Addison's disease is a long-term endocrine disorder in which the adrenal glands do not produce enough steroid hormones. Thus this disease is characterized by hypocortisolism (adrenal glucocorticoid or mineralocorticoid insufficiency).

At first discovered, the primary etiology of Addison's disease was tuberculosis infection. Tuberculosis was the main etiology of Addison's Disease (70%) in the 1930s. However, as Tuberculosis treatment and prophylaxis progressed, the reported cases of Tuberculosis-Addison's Disease decreased to 31% in the 1960s in England, 17% in the 1970s in Denmark, 3% in Italy recently. 

Currently, the main cause of Addison's disease in Europe is an autoimmune disease, with a percentage of 75–96% of cases, and Addison's disease due to tuberculosis is only about 10–15% of cases. This data contrasts with developing countries, where tuberculosis is still the main cause of Addison's disease.


How does TB cause Addison's disease?

Tuberculosis is the type of infection that most commonly causes Addison's disease. Adrenal insufficiency can be caused by TB infecting the adrenal glands or by side effects of antituberculosis drugs.

Mycobacterium tuberculosis bacteria spread to the adrenal glands via hematogenous or lymphatic routes, so most cases involve bilateral adrenal glands. Dissemination of these bacteria can occur during primary lung infection or reinfection or reactivation of the infection later. Generally, the infection spread is due to the diagnosis and late initiation of antituberculosis drugs or drug-resistant tuberculosis.

Nomura's study showed that 93% of patients with adrenal tuberculosis had a history of extra-adrenal tuberculosis, with pulmonary tuberculosis as the most common type. The appearance of Addison's disease manifestations preceded by nonadrenal tuberculosis has a mean interval of 31 years. In most cases, Addison's disease manifestations appear when tuberculosis is already inactive.

Adrenal insufficiency symptoms usually appear when adrenal tissue damage has occurred in more than 90%. Tuberculosis causes inflammation, necrosis, and destruction of bilateral cortical adrenal tissue.  Thereby, it makes decreased glucocorticoids' and mineralocorticoids' production. Clinical manifestations that can appear are:
  • fatigue, 
  • weight loss, 
  • fever, 
  • skin hyperpigmentation, 
  • hypotension, 
  • hyponatremia, 
  • hyperkalemia, 
  • and hypoglycemia.

Management of Addison's Disease due to Tuberculosis

a. How to treat Addison's Disease due to tuberculosis

Tuberculosis treatment is not always given when there is adrenal atrophy because most of TB-AD's cause is no longer active tuberculosis. However, if there is an enlarged adrenal gland, antituberculosis drug therapy is recommended. Several studies have shown that Tuberculosis treatment can restore adrenal function, but several other studies have also reported that antituberculosis drugs do not improve adrenal function.

Tuberculosis-Addison's Disease Treatment is a challenge because rifampicin has a strong effect on improving cytochrome P450. Cytochrome P450 acts to metabolize steroids in the liver. The interaction between steroids as a therapy for Addison's disease with rifampicin as a therapy for tuberculosis can reduce plasma steroid levels.

In some cases, due to low plasma steroid levels, rifampicin can cause an adrenal crisis. Therefore, the steroid dose is adjusted and increased if the patient is also receiving rifampicin. However, there is no specific standard regarding the number of doses that must be increased until now.

b. How to Prevent Adrenal Insufficiency

The steroid doses should also be adjusted if the patient is experiencing conditions requiring higher cortisol levels (stressful circumstances), such as fever, trauma, surgery, and critical conditions such as shock, myocardial infarction, and others. The steroid dose was also adjusted when administering rifampicin.

Perform an increasing dosage to prevent adrenal crises due to the conditions mentioned above. Adrenal crisis is a serious condition characterized by hypotension, hyponatremia, hyperkalemia, and hypoglycemia.


In developing countries, the common cause of Addison's disease is tuberculosis. Diagnosis of Addison's disease due to tuberculosis should be considered when dealing with a patient with clinical manifestations of adrenal insufficiency who has a tuberculosis history.

Treatment with antituberculosis drugs is not always necessary because inactive tuberculosis causes most TB-AD cases. However, if there is an enlarged adrenal gland, then antituberculosis drug therapy is recommended. If the patient has persistent adrenal cortex damage, long-term steroid therapy may be required. However, if steroids are given together with rifampicin, then the steroid dose needs to be increased because rifampicin can lower plasma steroid levels.


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