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Pituitary incidentaloma: a Pituitary Society international consensus guideline statement
Fleseriu, Maria; Gurnell, Mark; McCormack, Ann; Fukuoka, Hidenori; Glezer, Andrea; Langlois, Fabienne; Schwartz, Theodore H; Greenman, Yona; Agrawal, Nidhi; Akirov, Amit; Bancos, Irina; Capatina, Cristina; Castinetti, Frederic; Catalino, Michael; Christ-Crain, Mirjam; Das, Liza; Drincic, Andjela; Freda, Pamela U; Gadelha, Monica R; Giustina, Andrea; Hanzu, Felicia; Ho, Ken K Y; Isand, Kristina; Mallea-Gil, Susana; Mamelak, Adam N; Marcus, Hani J; Uygur, Meliha Melin; Molitch, Mark; Nachtigall, Lisa B; Nowak, Elisabeth; Pereira, Alberto M; Pineyro, Maria M; Shafiq, Ismat; Syro, Luis; Takahashi, Yutaka; Varlamov, Elena V; Vila, Greisa; Zada, Gabriel; Karavitaki, Niki; Melmed, Shlomo; ,
This Pituitary Society Consensus article presents an evidence-based consensus on the management of pituitary incidentaloma, defined as an unexpected sellar or parasellar finding incidentally discovered on an imaging study that was not performed for a clinically suspected pituitary lesion. Recommendations are offered for when endocrinology, neurosurgery and ophthalmology consultation, dedicated pituitary imaging, pituitary hormone testing and visual assessment are warranted for macroadenomas, microadenomas, cystic lesions and empty sella, as well as when surgical resection is indicated for incidental pituitary adenomas and cystic sellar lesions. Special considerations in patients with multiple endocrine neoplasia type 1, children and adolescents, older people, and pregnant women are addressed. The Consensus workshop concluded that diagnostic and management approaches should be individualized to the specific clinical context of an incidentally discovered pituitary lesion. Consultation with a multidisciplinary pituitary tumour centre of excellence should be considered in the presence of new or deteriorating lesion-specific signs or symptoms, particularly when surgical or other adjuvant interventions are being considered and when there is uncertainty about the most appropriate subsequent management.
PMID: 40555795
ISSN: 1759-5037
CID: 5886922
Enhanced detection of primary aldosteronism in hypertensive patients with obstructive sleep apnea using a novel diagnostic algorithm
Shah, Shruti N; Wright, Kyla; Suh, Insoo; Mahmoudi, Mandana; Agrawal, Nidhi
PURPOSE/OBJECTIVE:Primary aldosteronism (PA) is an underdiagnosed cause of secondary hypertension with significant health consequences. Expanding screening criteria may improve case detection and reduce the number of untreated patients. METHODS:We assessed PA screening rates in a cohort of 457 adults with comorbid obstructive sleep apnea (OSA) and hypertension (HTN). PA screening in a subset of the cohort (n = 97, 21%) was conducted using serum aldosterone, aldosterone-to-plasma renin activity ratio (ARR), and plasma renin activity (PRA). Screening results were compared between the 2016 Endocrine Society guidelines (serum aldosterone and ARR) and the Vaidya & Carey algorithm (serum aldosterone and PRA). RESULTS:The screened patients were predominantly male (mean age 58.6 years), with common comorbidities including hyperlipidemia (80%) and diabetes mellitus (31%). PA positivity rates differed significantly between screening criteria: 7% tested positive using Endocrine Society guidelines, while 33% screened positive using the Vaidya & Carey algorithm. Notably, 26% of patients with negative screens by Endocrine Society criteria were reclassified as positive, and 11 previously indeterminate cases were classified as negative due to absent renin suppression. Using the Vaidya & Carey algorithm with a stricter PRA suppression threshold, 25% of patients screened positive. CONCLUSION/CONCLUSIONS:The Vaidya & Carey algorithm may be an important tool in increasing detection of previously unidentified cases and clarifying the diagnosis of cases that were previously deemed indeterminate. Given the morbidity of untreated PA, more robust screening approaches are warranted. Prospective studies are needed to validate these findings across diverse populations.
PMID: 40526320
ISSN: 1559-0100
CID: 5870362
DNA methylation profiling of pituitary neuroendocrine tumors identifies distinct clinical and pathological subtypes based on epigenetic differentiation
Belakhoua, Sarra; Vasudevaraja, Varshini; Schroff, Chanel; Galbraith, Kristyn; Movahed-Ezazi, Misha; Serrano, Jonathan; Yang, Yiying; Orringer, Daniel; Golfinos, John G; Sen, Chandra; Pacione, Donato; Agrawal, Nidhi; Snuderl, Matija
BACKGROUND:Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neuroendocrine tumors. PitNETs can be challenging to classify, and current recommendations include a large immunohistochemical panel to differentiate among 14 WHO-recognized categories. METHODS:In this study, we analyzed clinical, immunohistochemical and DNA methylation data of 118 PitNETs to develop a clinico-molecular approach to classifying PitNETs and identify epigenetic classes. RESULTS:CNS DNA methylation classifier has an excellent performance in recognizing PitNETs and distinguishing the three lineages when the calibrated score is ≥0.3. Unsupervised DNA methylation analysis separated PitNETs into two major clusters. The first was composed of silent gonadotrophs, which form a biologically distinct group of PitNETs characterized by clinical silencing, weak hormonal expression on immunohistochemistry, and simple copy number profile. The second major cluster was composed of corticotrophs and Pit1 lineage PitNETs, which could be further classified using DNA methylation into distinct subclusters that corresponded to clinically functioning and silent tumors and are consistent with transcription factor expression. Analysis of promoter methylation patterns correlated with lineage for corticotrophs and Pit1 lineage subtypes. However, the gonadotrophic genes did not show a distinct promoter methylation pattern in gonadotroph tumors compared to other lineages. Promoter of the NR5A1 gene, which encodes SF1, was hypermethylated across all PitNETs clinical and molecular subtypes including gonadotrophs with strong SF1 protein expression indicating alternative epigenetic regulation. CONCLUSION/CONCLUSIONS:Our findings suggest that classification of PitNETs may benefit from DNA methylation for clinicopathological stratification.
PMID: 40295206
ISSN: 1523-5866
CID: 5833282
Cognitive decline in Cushing's syndrome: A systematic review
Katragadda, Anila; Kunadia, Jessica; Kirsch, Polly; Dorcely, Brenda; Shah, Shruti; Henig, Zachary; Job, Asha; Feelders, Richard A; Agrawal, Nidhi
The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.
PMID: 39506264
ISSN: 1365-2826
CID: 5778202
A case-based review of adult-onset craniopharyngioma [Case Report]
Meyer, Scott; Shah, Shruti N; Dancel-Manning, Kristen; Wang, Yuxiu; Young, Matthew; Agrawal, Nidhi
Craniopharyngiomas are histologically benign central nervous system tumors derived from embryonic epithelial cells of Rathke's pouch. The disease demonstrates a bimodal age distribution, occurring most often in patients 5-14 and 50-74 years of age. Common comorbidities include hypopituitarism, hypothalamic obesity, sleep apnea, visual impairment and neurocognitive disturbances. There are several key differences in the presentation, tumor characteristics and clinical outcomes between age groups. Childhood craniopharyngiomas are mostly adamantinomatous and often present as larger tumors with worse functional outcomes such as rates of obesity and neurological deficits. Adults experience similar but slightly adjusted rates of comorbidity with both the adamantinomatous and papillary subtypes. This review presents a case-based discussion of adult craniopharyngiomas, focusing on recent literature regarding their presentation, pathology and pathogenesis, diagnosis, treatment and long-term sequelae.
PMCID:12121368
PMID: 40444237
ISSN: 1664-2392
CID: 5854452
How to manage Cushing's disease after failed primary pituitary surgery
Agrawal, Nidhi; Urwyler, Sandrine A; Mehta, Sonal; Karavitaki, Niki; Feelders, Richard A
The first-line treatment for Cushing's disease is transsphenoidal adenomectomy, which can be curative in a significant number of patients. The second-line options in cases of failed primary pituitary surgery include repeat surgery, medical therapy, and radiation. The role for medical therapy has expanded in the last decade, and options include pituitary-targeting drugs, steroid synthesis inhibitors, and glucocorticoid receptor antagonists. Bilateral adrenalectomy is a more aggressive approach, which may be necessary in cases of persistent hypercortisolism despite surgery, medical treatment, or radiation or when rapid normalization of cortisol is needed. We review the available treatment options for Cushing's disease, focusing on the second-line treatment options to consider after failed primary pituitary surgery.
PMID: 39276376
ISSN: 1479-683x
CID: 5702682
Risk of intracranial meningioma in patients with acromegaly: a systematic review
Guo, Amy X; Job, Asha; Pacione, Donato; Agrawal, Nidhi
UNLABELLED:Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of insulin-like growth factor 1 (IGF-1) which leads to the insidious onset of clinical manifestations. The most common primary central nervous system (CNS) tumors, meningiomas originate from the arachnoid layer of the meninges and are typically benign and slow-growing. Meningiomas are over twice as common in women as in men, with age-adjusted incidence (per 100,000 individuals) of 10.66 and 4.75, respectively. Several reports describe co-occurrence of meningiomas and acromegaly. We aimed to determine whether patients with acromegaly are at elevated risk for meningioma. Investigation of the literature showed that co-occurrence of a pituitary adenoma and a meningioma is a rare phenomenon, and the majority of cases involve GH-secreting adenomas. To the best of our knowledge, a systematic review examining the association between meningiomas and elevated GH levels (due to GH-secreting adenomas in acromegaly or exposure to exogenous GH) has never been conducted. The nature of the observed coexistence between acromegaly and meningioma -whether it reflects causation or mere co-association -is unclear, as is the pathophysiologic etiology. SYSTEMATIC REVIEW REGISTRATION/UNASSIGNED:https://www.crd.york.ac.uk/prospero/, identifier CRD42022376998.
PMCID:11196394
PMID: 38919490
ISSN: 1664-2392
CID: 5702672
Health Care Disparities in Transsphenoidal Surgery for Pituitary Tumors: An Experience from Neighboring Urban Public and Private Hospitals
Gordon, Alex J; Dastagirzada, Yosef; Schlacter, Jamie; Mehta, Sonal; Agrawal, Nidhi; Golfinos, John G; Lebowitz, Richard; Pacione, Donato; Lieberman, Seth
PMCID:10581820
PMID: 37854536
ISSN: 2193-6331
CID: 5736132
The Current Status of Minimally Invasive Adrenalectomy for Aldosterone Producing Adenoma: Controversial Issues, and Realistic Expectations of Clinical Cure
Pachter, Hersch Leon; Arthurs, Likolani; Sant, Vivek; Underwood, Hunter; Kulkarni, Kopel; Parikh, Manish; Agrawal, Nidhi; Suh, Insoo; DiMaggio, Charles
ORIGINAL:0016978
ISSN: 2508-8149
CID: 5523542
Implementation of a formal sleep center-based screening protocol for primary aldosteronism in patients with obstructive sleep apnea
Wright, Kyla; Mahmoudi, Mandana; Agrawal, Nidhi; Simpson, Hope; Lui, Michael S; Pachter, H Leon; Patel, Kepal; Prescott, Jason; Suh, Insoo
BACKGROUND:There is a bidirectional association between primary aldosteronism and obstructive sleep apnea, with evidence suggesting that the treatment of primary aldosteronism can reduce obstructive sleep apnea severity. Current guidelines recommend screening for primary aldosteronism in patients with comorbid hypertension and obstructive sleep apnea, identifying potential candidates for treatment. However, emerging data suggest current screening practices are unsatisfactory. Moreover, data regarding the true incidence of primary aldosteronism among this population are limited. This study aimed to assess the primary aldosteronism screening rate among patients with obstructive sleep apnea and hypertension at our institution and estimate the prevalence of primary aldosteronism among this population. METHODS:Sleep studies conducted at our institution between January and September 2021 were retrospectively reviewed. Adult patients with a sleep study diagnostic of obstructive sleep apnea (respiratory disturbance index ≥5) and a diagnosis of hypertension were included. Patient medical records were reviewed and laboratory data of those with biochemical screening for primary aldosteronism were assessed by an experienced endocrinologist. Screening rates were compared before and after initiation of a screening protocol in accordance with the 2016 Endocrine Society guidelines. RESULTS:A total of 1,005 patients undergoing sleep studies were reviewed; 354 patients had comorbid obstructive sleep apnea and hypertension. Patients were predominantly male (67%), with a mean age of 58 years (standard deviation = 12.9) and mean body mass index of 34 (standard deviation = 8.1). The screening rate for primary aldosteronism among included patients was 19% (n = 67). The screening rate was significantly higher after initiation of a dedicated primary aldosteronism screening protocol (23% vs 12% prior; P = .01). Fourteen screens (21%) were positive for primary aldosteronism, whereas 45 (67%) were negative and 8 (12%) were indeterminate. Four had prior abdominal cross-sectional imaging, with 3 revealing an adrenal adenoma. Compared with patients without primary aldosteronism, patients with positive primary aldosteronism screens were more likely to have a history of hypokalemia (36% vs 4.4%; P = .002). The frequency of hyperlipidemia, diabetes mellitus, and left ventricular hypertrophy did not differ between patients with positive versus negative screens. CONCLUSION/CONCLUSIONS:Current screening practices for primary aldosteronism among patients with comorbid obstructive sleep apnea and hypertension are suboptimal. Patients evaluated at sleep centers may represent an optimal population for screening, as the prevalence of primary aldosteronism among this cohort appears high.
PMID: 36198493
ISSN: 1532-7361
CID: 5361722