Osilodrostat: A Review of Recent Clinical Studies and Practical Recommendations for its Use in the Treatment of Cushing Disease

ObjectiveCushing disease (CD) is characterized by chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. Surgery remains the first-line treatment option; however, medical therapy is essential if surgery is contraindicated or fails to achieve remission or when recurrence occurs after surgical remission. Osilodrostat (Isturisa), a novel steroidogenic inhibitor, is now approved for the treatment of CD in the United States and Cushing syndrome in Europe. Herein, we review pharmacology and data on the efficacy, safety, and clinical use of osilodrostat and provide guidance on its use in treating patients with CD.MethodsWe reviewed the literature and published clinical trial data of osilodrostat use in patients with Cushing syndrome. Detailed information related to the clinical assessment of osilodrostat use, potential drug-to-drug interactions, drug initiation, dose titration, and the monitoring of drug tolerability were discussed.ResultsClinical trial data demonstrated that osilodrostat, by virtue of inhibiting 11-β hydroxylase, potently and rapidly decreased the 24-hour urinary free cortisol levels and sustained these reductions, with improved glycemia, blood pressure, body weight, and quality of life as well as lessened depression. Osilodrostat may interact with certain drugs, resulting in QT prolongation, which requires careful assessment of concomitant medications and periodic monitoring using electrocardiogram, respectively. The common adverse effects include adrenal insufficiency, hypokalemia, edema, and hyperandrogenic symptoms, which can be minimized using a slower up-titration dosing regimen.ConclusionOsilodrostat is an effective, new treatment option for CD, with positive effects on cardiovascular and quality of life parameters as well as tolerable adverse effects. This article provides a review of the pharmacology of osilodrostat and offers practical recommendations on the use of osilodrostat to treat CD.     

American Association of Clinical Endocrinology Disease State Clinical Review: Evaluation and Management of Immune Checkpoint Inhibitor-Mediated Endocrinopathies: A Practical Case-Based Clinical Approach

ObjectiveThe aim of this case-based clinical review was to provide a practical approach for clinicians regarding the management of patients with immune checkpoint inhibitor (ICI)-mediated endocrinopathies.MethodsA literature search of PubMed, Embase, and Scopus was conducted using appropriate keywords. The discussions and strategies for the diagnosis and management of ICI-mediated endocrinopathies are based on evidence available from prospective, randomized clinical studies; cohort studies; cross-sectional studies; case-based studies; and an expert consensus.ResultsImmunotherapy with ICIs has transformed the treatment landscape of diverse types of cancers but frequently results in immune-mediated endocrinopathies that can cause acute and persistent morbidity and, rarely, death. The patterns of endocrinopathies differ between the inhibitors of the cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 or programmed cell death protein 1 ligand pathways but most often involve the thyroid and pituitary glands. The less common but important presentations include insulin-deficient diabetes mellitus, primary adrenal insufficiency, primary hypoparathyroidism, central diabetes insipidus, primary hypogonadism, and pancreatitis, with or without subsequent progression to diabetes mellitus or exocrine insufficiency.ConclusionIn recent years, with increasing numbers of patients with cancer being treated with ICIs, more clinicians in a variety of specialties have been called upon to diagnose and treat ICI-mediated endocrinopathies. Herein, we reviewed case scenarios of various clinical manifestations and emphasized the need for a high index of clinical suspicion by all clinicians caring for these patients, including endocrinologists, oncologists, primary care providers, and emergency department physicians. We also provided diagnostic and therapeutic approaches for ICI-induced endocrinopathies and proposed that patients on ICI therapy be evaluated and treated by a multidisciplinary team in collaboration with endocrinologists.     

Hypophysitis

ObjectiveHypophysitis is considered a rare inflammatory disease of the pituitary gland. For a long time, primary autoimmune hypophysitis has stood out as the most relevant type of hypophysitis. However, with the advent of immunotherapy for the treatment of malignancies and identification of hypophysitis as an immune-related adverse event, hypophysitis has garnered increasing interest and recognition. Therefore, awareness, early recognition, and appropriate management are becoming important as the indication for immunomodulatory therapies broaden.MethodsIn this review, we discuss the epidemiology, diagnosis, and treatment of hypophysitis with a focus on recent data and highlight subtypes of particular interest while recognizing the gaps in knowledge that remain.ResultsRegardless of cause, symptoms and signs of hypophysitis may be related to mass effect (headache and visual disturbance) and hormonal disruption that warrant prompt evaluation. In the vast majority of cases, a diagnosis of hypophysitis can be made presumptively in the appropriate clinical context with radiologic findings consistent with hypophysitis and after the exclusion of other causes.ConclusionAlthough subtle differences currently exist in management and outcome expectations between primary and secondary causes of hypophysitis, universally, treatment is aimed at symptom management and hormonal replacement therapy.     

Immune Checkpoint Inhibitor-Induced Adrenalitis and Primary Adrenal Insufficiency: Systematic Review and Optimal Management

ObjectiveImmune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte antigen 4 or programmed death 1 and its ligand (programmed death ligand 1) have been approved for the treatment of a variety of cancers. However, ICI therapy is associated with a risk of immune-related adverse events. In this study, we reviewed reported cases of adrenalitis and primary adrenal insufficiency (PAI)—rare but lethal endocrine immune-related adverse events—in patients who underwent ICI therapy.MethodsWe searched multiple databases (PubMed, Web of Science, Cochrane, and Scopus) up to February 2020 for case reports on adrenalitis and PAI caused by ICIs.ResultsWe identified 15 case reports on ICI-induced adrenalitis and PAI and reviewed their clinical presentation, characteristics, immunologic and imaging features, and treatment. We also developed a screening strategy for PAI in patients treated with ICIs.ConclusionGiven the morbidity and mortality associated with acute adrenal crisis, physicians—especially endocrinologists and oncologists—should be aware of this particular risk. PAI caused by autoimmune adrenalitis predominantly occurs in patients treated with programmed death 1 inhibitor monotherapy. PAI often coexists with other endocrinopathies and requires mineralocorticoid as well as glucocorticoid replacement. Even after withdrawal of ICIs, PAI can persist and requires lifelong replacement therapy.     

Overt and Subclinical Adrenal Insufficiency in Pulmonary Tuberculosis

BackgroundTuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency.MethodsThis cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required.ResultsEighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (μg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease.ConclusionThe prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.     

Severe Obesity Associated With Pituitary Corticotroph Hyperplasia and Neoplasia

ObjectiveTo investigate the incidence of corticotroph hyperplasia (CH) or lymphocyte infiltration in the pituitary of patients with obesity.MethodsThe pituitary and adrenal glands from 161 adult autopsies performed between 2010 and 2019 at our institution were reviewed. The clinical history, body mass index (BMI), and cause of death were recorded. Routine hematoxylin and eosin staining, reticulin staining, and immunohistochemical staining for adrenocorticotropic hormone, CD3, and CD20 were performed. The results were analyzed using the Fisher and chi-square statistics. Decedents were separated into 4 groups based on BMI (kg/m²): (1) lean (BMI, <25.0), (2) overweight (BMI, 25.0-29.9), (3) obesity class I (BMI, 30.0-34.9), and (4) obesity classes II to III (BMI, >34.9).ResultsCH/neoplasia was identified in 44 of 161 pituitary glands. Four (9.1%) of 53 lean patients had pituitary lesions, whereas 27.3% (12) of overweight, 22.7% (10) of obesity class I, and 40.9% (18) of obesity class II patients had hyperplasia (P < .0001). Small corticotroph tumors were identified in 15 patients; only 1 was a lean patient, and the tumor was associated with the Crooke hyaline change of nontumorous corticotrophs. The presence of CH and neoplasia was associated with adrenal cortical hyperplasia and lipid depletion. Microscopic foci of T and B lymphocytes were identified in the pituitaries of patients in each weight category; no independent association between BMI and lymphocyte inflammation was found.ConclusionOur data indicate an association between CH/neoplasia and obesity. It remains unclear whether obesity is the cause or effect of adrenocorticotropic hormone and cortisol excess.     

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence

ObjectiveCOVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19.MethodsWe performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19.ResultsCOVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted.ConclusionThe recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.     

PD-L1 Expression in Normal Endocrine Tissues Is Not Increased Despite High Incidence of PD-1 Inhibitor-Associated Endocrinopathies

ObjectiveTreatment with immune-checkpoint inhibitors often results in endocrine immune-related adverse events (irAEs), affecting the pituitary, thyroid, adrenal, and parathyroid glands and pancreas. The mechanism underlying the endocrine irAEs has not been fully elucidated, and it remains unclear why endocrine organs are so commonly affected. In the present study, we evaluated immunostaining patterns of programmed death-ligand 1 (PD-L1) in normal endocrine tissues to determine whether increased expression may explain the predilection of endocrinopathies in patients treated with programmed cell death-1 inhibitors.MethodsNormal formalin-fixed paraffin-embedded endocrine tissues (pituitary, thyroid, adrenal, pancreas, and parathyroid) were collected from our hospital’s pathology tissue archive. The tissues were assessed for membranous and cytoplasmic PD-L1 immunostaining using the Dako 22C3 pharmDx assay on an automated staining platform.ResultsWe examined 49 endocrine tissues, including 12 thyroid, 5 pancreatic, 17 adrenal, 5 parathyroid, and 10 pituitary samples. Samples with less than 1% membranous PD-L1–positive cells were considered negative, while those with more than 1% of PD-L1 membranous staining were considered positive. Immunostaining result of immune-related cells was also evaluated, considering the cytoplasmic PD-L1–positive cells with the same cutoff of 1%. None of the endocrine tissues demonstrated PD-L1 positivity higher than 1% in the relevant cells.ConclusionWhile our results do not suggest a role of PD-L1 expression in the pathogenesis of endocrine irAEs, they may serve as a basis for future studies further investigating the mechanisms of autoimmune, inflammatory, or malignant endocrine conditions.     

Personalized Treatment of Patients With Primary Aldosteronism

Primary aldosteronism (PA) is a highly prevalent yet underdiagnosed secondary cause of hypertension. PA is associated with increased cardiovascular and renal morbidity compared with patients with primary hypertension. Thus, prompt identification and targeted therapy of PA are essential to reduce cardiovascular and renal morbidity and mortality in a large population with hypertension. Unilateral adrenalectomy is preferred for lateralized PA as the only potentially curative therapy. Surgery also mitigates the risk of cardiovascular and renal complications associated with PA. Targeted medical therapy, commonly including a mineralocorticoid receptor antagonist, is offered to patients with bilateral PA and those who are not surgical candidates. Novel therapies, including nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are being developed as alternative options for PA treatment. In this review article, we discuss how to best individualize therapy for patients with PA.     

Utility of Epinephrine Levels in Determining Adrenal Vein Cannulation During Adrenal Venous Sampling for Primary Aldosteronism

ObjectiveIn patients with primary aldosteronism, adrenal venous sampling (AVS) is performed to determine the presence of unilateral or bilateral adrenal disease. During AVS, verification of catheter positioning within the left adrenal vein (AV) and the right AV by comparison of AV and inferior vena cava (IVC) cortisol levels can be variable. The objective of this study was to determine the utility of AV epinephrine levels in assessing successful AV cannulation.MethodsThis was a single institution, retrospective review of patients who underwent AVS with cosyntropin stimulation for primary aldosteronism between 2009 and 2018. Successful cannulation of the AV was defined by an AV/IVC cortisol ratio selectivity index (SI) ≥3:1. Epinephrine thresholds to predict catheter placement in the AV were determined using logistic regression. The calculated epinephrine thresholds were compared with previously published thresholds.ResultsAVS was performed on 101 consecutive patients and, based on the SI, successful cannulation of the left AV and right AV occurred in 98 (97%) and 91(90%) patients, respectively. The calculated optimal epinephrine threshold to predict AV cannulation was 364 pg/mL (sensitivity, 92.1%; specificity, 94.6%) and the calculated optimal AV/IVC epinephrine ratio threshold was 27.4, (sensitivity, 92.1%; specificity, 91.3%). Among the 14 patients with failed AV cannulation, 3 patients would have been considered to have successful AVS using AV epinephrine levels >364 pg/mL and AV/IVC epinephrine ratio >27.4 thresholds.ConclusionObtaining 2 right AV samples routinely as well as AV and IVC epinephrine levels during AVS could prevent unnecessary repeat AVS in patients with failed AV cannulation based on cortisol-based SI <3:1.     

Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression

Mass spectrometry(MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes.The metabolomes of cells,tissues,and organisms comprise a variety of molecules including lipids,amino acids,sugars,organic acids,and so on.Metabolomics mainly focus on the hydrophilic classes,while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes.The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases,but system-level understanding is largely lacking,which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies.While scientists are continuously striving to develop high-coverage omics approaches,integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation.Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape,enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology,facilitating the study of interconnection between lipids and other metabolites in disease progression.In this review,we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health.We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.     

A 30-Year,Single-Center Experience of Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia

ObjectiveThe aim was to assess the short- and long-term outcomes of unilateral adrenalectomy (UA) in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH).MethodsWe conducted a retrospective study of 124 patients with PBMAH who underwent UA.ResultsOne hundred sixteen patients were available for follow-up (median, 28.5 months). Cushingoid features remitted in 43 of 65 patients (70.8%) with overt Cushing syndrome (CS). Hypertension and diabetes mellitus improved in 79 of 96 (82.3%) and 29 of 42 patients (69.0%), respectively. Glucocorticoid insufficiency developed in 7 of 116 patients (6.0%) after the surgery, and it resolved in all the patients during follow-up. The mean 24-hour urinary free cortisol level decreased gradually from 456.02 ± 422.33 mg/24 h at baseline to 84.47 ± 70.06 mg/24 h within 3 months and then increased progressively in some patients. Sixty-four of the 116 patients (55.2%) had biochemical recurrence and 43 patients (67.2%) underwent contralateral adrenalectomy. The median time interval between the second operation and the first UA was 24 months. Patients with overt CS had a larger surgical-side or contralateral adrenal volume than patients without overt CS. Patients with a contralateral adrenal volume of >33.54 mL or with a preoperative urinary free cortisol level of >216.08 mg/24 h were more likely to have recurrence.ConclusionThe efficiency of UA is transient for the majority of patients, and the indications should be strictly limited to those with subclinical or milder CS. Patients who undergo successful UA still require close life-time follow-up for the recurrence of hypercortisolism.     

New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection

ObjectiveSince January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients.MethodsTo review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury.ResultsIn our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs.ConclusionFor clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs.     

New Diagnostic Cutoffs for Adrenal Insufficiency After Cosyntropin Stimulation Using Abbott Architect Cortisol Immunoassay

IntroductionThe accurate interpretation of the cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test requires method- and assay-specific cutoffs of the level of cortisol. Compared with a historical cutoff (18 μg/dL) for polyclonal antibody-based immunoassays, lower thresholds were proposed for the Roche Elecsys II assay, which uses a monoclonal antibody. However, cutoffs for other commonly adopted, monoclonal antibody-based cortisol assays were not yet available. Here, we established the thresholds for the level of cortisol specific to the Abbott Architect immunoassay by comparing the measurements of the level of cortisol using 3 immunoassays.MethodsThe ACTH stimulation test was performed in patients with suspected adrenal insufficiency (n = 50). The serum cortisol level was measured using the Abbott Architect, Roche Elecsys II, and Siemens Centaur assays. The results of the Abbott assay were also compared with those of liquid chromatography-tandem mass spectrometry. The receiver operating characteristic analysis was performed to derive new diagnostic thresholds for the Abbott assay using the polyclonal antibody-based Siemens assay as the reference method.ResultsThe concentrations of cortisol measured using the Abbott assay were similar to those measured using liquid chromatography-tandem mass spectrometry and the Roche Elecsys II assay but significantly lower than those measured using the Siemens assay. The optimized threshold for cortisol using the Abbott assay was 14.6 μg/dL at 60 minutes after stimulation (sensitivity, 92%; specificity, 96%) and 13.2 μg/dL at 30 minutes after stimulation (sensitivity, 100%; specificity, 89%).ConclusionWe recommend a threshold of 14.6 μg/dL for the level of cortisol at 60 minutes after ACTH stimulation for the Abbott assay. In comparison with the historical threshold of 18 μg/dL, the application of the new cutoff may significantly decrease false-positive results due to ACTH stimulation testing. The use of assay-specific cutoffs will be essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency.     

Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review

ObjectiveOptimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19.MethodsA systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for “steroid-induced diabetes” or “steroid-induced hyperglycemia.” Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality.ResultsInitial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19–related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens.ConclusionFew RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.     

Hereditary Endocrine Tumors and Associated Syndromes: A Narrative Review for Endocrinologists and Endocrine Surgeons

ObjectiveHereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance.MethodsA MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed.ResultsThe most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening, and surveillance.ConclusionMedical practitioners involved in the care of patients with endocrine tumors should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of such patients and affected family members.     

Oral Octreotide: A Review of Recent Clinical Trials and Practical Recommendations for Its Use in the Treatment of Patients With Acromegaly

ObjectiveAcromegaly is characterized by chronic growth hormone (GH) and insulin-like growth factor 1 (IGF-1) hypersecretion, often caused by a GH-secreting pituitary adenoma. Even though surgery remains the first line of treatment, medical therapy is essential if surgery is contraindicated, does not achieve remission, or does not prevent recurrence despite apparent surgical remission. Oral octreotide capsules (OOCs) that combine octreotide with a transient permeability enhancer technology are the first oral somatostatin receptor ligands (SRLs) approved in the United States for acromegaly.MethodsWe review the literature and clinical trial data on OOC therapy in patients with acromegaly and discuss the clinical assessment of OOC use, potential drug–drug interactions, drug initiation, dose titration, and monitoring of drug efficacy and tolerability.ResultsIn 4 pivotal clinical trials involving 238 patients with acromegaly treated with OOC, effective suppression of serum GH and IGF-1 levels, maintenance of disease control, decreased breakthrough symptoms and symptomatic improvement with non-inferiority of OOCs to injectable SRLs in maintaining biochemical response was seen. Additionally, the safety profile of OOC therapy is comparable to that of injectable SRLs. Most patients who completed the clinical trials of OOCs have also expressed preference for oral compared with injectable SRL administration.ConclusionOOCs are an effective treatment option for patients with acromegaly who previously responded to injectable SRLs, with the benefits of avoiding injection-related side effects. This article provides a review of the pharmacology, safety, and efficacy and offers practical recommendations on the use of OOCs to treat injectable SRL-responsive patients with acromegaly.     

Pituitary Incidentalomas: Best Practices and Looking Ahead

Pituitary Incidentalomas (PI) are pituitary lesions serendipitously identified on imaging. PIs have become common in clinical practice because of increased use of imaging and radiologic advances. The most frequently incidentally detected lesions in adults are pituitary adenomas, followed by cystic lesions, and rarely other types of tumors and infiltrative and inflammatory disorders. Biochemical screening for hyperprolactinemia and acromegaly is needed in all patients with PI, whereas testing for hyposecretion is recommended for lesions larger than 6.0 mm. Most PIs are small nonfunctioning adenomas or cysts, which can be conservatively managed. For larger lesions, a multidisciplinary approach including endocrinology, neurosurgery, and neuro-ophthalmology is required. For incidentally detected lactotroph, somatotroph, and corticotroph adenomas, disease-specific management guidelines apply. Prospective studies are needed to enhance our understanding of the long-term course and response to treatment.     

The Prevalence of Probable Familial Chylomicronemia Syndrome in a Southern California Population

ObjectiveTo estimate the prevalence of probable familial chylomicronemia syndrome (FCS) in a major Southern California Academic Center as well as to provide a systematic review of past FCS studies and management recommendations.MethodsElectronic medical records were queried based on single fasting plasma triglyceride (TG) levels of ≥880 mg/dL and at least 1 episode of acute pancreatitis. After the exclusion of secondary causes (diabetes, alcohol misuse, gallbladder disease, chronic kidney disease, uncontrolled hypothyroidism, estrogen, and drug use) and responses to lipid-lowering treatment, probable patients with FCS were identified. A systematic review of all published literature on the prevalence and management guidelines for FCS was then presented and discussed.ResultsOut of 7 699 288 charts queried, 138 patients with TG levels of ≥880 mg/dL and documented evidence of at least 1 episode of acute pancreatitis were identified. Nine patients did not have any documented secondary causes of chylomicronemia. Four of the 9 patients had >20% decrease in TG levels after lipid-lowering treatment, 2 patients were not responsive to lipid-lowering medication, and data on lipid-lowering medications were missing in 3 patients.ConclusionOur study estimates the prevalence of probable FCS at a range of 0.26 to 0.66 per million. Using the recommended criteria, probable FCS cases can be identified to allow early diagnosis and management.