Surgical treatment of subclinical Cushing syndrome / 中华泌尿外科杂志

Objective To discuss adrenalectomy effects on biochemical and metabolic impairment for patients with subclinical Cushing syndrome (SCS) due to an adrenal incidentaloma (AI) compared with conservative management.Methods Data from 87 patients with SCS due to AI in Peking Union Medical College Hospital between September 2011 and January 2016 were reviewed.Forty-eight patients underwent laparoscopic adrenalectomy (operative group), whereas 39 were managed conservatively (control group).No significant differences were found at baseline between the two groups concerning all the examined parameters, including age [(51.8 ± 10.2) years vs.(53.2 ± 12.1)years], male/female ratio (18/30 vs.20/19), size of adrenal mass [(3.01 ± 0.84) cm vs.(2.99 ± 1.01) cm], body mass index [(27.34 ±3.84) kg/m2 vs.(26.98 ± 3.99) kg/m2], adrenocorticotropic hormone (ACTH) [(2.01 ± 0.40) pmol/L vs.(1.96 ±0.42) pmol/L] and daily urinary free cortisol levels[(75.80 ± 39.71) mg vs.(71.06 ±31.35) mg], responsiveness to 1 mg of dexamethasone, arterial blood pressure, hypertensive patients (77.08％ vs.79.49％), glucometabolic control parameters, diabetic or impaired glucose tolerance patients (35.42％ vs.33.33％), lipid profile, dyslipidemia patients (70.83％ vs.71.79％).Results The duration of follow-up was 9-54 months in operative group, and 5-57 months in control group,respectively.In the operative group, laboratory corticosteroid parameters normalized in all patients but not in the control group.In the operative group, blood pressure of hypertensive patients improved or normalized (22 of 48).On the contrary, in the control group, cure or improvement was not achieved among the patients with hypertension, whereas worse condition was observed in 5 patients (P =0.004).No significant difference was found in glycemic control and blood lipid change between the two groups.However, a decrease in triglyceridaemia and HbA1c was found in operative group compared with the control group (P =0.011 and P =0.017, respectively).Substitutive corticosteroid treatment was administered in 3 patients due to postoperative adrenal insufficiency during hospital stay, and the duration of treatment was 9 weeks, 10 weeks and 12 weeks, respectively.Conclusion Laparoscopic adrenalectomy could be performed for patients with SCS due to AI.

Comparison of Surgical Outcomes of Laparoscopic Adrenalectomy Between Patients With Nonfunctioning Adrenal Adenomas and Subclinical Cushing Syndrome: A Single-Center Experience

PURPOSE: To examine and compare the perioperative outcomes of laparoscopic adrenalectomy (LA) and to determine its efficacy in patients with nonfunctioning adrenal adenomas (NFA) and subclinical Cushing syndrome (SCS). MATERIALS AND METHODS: We retrospectively analyzed the clinical data obtained from 79 consecutive patients who underwent LA for the treatment of either NFA (n=35) or SCS (n=44) between 2011 and 2016. All patients had undergone computed tomography, as well as endocrinological tests to confirm the diagnosis prior to the adrenalectomy. The primary endpoint was improved metabolic parameters relating to diabetes, hypertension, dyslipidemia, and obesity. RESULTS: Patients with SCS compared to those with NFA showed a higher occurrence of diabetes (29.5% vs. 11.4%), hypertension (59.1% vs. 34.3%), and dyslipidemia (43.2% vs. 14.3%). Patients with SCS showed a smaller median tumor size compared to those with NFA (2.5 cm vs. 5 cm). No significant perioperative complications ≥ Clavien-Dindo classification grade III were observed in any patient (SCS or NFA group). In terms of their metabolic profile, patients with SCS showed a significant postoperative improvement in hypertension (50.0%), diabetes (53.9%), dyslipidemia (31.6%), and obesity (29.2%). However, patients with NFA showed a postoperative improvement only in dyslipidemia (40.0%) and obesity (4.8%). CONCLUSIONS: Owing to absence of significant perioperative complications and the marked postoperative improvement in metabolic impairment, LA is a useful treatment strategy in patients diagnosed with SCS. In contrast, LA was not observed to show beneficial effects in correcting/improving the metabolic profile in patients presenting with NFA.

The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome

BACKGROUND: In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown. METHODS: Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test. RESULTS: Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001). CONCLUSION: The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

Clinical Characteristics and Metabolic Features of Patients with Adrenal Incidentalomas with or without Subclinical Cushing's Syndrome

BACKGROUND: The aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT) and to investigate metabolic features of subclinical Cushing's syndrome (SCS) in patients with adrenal incidentalomas in a tertiary hospital in Korea. METHODS: This retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing's syndrome, and aldosterone-secreting adenoma were performed. RESULTS: Most (n=218, 81.3%) cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%), 19 (7.1%) were diagnosed with SCS, nine (3.4%) with overt Cushing's syndrome, 12 (4.5%) with primary aldosteronism, and 10 (3.7%) with pheochromocytoma. Malignant tumors (both primary and metastatic) were rare (n=2, 0.7%). Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors. CONCLUSION: Functioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.

A Case of Incidentally Discovered Subclinical Cushing Syndrome in a Patient with Chronic Fatigue and Anxiety / 가정의학회지

Subclinical Cushing syndrome (SCS) is a hypothalamic-pituitary-adrenal axis abnormality characterized by autonomous cortisol secretion in patients with no typical signs or symptoms of Cushing syndrome. SCS patients may have adverse metabolic and cardiovascular effects due to slight, but continuous glucocorticoid secretion. Glucocorticoids also affect behavior, mood, neural activity, and a number of specific biochemical processes in the central nervous system. Here, we report a case of SCS due to an adrenal incidentaloma in a hypertensive diabetic patient who presented with chronic fatigue and anxiety that disappeared after the removal of the adrenal adenoma.

Síndrome de Cushing subclínica em populações de risco: [revisão] / Subclinical Cushing's syndrome in populations at risk: [review]

Os incidentalomas de adrenais (IA) são tumores freqüentes em humanos. A síndrome de Cushing (SC) endógena é rara e os adenomas de adrenais são responsáveis por 10 por cento dos casos de SC. A SC subclínica ocorre em IA com dinâmica do cortisol anormal e ausência de fenótipo característico de hipercortisolismo. A prevalência média de SC subclínica em IA é de 9 por cento. Dados de pequenas séries indicam que 20 por cento dos IA desenvolvem alterações bioquímicas quando acompanhados por 10 anos. A evolução da SC subclínica parece ser benigna, raramente ocorrendo aumento da massa e evolução para a SC clinicamente manifesta. Os incidentalomas e a SC subclínica têm sido correlacionados aos componentes da síndrome metabólica, especialmente ao diabetes mellitus do tipo 2. Embora o número de pacientes avaliados ainda seja pequeno, os estudos disponíveis demonstram que o tratamento do hipercortisolismo resulta em melhor controle metabólico e da pressão arterial. Esses achados levaram alguns autores a pesquisar a presença de SC subclínica em pacientes com diagnóstico prévio de diabetes mellitus. Os estudos realizados utilizando diferentes abordagens diagnósticas mostraram que nesse grupo de pacientes a incidência de SC subclínica é maior do que na população geral.

Based on autopsy studies, adrenal masses are among the most common tumors in humans. Endogenous Cushing's syndrome (CS) is unusual and adrenal adenomas account for 10 percent of all cases of CS. Patients with subclinical CS (SCS) present abnormal cortisol dynamics without obvious manifestations. The prevalence of hypercortisolism in clinically inapparent adrenal masses has been reported as 9 percent. Data from several small series of patients indicate that fewer than 20 percent develop hormone overproduction when followed for up to 10 years. Follow-up of patients with subclinical CS suggests that rarely masses increase in size or progress to overt CS. Adrenal incidentalomas and subclinical CS are related to metabolic disorders, in special to type-2 diabetes. The scarce available data suggest that treatment of hypercortisolism correct the metabolic abnormalities and blood pressure. Some studies evaluating the prevalence of subclinical CS in overweight type-2 diabetes patients suggest that it is considerably higher in populations at risk than in the general population.

Subclinical Cushing's syndrome: [review]

Subclinical Cushing's syndrome (CS) is attracting increasing interest since the serendipitous discovery of an adrenal mass has become a rather frequent event owing to the routine use of sophisticated radiologic techniques. Cortical adenoma is the most frequent type of adrenal incidentaloma accounting for approximately 50 percent of cases in surgical series and even greater shares in medical series. Incidentally discovered adrenal adenomas may secrete cortisol in an autonomous manner that is not fully restrained by pituitary feedback, in 5 to 20 percent of cases depending on study protocols and diagnostic criteria. The criteria for qualifying subclinical cortisol excess are controversial and presently there is no consensus on a gold standard for the diagnosis of this condition. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipemia has been described in patients with subclinical CS; however, there is still no clear demonstration of the long-term complications of this condition whose management remains largely empirical. Either adrenalectomy or careful observation associated with treatment of the metabolic syndrome have been suggested as treatment options.

A síndrome de Cushing subclínica (SCS) tem atraído interesse cada vez maior desde que a descoberta casual de uma massa adrenal se tornou um evento freqüente devido ao emprego rotineiro de técnicas sofisticadas de imagem. O adenoma cortical é o tipo mais freqüente de incidentaloma adrenal, correspondendo a cerca de 50 por cento dos casos em séries cirúrgicas e até mais do que isso em séries médicas. Adenomas adrenais descobertos incidentalmente podem secretar cortisol de maneira autônoma ou não controlada totalmente pelo feedback hipofisário, em 5 a 20 por cento dos casos, dependendo do protocolo de estudo e dos critérios diagnósticos. Os critérios para qualificar um excesso subclínico de cortisol são controversos e atualmente não existe consenso a respeito de "padrão ouro" para o diagnóstico dessa condição. Em pacientes com SCS, tem sido descrita uma freqüência elevada de hipertensão, obesidade central, intolerância à glicose, diabetes e hiperlipemia; entretanto, ainda não existe uma evidente demonstração de complicações a longo prazo dessa condição, cujo manejo permanece amplamente empírico. Tanto a adrenalectomia como a observação cuidadosa, associada com o tratamento da síndrome metabólica, têm sido sugeridos como opções terapêuticas.

A Case of Adrenocortical Adenoma Causing Subclinical Cushing's Syndrome Mistaken for Liddle's Syndrome / 대한내분비학회지

Subclinical Cushing's syndrome is defined as an autonomous cortisol hyperproduction without specific clinical signs of cortisol excess, but detectable biochemically as derangements of the hypothalamic-pituitary-adrenal axis function. We report a case of a 33-year-old woman with subclinical Cushing's syndrome caused by left adrenocortical adenoma, mistaken for Liddle's syndrome. The patient complained of fatigue. Laboratory findings showed metabolic alkalosis, hypokalemia, high TTKG (transtubular K concentration gradient), low plasma renin activity, and low serum aldosterone level, that findings implied as Liddle's syndrome. So we performed further study. Hormonal and radiologic studies revealed subclinical Cushing's syndrome with a left adrenal mass. The adrenal mass was resected and pathologically diagnosed as adrenocortical adenoma. After the resection of the left adrenal mass, patient's hormonal levels showed normal range.