​Hypocortisolism (a.k.a. Cortisol deficiency, adrenal insufficiency, adrenal fatigue) http://hormonerestoration.com/Cortisol.html I had decided not to give patients labels and drugs, but only to prescribe natural hormones and nutrients, I thought it would beeasy work--just replacing sex hormones that to correct age-related losses. From Dr. Rouzier's course I had learned aboutdiagnosing hypothyroidism according to symptoms and relatively low FT4 and FT3 levels, and optimizing T3 levels/effects withnatural desiccated thyroid (NDT).  I helped many people so much that they referred their suffering friends and relatives to me.They had fatigue, brain fog, depression, anxiety, headaches, etc. and had gotten little help from the drugs prescribed byphysicians. They were mostly women. I tried to help with ovarian hormone replacement when needed, and with NDT. Many ofresponded very well to NDT. Some, however, had no improvement at all. Some actually felt much worse, sometimes even afterjust one dose. Some immediately better on NDT, but later felt worse. Some of them also felt worse when I tried to correct theirestradiol or DHEA deficiencies. NDT and other hormones worsened their underlying, long-standing symptoms. I understood thatthese negative reactions to physiological doses/levels of natural hormones were not “side effects”. They indicated that there wassome other endocrine or metabolic disorder/deficiency that was being strongly affected by potent T4/T3 therapy, usually for theworse. The cause was not hard to find. All physicians are taught that thyroid replacement can worsen adrenalinsufficiency; but they think that adrenal insufficiency is extremely rare—confined to persons with obvious disease ordamage affecting their adrenal glands (Addison’s Disease) or their hypothalamic-pituitary system. They think that adrenalinsufficiency is always severe, even life-threatening. They cannot imagine that any apparently healthy patient in their office couldhave adrenal insufficiency. “Adrenal insufficiency” is actually another archaic medical term; what these patients were sufferingfrom was cortisol deficiency; better named "hypocortisolism". Hypocortisolism is unmasked when a person is given thyroidhormone because greater thyroid levels/effects increase both the metabolism of cortisol and the need for cortisol, therebyworsening the relative cortisol deficiency. With time I realized that T3 and cortisol have very powerful and complex interactions--they both counteract and enable each other's levels and effects. Oral T3 stimulates cortisol secretion, explaining why somepersons felt better immediately with starting NDT. Hypocortisolism is the explanation for most anomalous responses toT4 or T4/T3 therapy. In researching the various schools of BHRT, I had learned about “adrenal fatigue” and saliva cortisol testing throughcompounding pharmacies and saliva testing companies. I began to check saliva cortisol levels in these patients. Saliva testinghas been proven to be the best way to assess a person’s free cortisol levels throughout the day and night. I foundthat most of these patients had low-in range or low cortisol levels. As I became aware of the many manifestations ofhypocortisolism, I began to see it in more patients, again mostly women. They usually had relatively DHEAS levels on testing too,but a few had unusually high DHEAS levels. Their symptoms were typical of hypocortisolism and had no other apparent cause.Their history often provided clues. Their symptoms worsened under stress. They felt much better on cortisol-like (glucocorticoid)drugs like prednisone or Medrol®. They often had a history of negative reactions to thyroid, DHEA, or estradiol, because thesehormones counteract cortisol’s levels/effects. They often had inflammatory diseases/disorders. They had allergies and/or manyfood and environmental sensitivies. When hypocortisolism was the best explanation for their history, symptoms, and lab resutls, Ioffered them a trial of cortisol (hydrocortisone) supplementation in physiological doses to see if it would help. The effects wereoften dramatic, more so than with any other hormone. Many began to feel more normal after just one dose. Over a few days theiraches and muscle stiffness disappeared. They could think more clearly. They felt energetic for the first time in years, sometimesdecades. Their nausea disappeared and their allergies improved. Their inflammation subsided. Their headaches disappeared.They felt less anxious. They slept better. Their digestion improved. By the simplest clinical logic, such dramaticimprovements with physiological doses of cortisol proved that they had been suffering from hypocortisolism. Theyhad an endocrine disorder that  currently cannot be diagnosed by conventional endocrine practices. With time, I began to view almost all otherwise-unexplained fatigue, achiness, cognitive dysfunction anddepression are due to cortisol and/or thyroid deficiencies-- until proven otherwise. Through my experience andresearch I realized that a relative hypocortisolism is common in women—it is an aspect of the female reproductive endocrinesystem. This fact is the sufficient explanation for women’s much higher incidences of chronic fatigue, fibromyalgia, career burn-out, depression, anxiety, allergies, and autoimmune diseases. Since estradiol also counteracts cortisol, hypocortisolism plays arole in many feminine disorders: premenstrual syndrome, premenstrual dysphoric disorder, endometriosis, hyperemesisgravidarum and post-partum depression. Indeed many studies have demonstrated a hypoactive hypothalamic-pituitary-adrenalsystem in persons with these problems. I gradually came to realize that many of the symptoms and syndromes for which medicinehas no explanation are actually due, in full or in part, to hypocortisolism. This is why glucocorticoid drugs are so helpful for somany medical diseases, disorders and symptoms. Unable to diagnose the cortisol deficiency, physicians prescribe steroids ordrugs that stimulate the HPA-axis and increase cortisol levels: SSRI antidepressants (Prozac, Paxil, Lexapro, etc.) andamphetamines. Many drugs of abuse raise cortisol levels: marijuana, cocaine, ecstasy, nicotine, and even caffeine.Hypocortisolism plays a large role in many of the medical and psychiatric disorders that afflict people; disorders forwhich there is no explanation. These patients all get descriptive diagnoses and drugs. Cortisol is, in fact, the foundation of the entire endocrine system. It is essential for our adaptation to the demandsof life, and yet all other major hormones counteract it. If a person does not have sufficient cortisol effect, they simplecannot feel of function well. Their quality of life is low. They often cannot replace other hormones that they need--they feel worsewith taking other hormones. Cortisol is our primary stress-response hormone. It is known to help maintain blood sugar levels andto moderate the immune system and its reactions. However it has many other functions that we do not understand.Hypocoritisolism causes myriad symptoms: fatigue, aches and pains, brain fog, allergies, frequent infections, low blood pressure,low stress tolerance, anxiety, irritability, hypoglycemia, frequent nausea, PMS/PMDD, autoimmune diseases, excessive sweating,teeth grinding, restless legs, hot flashes and insomnia. Sufferers often say that they feel like they always have the flu--and it justgets worse or better at times. Indeed, cortisol secretion is much more variable than any other hormone. It is affected by manyinfluences--psychological, physical, life-style, drugs, etc. Stress usually brings on a worsening of the symptoms. Hypocortisolismpromotes hypoglycemia which causes irritability, confusion, headaches, hot flashes, sweating, palpitations, insomnia and panicattacks. Hypocortisolism varies from mild to severe. Many women suffer from a mild hypocortisolism that does not require cortisolsupplementation. They can feel better with simple lifestyle interventions that reduce cortisol demand or increase cortisolproduction. To reduce demand they must eliminate all unnecessary stress--they must learn to say "No". They should maintain aregular schedule and always get a good night's sleep. They must eliminate all sources of inflammation including foods to whichthey are allergic (gluten, dairy, soy, eggs, etc.), environmental allergens, and any infections (teeth, H. Pylori, intestinal dysbiosis,sinuses, etc.). (The best physicians to help identify and eliminate causes of inflammation are those trained in FunctionalMedicine.) Patients can increase their own cortisol production with vigorous daily exercise, especially in the morning.Hypocortisolism is the reason why many persons must exercise vigorously every day in order to feel and functionwell. If they do not exercise they suffer from hypocortisol symptoms. The conventional approach to the diagnosis of adrenal insufficiency is extremely insensitive. Physicians believe, inessence, that if a person can make a normal level of cortisol under any circumstances, then they do not have any seriousdisease of the HP system or adrenal glands and therefore no degree of hypocortisolism. The usual screening test that doctorsdo is an AM serum cortisol level. This is insensitive for a number of reasons. It's reported with a reference range of 5 to20mcg/dL, yet studies find that a result under 14mcg/dL in a symptomatic persons, is highly suggestive of hypocortisolism. Inaddition, one's cortisol level is raised after driving to a lab and anticipating a needle stick. This issues is appreciated by someendocrinologists, so they perform an ACTH stimulation test. They believe a normal results rules out hypocortisolism. It does not,as many studies have demonstrated. It only proves that the adrenal glands can make normal amounts of cortisol under maximalstimulation. he best test of free cortisol levels in the blood throughout the day is a diurnal salivary cortisol profile. Most doctorsdo not do saliva cortisol testing, and if they do the results are reported with lower limits of "undetectable", obviously incompatiblewith health. So as it is, physicians have no way of seeing the low free cortisol levels in their patients. Based on research doneby ZRT Laboratories, published studies, and my own experience, I have created these ranges for LabCorp/Quest LC/MS salivacortisol tests: Morning:  0.3 - 0.60  mcg/dL    (30 mins after awakening)     Labcorp range   0.025 - 0.60Noon:      0.1 - 0.20  mcg/dL    (right before lunch)                Labcorp range   <0.01 - 0.33Evening:  0.05 - 0.13  mcg/dL   (right before dinner)             Labcorp range   <0.01 - 0.20Night:      0.02 - 0.07  mcg/dL   (right before bedtime)           Labcorp range   <0.01 - 0.09 ZRT's own ranges, and those of other labs that use immunoassays are about 50% higher. See Testing for more information.Notice that LabCorp's lower limit for the AM saliva cortisol is almost zero, far below the level of 1.8 or 2.0 mcg/dL that definedadrenal insufficiency in some studies. This is due to applying the usual statistical methods to a symptom-unscreened populationwhose levels are skewed towards lower values. However, even saliva cortisol levels cannot tell the whole strogy. More than withany other hormone, serum cortisol levels do not accurately reflect its effects in the various tissues of the body. Cortisol secretionis highly variable and cortisol is activated and deactivated within cells by certain enzymes. So, as with the thyroidal system,the only reliable guide to a person's cortisol status is his/her symptoms. Sometimes persons with marked hypocortisolsymptoms have normal-appearing cortisol and DHEAS levels, and yet respond very well to cortisol supplementation. Much of thehypocortisolism in the population is due to relative cortisol resistance. There are many known mutations of the glucocorticoid andmineralocorticoid receptors. People can test themselves for these by ordering genetic testing through 23andMe or Ancestry.comand uploading the results to Nutrachacker.com for their complete mutations profile.However, the mutations we know about arejust the tip of an iceberg of biologic variables that affect cortisol effect in the tissues. For those who need it, cortisol supplementation improves mood, energy, mental functioning, sleep quality and theability to handle physical and emotional stress. It reduces allergies and controls autoimmune diseases. By definition,anyone with an active autoimmune disease is suffering from a relative cortisol deficiency. However, even if physicianssuspect cortisol deficiency, they are afraid to prescribe cortisol (hydrocortisone). They have no  experience withcortisol replacement, but have a lot of experience with the damaging effects of pharmacologic doses of non-natural “steroids”(prednisone, Medrol, dexamethasone). They inappropriately generalize this negative experience to cortisol supplementation.They believe that any dose of cortisol taken long-term will cause the negative effects of Cushing's syndrome. The FDA placesHC in the same drug class as all glucocorticoid drugs and so the FDA-mandated prescriber insert lists all the "side effects" everseen with overdosing with any steroid drugs. This DrugThink prevents physicians from understanding cortisol. The medicalprofession simply has not begun to understand cortisol or cortisol replacement. If a physician prescribes HC or aglucocorticoid, he suppresses ACTH and therefore endogenous cortisol and DHEA production. DHEAS levels quickly becomelow or undetectable. DHEA is an extremely important prohormone and hormone, yet is completely unknown toconventional medicine. There are thousands of studies detailing its contributions to health and the consequences ofdeficiency. It is the most abundant steroidal hormone in the human body (20 times more abundant than cortisol, 8000 times morethan estradiol or testosterone!). (See DHEA essay). DHEA is the body's natural cortisol antagonist and prevents many ofthe negative effects of cortisol. The suppression of DHEA by glucocorticoid therapy is the cause of many of itsdeleterious effects. DHEA is anabolic, it maintains bone, skin and blood vessels. For instance, studies show that women on 5to 10mg of prednisone (like 20 to 40mg of HC) daily will start gaining bone mass when given DHEA. DHEA also improves immunesystem function and insulin sensitivity. Patients who are taking cortisol or any glucocorticoid long-term must replaceDHEA to restore youthful DHEAS levels: around 200mcg/dL in women, 300mgc/dL in men (daily average). This usually takes10 to 25mg of sublingual DHEA daily for women, 25 to 50mg for men. If DHEA is swallowed, the dose needs to be 25 to 50%higher. In addition, physicians do not understand that glucocorticoid therapy always reduces thyroid levels/effectsto some degree. It reduces TSH secretion and T4-to-T3 conversion in a linear manner, depending on dose. This problem isinvisible to physicians who only check TSH levels. This iatrogenic hypothyroidism also causes many of the deleterious long-termeffects of steroids—including the weight gain. Even physiological cortisol supplementation reduces TSH production and T4-to-T3conversion to some degree. Therefore any person on cortisol supplementation therapy must be closely observed forsigns/symptoms and relatively low FT4/FT3 levels that would indicate hypothyroidism. If present, hypothyroidism should betreated with T4/T3 therapy. Any person on cortisol supplementation also requires sufficient sex steroid levels/effects. Whencortisol is properly balanced by sufficient thyroid, DHEA, sex steroid and growth hormone levels/effects, it causes no long-termhealth problems whatsoever. For certain, an excessive HC dose--out-of-balance with other hormones--will cause signs and symptoms of cortisol excess--similar to Cushing's syndrome. Excessive HC dosing will cause weight gain, facial puffiness, higher blood pressure and increasedblood sugar. Fortunately, as the natural hormone, HC promotes much more fluid retention than the artificial steroids. So over-dosing is much easier to detect. The doctor and patient simply have to look out for any evidence of over-dosing and reduce thedose if they appear. What is a good dose? Dr. William Jefferies pioneered the diagnosis and treatment of dysfunctionalhypocortisolism. (See his book: Safe Uses of Cortisol.) He gave patients 20 to 30mg of HC daily. Conventional endocrinologistsoften will give patients only 10 to 20mg/day, regardless of symptoms. These low doses may be sufficient in persons with nocortisol resistance, who are not rapid metabolizers, and who are deficient in DHEA, sex steroids and FT4/FT3--as are mostendocrinologists' patients. However, when all the cortisol-counteracting hormones are optimized, the HC doses reguired arehigher; typically 30 to 50mg daily. There is no blood test to determine the proper HC dose--it must be based upon symptoms andsigns. The physician and patient must work together to find the doses and timing of doses that will best reduce oreliminate all symptoms of hypocortisolism 24hrs/day, without creating any signs or symptoms of cortisol excess.Usually a person needs to take the largest dose of the day upon awakening, the 1 or 2 additional doses up to the late afternoonor early evening. Cortisol is naturally low in the evening and overnight so usually need not be taken then. If a person takes theirlast dose of HC before 4pm, their endogenous production system will still kick in overnight--a good result if obtainable. While HC dosing must ultimately be guided by symptoms, seeking the lowest doses that eliminate symptoms, saliva testing isaccurate when a person is swallowing HC tablets and can be used to for problem-solving, to determine if there isobvious over- or underdosing. However, the clinical effects of the HC doses and timing are what matter. Persons varytremendously in the HC doses and timing that they require. The best regimen has to be discovered by trial-and-error. The goalis always to find the lowest dose that works. It's generally best to get a large dose in the morning, and a smaller dose in themid-afternoon. A large AM dose mimics the large AM rise in cortisol and starts the day out right. Some people only need thelarge AM dose. But usually it is best to get two or three doses--with the last one being a smaller dose around dinner time. Cortisol supplementation should only be attempted by physicians who are willing and able to stay in close contact with patients--especially in the first few weeks of supplementation. Today this task is made much easier by e-mail. I strongly encouragepatients who are starting cortisol to e-mail me within days about their response to taking the hormone. I ask them to also e-mailme after dose changes. Thus within a couple weeks we can figure out whether cortisol supplementation is helpful for the patientor not. If not, he/she can quickly taper off the therapy without having suppressed their own production for long. I prescribe onlyone-month of HC to start with and insist upon discussing the therapy by phone at that time in order to determine if it should becontinued long-term and if the dose is appropriate for the patient. I also add DHEA replacement at that time if I haven't done soalready Deciding to supplement with cortisol is a serious matter, as cortisol is the body's major stress-response hormone.A person who requires cortisol supplementation to function and feel well didn't make enough cortisol prior to therapy, and willmake less cortisol in response to stress when they are taking cortisol--due to the variable suppression of their already-weakACTH-cortisol production. This suppression is not a sufficient reason to avoid supplementation; the patient has the right tochose. If patients feel/function much better with cortisol supplementation, they must decide whether the benefits are worth thesuppression of their own production. Of course, to make an informed decision they require accurate information. When takingcortisol, they must realize that they are taking over control of their body's stress-coping system. They must learn to increase thedose when they are under more stress, are more physically active, or are ill. They should wear some easily-noticed medical alertjewelry stating that they have "Adrenal Insufficiency". There are many options today. See this site for examples. The medicalalert jewelry will prompt medical care providers to look for a medical card, so patients should also carry a medical card containingthe diagnoses, personal identifying information, doctor's names and contact numbers, and medications. One can create amedical card online. Patients can obtain an emergency treatment card with specific recommendations for doctors here. Onecan also carry a USB drive that contains all relevant medical information. 

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