ISSN: 1301-2193 E-ISSN: 1308-9846
  • Turkish Journal of
    Endocrinology and Metabolism

Introduction

Primary adrenal insufficiency (PAI) is an endocrine disease caused by bilateral adrenocortical destruction. It manifests as fatigue, loss of appetite, weight loss, nausea, vomiting, hypotension and hyperpigmentation. Clinical symptoms are observed when more than 80% of both adrenal glands are damaged. In the previous reports in the literature, tuberculosis was the main cause of adrenal insufficiency in 70-90% of cases, but, today, the leading cause of PAI is autoimmunity. However, in developing countries, tuberculosis still continues to be a common cause of PAI.

Case Report

A 71-year-old female patient was admitted to the emergency department of our hospital with the complaints of fatigue, anorexia, nausea, weakness in the legs and inability to walk. Her complaints began in the last 2-3 months and intensified gradually. In her past medical history, 9 years ago she had the diagnosis of right infiltrative adrenal mass measuring 9x4x9 cm  surrounding the inferior vena cava and extending to right retrocaval region which was thought to be non-adenoma in nature. When questioned in detail, it was learned that hormonal tests had been performed, the results had been considered to be nonfunctional, and she had undergone adrenal biopsy. Pathological investigation showed malignant tumoral tissues. Therefore, right adrenalectomy and nephrectomy were performed. Light microscopic examination of the adrenalectomy specimen demonstrated epithelioid histiocytes, lymphocytes, plasmocytes, and granulomas consisting of Langhans-type multinucleate giant cells. Pathological examination report was consistent with granulomatous inflammation. In the pathological examination of the nephrectomy specimen and two lymph nodes, chronic pyelonephritis and granulomatous lymphadenitis were observed, respectively. Chest computed tomography (CT) scans were normal at that time. The patient did not attend follow-up visits after surgery, therefore, further investigations and assessments could not be performed.

On her admission to our emergency department, her axillary body temperature was 36.4 C, pulse rate-102 beats per minute, respiratory rate-24 breaths per minute and blood pressure was 80/60 mmHg. Her physical examination revealed mild hyperpigmentation on oral mucosa, palms and areolae. Laboratory tests showed elevated serum creatinine [1.7 mg/dL; normal range (NR): 0.6-1.3], hyponatremia (122 mmol/L; NR: 136-145) and hyperkalemia (7.8 mmol/dL; NR: 3.5-5.1). Electrocardiogram showed no evidence of hyperkalemia. Emergency dialysis was performed. Hypotension, hyperkalemia, and hyponatremia persisted after dialysis; therefore, the patient was investigated with a presumptive diagnosis of adrenal insufficiency. Adrenocorticotropic hormone and basal cortisol levels were 291 pg/mL (NR: 5-46) and 1.9 µg/dL (NR: 3.7-19.4), respectively. She was diagnosed as having PAI, and methylprednisolone (60 mg/day) was started. The steroid dose was reduced gradually and treatment with prednisone 5 mg/day and fludrocortisone 0.1 mg/day was continued. With glucocorticoid and mineralocorticoid treatment, the complaints of weakness and loss of appetite regressed, serum sodium and potassium levels returned to normal.

On the abdominal CT images, an adrenal mass measuring 78x40 mm was detected in the left adrenal gland (Figure 1). Peripheral, but not central, enhancement was observed after contrast agent administration. It was considered to represent the adrenal gland involvement of tuberculosis. Chest CT scans revealed lots of millimeter-sized nodules in both lungs, more prominent in the upper lobes (Figure 2). It was consistent with miliary tuberculosis. On CT images, no pathologic lymph node was observed. Tuberculin skin test was negative. Bronchoscopy was performed. In both bronchial trees, the mucosa was edematous, fragile, and prone to bleeding, and anthracotic plaques were observed. Bronchoalveolar lavage showed dominant mononuclear cells (80%). It was negative Ziehl-Neelsen stain for acid fast bacilli. Cytological examination was benign and galactomannan test was negative. Serological tests for cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, Salmonella, and Brucella were all negative. Cultures for Mycobacterium and fungus were negative. Ophthalmic examination was normal. There was no sign of active tuberculosis infection in other body sites of the patient.

An anti-tuberculosis treatment including isoniazid (300 mg/day), rifampicin (600 mg/day), ethambutol (1500 mg/day) and pyrazinamide (2000 mg/day) was started. It lasted for one year. During follow-up visits, regression of the nodules was observed in consecutive posteroanterior chest X-rays. On chest CT scans after treatment, nodules were totally disappeared (Figure 3). However, after treatment, the adrenal mass was similar in size and appearance on abdominal CT scans. Left adrenalectomy was performed. In the pathological examination of the specimen, there was a large necrotic area in the center, and mononuclear inflammatory cell infiltration, fibrosis and hyalinization in the peripheral regions of the mass (Figure 4). Besides, polymorphonuclear leukocytes were present around the mononuclear inflammatory cells. These findings were consistent with suppurative process on chronic granulomatous inflammation considering adrenal involvement of tuberculosis. After adrenalectomy the patient started replacement treatment and has been followed up with glucocorticoid and mineralocorticoid treatment since then.

Discussion

Tuberculosis is a disease caused by mycobacteria. Although its frequency decreased especially in developed countries worldwide, it is still a problem in underdeveloped regions of the world. Besides, nowadays, the increasing usage of immunosuppressant agents for different purposes leads to increased frequency of infections including tuberculosis. In immunocompromised patients, atypical organ involvements of tuberculosis are seen (1).

Adrenal tuberculosis is a result of hematogenous spread of systemic tuberculosis. Involvement of the adrenal gland is observed in 5-6% of cases with active disseminated tuberculosis (1,2,3). Adrenal insufficiency is a late finding of tuberculosis, and it is observed 10 to 15 years later after the onset of tuberculosis infection in the majority of cases (4). In adrenal tuberculosis, enlargement of adrenal gland and signs of extra-adrenal tuberculosis often exist (5). However, extra-adrenal tuberculosis can be clinically silent and active extra-adrenal tuberculosis cannot be diagnosed in approximately 12% of patients (2,3,6,7). In our case, at the time of detection of the first adrenal mass, there was no clinical manifestation of adrenal insufficiency because of the fact that contralateral adrenal gland was functioning. After surgery, the patient did not attend follow-up visits; therefore, further investigation for the detection of the primary focus of tuberculosis could not be performed. Due to the involvement of the remaining adrenal gland, the patient was admitted with the symptoms of acute adrenal insufficiency nine years after unilateral adrenalectomy.

Abdominal CT has a high sensitivity and specificity for distinguishing tuberculosis from other tumors of the adrenal gland (7,8). However, it provides guidance in determining the etiology of PAI. The adrenal glands are usually atrophic in autoimmune disorders while enlargement of the adrenal glands may be observed in especially early stages of adrenal tuberculosis. Atrophy of the glands may be observed in late stages. CT provides information about beginning of the adrenal gland involvement and it is important in deciding which regimen to start.

Calcification is a common finding in adrenal glands. However, enlargement of the adrenal glands can be seen without calcification in especially acute adrenal tuberculosis. Enlargement may be unilateral or bilateral (9).

In our patient, calcification was not detected on abdominal CT scans, but the staining pattern of the adrenal mass was consistent with the involvement of tuberculosis.

The effect of anti-tuberculosis treatment on improvement of adrenal function is controversial.

Although total functional improvement is rarely observed with anti-tuberculosis treatment, general consensus is that treatment cannot provide remission of the adrenal gland functions (4,8,9,10). Though nodules in the lungs disappeared with anti-tuberculosis treatment in our patient the adrenal mass did not get smaller. Therefore, adrenalectomy was performed.

In conclusion, adrenal tuberculosis may present with adrenal masses causing symptoms of adrenal insufficiency. Adrenal involvement of tuberculosis is one of the reasons for adrenal insufficiency. It is usually bilateral, but may also be unilateral. It should be kept in mind that adrenal insufficiency may not be observed in case of unilateral involvement. Extra-adrenal tuberculosis is usually clinically silent, thus, further investigations should be carried out to find the primary focus.

In cases with extra-adrenal primary focus, signs and symptoms of adrenal insufficiency should be questioned and if suspicious, further investigations of the adrenal glands should be carried out. If early diagnosis of adrenal involvement is achieved and anti-tuberculosis treatment is started in the early stage of the disease, complete or partial remission of adrenal gland functions may be provided. However, early diagnosis and treatment cannot be achieved in majority of cases.

Ethics

Informed Consent: Consent form was filled out by all participants.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: Pınar Şişman, Canan Ersoy, Concept: Pınar Şişman, Canan Ersoy, Design: Pınar Şişman, Hande Peynirci, Data Collection or Processing: Pınar Şişman, Ahmet Bilgehan Şahin, Analysis or Interpretation: Pınar Şişman, Özlem Saraydaroğlu, Literature Search: Pınar Şişman, Özen Öz Gül, Writing: Pınar Şişman.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

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