Inactive Pituitary Adenomas Research Articles

Central diabetes insipidus after transnasal adenomectomy:trends in development and recovery, clinical and laboratory characteristics

Background: Currently, there is an increase in the incidence of chiasmosellar neoplasms and respective neurosurgical interventions. The postoperative period may be complicated by vasopressin synthesis and secretion disorders. Both the development and abortion of the fluid and electrolyte disorders can be delayed. Due to a tendency for an earlier discharge of the patients, a proportion of the disorders remain unaddressed. There is no data on the evolution and time to regress of transient abnormalities in the published studies with a long-term postoperative follow-up.
 Aim: To assess the incidence, evolution and regression trends, clinical and laboratory characteristic of postoperative central diabetes insipidus (CDI).
 Materials and methods: The single center retrospective comparative study included 150 patients who had undergone transnasal adenomectomy for Cushings disease, acromegaly, prolactinomas, and hormonally inactive pituitary adenomas. Clinical and laboratory assessments were performed pre- and postoperatively. In the event of CDI, treatment with desmopressin was administered. Ninety six (96) patients aged 20 to 65 years (median age 43 [35; 54] years) were followed for at least 60 months after the procedure.
 Results: Median time to the onset of permanent CDI (pCDI) was Day 5 [1; 9.5] after surgery, that of transient CDI (tCDI) Day 1 [1; 4.5] with its remission by Day 30 [1.5; 199]. The maximally delayed onset was on Day 86 for the pCDI and Day 61 for tCDI; that to the remission of tCDI, 738 days. At discharge from the hospital, postoperative CDI was present in 34/150 patients (23%; 95% CI 1730), and in 25/150 of the patients (16%; 95% CI 1224) the disorder resolved. At 5 to 7 years after surgery, the prevalence of pCDI was 16% (95% CI 1024), that of tCDI 35% (95% CI 2745), 49% (95% CI 3959) of the patients had no abnormalities (respective absolute patient numbers being 15, 34, and 47 of 96 followed for at least 60 months). At Days 1 to 7 after surgery, the patients with pCDI and tCDI had more frequent complaints of dry mouth and thirst than those without the disorder. These complaints were verified by higher 24-hour fluid intake and diuresis at the day of surgery and Days 5 to 7 thereafter, compared to those in the patients without the disorders. At Days 57 after surgery, urine sodium and urine specific gravity were significantly lower, as was urine osmolality at all postoperative stages, compared to those in the patients without the disorders.
 Conclusion: Within 2 years after transnasal adenomectomy, the incidence of postoperative CDI is gradually decreasing (from 23% to 16%). Due to potentially delayed manifestation of water and electrolyte imbalance, it is recommended that these parameters should be monitored at least for 2,5 months after the discharge from hospital. Due to potentially delayed remission (12 months and more), follow-up and monitoring for 1.5 years is reasonable, with periodic assessment of sodium levels, fluid intake and excretion, and attempts to withdraw desmopressin.

Neuroimaging Assessment of Aggressive Pituitary Adenomas

Aggressive pituitary adenomas (APA) are adenomas that show rapid growth, invasiveness, frequent or multiple relapses, or are resistant to conventional therapies. Clinical-imaging assessment of aggressive pituitary adenomas with the aid of magnetic resonance imaging (MRI) plays an important role in early prediction, further disease outcomes and aggressive behavior of adenomas.
 Purpose of the Study: was to assess the correlation of neuroimaging data with the hormonal activity of APA.
 Materials and Methods: The study included 74 patients with aggressive pituitary adenomas. The average age of the patients was from 12 to 69. The patients underwent a basal assessment of the level of pituitary hormones: prolactin (PRL), GH (growth hormone), insulin-like growth factor-1 (IGF-1) and blood cortisol by the RIA method, as well as an MRI study. Knop's classification was used to assess the invasion.
 Results: The hormonal workup showed prevalence of inactive pituitary adenomas among aggressive adenomas. No correlation was found between the hormonal activity of aggressive adenomas and the volume of pituitary adenomas. Moreover, MRI data indicated that invasion into the cavernous sinus of the III degree and heterogeneity of the adenoma may be considered equivalents of aggressiveness.
 Conclusion: The established patterns support the need for visualization assessment of aggressive pituitary adenomas and strongly suggest the evaluation of the degree of aggression based on tumor heterogenecity, chiasm compression, hypo- and iso-intensity in T1 mode and hyperintensity in T2 modes.

Состояние показателей процессов апоптоза и ангиогенеза у больных с неактивными аденомами гипофиза

В статье авторы анализируют данные 71 пациента с неактивной аденомой гипофиза (НАГ) в возрасте от 18 до 70 лет. Выявлено отсутствие корреляционной связи между снижением показателя активности фермента eNOS и показателями регуляции про- и антиапоптоза, ангиогенеза, что свидетельствует о независимости этих процессов в механизмах формирования НАГ. У больных с НАГ и не-отягощенным семейным анамнезом возрастает показатель корреляционной связи eNOS с VEGFR-2, что свидетельствует об усилении процессов торможения ангиогенеза и пролиферативной активности ткани. Проведенные исследования не позволяют установить зависимость выявленных нарушений у больных с микроаденомой и макроаденомой, различия по полу, длительности заболевания, наследственно-генетическим признакам и т.д. Это подчеркивает необходимость проведения дальнейших исследований в данном направлении.

Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas

BackgroundPituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. Despite the appealing role of cyclooxygenase enzymes and their bioactive lipid products in cancer pathogenesis, their relevance to pituitary adenoma pathogenesis is debated and yet to be determined. Thus, the current study perused this relevance.MethodsThe expression level of the isoforms of cyclooxygenase (COX-1 and COX-2) was evaluated in hormone-secreting and in-active pituitary adenoma tumors and normal pituitary tissues through Real-Time PCR. The level of PGE2, as the main product of enzymes, was assessed using enzyme immunoassay kits in patients and healthy subjects.ResultsThe results of the current study demonstrated that COX-1 and COX-2 expression levels were increased in pituitary tumors including non-functional pituitary adenoma (NFPA), acromegaly, Cushing’s disease and prolactinoma compared with normal pituitary tissues. A significant expression level of COX-2 was observed in NFPA compared with the other pituitary tumors. Furthermore, the COX-2 expression level was significantly increased in macroadenoma and invasive tumors. The level of PGE2 was consistent with COX enzymes enhanced in pituitary adenoma tumors compared with healthy pituitary tissue. A significant elevation in the PGE2 level was detected in NFPA compared with hormone-secreting pituitary tumors. Additionally, the PGE2 level was increased in macroadenoma compared with microadenoma and in invasive compared with non-invasive pituitary tumors. The diagnostic values of cyclooxygenase isoforms and PGE2 were considerable between patients and healthy groups; however, COX-2 revealed more value in distinguishing endocrinologically active and non-active pituitary tumors.ConclusionsData from the current study provides expression patterns of COX-1, COX-2 and PGE2 in prevalent pituitary tumors and their association with patients’ clinical features which may open up new molecular targets for early diagnosis/follow up of pituitary tumor growth.

An ovarian hyperstimulation syndrome caused by gonadotropinoma in a young woman

From 14 to 54% of all pituitary adenomas are nonfunctioning pituitary adenomas (NPAs), their prevalence is estimated as 7.041.3 cases per 100 000 population. The most common type of NPAs (73% of cases) are gonadotropinomas. In most cases, gonadotropinoma is characterized by secretion of biologically inactive hormones, so the release of gonadotropins does not lead to the development of any clinical symptoms. For this reason the diagnosis of gonadotropinomas is most often performed on the basis of immunohistochemical analysis. However, in rare cases, gonadotropinomas secrete biologically active hormones, most often follicle-stimulating (FSH). Ovarian hyperstimulation syndrome due to gonadotropin-secreting pituitary tumors occurs in about 3% of women with hormonally inactive pituitary adenomas at reproductive age and in 8% of patients with verified gonadotropinomas. This clinical case describes a young patient with a rare pathology: FSH/LH-secreting macroadenoma of the pituitary, which led to the development of ovary hyperstymulation symdrome. The diagnosis of pituitary adenoma was performed due to the identified hyperprolactinemia one month before the development of visual impairment, which can be considered a late diagnosis. Surgical treatment of gonadotropinomy was carried out successfully and without complications, remission of the disease was achieved, visual function was restored, the patient successfully became pregnant.

ХАРАКТЕРИСТИКА НАРУШЕНИЙ РАЗВИТИЯ ПРИ ОБЪЕМНЫХ ЗАБОЛЕВАНИЯХ ГИПОФИЗА У ДЕТЕЙ И ПОДРОСТКОВ

The aim of the study was to study the nature of developmental disorders in children and adolescents with masses of the Turkish saddle. Material and methods. 44 children and adolescents with large tumors of the Turkish saddle (TS) were under our supervision in the neuroendocrinology department of the RSNPMCE MH RUz. Of 44 sick girls there were 20, boys 24. The average age of girls was 12.1 years, boys - 12.8 years. By the nature of the pathology, the patients were divided into 5 groups: I group. - inactive pituitary adenomas (NAG) - 23 patients (52.3%); II gr. - Itsenko-Cushing's disease - 5 (11.4%); III gr. - craniopharyngioma - 6 (13.6%); IV gr. - prolactinoma - 5 b-x (11.4%); V gr. - germinoma - 5 bx (11.4%). Results. The results obtained indicate that in children and adolescents there are TJ masses of various origins: inactive pituitary adenomas (52%), craniopharyngiomas (13.6%), corticotropinomas (11.4%), prolactinomas (11.4%), and others. The presence of diabetes insipidus (8.6%) indicates the severity of panhypopituitarism that developed as a result of the tumor. Conclusions: 1) disorders of growth and puberty are the most frequent manifestations of pituitary gland masses (34.0%), 2) pituitary tumors in children and adolescents often lead to hypo- and panhypopituitarism (n = 19, or 43.2%).

Studying of a condition of reproductive function of patients with the inactive pituitary adenomas (IPA)

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

Visualisation characteristic of the inactive pituitary adenoma (IPA)

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

ХАРАКТЕРИСТИКА НАРУШЕНИЙ РАЗВИТИЯ ПРИ ОБЪЕМНЫХ ЗАБОЛЕВАНИЯХ ГИПОФИЗА У ДЕТЕЙ И ПОДРОСТКОВ

The aim of the study was to study the nature of developmental disorders in children and adolescents with masses of the Turkish saddle. Material and methods. 44 children and adolescents with large tumors of the Turkish saddle (TS) were under our supervision in the neuroendocrinology department of the RSNPMCE MH RUz. Of 44 sick girls there were 20, boys 24. The average age of girls was 12.1 years, boys - 12.8 years. By the nature of the pathology, the patients were divided into 5 groups: I group. - inactive pituitary adenomas (NAG) - 23 patients (52.3%); II gr. - Itsenko-Cushing's disease - 5 (11.4%); III gr. - craniopharyngioma - 6 (13.6%); IV gr. - prolactinoma - 5 b-x (11.4%); V gr. - germinoma - 5 bx (11.4%). Results. The results obtained indicate that in children and adolescents there are TJ masses of various origins: inactive pituitary adenomas (52%), craniopharyngiomas (13.6%), corticotropinomas (11.4%), prolactinomas (11.4%), and others. The presence of diabetes insipidus (8.6%) indicates the severity of panhypopituitarism that developed as a result of the tumor. Conclusions: 1) disorders of growth and puberty are the most frequent manifestations of pituitary gland masses (34.0%), 2) pituitary tumors in children and adolescents often lead to hypo- and panhypopituitarism (n = 19, or 43.2%).

The occurrence of hyperprolactinemia in a hormonally inactive pituitary adenoma

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

Clinical and functional characteristics of giant pituitary adenomas in the population of patients in the Moscow region

The aim of this study was to identify the clinical and functional features of giant pituitary tumors with different hormonal activity. We analyzed data of clinical, laboratory, and instrumental examinations of 351 patients diagnosed with pituitary macroadenomas at the Moscow Regional Research Clinical Institute in the period between 2008 and 2017: there were 144 hormonally inactive pituitary adenomas and 207 hormonally active pituitary adenomas (65 prolactinomas and 142 somatotropinomas). Among 351 patients with pituitary macroadenomas, there were 32 (9.1%) giant adenoma cases: 18 (12.5%) 144 patients with hormonally inactive pituitary adenomas and 14 (6.8%) 207 patients with hormonally active pituitary adenomas 6 (3.9%) 65 prolactinomas and 6 (2.9%) 142 somatotropinomas. The volume of giant adenomas was somewhat larger among somatotropinomas 48 926 [35 067; 97 650] mm3 and prolactinomas 36 872 [15 281; 75 102] mm3 compared to that of hormonally inactive pituitary adenomas 26 933 [21 910; 42 895] mm3. Tumors had predominant suprasellar and posterosellar growth (31 (97.8%) and 29 (90.6%) cases, respectively). The most common first patient complaints were visual impairments (59.4%) and headache and/or dizziness (43.8%). Correspondingly, due to these complaints, 16 (50%) patients first consulted an ophthalmologist. Hypopituitarism detected before any treatment was present in 16 (50%) patients. In most cases, visual impairments and headaches/dizziness were the first manifestations of giant pituitary adenomas; therefore, ophthalmologists and neurologists should always refer patients with these complaints to MRI. Patients with identified giant pituitary tumors should be referred to an endocrinologist for exclusion of hypopituitarism and, if necessary, timely prescription of hormonal therapy.

Expression of osteogenesis regulatory genes in the bone tissue of patients with acromegaly and endogenous hypercorticism

Excessive hormone secretion during hypercorticism and acromegaly results in significant disturbances in bone remodeling, decrease in bone quality, and bone fractures following small traumas. However, the mechanisms of the development of such changes are not clear. In the present study, we examined specimens of bone tissue from patients with endogenous hypercorticism (increased cortisol secretion) and acromegaly (increased growth hormone secretion) obtained during transnasal adenomectomy. Our main purpose was to analyze the expression of genes responsible for osteogenesis in the bone tissue specimens from patients with hypercorticism and acromegaly, targeting an assessment of pathogenetic aspects associated with bone complications. The study included 19 specimens of bone tissue from patients with pituitary tumors (samples with acromegaly, Cushing disease, and inactive pituitary adenomas; the latter served as a control group). We revealed 14 genes (ACP5, ALPL, BGLAP, BMP7, CD40, COL1A1, COL1A2, IGF1, IGFBP2, IL6, LEP, LTA, MMP2, WNT10B) which appeared to be the most important and require further detailed study. The present study confirmed the key role of the Wnt-signaling pathway in the osteogenic process. In addition, we present new data on molecular mechanisms of development of skeletal complications in the case of cortisol and growth hormone oversecretion in humans.

Hyperprolactinemia as a manifestation of hormonally inactive pituitary adenoma

Hyperprolactinemia as a manifestation of hormonally inactive pituitary adenoma

Association of FGFR2 rs2981582, SIRT1 rs12778366, STAT3 rs744166 gene polymorphisms with pituitary adenoma.

The aim of the present study was to determine the association between sirtuin 1 (SIRT1), fibroblast growth factor receptor 2 (FGFR2) and signal transducer and activator of transcription 3 (STAT3) polymorphisms, and pituitary adenoma (PA) development, invasiveness, hormonal activity and recurrence. The present study included 143 patients with a diagnosis of PA. The reference group involved 808 healthy subjects. The genotyping of SIRT1 rs12778366, FGFR2 rs2981582 and STAT3 rs744166 was performed using the quantitative polymerase chain reaction method. The SIRT1 rs12778366 polymorphism analysis in the overall group revealed differences in the genotype distribution between patients with PA and control group subjects. The rs12778366 T/C genotype was observed to be different in non-invasive, non-recurrent and inactive PA subgroups compared with the control group, while the C/C genotype was observed to be different in invasive, recurrent and active PA subgroups compared with the control group. STAT3 rs744166 polymorphism analysis in the overall group revealed differences in the genotype distribution between patients with PA and the control groups. The rs744166 G/G genotype was observed to be different in invasive, non-recurrent and active PA subgroups compared with the control group, while the rs744166 A/A genotype was observed to be different in the active PA subgroup compared with the control group, and was also different in terms of invasiveness and recurrence in PA subgroups. The present study demonstrated that SIRT1 rs12778366 is associated with pituitary adenoma development while STAT3 rs744166 is associated with PA invasiveness, hormonal activity and recurrence.

Does MMP-9 Gene Polymorphism Play a Role in Pituitary Adenoma Development?

Purpose. To determine if the MMP-9 genotype has an influence on development of pituitary adenoma (PA). Methodology. The study enrolled n = 86 patients with PA and n = 526 healthy controls (reference group). The genotyping of MMP-9 was carried out using the real-time polymerase chain reaction method. Results. Our data demonstrated that the MMP-9 (–1562) C/C genotype was more frequent in PA group than in healthy controls (81.4% versus 64.6%, p = 0.002); C/C genotype was more frequently present in PA females compared to healthy control females, 81.5% versus 64.6%, p = 0.018, as well. MMP-9 (–1562) C/C genotype was frequently observed for all subgroups: noninvasive and invasive, nonrecurrence, and inactive PA compared to healthy controls: 81.8% versus 64.6%, p = 0.021; 81.0% versus 64.6%, p = 0.041; 81.8% versus 64.6%, p = 0.005; 100.0% versus 64.6%, p < 0.001, respectively. MMP-9 (–1562) C/C genotype was more frequent in inactive PA compared to active PA: 100.0% versus 71.4%; p < 0.001. Conclusion. MMP-9 (–1562) C/C genotype plays a role in nonrecurrence, inactive, and invasive as well as in nonivasive PA development.

Hormonally inactive pituitary adenoma in adolescence. A case report

Hormonally inactive pituitary adenoma in adolescence. A case report

Сравнительная характеристика нарушений физического и полового развития у детей и подростков (мальчиков) с различными объемными образованиями гипоталамо-гипофизарной области

В данной статье авторы анализируют результаты обследования 29 мальчиков-подростков с различными объемными образованиями гипоталамо-гипофизарной области. Установлено разно-образие нарушений роста и развития, таких как задержка роста (20,6 %), задержка роста и пубертата (20,6 %), истинное преждевременное половое развитие (13,8 %) и др. Наиболее часто встречались пациенты с неактивной аденомой гипофиза — 11 случаев из 29 (37,9 %). Наиболее часто задержка физического и полового развития наблюдалась у больных с неактивной аденомой гипофиза — в 6 случаях (20,6 %).

Влияние различных доз каберголина на процессы свободнорадикального окисления и содержание маркеров апоптоза в крови больных неактивной аденомой гипофиза

В крови, полученной от 90 больных неактивной аденомой гипофиза, установлено высокое содержание маркеров апоптоза — р53, Bcl-2 и ФНО-α. Каберголин, назначаемый в больших дозах, эффективнее и раньше восстанавливал маркеры апоптоза в крови больных, чем тот же препарат, назначенный в малой дозе.

Clinical Tumor Growth and Comparison with Proliferation Markers in Non-functioning (Inactive) Pituitary Adenomas

As the development of clinically silent pituitary adenomas is not yet fully understood, the radiologically measured growth of inactive pituitary adenomas should be compared with adenoma classification and immunostainings for proliferation markers. In 32 patients with non-functioning adenomas (NFA) from 45 operations with retrospectively available preoperative series of magnetic resonance imaging (MRI) we measured the largest growing diameter (LGD) in mm/ year. The adenomas were immunostained for Ki-67 (MiB-1), PCNA, p53 protein, IGF- and PTH-related protein. The positive nuclei for MiB-1, PCNA, and p53 protein were counted and their labelling indices (LI) were calculated. The clinical measurements were compared with these data and were statistically analysed (Spearman test, Whitney-U-test). The growth rate per year was available in 28 cases. We chosed three grades of LGD: less than 1.5 mm in diameter in 9 patients (32%), between 1.5 and 3.0 mm in 11 patients (39%) and more than 3.0 mm in 8 patients (29%). MiB-1 positive nuclei were found in 42% of adenomas, PCNA positive nuclei in 58% and p53 positive nuclei in 16%. IGF 1 was immuno-stained in 84% of adenomas. The mean LI for MiB-1 was 0.12 in adenomas growing less than 1.5 mm and 0.34 in adenomas growing more than 1.5 mm per year. For non-invasive adenomas, the MiB-1 LI was 0.03, for invasive adenomas it was 0.126 and for strongly invasive adenomas 0.212. The MiB-1 LI was lower in null cell adenomas than in FSH/LH adenomas. All these data for MiB-1 showed no statistically significant differences (p<0.05). PCNA LI in adenomas growing less than 1.5 mm per year was 0.51 in contrast to LI of 1.12 for those growing more than 1.5 mm. In non-invasive adenomas the PCNA LI was 0.796, in invasive adenomas 0.655 and in diffuse strongly invasive ones 1.011. Null cell adenomas had a lower PCNA LI than FSH/LH cell adenomas. Statistically significant differences were measured for the growth rate und the PCNA expression. P53 was immunostained in invasive adenomas only. There were no correlations to the clinical growth rate, but p53 expression correlated significantly to numbers of MiB-1 positive nuclei and PCNA positive nuclei. IGF-I expression was found to correlate inversely with age of patients. We recommend the use of PCNA if correlations to progression of tumor growth are wanted.

Influence of GH substitution therapy in deficient adults on the recurrence rate of hormonally inactive pituitary adenomas: a case–control study

Several studies documented metabolic and psychological benefits of GH substitution in deficient adults, most of them suffering from benign pituitary adenomas. Since GH substitution is considered to promote tumour regrowth, adequate treatment is performed with some reservation. Therefore, we aimed to elucidate the effect of GH replacement therapy on tumour recurrence following surgery. In patients with hormonally inactive pituitary adenomas undergoing tumour surgery, a retrospective case-control study was performed. Pre- and postoperative magnetic resonance (MR) images of GH-treated and untreated patients were matched for best fit by two independent observers. The treated patients were retrieved from the surveillance programme of the German KIMS database and the untreated from the database of the Department of Neurosurgery, University of Erlangen. A total of 55 matched pairs were followed for at least 5 years. Tumour recurrence and progression rates were determined according to the postoperative MR. There were 16 tumour progressions in the treatment group and 12 in the control group. Statistical analysis revealed no significant increase in either recurrence (P = 0.317) or progression (P = 0.617) within the follow-up period of 5 years when GH was adequately replaced. This study provides further observational data of substitution therapy in GH-deficient adults with pituitary adenomas. Comparing long-term surgical results, we found no evidence that GH substitution should be withheld in deficient patients. Even residual tumour does not constitute a contraindication to GH replacement. However, since pituitary tumours are slow growing, an observational period of 5 years may not have been long enough to verify any absolute influence on recurrence potential.