Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

BACKGROUND: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. OBJECTIVE: To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. DESIGN: Retrospective matched cohort analysis. SETTING: Academic medical center/pituitary center. PATIENTS: Patients with CD with surgical remission and surgically treated NFPA. MEASUREMENTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. RESULTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). LIMITATION: The small sample of patients with autoimmune disease limited identification of independent risk factors. CONCLUSION: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. PRIMARY FUNDING SOURCE: Recordati Rare Diseases Inc.

Genome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiation and are characterized by unrelenting growth and/or metastatic dissemination. Two groups of patients with PitNETs were sequenced: a prospective group of patients (n = 66) who consented to sequencing prior to surgery and a retrospective group (n = 26) comprised of aggressive/higher risk PitNETs. A higher mutational burden and fraction of loss of heterozygosity (LOH) was found in the aggressive, treatment-refractory PitNETs compared to the benign tumors (p = 1.3 × 10-10 and p = 8.5 × 10-9, respectively). Within the corticotroph lineage, a characteristic pattern of recurrent chromosomal LOH in 12 specific chromosomes was associated with treatment-refractoriness (occurring in 11 of 14 treatment-refractory versus 1 of 14 benign corticotroph PitNETs, p = 1.7 × 10-4). Across the cohort, a higher fraction of LOH was identified in tumors with TP53 mutations (p = 3.3 × 10-8). A machine learning approach identified loss of heterozygosity as the most predictive variable for aggressive, treatment-refractory behavior, outperforming the most common gene-level alteration, TP53, with an accuracy of 0.88 (95% CI: 0.70-0.96). Aggressive, treatment-refractory PitNETs are characterized by significant aneuploidy due to widespread chromosomal LOH, most prominently in the corticotroph tumors. This LOH predicts treatment-refractoriness with high accuracy and represents a novel biomarker for this poorly defined PitNET category.

The biochemical diagnosis of adrenal insufficiency with modern cortisol assays: Reappraisal in the setting of opioid exposure and hospitalization.

OBJECTIVE: We aimed to (1) examine the diagnosis of opioid-induced adrenal insufficiency, and (2) investigate the diagnostic value of a morning cortisol <83 nmol/L (3 µg/dl) for the diagnosis of adrenal insufficiency, using newer more specific cortisol assays and cut-offs. DESIGN: Retrospective study (5/2015-10/2020). PARTICIPANTS: Cohort 1 (N = 75): adults who underwent cosyntropin stimulation testing and opioid exposure for >30 days. Cohort 2 (N = 854): adults, with or without opioid exposure, who had a morning cortisol level measured the same day as stimulation testing. MEASUREMENTS: Peak cortisol during cosyntropin stimulation testing. Sensitivity and specificity of morning serum cortisol for adrenal insufficiency. RESULTS: The prevalence of adrenal insufficiency in patients with chronic opioid exposure who underwent cosyntropin stimulation testing was 4.0% using a cortisol cutoff of <405 nmol/L (14.7 µg/dl) versus 19% using the traditional cutoff of <500 nmol/L (18.1 µg/dl). For hospitalized patients with and without opioid-exposure, 14 of 22 (64%) patients with morning cortisol levels of <83 nmol/L (3 µg/dl) passed cosyntropin stimulation testing. A morning cortisol level of <348 nmol/L (12.6 µg/dl) had 100% sensitivity (95% confidence interval: 84.5%-100%) for the diagnosis of adrenal insufficiency. CONCLUSION: Applying a cutoff of <405 nmol/L (14.7 µg/dl), opioid-induced adrenal insufficiency is rare. Nearly 1 out of 6 patients would be reclassified as having adrenal insufficiency applying the guideline-recommended cutoff of <500 nmol/L (18.1 µg/dl). Serum morning cortisol <83 nmol/L (3 µg/dl) is not a valid diagnostic test for adrenal insufficiency in hospitalized patients, whether or not receiving opioids.

Quality of life after long-term biochemical control of acromegaly.

PURPOSE: To assess long-term quality of life (QoL) in patients with sustained biochemical control of acromegaly, comparing those receiving vs not receiving pharmacotherapy (primary analysis); to assess change in QoL over time (secondary analysis). METHODS: Cross-sectional study, with a secondary longitudinal component, of 58 patients with biochemically controlled acromegaly. All had participated in studies assessing QoL years previously, after having undergone surgery ± radiotherapy. One cohort received medical therapy [MED (n = 33)]; the other did not [NO-MED (n = 25)]. QoL was assessed by the 36-Item-Short-Form Health Survey (SF-36), Acromegaly Quality of Life Questionnaire (AcroQoL), Gastrointestinal Quality of Life Index (GIQLI), Symptom Questionnaire, and QoL-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). RESULTS: Mean (± SD) duration of biochemical control was 15.0 ± 6.4 years for MED and 20.4 ± 8.2 years for NO-MED (p = 0.007). 58% of subjects scored < 25% of normal on ≥ 1 SF-36 domain and 32% scored < 25% of normal on ≥ 4 of 8 domains. Comparing MED vs NO-MED and controlling for duration of biochemical control, there were no significant differences in QoL by SF-36, AcroQOL, GIQLI, Symptom Questionnaire, or QoL-AGHDA. Growth hormone deficiency (GHD) but not radiotherapy predicted poorer QoL. In MED, QoL improved over time in three AcroQoL domains and two GIQLI domains. In NO-MED, QoL worsened in two SF-36 domains and two Symptom Questionnaire domains; QoL-AGHDA scores also worsened in subjects with GHD. CONCLUSION: A history of acromegaly and development of GHD, but not pharmacologic or radiotherapy, are detrimental to QoL, which remains poor over the long-term despite biochemical control.

Effects of growth hormone receptor antagonism and somatostatin analog administration on quality of life in acromegaly.

OBJECTIVE: Acromegaly is associated with impaired quality of life (QoL). We investigated the effects of biochemical control of acromegaly by growth hormone receptor antagonism vs somatostatin analog therapy on QoL. DESIGN: Cross-sectional. PATIENTS: 116 subjects: n = 55 receiving a somatostatin analog (SSA group); n = 29 receiving pegvisomant (PEG group); n = 32 active acromegaly on no medical therapy (ACTIVE group). MEASUREMENTS: Acromegaly QoL Questionnaire (AcroQoL), Rand 36-Item Short Form Survey (SF-36) and Gastrointestinal QoL Index (GIQLI); fasting glucose, insulin and IGF-1 levels (LC/MS, Quest Diagnostics). RESULTS: There were no group differences in mean age, BMI or sex [(whole cohort mean ± SD) age 52 ± 14 years, BMI 30 ± 6 kg/m2 , and male sex 38%]. Mean IGF-1 Z-scores were higher in ACTIVE (3.9 ± 1.0) vs SSA and PEG, which did not differ from one another (0.5 ± 0.7 and 0.5 ± 0.7, P < .0001 vs ACTIVE). Eighty-three per cent of PEG previously received somatostatin analogs, which had been discontinued due to lack of efficacy (52%) or side effects (41%). There were no differences in the four QoL primary end-points (AcroQoL Global Score, SF-36 Physical Component Summary Score, SF-36 Mental Health Summary Score and GIQLI Global Score) between SSA and PEG. Higher HbA1c, BMI and IGF-1 Z-scores were associated with poorer QoL in several domains. CONCLUSION: Our data support a comparable QoL in patients receiving pegvisomant vs somatostatin analogs, despite the fact that the vast majority receiving pegvisomant did not respond to or were not able to tolerate somatostatin analogs.

GnRH agonist-associated pituitary apoplexy: a case series and review of the literature.

PURPOSE: To examine the clinical presentation and longitudinal outcome of Pituitary Apoplexy (PA) after gonadotropin-releasing hormone agonist (GnRHa) in a series of patients and compare to prior reports. METHODS: A retrospective chart review was performed on seven patients receiving GnRHa who developed PA. Prior reported cases were analyzed. RESULTS: Six men (median age 72 years) with prostate cancer and one woman (aged 22 years) undergoing oocyte donation presented with PA between 1990 and 2020. Most presented with within 24 h of the first dose, but two developed PA 1 to 5 months after GnRHa initiation. The main clinical manifestations were headache (100%), nausea and vomiting (86%). While no patients had a previously known pituitary tumor, all had imaging demonstrating sellar mass and/or hemorrhage at presentation. Among those surgically treated (5/7), 80% (4/5) of patients had pathologic specimens that stained positive for gonadotropins; the remaining patient's pathologic specimen was necrotic. At the time of PA, the most common pituitary dysfunction was hypocortisolism. Central adrenal insufficiency and central hypothyroidism were reversible in a subset. Pituitary imaging remained stable. CONCLUSIONS: This is the first report of a case series with PA after GnRHa administration with longitudinal follow-up. Although infrequent, PA can be life-threatening and should be suspected among patients receiving GnRHa, with or without a known pituitary adenoma, who develop acute headache, nausea and/or vomiting. Since hypopituitarism was reversible in a subset, ongoing pituitary function testing may be indicated.

Physicians' awareness of gadolinium retention and MRI timing practices in the longitudinal management of pituitary tumors: a "Pituitary Society" survey.

PURPOSE: In view of mounting attention related to possible brain retention of gadolinium-based contrast agents (GBCAs) in patients with normal renal function, our purpose was to detail results from a survey of pituitary experts to assess: 1) the timing interval and frequency of pituitary magnetic resonance imaging (MRI) following surgical and/or medical and/or radiation therapy of pituitary tumors, 2) awareness of the types of GBCAs used and their possible safety issues. METHODS: The Pituitary Society Education Committee composed a survey with 12 multiple choice questions, 8 of which specifically addressed the time interval and frequency of MRI in the longitudinal management of pituitary tumors. The survey was distributed at two meetings; the International Pituitary Neurosurgeons Society conference in San Diego, CA, on February 18th, 2018, and the Pituitary Society Membership and Career Development Forum, Chicago, IL on March 18th, 2018. RESULTS: There is consensus among pituitary endocrinologists and neurosurgeons that long-term repeated imaging is recommended in most pituitary tumors, although the precise strategy of timing varied depending on the specialist group and the specific clinical context of the adenoma. The data also suggest that International Pituitary Neurosurgeons Society neurosurgeons, as well as Pituitary Society neuroendocrinologists, are sometimes unaware of which contrast agents are used by their institution, and many are also unaware that evidence of long-term brain retention has been reported with the use of GBCAs in patients with normal function. CONCLUSIONS: International pituitary endocrinologists and pituitary neurosurgeons experts suggest ongoing MRIs for the management of pituitary tumors; strategies vary based on clinical context, but also on individual experience and practice.

Characterization of cyclic Cushing's disease using late night salivary cortisol testing.

OBJECTIVE: To characterize a cohort of patients with cyclic Cushing's disease (CD) in comparison with noncyclic CD using late night salivary cortisol (LNSC) and examine the diagnostic sensitivity of LNSC in comparison with that of 24-hour urine-free cortisol (UFC) in this population. DESIGN: Retrospective study of patients with CD seen in our institution between 2008 and 2017. PATIENTS: A total of 205 patients, including 17 (8%) with cyclic CD (based on a minimum of 3 peaks and 2 troughs in cortisol levels). In a secondary analysis, 38 patients (19%) with cyclic CD were identified (based on a criterion of at least 2 peaks and 1 trough). MEASUREMENTS: Data on presentation, laboratory tests and outcomes were extracted. The diagnostic sensitivity of LNSC vs UFC in establishing cyclic CD was calculated. Kaplan-Meier analyses of recurrence after transsphenoidal pituitary surgery (TSS) were performed. RESULTS: The interval between presentation and TSS was significantly longer in patients with cyclic CD (P < .0001) in comparison with those with noncyclic CD. The sensitivity of LNSC in establishing cyclic CD was 88% and was higher than that of UFC (12%, P = .007). There were no differences in remission and recurrence rates between patients with cyclic CD and those with noncyclic CD. CONCLUSIONS: Patients with cyclic CD account only for a minority of those with CD, but may require a lengthier diagnostic evaluation. The use of LNSC on multiple occasions provides a more sensitive method of detecting cyclic CD than UFC. Outcomes of TSS in cyclic CD are comparable to those with noncyclic disease.

CLINICAL OUTCOMES AND SELF-REPORTED SYMPTOMS IN PATIENTS WITH ACROMEGALY: AN 8-YEAR FOLLOW-UP OF A LANREOTIDE STUDY.

OBJECTIVE: The aim of this study was to evaluate the proportion of patients with acromegaly who remained on long-term lanreotide depot after completion of an open-label multicenter phase III clinical trial (SALSA: A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel), compare baseline and long-term follow-up symptoms scores, and correlate scores with individual longitudinal clinical outcomes. METHODS: Records of all subjects previously enrolled at the Massachusetts General Hospital site of SALSA were reviewed. Those who remained on lanreotide were interviewed and asked to complete a questionnaire that they had filled out in SALSA in 2007 regarding their current symptomatology and injection side effects, as well as to complete the Acromegaly Quality of Life Questionnaire. Furthermore, clinical, biochemical, and radiographic data related to acromegaly and its comorbidities were tracked throughout follow-up. RESULTS: Six out of 7 patients chose to remain on lanreotide, and 5 of them continued lanreotide depot through last follow-up, for up to 8 years or in 1 case until death. In all cases, lanreotide remained well tolerated, and insulin-like growth factor-1 levels and pituitary imaging remained well controlled on stable doses. While comorbidities persisted or developed, the self-reported symptom score after up to 8 years of therapy showed a significant decrease in frequency or resolution in symptoms that were reported at baseline. CONCLUSION: This study shows a significant decrease in frequency or resolution in self-reported symptoms in well-controlled patients receiving long-term lanreotide therapy. ABBREVIATIONS: AcroQoL = Acromegaly Quality of Life Questionnaire GH = growth hormone GI = gastrointestinal IGF-1 = insulin-like growth factor-1 SALSA = A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel.

Monotherapy with lanreotide depot for acromegaly: long-term clinical experience in a pituitary center.

PURPOSE: Long-acting somatostatin analogs are one of the main classes of medical therapy used for acromegaly and most patients require ongoing treatment. Few studies have evaluated the long-term efficacy and safety of lanreotide depot beyond 2 years. The goal of this study was to provide a long-term longitudinal assessment of efficacy and safety of lanreotide depot in lanreotide responders compared to a surgically cured control group. METHODS: In this retrospective longitudinal case-control study, patients with acromegaly receiving lanreotide depot monotherapy continuously for at least 24 months (N = 24) and surgically cured patients (N = 39) were compared. Serum IGF-1, pituitary MRIs, lanreotide dose, co-morbidities and adverse effects were assessed longitudinally. RESULTS: In the lanreotide group, IGF-1 remained normal and unchanged over 6 years; comparable to the surgery only group. There was no difference in prevalence of normal IGF-1 between the lanreotide and surgery only groups at 6 months (100 vs. 97 %), 6 years (89 vs. 90 %) and at last follow-up (96 vs. 92 %). Tumor size remained stable (79 %) or decreased (21 %) in the lanreotide group. In the surgery only group, tumor size remained unchanged in all patients. Hemoglobin A1C did not differ between lanreotide and surgery only groups (baseline 5.8 vs. 6.1 %; last follow-up 6.0 vs. 5.7 %). Two (8 %) of the lanreotide and none of the surgery only group developed new diabetes mellitus. CONCLUSION: Lanreotide depot maintains normalization of IGF-1 in 89 % of responders after 6 years, comparable to surgically cured controls, and controlled tumor size in all without significant adverse effects.

Proton therapy for low-grade gliomas: Results from a prospective trial.

BACKGROUND: In this prospective study, the authors evaluated potential treatment toxicity and progression-free survival in patients with low-grade glioma who received treatment with proton radiation therapy. METHODS: Twenty patients with World Health Organization grade 2 glioma who were eligible for radiation therapy were enrolled in a prospective, single-arm trial of proton therapy. The patients received proton therapy at a dose of 54 Gy (relative biological effectiveness) in 30 fractions. Comprehensive baseline and regular post-treatment evaluations of neurocognitive function, neuroendocrine function, and quality of life (QOL) were performed. RESULTS: All 20 patients (median age, 37.5 years) tolerated treatment without difficulty. The median follow-up after proton therapy was 5.1 years. At baseline, intellectual functioning was within the normal range for the group and remained stable over time. Visuospatial ability, attention/working memory, and executive functioning also were within normal limits; however, baseline neurocognitive impairments were observed in language, memory, and processing speed in 8 patients. There was no overall decline in cognitive functioning over time. New endocrine dysfunction was detected in 6 patients, and all but 1 had received direct irradiation of the hypothalamic-pituitary axis. QOL assessment revealed no changes over time. The progression-free survival rate at 3 years was 85%, but it dropped to 40% at 5 years. CONCLUSIONS: Patients with low-grade glioma tolerate proton therapy well, and a subset develops neuroendocrine deficiencies. There is no evidence for overall decline in cognitive function or QOL.

Psychotropic-induced hyperprolactinemia: a clinical review.

BACKGROUND: Psychotropic medications, particularly select antipsychotics, are a common cause of drug-induced hyperprolactinemia. As high prolactin may be associated with hypogonadism, reproductive dysfunction, and bone loss, it is important to recognize this condition and understand its management. OBJECTIVE: The aim of this review is to evaluate the causes, signs, and symptoms associated with hyperprolactinemia, to describe mechanisms through which psychotropic medications elevate prolactin, and to suggest an evidence-based management approach for patients with psychotropic drug-induced hyperprolactinemia. METHODS: A PubMed/MEDLINE search was conducted on the topic of psychotropic agents as a cause of hyperprolactinemia. The material with most relevance to current psychiatric practice and of highest level of evidence was included in this review. CONCLUSION: Hyperprolactinemia should be evaluated in adult patients receiving psychotropic agents if signs and symptoms associated with hyperprolactinemia are present. It is also important to exclude pituitary and hypothalamic disease by magnetic resonance imaging if hyperprolactinemia is not definitely caused by psychotropic medications. As bone loss may occur because of hyperprolactinemia-mediated hypogonadism, bone mineral density (BMD) should be evaluated in patients with persistent high prolactin and reproductive dysfunction. Aripiprazole or other prolactin-sparing atypical antipsychotics may be alternatives or aripiprazole can be considered as adjunctive therapy in select cases of psychotropic-induced hyperprolactinemia.

The effect of somatostatin analogs on vitamin D and calcium concentrations in patients with acromegaly.

PURPOSE: The goals of this study were to determine: (1) 25OH vitamin D (25OHD) and calcium levels in patients with acromegaly and their association with insulin-like growth factor (IGF-1) and (2) whether somatostatin analog (SSA) therapy effects calcium and 25OHD levels. METHODS: 125 patients with acromegaly were studied. Serum calcium and 25OHD levels were compared prior to and after vitamin D supplementation between patients receiving versus not receiving SSA in whom medical therapy included pegvisomant and/or dopamine agonists. Calcium and 25OHD levels were also evaluated longitudinally prior to and during short-term (mean 3 months, range 1-5) and long-term (mean 49 months, range 7-180) SSA administration. Vitamin D2 50,000 units weekly were given to 3 patients in the cross sectional and 1 in the longitudinal group; 400-4,000 units/day of D3 were given to 11 and 5 in respective groups. RESULTS: In patients with a comparable mean IGF-1 index and season of testing, mean serum levels of 25OHD prior to vitamin D supplementation did not differ in patients receiving versus not receiving SSA (30 ± 3 vs. 30 ± 1 ng/ml, p = 0.99) and the prevalence of vitamin D sufficiency was similar between SSA and non SSA groups (42 vs. 57%, p = 0.20), prior to vitamin D supplementation. In patients with a comparable mean IGF-1 index and season of testing, mean serum 25OHD levels in patients increased after vitamin D supplementation in both those who were (37 ± 2 ng/ml, N = 23, p = 0.007) and were not receiving SSA (35 ± 1 ng/ml, N = 69, p = 0.005) compared to pre-D supplementation levels but were not different between these groups, p = 0.95) after D supplementation. Calcium and albumin were normal throughout longitudinal follow up. Calcium correlated with IGF-1 index (ρ = 0.29, p = 0.001, N = 125). In the longitudinal subset, serum calcium decreased transiently, in patients receiving short-term SSA (pretreatment 9.9 ± 0.1 mg/dl vs. short-term SSA 9.5 ± 0.1, p = 0.004). After long-term SSA therapy, calcium increased compared to levels on short-term therapy (9.8 ± 0.1 mg/dl vs. 9.5 ± 0.1, p = 0.017) and were unchanged compared to baseline. Mean vitamin D levels were sufficient at baseline prior to SSA therapy (33 ± 5.0 ng/ml), and did not change during short term (29 ± 6 ng/ml, p = 0.85) and long term SSA therapy (35 ± 5 ng/ml, p = 0.43). CONCLUSIONS: Prior to and after vitamin D supplementation, patients with acromegaly receiving long-term SSA had vitamin D levels similar to those receiving other therapies, suggesting that long-term SSA therapy does not affect serum vitamin D. However, given the limitations of this retrospective study, further prospective studies evaluating the impact of SSA on vitamin D levels are necessary to confirm these findings definitively. Calcium levels are positively associated with IGF-1 index in patients with acromegaly. There is a transient decrease in calcium levels with short-term SSA use. The acute effect of SSA on calcium does not appear to be mediated by albumin, 25OHD or PTH and resolves with long-term SSA treatment. The transient decrease in calcium with short-term SSA use resolved with long-term SSA therapy.

Investigation of impulsivity in patients on dopamine agonist therapy for hyperprolactinemia: a pilot study.

The use of dopamine agonists (DAs) has been associated with increased impulsivity and impulse control disorders in several diseases, including Parkinson's disease. Such an effect of DAs on impulsivity has not been clearly characterized in hyperprolactinemic patients, where DAs are the mainstay of therapy. We studied the effects of DAs on impulsivity in hyperprolactinemic patients treated at a tertiary pituitary center, using validated psychometric tests. Cross-sectional study. Impulsivity was evaluated in 30 subjects, 10 hyperprolactinemic patients on DAs compared to two control groups; one comprising untreated hyperprolactinemic patients (n = 10) and a second group consisting of normoprolactinemic controls with pituitary lesions (n = 10). Measures of impulsivity included both self-report questionnaires as well as laboratory-based tasks. Hyperprolactinemic patients on DAs had a higher score (mean ± SD) in one self-report measure of impulsivity, the attention subscale of the Barratt Impulsiveness Scale (16.2 ± 2.7), as compared to the hyperprolactinemic control group (12.3 ± 2.5) and the normoprolactinemic group (14.7 ± 4.4) (p = 0.04). No statistically significant difference was found between groups with regards to the other impulsivity scales. In the DA-treated group, a correlation was observed between increased impulsivity (as assessed in the Experiential Discounting Task) and higher weekly cabergoline dose (r(2) = 0.49, p = 0.04). The use of DAs in hyperprolactinemic patients is associated with an increase in one aspect of impulsivity. This effect should be further characterized in larger, longitudinal studies.

Treatment of acromegaly with oral octreotide.

Acromegaly is a rare disease caused by a growth hormone excess, usually due to a secreting pituitary adenoma. Somatostatin receptor ligands (SRL) are the mainstay of medical therapy for patients with acromegaly who fail to achieve biochemical control post-operatively or are not eligible for surgical treatment. SRLs are typically administered as monthly injections and have shown to be effective in maintaining biochemical and radiological control of acromegaly. However, these injections may cause local adverse events and are associated with increased psychological burden in some patients. Oral octreotide provides a new alternative for patients responding to injectable SRLs. This new formulation has shown to have similar safety and efficacy profiles compared to injectable SRLs and may be a preferable option for some patients with acromegaly. The aim of this review is to provide an overview of the role of oral octreotide in the management of acromegaly.

Oral octreotide capsules for acromegaly treatment: application of clinical trial insights to real-world use.

INTRODUCTION: Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line of treatment, and medical therapy is used for patients with persistent disease following surgery, for adenoma recurrence, or for patients ineligible for, or declining, surgery. Approved somatostatin receptor ligands (SRLs) have been limited to injectable options, until recently. Oral octreotide capsules (OOC) are the first approved oral SRL for patients with acromegaly. AREAS COVERED: We review published reports and provide case study examples demonstrating practical considerations on the use of OOC. Using two hypothetical case scenarios, we discuss current treatment patterns, breakthrough symptoms and quality of life (QoL), efficacy of SRLs, OOC dose titration, evaluation of OOC treatment response, and incidence and management of adverse events. EXPERT OPINION: OOC are an option for patients with acromegaly including those who experience breakthrough symptoms, who have preference for oral therapies, or other reasons for declining injectable SRLs. OOC have been associated with improved patient-reported QoL measures compared with those reported for lanreotide and octreotide. Continued real-world experience will determine whether OOC, alone or in combination with other therapies, provides further advantages over current injectable acromegaly treatments.

The effect of testosterone levels on mood in men: a review.

BACKGROUND: The effects of both high and low levels of testosterone are wide ranging and can include changes in mood, often overlapping with symptoms of mood disorders. OBJECTIVE: We sought to review the literature on the correlation of high and low levels of testosterone on mood disorders in men. RESULTS: Based on limited studies, high levels of testosterone are related to increased rates of depression as well as hypomania, whereas low levels of testosterone are related to depressive disorders in certain subpopulations of patients. There is insufficient evidence to conclude that low testosterone level routinely leads to major depressive disorder in men. CONCLUSIONS: Physicians should consider screening for low testosterone levels in certain subgroups of depressed men.

Pathologic and clinical features of pituitary adenomas showing TSH immunoreactivity.

UNLABELLED: Patients with thyrotropin-secreting pituitary adenomas may present with mass effect, hypopituitarism, and/or hyperthyroidism. The spectrum of pathologic and clinical features of patients whose tumors demonstrate ß-thyrotropin immunoreactivity (ß-TSH IR) has not been characterized. To characterize the phenotype of patients with pituitary adenomas with positive ß-TSH IR, we conducted a retrospective analysis of patient records of all adult patients (n = 1,223) undergoing pituitary surgery in our institution over one decade (1999-2009). The search identified 166 adults with tumors which had ß-TSH IR. These patients were individually matched to 166 patients whose tumors revealed no ß-TSH IR. Clinical, pathological, imaging and biochemical data were extracted. 332 patients, aged 51.4 ± 15.1 years [150 women (45 %) and 182 men (55 %)], with pituitary adenomas (mean tumor diameter ± SD: 22.7 ± 9.0 mm) were studied. The degree of ß-TSH IR was associated with the presence of central hyperthyroidism (p < 0.0001) or goiter (p = 0.0217). Patients whose tumors expressed more extensive ß-TSH IR were less likely to develop pituitary apoplexy than those without ß-TSH IR (p = 0.0428). In addition, the degree of ß-TSH IR correlated with the presence of immunoreactivity for ß-FSH (p < 0.0001), ß-LH (p < 0.0001), alpha subunit (p < 0.0001), and GH (p = 0.0036). CONCLUSIONS: Pituitary adenomas expressing ß-TSH IR were more likely to demonstrate immunoreactivity for ß-FSH, ß-LH, GH or alpha subunit. Patients with such tumors were more likely to exhibit hyperthyroidism and goiter, but less likely to develop pituitary apoplexy than patients without ß-TSH IR. These findings suggest that ß-TSH IR is associated with specific phenotypic features in patients with pituitary adenomas.