Adrenal Tuberculosis Mimicking a Malignant Tumor with Primary Adrenal Insufficiency

Woo Seok Kim,Jin Hyung Lee 순천향대학교 순천향의학연구소 2017 Journal of Soonchunhyang Medical Science Vol.23 No.1

Adrenal tuberculosis is a relatively infrequent cause of primary adrenocortical insufficiency in developed countries. Isolated adrenal tuberculosis, especially with enlargement of adrenal glands, can cause diagnostic problems and requires differentiation from primary or secondary neoplasms. A 40-year-old woman presented to Soonchunhyang University Gumi Hospital with altered consciousness. She showed biochemical evidence of adrenal insufficiency without signs of tuberculosis. Abdominal computed tomography (CT) scan showed a calcified mass 3.3×2.3 cm in size and peripheral enhancement of the left adrenal gland. A laparoscopic adrenalectomy was performed for a diagnosis of left adrenal malignant tumor. The diagnosis of adrenal tuberculosis was confirmed by a final histological examination.

Effects of Nonylphenol on the Secretion of Catecholamines and Adrenocortical Hormones from Short- Term Incubated Rat Adrenal Glands

김희수,전용필,이성호 한국발생생물학회 2023 발생과 생식 Vol.27 No.4

Previously, we showed that a chronic-low-dose nonylphenol (NP) exposure resulted in histological changes with sexually dimorphic pattern in rat adrenal glands. We hypothesized that such structural changes are closely related to the hormonal secretory patterns. To test this hypothesis, we developed the short-term adrenal incubation method, and measured the levels of catecholamines and cortical steroids using the high-performance liquid chromatography with electrochemical detection (HPLC-ECD) and specific enzyme-linked immunosorbent assay, respectively. The norepinephrine (NE) levels in media from NPtreated female adrenal, except 100 pM NP, were significantly increased [control (CTL) vs 1 nM NP, p<0.001; vs 10 nM NP, p<0.05; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.01]. The NE secretion from male adrenal was higher when treated with 100 nM and 1 µM NP (CTL vs 100 nM NP, p<0.05; vs 1 µM NP, p<0.05, respectively). The aldosterone level in the female adrenal media treated with 100 pM NP was significantly decreased, on the other hand, that of media treated with 10 nM NP was significantly increased (CTL vs 100 pM NP, p<0.05; vs 10 nM NP, p<0.01). In male adrenal media, the aldosterone levels of 10 nM, 100 nM and 1 µM NP-treated media were significantly declined (CTL vs 10 nM NP, p<0.001; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.001). These results showed the NP treatment altered secretory pattern of aldosterone from adrenals of both sexes, showing sexual dimorphism. It may be helpful for understanding possible adrenal pathophysiology, and endocrine disrupting chemicals-related sexually dimorphic phenomena in adrenals.

다발성 전이를 가지고 태어난 선천성 신경모세포종 -1 부검례 보고-

명나혜,송상용,지제근 대한병리학회 1993 Journal of Pathology and Translational Medicine Vol.27 No.2

The adrenal peripheral clock: Glucocorticoid and the circadian timing system

Son, G.H.,Chung, S.,Kim, K. Raven Press [etc.] ; Academic Press 2011 Frontiers in neuroendocrinology Vol.32 No.4

The mammalian circadian timing system is organized in a hierarchy, with the master clock residing in the suprachiasmatic nucleus (SCN) of the hypothalamus and subsidiary peripheral clocks in other brain regions as well as peripheral tissues. Since the local oscillators in most cells contain a similar molecular makeup to that in the central pacemaker, determining the role of the peripheral clocks in the regulation of rhythmic physiology and behavior is an important issue. Glucocorticoids (GCs) are a class of multi-functional adrenal steroid hormones, which exhibit a robust circadian rhythm, with a peak linked with the onset of the daily activity phase. It has long been believed that the production and secretion of GC is primarily governed through the hypothalamus-pituitary-adrenal (HPA) neuroendocrine axis in mammals. Growing evidence, however, strongly supports the notion that the periodicity of GC involves the integrated activity of multiple regulatory mechanisms related to circadian timing system along with the classical HPA neuroendocrine regulation. The adrenal-intrinsic oscillator as well as the central pacemaker plays a pivotal role in its rhythmicity. GC influences numerous biological processes, such as metabolic, cardiovascular, immune and even higher brain functions, and also acts as a resetting signal for the ubiquitous peripheral clocks, suggesting its importance in harmonizing circadian physiology and behavior. In this review, we will therefore focus on the recent advances in our understanding of the circadian regulation of adrenal GC and its functional relevance.

Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review

유원상,구유정,이은경,안화영 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.6

Background: This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs. Methods: We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published. Results: A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic Tlymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone. Conclusion: Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.

Primary Bilateral Adrenal Non-Hodgkin’s Lymphoma Presented with Adrenal Insufficiency: A Case Report

이은영,김경민,김광준,노송미,김진석,양우익,임승길 대한내분비학회 2011 Endocrinology and metabolism Vol.26 No.1

Primary adrenal lymphoma is a very rare disease and it is known to have a poor prognosis. We report here on a case of primary adrenal insufficiency that was secondary to primary bilateral adrenal lymphoma. A 54-year old man was hospitalized because of easy fatigability,weight loss and consistent malaise for 6 months. The physical examination revealed hyperpigmentation on the anterior chest and hypotension. According these findings and symptoms, we did a rapid ACTH stimulation test with a clinical suspicion of adrenal insufficiency. He showed an inadequate adrenal response and so he was diagnosed with adrenal insufficiency. The abdominal CT images showed bilateral huge adrenal masses and increased uptake of the adrenal glands on PET. The pathologic diagnosis by ultrasound-guided gun biopsy of the right adrenal gland was diffuse large B cell lymphoma. The patient was administered combination chemotherapy with the R-CHOP regimen, and after 8-cycles of chemotherapy, he achieved complete remission of tumor according to the image studies and he recovered his adrenal function. Primary adrenal lymphoma, although a rare disease, should be considered in patients with bilateral enlargement of the adrenal glands and when the adrenal glands show increased uptake on a PET scan, and especially there is adrenal insufficiency.

부신 우연종에서 F-18 FDG PET/CT의 유용성: 악성 종양 환자에서 부신 전이의 감별진단

이홍제 ( Hong Je Lee ),송봉일 ( Bong Il Song ),강성민 ( Sung Min Kang ),정신영 ( Shin Young Jeong ),서지형 ( Ji Hyoung Seo ),이상우 ( Sang Woo Lee ),유정수 ( Jeong Soo Yoo ),안병철 ( Byeong Cheol Ahn ),이재태 ( Jae Tae Lee ) 대한핵의학회 2009 핵의학 분자영상 Vol.43 No.5

목적: 악성 종양 환자의 F-18 FDG PET/CT에서 우연히 발견된 부신 종양의 특성에 대해 알아보고 양성 및 악성 부신 종양을 감별하는 데 있어서 F-18 FDG PET/CT의 진단 능력에 대해 평가해 보았다. 대상 및 방법: 2005년 3월부터 2008년 8월까지 시행한 F-18 FDG PET/CT에서 우연히 부신 종양이 발견된 75명의 악성 종양 환자들(89개의 부신 종양)을 대상으로 하였다. 평균 연령은 60.8±10.2 (35-87)세였으며, 남자는 46명, 여자는 29명이었다. 정량 분석을 위해 89개의 부신 종양의 장경(cm), HU, SUVmax, SUVratio를 각각 측정하였다. 부신 종양의 SUVmax를 간의 8번 분절의 SUVmax인 SUVliver로 나눈 값을 SUVratio로 하였다. 부신 종양은 조직학적 확진, 방사선학적 평가(HU<0: 양성), 임상적 판단에 따라 최종 진단하였다. 결과: 양성과 악성 부신 종양을 감별하는데 크기, HU, SUVmax, SUVratio의 4가지 변수는 모두 유의한 차이가 있었다(p<0.05). 그리고, SUVratio가 가장 정확도가 높았다. SUVratio는 cut-off value 1.0에서 민감도 90.9%, 특이도 75.6%를 보였다. 1.5 cm 크기 이하의 작은 부신 종양에서는 양성과 악성 부신 종양을 감별하는데 SUVratio만 통계적으로 유의한 차이가 있었다(p<0.05). SUVratio는 cut-off value 1.0에서 민감도 80.0%, 특이도 86.4%를 보였다. 결론: 악성 종양 환자에서 우연히 발견된 부신 종양을 양성과 악성으로 감별 진단하는데 있어서 정량 분석을 통해 F-18 FDG PET/CT가 비조영증강(nonenhanced) CT에 비해서 더 정확한 정보를 제공할 수 있다고 생각된다. Purpose: We have evaluated characteristics of adrenal masses incidentally observed in nonenhanced F-18 FDG PET/CT of the oncologic patients and the diagnostic ability of F-18 FDG PET/CT to differentiate malignant from benign adrenal masses. Materials and Methods: Between Mar 2005 and Aug 2008, 75 oncologic patients (46 men, 29 women; mean age, 60.8±10.2 years; range, 35-87 years) with 89 adrenal masses incidentally found in PET/CT were enrolled in this study. For quantitative analysis, size (cm), Hounsfield unit (HU), maximum standardized uptake value (SUVmax), SUVratio of all 89 adrenal masses were measured. SUVmax of the adrenal mass divided by SUVliver, which is SUVmax of the segment 8, was defined as SUVratio. The final diagnosis of adrenal masses was based on pathologic confirmation, radiologic evaluation (HU<0:benign), and clinical decision. Results: Size, HU, SUVmax, and SUVratio were all significantly different between benign and malignant adrenal masses.(P<0.05) And, SUVratio was the most accurate parameter. A cut-off value of 1.0 for SUVratio provided 90.9% sensitivity and 75.6% specificity. In small adrenal masses (1.5 cm or less), only SUVratio had statistically significant difference between benign and malignant adrenal masses. Similarly a cut-off value of 1.0 for SUVratio provided 80.0% sensitivity and 86.4% specificity. Conclusion: F-18 FDG PET/CT can offer more accurate information with quantitative analysis in differentiating malignant from benign adrenal masses incidentally observed in oncologic patients, compared to nonenhanced CT.(Nucl Med Mol Imaging 2009;43(5):421-428)

부신 CT 검사에서 HU의 조영증강 및 선량 평가

권대철,최지원 (사)한국방사선산업학회 2018 방사선산업학회지 Vol.12 No.2

The purpose is to improve the accuracy of dose reduction and adrenal gland diagnosis by analyzing the HU and evaluating the effective dose of contrast CT scan of the adrenal gland in order to evaluate the accuracy of contrast enhancement of adrenal adenomas. We analyzed the dose information of patient DICOM file that underwent CT scan of adrenal gland examination. CT scan of the adrenal gland performed pre contrast, portal phase, a 3 minute delay and a 15 minute delay. The HU measurement selects the largest region of adrenal lesion. And, mean, standard deviation, and area of the adrenal lesion were analyzed by ROI. Absolute percentage washout (APW) and relative percentage washout (RPW) calculated and the adrenal adenomas diagnosed by threshold value of the percentage washout rate were above APW 60% and RPW 40%. Effective dose was calculated based on DLP of DICOM dose report for adrenal CT scan. HU analyzed of the adrenal gland by calculating APW and RPW. The APW and RPW were analyzed by 52% and 41.8% at 3 minute delay, 73.5% and 59% at 15 minute delay, respectively. The diagnosis of adrenal adenomas was consistent with APW (73.5%) and RPW (59%) above the threshold at 15 minute delay. The effective dose of adrenal CT scan was 16.08 mSv. Therefore, it is necessary for radiation dose reduction.

LETTER TO THE EDITOR : Aldosterone- and cortisol-co-producing adrenal adenoma without clinical features of Cushing syndrome

( Kyung Yoon Chang ),( Seong Yul Ryu ),( Jae Young Cho ),( Hyung Wook Kim ) 대한내과학회 2014 The Korean Journal of Internal Medicine Vol.29 No.5

Primary aldosteronism was originally described by an aldosterone-producing adenoma. Later, primary aldosteronism was recognized to occur as a result of a heterogeneous group of disorders, including adenoma, hyperplasia, or aldosterone- and cortisol- co-producing tumors. Here, we report a rare case of an aldosterone- and cortisol-co-producing adenoma in the presence of primary aldosteronism without the clinical features of Cushing syndrome. A 29-year-old woman with hypertension presented with seizure and lower extremity weakness. The patient was 166 cm tall, weighed 64.5 kg, and her blood pressure was 165/97 mmHg. No features of Cushing syndrome, such as moon face, purple striae, hirsutism, or central obesity, were evident. Laboratory data showed sodium, 145 mEq/L; potassium, 1.5 mEq/L; chloride, 94 mEq/L; calcium, 8.3 mg/ dL; phosphorus, 2.4 mg/dL; magnesium, 2.0 mg/dL; blood urea nitrogen, 6.5 mg/dL; and serum creatinine, 0.5 mg/dL. Spot urine potassium was 37.6 mEq/L, and the transtubular potassium gradient was 14%. Spot urine chloride was 90.2 mEq/L, and a blood gas analysis showed pH, 7.6; pCO2, 42.5 mmHg; pO2, 85 mmHg; HCO3, 44.2 mmol/L; and SpO2, 98%. Thyroid function tests were normal. Fasting plasma glucose and glycated hemoglobin were 96 mg/dL and 4.9%, respectively. Electrocardiography, chest anteroposterior views, brain computed tomography (CT), electroencephalography, and a cerebral spinal fluid study revealed normal findings. As shown in Table 1, hormone studies showed an increased plasma aldosterone concentration (PAC; 29.6 ng/ dL), suppressed plasma renin activity (PRA; 0.1 ng/mL/hr), and an increased PAC:PRA ratio (296), suggesting excess aldosterone. Basal PRA and PAC on the saline infusion test were 0.1 ng/mL/hr and 94.5 ng/dL, respectively. After infusion of 2 L of 0.9% saline over 4 hours, PAC was not suppressed (72.1 ng/dL). The 24-hour urinary free cortisol excretion increased to 566.1 μg/day. Serum cortisol levels were not suppressed with administration of doses of 1 (overnight), 2 (low dose), and 8 mg (high dose) dexamethasone, which were in concentrations of 8.26, 9.54, and 7.79 μg/dL, respectively. Plasma adrenocorticotrophic hormone (ACTH) was < 5 pg/mL, suggesting an ACTH-independent type of Cushing syndrome (Table 1). An adrenal CT scan revealed a 2.1 × 1.6 cm diameter, well circumscribed, homogeneous, low density nodule in the left adrenal gland. PRA was 0.16 ng/mL/hr, PAC was 54.9 ng/dL, and ACTH was 11.0 pg/mL in the supine position. After 4 hours of standing, PRA was 1.23 ng/mL/hr, PAC was 46.7 ng/dL, and ACTH was < 5 pg/mL. These results suggested an adrenal adenoma rather than bilateral adrenal hyperplasia due to the paradoxical drop in aldosterone with standing. We excluded adrenocortical carcinoma and pheochromocytoma based on the results of hormone studies (Table 1). We could not perform bilateral adrenal venous sampling or 131I-iodocholesterol scintigraphy due to patient refusal. We diagnosed this case as an aldosterone- and cortisol- co-producing adrenal adenoma based on the very high PAC, cortisol that was not suppressed by dexamethasone, and the adrenal mass on CT. Preoperative management involved 100 mg spironolactone daily and a potassium correction. Subsequently, a laparoscopic left adrenalectomy was performed. The cut surface of the tumor was homogeneous and golden yellow without necrotic features. A histological examination revealed that the adrenocortical adenoma was composed of both clear and compact cells. We performed immunohistochemistry for 3β-hydroxysteroid dehydrogenase (HSD-3β1) and cytochrome P450-17A1 using anti-HSD3β1 (1:50; Abcam, Cambridge, MA, USA) and anticytochrome P450-17A1 (1:50; Abcam), respectively, which suggested that the adrenal adenoma possibly produced both aldosterone and cortisol (Fig. 1). The patient`s hypertension and hypokalemia improved following the adrenalectomy. Just after the surgery, we injected 100 mg hydrocortisone intravenously to prevent an adrenal crisis and then tapered the oral prednisolone for 5 days. After surgery, hormone studies showed normalized PAC (3.1 ng/dL), PRA (0.32 ng/ mL/hr), PAC:PRA ratio (6.68), and 24-hour urinary free cortisol excretion (60.81 μg/day). The serum cortisol level after administration of a 1 mg dexamethasone dose (overnight) was 1.93 μg/dL. Ten days after surgery, we performed a rapid ACTH stimulation test, which demonstrated insuffi cient cortisol secretion. The preinjection plasma ACTH and cortisol levels were 29.6 pg/mL and 5.06 μg/dL, respectively. Plasma cortisol levels 30 and 60 minutes after a single intravenous injection of 250 μg tetracosactide (Synacthen [Alliance Pharma, Chippenham, UK], synthetic ACTH) were 8.14 and 8.94 μg/dL, respectively, indicating adrenal insuf- ficiency. We restarted oral prednisolone at a daily dose of 7.5 mg and tapered it over 5 months. After the patient decided to stop oral prednisolone 5 months after surgery, we confirmed normal cortisol secretion using the rapid ACTH stimulation test. Several clinical implications are important for aldosterone- and cortisol-co-producing tumors. First, these patients are associated with an increased risk of cardiovascular events, as the incidence of myocardial infarction, heart failure, and stroke increase [1]. Second, there is increased risk for metabolic complications such as glucose intolerance and hypertension [2]. Third, these tumors can lead to decreased bone mineral density and bone quality and an increased risk of fracture [3]. Fourth, cortisol co-secretion may cause false-negative results in adrenal venous sampling [4]. Finally, postoperative adrenal crisis and adrenal insuf- ficiency should be considered in the clinical management [5]. The prevalence of aldosterone- and cortisol-co-producing tumors is not exact. Clinicians should consider a cortisol co-secreting tumor in primary aldosteronism if cortisol is not suppressed by dexamethasone or an adenoma > 2.5 cm is present [4]. Treatment for an aldosterone- and cortisol-co-producing tumor is surgical excision. It should be noted that hydrocortisone replacement is necessary during and after adrenalectomy. In conclusion, we present this case to emphasize that an adrenal adenoma might be capable of secreting both aldosterone and cortisol without clinical features of Cushing syndrome. Therefore, the screening test for Cushing syndrome should be performed in patients with primary aldosteronism even if there are no clinical features of Cushing syndrome.

Adrenal Morphology as an Indicator of Long-Term Disease Control in Adults with Classic 21-Hydroxylase Deficiency

김택민,김정희,장한나,최만호,조정연,김상윤 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.1

Background: Monitoring adults with classical 21-hydroxylase deficiency (21OHD) is challenging due to variation in clinical and laboratory settings. Moreover, guidelines for adrenal imaging in 21OHD are not yet available. We evaluated the relationship between adrenal morphology and disease control status in classical 21OHD. Methods: This retrospective, cross-sectional study included 90 adult 21OHD patients and 270 age- and sex-matched healthy controls. We assessed adrenal volume, width, and tumor presence using abdominal computed tomography and evaluated correlations of adrenal volume and width with hormonal status. We investigated the diagnostic performance of adrenal volume and width for identifying well-controlled status in 21OHD patients (17α-hydroxyprogesterone [17-OHP] <10 ng/mL). Results: The adrenal morphology of 21OHD patients showed hypertrophy (45.6%), normal size (42.2%), and hypotrophy (12.2%). Adrenal tumors were detected in 12 patients (13.3%). The adrenal volume and width of 21OHD patients were significantly larger than those of controls (18.2±12.2 mL vs. 7.1±2.0 mL, 4.7±1.9 mm vs. 3.3±0.5 mm, P<0.001 for both). The 17-OHP and androstenedione levels were highest in patients with adrenal hypertrophy, followed by those with normal adrenal glands and adrenal hypotrophy (P<0.05 for both). Adrenal volume and width correlated positively with adrenocorticotropic hormone, 17-OHP, 11β-hydroxytestosterone, progesterone sulfate, and dehydroepiandrosterone sulfate in both sexes (r=0.33–0.95, P<0.05 for all). For identifying well-controlled patients, the optimal cut-off values of adrenal volume and width were 10.7 mL and 4 mm, respectively (area under the curve, 0.82–0.88; P<0.001 for both). Conclusion: Adrenal volume and width may be reliable quantitative parameters for monitoring patients with classical 21OHD.