Adrenal Hyperplasia or AFS?

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM

How Adrenal hyperplasia affects the bodyAdrenal hyperplasia and adrenal fatigue syndrome, or AFS, share a number of symptoms, and they can be confused for each other without good assessment. It’s important for you to know the similarities and differences in order to inform your healthcare professional and so you can help yourself deal with symptoms.

This article will deal with non-classic congenital adrenal hyperplasia, or NCAH, and its relationship to AFS.

What Is NCAH (Non-Classic Congenital Adrenal Hyperplasia)?

This form of adrenal hyperplasia is a fairly common autosomal recessive condition. It results from a 21-hydroxylase deficiency. Androgen excess is the most frequent clinical feature, instead of adrenal insufficiency with the classic form of the disorder. Females have this condition more frequently than males.

Clinical and research findings show this condition occurs in between 0.6% to 9% of women with excess androgen. Higher prevalence has been seen in some populations, including those of Ashkenazi Jewish, Mediterranean, Middle Eastern, and Indian heritage.

This condition is a milder form of congenital adrenal hyperplasia and has a later onset of symptoms. With this mild form, some people exhibit few, if any, symptoms. Many show an excess of the male hormone androgen. NCAH is caused by mutations in the CYP21A2 gene and is recessive.

Congenital Adrenal Hyperplasia

Generally speaking, NCAH is one of the three forms of congenital adrenal hyperplasia. The other two types are known as simple virilizing adrenal hyperplasia and salt wasting adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) affects the adrenal glands which produce several hormones, including corticosteroids, mineralocorticoids, and androgens. The first two of these hormones affect the body’s illness or injury response and the body’s salt and water levels, respectively. Androgens are the male hormones.

Enzyme deficiencies affect the adrenals’ ability to produce these hormones. A deficiency in the enzyme required for one of these hormones will result in an overproduction of the others.

A lack of 21-hydroxylase is the most common cause of CAH. Not having this enzyme prevents you from making cortisol and aldosterone, for salt-losing adrenal hyperplasia, and causes you to produce excess androgen. The excess of this male hormone will typically bring symptoms of abnormal sexual development.

CAH is the more severe form of this condition and is most often found early in life. If left unaddressed, adrenal crisis and even death may occur. There is no cure for CAH, but with appropriate care, sufferers can live a full life.

In the salt-wasting form of CAH, the body has trouble maintaining an appropriate level of salt in the blood. There is also a lack of cortisol and aldosterone produced by the adrenal glands. This form of CAH can result in shock, coma, or death if it isn’t found and remediated.

In the non-salt-wasting form of CAH, the shortage of the enzyme is not as severe. This shortage leads to sufficient levels of aldosterone, but insufficient cortisol production.

Those with CAH are much more likely to have adrenal fatigue than the general population. A person with CAH who comes under significant stress could easily progress much more quickly to the later stages of AFS due to natural low cortisol production.

AFS and the NeuroEndoMetabolic (NEM) Model

Any time the body comes under stress no matter the source, the response is the same. The hypothalamic-pituitary-adrenal (HPA) axis is activated, resulting in the adrenal glands secreting cortisol, the stress-fighting hormone. If the stress continues, as it does so often in our stress-filled culture, ultimately adrenal fatigue will set in. This means the adrenals no longer can produce enough cortisol, and symptoms of AFS begin. Continuing stress leads to more and more symptoms. In the later stages of this condition, the person suffering from it may become bedridden.

The NEM model and Adrenal hyperplasiaConventional physicians are not adequately trained to assess or remediate AFS. Their approach is to deal with individual symptoms or organs and suppress the symptoms to attempt relief. However, this is not adequate for AFS. Natural medicine practitioners who are trained in the NeuroEndoMetabolic (NEM) model of stress response will be enabled to assess how a person’s six major organ systems interact in the face of continuing stress. This interaction allows them to get to the root causes of the symptoms of AFS, and then put together a remediation plan that will not just control symptoms, but address these root causes.

Signs and Symptoms of Adrenal Hyperplasia

The two forms of adrenal hyperplasia, congenital and non-classical congenital, have both common and different signs and symptoms.

To begin, there are those who show no signs or symptoms of NCAH.

With NCAH, the symptoms typically are related to excess androgen.

Children who are assessed with this condition often will exhibit early signs of puberty such as growing pubic hair, underarm hair, and body odor. These signs may occur as early as 8 or 9 years of age.

Other signs of NCAH in children include greater height, faster growth, and faster maturation of skeletal bones. In girls, there may be an enlarged clitoris, while boys may show an enlarged penis. The increased maturation of the skeleton may lead to early epiphyseal fusion, resulting in shorter adult height.

Females are more often assessed with this condition in adolescence and adulthood. Much of this is due to the abundance of adrenergic symptoms. Typical symptoms include hirsutism, acne, hair loss, loss of ovulation, and menstrual dysfunction. One large study showed the most common symptoms to be hirsutism, followed by light or infrequent menstrual periods, and acne.

Adrenal hyperplasia and menstrationAnother study that investigated women with NCAH showed the most common presenting symptoms to be hirsutism, difficulty with menstruation, and reduced fertility.

As mentioned before, not all people with NCAH exhibit symptoms. A large genetic study of 330 family members showed a distribution of symptomatic versus non-symptomatic individuals. Of these subjects, nine were seen to have symptoms, and 42 individuals were asymptomatic but were affected by NCAH. The largest number, 242, were heterozygotic carriers. Out of the entire subject cohort, 37 were not affected by NCAH.

In that same study, the majority of males were not symptomatic. Most of the time, they were assessed only after a female in the family was determined to have NCAH.

The most frequent presenting symptom in women was lack of menstruation, either primary or secondary. Also seen frequently in women were chronic lack of ovulation and infertility. A similarity with polycystic ovary syndrome (PCOS) was also evident. Approximately half of women with NCAH will show physical changes in line with PCOS.

Fertility can be an issue in women with NCAH. The issue is not necessarily infertility, but subfertility. This comes due to the problems with ovulation often seen in adrenal hyperplasia.

Classical congenital adrenal hyperplasia in women appears to bring on increased levels of progesterone that interfere with the menstrual cycle and fertility. Elevated levels of progesterone may also be seen in women with NCAH. This leads to decreased quality of mucus in the cervix that can interfere with penetration by sperm and thus can cause infertility. In the follicular phase of the menstrual cycle, increased 17-OHP (a steroid hormone related to progesterone) or P4 (another steroid hormone related to progesterone) can lead to difficulties in the maturation of the endometrium and to difficulty with implantation of the embryo.

There are several risk factors for metabolic disorder seen in women with non-classic congenital adrenal hyperplasia. Insulin resistance, obesity, and high blood pressure are included in these risk factors. High androgen levels complicate issues contributing to atherogenic lipid profiles and thus increase the risk of metabolic disorders. Insulin sensitivity has been shown through research to be present in women with NCAH who are not obese. Much of the research into insulin sensitivity has resulted in mixed findings and typically use women with classical CAH as subjects.

Congenital Adrenal Hyperplasia and PCOS

Polycystic ovary syndrome, or PCOS, comes with a constellation of symptoms that is similar to both congenital adrenal hyperplasia and non-classical congenital adrenal hyperplasia. These similarities make it difficult to assess people with them correctly.

Adrenal hyperplasia and PCOSPCOS consists of two major factors: chronic anovulation, or non-production of eggs, and high levels of androgen. The lack of egg production and the possible lack of menstruation cause difficulties in the menstrual cycle. At the same time, high levels of androgen can cause symptoms such as more facial hair, sideburns, hair in the middle of the female chest, and male-pattern baldness. Acne over the back and on the face is also a result of excess androgens.

One way to determine whether PCOS is present is to perform an ultrasound to detect multiple cysts on the ovaries.

High insulin levels may be present in both conditions. The increased androgens may be responsible for these high levels in the ovaries. As with adrenal hyperplasia, women with PCOS often also have hypertension and obesity. One way to confirm the presence of high insulin levels is the darkening of the folds of skin around the neck, called acanthosis nigricans.

The most common form of CAH, a deficiency in 21-hydroxylase, causes increased androgen production in the womb. Female babies with this condition may appear more masculine at birth due to ambiguous genitalia, including an enlarged clitoris.

Baby boys will likely not show significant symptoms at birth, but the lower levels of aldosterone that can lead to a loss of salt is a condition that causes great concern. Potentially, babies with this issue can go into shock a week or two after birth, with very low sodium and very high potassium levels.

One of the differences between PCOS and CAH is in the location where the excess androgens, which ultimately convert into testosterone, are produced. In PCOS, the ovaries are the location for this excess. In CAH, the adrenals produce the excess androgen.

The Importance of Insulin

In all three conditions mentioned in this article, congenital adrenal hyperplasia, PCOS, and AFS, insulin and insulin resistance are important factors. What is the importance of insulin in these conditions?

Under normal conditions, insulin controls excess glucose in your blood, guiding it into your cells for energy production. When stress hits, your sensitivity to glucose lessens, leaving more glucose in your bloodstream. This is due to your body’s response to the stress, a biological attempt to either fight against or flee from whatever is stressing you.

Insulin resistance and Adrenal hyperplasiaNormally, this is an occurrence of short duration. But when stress continues, insulin resistance keeps more sugar in your blood. One result can be the type of symptoms seen in both PCOS and AFS, such as increased estrogen and testosterone, decreased ability to digest food, and decreased fertility.

Continuing stress also can lead to a roller coaster effect with increased levels of blood glucose leading to increased insulin levels in the blood to counter it. These increased levels of insulin lead to too little glucose in your blood, resulting in a downturn in your energy, usually in the middle of the afternoon. Typically in women with PCOS, this means foggy thinking, feeling grumpy, and having sugar cravings at that time of day.

These are also typical symptoms for anyone with AFS.

At the times when your blood glucose levels drop, your body releases adrenaline. This stresses your adrenal glands and pushes more glucose from your cells into your bloodstream. For short-term stresses, this system works well. But when stress continues, it begins taking a toll, leading to adrenal fatigue.

Congenital Adrenal Hyperplasia and AFS

The relationship between CAH and AFS stems from the hormone ACTH and its action on cortisol. Normally, the adrenal glands are stimulated by ACTH from the pituitary to produce the precursors of cortisol, the stress-fighting hormone.

Through a feedback system, the level of cortisol in the bloodstream will eventually reduce the release of ACTH, keeping an appropriate balance in play. Lower levels of ACTH takes the pressure off of the adrenal glands to produce cortisol.

In people with CAH, the level of cortisol does not increase in the bloodstream, thus keeping ACTH high and the adrenal glands continually stimulated. The process that converts precursors into cortisol is blocked in CAH. The result is continuing stimulation of the adrenals. If stress is added into this mix, the adrenals are bombarded with the need to produce cortisol.

A build-up of the precursors to cortisol results when the process of converting them is blocked. One of these precursors is testosterone, which brings on male characteristics seen in people with adrenal hyperplasia. With the levels of these precursors rising, some leaks into the bloodstream, causing other symptoms found in people with CAH.

Blocking this process of converting precursors into cortisol can lead to a reduction of aldosterone in the blood. This can lead to the serious condition of too little salt in the bloodstream.

Testing for Non-Classical Congenital Adrenal Hyperplasia

As with other conditions, typical medical assessments don’t always identify CAH or NCAH as the conditions underlying symptoms. In order to fully assess and more effectively remediate the condition, specific tests are needed.

While it is true that a deficiency in 21-hydroxylase is the main cause of CAH, it is not the only possible cause. It’s important to determine which of the steps in the three pathways for producing the steroids involved are blocked. This means other markers should also be assessed. There are subtle changes in the steroids that have to be evaluated, so sensitivity in the tests administered is vital.

Each of the steroids involved is based on cholesterol. Each one either adds or takes away a small factor in order to complete its product. One may add a hydrogen to an oxygen group. Another may remove an oxygen from a hydrogen group. Another may add a hydroxyl group. Each of these changes is subtle but leads to a very different hormone response.

Adrenal hyperplasia and medical testingRather than a single test for 17-hydroxyprogesterone, a panel of tests to be more specific may be best. The single test is adequate for determining the presence of a lack of 21-hydroxylase, but not adequate if other factors are involved, for example, a 3-beta-hydroxysteroid deficit.

The panel of tests can differentiate CAH from PCOS, and if the CAH is actually NCAH. With NCAH, there will be results that show a partial defect in 21-hydroxylase. Symptoms from the lack of cortisol, a marker for NCAH, would be similar to those seen in PCOS.

If NCAH is suspected, there are some specific tests for this condition. One is to measure 17-OHP. This is accomplished with a single morning blood draw to measure steroid levels of 17-hydroxyprogesterone, androstenedione, and testosterone.

Studies have shown lower testosterone levels in most women, with higher levels of androstenedione. Clinical results have shown elevated 17-OHP levels over 200 ng/dl strongly indicates the presence of NCAH, if the blood is drawn in the early follicular phase of the menstrual cycle.

To confirm this suspicion, an ACTH stimulation test can be performed. Blood is drawn prior to giving an intravenous dose of ACTH, then drawn again an hour after. People who do not have CAH will show increased cortisol in their bloodstream. Those with NCAH will show high levels of 17-OHP, a precursor from which cortisol is made. These levels can be compared with standardized tables to complete the assessment.

Another marker for the presence of NCAH is higher levels of deoxycorticosterone and 11-deoxycortisol. If these levels are high in the blood, they suggest NCAH due to a deficiency in 11beta-hydroxylase.

These levels will be elevated because 11beta-hydroxylase converts deoxycorticosterone to corticosterone which is a precursor to aldosterone. It also converts 11-deoxycortisol to cortisol.

If the NCAH is due to a deficiency in 11beta-hydroxylase, these symptoms will be present: hypertension and excess androgen. The hypertension is due to monogenic, low renin with low aldosterone levels.

Remediation of Congenital Adrenal Hyperplasia

For those people with NCAH who exhibit few or no symptoms, any remediation efforts may not be worth the potential risks. Psychological counseling is recommended for those women who may have the “male” symptoms that decrease the impression of femininity.

Medical remediation efforts can include regulating menstruation, decreasing levels of androgens and testosterone, making efforts to normalize the tissues and processes involved in menstruation and fertility, and maintaining normal cortisol levels.

Adrenal hyperplasia, diet and proteinDiet is important in these efforts. Whole foods, good quality proteins, healthy fats, and increased amounts of fruits and vegetables help. Organic foods are best. Drinking increased amounts of water and staying away from caffeine, sugar, and alcohol are strongly recommended.

Fertility is an important topic to be considered. Women with NCAH typically lose fertility earlier than other women. Couples probably should consider pregnancies prior to age 35. The use of medications to stimulate ovulation may be considered.

Glucocorticoids may be used in women to raise cortisol levels and to stimulate and support ovulation, thereby increasing fertility. With children and adolescents who have non-normal skeletal maturation and height, glucocorticoids may be used to increase cortisol also.

For people with CAH, lifetime maintenance with glucocorticoids may be necessary. Some of the glucocorticoids used are hydrocortisone, prednisone, and dexamethasone. Remediation efforts using these glucocorticoids should be at the lowest level possible that will still give the desired results. Regular medical remediation should only be undertaken for those who show symptoms. The overall goal is to reduce hyperandrogenism.

Natural Approaches to Remediation

For those wanting to deal with their NCAH symptoms naturally, there are some herbs and supplements to consider. Please keep in mind that natural approaches may take some time to show benefits, so be prepared to be patient. Be sure to consult with your healthcare professional before taking any herbs for NCAH.

Herbal Approaches

Chasteberry, vitex agnus-castus, is said to aid in the regulation of the menstrual cycle and to support ovulation. This herb appears to have an effect on hormones that influence pregnancy, breastfeeding, and menstruation. These same hormones may have an effect on some breast cancers. There appear to be no serious side effects to this herb. Possible side effects may include acne, menstrual bleeding, headache, stomach upset, and weight gain. Because of its potential effects on hormones, you should avoid using chasteberry if you’re breastfeeding, are pregnant, have breast cancer, or are taking birth control pills or hormone replacement.

Black cohosh, cimicifuga racemosa, is said to have an effect on lowering LH levels. Increased amounts of this hormone during the follicular phase of menstruation may lead to thickening of the endometrial lining prior to ovulation. Some mild side effects have been reported with this herb, such as upset stomach, cramping, headache, rash, and vaginal spotting or bleeding. If you’re pregnant or breastfeeding, you should avoid using black cohosh. In pregnant women, there is a risk of miscarriage. With the possibility of increased risk of breast cancer or worsening of existing breast cancer with this herb, it should be avoided if you have or have had breast cancer or if you are at high risk of developing breast cancer. This herb functions similarly to estrogen in the body, so if you have any condition that is sensitive to female hormones, you should avoid using it. If you have liver disease, a kidney transplant, or a protein S deficiency, you should avoid using black cohosh.

Saw palmetto, serenoa repens, may have an effect on modulating testosterone levels, thus helping in androgenic hair thinning and acne. Some mild side effects of saw palmetto may include dizziness, nausea, vomiting, headache, constipation, and diarrhea. Women who are pregnant or breastfeeding should avoid this herb. If you’re having surgery, saw palmetto should be stopped at least two weeks prior to the surgery.

Spearmint tea, mentha spicata, is said to have an effect on lowering testosterone levels. If you’re pregnant, avoid spearmint tea in excessive amounts due to possible damage to the uterus. Spearmint tea can decrease milk supply during breastfeeding. Possibly, using spearmint tea could make kidney disorders worse. For this reason, you should avoid it if you have any kind of kidney problem. The same holds true for liver problems.

D-chiro-inositol may have an effect on increasing ovulation and decreasing free testosterone. Mild side effects with adults can include nausea, tiredness, headache, and dizziness. Not enough information is known regarding its use during pregnancy and breastfeeding for its use to be considered safe. If you have bipolar disorder, you should avoid inositol.

Green tea aids in the increase of sex hormone binding globulin that binds to androgens and lowers the amount of androgen circulating freely. In moderate amounts, green tea is considered safe for use. For long-term use or in high doses, it may be unsafe.

Flaxseed is another herb that helps increase the sex hormone binding globulin to decrease the amount of free circulating androgens. Flaxseed should be taken with plenty of water to lower the possibility of blocking of the intestines due to the bulking effects of this herb. More than six tablespoons per day of raw or unripe flaxseed may be poisonous and should be avoided. Since this herb functions like estrogen, it should be avoided if you’re pregnant. Flaxseed may inhibit blood clotting, so if you have a bleeding problem, avoid using it. There is some evidence that flaxseed may lower blood sugar. If you have problems with blood sugar levels, you probably should avoid it. If you have a condition that is hormone sensitive, you should avoid flaxseed since it functions like estrogen. Since flaxseed may lower blood pressure, you should avoid using it if you have problems with low blood pressure. It may also increase triglycerides.

Adrenal hyperplasia and soySoy is said to aid in the production of the sex hormone binding globulin that will lower the amount of androgens circulating freely. Using soy on a long-term basis may be unsafe in that it could cause abnormal tissue growth in the uterus. Higher doses during pregnancy may be harmful to the fetus. Some research has suggested soy may increase the growth of some cancers. Soy may increase the risk of kidney stones.

Nettle root is another herb that is said to increase levels of sex hormone binding globulin that would bind to androgens and decrease the amount of free circulating androgens. It’s best to avoid using nettle root if you’re pregnant or breastfeeding. There is the possibility of this herb causing miscarriage. If you have diabetes, be sure to monitor blood sugar levels closely. Nettle is said to lower blood sugar levels. There is also the possibility of nettle parts lowering blood pressure. If you have problems with blood pressure, be sure to monitor yourself closely.

You might try other herbs and supplements to support adrenal health as well. Adrenal glandular supplements may be helpful if you test low for cortisol. Herbal mixtures with licorice root may increase energy and aid in your ability to tolerate stress.

If you’re using glucocorticoids, it’s important to add some supplements to your diet. In particular, glucocorticoids decrease bone density and also decrease absorption of vitamin D and calcium. Therefore, it’s important to add these two nutrients to your diet.

© Copyright 2017 Michael Lam, M.D. All Rights Reserved.

Dr. Lam’s Key Question

Adrenal hyperplasia and AFS share similar symptoms. In both CAH and NCAH, lower cortisol is problematic. In AFS, lower cortisol leads to significant problems. In CAH, lower cortisol leads to increased ACTH and continued pressure on the adrenals. In AFS, the adrenals are pressured to exhaustion and the development of symptoms. With adrenal hyperplasia, the enzymatic process that supplies hormones to the adrenals is insufficient, and AFS is more likely.

Adrenal hyperplasia