Opioid-induced adrenal insufficiency: diagnostic and management considerations.

The dramatic rise in opioid use over the last two decades has led to a surge in their harmful health effects. Lesser known among clinicians is the impact of opioids on the endocrine system, especially with regard to cortisol. Opioids can suppress the hypothalamus-pituitary-adrenal (HPA) axis and may result in clinically significant adrenal insufficiency, especially in those treated at higher doses and for a longer time.

Exploring the role of the tumor microenvironment in refractory pituitary tumor pathogenesis.

Purpose: Treatment-refractory pituitary tumors demonstrate characteristics resembling those of highly aggressive tumors, in which the local tumor microenvironment (TME) plays a dominant role in promoting aggressiveness and refractoriness. However, role of the TME in pituitary tumors is not well studied.

Methods: Literature on the TME and development of refractory pituitary tumors was reviewed RESULTS: TME harbors tumorigenic immune cells, cancer-associated fibroblasts (CAF), extracellular matrix, and other factors that have been shown to affect behavior of tumor tissue.

Fluid Restriction Reduces Delayed Hyponatremia and Hospital Readmissions After Transsphenoidal Surgery.

Context: Postoperative hyponatremia leads to prolonged hospital length of stay and readmission within 30 days.

Objective: To assess 3 strategies for reducing rates of postoperative hyponatremia and analyze risk factors for hyponatremia.

Design: Two retrospective analyses and 1 prospective study.

Adrenal Cushing's Syndrome Treated With Preoperative Osilodrostat and Adrenalectomy.

Background/objective: Reducing severity of Cushing's syndrome caused by an adrenal adenoma (adrenal Cushing's syndrome [ACS]) might decrease morbidity and mortality risk in adrenalectomy. We used off-label osilodrostat, approved in the United States for pituitary Cushing's disease, to reduce cortisol levels and disease severity before adrenalectomy 3 weeks later.

Case Report: A 48-year-old woman with a 6-year history of obesity, depression, and anxiety and 3-year history of diabetes and hypertension was admitted with vomiting and lumbar back pain.

Treatment of Cushing Disease With Pituitary-Targeting Seliciclib.

Context: Preclinical studies show seliciclib (R-roscovitine) suppresses neoplastic corticotroph proliferation and pituitary adrenocorticotrophic hormone (ACTH) production.

Objective: To evaluate seliciclib as an effective pituitary-targeting treatment for patients with Cushing disease (CD).

Methods: Two prospective, open-label, phase 2 trials, conducted at a tertiary referral pituitary center, included adult patients with de novo, persistent, or recurrent CD who received oral seliciclib 400 mg twice daily for 4 consecutive days each week for 4 weeks.

Operative approach and case volume are associated with negative resection margins for adrenocortical carcinoma.

Background: Surgical resection with negative margins is the treatment of choice for adrenocortical carcinoma (ACC). This study was undertaken to determine factors associated with negative resection margins.

Methods: National Cancer Database was queried from 2010 to 2016 to identify patients with AJCC/ENSAT Stage I-III ACC who underwent adrenalectomy.

Opioids and pituitary function: expert opinion.

Purpose: Opioids are highly addictive potent analgesics and anti-allodynics whose use has dramatically increased in recent decades. The precipitous rise in opioid dependency and opioid use disorder is an important public health challenge given the risks for severely adverse health outcomes. The long-term opioid impact on hypothalamic-pituitary axes is particularly underappreciated among both endocrinologists and primary care physicians.

Local non-pituitary growth hormone is induced with aging and facilitates epithelial damage.

Microenvironmental factors modulating age-related DNA damage are unclear. Non-pituitary growth hormone (npGH) is induced in human colon, non-transformed human colon cells, and fibroblasts, and in 3-dimensional intestinal organoids with age-associated DNA damage. Autocrine/paracrine npGH suppresses p53 and attenuates DNA damage response (DDR) by inducing TRIM29 and reducing ATM phosphorylation, leading to reduced DNA repair and DNA damage accumulation.

Adrenocortical Carcinoma: The Value of Lymphadenectomy.

Background: Adrenocortical carcinoma (ACC) staging does not account for the number of positive nodes. The prognostic value of quantitative metastatic nodal burden is unknown.

Methods: The National Cancer Database was retrospectively queried from 2004-2016 to identify patients with Stage I-III ACC undergoing adrenalectomy.

Consensus on diagnosis and management of Cushing's disease: a guideline update.

Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants.

Pheochromocytoma Crisis Presenting With ARDS Successfully Treated With ECMO-Assisted Adrenalectomy.

Objective: Pheochromocytoma (PCC) crisis caused by acute catecholamine release from an adrenal PCC or extra-adrenal paraganglioma can be difficult to diagnose and may require an unconventional management strategy to achieve good outcomes. We describe a case of PCC crisis presenting with acute respiratory distress syndrome (ARDS) that resolved with stabilization on veno-venous (VV) extracorporeal membrane oxygenation (ECMO) during adrenalectomy.

Case Description: A 30-year-old man with a history of severe alcohol use disorder and a prior hospital admission for alcohol withdrawal syndrome presented with sudden-onset hemoptysis, altered mental status, and severe dyspnea that rapidly deteriorated to ARDS requiring ECMO support.

Factors Associated with Non-Operative Management of Resectable Adrenocortical Carcinoma.

Introduction: Surgery is the initial treatment of choice for patients with resectable adrenocortical carcinoma (ACC). We sought to determine factors associated with non-operative management of resectable ACC.

Methods: 2004-2016 National Cancer Database (NCDB) was queried to identify patients with AJCC/ENSAT Stage I-III ACC.

Insulin-like Growth Factor 1 and Prolactin Levels in Chimpanzees (Pan troglodytes) Across the Lifespan.

As human and chimpanzee genomes show high homology for and , we analyzed the sera of 367 healthy chimpanzees obtained during routine physical examinations in a single colony and measured chimpanzee insulin-like growth factor (IGF)-1 and prolactin (PRL) levels across the lifespan using standard human immunoassays. Assuming chimpanzee IGF-1 levels peak during puberty as in humans, we randomly defined puberty as the age at which most IGF-1 levels were equal to or above the 90 percentile for each sex (males, ages ≥7.00 but <9.

Two Distinctive POMC Promoters Modify Gene Expression in Cushing Disease.

Context: Mechanisms underlying pituitary corticotroph adenoma adrenocorticotropin (ACTH) production are poorly understood, yet circulating ACTH levels closely correlate with adenoma phenotype and clinical outcomes.

Objective: We characterized the 5' ends of proopiomelanocortin (POMC) gene transcripts, which encode the precursor polypeptide for ACTH, in order to investigate additional regulatory mechanisms of POMC gene transcription and ACTH production.

Methods: We examined 11 normal human pituitary tissues, 32 ACTH-secreting tumors, as well as 6 silent corticotroph adenomas (SCAs) that immunostain for but do not secrete ACTH.

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches.

DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas.

Drivers of sporadic benign pituitary adenoma growth are largely unknown. Whole-exome sequencing of 159 prospectively resected pituitary adenomas showed that somatic copy number alteration (SCNA) rather than mutation is a hallmark of hormone-secreting adenomas and that SCNAs correlate with adenoma phenotype. Using single-gene SCNA pathway analysis, we observed that both cAMP and Fanconi anemia DNA damage repair pathways were affected by SCNAs in growth hormone-secreting (GH-secreting) somatotroph adenomas.

Excess growth hormone suppresses DNA damage repair in epithelial cells.

Growth hormone (GH) decreases with age, and GH therapy has been advocated by some to sustain lean muscle mass and vigor in aging patients and advocated by athletes to enhance performance. Environmental insults and aging lead to DNA damage, which - if unrepaired - results in chromosomal instability and tumorigenesis. We show that GH suppresses epithelial DNA damage repair and blocks ataxia telangiectasia mutated (ATM) kinase autophosphorylation with decreased activity.

Somatostatin receptor subtype 5 modifies hypothalamic-pituitary-adrenal axis stress function.

Pituitary corticotroph somatostatin receptor subtype 5 (SSTR5) signals to inhibit adrenocorticotrophin (ACTH) secretion. As ACTH deficiency results in attenuated adrenal cortisol production and an impaired stress response, we sought to clarify the role of SSTR5 in modifying the hypothalamic/pituitary/adrenal (HPA) axis. We generated Tg HP5 mice overexpressing SSTR5 in pituitary corticotrophs that produce the ACTH precursor proopiomelanocortin (POMC).

Silent corticotroph adenomas.

Purpose: Silent corticotroph adenomas (SCAs) present clinically as non-functioning adenomas (NFAs) but are immunopositive for adrenocorticotrophic hormone (ACTH) without biochemical and clinical manifestation of hypercortisolism. Pathologic examination of resected NFAs that demonstrate positive ACTH and/or TPIT expression confirms its corticotroph lineage. SCAs comprise up to 20% of NFAs and exhibit a higher rate of recurrence.

Consensus-driven in-hospital cortisol assessment after ACTH-secreting pituitary adenoma resection.

Purpose: Remission from Cushing disease (CD) after pituitary adenoma resection may be predicted by a postoperative reduction in serum cortisol level. A 2008 consensus statement recommends assessing morning cortisol levels during the first postoperative week, and replacing glucocorticoid (GC) if cortisol nadir of < 2 or < 5 µg/dL is achieved. We sought to evaluate adherence to consensus recommendations following adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma resection at our tertiary medical center, and assess time to cortisol nadir to better define the window for assessment and intervention.