ACTH: Adrenocorticotropic hormone

APW: Absolute percentage washout

CECT: Contrast-enhanced computed tomography

CT: Computed tomography

DCT: Delayed contrast enhanced CT

DEXA: Dual energy X-ray absorptiometry

HU: Hounsfield Unit

MDCT: Multi-detector computed tomography

MRI: Magnetic resonance imaging

RDW: Red cell distribution width

RPW: Relative percentage washout

USG: Ultrasonography

Adrenal tumors are common in humans, occurring in 9% of autopsy series. The prevalence of adrenal adenoma is reported to be age-related; the frequency of undiagnosed adenoma is 0.14 percent in patients aged 20–29 years and 7% in those older than 70 years. ¹ Primary adrenal tumors can be hyper-functioning, producing excess hormones and resulting in clinical symptoms, or non-functioning which is more common. However, 10-15% of patients with adrenal adenoma might exhibit clinical features of Cushing's syndrome. ² In the evaluation of adrenal tumors, abdominal ultrasound has a reported sensitivity of 96% for tumors smaller than 2 cm and 100% for tumors larger than 2 cm. Multi-detector computed tomography (MDCT) is the single most useful modality for identification and characterization. Magnetic resonance imaging (MRI) and functional imaging modalities such as nuclear scintigraphy are useful for a thorough evaluation when in doubt. ³ Computed tomography (CT) imaging can detect adrenal masses with diameters greater than 5 mm. Adrenal adenomas with typical imaging characteristics account for a vast majority of these benign adrenal masses. However, distinguishing between atypical adrenal adenomas and adrenal malignant lesions is critical, because a small percentage of these are potentially malignant lesions. ⁴ Furthermore, because imaging cannot reliably distinguish between functioning and non-functioning adenomas, the biochemical profile must be used. To identify abnormal adrenal function in an adenoma, NP-59 scintigraphy can supplement biochemical and radiological imaging results. ³ This case report highlights atypical findings in a functioning adrenal adenoma as well as possible differential diagnoses that could lead to a misdiagnosis.

We report a 16-year-old South Asian female who presented at the out-patient service of the Endocrinology department of Bir Hospital, Kathmandu with a chief complaint of increased weight for two years, primary amenorrhea and lethargy. The patient had not sought any prior medical attention or undergone any intervention in the past. She did not have any history of similar illness or genetic conditions in her family. Vitals taken showed blood pressure to be 180/130 mm Hg, pulse rate of 78 beats/minute, respiratory rate of 18 breaths/minute and temperature to be 98°F (36.7°C).

A thorough physical examination was performed: the patient had a moon-shaped face with facial hair, supra-clavicular hump, deepening of voice and purple abdominal striae were noted ( Figure 1). However, axillary and pubic hair was present and breast development was normal (Tanner stage 5). A suspicion of Cushing's syndrome was made and further investigations were sent ( Table 1). In addition, a bone densitometry scan was performed by dual energy X-ray absorptiometry (DEXA) showing a Z score of -2.8 in the spine along with a Z score of -0.8 and -1.5 in the right and left femur neck, respectively.

Adrenal tumors that are incidentally found on imaging are known as adrenal incidentalomas, which comprises benign adrenal masses to metastatic tumors. They are found during imaging of areas other than adrenal gland. The prevalence of adrenal incidentalomas is between 0.35% to 1.9% on CT scan. Among them, around 54 percent are found to be adrenal adenomas. ⁵ However, our case was imaged for the proven diagnosis of Cushing's syndrome. In the case of Cushing's syndrome in adults, only 20% of the cases are due to adrenal causes; however, in the first decade of life adrenal causes predominate majority of cases. Among the cases of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome, it was found that 95% of cases were due to adrenal adenomas or carcinomas, among which 65% consisted of hyper-functioning adrenal adenoma, similar to our case, while primary pigmented nodular adrenal dysplasia and ACTH-independent macronodular hyperplasia accounts for the rest of the cases. ⁶ On imaging, adrenal adenomas are usually well-defined ovoid to round nodules measuring 1-5 cm, with homogenous or slight heterogenous attenuation. Imaging cannot differentiate between functional and non-functional adenomas: this needs adrenal venous sampling. ⁷

An ultrasonography imaging was performed, which found a homogenous and hypoechoic lesion, consistent with the ultrasound imaging criteria for adrenal adenoma. However, in our case we also noted a tiny hyperechoic focus, which was likely a calcification within the mass. The size of the mass on USG was 4.8 cm and comparable to the range of 1.0-6.3 cm seen in an ultrasound study by Fan et al. in China. ⁸

Since MDCT is the imaging of choice in adrenal adenoma, an MDCT was performed and showed well-defined soft tissue density; density evaluation is highly sensitive and specific, as 70% of the cases consist of high lipid density in which <10HU is considered 71% sensitive and 98% specific. However, our case showed a HU of +41 and an adrenal CT washout was performed, showing an absolute percentage washout (APW) and relative percentage washout (RPW) of >60% and >40% respectively, highly suggestive of adenoma. ⁹ Moreover, it was also seen that RPW was more accurate than APW and a 15-minute delayed contrast enhanced CT (DCT) was more accurate than a 10-minute DCT for the diagnosis of adrenal adenoma. Compared to other modalities, washout CT provides the highest accuracy for characterization of adenoma. ¹ In our case, we calculated RPW and a 15-minute DCT practicing evidence-based medicine at our center. Contrary to the typical findings of adrenal adenoma, this case featured atypical findings which might hinder the accurate identification of the case. Adrenal adenomas with calcifications have been reported in about 14% of cases. This necessitates its differentiation from various other etiologies like adrenocortical carcinomas, myelolipomas and metastases. It was found that calcified adrenal adenomas represent 15% of calcified adrenal masses second only to adrenal cyst. ⁴

In our patient, bone densitometry scan showed a lowered Z score. The skeletal system's structural and functional impairment is a significant cause of morbidity and disability in Cushing’s syndrome patients, particularly given the high prevalence of vertebral fractures. Glucocorticoids reduce bone collagenous matrix synthesis while increasing its degradation. The reduction in osteoblast number and function appears to be central to the bone loss caused by glucocorticoid excess. Glucocorticoid-induced osteoporosis is reversible, but the recovery of bone loss is slow and takes about ten years. Fractures are common in patients with Cushing’s syndrome who have severe osteoporosis. ¹⁰

Adrenal adenomas can present with features of hormonal excess (functioning adenoma). Diagnosis of adrenal adenoma needs a multidisciplinary approach of clinical, biochemical and imaging studies. Cushing's syndrome is one of the presenting clinical feature in functioning adrenal adenoma. Adrenal adenoma presents a diagnostic puzzle when presented with atypical imaging findings in CT. It is essential to have the knowledge of atypical findings and follow an adrenal protocol when dealing with adrenal adenomas to prevent a misdiagnosis.

All data underlying the results are available as part of the article and no additional source data are required.

Written informed consent for publication of their clinical details and clinical images was obtained from the patient.