Accession # 00263417 Chuck Darrington 1312 9th St Rapid City, SD 57701 Ordering physician: Thomas Polucki DC DOB: 1960-06-11 Age: 57 Gender: Male Hormone Testing Summary Last Menstrual Period: Collection Times: 2017-06-16 04:15AM 2017-06-16 06:15AM 2017-06-15 05:15PM 2017-06-15 10:15PM All units are given in ng/mg creatinine Sex Hormones Age Range low limit your result high limit 8.0 22.1 27.0 25.0 43.3 115.0 Testosterone 18-25 50-115 26-40 41-60 40-95 30-80 >60 25-60 How to read the graphical representation of results Total Estrogen Testosterone (Sum of 8 Estrogen Metabolites) See Pages 2 & 3 for a thorough breakdown of sex hormone metabolites Total DHEA Production 20-40 40-60 >60 2500-5500 1700-3500 1000-2500 Adrenal Hormones See pages 4 and 5 for a more complete breakdown of adrenal hormones (ng/mg) Cortisol 500 400 300 200 Daily Free Cortisol Pattern Patient Values High Range Limit 100.0 333.0 1000.0 5500.0 2639.0 Total DHEA Production (DHEAS + Etiocholanolone + Androsterone) 4550.0 5633.0 100 310.0 10000.0 Low Range Limit 0 Waking (A) Morning (B) Afternoon (C) Night (D) 24hr Free Cortisol (A+B+C+D) cortisol Metabolized Cortisol (THF+THE) metabolism (Total Cortisol Production) Free cortisol best reflects tissue levels. Metabolized cortisol best reflects total cortisol production. Thank you for testing with us! ======================================================================================= Please be sure to always read below for any specific lab comments. More detailed comments can be found on page 7. - Please note the ranges for cortisol, cortisone, cortisol metabolites, melatonin and 8-OHdG have been updated (4.24.2017). S ee provider comments for more details. - The patient shows significantly higher free cortisol compared to metabolized cortisol. It may be advisable to check thyroid hormones if you have not. S ee comments in the notes for more details. ======================================================================================= Your DUTCH Complete report will include a summary (page 1), a list of all of the hormones tested and their ranges (pages 2,4) as well as a graphical representation of the results (pages 3,5). You will also see a steroid pathway for your reference (page 6) and provider notes. This report is not intended to treat, cure or diagnose any specific diseases. There is a series of videos in our video library at dutchtest.com that you may find useful in understanding the report. The following videos (which can also be found on the website under the listed names) may be particularly helpful in aiding your understanding: DUTCH Complete Overview (quick overview) Estrogen Tutorial; Androgen Tutorial; Cortisol Tutorial; Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 1 of 9
Accession # 00263417 Chuck Darrington 1312 9th St Rapid City, SD 57701 Sex Hormones and Metabolites Last Menstrual Period: Ordering physician: Thomas Polucki DC DOB: 1960-06-11 Age: 57 Gender: Male Collection Times: 2017-06-16 04:15AM 2017-06-16 06:15AM 2017-06-15 05:15PM 2017-06-15 10:15PM Category Test Result Units Normal Range Progesterone Metabolites b-pregnanediol Within range 142.0 ng/mg 75-400 a-pregnanediol Low end of range 22.0 ng/mg 20-130 Androgen Metabolites DHEAS Low end of range 208.0 ng/mg 60-2000 Androsterone Within range 1615.0 ng/mg 640-3000 Etiocholanolone Within range 816.0 ng/mg 460-1700 Testosterone Within range 43.3 ng/mg 25-115 5a-DHT Above range 32.6 ng/mg 9-16.7 5a-Androstanediol Within range 67.4 ng/mg 50-130 5b-Androstanediol Within range 179.6 ng/mg 65-250 Epi-Testosterone Low end of range 25.3 ng/mg 25-115 Estrogen Metabolites Estrone(E1) Within range 10.1 ng/mg 4-12 Estradiol(E2) Within range 1.2 ng/mg 0.5-1.6 Estriol(E3) Below range 0.7 ng/mg 2-6 2-OH-E1 Above range 8.9 ng/mg 0-3 4-OH-E1 Above range 0.5 ng/mg 0-0.5 16-OH-E1 Within range 0.3 ng/mg 0-0.8 2-Methoxy-E1 Above range 2.2 ng/mg 0-2 2-OH-E2 Above range 0.86 ng/mg 0-0.5 Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 2 of 9
HOW TO READ YOUR RESULTS: Hormones are presented on this page graphically in the order the body metabolizes them. Arrows represent conversion from one hormone to another. The stars represent the low and high limits of the reference ranges ( see example, right ). The number in the middle is your result. Reference Range Limit (low) your result Reference Range Limit (high) Progesterone Metabolism Pregnenolone 142.0 75.0 400.0 b-pregnanediol Progesterone A weighted average of 22.0 progesterone metabolites 20.0 130.0 Progesterone itself is not DHEA a-pregnanediol found in urine in Androstenedione measurable levels Androstenedione 5ß 5α Age Age-Dependent Ranges 18-25 50-115 60.0 208.0 26-40 40-95 2000.0 41-60 30-80 Testosterone >60 25-60 25.0 DHEAS 43.3 Testosterone Androgen Metabolism 115.0 20-40 40-60 >60 20-40 40-60 >60 20-40 40-60 >60 100-2000 30-300 DHEAS 20-100 Estrogen Metabolism 1000-3000 500-2500 Androsterone 250-2000 500-1700 350-1300 Etiocholanolone 250-1000 460.0 816.0 1700.0 640.0 1615.0 3000.0 Etiocholanolone Androsterone Testosterone 4.0 10.1 Estrone(E1) CYP3A4 12.0 0.5 1.2 Estradiol(E2) primary estrogens (E1, E2, E3) 1.6 2.0 CYP3A4 0.7 Estriol(E3) 6.0 5ß 5α Normal Estrogen Metabolism Less Androgenic Metabolites 65.0 179.6 250.0 5b-Androstanediol (5ß) Low 5α-DHT Most potent androgen 50.0 67.4 130.0 5a-Androstanediol High (5α) CYP1A1 (protective pathway) CYP1B1 0.5 0.0 4-OH-E1 COMT 0.3 0.0 16-OH-E1 0.5 0.8 2-OH 70% 4-OH 10% 16-OH 20% Patient Estrogen Metabolism 2-OH 4-OH 16-OH 91.7% 5.5% 2.8% 5a-Reductase Activity 5α-Reductase Activity is an overall score of the 5α (more androgenic) vs. 5ß (less androgenic) metabolites of androstenedione and testosterone. 4-Methoxy-E1 (Protective, but not enough in urine to measure) 4-OH-E1 Low High Methylation-activity 2-Methoxy/2-OH 2.2 0.0 2-Methoxy-E1 COMT 2.0 methylation (protective) 8.9 0.0 2-OH-E1 3.0 If not methylated, 4-OH-E1 can bind to and damage DNA Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 3 of 9
Accession # 00263417 Chuck Darrington 1312 9th St Rapid City, SD 57701 Advanced Adrenal Assessment Last Menstrual Period: Ordering physician: Thomas Polucki DC DOB: 1960-06-11 Age: 57 Gender: Male Collection Times: 2017-06-16 04:15AM 2017-06-16 06:15AM 2017-06-15 05:15PM 2017-06-15 10:15PM Category Test Result Units Normal Range Creatinine Creatinine A (Waking) Within range 1.06 mg/ml 0.3-3 Creatinine B (Morning) Within range 1.03 mg/ml 0.3-3 Creatinine C (Afternoon) Within range 0.71 mg/ml 0.3-3 Creatinine D (Night) Within range 1.32 mg/ml 0.3-3 Daily Free Cortisol and Cortisone Cortisol A (Waking) Within range 36.4 ng/mg 18-80 Cortisol B (Morning) Above range 266.4 ng/mg 50-200 Cortisol C (Afternoon) Within range 19.3 ng/mg 11-45 Cortisol D (Night) Within range 11.1 ng/mg 0-25 Cortisone A (Waking) Within range 95.2 ng/mg 50-140 Cortisone B (Morning) Above range 310.1 ng/mg 100-240 Cortisone C (Afternoon) Within range 69.7 ng/mg 40-115 Cortisone D (Night) Within range 41.4 ng/mg 0-70 24hr Free Cortisol Above range 333.0 ng/mg 100-310 24hr Free Cortisone Above range 516.0 ng/mg 250-500 Cortisol Metabolites and DHEAS b-tetrahydrocortisol (b-thf) Below range 1702.0 ng/mg 1750-4000 a-tetrahydrocortisol (a-thf) High end of range 683.0 ng/mg 175-700 b-tetrahydrocortisone (b-the) Within range 3249.0 ng/mg 2350-5800 Metabolized Cortisol (THF+THE) Low end of range 5633.0 ng/mg 4550-10000 DHEAS Low end of range 208.0 ng/mg 60-2000 DUTCH Complete Extras Category Test Result Units Normal Range Melatonin (*measured as 6-OH-Melatonin-Sulfate) Melatonin* (Waking) Low end of range 24.4 ng/mg 10-85 Oxidative Stress / DNA Damage, measured as 8-Hydroxy-2-deoxyguanosine (8-OHdG) 8-OHdG (Waking) Within range 4.2 ng/mg 0-8.8 Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 4 of 9
S T R E S S CRH Hypothalamus Pituitary Pineal Stress (or inflammation) causes the brain to release ACTH, which stimulates the adrenal glands to make hormones Reference Range Limit (low) your result Reference Range Limit (high) Total DHEA Production ACTH 10.0 24.4 85.0 Melatonin* (Waking) Age 20-40 40-60 >60 Range 2500-5500 1700-3500 1000-2500 Adrenal Gland DHEA 1000.0 5500.0 2639.0 A patient s catabolic vs anabolic balance can be estimated by observing relative DHEA (anabolic) vs cortisol (catabolic) production Total DHEA Production (DHEAS + Etiocholanolone + Androsterone) Cortisol Cortisol Metabolism Circulating Free Cortisol 4550.0 5633.0 10000.0 Metabolized Cortisol (THF+THE) (Total Cortisol Production) 600 500 Cortisone (ng/mg) 480 360 240 Daily Free Cortisone Pattern Patient Values High Range Limit (ng/mg) Cortisol 400 300 200 Daily Free Cortisol Pattern Patient Values High Range Limit 120 100 Low Range Limit 0 Waking (A) Morning (B) Afternoon (C) Night (D) Note: "Waking" samples reflect overnight production Low Range Limit 0 Waking (A) Morning (B) Afternoon (C) Night (D) 250.0 516.0 Cortisol and Cortisone interconv ert (11b-HSD) and are metabolized to THF & THE for excretion 100.0 333.0 500.0 310.0 24hr Free Cortisone (A+B+C+D) 24hr Free Cortisol (A+B+C+D) More cortisone metabolites (THE) NOTE: The balance between free cortisol and free cortisone reflects the kidney's conversion of cortisol to cortisone. See below for the overall preference between cortisol and cortisone. More cortisol metabolites (THF) NOTE: This 11b-HSD index measures the balance of cortisol and cortisone metabolites which best reflects the overall balance of active cortisol and inactive cortisone systemically. Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 5 of 9
Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 6 of 9
Provider Notes Thank you for testing with us! If this is your first report, you are encouraged to watch our educational videos on how to read the report. There are hyperlinks to these videos on the first page of a DUTCH Complete or in these comments (below). The videos can also be seen by going to www.dutchtest.com and visiting the video library. Comments in the report that are specific to the patient ARE IN ALL CAPS or may be bold. The other information is general information that we hope you will find useful in understanding the patient's results. These results are not intended to diagnose any specific conditions. Treatments based on results should be made by a qualified healthcare provider. Reference ranges for cortis ol, cortis one, athf, bthf, bthe, melatonin (6-OH-melatonins ulfate) and 8-OHdG have been updated (4.24.2017). The values are unchanged, but the former range limits were all set at the 80th percentile (20th - 80th percentile). This is being expanded (widened) s omewhat after carefully reviewing data from tens of thous ands of res ults to the 90th percentile (20th - 90th percentile). We are committed to continuous ly optimizing both the analytical and clinical accuracy of DUTCH testing, and these changes are part of those efforts. Androgen Metabolism: Testosterone is made in the testis and the adrenal glands however in men the adrenal production is a somewhat insignificant fraction. a-dht (a-dihydrotestosterone) is the most potent androgen (3X more than testosterone), but it is primarily made within the liver and target cells (it is a paracrine hormone) and not by the gonads. a-dht is s ubs equently deactivated to a-andros tanediol within target tis s ues and then conjugated (glucuronidation) for excretion. As s uch, a-andros tanediol may better repres ents a-dht even though its metabolic precurs or is more biologically active and well known however we do report both on the test. Only a fraction of a-dht formed actually enters circulation as a-dht (Toscano, 1987). The corresponding beta metabolites (for example b-dht) are not androgenic. Androgens help to promote proper s exual des ire and function, and generally contribute to attributes that are typically more pronounced in males than females (general and sexual aggression, muscle mass, increased facial/body hair, reduction of fat deposition, etc). As males age, they make less testosterone. Androgens are turned into estrogens (for men and women) so assessing metabolism also includes looking at estrogen levels. Note: a-andros tanediol and b-andros tanediol ranges have been updated as of 7.22.16 due to a recalibration. 5a-Reductas e Activity: The competing enzymes 5a and 5b-reductas e act on the androgens andros tenedione (creating andros terone and etiocholanolone located under the proges terone picture) and tes tos terone (creating a-dht and b-dht). They also metabolize progesterone, and cortisol. The alpha metabolites of androstenedione and testosterone are far more androgenic than their beta counterparts. Cons equently, increas ed 5a-reductas e activity may be accompanied by clinical signs of androgenicity (excess facial hair growth, scalp hair loss, acne, irritability, oily skin, prostate issues in men...etc). If the patient heavily favors the 5a pathway and there are concerns of excess androgenicity (or prostate cancer risk), this may be worth addressing. Estrogen Metabolism: While usually considered female hormones, estrogens are present in males also. In men elevated estrogen levels have been associated with weight gain, breast development, mood swings, cardiovascular and prostate problems. The primary concern for male patients is if they are making too much. Estrogens are produced from androstenedione and testosterone via a process called aromatization. Mos t es trogen is metabolized down into the healthier 2-OH pathway. Thes e 2-OH metabolites are cons idered protective in women (from breast cancer) but this is also true of men with respect to prostate cancer. It is ideal if the 2-OH pathway (from the 2nd pie chart) is heavily favored over the more potent 16-OH estrogens or the carcinogenic 4-OH estrogens. It is our position that the ratio of 2:16 OHE1 is not as relevant as has been thought historically (Obi, 2011). Providers may still wish to use this index and it can be calculated by simply dividing the two numbers. A male reference range for the ratio with our methodology is 2.6-6.6. The methylation activity gauge s hows how effectively the body makes methoxy es trogens from hydroxyes trogens. Normal or high methylation activity is important in protecting the body from the harmful 4-OH es trogens made in phas e 1 detoxification. Progesterone levels are of marginal value in men, although deficiency can be associated with some clinical conditions such as depression, fatigue, and low libido. DUTCH Adrenal: The HPA-Axis refers to the communication and interaction between the hypothalamus (H) and pituitary (P) in the brain down to the adrenal glands (A) that sit on top of your kidneys. When a physical or psychological stressor occurs, the hypothalamus tells the pituitary to make ACTH, a hormone. ACTH stimulates the adrenal glands to make the stress hormone, cortisol and to a lesser extent DHEA and DHEA-S. Normally, the HPA-axis production follows a daily pattern in which cortisol rises rather rapidly in the first 10-30 minutes after waking in order to help with energy, then gradually decreases throughout the day so that it is low at night for sleep. The cycle starts over the next morning. Abnormally high activity occurs in Cushing s Disease where the HPA-axis is hyper-stimulated causing cortisol to be elevated all day. The opposite is known as Addison s Disease, where cortisol is abnormally low because it is not made appropriately in response to ACTH s stimulation. These two conditions are somewhat rare. Examples of more common conditions related to less severely abnormal cortisol levels include fatigue, depression, insomnia, fibromyalgia, anxiety, inflammation and more. Only a fraction of cortisol is "free" and bioactive. This fraction of cortisol is very important, but levels of metabolized cortisol best represents overall production of cortisol therefore both should be taken into account to correctly assess adrenal function. Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 7 of 9
The Daily Free Cortisol Pattern: In healthy adrenal function, cortisol levels are expected to rise in the early morning and fall throughout the day, reaching the lowes t point around 1am and peaking 30-60min after waking. The waking s ample represents the total of free cortisol throughout the sleeping period. Cortisone is the inactive form of cortisol. Its pattern is of s econdary importance, but at times can give additional clarity and is provided on the adrenal page. Typical urine tes ting (24- hour collection) averages the daily production of cortis ol. This approach is not able to properly characterize individuals whos e cortisol patterns do not fit the typical rise then fall pattern through the day. Dysfunctional diurnal patters have been as s ociated with health-related problems s uch as fatigue and ins omnia. The daily total of free cortisol is approximated by summing the four measurements. This calculated value correlates to a 24- hour free cortisol value. It is helpful to compare the relative level of 24-hr free cortisol with metabolized cortisol to understand HPA-axis activity. The total of free cortisol for the day only represents about 1-3% of the total production. The total of the metabolites is a better marker for overall cortis ol production. OVERALL FREE CORTISOL LEVELS ARE ELEVATED, BUT METABOLIZ ED CORTISOL (THE BEST MARKER FOR OVERALL CORTISOL PRODUCTION) IS LOW. CORTISOL CLEARANCE MAY BE A BIT SLUGGISH, WHICH KEEPS FREE CORTISOL LEVELS ELEVATED IN SPITE OF LOW OVERALL PRODUCTION. HYPOTHYROIDISM AND OTHER CONDITIONS MAY LEAD TO SLOW CORTISOL METABOLISM. WHEN THE PATTERN IS THIS EXTREME (FREE LEVELS HIGH, WITH LOW METABOLIZ ED LEVELS), PROCEED WITH CAUTION AND TAKE INTO ACCOUNT THE INTERPLAY BETWEEN THE ADRENALS AND THYROID. This article s hows excellent correlation between cortis ol metabolis m rates and thyroid levels (article was formerly available without charge, but only the abs tract can be read without charge currently). The Cortisol-Cortisone Balance: Cortis ol, which is the active hormone, can convert into cortis one, the inactive form. They convert back and forth in different parts of the body. We tell which one you make more of by looking at whether cortisol metabolites (athf, bthf) or coritsone metabolites (bthe) are made more (compared to what is normal) in the gauge at the bottom of the adrenal page. The deactivation of cortis ol to cortis one (via enzyme 11b-HSD II) occurs predominantly in the kidneys, colon, and saliva glands. The local formation of inactive cortisone from cortisol in the kidney is strongly reflected in urine. Activation of cortisone to cortisol takes place primarily in the liver, adipose tissue, gonads, brain, and muscle. Within these same tissues (mostly the liver) the free hormones are also converted to their metabolites (cortisol to a/b-thf, cortisone to THE). Balance between the two is usually preferred, but making more cortisol than cortisone is sometimes good to help give you enough cortisol if your levels are low however a preference for the active cortisol is enhanced by central adipos ity, hypothyroidis m, inflammation, and s upplements s uch as licorice root extract. Cortis one formation is enhanced by growth hormone, es trogen, coffee and hyperthyroidis m. THE PATIENT'S THF/THE RATIO IMPLIES A PREFERENCE FOR CORTISONE (RELATIVE TO CORTISOL). THIS IS KEEPING CORTISOL LEVELS FROM BEING EVEN HIGHER THAN THEY ALREADY ARE (AND THEY ARE SOMEWHAT ELEVATED). THIS IMPLIES THAT ELEVATED CORTISOL HAS MORE TO DO WITH EXCESSIVE STIMULATION OF THE HPA-AXIS AND LESS TO DO WITH OVERACTIVE ENZ YME 11b-HSD I. ADDRESSING THE CAUSES THAT ARE STIMULATING THE HPA-AXIS SHOULD BE CONSIDERED. DUTCH welcomes 8-OHdG 8-OHdG (8-hydroxy-2-deoxyguanosine) results can be seen on page 4 of the DUTCH Complete report. It is a marker for estimating DNA damage due to oxidative stress (ROS creation). 8-OHdG is considered pro-mutagenic as it is a biomarker for various cancer and degenerative dis eas e initiation and promotion. It can be increas ed by chronic inflammation, increas ed cell turnover, chronic s tres s, hypertens ion, hyperglycemia/pre-diabetes/diabetes, kidney dis eas e, IBD, chronic s kin conditions (psoriasis/eczema), depression, atherosclerosis, chronic liver disease, Parkinson's (increasing levels with worsening stages), Diabetic neuropathy, COPD, bladder cancer, or insomnia. Studies have shown higher levels in patients with breast and prostate cancers. When levels are elevated it may be prudent to eliminate or reduce any causes and increase the cons umption of antioxidant containing foods and/or s upplements. The reference range for 8-OHdG is a more aggressive range for Functional Medicine that puts the range limit at the 80th percentile for each gender. A classic range (average plus two standard deviations) would result in a range of 0-6ng/mg for women and 0-10ng/mg for men. Seeking out the cause of oxidative stress may be more crucial if results exceed these limits. Reading the Report: The first page of the Dutch Complete lab report is a summary page while the second page of the Dutch Complete lab report and first page of the Dutch sex hormone and Dutch adrenal test are a classic lab report showing each result and the respective range of each hormone. Reference ranges shown are those of young healthy individuals. The graphical repres entation of res ults on the page that follows allows the viewing of hormone res ults within the biochemical flowchart to more easily see the relative level of each hormone. The gauge format shows the patient result (represented by the needle of the gauge) and the area between the stars represents the reference range. Reference ranges are typically s et at the 20th to the 80th percentile of young, healthy individuals (DHEAS for example). This means that a result at the low end of a range is lower than 80 percent of young, healthy individuals. Likewise a result at the high end of a range is higher than 80 percent of the population. Some reference ranges are set more widely. For example, s lightly elevated proges terone is not generally cons idered problematic, s o its metabolites have reference ranges that extend further (90th percentile instead of 80th). The fan style gauges are used for indexes/ratios such as on 5a-reductase activity, cortisol/cortisone, and estrogen methylation. Because these values are all based on ratios there are no values or units, but they give a general idea of a particular relationship and can tell you how turned up or turned down a particular process is. The middle of the gauge represents an average value, while the lines towards the edge represent results lower or higher than most (80%) of the population. Being outs ide of any range is not always cons idered unfavorable. For example, on the es trogen methylation gauge an elevated level means someone methylates estrogens very effectively which may have positive consequences. Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 8 of 9
What is actually measured in urine? In blood, most hormones are bound to binding proteins. A small fraction of the total hormone levels are "free" and unbound such that they are active hormones. These free hormones are not found readily in urine except for cortisol and cortisone (because they are much more water soluble than, for example, testosterone). As such, free cortisol and cortisone can be measured in urine and it is this measurement that nearly all urinary cortisol research is based upon. In the DUTCH Adrenal Profile the diurnal patterns of free cortisol and cortisone are measured by LC- MS/MS. All other hormones measured (cortisol metabolites, DHEA, and all sex hormones) are excreted in urine predominately after the addition of a glucuronide or sulfate group (to increase water solubility for excretion). As an example, Tajic (Natural Sciences, 1968 publication) found that of the tes tos terone found in urine, 57-80% was tes tos terone-glucuronide, 14-42% was testosterone-sulfate, and negligible amounts (<1% for most) was free testosterone. The most likely source of free sex hormones in urine is from contamination from hormonal s upplements. To eliminate this potential, we remove free hormones from conjugates. The glucuronides and sulfates are then broken off of the parent hormones, and the measurement is made. These measurements reflect well the bioavailable amount of hormone in most cases as it is only the free, nonprotein-bound fraction in blood/tissue that is available for phase II metabolism (glucuronidation and sulfation) and subsequent urine excretion. Disclaimer: the filter paper used for sample collection is designed for blood collection, so it is technically considered "res earch only" for urine collection. Its proper us e for urine collection has been thoroughly validated. Precision Analytical (Raymond Grimsbo, Lab Director) Chuck Darrington Page 9 of 9