Objectives. Dried Urine Testing for Comprehensive Hormones: Case Examples and Clinical Pearls

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1 Dried Urine Testing for Comprehensive Hormones: Case Examples and Clinical Pearls Carrie Jones, ND, MPH Medical Director Precision Analytical, Inc Objectives What is DUTCH and how is this test different? What is the research validating DUTCH testing? When do I use Dutch testing? Clinical Pearls and case study examples

2 What is the job of a lab test? ->To characterize the patient with respect to a particular biomarker Your patient needs lab testing 4-Spot Dried Urine (DUTCH) Assess diurnal pattern in 4 easy at-home collections throughout the day Free cortisol/metabolized cortisol DHEA and metabolites, melatonin Sex hormones (testosterone, progesterone metabolites, estrogen including estrogen metabolism) Billable to insurance, HSA/FSA Can indicate Addison s/cushing s 24-Hour Urine Collect urine in a jug over 24 hours no diurnal pattern, just one total number Reports cortisol (some labs free, some total ) and metabolized cortisol DHEA and metabolites, sex hormones and melatonin can be added to some tests Estrogen metabolism can be done Often covered by insurance Can indicate Addison s/cushing s Serum Single blood draw done during hours of lab or clinic No diurnal pattern unless multiple draws Total cortisol and DHEA-s or DHEA done at that single moment (no free or metabolized cortisol) Hormones progesterone, estrogen, total and free Test. no estrogen metabolism Often covered by insurance Test for Addison s or Cushing s Saliva Assess diurnal pattern by 4 saliva samples at home throughout the day Free cortisol and DHEA-s or DHEA Hormones (free) progesterone, estrogen, testosterone Metabolized cortisol, estrogen metabolism not reported Not often covered by insurance but HSA/FSA okay Can indicate Addison s/cushing s

3 The reason saliva became popular (Missing in 24hr urine testing and serum testing) Saliva Serum 24-Hr Urine 4-Spot Urine Urine Caveats Not OK if there are significant kidney issues Do not overhydrate

4 With DUTCH you get it all with easy collection Estrogen Metabolism Free cortisol graphed throughout the day Metabolized Cortisol Validation Data Urine free cortisol correlates very well to salivary free cortisol

5 Do Urine & Saliva Free Cortisol Agree? Internal Data (Precision Analytical) Do Urine & Saliva Free Cortisol Agree? Externally Published Data Urinary Free Cortisol Salivary Free Cortisol Jerjes, (2005, 2006)

6 Validation Data Urine free cortisol correlates very well to salivary free cortisol DUTCH Values correlate to 24-hour values Reproductive hormones correlate very well to serum values Dried samples correlate to liquid urine values Unpublished data, Precision Analytical

7 So when do I use Dutch testing? All sex hormone issues PMS PCOS Irregular cycles Fertility Men s health Peri-menopause and menopause Patients on hormones Thyroid issues Adrenal issues Fatigue, Adrenal Fatigue Insomnia stress Obesity/weight loss Anabolic/catabolic Pregnenolone Progesterone Estrogens Androgen metabolites and 5areductase Phase 1 metabolites Part of phase 2 detox

8 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 Reading the DUTCH Test Start at the top with pregnenolone (serum) Pregnenolone DHEA and Progesterone Progesterone alpha and beta metabolites DHEA DHEA-s/etiocholanolone/androsterone Testosterone alpha and beta metabolites 5-alpha reductase/5a-dht activity = androgenic? Testosterone Estrogens Estrogens phase 1 detox (2, 4, 16 OHE1) phase 2 detox = methylation

9 Metabolized cortisol Free Cortisone Free Cortisol Preference systemically Adrenal Hormone Recap Adrenal Cortex (outer layer) Zona Glomerulosa = Aldosterone Sodium/potassium/H2O balance Zona Fasciculata = corticosterone and cortisol Zona Reticularis = DHEA, DHEA-s, Androstenedione (metabolites etiocholanolone and androsterone; precursor to testosterone) Adrenal Medulla (inner layer) Norepinephrine (20%-25%) Epinephrine (75%-80%) Release triggered by Ach much quicker than HPA cortisol response due to preformed concentrations **At high levels, cortisol goes from Cortex to Medulla and converts norepi epi

10 Let s talk examples What is so important about metabolized cortisol?

11 Metabolized cortisol represents 80% of total cortisol production Free cortisol = 1% (Stewart and Krozowski, 1999). Typical Salivary Adrenal Fatigue result Low free cortisol levels all day

12 Which one is Adrenal Fatigue or insufficiency? Which one is Adrenal Fatigue or insufficiency?

13 What does this mean? It means patient #2 has a lot of cortisol in total! They are not in adrenal fatigue They do have low levels of FREE cortisol so they likely feel fatigued! Must address both WHY the metabolized cortisol is high and help that lower free cortisol. Q: Why is the metabolized cortisol elevated? (The Why portion of your patient)

14 What causes elevated metabolized (total) cortisol or an up-regulation in cortisol clearance? Long term stress Inflammation Obesity Increased inflammatory cytokines Increased 11bHSD1 Insulin dysregulation/resistance Hyper thyroid (or meds too high) THIS IS NOT ADRENAL FATIGUE! But they are stressed and tired Or stressed and wired They are fighting a fight Let s talk about the obesity example

15 Obesity and 11bHSD1 (11-beta-hydroxysteroid dehydrogenase-1) 11b-HSD1 found in every cell in the body Highest in fat, liver and brain More at risk for adipose gain, diabetes/fatty liver, and memory issues Converts inactive cortisone back into active cortisol (11bHSD2 converts it back to cortisone) 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 Male, mid-forties, central obesity If you just ran a free cortisol, and it was low, does that make sense?

16 Male, mid-forties, Central obesity: The full picture Very high metabolized cortisol Suboptimal free cortisol 11bHSD1 upregulated Relative Catabolic/Anabolic on DUTCH Anabolic Catabolic This person is very catabolic!

17 So what s happening? Inflammatory cytokines, insulin issues and stress are telling the brain to tell the Adrenals to make more cortisol 11bHSD1 is upregulated in fat tissue which causes more cortisone cortisol conversion creating more FAT GAIN With all this cortisol they are CATABOLIC (= glucose muscle mass) To compensate, the liver upregulates cortisol clearance out of the body So free cortisol declines due to the clearance Result = higher metabolized cortisol, higher 11bHSD1, lower free cortisol and excess fat around the middle! When cortisol clearance is abnormal, free cortisol measurements can be misleading without concurrent metabolite measurements (without knowing the entire HPA picture, your diagnosis and treatment of your patients might be leading you down the wrong path )

18 Let s talk Sex Hormones Progesterone DHEA metabolites 5a or 5b dominant? Estrogen Phase 1 Estrogen Phase 2

19 Let s talk estrogen! (Baseline test first, then re-test 3-6 months after treatment) Common Estrogen Issues PMS Heavy periods Endometriosis Tender/fibrocystic breasts Weight gain Mood swings Fertility challenges Peri-menopause/menopause Estrogen cancer risks: breast, uterine, cervical Men: Weight gain Breast development Fatigue Mood swings Erectile dysfunction Low libido Prostate cancer risk

20 Urine/Saliva/Serum shows Estrogen Dominance (male or female) Whoa! Sluggish clearance Estrogen Dominant (male or female) DUTCH testing gives you the WHY Whoa! Phase I detox Sluggish clearance

21 Before and After DIM (Phase 1) Much better! Let s talk DIM E1 and E2 2, 4 or 16OH E1 DIM: pushes E1 and E2 2OH E1 4OH E1 = more potent carcinogen because of the higher level of depurinating adducts (as opposed to stable adducts) When a quinone metabolites is formed reacts with DNA to form mostly depurinating adducts that break off from the DNA at N-3 and/or N-7 of Adenine or N-7 of Guanine leaving a DNA with a apurinic site (stable adducts stay attached to the DNA FYI) Poor repair of these sites mutations cancer NAC/glutathione prevent damage to DNA by inhibiting formation of catechol quinones and/or reacting with them to stop problems via GST gene Resveratrol non-competitive inhibitor of CYP1B1 to prevent E1/E2 4OH E1.

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23 Estrogen: Phase 2 problems (Genetics) General phase 2 methylation/comt support Magnesium Trimethyl glycine (TMG) Choline SAMe Methionine Folate/methyl B12

24 Do you give DIM for Phase 2 issues? Do you give DIM for Phase 2 issues? Is the problem at the 2 and 4OH? You may not always need DIM!

25 Worse Case Scenario: Estrogen Bad Bad Bad Knowing estrogen metabolism in men and women allows you to evaluate phase 1 vs. phase 2 treatment (They are different)

26 With DUTCH testing you get the complete picture in order to understand what the issues are and can address them properly Thank you. Carrie Jones, ND, MPH 2016