Gamma knife radiosurgery is effective in patients with thyrotropin-secreting pituitary adenomas.

PURPOSE: Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) is a rare cause of TSH-dependent hyperthyroidism. The first therapeutic option is surgery. Medical treatment with somatostatin analogs is also effective. To obviate the need for lifelong drug therapy, gamma knife radiosurgery (GKRS) might be considered in selected patients. We report the largest series of patients with TSHoma treated by GKRS at a single center. METHODS: This study was a retrospective analysis of 18 consecutive patients with TSHoma treated by GKRS between 1994 and 2022. Normalization of hyperthyroidism, when present at the time of surgery, and control of tumor growth were the main outcomes of the study. RESULTS: The median follow-up after GKRS treatment was 114 months (IQR, 57-213 months; range 17-285 months). No patients had growth of the residual tumor after GKRS. Remission of hyperthyroidism occurred in 9 of the 11 (81.8%) patients who were hyperthyroid before GKRS. The probability of hyperthyroidism remission three years after GKRS was 59.1% (95% CI 27.9-90.3%). No major side effects occurred after GKRS. One patient out of the 15 patients (6.7%) with normal baseline adrenal function and follow-up longer than 3 years developed new onset hypoadrenalism, while hypogonadism did not occur in the 13 patients with baseline normal function. CONCLUSION: Our study shows that GKRS is an effective and safe adjuvant treatment for selected patients with residual or recurring TSHoma. The option of GKRS as an alternative treatment to lifelong medical treatment with somatostatin analogs should be thoroughly discussed with the patients.

Targeted therapy in BRAF mutated aggressive papillary craniopharyngioma: a case report and overview of the literature.

BACKGROUND: Papillary craniopharyngiomas harbor the BRAF V600E mutation, which paves the way for using BRAF inhibitor molecules to treat tumors refractory to standard therapies. Single case reports confirmed the efficacy of targeted therapy. However, most reports were limited by the short follow-up. We describe the long-term course of a patient treated with dual-agent BRAF and MEK inhibitors and review the available literature. CASE REPORT: A 75-year-old male patient had recurrence of a papillary craniopharyngioma after transsphenoidal surgery and Gamma Knife radiosurgery. Review of the pathologic specimen confirmed the presence of the BRAF V600E mutation. Because of the few therapeutic options, we decided to initiate BRAF/MEK inhibitor combined therapy for six months. Rapid reduction of the tumor occurred, but three months after quitting combined medical therapy the tumor recurred. BRAF/MEK inhibitor therapy was resumed and the tumor again showed a marked reduction. The second course was maintained for 20 months and the tumor showed another recurrence within three months, which, again, responded to a third course of targeted therapy. CONCLUSIONS: Our study confirms the excellent response of papillary craniopharyngioma to combined BRAF and MEK inhibitors. However, rapid tumor recurrence is the rule when medical therapy is stopped. Resistance to a second and third course of targeted therapy did not occur, suggesting that tumor mutations affecting the response to drugs seems an uncommon event in papillary craniopharyngioma. The exact role of targeted therapy in the treatment algorithm of papillary craniopharyngiomas has still to be refined.

High prevalence of adrenal cortical adenomas in patients with cerebral meningiomas.

PURPOSE: Adrenal cortical adenomas (ACAs) represent one of the most common endocrine neoplasms. Recently, a genetic syndrome, characterized by tumor-suppressor ARMC5-gene mutations and causing primary macronodular bilateral adrenal hyperplasia with concomitant meningiomas of the central nervous system, has been described. Apart from this rare disorder and despite the well-known influence of steroid hormones on meningiomas, no data are available about the association between ACAs and meningiomas. METHODS: We investigated the prevalence of ACAs in a group of patients with cerebral meningioma undergoing unenhanced chest CT scans before attending surgical treatment. Patients with meningioma were age- and sex-matched in a 1:3 ratio with hospitalized patients for COVID-19. RESULTS: Fifty-six patients with meningioma were included and matched with 168 control patients with COVID-19. One-hundred forty-four (66.1%) were female and the median age was 63 years. Twenty ACAs were detected in the overall population (8.9% of the subjects): 10 in patients with meningioma (18%) and the remaining 10 (6%) in the control group (p = 0.007). Multivariate analysis showed that age and presence of meningioma were statistically associated with the presence of ACAs (p = 0.01, p = 0.008). CONCLUSION: We report, for the first time, a higher prevalence of ACAs in patients with meningioma as compared to age- and sex-matched controls. Larger studies are needed to confirm our data and to clarify the characteristics of the ACAs in patients with meningioma. Whether the detection of ACAs should prompt a neuroimaging evaluation to exclude the presence of meningiomas needs also to be considered.

[The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19]. / Utilidad de las escalas de sepsis para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 fuera de las Unidades de Cuidados Intensivos.

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥ 4 was found to be the best cutoff point for predicting respiratory failure.

Gamma knife radiosurgery in patients with Nelson's syndrome.

PURPOSE: Nelson's syndrome (NS) is a long-term complication of bilateral adrenalectomy in patients with Cushing's disease. The best therapeutic strategy in NS has not been well defined. Gamma knife radiosurgery (GKRS) is very effective to stop the growth of the pituitary adenoma, which is the main goal of the treatment of patients with NS. We report the largest series of patients with NS treated by GKRS at a single center. METHODS: The study was an observational, retrospective analysis of 28 consecutive patients with NS treated by GKRS in our department between 1995 and 2019. All patients had a growing ACTH-secreting pituitary adenoma. The main outcome of the study was to assess by the Kaplan-Meier method the risk of tumor progression after GKRS. RESULTS: The median follow-up after GKRS treatment was 98 months (IQR 61-155 months, range 7-250 months). Two patients (7.1%) had a recurrence of disease during follow-up. The 10-year progression-free survival was 91.7% (95% CI 80.5-100%). No patient had deterioration of visual function or oculomotor function after GKRS. New onset of hypogonadism and hypothyroidism occurred in 18.8% and 14.3% of the patients at risk. CONCLUSION: Our study confirms that GKRS may stop the tumor growth in the majority of patients with NS, even though very aggressive adenomas may ultimately escape this treatment. Safety of GKRS was good in our experience, but due attention must be paid to planning the distribution of radiation to critical structures, especially in patients previously treated by radiation.

Primary sellar melanocytoma: pathological, clinical and treatment review.

BACKGROUND: Sellar melanocytomas represent a small subgroup of primary melanocytic tumors. They arise from melanocytes located in the meningeal lining of the sellar floor or in the diaphragma sellae and this location is very uncommon. Usually, sellar melanocytomas are benign and slow-growing tumors with a high likelihood of recurrence. PURPOSE: To our knowledge, due to the rarity of this condition, there are no guidelines regarding their diagnosis and treatment in the medical literature to date. We have developed a narrative review, analyzing the available studies regarding primary sellar melanocytomas reported in the medical literature. We have found ten papers on this topic and all of them are case reports. In all patients, tumor diagnosis was performed after the occurrence of neurological symptoms, in particular progressive visual loss or endocrinological disorders. The diagnosis is difficult, and it requires several preoperative and postoperative investigations, but histological examination is crucial. CONCLUSIONS: Transsphenoidal surgery is the first-choice treatment. In case of tumor's recurrence or regrowth, the role of radiation therapy and chemotherapy is not entirely clear.

Analysis of characteristics and outcomes by growth hormone treatment duration in adult patients in the Italian cohort of the Hypopituitary Control and Complications Study (HypoCCS).

PURPOSE: To examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients. METHODS: In the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables. RESULTS: At baseline, treatment duration groups did not differ significantly for age, gender, body mass index, GHD onset, IGF-I SDS, lipid profile, and quality of life. Mean initial GH dose did not differ significantly according to treatment duration group in any subgroup, except female patients, with highest mean dose seen in the longest duration group. In the longest duration group for patients overall, adult-onset patients and male patients, there were significant decreases in GH dose from baseline to last visit, and in total and low-density lipoprotein (LDL)-cholesterol concentrations. IGF-I SDS increased, to a greater extent, in the longest duration group for patients overall and female patients. CONCLUSIONS: The results show that long-term GH treatment is associated with decreasing GH dose, increased IGF-I, decreased LDL-cholesterol and the presence of surrogate markers that help to give confidence in a diagnosis of GHD.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

Update on the imaging diagnosis of otosclerosis. / Actualización en el diagnóstico radiológico de la otosclerosis.

Otosclerosis is a primary osteodystrophy of the temporal bone that causes progressive conductive hearing loss. The diagnosis is generally clinical, but multidetector CT (MDCT), the imaging technique of choice, is sometimes necessary. The objective of this article is to systematically review the usefulness of imaging techniques for the diagnosis and postsurgical assessment of otosclerosis, fundamentally the role of MDCT, to decrease the surgical risk.

Does the COPD assessment test (CAT(TM)) questionnaire produce similar results when self- or interviewer administered?

PURPOSE: The COPD assessment test (CAT) is a questionnaire that assesses the impact of chronic obstructive pulmonary disease (COPD) on health status, but some patients have difficulties filling it up by themselves. We examined whether the mode of administration of the Spanish version of CAT (self vs. interviewer) influences its scores and/or psychometric properties. METHODS: Observational, prospective study in 49 Spanish centers that includes clinically stable COPD patients (n = 153) and patients hospitalized because of an exacerbation (ECOPD; n = 224). The CAT was self-administered (CAT-SA) or administered by an interviewer (CAT-IA) based on the investigator judgment of the patient's capacity. To assess convergent validity, the Saint George's Respiratory Disease Questionnaire (SGRQ) and the London Chest Activity of Daily Living (LCADL) instrument were also administered. Psychometric properties were compared across modes of administration. RESULTS: A total of 118 patients (31 %) completed the CAT-SA and 259 (69 %) CAT-IA. Multiple regression analysis showed that mode of administration did not affect CAT scores. The CAT showed excellent psychometric properties in both modes of administration. Internal consistency coefficients (Cronbach's alpha) were high (0.86 for CAT-SA and 0.85 for CAT-IA) as was test-retest reliability (intraclass correlation coefficients of 0.83 for CAT-SA and CAT-IA). Correlations with SGRQ and LCADL were moderate to strong both in CAT-SA and CAT-IA, indicating good convergent validity. Similar results were observed when testing longitudinal validity. CONCLUSIONS: The mode of administration does not influence CAT scores or its psychometric properties. Hence, both modes of administration can be used in clinical practice depending on the physician judgment of patient's capacity.

Multidisciplinary psoriasis and psoriatic arthritis unit: report of 4 years' experience.

INTRODUCTION AND OBJECTIVES: Up to 30% of patients with psoriasis develop joint disease, the course of which can be improved by early diagnosis and treatment. The aim of this study was to describe our experience with a new multidisciplinary psoriasis and psoriatic arthritis unit over a period of 4 years (2009-2012). MATERIAL AND METHODS: Implementation of a PSOriasis Rheumatology and Dermatology unit (PSORD) to provide patient care and physician training. In the first phase of the project, referral criteria for the unit were defined and several meetings were organized to train and prepare the specialists involved in the program. In the second phase, a schedule was drawn up for monthly patient visits with the PSORD team. Starting in 2011, training was offered to dermatologists and rheumatologists from other hospitals interested in implementing a similar model. RESULTS: A total of 259 visits (71% first visits, 8% no-shows) were scheduled during the period analyzed, with a median of 8 visits (range, 2-14 visits) per session. Sixty-three percent of the patients were referred from the rheumatology department. Diagnosis and treatment were modified in 32% and 47% of cases, respectively. Three training courses were held with 15 physicians from 6 hospitals, 3 of which created similar units. CONCLUSIONS: The PSORD model improved the management of difficult-to-diagnose and/or uncontrolled disease, the early diagnosis and treatment of psoriatic arthritis, and collaboration between dermatologists and rheumatologists. Finally, the model lends itself to being exported to other settings.

Health care costs of complex perianal fistula in Crohn's disease.

AIM: To evaluate the use of health care resources and the associated costs of complex perianal Crohn's disease (CD) from the National Health System perspective. METHODS: We conducted a multicenter, retrospective, observational study in which gastroenterologists from 11 hospitals in the Community of Madrid took part. Data was collected on the direct healthcare resources (pharmacological treatments, surgical procedures, laboratory/diagnostic tests, visits to specialists and emergency departments, and hospitalizations) consumed by 97 adult patients with complex perianal CD which was active at some point between January 1, 2005, and case history review. RESULTS: We recorded 527 treatments: 73.1% pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and 26.9% surgical. Mean annual global cost was €8,289/patient, 75.3% (€6,242) of which was accounted for by pharmacological treatments (€13.44 antibiotics; €1,136 immunomodulators; €5,093 biological agents), 12.4% (€1,027) by hospitalizations and surgery, 7.7% (€640) by medical visits, 4.2% (€350) by laboratory/diagnostic tests, and 0.4% (€30) by emergency department visits. CONCLUSIONS: Pharmacological therapies, and in particular biological agents, are the main cost driver in complex perianal CD; costs due to surgery and hospitalizations are much lower.

The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19.

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤200mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥4 was found to be the best cutoff point for predicting respiratory failure.

The role of radiation therapy in the management of non-functioning pituitary adenomas.

Surgical removal of non-functioning pituitary adenoma (NFPA) is the first-choice therapeutic option, but radical removal of the tumor cannot be accomplished in all patients. The best strategy to prevent regrowth of NFPA is still a matter of debate. Adjuvant radiotherapy is very effective in reducing recurrence rate after incomplete removal of NFPA, but concerns still exist about long-term toxicity of radiation. Different modalities have been developed to irradiate the pituitary region. One major distinction is between radiation techniques that deliver the total dose in multiple sessions using 3 fixed radiation beams and radiosurgical equipment that delivers the total dose to the target volume in a single treatment session. Progression-free survival of patients with NFPA treated by adjuvant radiotherapy is well above 90% at 5 yr in most studies and diminishes only slightly at 10 yr. Very few studies have a more prolonged follow-up. In comparison, the 5- and 10-yr estimated recurrence rate without adjuvant radiotherapy ranged from 15% to 51% and from 44% to 78%, respectively. Complications of radiation include rare but severe side-effects, such as secondary brain neoplasm, optic neuropathy, cerebrovascular accidents, and more frequent but less severe complications, such as pituitary deficiency. Optimal management of patients with residual or recurring NFPA after surgical debulking can be achieved through the judicious use of different treatment options, necessitating close cooperation between neurosurgeons, endocrinologists, and radiation oncologists.

Routine feasibility of postoperative chemoradiotherapy in head and neck squamous cell carcinoma at high risk of recurrence.

OBJECTIVE: To assess the feasibility in routine practice of postoperative chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC) at high risk of recurrence. METHOD: A single-center retrospective study recruited all patients receiving postoperative cisplatin chemoradiotherapy for HNSCC at high risk of recurrence. The main endpoints were the rate of complete postoperative chemoradiotherapy and the impact of various clinical factors. Secondary endpoints comprised the impact of completion of therapy on survival and on acute and late toxicity. RESULTS: One hundred and six patients were included. 24.5% showed severe comorbidity. Chemoradiotherapy was complete in 61 patients (57.5%). Radiation therapy was interrupted for >3 days in 16 patients (15.1%). The 3rd concomitant cisplatin course could not be implemented in 34 patients (32.1%). Low pre-treatment glomerular filtration rate was significantly associated (p=0.003) with treatment interruption; >5% weight-loss during treatment showed suggestive association (p=0.026). Completion of treatment was not associated with any significant difference in overall survival (p=0.441) or progression-free survival (p=0.81). 14.9% of patients showed post-treatment kidney failure; there were 10 cases of osteoradionecrosis (9.4%). CONCLUSION: The rate of complete postoperative chemoradiotherapy was comparable to that reported in clinical trials, despite frequent comorbidity and poor nutritional status. Early nutritional support is a key factor for treatment under optimal conditions.

PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients.

BACKGROUND: It has been reported that KRAS mutations (and to a lesser extent KRAS mutations with the BRAF V600E mutation) negatively affect response to anti-epidermal growth factor receptor (EGFR) mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear. PATIENTS AND METHODS: We analysed formalin-fixed samples from a cohort of 32 mCRC patients treated with cetuximab by means of EGFR immunohistochemistry, EGFR and PTEN FISH analysis, and KRAS, BRAF, PI3KCA, and PTEN genomic sequencing. RESULTS: Ten (31%) of 32 patients showed a partial response to cetuximab and 22 (69%) did not [nonresponder (NR)]. EGFR immunophenotype and FISH-based gene status did not predict an anti-EGFR mAb response, whereas KRAS mutations (24%) and PI3K pathway activation, by means of PI3KCA mutations (13%) or PTEN mutation (10%)/loss (13%), were significantly restricted to, respectively, 41% and 37% of NRs. CONCLUSION: These findings suggested that KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab. In line with this, patients carrying KRAS mutations or with activated PI3K profiles can benefit from targeted treatments only by switching off molecules belonging to the downstream signalling of activated EGFR, such as mammalian target of rapamycin.

Taurine chloramine inhibits functional responses of human eosinophils in vitro.

BACKGROUND: Eosinophils are prominent effectors of allergic inflammation. Taurine-chloramine (TauCl), a derivative of the amino acid taurine, shows antioxidant properties in different cell systems but its effects on eosinophils have not been reported. OBJECTIVE: To study the effects of TauCl and taurine on functional responses of isolated human eosinophils activated by different stimuli. METHODS: Human eosinophils were purified from the blood of healthy donors by a magnetic bead separation system. The effects of TauCl and taurine (0.1-1 mM) were investigated on the generation of superoxide anion (ferricytochrome-c reduction microassay), calcium signal (fluorimetry), p47phox-p67phox translocation (Western blot), leukotriene C4 (LTC4) production (enzymeimmunoassay), eosinophil peroxidase (EPO) release (spectrophotometry), eosinophil cationic protein (ECP) release (radioimmunoassay), apoptosis (flow cytometry with annexin V-propidium iodide), and nuclear factor-kappaB (NF-kappaB) activation (Western blot). RESULTS: TauCl inhibited superoxide anion generation triggered by N-formyl-Met-Leu-Phe (fMLP; 30 nM), phorbol myristate acetate (1 nM) and serum opsonized zymosan (0.5 mg/mL) with similar potency (IC50 approximately 200 microM) for the three stimuli, while taurine (0.1-1 mM) was scarcely effective. TauCl but not taurine inhibited p47phox-p67phox translocation. TauCl (200 microM) and taurine (1 mM) did not modify the [Ca2+]i responses to fMLP. TauCl inhibited the release of EPO (IC50 approximately 200 microM) and reduced ECP and LTC4 production from fMLP-activated eosinophils while taurine was without significant effects. TauCl (1 mM) did not change constitutive apoptosis but significantly attenuated the ability of granulocyte-monocyte colony-stimulating factor (GM-CSF) and IL-5 to prevent apoptosis. The activation of eosinophil NF-kappaB induced by GM-CSF and IL-5 was suppressed by TauCl. CONCLUSION: Taurine is without significant in vitro effects on human eosinophil functions but its derivative TauCl inhibits oxidative burst and generation of inflammatory mediators, and reverses the survival effect produced by inflammatory cytokines. Therefore, endogenous TauCl may help to suppress excessive inflammatory response in eosinophils at inflammatory sites.

Immunohistochemical analysis of VEGF-C/VEGFR-3 system and lymphatic vessel extent in normal and adenomatous human pituitary tissues.

The angiogenic growth factor Vascular Endothelial Growth Factor-C (VEGF-C) and its receptor VEGFR-3 are also known to be implicated in the development of lymphatic vessels. We assessed the expression of VEGF-C and VEGFR-3, together with blood and lymphatic vessel extents and proliferation index (PI) values, by immunohistochemistry (IHC) in 6 normal human pituitary glands and 53 pituitary adenomas of different tumour grade, on consecutive tissue sections. VEGF-C was detected in around 10% of the endocrine cells in normal pituitary tissue, while this gland was devoid of lymphatic vascularization and showed very few vessels positive for VEGFR-3. Concerning tumour tissue, most of the adenomas showing VEGF-C immunoreactivity (21/47) were positive in 60% of the tumour cells and the ones positive for VEGFR-3 showed a number of immunostained vessels higher than those observed in the normal pituitary. Most of the tumours positive for VEGFR-3 did not show any LYVE-1 positive vessels (18/53), suggesting that at least in these cases, VEGFR-3 is expressed on blood vessels. Nevertheless, we observed a significant association between low expression of VEGFR-3 and low lymphatic vessel number, suggesting that VEGFR-3 might be involved in the starting of DE NOVO lymphangiogenesis in this tumour type. Moreover, tumours bearing lymphatic vessels showed the tendency to shift towards a more aggressive behaviour (high tumour grade and high PI). In conclusion, the VEGF-C/VEGFR-3 system might be involved in controlling tumour angiogenesis in the pituitary adenomas lacking lymphatic vessels, but may also play a role in starting the process of tumour lymphangiogenesis.

Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.