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Addison’s Disease

Case scenarios 

Case 01

A 20-year-old unconscious female was admitted to the emergency unit. Her anxious parents said that she complained about dizziness and vomited on the previous day. She has had a headache for one month period and had taken medications for that. The worried and tearful parents had no idea what was wrong with their daughter. On examination, she was severely hypotensive, and basic investigations revealed hyponatremia and hyperkalemia.  

Case 02.

A 45-year-old male presented to the out-patient department complaining about abdominal pain for a five-month duration. He also complained about anorexia for three months, and he also had constipation. He had no fever or vomiting. Though he was a known patient of type-1 diabetes, he had good control over blood sugar levels. On examination, he had a brown pigmentation in his wrist.

Case 03. 

A five-year-old girl was brought to the out-patient department because her mother was worried that she was ill-looking for about two months. The mother complained that she was different in her behavior. Though she had been an active girl earlier, she had not been playing and had shown difficulty in walking in the last month. Her body mass index was lower than the reference level, and she looked drowsy. On examination, her lower limb muscle power was reduced, and she had a buccal mucosal pigmentation.  

Even though these patients presented differently, all of them had the same diagnosis in the end, and it was Addison’s disease (AD). So, let us take an overall look at these three cases. How does all these fit in the same frame?

What is Addison’s Disease? 

Addison’s disease is an endocrine disorder caused by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids, mineralocorticoids, and sex steroids. These hormones play a vital role in our body. So, it would be clear to you that deficiency of these hormones can alter the metabolism in our body and cause a variety of problems.  

Autoimmunity is the main factor that triggers the destruction of the adrenal cortex leading to AD. Also, infectious diseases, bilateral adrenal removal by surgery, bilateral adrenal hemorrhage, bilateral adrenal metastasis destroying the adrenal cortex, genetic disorders, and some medications can lead to AD. 

What will Bring a Patient with AD to a Physician? 

Patients with AD can present due to adrenal crisis or due to insidious and non-specific symptoms.  

An adrenal crisis is an emergency situation where we have to attend immediately. What do you think the adrenal crisis presentation would look like? Just have look at our first patient, who presented with acute symptoms.

In an adrenal crisis, the patient would be severely hypersensitive and dehydrated. They also may present with persistent vomiting, profound muscle weakness, headache, extreme sleepiness, or even coma. 

Patients with insidious and chronic symptom onset often report vague and non-specific symptoms. They may complain about weight loss, malaise, weakness, fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, constipation, syncope, myalgia, and joint pain. They also may show confusion and depression. The severity of the symptoms would be different from one patient to another.

Grey-brown pigmentation is a predominant sign seen in most cases. This is due to the altered activity of adrenocorticotropic hormone action on melanocytes. This is an initial sign in most AD patients. In AD, symptoms may develop slowly, even over several months. Often, it progresses so slowly that symptoms can be left unnoticed for a long period of time.   

What Conditions should We Include in the Differential Diagnoses?

As the symptomatology of AD varies significantly, we have to think about a variety of diseases that can cover the relevant symptoms. So, we have to consider AD, other endocrine disorders, neurological disorders, gastrointestinal disorders, and also systemic diseases. We have to take a proper history to narrow down the possibilities. Let us look into some common differential diagnoses considered with AD. 

Altered activity in the immune system cause destruction of the adrenal cortex leading to reduced hormone production. In these patients, the early production would be due to mineralocorticoid deficiency with signs – typically, postural dizziness, increased thirst, salt cravings, and increased urination. They may also show increased pigmentation.  

As this is an autoimmune condition, these patients can have symptoms of other autoimmune diseases. Most commonly, they will have autoimmune thyroiditis or type 1 diabetes mellitus.  

Tuberculosis, fungal infections, and histoplasmosis are the main infectious diseases that can lead to adrenal failure. HIV is also a growing cause reported around different regions over the world. 

Adrenal tuberculosis usually occurs as a complication of lung, gastrointestinal, or kidney tuberculosis. 

Caseous necrosis of the adrenal gland can cause cortical and medullary tissue destruction.  

The pituitary gland secretes adrenocorticotropic hormone (ACTH), which stimulates adrenal cortical hormone production, and many other hormones. Pituitary disease can cause different presentations. So, what could predominate? Signs of glucocorticoid deficiency can predominate in this, notably, loss of weight, muscle weakness, and anorexia. They also may have skin pigmentation, and children may show hypoglycemia.  

This is an autoimmune condition that causes destruction of the pancreas, and a reduced level of insulin cause deranged glucose metabolism. Excessive fatigue, sleepiness, increased thirst, and urination are some common features of this condition.  

Celiac disease is a chronic autoimmune disorder that commonly affects the small intestine. These patients may present with abdominal pain, anorexia and also skin pigmentation, dermatitis herpetiformis.  

There are so many other diseases we have to think of as differential diagnoses for AD. For example, we may have to think about chronic fatigue syndrome, depression, hypothyroidism, syndrome of inappropriate antidiuretic hormone, and lymphoma. Considering our cases, we have to select diseases that go with each presentation. Once selected the diseases, we can narrow down our differentials with the help of examination findings and investigations.  

How can examination keep us on track? 

You might feel it is difficult to recognize the AD, as its symptoms cover a lot of ground. But through examination, we can look into signs which are more likely to be due to AD. If the patient is stable, we can take our time to examine the patient. But, if the patient is in adrenal crisis, there would be no time for a detailed examination. 

What should we assess in stable patients? 

General examination 

How to Arrive at a Diagnosis with Investigations? 

If you are suspecting adrenal crisis, it is better to do an urgent blood test for ACTH and cortisol. In spite of waiting for results, you have to start the treatment s for the patient immediately.

If the patient is having a stable presentation, required investigations should be done before any treatment.  

So, when a patient presents with symptoms susceptible to AD, we should have a high clinical suspicion and do necessary investigations. In most cases, AD patients will have glucocorticoid deficiency with or without other adrenal hormone deficiencies. So mainly, the ACTH stimulation test and ACTH assay play a major role in diagnosing AD. Low cortisol level than baseline in ACTH stimulation test and low ACTH level than baseline in ACTH assay will confirm the diagnosis of AD. 

When we come to AD diagnosis, what we have to think next is, what is the cause for AD? For this, we can do some other investigations.  

There are some other tests that are supportive in AD diagnosis and management. For example, we can do basic investigations like full blood count, thyroid function tests, blood glucose level, and plasma calcium. However, we always have to avoid unnecessary investigations and consider the benefits over adverse effects when doing the investigations. 

How to Treat a Patient with Addison’s Disease? 

We have to make a treatment plan according to the patient’s condition and the resources we have. The goal of the treatment is to restore adrenal function and bring back the normal metabolism in the body. 

If the patient is in an adrenal crisis, what should we do?

First, remember we have to work against the clock, as this is an emergent situation. We should give a bolus of Hydrocortisone 100mg in intravenous or intramuscular routes. Then we should continue an intravenous infusion of hydrocortisone at the rate of 200mg per 24hours.  

Along with these, we have to start fluid resuscitation. We have to give 1000ml normal saline infusion in the first hour and 4-6 liters of normal saline during the first 24hours. 

This is the immediate treatment plan for our first patient. We also have to thoroughly monitor her progress with our treatments.  

What to do in chronic AD? 

Chronic AD patients will need daily steroid therapy. They can feel unwell, even by missing one dose.

Here are the main drugs we mainly use in AD treatment. 

In our second and third cases, we need to make a treatment plan specific for our two patients. We have to select the drugs and doses accordingly. Most of the patients with AD need lifelong steroid therapy. As always, it is vital to consider adverse effects in our treatment plan.

We also have to educate patients about AD. This is an essential part of patient management. Prevention of developing an adrenal crisis is always better than cure. So, we have to educate patients about triggering factors for adrenal crisis. We also have to tell them how they can contribute to manage their disease and what to do in an emergency. 

In all three cases, we have to educate them clearly about their condition. We should try to make them ‘expert patients. ‘ 

Following up AD patients

Once we treat, we cannot forget about AD patients. We have to follow them and monitor their progress. 

Conclusion

AD is a hormone deficiency syndrome that is notoriously variable in its presentation, and in some cases, it can be rapidly deteriorating. Though AD is a rare disease, it can be seen in all age groups. Similar patients presentations should be dealt with high clinical suspicion as early diagnosis and prompt interventions can save lives!

References