A Young Man Suspicious for Cushing's Syndrome With Coronavirus Disease-19 (COVID-19): A Case Report

The 2019 global Coronavirus syndrome pandemic (COVID-19) has entered more than two hundred countries around the world, involving <82 million persons and >1,800,000 deaths (until January, 1st 2021). We report on COVID-19 infection in the context of a Cushing's syndrome (CS) from Iran. A 36-year-old man with proximal myopathy, plethora, and striae with central obesity was evaluated for Cushing's syndrome. During the high dose dexamethasone test, the patient developed symptoms of cough, low-grade fever, and weakness then was admitted to the ICU with a diagnosis of COVID-19. Despite treatment according to national protocols for COVID-19, the patient unfortunately died. In this report, we intend to discuss the various aspects of Cushing's syndrome and severe COVID-19 infection.

Estrogen-secreting adrenocortical tumor in a postmenopausal woman: a challenging diagnosis

Summary Adrenocortical carcinoma (ACC) is a malignant disorder with rapid evolution and severe prognosis in adults and most produce cortisol and androgen. Estrogen-secreting adrenocortical carcinomas are extremely rare, especially in women, tend to be larger and have worse prognosis compared with other types of ACCs. We report the case of a 58-year-old woman who presented with bilateral breast enlargement and postmenopausal genital bleeding. She presented high estradiol (818 pg/mL – 25 times above upper normal limit for postmenopausal women) and testosterone (158 ng/dL – 2 times above upper normal limit) levels and no suppression of cortisol after overnight 1 mg dexamethasone test (12.5 µg/dL; normal reference value: < 1.8 µg/dL). The patient had no clinical features of cortisol excess. MRI showed a 12 cm tumor in the right adrenal. Clinical findings of bilateral breast enlargement and postmenopausal genital bleeding with no signs of hypercortisolism associated with hormonal findings of elevated estradiol and testosterone levels would indicate either an ovarian etiology or an adrenal etiology; however, in the context of plasma cortisol levels non-suppressive after dexamethasone test and the confirmation of an adrenal tumor by MRI, the diagnosis of an adrenal tumor with mixed hormonal secretion was made. The patient underwent an open right adrenalectomy and pathological examination revealed an ACC with a Weiss’ score of 6. Estradiol and testosterone levels decreased to normal range soon after surgery. She was put on mitotane treatment as adjuvant therapy, but due to side effects, we were unable to up-titrate the dose and she never achieved serum mitotane dosage above the desired 14 µg/mL. The patient remained in good health without any local recurrence or metastasis until 5 years after surgery, when increased levels of estradiol (81 pg/mL – 2.5 times above upper normal limit) and testosterone (170 ng/dL – 2.1 times above upper normal limit) were detected. MRI revealed a retroperitoneal nodule measuring 1.8 × 1.2 cm. The pathological finding confirmed the recurrence of the estrogen-secreting ACC with a Weiss’ score of 6. After the second procedure, patient achieved normal estrogen and androgen serum levels and since then she has been followed for 3 years. The overall survival was 8 years after the diagnosis. In conclusion, although extremely rare, a diagnosis of an estrogen-secreting ACC should be considered as an etiology in postmenopausal women presenting with bilateral breast enlargement, genital bleeding and increased pure or prevailing estrogen secretion. Learning points Estrogen-secreting adrenocortical carcinomas are exceedingly rare in adults and account for 1−2% of adrenocortical carcinomas. Estrogen-secreting adrenal tumors can be present in females, but are even more rare, we found few cases described in the literature. In women, they present with precocious puberty or postmenopausal bleeding. Feminization in the context of an adrenal tumor is considered almost pathognomonic of malignancy. Feminizing ACCs tend to be larger and with worse prognosis compared with nonfeminizing ACCs.

Is There Value in Routine Screening for Cushing’s Syndrome in Patients with Diabetes?

Context: Subclinical Cushing’s syndrome has been described among diabetic populations in recent years, but no consensus has emerged about the value of screening. Methods: We enrolled 201 consecutive patients attending our diabetes clinic and 79 controls. Patients with at least two of the following three criteria were offered screening using a 2300 h salivary cortisol test: glycosylated hemoglobin of at least 7%, body mass index of at least 25 kg/m2, and a history of hypertension or blood pressure of at least 140/90 mm Hg. Results are expressed as mean ± sem. Results: Mean nighttime salivary cortisol levels were similar in the two groups (8.5 ± 1.0 nmol/liter for diabetic patients vs. 5.8 ± 1.0 nmol/liter for controls). Forty-seven patients (23%) had a value of at least 10 nmol/liter, which was set as a conservative threshold above which further investigation would be performed. Thirty-five (75%) agreed to further testing with a 1-mg overnight dexamethasone test. Of the remaining 12 patients, 10 were followed up clinically for at least 1 yr, and no evidence was found of the syndrome evolving. In 28 patients, serum cortisol suppressed to 60 nmol/liter or less. Of the seven patients who failed this test, four agreed to a 2 mg/d 48-h dexamethasone test, with serum cortisol suppressing to 60 nmol/liter or less in all four. Three declined this test but had normal 24-h urinary free cortisol levels. No patient had clinical features of hypercortisolism. Conclusions: The 1–3% detection rates of three recently published series have not been realized at our center where we studied a group using criteria making patients more likely to have hypercortisolism. Our results do not support the validity of screening patients without clinical features of Cushing’s syndrome in the diabetes clinic.

Use of dexamethasone for the differential diagnosis of dwarfism

The capacity of somatotrophs to respond with secretion of growth hormones to dexamethasone administration was studied in children with different forms of dwarfism. In cases of growth delay caused by deficiency of growth hormone the content of STH during dexamethasone test was at the basal level. In the rest cases blood plasma (serum) STH levels increased at the 180th min after dexamethasone administration. A 6 to 50-fold increase of blood STH level was observed in the presence of intact somatotropic function of the hypophysis. Dexamethasone is recommended for the assessment, of the function of somatotrophic state in practical medicine.