American Journal of
Case Reports
| Received: | 2022.05.19 |
| Accepted: | 2022.06.30 |
| Available online: | 2022.07.27 |
| Published: | 2022.08.29 |
An Unusual Presentation of Adrenocortical Carcinoma (ACC): Panic Attacks and Psychosis
Authors’ Contribution:
Study Design A
Data Collection B
Statistical Analysis C Data Interpretation D
Manuscript Preparation E Literature Search F Funds Collection G
ABDEFG Yassine Kilani İD
EFG Aye Myat Mon
BEG Trisha Laxamana
BEG Syeda Ashna Fatima Kamal
BEG Rahul Zain
EFG Haris Sohail İD
EG Mubarak H. Yusuf İD
EG Julia Vargas-Jerez
EG Tasneem Zahra
Corresponding Author:
Yassine Kilani, e-mail: yassinekilanimd@gmail.com, kilaniy@nychhc.org
Financial support:
None declared
Conflict of interest: None declared
Patient:
Female, 52-year-old Adrenocortical carcinoma
Final Diagnosis:
Symptoms: Flushing . hot flashes . panic attack . psychosis
Medication:
—
Clinical Procedure:
—
Specialty:
Endocrinology and Metabolic
Objective: Background:
Unusual clinical course
Adrenocortical carcinoma (ACC) is a very rare disease, with an incidence of 1.02 per million population per year. The most commonly secreted hormone in ACC is cortisol, often presenting as a rapidly progressive Cushing syn- drome (CS). We describe a case of ACC with an unusual presentation, mainly with psychiatric manifestations, including panic attacks and hallucinations.
Case Report: A 52-year-old woman presented with episodes of acute anxiety, hallucinations, palpitations, hot flashes, gas- trointestinal upset associated with paroxysmal hypertension, tachycardia, and flushing for 1 week. The initial workup was aimed at ruling out causes of acute psychosis and/or anxiety such as substance use, and organ- ic diseases such as pheochromocytoma (PCC). Our initial suspicion of PCC was ruled out based on the nega- tive serum and urinary metanephrines (MN) and normetanephrines (NMN). Recurrent metabolic alkalosis and hypokalemia despite fluid and potassium supplementation prompted us to work up for hyperaldosteronism. Her renin level was elevated and the aldosterone level was appropriately suppressed. Elevated cortisol, posi- tive dexamethasone (DXM) suppression test, low adrenocorticotropic hormone (ACTH), imaging revealing an adrenal mass, and postoperative histology confirmed the diagnosis of cortisol-producing ACC. Conclusions: It is essential to recognize psychiatric presentations of CS to achieve early diagnosis and prevent mortality and morbidity. Panic attacks, a common presentation of CS, can present with features mimicking pheochromocyto- ma (PCC), including palpitations, sweating, tachycardia, and paroxysmal hypertension. A comprehensive work- up is warranted to reach a diagnosis, with a combination of hormonal levels, imaging, and histology.
Keywords: Adrenocortical Carcinoma . Cushing Syndrome . Panic Disorder . Pheochromocytoma
Full-text PDF: https://www.amjcaserep.com/abstract/index/idArt/937298
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Department of Internal Medicine, Lincoln Medical Center, Bronx, NY, USA
Background
Adrenocortical carcinoma (ACC) is a very rare disease, with an incidence of 1.02 per million population per year in a popu- lation-based study in the United States [1]. Up to 60% of pa- tients with ACC present with symptoms of adrenal steroid hor- mone excess [2]. The most commonly secreted hormone in ACC is cortisol, often presenting as a rapidly progressive Cushing syndrome [3,4]. We describe a case of ACC with an unusual clinical presentation, mainly with psychiatric manifestations, including panic attacks and hallucinations, associated with paroxysmal hypertension, tachycardia, flush, and hot flashes.
Case Report
History of Present Illness
Our patient was a 52-year-old woman who was brought in by Emergency Medical Services, accompanied by her sister due to acute episodes of anxiety and aggressive and bizarre behav- ior at home that started during the previous week. These ep- isodes were accompanied by increased sweating, hot flashes, flushing, palpitations, and gastrointestinal upset, without any identifiable precipitating factor. She denied any prior similar episode in the past. She endorsed a 9-kg weight loss over the last 3-4 months. She denied headaches, visual changes, loss of consciousness, tremors, weakness, chest pain, shortness of breath, diarrhea, easy bruising, striae, arthralgia, and myalgia.
Past Medical History
Her past medical history was significant for recently diagnosed hypertension (weeks prior) and diabetes mellitus (DM) (months prior). She and her sister denied any personal or family history of psychiatric disorders (including mood disorders, psychotic disorder, substance use disorders, psychiatric hospitalizations, and suicide attempts). She had a surgical history of total ab- dominal hysterectomy and cholecystectomy years prior. Her family history included a father with diabetes mellitus, and re- nal cancer in another sister (now deceased). Her medications included lisinopril, metformin, and glimepiride. Glimepiride was switched to ertugliflozin following an episode of hypo- glycemia. She denied alcohol use, smoking, or illicit drug use.
Physical Examination
Initial physical examination showed a temperature 37.2℃, a blood pressure of 135/86 mmHg, a heart rate of 115/min, a re- spiratory rate of 18/min, and oxygen saturation of 98% on room air. Body mass index (BMI) was 22.17 kg/m2. The patient was alert and oriented to time, place, and person. She was anxious, tearful, and appeared to have intermittent visual hallucinations
along with persecutory and psychotic delusions. Skin inspec- tion revealed flushing of the face and the chest, without any visible lesions. The chest was clear on auscultation bilateral- ly, with normal heart sounds, a soft abdomen with mild epi- gastric tenderness, and no edema. She was placed on contin- uous telemetry for monitoring of her vital signs.
Laboratory Workup
An ECG showed sinus tachycardia (115 beats/min), with pos- sible right atrial enlargement (RAE), and left ventricular hyper- trophy (LVH) with repolarization changes (Figure 1). A com- prehensive urine drug screen panel was negative. Laboratory findings are summarized in Table 1. Our differential diagno- ses for leukocytosis, lymphopenia, and neutropenia includ- ed infection, autoimmune disease, Human Immunodeficiency Virus (HIV) infection, and hypercortisolism. Urinalysis was pos- itive (positive leukocyte esterase, nitrites, leukocyturia, bacte- riuria), so a urine culture was performed. Antinuclear antibodies (ANA) and anti-double stranded DNA (DsDNA) were negative and ruled out systemic lupus erythematosus. Hypokalemia and metabolic alkalosis prompted us to screen for causes of hyperaldosteronism. Further laboratory workup ruled out pri- mary/secondary hyperaldosteronism and pheochromocytoma (Table 1). The diagnosis of CS was made based on elevated 24-h free urinary cortisol, elevated serum AM Cortisol at 37.9 mcg/dL, and positive dexamethasone (DXM) suppression test (inappropriate suppression of morning serum cortisol after 1 mg DXM administration: 30 ug/dL). ACTH level was low, indi- cating a peripheral cause of CS.
Imaging
A computed tomography (CT) scan of the head without con- trast was unremarkable, with the exception of mild diffuse ce- rebral atrophy. A CT of the abdomen and pelvis showed a right adrenal heterogeneous mass with calcifications (Figure 2). Differential diagnoses for this mass included adrenal carcino- ma, pheochromocytoma, or, less likely, lipid poor adenoma. CT of the chest with contrast revealed a 4-mm semisolid left lower lung lobe nodule and an 8-mm ground-glass nodule in the right upper lobe.
Treatment and Follow-Up
Prior to the diagnosis, the patient was medically managed with intravenous (i.v.) fluids and electrolytes repletion, trime- thoprim-sulfamethoxazole (TMP-SMX) for urinary tract infec- tion, amlodipine and lisinopril for hypertension, labetalol for tachycardia, insulin for DM, and antipsychotics. After the di- agnosis of ACC was suspected based on the imaging and the hormonal panel, she was medically cleared for surgery and un- derwent a right adrenal tumor resection.
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To prevent postoperative adrenal insufficiency, the patient re- ceived an initial dose of i.v. hydrocortisone (HC) 50 mg every 4 h on the surgery day, which was tapered down on postop- erative days 1, 2, and 3 to 50 mg every 6, 8, and 12 h, respec- tively. On day 4, she received oral HC 50 mg at 8 AM, and 25 mg at 4 PM. She was discharged on the same day, and con- tinued on oral HC 25 mg twice daily and potassium supple- mentation. The postoperative course was uncomplicated, with resolution of the psychiatric and cardiovascular symptoms. She was alert, calm, and oriented, with a normal blood pres- sure of 105/65 mmHg and heart rate of 74/min at follow-up.
Histology results available after 8 days were consistent with low-grade ACC with a free tumor margin. Tumor cells were pos- itive for SF-1, Melan-A, and Inhibin and negative for INSM1 and chromogranin. A PET-CT scan showed no evidence of lymph node or bone metastasis, and revealed a mildly hypermetabol- ic pulmonary nodule and a right upper lobe ground-glass nod- ule without FDG uptake, both possibly neoplastic. She contin- ues to follow up with Endocrinology, Cardiology, and Oncology. Further germline testing of the tumor is pending.
Discussion
Adrenocortical carcinoma (ACC) is a very rare disease, with an incidence ranging from 0.72 to 2 per million population per
year [1,4-6]. Most cases are sporadic, while some are inherit- ed due to genetic mutations (MEN-1, Li-Fraumeni, Beckwith- Wiedemann syndrome, Lynch syndrome) [7].
Most ACCs are functional, and present with symptoms of ste- roid hormone excess [2]. The most commonly secreted hor- mone is cortisol, resulting in Cushing syndrome (CS). In patients with ACC, the clinical symptoms tend to develop rapidly, usu- ally over 3-6 months [4]. Diagnosing CS can be difficult due to its wide range of manifestations, including dermatologic (acne, facial plethora/flushing, thin skin, easy bruising, purple striae over the abdomen, and hirsutism), musculo-skeletal (proximal muscle weakness and atrophy, and osteoporosis), psychiatric (psychosis, panic disorder, depression, and irritability), immu- nological (susceptibility to infection, neutrophilia, and eosino- penia), and metabolic or endocrine (weight gain, fat redistribu- tion with buffalo hump and moon face, hypertension, glucose intolerance, dyslipidemia, electrolyte imbalances, amenorrhea in women, and decreased libido in both genders) [8].
Our patient had a recent history of hypertension, diabetes melli- tus, and weight loss within months prior to admission. The usu- al weight gain seen in patients with CS is commonly replaced by weight loss in ACC [9]. She presented with acute onset and recurrent episodes of psychosis, panic attacks, paroxysmal hy- pertension, tachycardia, flushing, and sweating. After ruling out substance use, differential diagnoses included panic disorder
| Results (reference range) | |
|---|---|
| Complete blood count | Hemoglobin 15.0 (12.0-16.0 g/dL) Platelets 333 (150-450×103/mcL) White blood cells 11.71(4.80-10.80×103/mcL) Neutrophils 80.7 (44.0-70.0%) Lymphocytes 12.0 (20.0-45.0%) Monocytes 6.1 (2.0-10.0%) Eosinophils 0.0 (1.0-4.0%) Basophils 0.3 (0.2-1.8%) |
| Basic metabolic panel | Sodium 147 mmol/L (136-145 mmol/L) Potassium 2.7 mmol/L (3.5-5.1 mmol/L) Chloride 99 mmol/L (98-107 mmol/L) Calcium 10.4 mg/dL (8.4-10.5 mg/dL) Bicarbonates 33 mmol/L (22-29 mmol/L) Glucose 260 mg/dL (74-109 mg/dL) BUN 17.0 mg/dL (6.0-23.0 mg/dL) Creatinine 0.59 mg/dL (0.50-0.90 mg/dL) |
| Urine electrolytes (random) | Sodium 47 mmol/L Potassium 25 mmol/L (20 mmol/L) Chloride 35 mmol/L |
| Diabetes mellitus testing | HbA1c 8.1 (4.0-5.6%) |
| Thyroid function tests | TSH 1.41 (0.27-4.20 uIU/mL) |
| Adrenal function tests | Serum aldosterone <3.0 (<23.2 ng/dl) |
| Renin activity 3.651 (0.167-5.380 ng/ml/hr) Serum Normetanephrine 48.8 (0.0-244 pg/mL) Serum metanephrine 27.6 (0.0-88.0 pg/mL) 24-hour urinary metanephrine 112 (36-209 mcg/24h) 24-hour urinary normetanephrine 362 (131-612 mcg/24h) 24-hour urinary cortisol 735 (3.5-45 mcg/24h) Morning serum cortisol 37.9 mcg/dL (6.0-18.4 mcg/dL) Morning serum cortisol after 1mg DXM: 30 mcg/dL (6.0-18.4 mcg/dL) ACTH < 1.5 ug/dL (7.2-63.3 mcg/dL) | |
| Neuroendocrine tumor screen | Chromogranin A level 85.8 (0.0-101.8 ng/ml) |
(PD) and PCC. A full laboratory evaluation was warranted to exclude PCC. The diagnosis of PCC is based on the serum and urine metanephrines, and imaging of the adrenal glands [10].
During our literature review, we tried to identify cases of CS that presented with paroxysms of hyperadrenergic symptoms. Reports of adrenal tumors combining features of CS and PCC are available, the most common being ACTH producing PCC, which is a rare cause of ectopic ACTH syndromes (3%) [11], and numerous cases have been reported [12-16]. However, such cases have elevated serum/urinary metanephrines, normeta- nephrines, and elevated serum ACTH levels, which was not the case in our patient; therefore, PCC was ruled out, and the patient was diagnosed with CS secondary to ACC. The most likely differential diagnosis for the clinical presentation in
this patient with CS was panic attacks. Indeed, panic disor- der is one of the most common psychiatric manifestations of CS (53%) [17]. It is characterized by the presence of recurrent episodes of panic attacks, defined by an abrupt surge of in- tense fear of losing control, “going crazy”, or dying, associat- ed with 4 or more symptoms or physical signs, which include sweating, shaking, chills or heat sensations, dizziness, light- headedness, palpitations, tachycardia, chest pain or discomfort, shortness of breath, feeling of choking, nausea or abdominal distress, chills or heat sensations, paresthesias, and derealiza- tion or depersonalization. As it is the case in our patient, pan- ic attacks can occur as often as several times a day, and with- out prodromes [18]. Other reported psychiatric manifestations in CS include depression (55-81%), anxiety (12%), mania or hypomania (3-27%), psychosis (8%), and confusion (1%) [17].
100 mm
100 mm
Similar to our case, there are a few reports of CS presenting with acute psychosis in the literature [19,20].
Conclusions
Adrenal tumors can have overlapping symptoms. It is essen- tial to recognize psychiatric presentations of cortisol-produc- ing ACC to achieve early diagnosis and prevent mortality and morbidity. A full diagnostic workup is warranted to rule out dif- ferential diagnoses for adrenal masses, with a combination of
hormonal levels, imaging, and histology. ACC is a very aggres- sive malignancy and the overall prognosis is poor. However, some studies have shown improved survival in patients with early diagnosis and curative resections.
Declaration of Figures’ Authenticity
All figures submitted have been created by the authors who confirm that the images are original with no duplication and have not been previously published in whole or in part.
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