Keywords
Adrenal - bilateral - lymphoma - primary
Background
Primary adrenal insufficiency (PAI) is a rare condition. The described prevalence
in Western countries is 39–144 per million individuals.[[1]] The age of onset varies, with a median of 34 years according to a cross-sectional
study.[[2]] The presentation of PAI secondary to infiltration of both the adrenal glands by
cancer is even rarer, and one of the common cancers that may involve the adrenal gland
is lymphoma. We report a case of a 62-year-old woman who presented with symptoms and
signs of PAI secondary to diffuse bilateral non-Hodgkin lymphoma of the adrenal glands.
Case Report
A 63-year-old Saudi female patient with long-standing diabetes mellitus type 2 requiring
insulin and hypertension diagnosed in a primary health-care center presented to Qatif
Central Hospital in the East of Saudi Arabia Emergency Department with a 6-month history
of vague complaints that included fatigue, body ache, poor appetite, weight loss,
and subjective fever and a 3-week history of postural dizziness, asthenia, and frequent
loose bowel motions. The family noticed a gradual decline in insulin requirement with
frequent hypoglycemia in the previous 1–2 months, and they also noticed the darkening
of sun-exposed areas over the face and hands. The patient sought medical help during
her illness and was prescribed antidepressants with no improvement.
Clinically, she looked depressed and dehydrated and showed a postural drop in blood
pressure (110/72 mmHg) in a supine position and 85/60 mmHg in a setting position.
She was noticed to have mucocutaneous hyperpigmentation over the mucosa and palmar
crease [[Figure 1]]. The head-and-neck examination was not relevant, as it showed no organomegaly or
lymphadenopathy in the cervical or axillary areas, and there was no lower limb edema.
The initial assessment focused on ruling out adrenal insufficiency versus sepsis or
hidden malignancy. An extensive workup was performed, and significant findings included
low serum sodium (117), high serum potassium (5.7), normal blood cultures, and normal
renal and liver panels. The morning adrenocorticotropic hormone (ACTH) was high at
190 pmol/L (5–60) with a low morning cortisol of 8.36 nmol/L (6.2–19.4); other hormonal
profiles were not remarkable. A Synacthen test was not available in the center, but
signs and symptoms such as high ACTH and low morning cortisol confirmed PAI. The most
common etiology of Addison's disease is autoimmune destruction of the adrenals, usually
present in younger patients, specifically in female patients; because the patient
lacked other autoimmune diseases, an adrenal computed tomography (CT) was ordered
to exclude a secondary cause of adrenal destruction other than autoimmune disease.
The CT showed diffuse bilateral adrenal enlargement with low attenuation in the noncontrast
study, and the findings were heterogeneous, with a few enlarged abdominal lymph nodes,
suggesting an infiltrative process [[Figure 2]]. A CT-guided trucut biopsy of the right adrenal gland was performed after excluding
pheochromocytoma and revealed nongerminal center (activated) B-cell-like diffuse large
B-cell lymphoma (DLBCL). Immunohistochemical markers showed that CD20 was strongly
positive in neoplastic cells, CD5 was positive in background T-cells, CD10 and BCI-6
were both negative, and MUM1 was strongly positive in neoplastic cells [[Figure 3]] and [[Figure 4]]. The patient was started initially on an intravenous (IV) hydrocortisone stress
dose of 50 mg every 8 h for 24 h and then 25 mg via IV every 8 h for the next 24 h.
She eventually showed a significant clinical improvement in the form of stability
of blood pressure and resolution of hyponatremia and hypoglycemia. The patient had
no more diarrhea and was able to stand and move alone. After the resolution of the
symptoms and stability of the patient's general condition, she was shifted to a maintenance
dose of steroids. She required a higher physiological dose to stay asymptomatic. She
required 20 mg cortisol tablets in the morning and 10 mg cortisol tablets in the evening
with fludrocortisone 0.05 mg OD. She was referred to a tertiary health center for
further staging and was started on active treatment for lymphoma.
Figure 1: Hyperpigmentation of the tongue and oral mucosa
Figure 2: No contrasted adrenal computed tomography showing bilateral adrenal enlargement,
and the areas are hypodense and maintain their overall shape
Figure 3: Histopathology with immunohistochemistry markers H and E stain: Diffuse large B-cell
lymphoma
Figure 4: Histopathology with immunohistochemistry markers, CD20: Strongly positive in the
neoplastic cells
Discussion
PAI secondary to the destruction of the adrenal glands can arise due to multiple etiologies.
The most common etiology is an autoimmune disease, which represents 70%–90% of cases.
When the disease was discovered in 1885, tuberculosis was its most common cause, but
it is now the cause of less than 20% of cases worldwide. Other rare causes of PAI
are adrenal hemorrhage, infarction, other infectious diseases, drugs, or metastatic
cancer or lymphoma.[[3]],[[4]]
Our patient presented with signs and symptoms of PAI, and the etiology in this age
group could be isolated idiopathic or autoimmune.[[5]] In accordance with the Endocrine Society, clinical practice guideline of 2016 for
the diagnosis of PAI, the diagnosis of the underlying cause, should include a validated
assay of autoantibodies against the 21-hydroxylase enzyme, but this was not available
in our center. Other causes of PAI should be sought out.[[6]] Therefore, an adrenal CT scan was requested, and it showed bilateral adrenal enlargement,
which raised the suspicion for nonimmune-mediated PAI, in which the adrenal glands
are expected to be either normal early in the course of the disease or atrophied.
However, bilateral adrenal enlargement could result from granulomatous infectious
causes, such as tuberculosis, histoplasmosis, or blastomycosis, or be due to acute
adrenal hemorrhage and infarction or cancer invasion into the adrenal glands.[[7]] In the literature, lymphoma has been reported to involve the adrenal glands and
to result in PAI in multiple case reports.[[8]] It is a cancer that arises from white blood cells and has been traditionally divided
into two large subtypes: Hodgkin and non-Hodgkin lymphoma. B-cell lymphoma is the
most common subtype of non-Hodgkin lymphoma; almost 85% of patients with lymphoma
have this variant. Lymphomas can potentially arise from any lymphoid tissue located
in the body; however, primary adrenal non-Hodgkin lymphoma is extremely rare,[[8]] representing less than 1% of the cases. The two most common subtypes are DLBCL
(78%) and peripheral T-cell lymphoma (7%) according to the 2008 WHO definitions.[[9]]
Both the adrenal glands may be involved in more than 70% of cases when PAI should
be ruled out. In our patient, CT-guided trucut biopsy confirmed the diagnosis of the
non-Hodgkin lymphoma DLBCL. The disease is rare and rapidly progressive, and aggressive
intervention should not be delayed. Although our patient deteriorated rapidly and
passed away before starting the chemotherapy regimen, the literature shows improved
outcomes with the advent of rituximab-containing chemotherapeutic regimens. A review
of 31 patients from 14 Korean institutions who were treated for adrenal DLBCL with
rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone suggests encouraging
results in which the achievement of complete remission is predictive of survival.[[9]],[[10]]
Conclusion
The involvement of the adrenal glands in lymphoma is rare, and DLBCL is the most common
type of lymphoma. The patient can present with variable symptoms and a wide range
of findings. PAI as the first presentation, as was seen in our patient, is extremely
rare.
Declaration of patient consent
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In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed
