scholarly journals Bilateral Adrenal Hyperplasia: Pathogenesis and Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1397
Author(s):  
Benjamin Chevalier ◽  
Marie-Christine Vantyghem ◽  
Stéphanie Espiard
Keyword(s):  
Carney Complex ◽  
Current Data ◽  
Adrenal Hyperplasia ◽  
Systematic Screening ◽  
Unilateral Adrenalectomy ◽  
Paracrine Regulation ◽  
Causal Genes ◽  
Bilateral Adrenal Hyperplasia ◽  
Pka Pathway

Bilateral adrenal hyperplasia is a rare cause of Cushing’s syndrome. Micronodular adrenal hyperplasia, including the primary pigmented micronodular adrenal dysplasia (PPNAD) and the isolated micronodular adrenal hyperplasia (iMAD), can be distinguished from the primary bilateral macronodular adrenal hyperplasia (PBMAH) according to the size of the nodules. They both lead to overt or subclinical CS. In the latter case, PPNAD is usually diagnosed after a systematic screening in patients presenting with Carney complex, while for PBMAH, the diagnosis is often incidental on imaging. Identification of causal genes and genetic counseling also help in the diagnoses. This review discusses the last decades’ findings on genetic and molecular causes of bilateral adrenal hyperplasia, including the several mechanisms altering the PKA pathway, the recent discovery of ARMC5, and the role of the adrenal paracrine regulation. Finally, the treatment of bilateral adrenal hyperplasia will be discussed, focusing on current data on unilateral adrenalectomy.

Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia: Analysis of 71 Cases

2019 ◽  
Vol 128 (12) ◽  
pp. 827-834
Author(s):  
Mohammad Sheikh-Ahmad ◽  
Gabriel Dickstein ◽  
Ibrahim Matter ◽  
Carmela Shechner ◽  
Jacob Bejar ◽  
...  
Keyword(s):  
Medical Center ◽  
Urinary Free Cortisol ◽  
Adrenal Hyperplasia ◽  
Unilateral Adrenalectomy ◽  
Long Period ◽  
Pubmed Database ◽  
Free Cortisol ◽  
Adrenal Masses ◽  
Current Article

Abstract Objective Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by benign bilateral enlarged adrenal masses, causing Cushing’s syndrome (CS). The aim of the current article is to define the role of unilateral adrenalectomy (UA) in treating patients with CS related to PBMAH. Methods A PubMed database search was conducted to identify articles reporting UA to treat PBMAH. We also report cases of PBMAH from our medical center treated by UA. Results A total number of 71 cases of PBMAH (62 cases reported in the literature and 9 cases from our center) are presented. Most patients were women (73.2%) and most UA involved the left side (64.3%). In most cases, the resected gland was the larger one. Following UA, 94.4% of cases had remission of hypercortisolism. Recurrence rate of CS was 19.4% and hypoadrenalism occurred in 29.6%. After UA, when the size of the remained adrenal gland was equal or greater than 3.5 cm, CS persisted in 21.4% of cases, and recurrence occurred in 27.3% of cases (after 20±9.2 months). However, when the size of the remained gland was less than 3.5 cm, CS resolved in all cases and recurrence occurred in 21.2% of cases after a long period (65.6±52.1 months). High levels of urinary free cortisol (UFC) were not correlated with post-surgical CS recurrence or persistence. Conclusions UA leads to beneficial outcomes in patients with CS related to PBMAH, also in cases with pre-surgical elevated UFC or contralateral large gland.

scholarly journals MON-LB44 Cushing’s Syndrome and Illegal Receptors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Caroline Poku ◽  
Randa Sharag Eldin ◽  
Abubakr Hassab Elrasoul Babiker Mohamed ◽  
Sadiq Sobia
Keyword(s):  
Cushing’S Syndrome ◽  
Hormone Receptors ◽  
Age Distribution ◽  
Cushing's Syndrome ◽  
Endocrine Surgery ◽  
Adrenal Hyperplasia ◽  
Unilateral Adrenalectomy ◽  
Production Studies ◽  
Bilateral Adrenal Hyperplasia ◽  
Adrenal Masses

Abstract Case presentation: A 48-year-old female with HTN presented to the endocrinology clinic for the evaluation of incidental bilateral adrenal masses noted on chest CT for dyspnea workup. At the time of the presentation, she reported generalized fatigue, significant weight gain in the past year and shortness of breath. Her physical exam was remarkable for central obesity. Lab work showed elevated cortisol after 1 mg dexamethasone suppression test x 2 and elevated 24- hour urine cortisol. Plasma free metanephrine levels and aldosterone/ renin ratio were normal. MRI abdomen was done and showed bilateral adrenal masses (left: 5.6 cm, right: 3.2 cm). Patient was diagnosed with Cushing’s syndrome secondary to primary bilateral adrenal hyperplasia and was referred to endocrine surgery who recommended unilateral adrenalectomy. The decision was made to remove the larger left side adrenal mass. On post-operative day one her am cortisol decreased to 2.1 and she was started on hydrocortisone 20 mg in the morning and 10 mg in the evening. Discussion: Primary bilateral adrenal hyperplasia is a rare cause (< 2 %) of endogenous Cushing’s syndrome, usually occurs in a bimodal age distribution, in childhood and in the fifth- sixth decades. Presentation is variable with most patients having no symptoms or subclinical Cushing’s. The theory is the larger nodule size corelates with the higher cortisol production. Studies have shown between 60-70% of cases has aberrant ectopic hormone receptors which leads to increased cortisol production not only from ACTH but also from other ligands such as serotonin and vasopressin. Aberrant receptor testing examines whether cortisol or other steroid production increases in response to either physiologic or pharmacologic stimulus. Multiple genetic mutations have been associated, the most frequent is mutations in the Armadillo repeat- containing 5 gene identified in 2013. Treatment can either be medical or surgical. Medical therapy can be initiated if testing for an aberrant receptor is positive. In recent years there has been a trend towards doing unilateral adrenalectomy instead of bilateral, with initial remission of symptoms reported in about 84% of cases after unilateral adrenalectomy although there is a small risk of recurrence. Post operatively after unilateral adrenalectomy patients should be monitored for adrenal insufficiency. Our patient declined aberrant receptor testing and opted for surgery and is doing well post operatively. Conclusion: Primary bilateral adrenal hyperplasia is a rare cause of endogenous Cushing’s syndrome which can be treated either medically or surgically.

scholarly journals Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism

2020 ◽  
Vol 52 (06) ◽  
pp. 379-385
Author(s):  
Lucie S. Meyer ◽  
Siyuan Gong ◽  
Martin Reincke ◽  
Tracy Ann Williams
Keyword(s):  
Angiotensin Ii ◽  
Primary Aldosteronism ◽  
Functional Role ◽  
Adrenal Hyperplasia ◽  
Endocrine Hypertension ◽  
Bilateral Adrenal Hyperplasia ◽  
Aldosterone Producing Adenoma ◽  
Agonistic Autoantibodies

AbstractPrimary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA.

The Role of Unilateral Adrenalectomy in ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH)

2008 ◽  
Vol 32 (5) ◽  
pp. 882-889 ◽  
Author(s):  
Maurizio Iacobone ◽  
Nora Albiger ◽  
Carla Scaroni ◽  
Franco Mantero ◽  
Ambrogio Fassina ◽  
...  
Keyword(s):  
Adrenal Hyperplasia ◽  
Unilateral Adrenalectomy

scholarly journals Systemic Hormonal Unloading in Unilateral Adrenalectomy in a Patient with Bilateral Adrenal Hyperplasia: A Case Report

2019 ◽  
Vol 3 (1) ◽  
pp. 303-308
Author(s):  
Ma. Felisse Carmen Gomez ◽  
Florence Rochelle Gan ◽  
Erick Mendoza ◽  
Leilani B Mercado-Asis
Keyword(s):  
Case Report ◽  
Adrenal Hyperplasia ◽  
Unilateral Adrenalectomy ◽  
Bilateral Adrenal Hyperplasia

Three-Quarters Adrenalectomy for Infantile-Onset Cushing Syndrome due to Bilateral Adrenal Hyperplasia in McCune-Albright Syndrome

2017 ◽  
Vol 88 (3-4) ◽  
pp. 285-290 ◽  
Author(s):  
Tomoyo Itonaga ◽  
Hironori Goto ◽  
Manabu Toujigamori ◽  
Yasuharu Ohno ◽  
Seigo Korematsu ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Adrenal Crisis ◽  
Adrenal Hyperplasia ◽  
Unilateral Adrenalectomy ◽  
Mccune Albright Syndrome ◽  
Total Adrenalectomy ◽  
Bilateral Adrenal Hyperplasia ◽  
New Treatment ◽  
Albright Syndrome ◽  
Mccune Albright

Background: Bilateral adrenalectomy is performed in cases with infantile-onset Cushing syndrome due to bilateral adrenal hyperplasia in McCune-Albright syndrome (MAS) because severe Cushing syndrome with heart failure and liver dysfunction can have a lethal outcome. This procedure can completely ameliorate hypercortisolism, although lifetime steroid replacement therapy and steps to prevent adrenal crisis are necessary. Recently, the efficacy of unilateral adrenalectomy has been reported in adult cases of bilateral macronodular adrenal hyperplasia, but there is no consensus regarding the appropriate surgical treatment for bilateral adrenal hyperplasia in MAS. Objective: A 6-month-old girl presented with café-au-lait spots, short stature, central obesity, a moon face, and hypertension. Endocrinological tests and imaging studies led to the diagnosis of ACTH-independent Cushing syndrome due to bilateral adrenal hyperplasia induced by MAS. “Three-quarters adrenalectomy”, namely right-sided total adrenalectomy and left-sided half adrenalectomy, was carried out. An activating mutation of the GNAS1 gene (p.Arg201Cys) was identified in the adrenal tissues. Since the operation, our patient has been in a state of clinical remission for more than 2 years. Conclusion: Our original surgical intervention, three-quarters adrenalectomy, may be a new treatment option for Cushing syndrome associated with MAS.

scholarly journals Prkar1a gene knockout in the pancreas leads to neuroendocrine tumorigenesis

2017 ◽  
Vol 24 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Emmanouil Saloustros ◽  
Paraskevi Salpea ◽  
Matthew Starost ◽  
Sissi Liu ◽  
Fabio R Faucz ◽  
...  
Keyword(s):  
Immunohistochemical Staining ◽  
Gene Knockout ◽  
Suppressor Gene ◽  
Carney Complex ◽  
Null Alleles ◽  
Pancreatic Tumors ◽  
Overnight Fasting ◽  
Mouse Cells ◽  
Pka Pathway

Carney complex (CNC) is a rare disease associated with multiple neoplasias, including a predisposition to pancreatic tumors; it is caused most frequently by the inactivation of thePRKAR1Agene, a regulator of the cyclic AMP (cAMP)-dependent kinase (PKA). The method used was to create null alleles ofprkar1ain mouse cells expressingpdx1(Δ-Prkar1a). We found that these mice developed endocrine or mixed endocrine/acinar cell carcinomas with 100% penetrance by the age of 4–5 months. Malignant behavior of the tumors was seen as evidenced by stromal invasion and metastasis to locoregional lymph nodes. Histologically, most tumors exhibited an organoid pattern as seen in the islet-cell tumors. Biochemically, the lesions exhibited high PKA activity, as one would expect from deletingprkar1a. The primary neuroendocrine nature of these tumor cells was confirmed by immunohistochemical staining and electron microscopy, the latter revealing the characteristic granules. Although the Δ-Prkar1amice developed hypoglycemia after overnight fasting, insulin and glucagon levels in the plasma were normal. Negative immunohistochemical staining for the most commonly produced peptides (insulin, c-peptide, glucagon, gastrin and somatostatin) suggested that these tumors were non-functioning. We hypothesize that the recently identified multipotentpdx1+/insulin−cell in adult pancreas, gives rise to endocrine or mixed endocrine/acinar pancreatic malignancies with completeprkar1adeficiency. In conclusion, this mouse model supports the role ofprkar1aas a tumor suppressor gene in the pancreas and points to the PKA pathway as a possible therapeutic target for these lesions.

scholarly journals Clinical and genetic heterogeneity of micronodular adrenal hyperplasia

2021 ◽  
Vol 15 (1) ◽  
pp. 27-35
Author(s):  
A. Chevais ◽  
D. G. Beltsevich ◽  
A. Yu. Abrosimov ◽  
D. A. Derkatch ◽  
A. A. Lazareva
Keyword(s):  
Cushing Syndrome ◽  
Gene Mutations ◽  
Carney Complex ◽  
Clinical Aspects ◽  
Adrenal Hyperplasia ◽  
Unilateral Adrenalectomy ◽  
Pathogenic Variants ◽  
Familial Form ◽  
Genes Encoding ◽  
Genetically Determined

Micronodular adrenal hyperplasia is a rare cause of ACTH-independent Cushing syndrome. It can be divided into two entities: primary pigmented nodular adrenocortical disease (PPNAD) and non-pigmented micronodular adrenocortical disease, among which familial and sporadic forms are distinguished. The most common is the genetically determined familial form PPNAD, as one of the components of Carney complex. The vast majority of patients have identifiable pathogenic variants in the PRKAR1A gene. In addition to the PRKAR1A gene mutations, inactivating mutations in the genes encoding phosphodiesterases (PDE11A4 and PDE8B), as well as PRKACA gene amplification, have been described in individuals with isolated forms. Despite the relative antiquity of the description of micronodular adrenal hyperplasia and the Carney comlex, a detailed study of pathophysiological mechanisms, genetic and clinical aspects of this pathology, nowadays, clinicians continue to face «atypical» cases. Thus, the nature of this disease is not well understood and requires further research. This review presents the accumulated data on micronodular adrenal hyperplasia, genetics aspects, and also describes 2 unique clinical cases of isolated PPNAD with unilateral adrenalectomy results.

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