Gland and Hormone Related Diseases

All Conditions

Neoplasms

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Rare Diseases

Cushing Syndrome

Adrenocortical Hyperfunction

Adrenocortical Adenoma

Adrenal Gland Neoplasms

Adenoma

Syndrome

Endocrine Gland Neoplasms

Adrenal Gland Diseases

Endocrine System Diseases

Adrenal Cortex Neoplasms

Adrenal Cortex Diseases

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Hyperadrenalism

Adenoma of the Adrenal Gland

Anti-Inflammatory Agents

All Drugs and Chemicals

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Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Epinephrine

Racepinephrine

Epinephryl borate

Patients with incidentally discovered adrenal mass with 1mg-DST serum cortisol levels lower than 50 nmol/L

Patients with incidentally discovered adrenal mass with 1mg-DST serum cortisol levels greater than 50 nmol/L receiving conservative management

Patients with incidentally discovered adrenal mass with 1mg-DST serum cortisol levels greater than 50 nmol/L receiving adrenalectomy according to the 2016 European Society of Endocrinology guidelines

Adrenalectomy accordint to 2016 ESE guidelines

Adrenalectomy

Andrea M Isidori, MD, PhD

Marianna Minnetti

Emilia Sbardella

Andrea M Isidori, MD, PHD

The investigators hypothesize that cardiovascular and metabolic alterations can occur in patients with adrenal adenomas and possible Autonomous Cortisol Secretion (pACS). Investigators hypothesize that adrenalectomy in selected patients, following the 2016 ECE guidelines, can improve metabolic parameters and cardiovascular risks and features.

Adrenal incidentalomas are clinically silent masses discovered inadvertently during diagnostic imaging procedures performed for unrelated reasons. Depending on the criteria applied, up to 50% of patients with adrenal incidentalomas may have biochemical evidence of cortisol excess. Possible autonomous cortisol secretion (pACS), as defined in the 2016 European Society of Endocrinology Guidelines, is characterized by a partial, incomplete suppression of the hypothalamic-pituitary-adrenal (HPA) axis without the typical signs of overt cortisol hypersecretion.

Investigators will perform a prospective longitudinal study in patients with adrenal incidentalomas associated with possible autonomous cortisol secretion, aiming to assess the effect of surgical and conservative management on cardiovascular and metabolic features.

Data will be detected at baseline, at 1 and at 5 years follow-up to quantitatively identify the different cardiovascular and metabolic alterations in: (1) patients with non-functioning adrenal adenoma; (2) patients with possible autonomous cortisol secretion receiving conservative management; (3) patients with possible autonomous cortisol secretion receiving adrenalectomy according to the 2016 European Society of Endocrinology guidelines; (4) patients without adrenal masses.

Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations

Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations (ITACA Study)

Change of Left Ventricular Hypertrophy will be evaluated by transtoracic echocardiography. Patients will be examined in the left lateral decubitus position according to the American Society of Echocardiography guidelines.

Perform non-invasive measurement of arterial stiffness

Perform twenty-four-hour systolic and diastolic ambulatory blood pressure monitoring

Perform blood sampling for coagulative function

Bone mineral density change in spine and femur

Perform adrenal chemical shift MRI or adrenal CT scan (if MRI is contraindicated)

Perform the Pittsburgh Sleep Quality Index (PSQI). Sleep disturbances will be evaluated by The Pittsburgh Sleep Quality Index (PSQI). This questionnaire contains 19 self-related questions which are combined to create 7 component scores with a range of 0-3 points (0:no difficulty, 3: severe difficulty). Global score is the result to the addition of all component scores with a range of 0-21 points (0:no difficulty, 21: severe difficulty).

Frequencies and severity of infectious diseases will be evaluated by modified Infectious Diseases Questionnaire (GNC).

This questionnaire includes questions on infectious diseases of upper and lower respiratory tract, gastrointestinal tract, skin and urogenital tract and flu contracted during the previous 12 months. Questions investigate on the number and duration of infections, necessity of antibiotic or antifungal therapy, hospital stay and days of absence from work. Final score represents the frequency of infections.

Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self-administered questionnaire SF-36-Item Health Survey questionnaire.

This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component).

Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health state.

Psychometric evaluation will be assessed by the score of Beck depression Index: a 21-item measure of depressive symptoms. Each answer is scored on a scale value (from 0 to 3 points). The global score is obtained adding all single scores, with a range of 0-63. Higher score constitutes worse burden of symptoms (0-13: minimal depression, 14-19: mild depression, 20-28: moderate depression, 29-63: severe depression).

Perform the Female Sexual Function Index (FSFI) questionnaire. This is a 19-item questionnaire that covers six domains: desire, arousal, lubrication, and orgasm, satisfaction, and pain. The ranges of the domain scores are as follows: for desire 1.2 - 6.0, for arousal, lubrication, orgasm and pain 0 - 6.0 and for satisfaction 0.8 - 6.0. The higher scores of the six domains indicate better sexual functioning about that domain. The overall FSFI score is obtained by summing the six domain scores. The overall FSFI scores range from 2.0 to 36.0, with higher scores indicating better sexual functioning.

Perform the International Index of Erectile Function (IIEF) questionnaire in man. The IIEF is an internationally validated test. It is used to assign a score of erectile dysfunction: severe score 1 to 10; moderate score 11 to 16; low to moderate score 17 to 21; Low score 22 to 25; no erectile dysfunction score 26 to 30

Measurement of HOMA index calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5.

Measurement of Total Cholesterol, LDL cholesterol, HDL cholesterol, Triglyceredes

University of Roma La Sapienza

Full Professor of Endocrinology

Nutritional and Metabolic Diseases

Metabolic Syndrome

patients who receive conservative treatment

surgery

Jae Hyeon Kim, M.D, Ph.D.

Seo Young Sohn

Jae Hyeon Kim

Jung-Min Koh

Kee-Ho Song

Yumie Rhee

Objective:

To determine the metabolic effects of the adrenalectomy in subclinical Cushing's syndrome of adrenal incidentaloma.

Methods:

234 subclinical cushing syndrome and adrenal incidentaloma will be randomly assigned into two groups(e.g adrenalectomy group and conservative treatment group).

Long-term Beneficial Metabolic Effects of Adrenalectomy in Subclinical Cushing's Syndrome of Adrenal Incidentaloma

Long-term Effects of Adrenalectomy on Metabolic Syndrome, Glucose Metabolism, Lipid Metabolism, and Bone Metabolism in Subclinical Cushing's Syndrome of Adrenal Incidentaloma

Asan Medical Center

Severance Hospital

Konkuk University Medical Center

Samsung Medical Center

Associate Professor

Immune System Diseases

Adrenal Insufficiency

Hyperaldosteronism

Addison Disease

Hypoaldosteronism

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Addison's Disease

Anti-Infective Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Adrenergic beta-Agonists

Bronchodilator Agents

Anti-Asthmatic Agents

Mydriatics

Sympathomimetics

PA patients with AVS-confirmed lateralisation to the left adrenal and signed study consent will be included in this study group. EUS will be performed. If EUS identifies an adrenal nodule in the left adrenal, EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure will be performed. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.

PA patients with suspicion of aldosterone overproduction in their left adrenal, but without fulfilling the strict AVS lateralization criteria, either due to a non-representative AVS, or a representative AVS but without significant left-sided lateralization (LI \< 4), and where the study investigators consider EUS-RFA treatment as an aldosterone-reducing procedure to be of high potential clinical and biochemical benefit for the patient, will be included in this study group after signed consent. EUS will be performed. If EUS identifies an adrenal nodule in the left adrenal, an EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.

MACS patients with AVS-confirmed lateralisation the left adrenal gland and CT showing left-sided tumour will be included in this study group after signed consent. EUS will be performed, and a EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.

MACS patients with AVS-confirmed bilateral cortisol overproduction and bilateral tumours will be included in this study group after signed study consent. EUS will be performed, and EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.

Patients will fast, receive prophylactic antibiotics and conscious sedation prior to the endoscopic procedure.The procedure is performed with a standard linear echo-endoscope with a 3.7 mm or larger working channel. The left adrenal is identified from the fundus of the stomach. Color-Doppler is used to map adrenal vascularity. Ultrasound contrast is used to demarcate the border of the tumour. EUS-guided fine needle tissue sampling from tumour tissue is performed. The RFA ablation catheter is water-cooled and stable temperature is maintained at 70-75 degrees celsius until formation of heat bubbles can be seen on EUS. If necessary, the procedure is repeated after moving the probe until the whole adenoma volume is ablated. Ultrasound contrast medium is used after the procedure to ensure that the target for the ablation is non vascularized, before termination. The patients will be observed at the postoperative unit a few hours, and further in the ward for 24h

EUS-RFA of left adrenal tumour in PA with AVS-verified left lateralisation

EUS-RFA of left adrenal tumour in PA, "debulking group"

EUS-RFA of left adrenal tumour in MACS with AVS-verified left lateralisation

EUS-RFA of left adrenal tumour in MACS with bilateral overproduction, "debulking group

Marianne Grytaas, MD phd

Roald Havre, MD PhD

Kristian Løvås, MD Phd

In this study, the investigators will perform endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) treatment of left-sided adrenal tumours in patients with primary aldosteronism (PA) and in patients with mild autonomous cortisol secretion (MACS). Four different study groups will all receive EUS-RFA of left-sided adrenal tumours. Clinical and biochemical outcome as well as procedural safety will be evaluated. In study patients with verified lateralised aldosterone or cortisol overproduction to the left adrenal, outcome will be compared with control groups performing conventional unilateral adrenalectomy.

Study group 1: PA patients with AVS-verified left sided lateralisation and a EUS-detectable tumour in the left adrenal for EUS-RFA treatment.

Study group 2: PA patient with suspected left-sided overweight of aldosterone production and a EUS-detectable tumour but without strict lateralisation of their aldosterone overproduction, for EUS-RFA treatment as an aldosterone "debulking" procedure.

Study group 3: patients with MACS with AVS-verified lateralisation of cortisol overproduction to the left adrenal and EUS-detectable tumour for EUS-RFA treatment Study group 4: patients with MACS with bilateral adrenal tumours and verified bilateral overproduction of cortisol for EUS-RFA treatment as a cortisol "debulking" procedure.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with worse cardiovascular outcome than primary hypertension. Early diagnosis and treatment is paramount to avoid excess morbidity and death. The two main forms of PA are unilateral PA, often caused by an aldosterone-producing adenoma (APA), and bilateral PA. Differentiation between unilateral and bilateral disease determines treatment options. Adrenal vein sampling (AVS) is the recommended procedure to determine PA subtype, unilateral or bilateral. For unilateral PA surgery with unilateral adrenalectomy is recommended treatment. For PA without fulfilling lateralisation criteria, life-long medical treatment is recommended.

Mild autonomous cortisol production (MACS) is present in 20-30% of all adrenal incidentalomas, and is associated with the metabolic syndrome (hypertension, diabetes, obesity and osteoporosis). Therefore these patients carry increased risk of developing cardiovascular disease. Optimal treatment is debated, and based on the degree of MACS, degree of metabolic complications, and the patient's own opinion. Unilateral adrenalectomy is an option if the overproduction is unilateral, but in 15 % of cases, the overproduction is bilateral, and treatment strategy even more troublesome.

The left adrenal is situated in near proximity to the stomach and is easily reached by endoscopic ultrasound (EUS), and may be targeted for RFA, treating an aldosterone- or cortisol-producing tumour only, and spearing the remaining adrenal. In this study we introduce EUS-RFA as a new treatment option in the following patient groups:

Study group 1: PA patients with AVS-verified left sided lateralisation and a EUS-detectable tumour in the left adrenal for EUS-RFA treatment.

Study group 2: PA patient with suspected left-sided overweight of aldosterone production and a EUS-detectable tumour but without strict lateralisation of their aldosterone overproduction, for EUS-RFA treatment as an aldosterone "debulking" procedure.

Study group 3: patients with MACS with AVS-verified lateralisation of cortisol overproduction to the left adrenal and EUS-detectable tumour for EUS-RFA treatment Study group 4: patients with MACS with bilateral adrenal tumours and verified bilateral overproduction of cortisol for EUS-RFA treatment, as a cortisol "debulking" procedure.

For all study groups, if CT scan shows an adrenal nodule to the left adrenal, nodule size must be \< 40 mm and enhancement value must fulfill criteria for a benign adenoma. Patients consenting to the EUS-RFA will have a EUS performed. If EUS of the left adrenal identifies an adrenal nodule, a fine needle tissue sampling will be performed. Thereafter EUS-guided RFA procedure of the tumour will be performed. After RFA treatment, the fine needle tissue sampling will undergo morphological and functional characterisation, including application of specific imaging mass cytometry for detection of aldosterone- or cortisol producing cells.

Clinical and biochemical outcome after EUS-RFA will be evaluated by the international PASO-criteria (PA) or ENSAT/ECE criteria (MACS). In patients with lateralised PA or lateralised MACS, clinical and biochemical outcome and postoperative hypoaldosteronism or hypocortisolism will be compared with conventional unilateral adrenalectomy. Inn all patients, procedural safety will be evaluated.

Four EUS-RFA intervention study groups Group 1: PA with lateralisation to left adrenal and left-sided tumour for EUS-RFA Group 2: PA with suspected left-sided overweight of aldosterone overproduction but not AVS-verified left-sided lateralisation for EUS-RFA as "debulking" procedure Group 3: MACS with unilateral tumour in the left adrenal and unilateral cortisol overproduction verified by AVS, for EUS-RFA Group 4: MACS with bilateral adrenal tumours and AVS-verified bilateral cortisol overproduction for EUS-RFA as "debulking" procedure

Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism

Endoscopic Ultrasound-guided Radiofrequency Ablation as a Novel Treatment Option Compared With Adrenalectomy in Left-sided Primary Aldosteronism

Biochemical outcome will be evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 3 and 1 year

Clinical outcome will be evaluated by international standardised PASO criteria at follow-up visits after 1 year

Biochemical outcome will be evaluated at follow-up visits after 3 and 1 year, evaluated by the international European Network for Study of Adrenal Tumour (ENSAT) /European Society of Endocrinology (ESE) criteria

Clinical outcome will be evaluated at follow-up visits after 3 and 1 year, evaluated by the international ENSAT/ESE criteria

Procedural complications of EUS-RFA compared with unilateral adrenalectomy will be performed using the Clavien-Dindo classification.

Length of hospital stay after EUS-RFA will be compared with adrenalectomy, and will be evaluated at follow-up after 3 months

Number of participants with postoperative hypoaldosteronism after EUS-RFA will be compared with unilateral adrenalectomy by biochemical assessment at 3 months after treatment

Number of participants with postoperative hypocortisolism after EUS-RFA will be compared with unilateral adrenalectomy. In patients with an abnormal pre-treatment 1 mg dexamethasone suppression test or a low morning cortisol \< 300 nmol/L after RFA or adrenalectomy, individual advise of cortisone acetate replacement therapy will be given and an stimulation adrenocorticotropic hormone (ACTH) test will be performed in the Endocrinology Out-patient clinic \~ 6 weeks of discharge

Change in health-related quality of life after treatment compared with pre-treatment, will be measured by the validated RAND-36 Health Survey, and will be compared in the EUS-RFA group and adrenalectomy group.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations	NCT04127552	Adrenal Inciden... Hypercortisolis... Adrenal Tumor	Adrenalectomy	18 Years - 80 Years	University of Roma La Sapienza
Long-term Beneficial Metabolic Effects of Adrenalectomy in Subclinical Cushing's Syndrome of Adrenal Incidentaloma	NCT01382420	Cushing Syndrom...	surgery	20 Years - 70 Years	Samsung Medical Center
Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism	NCT05368090	Primary Aldoste... Aldosterone-Pro... Hypercortisolis...	EUS-RFA of left... EUS-RFA of left... EUS-RFA of left... EUS-RFA of left...	18 Years - 80 Years	Haukeland University Hospital

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