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Growth hormone (GH) activity might be implicated in male reproductive function. One previous study has suggested significantly reduced semen quality in untreated acromegalic patients due to both reduced sperm counts and sperm motility. A retrospective study comprising ten uncontrolled hypogonadal acromegalic patients (median age 29 years) who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations were compared to those of ten non-acromegalic hypogonadal men with pituitary disease (age 31 years) and those of young healthy men. Acromegalic patients vs. non-acromegalic patients had a higher percentage of progressive motile spermatozoa (62 vs. 47%, p = 0.04). Eight of ten acromegalic patients and 82% of controls had total sperm counts above 39 million and progressive motile spermatozoa above 32% (p = 0.55), corresponding to the WHO 2010 reference levels for expected normal fertility for these variables. Non-acromegalic patients vs. healthy controls had reduced percentage of progressive motile spermatozoa (47 vs. 57%, p = 0.02) and only five of ten patients had semen quality above the WHO reference level, which was significantly lower than observed in healthy controls (p = 0.022). Total sperm counts were similar between both patient groups and controls. There were no differences in reproductive hormone levels between acromegalic patients vs. non-acromegalic patients (p-values between 0.10 and 0.61). Compared to healthy controls both patient groups had severely reduced serum testosterone, calculated free testosterone. Despite severe hypoandrogenism acromegalic patients had semen quality similar to healthy controls based on determination of the number of progressively motile spermatozoa. By contrast non-acromegalic pituitary patients had reduced sperm motility. Our data do not support reduced semen quality in acromegaly.

Purpose Highlight and characterize manifestations, diagnostic/management approaches and outcomes in a contemporary cohort of patients with pituitary metastases (PM) from a large European pituitary center—over 10 years. Methods Retrospective review of PM cases between 1/2009 and 12/2018. Clinical, laboratory, imaging data at PM detection and during follow-up were analysed. Results 18 cases were identified (14 females; median age at diagnosis 61.5 years). Most common primary malignancies were lung (39%) and breast (32%). Most frequent presenting manifestation was visual dysfunction (50%). Gonadotrophin, ACTH, TSH deficiency were diagnosed in 85%, 67%, 46% of cases, respectively; diabetes insipidus (DI) was present in 17%. 33% of cases were detected during investigation for symptoms unrelated to PM. PM management included radiotherapy (44%), transsphenoidal surgery (17%), transsphenoidal surgery and radiotherapy (6%) or monitoring only (33%). One-year survival was 49% with median survival from PM detection 11 months (range 2–47). Conclusions In our contemporary series, clinical presentation of PM has evolved; we found increased prevalence of anterior hypopituitarism, decreased rates of DI and longer survival compared with older literature. Increased availability of diagnostic imaging, improvements in screening and recognition of pituitary disease and longer survival of patients with metastatic cancer may be contributing factors.

Measuring IGF-1, a biomarker for GH activity, is critical to evaluating disordered hypothalamic-pituitary GH axis. Inconsistent IGF-1 measurements among different immunoassays are well documented. We switched from Immulite 2000 immunoassay to narrow-mass-extraction, high-resolution liquid chromatography mass-spectrometry (LC-MS) compliant with recent consensus recommendations on assay standardization. Comparability of these two assays in patients with pituitary disease in a clinical practice setting is not known. We sought to compare IGF-1 levels on Immulite 2000 and LC-MS in samples from naive and treated patients with secretory and non-secretory pituitary masses. We prospectively collected serum samples from 101 patients treated at the Cedars-Sinai Pituitary Center between February 2012 and March 2014. We intentionally recruited more patients with acromegaly or GH deficiency to ensure a clinically representative cohort. Samples were classified as in or out of the respective reference ranges. Bland–Altman analysis was used to assess agreement between assays. Twenty-four percent of samples were classified differently as below, in, or above range. Agreement between the assays was poor overall, with a significant bias for immunoassay reporting higher values than LC-MS. This pattern was also observed in patients with acromegaly and those with ≥ 2 pituitary hormone deficiencies. IGF-1 results may differ after switching from an older immunoassay to a consensus-compliant assay such as LC-MS. Clinicians should consider the potential impact of assay switching before altering treatment due to discrepant results, particularly in patients monitored over time, such as those with acromegaly and GH deficiency.

Introduction: With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods: To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results: After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions: Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.

In this study, we set out to define our institutional criteria for patient eligibility for transsphenoidal resection of parasellar meningiomas, and to report our experience with extended transnasal approaches for these lesions. We aimed to discuss the important considerations of patient selection and risk stratification to optimize outcomes for patients with these difficult lesions, and also include considerations that should be reviewed during surgical approach selection. Medical records from Brigham and Women’s Hospital were retrospectively reviewed for all patients who underwent transsphenoidal surgery for pituitary disease with the senior author from April 2008 to March 2017 (938 procedures). Patients undergoing surgery for anterior skull base meningioma were identified and patient data were collected. Seven patients (four women, three men) underwent transsphenoidal resection (five endoscopic, one microscopic, and one hybrid endoscopic/microscopic) of pathologically-confirmed anterior skull base meningiomas during the study period. Five patients presented with visual field deficits, three presented with headache, two presented with hypopituitarism, and one woman presented with infertility. The median maximum tumor diameter was 1.7 cm (range 1.4–4.2 cm). Six patients underwent subtotal resection, and one underwent gross total resection. The median MIB-1 index was 2.3 (range 1.0–7.6). Complications included two readmissions (one on POD11 for small bowel obstruction, one on POD48 for epistaxis), and the development of new onset thyroid deficiency and transient diabetes insipidus in one patient. Two patients had reoperations by craniotomy for tumor recurrence after 5 and 6 years, respectively. Although more commonly treated transcranially, anterior skull base meningiomas are sometimes amenable to resection transphenoidally. Patient selection is critical, and multiple factors, including tumor size, consistency, and location, patient and surgeon preference, and presenting symptoms each affect the optimum surgical approach. We have developed criteria for patient selection so that transsphenoidal surgery can be used to resect or debulk anterior skull base meningiomas safely and with favorable outcomes.

To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990–2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. IGF-I SDS correlated negatively with the number of altered pituitary axes (p

The aim of this study was to assess diagnostic values of insulin tolerance test (ITT), glucagon stimulation test (GST), and insulin like growth factor-I (IGF-I) level, to find optimal GH cut-off values for GST, and to evaluate efficiencies of patient age, gender, body-mass index (BMI), and additional pituitary hormone deficiencies (PHDs) in the diagnosis of growth hormone deficiency (GHD). This retrospective study involved 216 patients with a pituitary disease and 26 healthy controls. Age, gender, BMI, medical histories, and hormonal data including baseline and stimulated hormone values were evaluated. Three cut-off values for peak GH responses to stimulation tests were evaluated: (a) 3.00 µg/L on ITT, (b) 3.00 µg/L on GST, and (c) 1.07 µg/L on GST. According to the ITT, GST with 3.00 µg/L cut-off, and GST with 1.07 µg/L cut-off, GHD was present in 86.1, 74.5, and 54.2 % patients, respectively. Patient age, BMI, and number of PHDs, but not gender, were found to be correlated with IGF-I and peak GH concentrations. All patients with an IGF-I concentration ≤95 ng/ml or ≥3 PHD had GHD. None of the patients with adequate GH response to the GST with 1.07 µg/L cut-off, but blunted responses to ITT and GST with 3.00 µg/L cut-off, had ≥3 PHDs. 12 out of 26 (46.2 %) healthy subjects failed the GST with 3.00 µg/L cut-off, but not with 1.07 µg/L cut-off. Patient age, IGF-I, BMI, and number of PHDs are efficient factors associated with the diagnosis of GHD. A 4 h GST with a diagnostic GH threshold of 1.07 µg/L seems to be a good diagnostic method for GHD.

In order to perform trans-sphenoidal endoscopic pituitary surgery safely and efficiently it is important to identify anatomical and pituitary disease features on the pre-operative CT and MRI scans; thereby minimising the risk to surrounding structures and optimising outcomes. We aim to create a checklist to streamline pre-operative planning. We retrospectively reviewed pre-operative CT and MRI scans of 100 adults undergoing trans-sphenoidal endoscopic pituitary surgery. Radiological findings and their incidence included deviated nasal septum (62%), concha bullosa (32%), bony dehiscence of the carotid arteries (18%), sphenoid septation overlying the internal carotid artery (24% at the sella) and low lying CSF (32%). The mean distance of the sphenoid ostium to the skull base was 10 mm (range 2.7–17.6 mm). We also describe the ‘teddy bear’ sign which when present on an axial CT indicates the carotid arteries will be identifiable intra-operatively. There are significant variations in the anatomical and pituitary disease features between patients. We describe a number of features on pre-operative scans and have devised a checklist including a new ‘teddy bear’ sign to aid the surgeon in the anatomical assessment of patients undergoing trans-sphenoidal pituitary surgery.

I feel very fortunate and privileged to have been selected as the 19 President of the Pituitary Society. When such a thing happens, it makes one realize how much we depend upon all of the work and knowledge obtained by others previously. The history of neuroendocrinology and pituitary disease is a rich one, if relatively short. Some date this back to the initial description of Acromegaly by Pierre Marie in 1886, but other dates could suffice as well. To help keep the history of neuroendocrinology and the study of pituitary disease alive, I have elected to create a quiz, highlighting some of the major discoveries and persons in this field. Because of space and time constraints, the number of questions and answers necessarily has to be limited and idiosyncratic, and many other advances and important investigators have, unfortunately, been omitted. So, you other important investigators please do not be too miffed that I have not cited you here. Well, let’s see how you do.

Purpose Recent guidelines suggest that a single prolactin measurement is adequate to confirm hyperprolactinaemia. This may lead to unnecessary investigation of artefactual hyperprolactinaemia. Prolactin measurement drawn from an indwelling cannula after rest removes stress as a con-founding variable. The objective was to determine the frequency of true hyperprolactinaemia amongst patients referred following a single prolactin measurement. Methods A cannulated study was considered if prolactin on referral(‘ReferralProlactin’)was\5,500 mU/L(260 ng/mL) but [410 mU/L (19 ng/mL) in males or [510 mU/L (24 ng/mL) in females, irrespective of clinical context. Case-notes of 267 patients undergoing cannulated prolactin measurement over a 10-year period (2000–2010) were reviewed. Pre-existing pituitary disease, dopamine antago-nist use, and macroprolactinaemia were excluded. Morning ante-cubital vein cannulation was followed immediately by withdrawal of ‘Repeat Prolactin’ sample. After 120-min bed-rest, ‘Resting Prolactin’ was withdrawn through the cannula. Results 235 patients were included for analysis. 64 (27 %) were within normal range; following Repeat Prolactin in 41 (17 %) and Resting Prolactin in 23 (9 %) cases. Referral Prolactin was higher in patients with true hyperprolactina-emia, 1,637 ± 100 mU/L (77.2 ± 4.7 ng/mL) than with artefactualhyperprolactinaemia,1,122 ± 68 mU/L(52.9 ± 3.2 ng/mL; P\0.001) but there was substantial overlap. 21 out of 171 cases (12 %) with true hyperprolactinaemia had a macroadenoma. Presenting symptoms did not pre-dict true hyperprolactinaemia. Referral Prolactin of 2,000 mU/L (94 ng/mL) had 97 % specificity to identify true hyperprolactinaemia. Conclusions Reliance on a single, non-rested prolactin value may lead to over-diagnosis of hyperprolactinaemia. A resting sample should be considered with random values \2,000 mU/L (94 ng/mL).

Background Patients report persisting impairment in quality of life (QoL) after treatment for pituitary disease. At present, there is no questionnaire to assess (a) whether patients with pituitary disease are bothered by these consequences, and (b) their needs for support. Objective To develop and validate a disease-specific questionnaire for patients with pituitary disease which incorporates patient perceived bother related to the consequences of the disease, and their needs for support. Methods Items for the Leiden Bother and Needs Questionnaire for patients with pituitary disease (LBNQ-Pituitary) were formulated based on results of a recent focus group study (n = 49 items). 337 patients completed the LBNQ-Pituitary and six validated QoL questionnaires (EuroQoL-5D, SF-36, MFI-20, HADS, AcroQol, CushingQoL). Construct validity was examined by exploratory factor analysis. Reliabilities of the subscales were calculated with Cronbach’s alphas, and concurrent validity was assessed by calculating Spearman’s correlations between the LBNQ-Pituitary and the other measures. Results Factor analyses produced five subscales (i.e., mood problems, negative illness perceptions, issues in sexual functioning, physical and cognitive complaints, issues in social functioning) containing a total of 26 items. All factors were found to be reliable (Cronbach’s alphas all ≥.765), and the correlations between the dimensions of the LBNQ-Pituitary and other questionnaires (all P ≤ .0001) demonstrated convergent validity. Conclusions The LBNQ-Pituitary can be used to assess the degree to which patients are bothered by the consequences of the pituitary disease, as well as their needs for support. It could also facilitate an efficient assessment of patients’ needs for support in clinical practice. We postulate that paying attention to needs for support will lead to optimal patient care (e.g., improvement in psychosocial care), and positively affect QoL. Electronic supplementary material The online version of this article (doi:10.1007/s11102-016-0707-4) contains supplementary material, which is available to authorized users.

Apoplexy of pituitary adenomas with subsequent hypopituitarism is a rare but well recognized complication following cardiac surgery. The nature of cardiac on-pump surgery provides a risk of damage to the pituitary because the vascular supply of the pituitary is not included in the cerebral autoregulation. Thus, pituitary tissue may exhibit an increased susceptibility to hypoperfusion, ischemia or intraoperative embolism. After on-pump procedures, patients often present with physical and psychosocial impairments which resemble symptoms of hypopituitarism. Therefore, we analyzed whether on-pump cardiac surgery may cause pituitary dysfunction also in the absence of pre-existing pituitary disease. Twenty-five patients were examined 3-12 months after on-pump cardiac surgery. Basal hormone levels for all four anterior pituitary hormone axes were measured and a short synacthen test and a growth hormone releasing hormone plus arginine (GHRH-ARG)-test were performed. Quality of life (QoL), depression, subjective distress for a specific life event, sleep quality and fatigue were assessed by means of self-rating questionnaires. Hormonal alterations were only slight and no signs of anterior hypopituitarism were found except for an insufficient growth hormone rise in two overweight patients in the GHRH-ARG-test. Psychosocial impairment was pronounced, including symptoms of moderate to severe depression in 9, reduced mental QoL in 8, dysfunctional coping in 6 and pronounced sleep disturbances in 16 patients. Hormone levels did not correlate with psychosocial impairment. On-pump cardiac surgery did not cause relevant hypopituitarism in our sample of patients and does not serve to explain the psychosocial symptoms of these patients.

The objective of this study was to evaluate the frequency of acromegaly in adults with diabetes mellitus (DM) or glucose intolerance (GI) and to estimate its prevalence in the general population. A total of 2,270 patients with DM or GI and age from 20 to 70 years were studied. Patients with known pituitary disease and pregnant women were excluded. Serum IGF-1 was measured in all subjects and, if elevated, a new measurement was obtained together with the measurement of GH in the oral glucose tolerance test (OGTT). Patients with persistently elevated IGF-1 and inadequate suppression of GH were submitted to magnetic resonance imaging (MRI). Acromegaly was not suspected by the assistant physician in any of the patients. Six patients had persistently elevated IGF-1 and inadequate suppression of GH in the OGTT (without other conditions associated with GH or IGF-1 elevation). Pituitary adenoma was detected by MRI in three patients, and two subjects presented an acromegalic phenotype. Two patients were submitted to transsphenoidal surgery, with immunohistochemistry confirming immunoreactivity for GH. Another patient was treated with octreotide LAR which resulted in the normalization of IGF-1 and GH. Considering a prevalence of DM or GI of 20% in adults and the occurrence of these co-morbidities in 55% of patients with acromegaly, the frequency of 3/2,270 found in this study permits to estimate 480 cases/1,000,000 adults. The present results suggest that the prevalence of acromegaly is underestimated and further studies are needed to evaluate the cost-effectiveness of biochemical screening in certain groups of patients.

External beam radiotherapy has been used in the management of pituitary adenomas for nearly a century, preventing tumor regrowth following surgery for non-functioning pituitary adenomas and suppressing functional hypersecretion in those which are hormonally active. However, it has been linked with a number of potentially significant complications including formation of secondary intracranial tumors, cognitive impairment, hypopituitarism and cerebrovascular disease, as well as increased mortality. Radiation may cause a variety of vascular injuries and hemodynamic changes to the cerebral vasculature, and several authors have reported cerebrovascular complications and an increase in cerebrovascular mortality in patients receiving radiotherapy for pituitary and other central nervous system tumors. Ten years following pituitary radiotherapy, over 50% of patients develop deficiencies in one or more anterior pituitary hormones. A number of studies have demonstrated increased mortality in patients with hypopituitarism, predominantly due to cerebrovascular and cardiovascular disease. However, no clear answer has emerged with regards to causation, and pituitary radiotherapy has only been linked directly to mortality in one of these studies. Questions remain unanswered, and the use of conventional external beam radiotherapy in the management of pituitary disease must involve a critical risk-benefit analysis in each case.

The diagnosis of adult growth hormone deficiency (AGHD) and acromegaly involves assessment of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations. The diagnosis of AGHD typically requires a provocative test of GH reserve, but is supported by demonstration of low-serum IGF-1 levels. Therapeutic monitoring of rhGH replacement is performed utilizing measurement of serum IGF-1 concentrations. In patients with suspected acromegaly, the diagnosis is confirmed by elevated serum IGF-1 levels and further validated by the presence of elevated GH levels both before and following an oral glucose load. A goal of acromegaly therapy is to normalize IGF-1 concentrations, and, depending on the therapeutic modality, GH levels as well. Using case based clinical scenarios, we have presented a standard approach to the biochemical diagnosis and therapeutic monitoring of these disorders.

Although serum insulin-like growth factor I (IGF-I) concentrations have utility as a screening test for growth hormone (GH) deficiency in children and young adults, they are less accurate for screening in adults over 40 years of age. There are two main limitations in the clinical use of IGF-I levels as a marker of GH secretion. First, IGF-I synthesis is not only regulated by GH but also by nutrient supply and by other hormones; second, low IGF-I levels in the presence of normal or increased GH secretion may reflect a peripheral resistance to GH action. Although serum IGF-I cannot be used as a stand-alone test for the diagnosis of adult GH deficiency, very low IGF-I levels in the context of documented hypothalamic or pituitary disease may be helpful in identifying patients with a high probability of GH deficiency. In the presence of two or more additional pituitary hormone deficiencies, an IGF-I level

Most pituitary lesions are detected during the investigation of symptoms associated with hormonal dysfunction and vision abnormalities. When the lesion is identified in an image performed for reasons not related to the tumor, the term incidentaloma applies. Our aim was to describe the diagnosis behind pituitary incidentalomas, patient characteristics and their follow up. We searched for the terms «pituitary», «hypophysis» and «incidentaloma» in the requisitions and reports of all CTs and MRIs performed between 1st September 2008 and 30th October 2013. We retrieved demographic data as well as information regarding presentation and follow-up. We detected 71 pituitary incidentalomas, 3 in children/adolescents. In adult patients, mean age was 51.6 ± 18.46 years and 42 were female (61.8 %). The most frequent reason for imaging was headache (33.8 %). The image that first detected the incidentaloma was CT scan in 63.2 and 17.6 % patients presented symptoms that could have led to earlier diagnosis. Pituitary adenoma is the most prevalent lesion (n 48; 70.6 %), followed by Rathke’s cleft cyst (n 9; 13.2 %). Hormonal evaluation revealed hypopituitarism in 14 patients and hypersecretion in 6: 5 prolactinomas and 1 somatotroph adenoma. Twenty-one (28.8 %) patients underwent surgery and there was no malignancy. In concordance with available literature, adenomas are the most frequent incidentally found pituitary lesions. Hormonal dysfunction is quite prevalent, including symptomatic presentations, which suggests that there seems to be a low sensitivity for the diagnosis of pituitary disease.

Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels

Vascular complication of transsphenoidal can lead to mortality and serious morbidity. In a series of 3,061 transsphenoidal operations for pituitary disease, 24 such complications were encountered, seven of which were fatal. The anatomic substrate for such complications is discussed, along with technical aspects of surgery and other methods for the avoidance of vascular complications.

During the last 20 years a tremendous improvement in the care of patients with pituitary tumors and of hypopituitarism has been achieved. If we resolve most of the possible causes of the increased cardiovascular disease and stroke mortality a normal survival is expected in these patients. Recently, a large population based study showed a decline in the risk of non-fatal stroke and of non-fatal cardiac events in GH deficient patients. This improvement was achieved by complete hormone replacement, including long term GH replacement, together with prescription of cardio protective drugs. If we follow the latest achievements in pituitary imaging, surgery techniques, hormone substitutions, cardio protective medications, we would expect a normal longevity in these patients. This review will focus on; (1) pituitary insufficiencies and hormone substitutions, (2) modes of cranial radiotherapy, and (3) new techniques in the surgery of a pituitary adenoma.

The objective of this study was to screen for acromegaly by application of a simple questionnaire in patients seen at primary health care units. A total of 17,000 patients of both genders >18 and

Background: The diagnosis of growth hormone deficiency (GHD) relies on provocative tests of GH reserve. The aim in these tests is to obtain an objective, biochemical-based, measure of gland function, but clinicians and researchers rely on the GH peak, as a surrogate of the 24-hour pituitary secretion. However, on a mathematical basis the area under the secretory curve (AUC) should be more valid for this evaluation. Objectives: To validate which variable provided by a provocative test of GH secretion is mathematically more robust for supporting the clinical diagnosis. Adult normal subjects and GHD patients were challenged with the combined stimulus GHRH + GHRP-6. The diagnostic efficacy of the GH peak, and the AUC were compared by the receiver operating characteristic (ROC) curve methodology. Patients and methods: 146 patients with GH deficiency due to organic pituitary disease and 184 healthy subjects were administered GHRH 1 μg/Kg iv, plus GHRP-6 1 μg/Kg iv, and GH was determined. Four variables were studied: (a) the GH peak; (b) the “standar” AUC, (c) the “stimulate” AUC and (d) the basal value, used as internal control. Results: Under ROC curve analysis, the basal variable was devoid of diagnostic capability, while the other variables performed strikingly well, the ROC curve area for the GH peak was 0.9997; and for the AUC 0.9993, with no statistical differences. Conclusions: The variables provided by measuring the GH peak and the area under the curve were similarly effective for diagnosis, although on clinical grounds, the peak was more convenient as needed no calculation. If results for other test were similar the time-honored method of measuring the GH peak could be considered mathematically validated.