Cushing Syndrome Caused by ACTH-independent Macronodular Adrenal Hyperplasia / 대한내과학회지

Adenocorticotropic hormone-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. It is characterized by multinodular enlargement of the adrenal glands and hypercortisolism. Although bilateral adrenalectomy is the standard therapy, unilateral adrenalectomy is an effective alternative. Here we present a case of a 71-year-old female referred to the Endocrinology Department for further evaluation of bilateral adrenal macronodular hyperplasia. Based on dynamic hormone tests and imaging studies, she was diagnosed with AIMAH. Due to persistent hypercortisolism, she underwent completion contralateral surgery after unilateral adrenalectomy. This case demonstrates that unilateral adrenalectomy should be considered in a patient presenting with obvious symptoms of hypercotisolism and relatively asymmetric adrenal enlargement.

Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders

OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.

Analysis on the clinic and pathologic features of hypertension patients with ACTH-independent adrenal hyperplasia / 中华内分泌外科杂志

Objective To investigate clinical and pathologic features of hypertension patients with adre -noeorticotropic hormone ( ACTH)-independent adrenal hyperplasia , and to analyze the relationship between them . Methods The data of patients with ACTH-independent adrenal hyperplasia and hypertension was collected in Department of Urology , the First Affiliated Hospital of Zhengzhou University from Jan .2012 to Dec.2012.The clinical manifestations , endocrine examination results , imaging findings and the pathological changes of adrenal gland were retrospectively analyzed .Results 75 cases were followed-up.Among them, 39 cases were male and 36 were female.Their ages ranged from 20 to 74 years(with 47 as the average).Pathological results showed that diffusive hyperplasia was observed in 42 cases, tubercle hyperplasia in 26 cases, mixed corticomedullary patho-logical changes in 6 cases, and medullary hyperplasia in 1 case.No significant difference was found among diffu-sive, tubercle and mixed corticomedullary hyperplasia in clinical manifestations except for headache , endocrine examination results, or imaging findings(P>0.05).Conclusion There is no relation between clinical manifes-tations, endocrine examination results , imaging findings and pathological changes in adrenal gland for patients with ACTH-independent adrenal hyperplasia and hypertension .

Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with abnormal cortisol secretion mediated by catecholamines

No abstract available.

Perioperative management of high risk ACTH-independent macronodular adrenal hyperplasia: Report of one case / 中华内分泌代谢杂志

Objective To improve the diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia(AIMAH).Methods A 51-year-old female patient with Cushing's syndrome caused by AIMAH was reported.Elevated early morning plasma cortisol levels,increased 24 h urinary free cortisol excretion,and loss of the normal circadian rhythm in cortisol secretion were presented.There was no suppression of cortisol secretion by administration of low-and high-dose overnight dexamethasone suppression test.Cardio-pulmonary function was very bad with the highest blood pressure reaching 300/120 mm Hg( 1 mm Hg=0.133 kPa).Initially,she was treated with mitotane(60 mg/d),but was not effective.After taking ketoconazole (800 mg/d)for 5 days,cardio-pulmonary function was not effectively improved with blood pressure only descending to 180/120 mm Hg.Orthopnoea appeared and Spo2fell once to 75％.The patient had to undergo right total adrenalectomy immediately.ResultsThe mass resected was 10 cm× 10 cm in size and weighted 67.5 g.Histological examination of the removed adrenal revealed nonpigmented macronodular cortical hyperplasia.The patient continued to take ketoconazole (400-800 mg/d)from the 6th day of the operation without steroid replacement therapy in that period.With normal cortisol levels( plasma cortisol at 8:00 was 18.65 μg/dl,24 h urinary free cortisol was 78.75 μmol),she left hospital after the general condition had been improved.During the following updated 10 months follow up,the indexes of her laboratory examination were maintained normal.ConclusionIndividualized therapy should be adopted for the patient with AIMAH.The medication is useful to suppress the adrenal gland cortisol production for those with progression of symptoms,very high blood pressure,hypokalemia and hypoproteinemia.Once the cardio-pulmonary function improves,the target organ should be resected as soon as possible.The supplement of cortisol is not appropriate during the perioperative period.The unilateral adrenalectomy is an effective treatment for AIMAH.

ACTH-Independent Macronodular Adrenal Hyperplasia

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an uncommon cause of Cushing's syndrome (CS). The pathophysiology of this disorder is heterogeneous in its molecular origin and also in its clinical presentation. AIMAH can present mainly as an incidental radiological finding with sub-clinical CS or rarely with overt CS. In a few familial cases reported with AIMAH, specific aberrant G-protein coupled receptors were expressed in the adrenals of all affected members, but sporadic cases are more common. The aberrant adrenal function of G-protein coupled receptors can lead to cell proliferation and abnormal regulation of steroidogenesis. Unilateral or bilateral adrenalectomy has been the most frequently used treatment for this adrenal disorder; alternatively, the identification of aberrant receptors using in vivo protocol of investigation can offer specific pharmacological approach to control abnormal steroidogenesis and possibly prevent AIMAH progression.

Hiperplasia suprarrenal macronodular bilateral independiente de ACTH: caso clínico / ACTH independent bilateral macronodular adrenal hyperplasia: report of one case

ACTH Independent cushing syndrome, involving both adrenal glands, represents a minority of endogenous hyperadrenocorticisms and is caused by infrequent diseases. ACTH independent macronodular adrenal hyperplasia (AIMAH) is one of them and is caused by aberrant cortical adrenal receptors expression that are able to stimulate cortisol secretion. We report a 62 years old male, presenting with hypertension, weight gain, urinary lithiasis and osteopenia. The diagnosis of Cushing's syndrome was made with a morning cortisol level after 1 mg nocturnal dexamethasone of 8.2 ug/dL. Urinary free 24 hour cortisol levels were normal, circadian rhythm of cortisol was maintained and ACTH was <5 pg/mL. Abdominal magnetic resonance imaging showed bilateral nodular adrenal enlargement. The functional study, looking for abnormal receptors, showed a potent cortisol secretory response after stimulation with vasopressin.

Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

ACTH-Independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome (CS), in which clinical features usually become apparent only after several decades of life. This form of adrenal hyperplasia typically produces excess cortisol with overt or subclinical CS, but concurrent secretion of mineralocorticoids or sexual steroids can also occur. The diagnosis is suspected by bilateral adrenal nodules larger than 1 cm on incidental imaging studies or following the demonstration of ACTH-independent hormonal hypersecretion. The pathophysiology of this entity is heterogeneous and has been intensely explored in recent years. Several G-protein coupled receptors aberrantly expressed in the adrenal cortex have been implicated in the regulation of steroidogenesis and in the initial cell proliferation in AIMAH. Several familial cases of AIMAH have been recently described with the same pattern of aberrant hormone receptors in all affected members of the family. It is probable that additional somatic genetic events related to cell cycle regulation, adhesion and transcription factors occur in addition over time in the various nodules; other mechanisms, as Gsp or ACTH receptor mutations and paracrine adrenal hormonal secretion have been rarely identified as the molecular mechanism in some cases. When systematically screened, most patients with AIMAH exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. The identification of these receptors creates the possibility of a specific pharmacological treatment isolated or associated with adrenalectomy.

A hiperplasia adrenal macronodular independente de ACTH (AIMAH) é uma causa rara de síndrome de Cushing (SC) endógena, na qual alguns aspectos clínicos só se tornam evidentes depois de várias décadas de vida. Esta forma de hiperplasia adrenal caracteristicamente produz excesso de cortisol resultando na síndrome de Cushing franca ou subclínica, embora a secreção concomitante de mineralocorticóide, estrógeno e andrógenos também possa ocorrer. A suspeita diagnóstica é feita pela presença de nódulos adrenais bilaterais maiores que 1 cm, como achado incidental em exames de imagem ou pela demonstração de hipersecreção hormonal independente de ACTH. A fisiopatologia desta doença é heterogênea e tem sido intensamente estudada nos últimos anos. Vários receptores acoplados à proteína G, com expressão aberrante no córtex adrenal, têm sido implicados na regulação da esteroidogênese e no início da proliferação celular que ocorre na AIMAH. Diversos casos familiais de AIMAH foram recentemente descritos, e um mesmo padrão de expressão anormal dos receptores aberrantes foi observado em todos os membros afetados das famílias investigadas. Ao longo do tempo, é provável que ocorram, nos nódulos, eventos genéticos adicionais relacionados à regulação do ciclo celular, adesão e fatores de transcrição. Outros mecanismos moleculares, como mutações nos genes da proteína Gsa e do receptor de ACTH, ou secreção hormonal parácrina na adrenal, têm sido raramente identificados em alguns casos. A maioria dos pacientes com AIMAH, quando sistematicamente investigados, desenvolve uma produção anormal de cortisol em resposta a vários ligantes, sugerindo a presença de receptores adrenais aberrantes. A identificação destes receptores cria a possibilidade para um tratamento farmacológico específico isolado ou associado à adrenalectomia.

A Case of Bilateral Macronodular Adrenal Hyperplasia with Cushing's Syndrome Treated by Unilateral Adrenalectomy / 대한내분비학회지

In order to differentiate the causes of Cushing's syndrome; whether it is pituitary or adrenal-dependent, a high dose dexamethasone suppression test is usually performed but this does not always correlated with the imaging diagnosis. We report a case of bilateral macronodular adrenal hyperplasia, which was thought to be independent to adrenocorticotrophin (ACTH) stimulation. At first we thought it was pituitary-dependent Cushing's syndrome, due to its suppression by high dose dexamethasone. However, we found no abnormal findings on the brain sella magnetic resonance image (MRI). A significant finding, however, we found bilateral adrenal masses on the abdominal computed tomography (CT). We performed percutaneous selective adrenal venous sampling (PSAVS), and confirmed hypercortisolism of the left adrenal mass only. Therefore, we decided to remove the left adrenal gland to preserve the residual function of the right adrenal gland. After the left adrenalectomy, the patient became normotensive, and their buffalo hump disappeared, and her 24 hour urinary free cortisol level returned to normal.

A Case of AVP Dependent Bilateral Macronodular Adrenal Hyperplasia / 대한내분비학회지

Adrenocorticotropin (ACTH) independent bilateral macronodular adrenal hyperplasia (AIMAH) is a rare form of Cushing's syndrome, in which unique endocrinological, clinical and histopathological features have been described. In AIMAH, cortisol secretion is autonomous and independent of ACTH, thus plasma ACTH levels are persistently suppressed. Various etiological mechanisms have been proposed to explain the development of AIMAH, the development of aberrant adrenal sensitivity to gastric inhibitory polypeptide (GIP), vasopressin, beta-adrenergic receptor agonists or the presence of circulating adrenal stimulating immunoglobulins have been suggested. We report on a 46-year-old female who had Cushing's syndrome, due to AIMAH, with a positive response to vasopressin.