Sir,
A 38-year-old woman without previous medical history initially presented menstrual abnormality for 2 months. Later on, elated mood increased goal-direct behavior, decreased need for sleep, grandiose delusion, poor concentration, hypertalkativeness, and psychomotor agitation were followed, which required urgent hospitalization. In addition, physical examination showed hirsutism, buffalo hump, peripheral edema, and acne. Laboratory tests revealed hypokalemia, metabolic alkalosis, elevated serum levels of testosterone, and elevated serum and urine levels of cortisol. Low- and high-dose of dexamethasone suppression test demonstrated the result of nonsuppression of adrenocorticotropic hormone level. Pituitary magnetic resonance imaging revealed no obvious pituitary tumor. Whole body positron emission tomography (PET) scan revealed fluorodeoxyglucose-avid pulmonary nodule at the right lung base. Resection of the tumor was carried out. Pathology demonstrated atypical carcinoid tumor. Hypokalemia and excess cortisol improved gradually after the operation. No residual tumor was found by PET-computed tomography scan. The patient no longer needed mood-stabilizer or antipsychotics after the operation. Bipolar disorder due to another medical condition: lung atypical carcinoid tumor-induced ectopic Cushing's syndrome was diagnosed according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. She remained symptoms free at 12- and 36-month follow-up.
Lung atypical carcinoid tumor-induced Cushing's syndrome is a rare and complex condition and being a diagnostic challenge for clinicians. Excessive cortisol released by ectopic Cushing's disease impaired hypothalamic–pituitary–adrenal (HPA) axis, which may subsequently deteriorated cognitive function and increased risks for mood disorders. Excessive glucocorticoid exposure had a mood-changing effect, with depression being the most common presentation.[1] However, high levels of glucocorticoids did not always have a depressogenic effect. Bipolar disorder, including manic and hypomanic episodes, had been reported in Cushing's syndrome.[2]
Bronchopulmonary carcinoids were considered being the most prevalent causes of ectopic Cushing's syndrome, which were separated into low-grade malignancy typical carcinoids and moderate-grade malignancy atypical carcinoids depending on the degree of mitotic activity and necrosis.[3] Compared to typical carcinoids, atypical carcinoids are extremely rare and are associated with unfavorable clinical outcomes.
Definite mechanism of bipolar disorder remained unknown, while hypercortisolemia may played important roles. Cortisol could modulate the activity of neural structures on glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs).[4] Bipolar disorder is associated with abnormal GR signaling in the dorsolateral prefrontal cortex (DLPFC) and reduced transcription of the MR gene in the DLPFC and orbitofrontal cortex. These abnormalities might be the consequence of chronic exposure to high levels of cortisol and can also constitute the basis of abnormal neural responses to glucocorticoids. Evidence suggested that bipolar disorder is characterized by a disruption of the reciprocal interactions between the HPA axis and the central nervous system.
In conclusion, some clinical characteristics pointed to the possibility of organic psychiatric disorder. For example, unusual onset age of bipolar disorder without family psychiatry history with hypokalemia and metabolic alkalosis were all important clues implying underlying organic etiologies. Early diagnosis and prompt initiation of treatment in the disease process may lead to better outcome and avoid unnecessary psychotropic agents as well as medication-related adverse effects.
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Conflicts of interest
There are no conflicts of interest.
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