testing options? DUTCH test (dried urine test for comprehensive hormones) Collection by urinating on 4-5 strips of filter paper throughout the day reports the diurnal pattern reports free cortisol and free cortisone levels reports metabolized cortisol (about 80% of cortisol production) gives relative activity of 11bHSD enzyme based on cortisol and cortisone metabolites Serum Requires a blood draw No diurnal pattern Results are a combination of bound and unbound cortisol in one lump sum 24-hour urine Requires collection of urine in one jug for 24 hours No diurnal pattern Does metabolized cortisol Does do free cortisol Saliva Collection by spitting in a tube 4 times throughout the day reports the diurnal pattern Tests free cortisol Does not test metabolized cortisol no good look at cortisol production Does not test cortisone Does not look at 11bHSD

57 What do you really need to know? Cortisol Production/Clearance How much is made by the glands and cleared in total? Free Cortisol How much is free and available? Cortisol Pattern What is my diurnal (up and down) rhythm through the day?

58 What are my testing options? DUTCH test (dried urine test for comprehensive hormones) Collection by urinating on 4-5 strips of filter paper throughout the day reports the diurnal pattern reports free cortisol and free cortisone levels reports metabolized cortisol (about 80% of cortisol production) gives relative activity of 11bHSD enzyme based on cortisol and cortisone metabolites Serum diurnal pattern Free cortisol Metabolized cortisol Cortisone 24-hour urine Requires collection of urine in one jug for 24 hours diurnal pattern Does metabolized cortisol Does do free cortisol Saliva Collection by spitting in a tube 4 times throughout the day reports the diurnal pattern Tests free cortisol metabolized cortisol no good look at cortisol production and 11bHSD Cortisone

59 Those who are new to Spot urine testing: Urinary Free Cortisol Salivary Free Cortisol Jerjes, (2005, 2006)

60 Do Urine & Saliva Free Cortisol Agree? 3 Saliva samples over 2hrs compared to urine samples collected over the same 2hrs

61 Dried vs. Liquid Urine

62 Do 24-hour and spot urine agree? Unpublished data, Precision Analytical

63 Let s go back what are you testing? CORTISOL PRODUCTION LEVELS & CIRCULATING FREE CORTISOL LEVELS ARE NOT EXACTLY THE SAME THING

64 What is so important about metabolized cortisol? Metabolized cortisol represents 80% of total cortisol production Free cortisol = 1% (Stewart and Krozowski, 1999).

65 Tell me more Remember: Cortisol is made in the adrenals or converted into cortisol via 11bHSD1 Free cortisol = <5% circulating in serum, it is the active cortisol and can bind to receptors The rest is bound to CBG and albumin Metabolized cortisol: Primarily occurs in liver Represents about 80% of cortisol production however if the liver is fast or sluggish influences the results Answers the question: How much cortisol is being made in-total?

66 Wait, What is 11bHSD1 and 11bHSD2? 11-Beta hydroxysteroid dehydrogenase

67 Wait, What is 11bHSD1 and 11bHSD2? 11-Beta hydroxysteroid dehydrogenase 11bHSD2 converts cortisol inactive cortisone with NAD in the distal nephron of the kidney, sweat gland, salivary glands and colon. The inactivation happens at sites where aldosterone induces an effect on sodium It is upregulated by: stress, post-acute illness, estrogen, retinoic acid and DHEA It is downregulated by ACTH, progesterone, GH also, glycyrrhetinic acid (licorice), stress modifying activities and nitric oxide 11bHSD2 activity helps prevent glucocorticoids from getting access to mineralcorticoid receptors

68 Wait, What is 11bHSD1 and 11bHSD2? 11-Beta hydroxysteroid dehydrogenase 11bHSD1:converts cortisone cortisol with NADPH in the liver, adipose tissue, lung, skeletal muscle, vascular smooth muscle, anterior pituitary, brain and adrenal cortex It is upregulated by glucocorticosteroids, T4, inflammatory cytokines,obesity, glycyrrhetinic acid (licorice) It is downregulated by magnolia, skullcap, zizyphus, polymethoxylated flavonoids (nobiletin and tangerentin), insulin, estrogen, growth hormone

69 Obesity and 11bHSD1 (11-beta-hydroxysteroid dehydrogenase-1) 11b-HSD1 found in every cell in the body More at risk for adipose gain, diabetes/fatty liver, and memory issues More cortisol = more fat storage esp. when 11bHSD1 is coming from right within the fat cell Even with low controlled systemic cortisol, if 11bHSD1 is upregulated in the fat cell, it sees higher cortisol = cortisol gets amplified = fat gain

70 How do I test 11bHSD activity? Research says you have to look at urinary cortisol and cortisone metabolites THF (cortisol) to THE (cortisone) ratio

71 Do we need to test both metabolized and free Cortisol in order to help our patients?

72 This free cortisol is low = Adrenal fatigue? Free Cortisol Metabolized cortisol

73 Look to the metabolized cortisol! Free Cortisol Metabolized cortisol

74 How do I address my patients?

75 Gut

76 Treatment Basics: Immediately get blood sugar under control Don t skip meals puts you into fight/flight and requires cortisol to rise to counter hypoglycemia Eat healthy Avoid gluten research is huge on this. Avoid food intolerances in general. Minimize sugar = address their blood sugar/insulin issues! Avoid aspartame and MSG = damages the hypothalamus Glutamate is an excitatory hormone and can destroy brain neurons Eliminate the inflammation and test for infections This is critical! Definitely clean up the gut first! Reduce stress, find joy/love, do things that make you happy, daily positive affirmations Say no, set limits, set boundaries, nourish relationships Get enough water daily Minimize alcohol = general hypothalamic depressant Eliminate environmental toxins Exercise most days of the week if they are able consider interval training/weight lifting Sleep at least 7 hours per night to hit all REM cycles, increase GH and increase melatonin Get a massage or acupuncture, see a therapist

77 What Are Adaptogens?

78 According to herbalist David Winston, they work through the HPA and sympatho- regulatory system and help reduce cortisol induced mitochondrial dysfunction Wikipedia says: Adaptogens or adaptogenic substances, compounds, herbs or practices refer to the pharmacological concept whereby administration results in stabilization of physiological processes and promotion of homeostasis, for example, decreased cellular sensitivity to stress.

79 It must be adrenal Fatigue I took adaptogens and felt better!

80 Commonly accepted Adaptogens: Ashwagandha American Ginseng (Panax quin) Asian Ginseng (Panax) Cordyceps sinensis Eleutherococcus Rhodiola

81 Probably Adaptogen but mixed reviews: Maca Codonopsis poor man s ginseng Schisandra berry Astragalus Rhaponticum cathamoides (root) Reishi (Ganoderma)-mushroom Gynostemma pentaphyllum Shilajit- tar in Himalayans and Tibetan mountains.

82 Basic Nutrients for the HPA axis: Vitamin C Pantothenic acid (B5) Zinc Iron Magnesium Selenium

83 Brain/Amino Acid Support for the HPA: Theanine in the leaves of green tea, non-sedating relaxant, reduces anxiety, helps increase alpha waves in the brain ( relaxed-awakeness waves ) Dose: mg Phenibut (β-phenyl-γ-aminobutyric acid =GABA Analogue), able to cross the BBB when technically GABA should not, inhibitory neurotransmitter/central depressant, reduces anxiety Dose: mg 5-HTP supports serotonin to balance norepi/epi, careful if someone is already on an SSRI, helps with mood, sleep and appetite Dose: mg Glycine helps calm and relax the brain Dose: mg Tyrosine sublingual or liposomal appear to help the brain more while capsules appear to help the adrenals more, supports dopamine/epi/norepi, can be supportive of thyroid (T-4, T-3) Dose: mg DLPA converts into tyrosine to support dopa/norepi/epi, increases enkephalins to lower pain, avoid with PKU patients Dose: mg L-dopa increases dopamine, responsible for feels of pleasure and satisfaction, low levels = cravings and addiction. Dose: mg (Macuna)

84 Adrenal Essence: B6, B5, Cordyceps, Rhodiola, PABA, Panax Adrenal Manager: B vitamins, Mg, Zinc, bioflavonoid complex, l-tyrosine, glandulars, rhodiola, grape extract B Activ: Active B vitamins AdrenaMax: l-tyrosine, NAC Cortisolv: Relora, ashwagandha, l-theanine, Banaba, Rhaponticum carth. SerenX: Rehmannia, schisandra, zizyphus, Chinese asparagus, Dong quai, Panax etc. Mood Food ES: taurine, 5HTP, l-theanine, GABA RelaxMax: myo-inositol, taurine, GABA, l-theanine Sedalin: Magnolia and zizyphus

85 Let s get DUTCH specific!

86 Main DUTCH Cortisol Patterns: o All low o All high o Low free, high metabolites Increased clearance resulting in low free levels o High free, low metabolized Typical thyroid pattern

87 Low Free Cortisol and Metabolized Cortisol Lower end DHEA Low metabolized cortisol Deactivating to cortisone systemically Low free cortisol

88 Low Free Cortisol and Metabolized Cortisol Likely a lack of communication from the brain down to the adrenals o Find the cause Double check suppression from steroids (oral, injected, topical, inhalers and intranasal spray) Double check suppression from opioid pain medications Double check suppression from Accutane Ask about history of TBI possibly damaging hypothalamus and/or pituitary Is it Addisons? Double check full thyroid panel with rt3 and antibodies A. Adrenal and brain glandulars B. DHEA if DHEAs and metabolites are low C. Consider hydrocortisone = Cortef supplied in 5mg, 10mg and 20mg tabs D. Nutrients and Brain support E. Adaptogens F. Licorice - watch hypokalemia and HTN

89 High free and metabolized cortisol: Elevated DHEA Borderline elevated metabolized cortisol Prefers inactive cortisone systemically Elevated free cortisol

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91 What causes elevated metabolized (total) cortisol or an up-regulation in cortisol clearance? Long term stress Inflammation/infection/pain Obesity Increased inflammatory cytokines Increased 11bHSD1 Insulin dysregulation/resistance Hyper thyroid (or meds too high)

92 High Cortisol due to inflammation/obesity

93 High free and metabolized cortisol: Find what is hyper stimulating them and ADDRESS THE CAUSE: o Stress, inflammation, infection, pain, insulin resistance, blood sugar issues, obesity, hyperthyroid or too much thyroid medication o r/o Cushing s if you suspect it Be aware that high cortisol might be important! If you lower their cortisol and they feel WORSE, then the cortisol is acting anti-inflammatory A. Nutrients and Brain support B. Flower essence White Chestnut for mind racing, obsessive repetitive thoughts that won t alleviate C. Calming adrenal herbs D. Meditation research shows that as little as 10-20min twice/day has significant impact a. Listen to meditative music, download apps, sit quietly and focus on breathing, MUSE headband

94 What about when the dials aren t all low or all high?

95 Low Free Cortisol and High Metabolized Cortisol: High metabolized cortisol (production and/or clearance) Favors cortisol metabolites systemically: inflammation, obesity, hypothyroid and licorice Lower end free cortisol likely getting cleared out of the body quickly

96 Low Free Cortisol and High Metabolized Cortisol: High metabolized cortisol due to: Stress, inflammation, infection, pain, insulin resistance, blood sugar issues, obesity, hyperthyroid or too much thyroid medication As a result, the free cortisol goes down as it s being cleared out the liver very quickly Address the cause Consider testing CBG/transcortin, if it s high then free cortisol will be low Adaptogens Nutrients and Brain Support

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98 What causes a decreased metabolized (total) cortisol or decreased cortisol clearance? Hypothyroid (not enough meds) HPA miscommunication Hypothalamus to pituitary = poor Pituitary to the Adrenals = poor Adrenals not responding optimally Corticosteroids Oral, injected, topical, inhaled, intranasal Opioid pain medications (also causes 2ndary hypogonadism) Codeine, morphine, oxy, hydrocodone, tramadol, fentanyl, methadone Accutane TBI Anorexia Poor liver function

99 (Higher)Free Cortisol and Low Metabolized Cortisol Low metabolized cortisol Normal free cortisol

100 Hypothyroid The most common reason Metabolized Cortisol is low and Free Cortisol is elevated

101 High Free and low metabolized = hypothyroid Low met. Cortisol (sluggish thyroid = cortisol clearance) Usually favors cortisol High free cortisol ( cortisol clearance = free cortisol backs up)

102 (Higher)Free Cortisol and Low Metabolized Cortisol Check a full thyroid panel with antibodies and rt3 when the thyroid slows down or becomes sluggish, it slows everything down including the metabolism of cortisol. As a result, the metabolized cortisol decreases and the free cortisol increases. Could be due to overall sluggish liver clearance A. Adaptogens B. Nutrients and Brain Support C. Evaluate the liver and detox

103 The DUTCH test seems cool What else does it test?

104 The DUTCH test Estrogen Estrogen Metabolites Progesterone Testosterone DHEA-s DHEA metabolites 5a-DHT 5a-reductase activity

105 Estrogen Dominance Common causes: SNP issues Ie.CYP1B1, CYP1A1, CYP3A4, COMT Estrogens in environment Supplementation Relatively low Progesterone Phase 1 detox issues Phase 2 detox issues

106 Estrogen Dominant Symptoms (male or female) Why? Whoa! Sluggish clearance

107 Before and After DIM (Phase 1) Much better!

108 Estrogen: Phase 2 problems

109 Do you give DIM for Phase 2 issues?

110 Do you give DIM for Phase 2 issues? Is the problem at the 2 and 4OH?

111 General phase 2 methylation/comt support Magnesium P5P Trimethyl glycine (TMG) Choline SAMe Methionine Folate/methyl B12

112 Worse Case Scenario: Estrogen Bad Bad Bad

113 Knowing estrogen metabolism in men and women allows you to evaluate phase 1 vs. phase 2 treatment (They are different)

114 Having the most comprehensive, easy to collect adrenal and hormone test available allows you to make a greater impact on your patients at a deeper level.

115 and that concludes our talk Thanks for listening!