BACKGROUND: The dopaminergic agonist cabergoline (CAB) has been used in the pharmacological treatment of Cushing’s disease (CD). The effect is attributed to the frequent expression of the dopamine receptor subtype 2 in corticotroph tumors. However, in vivo studies have demonstrated the normalization of 24-h urinary cortisol (24-h UC) in approximately 30-40% of patients over the long term, mainly after surgical failure.OBJECTIVE: To evaluate the effect of CAB as monotherapy in the early preoperative period and on the recurrence of CD.METHODS: A single-center retrospective study was conducted in a tertiary referral center. Twenty-one patients with confirmed CD were included. The median age was 32 years (13-70), 86% were female, 10 had microadenomas, and 11 had macroadenomas. They were diagnosed from 1986 to 2016 and used CAB as monotherapy either in the preoperative period (n=7, CABi) or upon recurrence before any other treatment (n=14, CABr). A ‘complete response’ was considered 24-h UC normalization and a ‘partial response’ was considered a 24-h UC reduction of >50%. UC was obtained at the last follow-up evaluation. The normalization of late-night salivary cortisol (LNSC) after CAB use was evaluated in most patients, as well as the tumor diameter by pituitary MRI, before and after CAB treatment.RESULTS: Complete response was achieved in 29% (6/21) of subjects after 14.9±16.4 months of treatment, with an average dose of 2.2±1.0 mg/week. Partial response occurred in 9.5% (2/21). LNSC normalized in 35% (6/17) of patients, and no variation in tumor diameter before and after CAB use was observed (n=13): 6.8±6.8 vs. 7.2±7.1 mm. There was no normalization of 24-h-UC in the CABi subgroup at the end of the treatment, whereas 43% (6/14) of patients in the CABr subgroup reached complete response. The CABi subgroup was treated for 4.7±1.9 months, and the CABr subgroup was treated for 20.1±18.1 months. Both groups were administered similar doses of CAB (CABi 2.1±0.9 and CABr 2.3±1.1 mg/week). Interestingly, the difference between the subgroups’ complete response was evident early on in the three months of treatment: no patients in the CABi subgroup vs. 6/10 (60%) in the CABr subgroup (p=0.035), despite a lower dose in the CABr subgroup (1.1 vs. 1.6; p=0.008). The normalization of LNSC occurred in 20% of the CABi subgroup and in 42% of the CABr subgroup.CONCLUSIONS: The normalization of 24-h UC and LNSC occurred in approximately 30% of all patients, mainly in those who used CAB for the recurrence of CD. Despite the small number of subjects in the CABi subgroup, the absence of hormone control in this subgroup discourages the use of this medication as primary therapy or as a preoperative treatment option.

Context Invasive and somatostatin receptor ligand (SRL)-resistant pituitary tumors represent a challenge in the clinical practice of endocrinologists. Efforts have been made to elucidate reliable makers for both. Survivin and eukaryotic translation initiation factor-binding protein 1 (4EBP1) are upregulated in several cancers and involved in apoptosis and cell proliferation. Objective We explored the role of these markers in somatotropinomas. Methods Immunostains for survivin and 4EBP1, and also for somatostatin receptor type 2 (SSTR2), Ki-67, and cytokeratin 18, were analyzed in tissue microarrays containing 52 somatotropinoma samples. Tumor invasiveness was evaluated in all samples while drug resistance was evaluated in 34 patients who received SRL treatment. All these parameters were correlated with first-generation SRL (fg-SRL) responsiveness and tumor invasiveness. Results Low survivin expression (P = 0.04), hyperintense signal on T2 weighted image (T2WI) (P = 0.01), younger age (P = 0.01), sparsely granular adenomas (SGA) (P = 0.04), high postoperative growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels (P = 0.049 and P < 0.001, respectively), and large postoperative tumor size (P = 0.02) were associated with resistance to fg-SRL. Low survivin and SSTR2 expression and high 4EBP1 expression were associated with SGA (P = 0.04, P = 0.01, and P = 0.001, respectively). Younger age (P = 0.03), large tumor pre- and postoperative (P = 0.04 and P = 0.006, respectively), low SSTR2 expression (P = 0.03), and high baseline GH and IGF-1 (P = 0.01 and P = 0.02, respectively) were associated with tumor invasiveness. However, survivin, 4EBP1, Ki-67, and granulation patterns were not associated with tumor invasion. Conclusion This study suggests that low survivin expression is predictive of resistance to fg-SRL in somatotropinomas, but not of tumor invasiveness.

Abstract Disclosure: M. Gadelha: Advisory Board Member; Self; Novo Nordisk, Recordati, Crinetics Pharmaceuticals. Speaker; Self; Recordati, Novo Nordisk, Ipsen, Crinetics Pharmaceuticals. M.D. Bronstein: None. E. Grineva: Advisory Board Member; Self; Ipsen, Merck, Pfizer, Inc. Speaker; Self; Recordati, Ipsen, Pfizer Berlin Chemie, Teva Pharmaceutical Industries Ltd., A. Menarini, Siemens Healthineers. N. Kapoor: None. C. De Block: Consulting Fee; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, A Menarini Diagnostics, Eli Lilly & Company, Insulet Corporation, Medtronic, Novo Nordisk, Roche Pharmaceuticals. Research Investigator; Self; AstraZeneca, Boehringer Ingelheim, Indigo Diabetes, Novo Nordisk. Speaker; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, A Menarini Diagnostics, Eli Lilly & Company, Insulet Corporation, Medtronic, Novo Nordisk, Roche Pharmaceuticals. J.M. Escalante Pulido: None. G. Rollin: Advisory Board Member; Self; Merck Serono. Speaker; Self; Novo Nordisk, Abbott Laboratories, AstraZeneca, Merck Serono. R. Baggenstoss: None. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. W. Gallardo: Speaker; Self; Pfizer, Inc., Merck, Ipsen, Novartis Pharmaceuticals. Introduction: A robust clinical development program of 14 trials demonstrated that the second-generation somatostatin receptor ligand, pasireotide, is an effective treatment for patients (pts) with rare endocrine disorders, including acromegaly and Cushing’s disease (CD). Pts with acromegaly or CD have significant morbidity, reduced quality of life and, if inadequately treated, a higher mortality risk than the general population. This 8-year interim analysis evaluated the long-term safety of pasireotide treatment in pts with acromegaly, CD or other endocrine disorders. Methods: This ongoing, open-label, multicenter study allows continued treatment for pts who completed a previous pasireotide parent trial (NCT01794793). Pts who continued to receive clinical benefit, as determined by the investigator in the parent study, entered the rollover study and remained on pasireotide. Depending on the route of administration in the parent study, pts received pasireotide long-acting release (LAR; n=303) or subcutaneous (sc; n=38) as monotherapy (n=36), or sc in combination with cabergoline (n=2). The primary objective was to evaluate long-term safety, determined by frequency of adverse events (AEs)/serious adverse events (SAEs). Results: Overall, 341 pts from 29 countries have entered the study from 14 parent studies; 228 pts had acromegaly, 64 CD and 49 other endocrine disorders, including melanoma, dumping syndrome and neuroendocrine tumors. Median (min−max) exposure to all pasireotide formulations from rollover baseline to data cut-off and across all indications was 45.3 months (0.9−100.8). Median (min−max) dose from rollover baseline was 45.4 mg/month (5.3−128.3) with pasireotide LAR and 1200 µg/day (300−1800) with pasireotide sc. In total, 89 (26.1%) pts discontinued treatment; the most common reason was consent withdrawal (n=21, 6.2%). Most common AEs during rollover (≥10% in all pts) were nasopharyngitis (acromegaly n=13, 5.7%; CD n=14, 21.9%; other diseases n=14, 28.6%), hyperglycemia (acromegaly n=29, 12.7%; CD n=2, 3.1%; other diseases n=7, 14.3%), back pain (acromegaly n=20, 8.8%; CD n=7, 10.9%; other diseases n=8, 16.3%) and headache (acromegaly n=21, 9.2%; CD n=6, 9.4%; other diseases n=7, 14.3%). SAEs were reported in 87 (25.5%) pts; the most common were cholelithiasis and COVID-19 (both n=9, 2.6%). Overall, 18 (5.3%) pts discontinued treatment because of AEs. Incidence of new hyperglycemia-related AEs during rollover was low. No new safety signals were identified. Conclusions: Hyperglycemia is an expected AE during pasireotide treatment, often occurring in the first 3 months of therapy. These data in pts with acromegaly, CD or other endocrine disorders support pasireotide as a well-tolerated long-term treatment and affirm that pts continue to receive long-term benefit, with a low discontinuation rate over 8 years. Presentation: Thursday, June 15, 2023

Hyperprolactinemia can be caused by several conditions and its effects on the hypothalamic-pituitary-gonadal axis are understood in more detail. Nevertheless, in recent decades, other metabolic effects have been studied and data pointed to a potential increased cardiovascular disease (CVD) risk. A recent study showed a decrease in total and LDL- cholesterol only in men with prolactinoma treated with dopamine agonists (DA) supporting the previous results of a population study with increased CVD risk in men harboring prolactinoma. However, other population studies did not find a correlation between prolactin (PRL) levels and CVD risk or mortality. There is also data pointing to an increase in high-density lipoprotein levels, and decreases in triglycerides, carotid-intima-media thickness, C-reactive protein, and homocysteine levels in patients with prolactinoma on DA treatment. PRL was also implicated in endothelial dysfunction in pre and postmenopausal women. Withdrawal of DA resulted in negative changes in vascular parameters and an increase in plasma fibrinogen. It has been shown that PRL levels were positively correlated with blood pressure and inversely correlated with dilatation of the brachial artery and insulin sensitivity, increased homocysteine levels, and elevated D-dimer levels. Regarding possible mechanisms for the association between hyperprolactinemia and CVD risk, they include a possible direct effect of PRL, hypogonadism, and even effects of DA treatment, independently of changes in PRL levels. In conclusion, hyperprolactinemia seems to be associated with impaired endothelial function and DA treatment could improve CVD risk. More studies evaluating CVD risk in hyperprolactinemic patients are important to define a potential indication of treatment beyond hypogonadism.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract Disclosure: A.R. Moreira: None. E.B. Trarbach: None. A. Glezer: None. G.A. Maciel: None. C.B. Bueno: None. A.S. Monteiro: None. M. Padula: None. I.P. Grande: None. M.D. Bronstein: None. Introduction: Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recent studies identified variants in PRL-R gene in patients with prolactinoma and two of them Glu400(376)Gln/p.Asn516(492)Ile, were more common in patients compared to controls. Functional analysis of the p.Asn516(492)Ile variant showed an increase in Akt expression and cell proliferation induced by PRL. However, the association between PRL-R variants and response to cabergoline (CAB) treatment has not been investigated. Objective: This study aims to analyze the PRL-R gene in an extensive cohort of patients with sporadic prolactinomas and evaluate its association with clinical, laboratorial and tumor imaging characteristics, as well as CAB treatment resistance. Methods: DNA was extracted from peripheral blood samples of 178 patients with prolactinoma and 146 were classified according to cabergoline response. The PRL-R gene was analyzed by PCR techniques and automated Sanger-type sequencing. Four in silico tools were used for analysis. Results: We found six PRL-R variants: p.Ile100(76)Val (n=18), p.Ile170(146)Leu (n=6), p.Glu400(376)Gln/p.Asn516(492)Ile (n=3), p.Glu470Asp (n =1) and p.Ala591Pro (n=1), the last two described for the first time in prolactinomas´ patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis. PRL-R variants were associated with male sex (P=0.015), higher serum PRL levels (P=0.007), larger tumors (P=0.001), higher frequency of macroadenomas (P=0.031) and cabergoline resistance (P<0.001). Considering together only the PRL-R variants classified as pathogenic/probably pathogenic (p.Ile170(146)Leu, p.Glu400(376)Gln/Asn516(492) and p.Ala591Pro) versus the benign variants (p.Ile100(76)Val, p.Glu470Asp and wild type) we also observed a higher levels of serum PRL (P=0.008), largest tumor diameter (P=0.028) and higher frequency of CAB resistance (P=0.048).Conclusion: Our study showed a higher frequency of the PRL-R variants p.Glu400(376)Gln/p.Asn516(492)Ile, and p.Ala591Pro in patients with prolactinomas when compared to Brazilian and international databases, suggesting that these variants could play a role in the prolactinoma tumorigenesis. Patients with PRL-R variants presented male predominance, higher serum PRL levels, larger tumor size at diagnosis and higher frequency of CAB resistance. More studies evaluating germinative and somatic PRL-R variants are needed to clarify the PRL/PRL-R system role in the tumorigenesis and progression of prolactinomas and their interesting association with CAB resistance. Presentation: Friday, June 16, 2023

DEAR COLLEAGUES, After 8 years and feeling accomplished, I am leaving the role of Editor-in-chief of our beloved Archives of Endocrinology and Metabolism – AE&M. Invited by the former president of SBEM, Dr. Nina Rosa Musolino, I accepted this mission proposing some changes, starting with altering the written language to English, seeking greater entrance in international endocrinology. In this way, the Arquivos Brasileiros de Endocrinologia e Metabologia became the Archives of Endocrinology and Metabolism. […] Farewell message from the Editor-in-chief

Abstract Purpose. The aim of this study was to evaluate the role of serum tumor markers for the differential diagnosis of ACTH-dependent Cushing’s syndrome (ADCS). Methods. This study included 185 patients with ADCS, 153 with Cushing’s disease (CD) and 32 with ectopic ACTH syndrome (EAS) who were evaluated between 1991 and 2019 and had at least one tumor marker measured at the time of diagnosis. Results. At least one elevated tumor sample was verified in 33% of CD and in 72% of EAS patients. Two or more elevated tumor samples were found in 9% of CD and 44% of EAS. In CD, gastrin was the most common abnormality in 21% of cases. In EAS, urinary 24-h 5-hydroxy indol acetic acid was the most frequent alteration in 80%, followed by chromogranin in 67%. Higher concentrations and a higher percentage of patients with changes in the tumor markers gastrin, CEA and chromogranin were found in patients with EAS in relation to CD. Analyzing the best values of tumor markers to differentiate patients with EAS and CD, significant differences were found in gastrin, calcitonin, CEA and chromogranin but with an overlap between subgroups. A positive direct correlation between hormonal parameters and tumor marker data was commonly verified in patients as a whole group. Conclusion. Abnormalities in serum tumor markers at the time of diagnosis were more common in EAS than CD patients. However, due to significant overlap between the subgroups, no single tumor marker presented high applicability for the differential diagnosis of ADCS.

Pregnancy is associated with the activation of the hypothalamus–pituitary–adrenal axis, which can cause a misdiagnosis of Cushing’s syndrome. The aim of this study is to evaluate the impact of pregnancy after pituitary surgery on the recurrence rate in Cushing’s disease (CD) patients. This was a retrospective study in a tertiary center. Between 1990 and 2020, 355 CD patients underwent pituitary surgery. Of those, we included 113 female patients who were ≤ 45 years old (median age of 32 years, 14–45), PS remission, a follow-up of ≥6 months (median of 122 months, 6–402) and an available obstetric history. Recurrence was defined as the diagnosis of Cushing’s syndrome via at least two altered first-line methods. The patients were divided into two subgroups according to pregnancy: no pregnancy or pregnancy prior to CD diagnosis (NP/PP) and pregnancy after CD pituitary surgery (PA). Overall, recurrence occurred in 43 out of 113 patients (38

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Context: Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. Objective: To develop a prediction model of therapeutic response of acromegaly to fg-SRL. Methods: Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). Results: A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P=.014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. Conclusion: We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

Non-functioning pituitary adenomas (NFPA) usually present with symptoms of mass effect. Thus, the first-line treatment generally consists of transsphenoidal surgery. Since these tumors are usually large and invasive, post-surgical tumor remnants are common. Active surveillance is the follow-up strategy adopted by most pituitary centers, although the prevalence of residual tumor growth may reach 50% in 5-10 years, often leading to repeat surgery, radiation therapy, or both. NFPA remain the only pituitary tumor type for which no medical therapy has been approved. In this debate, we consider the evidence in favor and against using cabergoline to treat progressing NFPA.

Context: The SAGIT (R) instrument (SAGIT) has been developed to enable accurate characterization of acromegaly disease activity. Objective: We evaluated the ability of SAGIT to discriminate acromegaly disease control status. Methods: This multicenter, noninterventional, prospective and retrospective, longitudinal study, conducted at academic and private clinical practice sites, included patients aged >= 18 years with a diagnosis of controlled (n = 109) or non-controlled (n = 105) acromegaly, assessed by clinical global evaluation of disease control (CGE-DC) questionnaire, investigator therapeutic decision, and international guidelines. Control status was not determined at baseline for 13 patients. Since 9 patients were enrolled retrospectively, all presented analyses are based on the prospective population (N = 227). Patients were assessed over a 2-year follow-up period. Classification and regression tree (CART) analyses were performed to investigate how SAGIT components at baseline (signs/symptoms [S], associated comorbidities [A], growth hormone levels [G], insulin-like growth factor 1 levels [II, tumor features [T]) discriminate between controlled and non-controlled acromegaly. Results: Baseline mean subscores S, G, I, andT were significantly lower in patients with CGE-DC controlled vs CGE-DC non-controlled acromegaly. SAGIT components I and G for CGE-DC and S, A, G, I, andT for the clinician's therapeutic decision were retained by CART analyses. For international guidelines, only SAGIT component I was retained.The risk for undergoing >= 1 treatment change during the study was 3.44 times greater for CGE-DC non-controlled acromegaly relative to CGE-DC controlled acromegaly. Conclusion: The SAGIT instrument is a valid and sensitive tool to comprehensively and accurately assess acromegaly severity.

Context: Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VFs). Objective: To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers, Wnt inhibitors, bone mineral density (BMD), microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared with healthy control group (HC). Design, setting, and patients: Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA), and 53 HC. Serum procollagen type 1 N-terminal propeptide, beta-carboxy-terminal crosslinked telopeptide of type 1 collagen, osteocalcin, sclerostin, and DKK1 were measured in blood samples. dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) and vertebral fractures evaluation were also assessed simultaneously. Main outcome and results: AcroA showed significantly lower sclerostin and higher DKK1 compared with HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity, and increased cortical area and cortical thickness compared with HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (R= 0.45, P= 0.044). Mild VFs were present in approximately 30% of patients. Conclusions: Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure, and increased VF. Sclerostin was not correlated with any HR-pQCT parameters; however, DKK1 was correlated with cortical porosity in tibia (P= 0.027). Additional studies are needed to clarify the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.

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. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Objective: A previous 12-month comparative trial with CriscyTM (r-hGH Crist?alia), a biosimilar recombinant growth hormone, demonstrated equivalent efficacy and safety to GenotropinTM. This extension trial evaluated the effects of switching patients treated with GenotropinTM to the biosimilar CriscyTM over an additional 6-month treatment period, comparing efficacy, safety, and immunogenicity parameters with patients remaining in the CriscyTM arm. Design. This extension study included 11 research centers and 81 patients who participated in the CERES study (Czepielewski et al., 2019 [1]). Participants from the GenotropinTM arm (n = 39) had the drug replaced by CriscyTM and the remaining participants were kept in the CriscyTM arm (n = 42) for an additional 6-month period to evaluate immunogenicity, efficacy (growth rate, height SDS), and safety (laboratory tests, and adverse events). Results: Before the switch, both CriscyTM and Genotropin groups were similar concerning demographics, and auxological measures: age, sex, height, height SDS, weight, and BMI. Height velocity (HV) after 18 months of treatment was 8.7 ? 1.56 cm/year for CriscyTM group and 8.9 ? 1.36 cm/year for GenotropinTM group in the ITT population (p = 0.43). The auxological parameters and IGF-1 and IGFBP-3 SDS were comparable between both groups of patients. No participants were excluded from the study due to adverse events. There were no clinical or statistical relevant differences between the treatment groups concerning frequency, distribution, intensity, and AEs outcome. Similarly, no new anti-r-hGH (ADA) cases among patients that switched from GenotropinTM to CriscyTM were reported. No neutralizing antibody (nAb) was detected in either group. Conclusions: This trial showed that switching from originator recombinant human growth hormone to CriscyTM had no impact on efficacy, safety, nor immunogenicity as compared to continued treatment with CriscyTM. Growth rates and ADA incidence remained the same as seen before the switch.

OBJECTIVE:The cyclicity (CIC) of cortisol spontaneously occurs in a minority of patients with Cushing syndrome (CS). When it arises, diagnostic and therapeutic approaches become more challenging. This study aimed to report a patient with Cushing disease (CD) who achieved normalization of cortisol and CIC pattern with pasireotide long-acting release (pasi/LAR).METHODS:A 43-year-old female patient related an 8-month history of CS. An 8-mm pituitary nodule depicted by magnetic resonance imaging, serum cortisol suppression of >50% after 8 mg of dexamethasone therapy, and the absence of other lesions were compatible with a CD diagnosis. The patient presented with a CIC pattern with 1 episode before and 17 episodes after an unsuccessful pituitary surgery.RESULTS:Medical treatment with cabergoline alone up to 3.5 mg/wk and a combined treatment with ketoconazole 400 mg/d did not improve CIC CS. Pasi/LAR was initiated at a dose of 20 mg/mo. A few days after the first dose, the patient experienced symptoms suggestive of adrenal insufficiency. The medication and dose were maintained for 24 months. During this period, there was a normalization of UFC levels and progressive clinical improvement. Additionally, new episodes of CIC were not observed.CONCLUSION:A CD patient with a challenging issue of CIC was reported. The condition was not controlled after pituitary surgery and by the combined treatment with cabergoline and ketoconazole, although hypercortisolism was abated by the continuous use of pasi/LAR. To our knowledge, this is the first report as regards the use of this medication to control CIC in a patient with CD.

The WHO Classification of Endocrine Tumours 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. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.