Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

A severe COVID-19 case with schizophrenia as well as other chronic diseases

The prognosis of COVID-19 (coronavirus disease 2019) is usually poor when it occurs in aged adults or in patients with chronic diseases, which brought a great challenge to clinical practice. Furthermore, widespread depression, anxiety, and panic related to SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) infection affected treatment compliance and recovery. Here we report the successful treatment of a 57-year-old male with severe COVID-19, schizophrenia, hypertension, and type 2 diabetes. The patient's negative emotions (such as tension, panic, and anxiety), particularly his aggression and paranoia, seriously hindered treatment, leading to a deteriorating condition. Psychological counseling and supportive psychotherapy were given but the effect was weak. To improve adherence, risperidone and quetiapine fumarate were replaced by olanzapine for anti-schizophrenic treatment to reduce insomnia and anxiety side effects, associated with sedative-hypnotic drugs as well as psychological counseling. The treatment compliance of the patient improved significantly. The patient's serum alanine aminotransferase increased abnormally in the late stage of hospitalization, suggesting potential liver damage after complex medication strategies. We also monitored the changes of lymphocyte subsets and retrospectively analyzed the virus-specific antibody response. The results suggested that dynamic monitoring of lymphocyte subsets and virus-specific antibody response could facilitate disease progression evaluation and timely treatment plan adjustments. An effective psychotropic drug intervention associated with psychological counselling and psychotherapy are essential for the successful adherence, treatment, and rehabilitation of psychiatric disorders in COVID-19 patients.