Diagnosis Of Nonfunctioning Pituitary Adenoma Research Articles

Extraocular Muscle Enlargement in Acromegaly.

To determine whether acromegaly is associated with increased extraocular muscle (EOM) size at time of presentation. Patients with a new diagnosis of acromegaly in a single tertiary care clinic with a CT scan that adequately delineated the EOMs were included. Control subjects were age- and sex-matched patients with a new diagnosis of nonfunctioning pituitary adenoma. Retrospective chart review was performed to extract baseline clinical and laboratory parameters including growth hormone, insulin-like growth factor 1, thyroid stimulating hormone, free T3, and free T4. A single neuroradiologist analyzed all CT scans and measured the maximum diameter and cross-sectional area of the superior rectus, inferior rectus, medial rectus, and lateral rectus in both eyes of all patients. We evaluated 17 patients with acromegaly and 18 control subjects. Mean maximum diameter of the superior, inferior, medial, and lateral recti were 4.80 mm (SD = 0.81), 4.67 mm (SD = 0.54), 4.86 mm (SD = 0.77), and 4.53 mm (SD = 0.70) respectively, in the acromegaly group. In the control group, they were 3.62 mm (SD = 0.58),3.71 mm (SD = 0.46), 3.66 mm (SD = 0.32), and 3.21 mm (SD = 0.44), respectively. The maximum diameter and cross-sectional area of all 4 EOMs measured in the acromegaly group were significantly larger ( P < 0.001) compared with the control group. Patients with acromegaly present with significantly enlarged EOMs compared with control subjects with nonfunctioning pituitary adenomas.

A case of pituitary gland abscess associated with granulomatous hypophysitis

BackgroundGranulomatous hypophysitis is a rare disease that presents with chronic inflammation of the pituitary gland. In this study, we reported a case of granulomatous hypophysitis associated with a pituitary abscess.Case presentationA 39-year-old woman presented with a 2-year history of infertility. For the past six months, she has suffered from amenorrhea, decreased libido, headaches, and vertigo. She was referred to our hospital with a suspected diagnosis of nonfunctioning pituitary adenoma based on her presentation and brain MRI findings. She underwent trans-sphenoidal surgery (TSS). Direct observation during surgery revealed drainage of malodor pus and pituitary gland abscess. The histopathological evaluation also showed granulomatous hypophysitis and neutrophilic microabscess formation.The patient was initially treated with high doses of ceftriaxone (2 g twice daily) and metronidazole (500 mg (mg) four times per day). Also, the patient received cortisol replacement therapy after the operation. After obtaining the antibiogram and culture results, the treatment regimen was continued for 4 weeks postoperatively, followed by amoxicillin-clavulanate (500/125 mg three times daily) for a total duration of 12 weeks.ConclusionThe patient recovered uneventfully and the postoperative MRI was normal without any remnant lesions.

Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study.

The treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow-up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment. Retrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow-up terminated if the patient underwent surgery, received cabergoline or was lost to follow-up. Data collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm. The cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow-up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty-three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth. Observation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.

PMON170 Treating human primary non-functioning pituitary adenoma cells with cabergoline

Abstract Clinically non-functioning pituitary adenomas (NFPAs) represent the second most common subtype of pituitary tumours, representing 15-43% of all pituitary adenomas. NFPAs are usually benign tumours with no clinical evidence of hormonal hypersecretion. In most of the cases the tumours are arising from the gonadotroph linage, but silent corticotroph, somatotroph, thyrotroph and rarely lactotroph cell characteristics can be discovered with immunostaining. As a result of lack of hormonal hyper-secretion, the diagnosis of NFPAs is made most often when the patient presents with mass effects due to a macroadenoma. NFPAs are most common tumour types in surgical series, and their primary treatment is indeed surgery. However, complete resection is achieved only in about 66% of the cases, and 20% of gross total resected tumours recur after 10 years. Over the past few decades, remarkable progress has been achieved regarding medical treatment options for pituitary tumours. However, NFPAs remain the only subtype with no widely accepted pharmacological treatment. Dopamine receptor type 2 (DRD2) and somatostatin receptor (SST) expression have been demonstrated in NFPAs, prompting the investigation of dopamine agonists and somatostatin analogues as potential treatment strategies. The DRD2 agonist cabergoline is already used as first-line treatment of prolactinomas to induce tumour shrinkage and reduce prolactin secretion. Here we aim to investigate the efficacy of cabergoline on human NFPA tissue. We assessed DRD2 expression levels via immunohistochemistry and qPCR in a large cohort of NFPAs (n=40) and in few prolactinomas (n=10). D2DR has two different isoforms, long (D2RL) and short (D2RS), which are differently expressed and can induce different effects on cell viability. In cabergoline-sensitive prolactinomas D2RS is the predominant isoform. NFPAs shown 10-fold and 5-fold decrease expression of D2RS and D2RL compared to prolactinomas, respectively. Additionally, in NFPAs we observed a significant decrease of cAMP production after cabergoline treatment (45% ±7; p&amp;lt;0.0001); however, viability after one-week cabergoline treatment showed only 4% (±0.7; p&amp;lt;0.0002) reduction, compared to a 10% decrease in prolactinomas (p&amp;lt;0.05). We also observed no difference in secretion of chromogranin A release in NFPAs upon treatment with cabergoline. We have also seen in NFPAs downregulation of Ga i2 protein expression levels, highlighting the general decrease of expression levels in the dopamine pathway (50% less, p&amp;lt;0.004). Our data suggest that the difference in cabergoline responses between NFPAs and prolactinomas may be due to their distinct expression of D2DR isoforms, which differ by 29 amino acids in the third cytoplasmic loop, essential for G-protein binding. It has been shown that D2RL, but not D2RS, requires Gai2. The difference in D2R isoform expression could translate to distinct G-protein activation, ultimately leading to the contrasting viability results after cabergoline treatment. Taken together, these data will help inform future treatment strategies for patients with NFPAs. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Early Retinal Microcirculation in Nonfunctioning Pituitary Adenomas Without Visual Field Defects Using Optical Coherence Tomography Angiography.

For patients with nonfunctioning pituitary adenoma (NFPA) without manifesting visual acuity impairment or visual field defect (VFD), more sensitive and objective assessment methods will allow earlier detection before irreversible damage to the visual system. This study aimed to evaluate retinal vessel densities (VDs) alterations in these patients using optical coherence tomography angiography and to determine its diagnostic abilities. Between patients with NFPA without VFDs and age-matched, sex-matched healthy control individuals, comparisons of visual field metrics, retinal structural thickness, and microcirculation were conducted after adjusting for axial length (AL) and signal index of scans. Receiver operating characteristic (ROC) curves were further depicted to assess the diagnostic performance of significant parameters. To explore the impact of symptom duration, tumor size, and axial length on the significant parameters, multivariate regression analysis was conducted. This cross-sectional study reviewed 107 patients with NFPA. Twenty-seven eyes of patients with NFPA without VFDs and 27 eyes of healthy controls were enrolled. Compared with healthy controls, patients with NFPA without VFDs had similar foveal avascular zone areas and perimeters, macular ganglion cell complex (mGCC) and peripapillary retinal nerve fiber layer thicknesses, and macular VDs. Only the VD in the radial peripapillary capillary (RPC) segment of the inferior temporal (IT) sector was much lower in the patient group. The 2 largest area under the ROC curves were the focal loss volume (FLV) of the mGCC and the VD in the RPC of the IT sector, both of which were significantly related to symptom duration and tumor size. At the early stage of NFPA before VFD and retinal thickness thinning, fundus microcirculation impairments may occur initially in the microvascular density of the RPC segment of the IT sector. The FLV and the VD of RPC at the IT sector may provide a basis for the early diagnosis of NFPA without VFD in clinical practice.

Retinal Microvascular Alterations Detected by Optical Coherence Tomography Angiography in Nonfunctioning Pituitary Adenomas.

PurposeVisual impairment assessment plays a significant role in diagnosis and clinical decisions in nonfunctioning pituitary adenoma (NFPA). Retinal microvascular alterations may potentially reflect the visual impairment. The purpose of this study was to evaluate fundus microvascular alterations in patients with NFPA.MethodsComparisons of visual field, retinal structure, and microcirculation were conducted between patients with NFPA and age- and sex-matched healthy controls. Multivariate regression modeling was used to assess the relationship between symptom duration, sellar mass size, and fundus vessel density (VD) of patients. Receiver operating characteristic (ROC) curves were depicted to determine the diagnostic performance of significant parameters to discriminate eyes with NFPA from healthy eyes.ResultsForty eyes of patients and 40 eyes of healthy individuals were enrolled. Compared to healthy controls, patients with NFPA had a larger foveal avascular zone area and thinner ganglion cell complex thickness. The VDs of patients presented an obvious decrease in radial peripapillary capillary (RPC) and an increase in the deep capillary plexus segment of the perifoveal area. The peripapillary VDs of patients were significantly related to sellar mass size. The area under the ROC curve of VD in the RPC segment of the temporo-inferior sector was the largest (0.801; 95% confidence interval, 0.70–0.90; P < 0.001).ConclusionsThe fundus of patients with NFPA demonstrated significant and characteristic microvascular impairments. The VDs were also significantly associated with sellar mass size.Translational RelevanceRetinal microvascular alterations detected by optical coherence tomography angiography are characteristic and related to sellar mass size, which may provide information that facilitates the diagnosis of NFPA.

52P MiRNA profile associated with the invasiveness in non-functioning pituitary adenomas

Non-functioning pituitary adenomas (NFPAs) account for nearly 35% of all pituitary tumours but since no hormonal hypersecretion has been observed, the diagnosis of NFPAs remains difficult. Although the NFPAs are considered benign, in a proportion of patients, tumour recurrence and invasion have been observed. So far, no biomarkers for NFPAs monitoring are available. Differentially expressed microRNAs (miRs) have been shown biomarker potential in many solid tumours. In the present study, miRs expression profiles were analysed in patients with invasive (with or without recurrence) and non-invasive NFPAs.

Presentation, Management, and Outcomes of Nonfunctioning Pituitary Adenomas: An Experience from a Developing Country.

ObjectiveThe goal of this study was to evaluate the presentation, management, and clinical outcome of nonfunctioning pituitary adenomas (NFPAs) in a tertiary care setup.MethodsWe conducted a retrospective review of patient records of 157 patients with the diagnosis of NFPA managed at Aga Khan University Hospital, a tertiary care hospital in Karachi, Pakistan from January 1, 2007, to December 31, 2017. We collected data on basic demographic characteristics, signs, and presenting symptoms, management, and outcomes. Data analysis was performed by using Stata, Version 12 (StataCorp LLC, College Station, TX).ResultsMost patients in the study were men (59%), and the mean age of the study population was 48 ± 14 years. The main presentations of NFPA were visual disturbance (77%) and headache (55%). In 78% of patients, the tumor was >1 cm on MRI. Most (87%) of patients underwent surgical resection, and of those, 93% received transsphenoidal surgery that was well tolerated. In the study population, 31% of patients had transient, 9% had permanent diabetes insipidus, and 25% developed hyponatremia. Of those in the study, 53% had low cortisol, 57% had hypothyroidism, and 27% needed sex hormone replacement after surgery. Residual tumor was confirmed in 43% of patients by postoperative MRI. Tumor recurrence and regrowth occurred in 17 patients and required repeat resection or radiosurgery.ConclusionIn Pakistan, patients with NFPAs are more likely to present during the later stage, with larger adenoma and compressive symptoms compared to patients in developed countries. For the detection of residual disease and tumor recurrence, close screening and a multidisciplinary approach are needed after surgery.

Non-invasive radiomics approach potentially predicts non-functioning pituitary adenomas subtypes before surgery.

To make individualised preoperative prediction of non-functioning pituitary adenoma (NFPAs) subtypes between null cell adenomas (NCAs) and other subtypes using a radiomics approach. We enrolled 112 patients (training set: n = 75; test set: n = 37) with complete T1-weighted magnetic resonance imaging (MRI) and contrast-enhanced T1-weighted MRI (CE-T1). A total of 1482 quantitative imaging features were extracted from T1 and CE-T1 images. Support vector machine trained a predictive model that was validated using a receiver operating characteristics (ROC) analysis on an independent test set. Moreover, a nomogram was constructed incorporating clinical characteristics and the radiomics signature for individual prediction. T1 image features yielded area under the curve (AUC) values of 0.8314 and 0.8042 for the training and test sets, respectively, while CE-T1 image features provided no additional contribution to the predictive model. The nomogram incorporating sex and the T1 radiomics signature yielded good calibration in the training and test sets (concordance index (CI) = 0.854 and 0.857, respectively). This study focused on the preoperative prediction of NFPA subtypes between NCAs and others using a radiomics approach. The developed model yielded good performance, indicating that radiomics had good potential for the preoperative diagnosis of NFPAs. • MRI may help in the pre-operative diagnosis of NFPAs subtypes • Retrospective study showed T1-weighted MRI more useful than CE-T1 in NCAs diagnosis • Treatment decision making becomes more individualised • Radiomics approach had potential for classification of NFPAs.

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed. A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs. They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

Ovarian hyperstimulation syndrome due to follicle-stimulating hormone-secreting pituitary adenomas.

Gonadotroph adenomas are pituitary adenomas with inefficient and variable secretory characteristics, that is why they are usually considered as a subgroup of nonfunctioning pituitary adenomas (NFPA) and are recognized only at immunohistochemistry. When gonadotroph adenomas secrete active hormones, they may cause spontaneous ovarian hyperstimulation syndrome (OHSS) in premenopausal women. Aim of our study is to describe three women with OHSS diagnosed before the removal of the adenoma and to calculate the prevalence of OHSS in premenopausal women with a clinical diagnosis of NFPA. We reviewed clinical records of premenopausal women that underwent neurosurgery for NFPA at our centre between 1993 and 2014. OHSS was diagnosed in patients with high levels of FSH, suppressed LH, hyperestrogenism, abdominal symptoms, polymenorrhea, enlarged ovaries with cysts or previous surgery for ovarian cysts. 171 women were included into the study; 62 (36.6%) had a gonadotroph adenoma diagnosed at immunohistochemistry. Two patients were retrospectively diagnosed as having OHSS due to gonadotroph adenoma and three had OHSS diagnosed before neurosurgery. The prevalence of OHSS was 2.9% in the overall group of patients with NFPA and 8.1% among patients with a gonadotroph adenoma detected at immunohistochemistry. Frequency of OHSS due to a gonadotroph adenoma is not negligible. Increased awareness of the characteristic clinical and hormonal picture should permit an early detection of this condition in premenopausal women with a pituitary adenoma.

Non-functioning pituitary adenoma: When and how to operate? What pathologic criteria for typing?

After diagnosis of non-functioning pituitary adenoma and impact assessment (pituitary deficiency, visual field disorder), the question of management arises between surgery and surveillance. This part of the Consensus document aims to clarify the principal situations encountered in clinical practice (visual disorder, pituitary deficiency, asymptomatic adenoma, etc.), so as to determine which ones indicate surgery and which ones simple surveillance. Particular contexts are also dealt with (elderly patients, young women hoping for pregnancy, etc). The principal surgical techniques (microscopy, endoscopy, etc.) are also considered. Finally, in case of surgery, the principal pathologic criteria are specified (immunolabeling, proliferation markers, etc.).

Clinical characteristics and treatment outcome of 485 patients with nonfunctioning pituitary macroadenomas.

Background. Nonfunctioning pituitary adenomas (NFPAs) are the most common benign lesions of the pituitary gland. Objective. To describe our experience with the management of NFPA. Study Design and Methods. Retrospective evaluation of NFPA patients managed between 2008 and 2013. We analyzed data regarding clinical presentation, imaging diagnosis, hormonal status, surgical, radiotherapeutic, and pharmacological treatment, and outcome. Results. 485 patients (54% men, mean age 53 ± 14 years) were followed for a median of 6.5 years. Visual field abnormalities and headaches were the presenting complaints in 87% and 66%, respectively. The diagnosis of NFPA was made incidentally in 6.2%, and 8% presented with clinical evidence of apoplexy. All patients harbored macroadenomas, with a median volume of 10306 mm3; 57.9% had supra- or parasellar invasion and 19.6% had tumors larger than 4 cm. Central hypothyroidism, hypogonadism, and hypocortisolism were present in 47.2%, 35.9%, and 27.4%, respectively. Surgical resection was performed at least once in 85.7%. Tumor persistence was documented in 27% and was related to the size and invasiveness of the lesion. In selected cases, radiotherapy proved to be effective in controlling or preventing tumor growth. Conclusions. The diagnosis and treatment of NFPA are complex and require a multidisciplinary approach.

Management of Complications in Endoscopic Endonasal Surgery for Pituitary Adenomas

Objective: To describe a case series of patients with pituitary adenomas with endoscopic endonasal transsphenoidal approach, the technique performed and complications in our centre. Methods: The technique performed in a series of 98 consecutive patients, and description of their complications and the protocol followed to treat these complications. Results: 120 patients where submitted to Skull Base Endoscopic Surgery, of which 98 (81.66%) had diagnosis of non-functioning pituitary adenoma in a two year period. Complications described are postoperative cerebrospinal fluid leaks (6.12%), vascular injury (3.06%) and cranial nerve injury (2.04%). Conclusion: A specific protocol is followed in our institution to treat different complications in pituitary adenoma transnasal endoscopic surgery in order to improve outcomes. Prompt and diligent identification of complications is of utmost importance for their treatment.

Male Gonadotroph Adenoma: Report of Three Cases and a Review of the Literature

We herein report three cases of gonadotroph adenoma in men (36-72 years of age) presenting with visual impairment and suprasellar masses measuring approximately 20 to 30 mm in diameter. Endocrinological examinations were normal, except for slightly increased follicle stimulating hormone (FSH) levels in two cases. Based on the tentative diagnosis of non-functioning pituitary adenoma, transsphenoidal surgery was performed, which revealed that the tumors consisted of FSH- and LH-positive cells. As gonadotroph adenoma is very common among patients with clinically silent pituitary adenoma, it should be diagnosed using pathological examinations.

A Primary Proteomic Analysis of Serum from Patients with Nonfunctioning Pituitary Adenoma

The early diagnosis of nonfunctioning pituitary adenoma (NFPA) is difficult. The objective of this study was to find specific protein biomarkers to aid in the early detection of NFPA. Serum samples from 34 patients with NFPA and 34 age- and sex-matched healthy control subjects were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. The spectra were generated, protein peak clustering was performed and classification analyses were carried out using a decision tree classification algorithm. Nine differentially expressed serum proteins were identified in the patients with NFPA compared with the control subjects. Both the sensitivity and specificity of the decision tree classification algorithm were 82.4% for NFPA. Nine new serum protein biomarkers for NFPA were identified. SELDI-TOF-MS coupled with data mining tools might provide a novel approach for the early diagnosis of NFPA and population screening for the disease.

A non-functioning pituitary adenoma initially mimicking a microprolactinoma: The case for long-term follow-up of patients with mild hyperprolactinemia?

A correct differential diagnosis of patients with mild hyperprolactinemia is essential to select the most appropriate treatment modality. A 50-yr-old woman presented to our Department for evaluation of an intra- and suprasellar mass causing progressive visual defect. Mild hyperprolactinemia causing menstrual irregularities was diagnosed in February 1989. In 1992, serum PRL levels ranged from 50 to 70 microg/l and magnetic resonance imaging (MRI) of the hypothalamic-pituitary region showed the presence of a 7 mm microadenoma. Bromocriptine therapy resulted in normalization of PRL levels and menstrual cycle, while a repeat MRI showed no change. Menses stopped in March 1998, when the patient was 46 yr old. Subsequently, the patient complained of worsening headaches and, starting from July 2001, visual disturbances. In March 2002, MRI showed a large pituitary tumor, measuring 40x37x28 mm. In May 2002, the patient was operated through the transsphenoidal approach with apparent total tumor removal. Histological examination confirmed a pituitary adenoma that stained negative for all pituitary hormones. Four months after surgery, the patient reported an improvement of visual function. MRI of the hypothalamic-pituitary region, performed 4, 13 and 25 months after surgery, showed a partially empty sella with no evidence of residual tumor. This case suggests that, to exclude the alternative diagnosis of nonfunctioning pituitary adenoma or another mass lesion of the hypothalamic-pituitary region, repeat neuroimaging studies during long-term follow-up may be advisable in patients with presumed microprolactinoma who did not show reduction of the tumor during dopaminergic therapy.

Effect of aging on serum gonadotropin levels in healthy subjects and patients with nonfunctioning pituitary adenomas.

Nonfunctioning pituitary adenomas (NFPA), which represent about one-quarter of human pituitary tumors, occur in middle or old age. Determination of gonadotropin levels, which are not expected to be high during the early postmenopause in normal women and which are low in women with NFPA, is important to distinguishing hypogonadal status due to the normal decline of gonadal function from that due to hypothlalamic-pituitary dysfunction. The aim of the study was to verify whether this difference still persists in old subjects, despite the physiological decline of gonadotropins in the last decades of life. The study included 154 healthy subjects (aged 50-104 years) and 47 patients with NFPA (aged 50-80 years). Blood samples were collected after an overnight fast and hormone levels were measured by two immunofluorimetric assays. In healthy women the highest serum levels of gonadotropins were present in the 50-60 year age group, with a slight but progressive age-associated decrease in serum FSH and LH being observed thereafter. In healthy men serum gonadotropin levels were stable up to 70 years, increased up to 75-85 years and thereafter gradually decreasing. Female patients with NFPA showed levels of gonadotropins which were far lower than controls. Only three patients had levels of both FSH and LH above the 2.5 centile for normal subjects. A high sensitivity and specificity of gonadotropin measurements (about 90%) for the diagnosis of NFPA was observed in female patients aged 50-80 years. In male subjects, a large overlap of gonadotropin values in NFPA and controls, namely over the 50-70 years age range, was observed. Our study demonstrates that despite the gradual decline of gonadotropin levels in healthy postmenopsausal women, the reduction of both FSH and LH persists in old patients with NFPA, suggesting that measurement of gonadotropin levels could prove useful in the evaluation of pituitary lesions even in old women. More subtle differences seem to occur in male subjects.

Immunohistochemical Heterogeneity Within Clinically Nonfunctioning Pituitary Adenomas.

To investigate whether adenohypophysial hormone expression is heterogeneous within individual clinically nonfunctioning pituitary adenomas, immunohistochemical examinations were performed on tissues obtained by multiple sampling of 11 adenomas. Stained sections were assessed by morphometric image analysis as well as semiquantitative estimation under microscopy. All tumors except one were immunopositive for one or more gonadotropins. Results were divided into five grades based on the proportion of immunoreactive cells per section. Semiquantitative estimation showed only a one-grade difference among samples from the same tumor in four cases for FSHB and in two cases for LHB. These qualitative similarities between multiple samples were confirmed by morphometric image analysis. From the practical standpoint of making a diagnosis of nonfunctioning pituitary adenoma, it is not necessary to take into account immunohistochemical heterogeneity within an individual tumor, and immunohistochemical findings in a given sample obtained at surgery can be regarded as representative of the entire adenoma.

Abnormal response of luteinizing hormone beta subunit to thyrotrophin‐releasing hormone in patients with non‐functioning pituitary adenoma

It has been suggested that the response of free beta-subunit of LH (LH beta) to TRH is the most useful in-vivo marker of gonadotroph adenomas in patients with non-functioning pituitary adenomas (NFPA). The aim of the present study was to investigate LH beta secretion in patients with NFPA in whom other markers of gonadotroph adenomas, such as supranormal basal concentrations or responses of intact gonadotrophins to TRH, were absent. Serum basal levels of LH beta LH and FSH were evaluated in 80 patients with NFPA showing normal levels of intact gonadotrophin, 20 with PRL-secreting adenomas, 25 with GH-secreting adenomas and 58 healthy subjects. Moreover, LH beta, LH, FSH and alpha-subunit (alpha-SU) were evaluated in 27 patients with NFPA in whom intact gonadotrophin responses to TRH were absent, 8 with PRL-oma, 7 with GH-oma and 17 healthy subjects before and 20, 30 and 60 minutes after the intravenous administration of either 200 micrograms TRH or placebo. A response was considered present when serum LH beta increased by at least 50% above basal levels. LH beta was evaluated using a new assay based on the sequestration of the combined and free alpha-SU by an anti alpha-SU biotinylated monoclonal antibody (MAb) and the subsequent measurement of the LH beta by an IFMA method employing two MAbs directed towards two different epitopes on LH beta. Intact LH and FSH were assayed with an IFMA method and alpha-SU with an IRMA method. In basal conditions, no significant difference in the mean values of LH beta was observed among patients with different types of tumour and normal controls. In 9 of 27 (33%) patients with NFPA, TRH caused an abnormal elevation of serum LH beta (net increase 410 +/- 403%, range 71-1300) which was completely dissociated from changes in intact gonadotrophins. Of the 5 patients who had a TRH test repeated after transsphenoidal surgery, abnormal LH beta responses disappeared in 2 and were maintained in 3. Disappearance of LH beta response occurred only in patients in whom improvement of visual field and radiological imaging after adenomectomy was observed. In contrast, in all patients with pituitary tumours other than NFPA and healthy subjects a response to TRH was absent (net increase ranging from 0 to 23%). Immunofluorescence, performed on 14 NFPA removed from patients either responsive or unresponsive to TRH, showed a variable proportion of cells positive for LH beta, without a significant difference between the two groups. These results indicate that measurement of basal LH beta is of poor value in the diagnosis of non-functioning pituitary adenomas and the identification of gonadotroph adenomas among non-functioning pituitary adenomas. Conversely, an abnormal response of free LH beta to TRH occurs in about a third of patients with low/normal basal gonadotrophins unresponsive to TRH stimulation.