ACTH-independent massive bilateral adrenal disease (AIMBAD): A subtype of Cushing's syndrome with major diagnostic and therapeutic implications

1994 ◽  
Vol 131 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Steven A Lieberman ◽  
T Ross Eccleshall ◽  
David Feldman
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Glands ◽  
Medical Center ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Bilateral Adrenalectomy ◽  
Preoperative Treatment ◽  
Therapeutic Implications ◽  
Adrenal Imaging ◽  
Adrenal Disease

Lieberman SA, Eccleshall TR, Feldman D. ACTH-independent massive bilateral adrenal disease (AIMBAD): a subtype of Cushing's syndrome with major diagnostic and therapeutic implications. Eur J Endocrinol 1994:131:67–73. ISSN 0804–4643 A 49-year-old man with classic manifestations of Cushing's syndrome had undetectable levels of ACTH, lack of suppression of hypercortisolism with dexamethasone in doses of 2, 8, or 16 mg per day, bilaterally enlarged adrenal glands on MRI, and bilateral adrenal uptake of iodocholesterol. Preoperative treatment with ketoconazole lowered blood pressure and serum cortisol and produced symptoms of steroid withdrawal. Bilateral adrenalectomy revealed massively enlarged adrenal glands (left: 199 g, right: 93 g). Sequencing of the gene encoding the stimulatory G protein, Gsα, did not show either of two activating mutations previously reported in patients with McCune–Albright syndrome or acromegaly. Twenty-three previous cases of Cushing's syndrome due to ACTH-independent massive bilateral adrenal disease (AIMBAD) have been reported. AIMBAD may cause confusion in the differential diagnosis of Cushing's syndrome as endocrine testing suggests a unilateral, ACTHindependent process while adrenal imaging demonstrates bilateral abnormalities. Bilateral adrenalectomy is curative and appears to carry little risk of Nelson's syndrome. The pathogenesis of AIMBAD appears to be heterogeneous, as recent reports have demonstrated GIP-mediated hypercortisolism and familial AIMBAD. Transition from Cushing's disease to ACTH-independence is not supported by the available data. Future cases of AIMBAD should be investigated carefully to further elucidate the pathogenesis of this disorder. David Feldman, Division of Endocrinology, Dept. of Medicine, Room S-005, Stanford University Medical Center, Stanford, CA 94305, USA

scholarly journals Primary Macronodular Adrenal Hyperplasia Associated With Autosomal Dominant ARMC5 Mutation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A154-A154
Author(s):  
Sarah Elizabeth Kerut ◽  
Angela Subauste
Keyword(s):  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Adrenal Glands ◽  
Autosomal Dominant ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Adrenal Hyperplasia ◽  
Urinary Cortisol ◽  
Adrenocortical Hyperplasia

Abstract Background: Primary macronodular adrenal hyperplasia (PMAH) is an uncommon cause of Cushing’s syndrome. In some cases, this is an inherited disorder due to a mutation in the armadillo repeat-containing 5 (ARMC5) gene. Clinical Case: A 43-year-old African American woman presented to clinic with weight gain, worsening type 2 diabetes mellitus, and symptomatic hypertensive cardiomyopathy. Physical exam was significant for central obesity, bilateral supraclavicular fat pads, acanthosis nigricans and wide striae over the abdomen. Her serum cortisol was 13.8 mcg/dL after 1 mg of dexamethasone (n<1.8 mcg/dL), urinary cortisol was 180 mcg in 24 hours (n=3.5–45 mcg/24h) and two midnight salivary cortisol tests were 227 and 118 ng/dL (n<100 ng/dL). Her ACTH was 2.4 pg/mL (n=7.2–63.3 pg/mL). Computed tomography (CT) of the abdomen showed nodularity, diffuse thickening and low-density (<10 Hounsfield units) of the bilateral adrenal glands. She underwent bilateral adrenalectomy for a diagnosis of PMAH. Pathology showed nodular adrenocortical hyperplasia; the right and left adrenal glands measured 75 grams and 68 grams, respectively. She was started on hydrocortisone and fludrocortisone postoperatively. Over the following two years, she had a 68-pound weight loss, an 86% reduction in her daily insulin requirement and a 10% improvement in her left ventricular ejection fraction. Approximately two years later, the patient’s brother was referred for bilateral macronodular hyperplasia incidentally discovered on a CT of the abdomen. He had a history of hypertension and type 2 diabetes mellitus with cushingoid features on exam. His serum cortisol was 20.7 mcg/dL after 1 mg of dexamethasone, urinary cortisol was 65.1 mcg in 24 hours, two midnight salivary cortisol tests were 232 and 404 ng/dL and ACTH was 2.0 pg/mL. Upon obtaining further family history, the patients reported clinical features of Cushing’s syndrome in their paternal grandmother but denied features in either parent. The second patient had genetic testing which showed a mutation in the ARMC5 gene, c.1777C>T, p.R593W, a mutation previously described. Due to clinical signs of Cushing’s syndrome, he underwent bilateral adrenalectomy in which pathology showed right and left nodular adrenocortical hyperplasia measuring 110 and 73 grams, respectively. He is doing well postoperatively. The patients recently reported their aunt was diagnosed with PMAH and mild Cushing’s syndrome. She had a unilateral adrenalectomy of the larger adrenal gland and is doing well postoperatively. Conclusion: In some cases, Cushing’s syndrome is an inherited disorder. Autosomal dominant mutations in the ARMC5 gene are occasionally seen in PMAH, which causes less than 2% of endogenous Cushing’s syndrome. For all patients diagnosed with PMAH, clinicians should consider screening their family members with a dexamethasone suppression test.

scholarly journals SUN-390 A Rare Case of Bilateral Macronodular Adrenal Hyperplasia Discovered Incidentally

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Carlos Penaherrera ◽  
Remy Mimms ◽  
Amruta Pandit ◽  
Ahmed Mohammed ◽  
Shashi Raja ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Glands ◽  
Epigastric Pain ◽  
Cushing's Syndrome ◽  
Bilateral Adrenalectomy ◽  
Shortness Of Breath ◽  
Laboratory Studies ◽  
Adrenal Hyperplasia ◽  
Imaging Characteristics ◽  
Suppression Test

Abstract Introduction: Asymptomatic adrenal masses are often discovered incidentally while testing for unrelated conditions. A very uncommon finding is thickening and increased nodularity of both adrenal glands, which can lead to the patient being diagnosed with subclinical Cushing's syndrome, Conn's syndrome, or both. Case presentation: A 45-year-old African-American man presented to the hospital with a one-month history of increased abdominal girth, bilateral lower extremity edema and shortness of breath, with progressive epigastric abdominal pain which prompted admission. His medical history was relevant for obesity, coronary artery disease and heart failure with reduced ejection fraction. On examination he had a blood pressure of 152/99 mmHg, was diaphoretic, and complained of constant epigastric pain. Multiple purple and pale striae were visible along his abdomen, and he had pitting edema in both lower extremities. His initial laboratory studies showed a potassium of 2.6 mEq/L. A CT scan of the abdomen was relevant for bilaterally enlarged and tortuous adrenal glands, which the patient had no previous knowledge of. Diuresis greatly improved his edema and shortness of breath. Additional laboratory tests showed persistent hypokalemia, normal plasma renin activity and aldosterone, elevated fasting cortisol, normal metanephrines in 24-hour urine collection, and low ACTH level. A suppression test done by administering dexamethasone 0.5 mg every 6 hours for 2 days, was able to suppress the elevated cortisol levels. He was started on spironolactone, and underwent MRI of the abdomen, which confirmed bilateral multinodular adrenal hyperplasia with no imaging characteristics of pheochromocytoma. The patient was discharged home once his clinical status improved. Laboratory studies done at follow-up appointments showed persistently elevated cortisol, normal aldosterone to renin ratio, normal levels of plasma metanephrines and suppressed levels of ACTH. He was also referred to surgery for eventual bilateral adrenalectomy. Discussion: Primary bilateral macronodular adrenal hyperplasia (BMAH) is a very rare cause of endogenous Cushing's syndrome, representing less than 2% of cases. It is characterized by enlarged adrenal glands containing pigmented nodules that secrete excess cortisol and/or aldosterone (1). BMAH is often an incidental finding in patients with subclinical hyper-cortisolism. A low level of plasma ACTH along with bilaterally enlarged adrenal glands on imaging suggest the diagnosis, and this is confirmed with a dexamethasone suppression test. Accurate detection is important for guiding management, which includes pharmacological therapy and bilateral adrenalectomy. Reference: 1. De Venanzi A, Alencar GA, Bourdeau I, Fragoso MCBV, Lacroix A. Primary bilateral macronodular adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes. 2014 Jun;21(3):177-84.

Investigation of atrophic adrenal glands in Cushing's syndrome model rats induced by the administration of dexamethasone

2017 ◽  
Author(s):  
Toshiro Seki ◽  
Atsushi Yasuda ◽  
Natsumi Kitajima ◽  
Masami Seki ◽  
Masayuki Oki ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Glands ◽  
Cushing's Syndrome

Stress-induced Cushing's syndrome in fur-chewing chinchillas

2002 ◽  
Vol 50 (2) ◽  
pp. 133-142 ◽  
Author(s):  
Marina Tišljar ◽  
D. Janić ◽  
Ž. Grabarević ◽  
Keyword(s):  
Cushing’S Syndrome ◽  
Sebaceous Gland ◽  
Adrenal Glands ◽  
Clinical Symptoms ◽  
Cushing's Syndrome ◽  
Calcium Salts ◽  
Epidermal Atrophy ◽  
Gland Atrophy

One of the most serious problems in the chinchilla industry is 'fur-chewing', when the chinchilla bites off areas of its own or some other animal's fur. The condition generally develops in both genders at the age of 6-8 months. In chinchilla farms in Croatia an incidence of 15-20% has been observed. A pathomorphological, microbiological and parasitological investigation was conducted on eleven 6- to 11-month-old chinchillas of both sexes with clinical symptoms of 'fur-chewing' and three chinchillas without such signs. Histopathology of the adrenal glands and of the chewed skin revealed changes typical of Cushing's syndrome in 'fur-chewed' chinchillas, such as hyperkeratinisation of the epidermis, epidermal atrophy, pronounced follicular and sebaceous gland atrophy, hyperkeratinisation of the follicles with comedo formations and the presence of calcium salts in subcutis.

scholarly journals Efficacy of pasireotide in controlling severe hypercortisolism until cardiac transplantation

2017 ◽  
Vol 2017 ◽  
Author(s):  
Roberto Attanasio ◽  
Liana Cortesi ◽  
Daniela Gianola ◽  
Claudia Vettori ◽  
Fulvio Sileo ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Cushing’S Syndrome ◽  
Cardiac Transplantation ◽  
Serum Cortisol ◽  
Primary Treatment ◽  
Cushing's Syndrome ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment ◽  
Undergo Heart Transplantation

Summary Cushing’s syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function. Physical examination showed severely impaired general status, signs of hypercortisolism and multiple vertebral compression fractures. We administered teriparatide, and the few evaluable parameters supported the diagnosis of ACTH-dependent hypercortisolism: serum cortisol was 24.2 µg/dL in the morning and 20.3 µg/dL after overnight 1 mg dexamethasone, urinary free cortisol (UFC) was 258 µg/24 h and ACTH 125 pg/mL. Pituitary CT was negative. Pasireotide 300 µg bid was administered and uptitrated to 600 µg bid. Treatment was well tolerated, achieving dramatic improvement of clinical picture with progressive normalization of serum cortisol and ACTH levels as well as UFC. After 4 months, the patient underwent successful heart transplantation. Many complications ensued and were overcome. Pituitary MRI was negative. On pasireotide 300 µg bid and prednisone 2.5 mg/day (as part of immunosuppressive therapy), morning serum cortisol and ACTH were 15.6 µg/dL and 54 pg/mL respectively, UFC was 37 µg/24 h, fasting glucose: 107 mg/dL and HbA1c: 6.5%. In conclusion, primary treatment with pasireotide achieved remission of hypercortisolism, thus allowing the patient to undergo heart transplantation. Learning points: Untreated Cushing’s syndrome is associated with ominous prognosis. First-line treatment is surgery (at pituitary or adrenal, according to disease localization). A few drugs are available to treat hypercortisolism. Pasireotide is a multi-ligand somatostatin analog approved for treatment of hypercortisolism. Primary treatment with pasireotide was effective in a patient with severe Cushing’s syndrome, allowing him to undergo heart transplantation.

Serum cortisol concentrations during low dose dexamethasone suppression test to screen for Cushing's syndrome

BMJ ◽  
1985 ◽  
Vol 290 (6462) ◽  
pp. 158-159
Author(s):  
L. Kennedy ◽  
D. Hadden ◽  
B. Atkinson ◽  
B Sheridan ◽  
H. Johnston
Keyword(s):  
Cushing’S Syndrome ◽  
Low Dose ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Dexamethasone Suppression Test ◽  
Suppression Test ◽  
Dexamethasone Suppression

STUDIES ON THE IN VITRO PRODUCTION OF CORTICOSTEROIDS BY ADRENAL GLANDS FROM NORMOTENSIVE INDIVIDUALS AND HYPERTENSIVE PATIENTS

1962 ◽  
Vol 40 (1) ◽  
pp. 285-301 ◽  
Author(s):  
Jean Davignon ◽  
Erich Koiw ◽  
Wojciech Nowaczynski ◽  
Gilles Tremblay ◽  
Jacques Genest
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Glands ◽  
Cushing's Syndrome ◽  
The Other ◽  
Malignant Hypertension ◽  
Unit Weight ◽  
Chromatographic Technique ◽  
Acth Stimulation ◽  
The Mean

The production of aldosterone and other corticosteroids by adrenal glands surgically removed from 5 normotensive subjects with renal disease of various types, 11 patients with arterial hypertension, and 2 with Cushing's syndrome was investigated in vitro by the incubation chromatographic technique. The rate of steroid formation per unit weight of tissue was markedly lower in severe and malignant hypertension and slightly higher in benign hypertension as compared with the rate in normotensive controls. The amount of steroid released varied widely from one gland to the other and showed marked overlapping between the various groups; these variations were most prominent in benign hypertension, less in the normotensive group, and least evident in severe and malignant hypertension. The response of steroidogenesis to ACTH stimulation in vitro was slightly reduced in severe and malignant hypertension. The mean output of aldosterone by adrenal glands from hypertensives was slightly above the mean value obtained with normotensive control glands. The percentage of aldosterone formation in respect to total steroid production was roughly correlated with the severity of hypertension. In four hyperplastic adrenals obtained from two cases of Cushing's syndrome, the in vitro formation of steroids per unit weight of tissue and the response to ACTH did not differ significantly from that found in glands obtained from the other patients under study. The value of in vitro studies for the assessment of the functional capacity of the adrenal cortex is discussed.

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