Novel SUZ12 mutations in Weaver-like syndrome.

SUZ12 is a core component of polycomb repressive complex 2 (PRC2) along with EZH2 and EED. Recently, germline mutations in the SUZ12, EZH2 and EED genes have been reported in Weaver syndrome (WS) or Weaver-like syndrome, suggesting a functional link between PRC2 deficits and WS. However, only one case of a SUZ12 mutation presenting with Weaver-like syndrome has been reported. Here, we report a missense and a frameshift mutation in SUZ12 (c.1797A>C; p.Gln599His and c.844_845del; p.Ala282Glnfs*7), both of which are novel, in two individuals. Their clinical features included postnatal overgrowth, increased bifrontal diameter, large ears, round face, horizontal chin crease and skeletal anomalies, but did not fulfill the WS diagnostic criteria. These data provide strong evidence that SUZ12 mutations cause Weaver-like syndrome.

Different Cerebellar Ataxia Phenotypes Associated with Mutations of the PNPLA6 Gene in Brazilian Patients with Recessive Ataxias.

Autosomal recessive cerebellar ataxias (ARCAs) represent a heterogeneous group of inherited disorders. The association of early-onset cerebellar ataxia with hypogonadotropic hypogonadism is related to two syndromes, known as Gordon Holmes syndrome (GHS-ataxia and pyramidal signs with hypogonadotropic hypogonadism) and Boucher-Neuhäuser syndrome (BNS-ataxia with chorioretinal dystrophy). Mutations in the PNPLA6 gene have been identified as the cause of hereditary spastic paraplegia and complex forms of ataxia associated with retinal and endocrine manifestations. We reported two Brazilian patients with sporadic, progressive cerebellar ataxia, associated with hypogonadotropic hypogonadism, in whom the GHS and BNS were confirmed by the demonstration of compound heterozygote mutations in the PNPLA6 gene. Genetic analysis of the patient 1 revealed compound heterozygous mutations, one allele in exon 34 and the other allele in exon 29. Genetic exam of the patient 2 also demonstrated compound heterozygous mutations. Three were novel mutations. The missense mutation c.3373G> A, found in the BNS patient, was previously related to Oliver-McFarlane syndrome. These different mutations in this gene suggest a complex phenotype associated disease spectrum.

Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine.

CONTEXT: Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. OBJECTIVE: To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). METHODS: This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had insulin-like growth factor I (IGF-I) ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0×ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary (ASD) score, and maintenance of mean 5-sample growth hormone (GH) <1.0 ng/mL. RESULTS: The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0×ULN (odds ratio: 126.53; 95% CI: 13.73, >999.99; P<.0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (±SE) change in IGF-I of 0.04±0.09×ULN versus 0.83±0.1×ULN (P<.0001); mean (±SE) change in ASD score of -0.6±1.5 versus 4.6±1.6 (P=.02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) versus 5/18 (27.8%) patients (odds ratio: 16.61; 95% CI: 2.86, 181.36; P=.0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. CONCLUSION: Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.

Evaluating home injection compared with healthcare-setting injection of somatostatin analogs: a systematic literature review.

PURPOSE: A systematic literature review was conducted to assess the use of home injections (self/partner/healthcare provider [HCP]-administered) of somatostatin analogs (SSAs) as an alternative to healthcare-setting injections in patients with acromegaly and neuroendocrine tumors (NETs). METHODS: MEDLINE/Embase/the Cochrane Library (2001-September 2021), key congresses (2019-2021), and bibliographies of relevant systematic reviews were searched. Eligible studies reported on efficacy/effectiveness, safety, adherence, patient-reported outcomes (PROs), and economic outcomes in populations receiving home injections of SSAs. RESULTS: Overall, 12 studies were included, all reporting on SSAs (lanreotide Autogel/Depot or octreotide long-acting release) in acromegaly or NETs. Across four studies, home injection was associated with similar disease control in patients with acromegaly/NETs compared with healthcare-setting administration. High rates of treatment adherence were shown in two studies of patients with acromegaly receiving lanreotide injections at home. Two studies reported non-serious adverse events; incidence of adverse reactions was similar in both the home and healthcare administration settings. Preference for injection setting varied between studies and indications; nonetheless, higher satisfaction/convenience (>75% patients) was reported for home injections. Self- or partner-injection was associated with economic savings compared with administration in the healthcare setting across five studies. CONCLUSION: Efficacy/effectiveness, adherence, and safety outcomes of SSAs in the home injection setting were similar to those in the healthcare setting, with high reported satisfaction and convenience. Self/partner injection also resulted in cost savings. These findings provide a basis to understand outcomes related to home injection and encourage healthcare providers to discuss optimal treatment choices with their patients.

Thyroid and Breast Cancer in 2 Sisters With Monoallelic Mutations in the Ataxia Telangiectasia Mutated (ATM) Gene.

The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of the breast at 44 and 42 years. The 2 children of the younger sister developed ataxia-telangiectasia; the son also developed lymphoblastic lymphoma and his sister died secondary to acute lymphoblastic leukemia (ALL). They were found to be compound heterozygous for ataxia telangiectasia mutated (ATM) gene mutations (c.3848T>C, p.L1283P; and c.802C>T, p.Q268X). Exome sequencing of the 2 sisters (mother and aunt of the children with ataxia-telangiectasia) led to the detection of the pathogenic monoallelic ATM mutation in both of them (c.3848T>C; minor allele frequency [MAF] < 0.01) but detected no other variants known to confer a risk for PTC or breast cancer. The findings suggest that monoallelic ATM mutations, presumably in conjunction with additional genetic and/or nongenetic factors, can confer a risk for developing PTC and breast cancer.

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogs.

Daily recombinant human GH (rhGH) is currently approved for use in children and adults with GH deficiency (GHD) in many countries with relatively few side-effects. Nevertheless, daily injections can be painful and distressing for some patients, often resulting in non-adherence and reduction of treatment outcomes. This has prompted the development of numerous long-acting GH (LAGH) analogs that allow for decreased injection frequency, ranging from weekly, bi-weekly to monthly. These LAGH analogs are attractive as they may theoretically offer increased patient acceptance, tolerability, and therapeutic flexibility. Conversely, there may also be pitfalls to these LAGH analogs, including an unphysiological GH profile and differing molecular structures that pose potential clinical issues in terms of dose initiation, therapeutic monitoring, incidence and duration of side-effects, and long-term safety. Furthermore, fluctuations of peak and trough serum GH and IGF-I levels and variations in therapeutic efficacy may depend on the technology used to prolong GH action. Previous studies of some LAGH analogs have demonstrated non-inferiority compared to daily rhGH in terms of increased growth velocity and improved body composition in children and adults with GHD, respectively, with no significant unanticipated adverse events. Currently, two LAGH analogs are marketed in Asia, one recently approved in the United States, another previously approved but not marketed in Europe, and several others proceeding through various stages of clinical development. Nevertheless, several practical questions still remain, including possible differences in dose initiation between naïve and switch-over patients, methodology of dose adjustment/s, timing of measuring serum IGF-I levels, safety, durability of efficacy and cost-effectiveness. Long-term surveillance of safety and efficacy of LAGH analogs are needed to answer these important questions.

Corrigendum: Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogues.

[This corrects the article DOI: 10.3389/fendo.2021.637209.].

Bariatric Surgery for Hypothalamic Obesity in Craniopharyngioma Patients: A Retrospective, Matched Case-Control Study.

CONTEXT: Craniopharyngioma is a sellar tumor associated with high rates of pituitary deficiencies (~ 98%) and hypothalamic obesity (~ 50%). OBJECTIVE: This work aims to determine the efficacy regarding long-term weight loss after bariatric surgery in obese craniopharyngioma patients with hypothalamic dysfunction. METHODS: This retrospective, case-control, multicenter, international study included obese craniopharyngioma patients (N = 16; of whom 12 are women) with a history of bariatric surgery (12 Roux-en-Y gastric bypass, 4 sleeve gastrectomy; median age 21 years [range, 15-52 years], median follow-up 5.2 years [range, 2.0-11.3 years]) and age/sex/surgery/body mass index-matched obese controls (N = 155). Weight loss and obesity-related comorbidities up to 5 years after bariatric surgery were compared and changes in hormonal replacement therapy evaluated. RESULTS: Mean weight loss at 5-year follow-up was 22.0% (95% CI, 16.1%-27.8%) in patients vs 29.5% (95% CI, 28.0%-30.9%) in controls (P = .02), which was less after Roux-en-Y gastric bypass (22.7% [16.9%-28.5%] vs 32.0% [30.4%-33.6%]; P = .003) but at a similar level after sleeve gastrectomy (21.7% [-1.8% to 45.2%] vs 21.8% [18.2%-25.5%]; P = .96). No major changes in endocrine replacement therapy were observed after surgery. One patient died (unknown cause). One patient had long-term absorptive problems. CONCLUSION: Obese patients with craniopharyngioma had a substantial mean weight loss of 22% at 5-year follow-up after bariatric surgery, independent of type of bariatric surgery procedure. Weight loss was lower than in obese controls after Roux-en-Y gastric bypass. Bariatric surgery appears to be effective and relatively safe in the treatment of obese craniopharyngioma patients.

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

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

Influence of the exon 3-deleted/full-length growth hormone (GH) receptor polymorphism on the response to GH replacement therapy in adults with severe GH deficiency.

CONTEXT: There is considerable individual variation in the clinical response to GH replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. OBJECTIVE: The aim of the study was to assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD. DESIGN AND PATIENTS: A total of 124 adult GHD patients (79 men; median age, 50 yr) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (group 1) and those bearing at least one d3-GHR allele (group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). INTERVENTION: GH dose was individually titrated to obtain normal serum IGF-I levels. MAIN OUTCOME MEASURES: GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. RESULTS: Seventy-two (58%) patients had fl/fl genotype and were classified as group 1, whereas 52 (42%) had at least one d3-GHR allele and were classified as group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. CONCLUSION: The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.

Sarcopenia in heart failure with reduced ejection fraction.

AIMS: To evaluate the prevalence of pre-sarcopenia and sarcopenia and their relationship with clinical variables, physical activity, quality of life, and diet in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). METHODS: We performed a cross-sectional study in patients with HFrEF and matched controls. Clinical, laboratory analysis, dual-emission X-ray densitometry, handgrip strength, and physical activity level questionnaire assessments were performed. Echocardiography, quality of life, gait speed, and 24-hour nutritional recall questionnaire were also analyzed. Pre-sarcopenia and sarcopenia were defined according to the European Working Group on Sarcopenia in Older People with the cut-off points of the Foundation for the National Institute of Health. RESULTS: 79 patients and 143 controls were enrolled. Pre-sarcopenia was found in 30.4%, and sarcopenia in 10.1% of the patients. Pre-sarcopenic patients were older and shorter, and had more fractures, higher calcemia, and creatinine (P < 0.05). Sarcopenic patients were older and had higher creatinine and TSH (P < 0.05). After multiple logistic regression analysis, only age was associated with pre-sarcopenia (OR: 1.046; CI 1.004-1.095; P = 0.04) and SP (OR: 1.119; CI 1.039-1.229; P = 0.008). Women with HFrEF presented higher lean mass than controls (P < 0.001), but were weaker (P < 0.001), while men presented lower lean mass (P < 0.001). Low gait speed was associated with right ventricular dysfunction (P = 0.016) and lower left ventricular ejection fraction (P = 0.037). CONCLUSION: Pre-sarcopenia and sarcopenia were associated with aging. Despite having higher lean mass, women with HFrEF were weaker. Low gait speed was associated with biventricular systolic dysfunction.

Brazilian multicenter study on pegvisomant treatment in acromegaly.

OBJECTIVE: Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. SUBJECTS AND METHODS: Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. RESULTS: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. CONCLUSIONS: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Association between undercarboxylated osteocalcin, bone mineral density, and metabolic parameters in postmenopausal women.

OBJECTIVE: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. SUBJECTS AND METHODS: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. RESULTS: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). CONCLUSION: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

Bone density and bone turnover markers in patients with epilepsy on chronic antiepileptic drug therapy.

In this comparative, cross-sectional study, we evaluated 55 patients with epilepsy on chronic use of antiepileptic drugs (AED); [(38 females and 17 males, 35 +/- 6 years (25 to 47)] and compared to 24 healthy subjects (17 females/7 males). Laboratorial evaluation of bone and mineral metabolism including measurements of bone specific alkaline phosphatase (BALP) and carboxyterminal telopeptide of type I collagen (CTX-I) were performed. Bone mineral density (BMD) was measured by DXA. BALP and CTX-I levels did not differ significantly between the groups. CTX-I levels were significantly higher in patients who were exposed to phenobarbital (P< 0.01) than those who were not. Patients presented BMD of both sites significantly lower than the controls (0.975 +/- 0.13 vs. 1.058 +/- 0.1 g/cm(2); p= 0.03; 0.930 +/- 0.1 vs. 0.988 +/- 0.12 g/cm(2); p= 0.02, respectively). Total hip BMD (0.890 +/- 0.10 vs. 0.970 +/- 0.08 g/cm(2); p< 0.003) and femoral neck (0.830 +/- 0.09 vs. 0.890 +/- 0.09 g/cm(2); p< 0.03) were significantly lower in patients who had been exposed to phenobarbital, in comparison to the non-phenobarbital users. In conclusion, patients on AED demonstrate reduced BMD. Among the AED, phenobarbital seems to be the main mediator of low BMD and increases in CTX-I.

MECHANISMS IN ENDOCRINOLOGY: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism.

Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system. As the first genetic variant to potentially influence the individual response to rhGH therapy in children with growth disorders, polymorphism in the GH receptor (GHR) has attracted a great interest as a target for pharmacogenetics. Studies have been conducted to compare the functional and molecular effects of the full-length GHR (fl-GHR) isoform with the exon 3 deleted (d3-GHR) isoform in children and adults treated with rhGH therapy. Additionally, the impact of the GHR polymorphism has been investigated in relation to the clinical status and response to medical treatment in acromegaly, especially to the GHR antagonist drug pegvisomant. We have performed a narrative review of the studies performed to date on the association of GHR polymorphism with rhGH response in children and adults, and its potential influence in the medical management of acromegaly. In addition, data from studies on the general population and in other chronic diseases examining a role of this genetic variant in the regulation of growth and metabolism are summarized.

Fragility Fracture Incidence in Chronic Obstructive Pulmonary Disease (COPD) Patients Associates With Nanoporosity, Mineral/Matrix Ratio, and Pyridinoline Content at Actively Bone-Forming Trabecular Surfaces.

Chronic obstructive pulmonary disease (COPD) is associated with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and altered microstructure by bone histomorphometry and micro-computed tomography. Nevertheless, not all COPD patients sustain fragility fractures. In the present study, we used Raman microspectroscopic analysis to determine bone compositional properties at actively forming trabecular surfaces (based on double fluorescent labels) in iliac crest biopsies from 19 postmenopausal COPD patients (aged 62.1 ± 7.3 years). Additionally, we analyzed trabecular geometrical centers, representing tissue much older than the forming surfaces. Eight of the patients had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. None of the patients had taken oral glucocorticoids. The monitored parameters were mineral/matrix ratio (MM), nanoporosity, and relative glycosaminoglycan (GAG), lipid, and pyridinoline contents (PYD). There were no significant differences between the glucocorticoid-treated patients and those who did not receive any. On the other hand, COPD patients sustaining fragility fractures had significantly lower nanoporosity and higher MM and PYD values compared with COPD patients without fragility fractures. To the best of our knowledge, this is the first study to discriminate between fracture and non-fracture COPD patients based on differences in the material properties of bone matrix. Given that these bone material compositional differences are evident close to the cement line (a major bone interface), they may contribute to the inferior bone toughness and coupled with the lower lumbar spine bone mineral density values result in the fragility fractures prevalent in these patients. © 2016 American Society for Bone and Mineral Research.

Serum levels of leptin and adiponectin and clinical parameters in women with fibromyalgia and overweight/obesity.

OBJECTIVES: The objectives of this study were to evaluate the serum levels of adipokines in women with fibromyalgia with and without overweight/obesity, and to correlate the adipokines levels with clinical parameters associated with fibromyalgia and adipose tissue mass (body fat). SUBJECTS AND METHODS: The study included 100 women divided into four groups: (a) fibromyalgia and overweight/obesity; (b) fibromyalgia and normal weight; (c) controls and overweight/obesity; and (d) controls and normal weight. Patients and controls were evaluated for clinical, anthropometric, and fibromyalgia-related parameters. Assessments included serum levels of leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP). Levels of adipokines were further adjusted for fat mass. RESULTS: Fibromyalgia patients with overweight/obesity or normal weight had no differences in clinical parameters. Unadjusted leptin levels were lower in fibromyalgia patients than controls, a finding that was more remarkable in fibromyalgia patients with overweight/obesity. Leptin levels had no correlation with clinical parameters of fibromyalgia or inflammation markers (MCP-1 and CRP), and adiponectin levels showed no difference between groups. CONCLUSIONS: No correlation was observed between adjusted leptin levels and clinical parameters of fibromyalgia. Patients with fibromyalgia and overweight/obesity presented lower levels of leptin than controls with overweight/obesity.

A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism.

Clinically nonfunctioning pituitary adenomas (NFPA) are the most common pituitary tumors after prolactinomas. The absence of clinical symptoms of hormonal hypersecretion can contribute to the late diagnosis of the disease. Thus, the majority of patients seek medical attention for signs and symptoms resulting from mass effect, such as neuro-ophthalmologic symptoms and hypopituitarism. Other presentations include pituitary apoplexy or an incidental finding on imaging studies. Mass effect and hypopituitarism impose high morbidity and mortality. However, early diagnosis and effective treatment minimizes morbidity and mortality. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism is to provide a review of the diagnosis and treatment of patients with NFPA, emphasizing that the treatment should be performed in reference centers. This review is based on data published in the literature and the authors' experience. Arch Endocrinol Metab. 2016;60(4):374-90.