HPA Stress Profile with Cortisol Awakening Response

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1 BioHealth Laboratory s Clinical Resources CASE STUDY HPA Stress Profile with Cortisol Awakening Response HPA Stress Profile with CAR +5 (#205-CAR) Introduction Rebecca presents with some specific health complaints, including periodic depression, extreme fatigue, headaches, poor sleep, menstrual cramping, irregular menses and loss of sex drive. She constantly feels overwhelmed which is made worse by the chronic and unrelenting fatigue. Her ability to handle stress of any kind is greatly diminished and the slightest stressor seems to push her over the edge. She has worked with her primary care physician for several years and has been tested for thyroid dysfunction, anemia and cancer screens. All tests were deemed normal. She has sporadically used various medications over the last several years, for sleep and depression, including Paxil, Lexapro and Clonidine. The Paxil was most successful in helping with depression, but she is not currently taking medication and wishes to treat her issues as naturally as possible. As a teenager, she was on birth control pills for acne and menstrual cramping, but has been off of these for over 20 years. Patient Complaints: Fatigue difficulty getting out of bed in the morning, needs coffee throughout the day, energy is worse by mid-afternoon, relieved temporarily by rest, but overall about 30% of what it used to be in her 20 s and 30 s. Headaches described as pressure in back of head that radiates to forehead above eyes. Worse in afternoons when her fatigue is worse. No aura or other symptomology associated with migraines. Can be relieved with Ibuprofen, rest and coffee. The headaches seem to occur within the week before her period. Depression described as periods of feeling down and lack of motivation. Began to have these feelings in her mid-30 s. Paxil helped somewhat with these symptoms but she did not want to stay on a medication. She feels that her depression is linked to her worsening fatigue and other health issues. Menstrual cramping and irregularity suffered with significant menstrual cramping when teenager and resolved with birth control pills. Menses has become more erratic over the past 3 years. She has noticed that her cycle length is shortening to 26 days from what used to be a 28-day cycle. She reports more PMS and cramping 3-5 days before her period. Sleep described as restless sleep that is worse when a lot of life stress is occurring such as kid s projects, school activities, sports and when her husband is away traveling. She finds that she has difficulty falling asleep because she feels more energetic at night and stays up too late hoping to catch up on the things she did not get done during the day. Many nights she does not fall asleep until after midnight. Sex drive has felt less motivation for sexual relations over the past several years. She wants to have more intimate feelings for husband, but lacking motivation and desire. She is concerned that her fatigue is affecting her relationship. Patient Description: Rebecca is a 48 year-old Caucasian female, 5 feet 6 inches tall, 135 lbs, BMI = 16. Rebecca is married with three children ages 12, 15 and 17. Her kids are active in sports and school events. This keeps her active on the weekends and during the school year. She used to exercise about 4 times a week doing Pilates, weight training and running but can no longer tolerate any exercise beyond walking and activities of daily living. Exercise was her avenue of stress relief and would help with feelings of depression but now it leaves her feeling even more exhausted. She feels worse in terms of her energy and depression since she cannot exercise. Rebecca works part-time as a barista to make extra money and keep herself busy while the kids are in school. This has become a social outlet as well. Her husband is an attorney who keeps long hours and often travels for work. However, she describes their relationship as strong and healthy, but the lack of sex drive is a source of frustration in their relationship. History of Present Illness: Her current health complaints have been ongoing for many years but have gotten considerably worse in the past year. She doesn t recall a specific one-time event that triggered problems, but does acknowledge that her husband s years in law school were challenging financially while raising 3 young children. BioHealth Laboratory Hawthorne Blvd #150, Torrance, CA (USA/Canada)

2 Past Medical History: Periodic use of selective serotonin reuptake inhibitors of Paxil and Lexapro. The Paxil was used for approximately 4 years with moderate relief of depression. Acid blockers for relief of symptoms associated with heartburn x 4+ years. Previous use of birth control pills for approximately 20 years starting when she was 15 years old. No prior hospitalizations or surgeries Dietary History: Breakfast coffee and cream, toast with butter. Sometimes has a smoothie. Lunch chicken salad, sandwich, chips, smoothie. Sometimes will skip lunch if at work. Dinner beef, chicken or fish, mixed vegetables. Pasta dishes and salads. Snacks/Desserts yogurt, apples and nuts, ice cream, chocolate, cookies. Beverages coffee (two to three cups daily), water, diet soda. Social History: No smoking or drug use Two to three glasses of wine per week Physical Exam/Observations: sounds all four quadrants Tendon reflexes normal Soft spoken, pleasant, good memory recall, appears fatigued Heart rate 68, blood pressure 105/68 (seated) Orthostatic Blood Pressures: Lying 110/70, Standing 98/60 Lungs clear to auscultation, no murmurs Abdominal exam clear of pain on palpation, no masses, bowel Perceived Stress Survey Results: 32 Scale 0-13 low, moderate, hightendon reflexes normal Patient Test Results: Blood Tests from PCP: - Comprehensive metabolic panel normal for electrolyte imbalances and liver dysfunction. - Complete blood count with differential normal - Thyroid panel deemed normal, but only tested for TSH and T4 - Anemia panel no evidence of iron or B12 anemia - Lipid panel showed total cholesterol at 132 General Impressions: Rebecca s symptoms of depression, fatigue, menstrual irregularities, sleep problems and low sex drive are very characteristic of adrenal and HPA axis dysfunction, sleep dysregulation and sex hormone imbalances. The depression does not appear to be severe and is more situational based on lifestyle factors and how she is feeling physically. It would not be rated as pathological, but instead resolves/improves with improved sleep and exercise and an improved ability to deal with stress. Rebecca s Perceived Stress Survey score is 32 on a scale of Her PSS score falls in the range of a high level of stress. This survey is reflective of her inability to handle stressors without initiating a overreactive stress response causing her to feel easily overwhelmed. Her PCP ruled out hypothyroidism as a cause for her complaints, however, the lab data only included a thyroid stimulating hormone (TSH) level and total T4. This should be evaluated more thoroughly with free fraction T4 and T3 (or at least a Total T3) and thyroid antibodies if not done in the past few years. The low cholesterol at 132 may be a contributing factor to hormone imbalances. Cholesterol is a precursor to steroid hormones which are central to adrenal hormone and sex hormone production. Initial Plan of Action: Rebecca will be advised to perform a HPA Stress Profile with CAR +5 (#205-CAR) from BioHealth Laboratory. This test evaluates the Cortisol Awakening Response and the Diurnal Cortisol Rhythm, morning DHEA-S, molar ratio of cortisol to DHEA-S, estradiol, estriol, progesterone, testosterone and melatonin. It is most important to evaluate for HPA axis dysfunction and cortisol output problems as a primary cause of fatigue and menstrual irregularities. The adrenals play a central role in maintaining cortisol output for normal glucose metabolism, but also help with ovarian pacing of sex hormone production. Also, chronic stress can compromise DHEA-S values which can adversely affect estrogen and testosterone which could explain her problems of irregular menses, menstrual cramping and poor sex drive. Rebecca is also of perimenopausal age so it is not unlikely that she is experiencing some changes due to ovarian timing and output of sex hormones. Perimenopausal symptoms can be made worse by HPA axis dysfunction. The HPA Stress Profile with CAR +5 also evaluates for melatonin which, if low, could help explain her difficulty getting normal sleep. Evaluating the Cortisol Awakening Response allows us to see the long-term effects of stress on the HPA axis. Knowing the status of the HPA axis can help us to identify causative factors for some of her complaints and be more specific with our therapies and guidance in lifestyle recommendations. BioHealth Laboratory Hawthorne Blvd #150, Torrance, CA (USA/Canada)

3 Lab Testing: HPA Stress Profile with CAR +5 (#205-CAR) Patient Test Results: Cortisol Waking 5.0 Cortisol Cortisol Cortisol Noon 4.0 Cortisol Afternoon 3.2 Cortisol Nighttime 2.8 Cortisol Total 21 DHEA-S Waking 1.3 Cortisol:DHEA Ratio 3.85 Estradiol 2.1 pg/ml Estriol 10.2 pg/ml Progesterone 130 pg/ml Melatonin 8.0 pg/ml Testosterone 18 pg/ml Overview of Rebecca s HPA Stress Profile with CAR +5 As suspected Rebecca s #205-CAR panel shows low cortisol values throughout the day. Her noon time value was 4.0 and her afternoon value was 3.2. These low mid-day values could certainly contribute to the fatigue she feels particularly in the afternoon. Her Cortisol Awakening Response is overall low. Her waking cortisol value is low at 5 and her second sample taken 30 minutes later is also low at 11 although it shows a 120% (normal is 35-60%) rise from her waking sample. Her final sample in the CAR is at the low end of normal at 8 showing a 60% (normal is <33%) drop from the previous value. These values show a pattern of chronic stress leading to burnout in the HPA axis. She wakes with a very low cortisol which contributes to her feeling of not being able to get out of bed in the morning. Once she gets up, she demonstrates a 120% rise in her cortisol likely due to feeling stressed about her day she has to get the kids ready and off to school and get herself to work. By the 60-minute mark, her cortisol has dropped 60% which exceeds the normal drop in cortisol. This leaves Rebecca feeling like she is dragging by the time she gets to work. She can t wait to get another cup of coffee to keep her going. Her nighttime cortisol value is normal at 2.3 but it is at the higher end of normal and seems relatively high when compared to rest of the cortisol values in her test, including the values in the CAR. This relatively high nighttime cortisol may be contributing to her inability to relax in the evening and may be the reason she feels more energized at night as compared to the rest of the day. Because she feels best at night, she tends to stay up too late which starts the cycle of fatigue all over again the next day. Her DHEA-S value is below the reference range at 1.3 which is contributing to low overall estradiol and testosterone. The cortisol to DHEA-S ratio is within the normal range at 3.8, however, both cortisol and DHEA-S are below the reference range. The normal ratio indicates that there is enough DHEA-S to balance the effects of what little cortisol she has. Although her progesterone is within the normal range at 130 pg/ml, her samples were collected on day 21 of her cycle which would be the peak of progesterone production. Considering where she was in her cycle, her progesterone ideally should have been higher given the reference range of pg/ml. Testosterone was low at 18 pg/ml. Melatonin level was low at 8.0 pg/ml and her nighttime cortisol was normal at 2.8 pg/ml. Although this is a normal nighttime cortisol level, it is at the higher end of the range. With all other cortisol values being low, the nighttime value might be relatively high. This cortisol value along with low melatonin would account for her difficulty falling asleep and staying asleep through the night Plan of Action Based on Clinical Presentation and Lab Test Dietary intervention: - Blood sugar control is vital to helping decrease pressure on adrenal cortisol demand. She was given instructions for eating breakfast, lunch and dinner avoiding skipping meals. Important to balance protein, fats and carbohydrates. Healthy snacks in between meals were encouraged. Caffeine consumption should be limited to no more than 2 cups of coffee daily and it was encouraged to at least brew ½ caffeinated/decaf. Exercise: - Moderate walking, activities of daily living or gentle yoga is best for now until Rebecca shows consistency with improved sleep and energy throughout the day. Once she sees improvement in these areas, she can introduce more intense exercise 3 days per week. Lifestyle: - Bed by 10 pm and incorporate relaxing activities to decrease sympathetic nervous system activity. Avoid anything that is mentally stimulating. - If possible, reduce work hours until energy and sleep are more stable. Supplement Program: - Adrenal support formula 2 capsules with breakfast and 2 capsules with lunch. BioHealth Laboratory Hawthorne Blvd #150, Torrance, CA (USA/Canada)

4 - Mineral supplement with calcium and magnesium 3 tablets in the evening - Blood sugar suport formula 2 capsules with each glycemic balanced meal - Pregnenolone 10 drops under the tongue, held for 2 minutes before swallowing. No food in mouth for at least 30 minutes. - DHEA 3 drops under the tongue, held for 2 minutes before swallowing. No food in mouth for at least 30 minutes. - Licorice Root Extract 10 drops between 5 to 7 am, 5 drops between 10 to 11 am, and 5 drops between 2 to 3 pm. Add drops to mouth after taking Pregnenolone and DHEA first. - Herbal Adaptogen Formula of Rhodiola, Magnolia, Ashwaganda. - Phosphorylated serime 2 capsules in the evening. - Melatonin SL one tablet 30 minutes before bedtime. If continues to wake in the middle of the night then add Melatonin PR (long-acting) near bedtime as well. - Follow-up consultation every 3 to 4 weeks, repeat #205 CAR HPA Stress Panel +5 in 90 days. BioHealth Laboratory Hawthorne Blvd #150, Torrance, CA (USA/Canada)

5 HPA Stress Profile +5 with CAR Hawthorne Blvd. # 150, Torrance, CA / for Rebecca Stein Accession #T Authorizing Clinician Patient Received Samples BioHealth Laboratory Rebecca Stein Gender: Female 12/05/ Hawthorne Blvd, Suite 150 DOB: 11/26/1968 Torrance, CA HPA Stress Profile +5 with CAR (#205-CAR) Reported 12/05/2016 Cortisol Awakening Response (CAR) with Cortisol Diurnal Rhythm 25 Cortisol Waking Noon Afternoon Nighttime CAR Lower Patient Upper Time of Waking: 7:13 AM Perceived Stress Score: 32 Cortisol and DHEA-S Results Parameter Result Reference Range Units Cortisol - Waking * Cortisol - Waking Cortisol - Waking * Cortisol - Noon Cortisol - Afternoon Cortisol - Nighttime Cortisol - Sum DHEA-S Waking Cortisol:DHEA-S Ratio 7.9 : : 1 Molar Ratio The Perceived Stress Scale (PSS) is the most widely used physiological instrument for measuring the perception of stress. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. The PSS score should to be taken context of several demographic categories: Gender, age, race, education, employment and income. For more information on how to use the PSS score in the context of particular demographics please see the article. The Perceived Stress Scale and HPA Assessment. In the future, demographic categories will be built into PSS forms and adjusted scores will be provided on test reports. * Waking cortisol values are variable - see CAR guidelines below for data interpretation. Cortisol and DHEA-S values used in the Cortisol:DHEA-S molar ratio are reported from the waking +30 sample. DHEA-S reference ranges are loaded dynamically based on patient age and gender. The Cortisol Sum includes the +30 minute, noon, afternoon, and nighttime values. Lab Director: Manuel Baculi, MD CLIA ID: 05D Incorrect sample handling may affect results. Results are not intended to diagnose, treat, cure, or prevent any disease or replace medical advice from a qualified health care provider. Page 1 of 4

6 HPA Stress Profile +5 with CAR Hawthorne Blvd. # 150, Torrance, CA / for Rebecca Stein Accession #T Authorizing Clinician Patient Received Samples BioHealth Laboratory Rebecca Stein Gender: Female 12/05/ Hawthorne Blvd, Suite 150 DOB: 11/26/1968 Torrance, CA HPA Stress Profile +5 with CAR (#205-CAR) Reported 12/05/2016 Cortisol Awakening Response (CAR) Cortisol Waking +30 min +60 min Lower Cortisol Result Upper Cortisol Result Value () Guideline Waking Waking +30 Minutes Waking +60 Minutes * * * These guideline ranges are based on the available literature, as cited, and are interim ranges pending a comprehensive analysis of patient data. These guidelines are for research purposes only. The results should be interpreted in the context of patient symptoms, intake data, and relevant diagnostic information. Cortisol Awakening Response (CAR) is the rise in cortisol levels observed at 30 minutes post-awakening (approximately 35-60% above the waking value) followed by an expected decline one hour after waking. The behavior of cortisol is an important physiological response to anticipation of the day ahead and is a key indicator of HPA axis reactivity. The waking, 30 minute, and 60 minute cortisol results comprise something of a "mini stress test" and capture the dynamic rise and decline of cortisol in the first hour after awakening, preceding the steady decline of cortisol throughout the day (known as "diurnal rhythm"). CAR Result Rise: Percent of cortisol change from waking to waking +30 minutes. Decline: Percent of cortisol change from waking to waking +60 minutes. % Change % 60.00% Guideline 35-60% <33% Interpretation The 30 minute post-awakening collection should show an approximately 35-60% increase from awakening cortisol value. The 60 minute post-awakening collection captures the expected decrease in cortisol concentration (approximately 0-33% above baseline value). Lab Director: Manuel Baculi, MD CLIA ID: 05D Incorrect sample handling may affect results. Results are not intended to diagnose, treat, cure, or prevent any disease or replace medical advice from a qualified health care provider. Page 2 of 4

7 HPA Stress Profile +5 with CAR Hawthorne Blvd. # 150, Torrance, CA / for Rebecca Stein Accession #T Authorizing Clinician Patient Received Samples BioHealth Laboratory Rebecca Stein Gender: Female 12/05/ Hawthorne Blvd, Suite 150 DOB: 11/26/1968 Torrance, CA HPA Stress Profile +5 with CAR (#205-CAR) Reported 12/05/2016 Cortisol:DHEA-S Ratio Parameter Result Reference Range Cortisol - Waking DHEA-S - Waking Cortisol:DHEA-S Ratio 7.9 : : 1 Units Molar Ratio The Cortisol to DHEA-S ratio provides a snapshot of the waking values of these hormones and is reported specific to the age and gender of the patient. In general, an elevated cortisol:dhea-s ratio is indicative of progressive HPA axis dysfunction in which acute and/or chronic stressors have taken their toll on homeostasis. The cortisol:dhea-s ratio is generally considered to be a measure of catabolic vs. anabolic activities, but it may be better described as the overall burden of glucocorticoid signaling on tissues, since DHEA acts not only as an anabolic hormone, but appears to function to down-regulate the cellular effects of cortisol. Therefore, the signaling burden of cortisol is not just a function of available free cortisol, but of the DHEA-S available as an opposing signal. Comments: Cortisol has one of the most distinct circadian rhythms in human physiology. This is regulated by the central clock located in the suprachiasmatic nucleus of the hypothalamus. Cortisol acts as a secondary messenger between central and peripheral clocks, hence its importance in the synchronization of body circadian rhythms. Optimal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is critical for a successful response to any stressor as well as in non-stressful situations. Dysregulation of the HPA axis in basal conditions or in response to acute or chronic (including psychosocial) stress is closely related to the onset and/or progression of many diseases. The anabolic steroid, dehydroepiandosterone sulfate (DHEA-S), is secreted from the adrenal cortex. It plays a significant role in the body as a precursor to sex steroids as well as a role in HPA axis response to stress. References: 1. Clow, A., et al., The cortisol awakening response: More than a measure of HPA axis function.neurosci.biobehav. Rev. 2010, doi: /j.neubiorev Guilliams, Thomas G. The Role of Stress and the HPA Axis in Chronic Disease Management. Stevens Point: Point Institute, Print. 3. Wust S, Wolf J, Hellhammer DH, Federenko I, Schommer N, Kirschbaum C. The cortisol awakening response - normal values and confounds. Noise Health [serial online] 2000 ;2: Ferrari, E. et al., Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates. European Journal of Endocrinology (2001) Kroboth, PD et al., DHEA and DHEA-S: a review. J Clin Pharmacol (4): Orentreich, N., Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. Lab Director: Manuel Baculi, MD CLIA ID: 05D Incorrect sample handling may affect results. Results are not intended to diagnose, treat, cure, or prevent any disease or replace medical advice from a qualified health care provider. Page 3 of 4

8 HPA Stress Profile +5 with CAR Hawthorne Blvd. # 150, Torrance, CA / for Rebecca Stein Accession #T Authorizing Clinician Patient Received Samples BioHealth Laboratory Rebecca Stein Gender: Female 12/05/ Hawthorne Blvd, Suite 150 DOB: 11/26/1968 Torrance, CA HPA Stress Profile +5 with CAR (#205-CAR) Reported 12/05/2016 Parameter Result Units Reference Range Estradiol 1.2 pg/ml FEMALE: Follicular Phase Midcycle Luteal Phase Postmenopausal Physiological Range pg/ml pg/ml pg/ml pg/ml pg/ml MALE: pg/ml Estriol <0.5 pg/ml FEMALE: 2-98 pg/ml MALE: pg/ml Progesterone 63.8 pg/ml FEMALE: Premenopausal Postmenopausal Physiological Range pg/ml pg/ml pg/ml MALE: pg/ml Melatonin (Bedtime) 21.6 pg/ml (MALE/FEMALE) Testosterone 28.6 pg/ml FEMALE: pg/ml MALE: pg/ml Estrone Secretory IgA (Saliva) Lab Director: Manuel Baculi, MD CLIA ID: 05D Incorrect sample handling may affect results. Results are not intended to diagnose, treat, cure, or prevent any disease or replace medical advice from a qualified health care provider. Page 4 of 4