What Is Hypoadrenalism

Featured, Hypoadrenalism | admin | December 2, 2009

Hypoadrenalism refers to the state wherein the adrenal glands do not function properly, they function below the required levels. These glands are small in size and are present above each kidney. This means that there are two adrenal glands, which are important from the point of view that both of them are the producers of variety of hormones. The two glands are also known as manufacturer of the ‘chemical messengers’. Each adrenal gland are made up of the following two parts:

The adrenal cortex, which is the external ring
The adrenal medulla, which is the internal core

Both these parts functions separately to produce different hormones and offer different control mechanisms. The adrenal cortex is responsible for producing the steroid hormone named cortisol, which plays an important role in responding to physical stress. The production of cortisol is controlled by the adrenocorticotropin (ACTH) hormone, which is produced by the pituitary gland located at the bottom of the brain. In short, the release of ACTH by pituitary gland controls the production of steroid hormones in the adrenal glands. Let’s know how.

If there is a low quantity of cortisol in the blood due to less production of the hormone in the adrenal gland, the pituitary gland detects this low level of cortisol in the blood. To maintain the normal level of the cortisol steroid hormone, the pituitary gland will then elevate the release of ACTH, which in turn, excites the adrenal cortex to lift up the production of cortisol.

On the other hand, if excessive cortisol is produced by the adrenal glands, its level in the blood would rise, which when sensed by the pituitary gland would result in stopping the secretion of ACTH. This would directly regulate the production of cortisol.

It was important to know about cortisol as stated above before going ahead with hypoadrenalism because several of its symptoms are the direct result of the deficiency of cortisol. Moreover, if this deficiency is not treated, it can make a patient face serious consequences including death.

Causes of Hypoadrenalism

There are two types of hypoadrenalisms, which are stated below.

Primary hypoadrenalism or Addison’s disease
Secondary hypoadrenalism or ACTH deficiency

Let’s go through each of their symptoms separately.

Causes of Primary Hypoadrenalism or Addison’s Disease

Failure of the adrenal glands is the cause of Primary hypoadrenalism, also known as the Addison’s disease. This is generally known as an ‘autoimmune’ disease wherein antibodies are generated by the immune system.

There is no viral or bacterial attack, but the attack is on the tissues of the body by these antibodies. In primary hypoadrenalism, the antibodies actually damage the adrenal cortex leaving behind the scars. These antibodies attacking the adrenal cortex can be found in the blood of certain victims.

This disease is chronic (long-standing) in nature and can be detected before the damage is done to the adrenal cortex. Patients with this disease are also vulnerable to other organ-specific autoimmune diseases, which are listed below.

Autoimmune thyroid disease
Hypoparathyroidism
Pernicious anaemia
Vitiligo
Coeliac disease (not autoimmune)

According to a research, Addison’s disease found in approximately 6 among every 1,00,000 people in the North East Thames region. This means that this condition is rare.

Unfortunately, there is no scientific evidence to show the prevention of autoimmune assaults by any treatment.

Causes of Secondary Hypoadrenalism or ACTH Deficiency

This is the most common type of hypoadrenalism. Any disease or disorder of the pituitary gland and consumption of cortisol-like steroids for other medical conditions such as asthma are the causes of secondary hypoadrenalism or ACTH deficiency. This in turn results in the failure of the adrenal glands as an indicator of the pituitary disorder.

Tuberculosis as the Other Cause

Tuberculosis of the adrenal glands is one more factor that leads to hypoadrenalism. It damages the entire adrenal gland including the cortex and medulla. Such a destruction of the adrenal glands is permanent, which means that there is no way to cover up the loss even after it is detected through hormone deficiencies. Generally, when at least 80 percent of both the adrenal glands are in a damaged condition, the deficiencies of hormones become medically apparent. Tuberculosis is also detected in other organs such as the lungs.

Tuberculosis actually is the major cause of the primary hypoadrenalism in the U.K. in the past. Until today, it is the common cause of the Addison’s disease in the underdeveloped countries.

Rare Causes

There are several diseases that rarely influence the adrenal glands, which can lead to any type of hypoadrenalism.

Related to Primary Hypoadrenalism or Addison’s Disease

Listed below are its causes.

Adrenoleukodystrophy, which refers to an inherited disease wherein the adrenal glands deteriorates and the myelin sheath (insulation) that covers the brain’s nerve fibres, is missing.
Amyloidosis, which refers to a condition wherein amyloid, a strange substance, gets placed in different tissues that damages their function
Bilateral adrenalectomy, which is nothing but the surgical eradication of the adrenal glands
Congenital adrenal hyperplasia, which refers to a genetic condition wherein a defect in an enzyme creates problems for the adrenal glands to generate steroid hormones
Drugs such as ketoconazole (Nizoral), metyrapone (Metopirone), and mitotane
Familial glucocorticoid deficiency (ACTH receptor mutation)
Haemochromatosis
Haemorrhage in patients taking anticoagulant drugs or suffering from septicaemia (blood poisoning)
HIV-related adrenal inflammation
Metastatic cancer (whose origin lies in some other part of the body)
Sarcoidosis

Related to Secondary Hypoadrenalism or ACTH Deficiency

This is due to any damage of defect in the pituitary gland that influences the normal functioning of the adrenal glands. We know that the pituitary gland maintains the normal levels of cortisol by adjusting the cortisol quantity in the blood. But, the gland cannot make out whether the cortisol in the blood is due to the production by the adrenal gland or due to the synthetic steroid absorbed from the drugs or creams. Therefore, the probable causes of the secondary hypoadrenalism are as follows:

Absorbing steroid from medicines and creams, as this will result in decreased secretion of ACTH by the pituitary that will render the adrenal cortex being consequently inactive.
Sudden halt of the steroid treatment, which indicates abrupt deficiency of cortisol as the adrenal gland does not start manufacturing cortisol until a few weeks or months. This is why the patients taking the steroid treatment from a reasonable period should not stop their medicines suddenly.
Pituitary disease, disorder, or conditions

Symptoms of Hypoadrenalism

Listed below are the symptoms of hypoadrenalism.

Fainting
Dizziness
Weakness, fatigue
Weight loss
Vague stomachaches (in 50 percent patients)
Gut symptoms (in 50 percent patients)
Increased skin pigmentation (most common in Addison’s disease due to increased ACTH levels that activate pigment cells – melanocytes in the skin)
Mental problems such as depression (rare)
Joint and muscle pains
Acute critical back pain due to bleeding into the adrenal glands (bleeding is due to anticoagulants like warfarin that stops blood clots or due to meningococcal septicaemia)
Hypotension (low blood pressure due to loss of cortisol)

Diagnosis

Failure to check for hypoadrenalism, especially when a patient is sick, might lead to collapse and demise. A doctor will look for the following factors to diagnose hypoadrenalism.

Pigmentation:
One of the factors that is looked for to diagnose Addison’s disease is its pigmentation. This can be seen in exposed or disturbed skin areas such as the knuckles and elbows. In addition, sometimes, the inner wall of the cheek and any scar just prior to the disease also exhibit pigmentation.
Symptoms of the Organ-specific Autoimmune Diseases:
Such disorders include vitiligo that are patches of abnormal pale skin and thyroid diseases like goitre (swelling of the neck). Blood tests are done to check for other such diseases by checking thyroid function, folate, iron, vitamin B12, and antibodies to other organs (thyroid, gastric parietal cells, and endomysium). If the patient is suffering from pernicious anaemia, the blood count will evidently show increased number of eosinophils (a white blood cell) and large red cells (abnormal macrocytes).
Abnormal Blood Pressure:
This occurs in case of severe cortisol deficiency. The patient might suffer from postural hypotension that is nothing but fall in blood pressure while standing. A very low blood pressure might make the patient collapse. In the Addison’s disease, the highest blood pressure is even less than 110 mmHg.
Low Levels of Sodium and Increased Level of Potassium:
This occurs when there is severe deficiency of cortisol and aldosterone (steroid hormone) and is detected by performing the blood tests. In addition, patients might have a high level of calcium, which is evidently found in 10 percent of victims of the Addison’s disease. According to a study, the potassium levels might be normal in 40 percent of such victims.
Low Blood Sugar:
This is happens rarely except in children or in patients who have been undernourished for a reasonable period, for example, after a major surgery.
Low Cortisol Level:
A cortisol level less than 200nmol/l requires diagnosis, as it is seriously abnormal. On the other hand, a level of 550nmol/l or above rules out the need of diagnosis.

The endocrine unit also goes for special investigations, which include Synacthen tests, chest X-ray for tuberculosis, and measuring adrenal hormones along with ACTH, aldosterone, plasma renin activity, noradrenaline, and adrenaline.

The Synacthen Test:
It includes injecting synthetic ACTH into a vein and then testing the cortisol response in the blood. In a situation of hypoadrenalism, a low dose of 250 micrograms will not prove normal. If high doses of Synacthen (1mg) are given for many days, it results in normal cortisol level in patients with secondary hypoadrenalism.
Scans:
Sometimes, a CT scan of the adrenals is also undertaken to seek calcium deposits, which is an indicator of tuberculosis. In addition, a skin test for tuberculosis is also suggested.
Measuring ACTH Levels:
The ACTH level is greater than 80ng/l in patients with primary hypoadrenalism, as the pituitary gland attempts to increase the cortisol level. However, one cannot predict the ACTH level if the ACTH deficiency is due to pituitary disease or steroid suppression. It is usually less than 10ng/l.

Problems with the Diagnosis

A few patients, in whom the hypoadrenalism is not diagnosed, are wrongly diagnosed as having an abdominal disease such as appendicitis. It is only after the operation that hypoadrenalism is diagnosed, as the appendix is normal and scars becomes brown in color.

The problem related to the diagnosis is that hypoadrenalism is just not taken into consideration. After detecting hypoadrenalism, there might be further problems in finding out the reasons of the adrenal failure, which require more special tests.

Treatment of Hypoadrenalism

The first point of contact is your GP. He/She might take blood samples for checking the salt levels, cortisol level, and kidney function. As the sample is taken, hydrocortisone is immediately given as a replacement for cortisol. Next, the GP will refer you to a specialist endocrine unit. Listed below are the treatments for hypoadrenalism.

Oral Hydrocortisone (Hydrocortone Tablets):
This is the best replacement of cortisol. It is quite similar to natural cortisol produced by the adrenals and its level is easily detected in the blood. To measure the effectiveness of this tablet, know the accurate level of cortisol before taking the first tablet of the day and then check the level at regular intervals after taking the tablets. This is known as a ‘hydrocortisone day curve’. Actually, in our normal body, the level of cortisol is high in the morning and then it gradually decreases in the afternoon and evening. To maintain this normal swing, the cortisol level is maintained at a high level in the morning (not more than 1000nmol/l) and lower in the afternoon and evening (between 100 and 300nmol/l). This is met by taking the dose of 10 mg after waking in the morning and 5 mg each before lunch and dinner.
Oral Fludrocortisone (Florinef):
It is a synthetic form that covers up the deficiency of another adrenal cortex hormone called aldosterone found in patients with primary hypoadrenalism. It is taken after waking up in the morning as a single tablet of usually 100 micrograms.
Other Corticosteroids:
This includes cortisone acetate, prednisolone (Deltacortril), and dexamethasone. But, it is not easy to determine the accurate dose of prednisolone and dexamethasone, which might lead to many other problems. These include avascular hip necrosis (damage to the part that forms the hip joint), osteoporosis, hypertension, and deterioration of diabetes mellitus. Further, the body must convert cortisone acetate into an active steroid, but this also varies among patients.

If a patient taking oral hydrocortisone starts suffering from fever or mild diarrhea and vomiting, he/she should double the dose for next 48 or 72 hours. Further, if a major surgery or illness has taken place, an intramuscular or intravenous injection of hydrocortisone needs to be taken to cope with the biological stress.

Lastly, all patients of hypoadrenalism can access the specialist advice and treatment anytime and should visit the specialist endocrine clinic at least once a year.

Show You Care

Patients suffering from hypoadrenalism are subject to life-long treatment and are advised to take certain precautions, as the result of non-compliance can be even death. The main point to bear in mind is that the one needs more amount of cortisol when undergoing through physical stress, for example, during the time of surgery. Therefore, all patients:

Should keep a warning card that provides details on their condition including the need of adrenal replacement whenever required to protect themselves from coma or collapse.
Should keep extra hydrocortisone tablets and injections at home or out of home.

Just remember that proper treatment and supervision results in normal life expectancy.