Objectives - FxMed...•Converts inactive cortisone back into active cortisol (11bHSD2 converts it...
Transcript of Objectives - FxMed...•Converts inactive cortisone back into active cortisol (11bHSD2 converts it...
Carrie Jones, ND, MPH Medical Director– Precision Analytical, Inc.
©2016
Dried Urine Testing for Comprehensive Hormones: Case Examples and Clinical Pearls
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
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
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
With DUTCH you get it all with easy collection
Metabolized Cortisol
Free cortisol graphed
throughout the day
Estrogen Metabolism
Validation Data • Urine free cortisol correlates very well to
salivary free cortisol
Do Urine & Saliva Free Cortisol Agree? – Internal Data (Precision
Analytical)
Jerjes, (2005, 2006)
Urinary Free Cortisol Salivary Free Cortisol
Do Urine & Saliva Free Cortisol Agree? – Externally Published Data
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
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
Phase 1 metabolites
Part of phase 2 detox
Androgen metabolites and 5a- reductase
Pregnenolone
Cholesterol
Progesterone
Cortisol
Pregnenolone
Cholesterol
Progesterone
Cortisol
WHICH MODEL IS CORRECT?
Circulating Hormone
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
In Mitochondria of 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
Metabolized cortisol
Free Cortisol Free Cortisone
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 Achmuch quicker than HPA cortisol response due to preformed concentrations
• **At high levels, cortisol goes from Cortex to Medulla and converts norepi epi
Let’s talk examples
What is so important about metabolized cortisol?
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
Which one is “Adrenal Fatigue” or insufficiency?
Which one is “Adrenal Fatigue” or insufficiency?
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)
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
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?
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!
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 cortisonecortisol 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 )
Let’s talk Sex Hormones
Progesterone
DHEA metabolites
Estrogen Phase 1
Estrogen Phase 2
5a or 5b dominant?
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
Urine/Saliva/Serum shows Estrogen Dominance (male or female)
Whoa!
Sluggish clearance
Estrogen Dominant (male or female) DUTCH testing gives you the WHY
Whoa!
Sluggish clearance
Phase I detox
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/E24OH E1.
http://www.gestaltreality.com/wp-content/uploads/2012/07/Estrogen-estradiol-metabolism-CYP3A4-quinone-oxidative-CYP1B1.jpg
http://www.gestaltreality.com/wp-content/uploads/2012/07/Estrogen-estradiol-metabolism-CYP3A4-quinone-oxidative-CYP1B1.jpg
Estrogen: Phase 2 problems (Genetics)
General phase 2 methylation/COMT support
• Magnesium
• Trimethyl glycine (TMG)
• Choline
• SAMe
• Methionine
• Folate/methyl B12
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!
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)
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 [email protected]
©2016