Search

Pituitary incidentalomas are discovered in approximately 10% to 40% of brain images. A complete patient history, physical examination, and dedicated pituitary function testing are needed, and subsequent results should lead to appropriate patient management. However, most lesions are asymptomatic pituitary adenomas or Rathke cleft cysts with a benign course. Many lesions can be clinically significant, including prolactinomas or other pituitary adenomas that warrant specific pituitary disease treatment. In other cases, mass effect causing visual compromise or refractory headache indicates a need for surgery. Here, various facets of a complex evaluation and treatment algorithm for pituitary incidentalomas are reviewed.

Context Aldosterone has been recently characterized as a 'stress hormone'. Stress per se elicits a sizable rise in aldosterone secretion, which could be replicated by the administration of a low dose (0.03-1 μg, IV) of adrenocorticotropic hormone (ACTH). Whether or not the aldosterone response to ACTH could be selectively impaired, that is, in association with intact cortisol response, is presently unknown. Objective To determine whether or not the aldosterone response to low dose of ACTH is impaired in subjects referred to assess the hypothalamic-pituitary-adrenal axis (HPA). Design Retrospective analysis. Setting Outpatient referral endocrine day care centre. Patients One hundred and ninety-five consecutive subjects who underwent the low dose (1 μg) ACTH test, in whom decreased cortisol reserve was suspected due to former/present glucocorticoid excess, pituitary disease or/and unexplained weakness. Main outcome measures The outcome was the detection of lack of aldosterone response, defined as a rise Results In all, 46/195 subjects had subnormal aldosterone response as compared with 52/195 subjects showing diminished cortisol response. Nine subjects had combined deficient aldosterone and cortisol response. In the 37 subjects with isolated subnormal aldosterone response common associations were the use of exogenous glucocorticoids, mostly prednisone (n = 16); former Cushing disease (n = 2); nonfunctioning pituitary adenoma (n = 8); hypothyroidism (n = 11); the use of statins (n = 11), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (n = 6), sex steroids in transgenders and orthostatic hypotension (n = 3). Twenty-seven percent (25/93) of the subjects with recent exposure to glucocorticoids had impaired aldosterone response to ACTH. Conclusion Blunted aldosterone response to ACTH in the absence of hypoaldosteronism was seen in ~27% of subjects referred for HPA assessment using the low dose 1 μg ACTH test. Exposure to glucocorticoid excess was often linked to this impairment, independent of the cortisol response to ACTH.

To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

Objective To determine the utility of measuring free T4 index (FT4I) in patients with low free T4 (FT4) levels using immunoassay and normal thyroid-stimulating hormone for the evaluation of secondary hypothyroidism. Methods We performed a retrospective medical chart review of patients seen at a single institution as outpatients who had a simultaneously normal thyroid-stimulating hormone level, low FT4 level, and any FT4I measured between June 2014 and October 2016. Demographic, laboratory, and imaging data were collected. Using FT4I as the reference for diagnosis of hypothyroidism, the sensitivity and specificity of the FT4 immunoassay’s lower-limit thresholds were determined. Within each threshold group, available brain imaging and biochemical evaluation were categorized according to the presence or absence of pituitary disease. Results A total of 155 sets of result pairs (FT4 and FT4I) performed on 118 subjects were analyzed. The lower limit of a normal FT4 level by immunoassay at this institution was 0.93 ng/dL, though all pairs with FT4 ≥0.89 ng/dL had a normal FT4I. All pairs with FT4 ≤0.67 ng/dL had a low FT4I. No pituitary macroadenomas were identified in any subject, though the rates of pituitary imaging in this patient sample were low. Conclusion Patients with a borderline low FT4 level by immunoassay often have normal FT4I. In such patients at our center, significant structural and biochemical pituitary pathology was uncommon.

The hypothalamic-pituitary axis is responsible for the neuroendocrine control of several organ systems. The anterior pituitary directly affects the functions of the thyroid gland, the adrenal glands, and gonads, and regulates growth and milk production. The posterior hypophysis, through nerve connections with the hypothalamic nuclei, releases vasopressin and oxytocin responsible for water balance and social bonding, sexual reproduction and childbirth, respectively. Pituitary gland hormonal excess or deficiency results in dysregulation of metabolic pathways and mechanisms that are important for the homeostasis of the organism and are associated with increased morbidity and mortality. Cardiovascular (CV) disorders are common in pituitary disease and have a significant impact on survival. Hormonal imbalance is associated with CV complications either through direct effects on the heart structure and function and vasculature or indirectly by altering the metabolic profile. Optimal endocrine control can prevent or reverse CV defects and preserve survival and quality of life. In this review, we discuss the effects of pituitary hormone excess and deficiency on the CV system. Specifically, we assess the impact of Somatotroph, Corticotroph, Gonadotroph, and Lactotroph anterior pituitary axes on the CV system. The effect of posterior pituitary function on the CV system is also explored.

Immune-checkpoint inhibitors (ICI) are monoclonal antibodies which target molecules to enhance antitumor response. Several adverse events have been described and the major ICI-related endocrinopathies are thyroid dysfunction and hypophysitis. Its occurrence has been associated with improved outcomes, but it is still to be proven. We performed a retrospective study of patients treated with ICI between 2014 and 2019 at an oncologic center to characterize thyroid function test abnormalities (TFTA) and to evaluate clinical outcomes. We excluded patients without regular monitoring of thyroid function, with previous thyroid or pituitary disease, previous head/neck radiotherapy and who performed only one ICI cycle. We included 161 of 205 patients treated with pembrolizumab, nivolumab or ipilimumab for several neoplasms, with a median duration of 18.9 weeks (9.1-42.6) of ICI treatment and 49.4 weeks (26.5-75.8) of follow-up. New-onset TFTA was diagnosed in 18% of patients (n = 29), in median at 10.6 weeks (6.1-31.1) of ICI therapy. On the whole, 8.7% had primary hypothyroidism, 4.3% central hypothyroidism, 2.5% biphasic thyroiditis and 2.5% thyrotoxicosis. Patients who experienced primary or central thyroid dysfunction had a significantly improved overall response rate (58.6% vs 34.2%, p = 0.015) and overall survival (3.27 vs 1.76 years, p = 0.030), compared to the control group. The risk of mortality was two times higher for control group (adjusted HR = 2.43, 95% CI 1.13-5.23, p = 0.023). This study recognizes that primary and central thyroid dysfunction can be a predictive clinical biomarker of a better response to ICI across several neoplasms.

The aim of this retrospective reference interval observational study was to determine the mensuration of the pituitary gland (hypophysis cerebri) by analyzing CT studies in rabbits without clinical evidence of pituitary disease or central neurologic signs. Though diseases of the rabbit pituitary gland are uncommon, the pituitary gland is essential in regulation of the rabbit's endocrine system, as in other species. Currently, there are minimal published studies that detail the rabbit head anatomy on cross-sectional imaging, and even less specifically examining the pituitary gland. The pituitary gland was measured by one observer at a single time point from transverse and reconstructed sagittal CT images in a soft-tissue algorithm in 62 rabbits for a total of 66 rabbit head CT studies. The rabbits ranged from 0.84 to 14 years in age (mean ± SD: 5.46 ± 3.05 years) and 0.92 to 4.95 kg in weight (2.21 ± 0.83 kg). Linear pituitary measurements were performed using electronic calipers. The mean ± SD pituitary height was 4.22 ± 0.57 mm, width was 4.48 ± 0.71 mm, and length was 6.02 ± 0.70 mm. The pituitary gland height-to-brain area ratio was 1.10 ± 0.16 mm-1 , which is much higher than the values reported in normal dogs and cats. The age, weight, and sex of the rabbits were not found to have a significant impact on pituitary gland mensuration. These measurements could be useful as a reference range for future rabbit head CT studies and to rule out pituitary enlargement or disease when evaluating rabbit pituitary glands.

Magnetic resonance (MR) imaging is an essential tool in the diagnosis and management of pituitary diseases, indispensable for making correct treatment decisions. Successful management and follow-up of pituitary pathology requires an understanding of the MR appearance of normal and abnormal structures in the sellar region. This review will describe the MR appearance of the normal and abnormal pituitary gland and proposes an algorithm for the management strategy of some of the most common abnormalities in or around the sella.

Pituitary develops from oral ectoderm in contact with adjacent ventral hypothalamus. Impairment in this process results in congenital pituitary hypoplasia (CPH); however, there have been no human disease models for CPH thus far, prohibiting the elucidation of the underlying mechanisms. In this study, we established a disease model of CPH using patient-derived induced pluripotent stem cells (iPSCs) and 3D organoid technique, in which oral ectoderm and hypothalamus develop simultaneously. Interestingly, patient iPSCs with a heterozygous mutation in the orthodenticle homeobox 2 (OTX2) gene showed increased apoptosis in the pituitary progenitor cells, and the differentiation into pituitary hormone-producing cells was severely impaired. As an underlying mechanism, OTX2 in hypothalamus, not in oral ectoderm, was essential for progenitor cell maintenance by regulating LHX3 expression in oral ectoderm via FGF10 expression in the hypothalamus. Convincingly, the phenotype was reversed by the correction of the mutation, and the haploinsufficiency of OTX2 in control iPSCs revealed a similar phenotype, demonstrating that this mutation was responsible. Thus, we established an iPSC-based congenital pituitary disease model, which recapitulated interaction between hypothalamus and oral ectoderm and demonstrated the essential role of hypothalamic OTX2.

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.

Pituitary stalk lesions can represent a wide range of pathologies. The exact cause is often unknown due to hesitancy to proceed with biopsy. We present a 16-year-old adolescent who presented with delayed puberty, short stature and bilateral cryptorchidism. He was found to have a thickened pituitary stalk of uncertain etiology with partial hypopituitarism (gonadotrophin and growth hormone deficiency) on further assessment. The presence of bilateral cryptorchidism and micropenis represents lack of “mini puberty,” a phenomenon of activation of the hypothalamic - pituitary-gonadal (HPG) axis in -utero or within the first few months of life.1 These key clinical features have been useful to establish an early temporal relationship and suggest a congenital origin of disease. This enabled a more conservative approach of surveillance to be employed as opposed to invasive pathological examination with pituitary stalk biopsy.

The function of the thyroid gland is to secrete sufficient amount of thyroid hormones for regulation of cellular metabolism throughout the body. Patients need medical care for hyper functioning (hyperthyroidism) or hypo functioning (hypothyroidism) of the thyroid gland. Hypothyroidism is a very common disease affecting 0.5% to 0.8% of the adult population in the world. Primary hypothyroidism results in a decreased production of thyroid hormones despite adequate or increased levels of TSH and accounts for 95% of all cases of hypothyroidism. Secondary hypothyroidism results due to hypothalamic or pituitary disease that accounts for 5% of cases of hypothyroidism [1]. Hypothyroidism can cause decreased myocardial contractility, baroreceptor dysfunction, weight gain, non-pitting edema, hyponatremia, decreased ventilatory response to hypoxia and hypercarbia, diminished gastrointestinal function and impaired drug metabolism. Feeding jejunostomy is a surgical procedure by which a tube is inserted in the lumen of the proximal jejunum, primarily to provide enteral nutrition or administer medications. This procedure becomes a vital path for providing nutrition and medication when a person becomes unable to swallow due to obstruction of the food pipe [2]. Carcinoma larynx is a disease in which malignant cells originate from larynx mostly squamous-cell carcinomas which can invade the surrounding structures. Here, we report on the anaesthetic management of a patient of carcinoma larynx with overt hypothyroidism for feeding jejunostomy.

Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including primary tumors, metastases, and lympho-proliferative diseases) and multifaceted. Patients with hypophysitis typically present with headaches, some degree of anterior and/or posterior pituitary dysfunction, and enlargement of pituitary gland and/or stalk, as determined by imaging. Most hypophysitis causes are autoimmune, but other etiologies include inflammation secondary to sellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as immunoglobulin G4-related hypophysitis, immunotherapy-induced hypophysitis, and paraneoplastic pituitary-directed autoimmunity are also included in a growing spectrum of this rare pituitary disease. Typical magnetic resonance imaging reveals stalk thickening and homogenous enlargement of the pituitary gland; however, imaging is not always specific. Diagnosis can be challenging, and ultimately, only a pituitary biopsy can confirm hypophysitis type and rule out other etiologies. A presumptive diagnosis can be made often without biopsy. Detailed history and clinical examination are essential, notably for signs of underlying etiology with systemic manifestations. Hormone replacement and, in selected cases, careful observation is advised with imaging follow-up. High-dose glucocorticoids are initiated mainly to help reduce mass effect. A response may be observed in all auto-immune etiologies, as well as in lymphoproliferative diseases, and, as such, should not be used for differential diagnosis. Surgery may be necessary in some cases to relieve mass effect and allow a definite diagnosis. Immunosuppressive therapy and radiation are sometimes also necessary in resistant cases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced ‘lockdowns’ are the new ‘norm’ as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population.

Context IGF-I is important for postnatal growth and may be of diagnostic value in infants suspected of pituitary disease; however, little is known about the impact of IGF-I and its determinants on infant growth. Importantly, detailed reference ranges for IGF-I and IGF binding protein-3 (IGFBP-3) concentrations during infancy are lacking. Objective To evaluate the rapid changes in weight and length as well as their determinants in healthy infants, and to establish age- and sex-specific reference curves for IGF-I and IGFBP-3 in children aged 0 to 1 years. Design Prospective longitudinal study. Setting Cohort study. Participants A total of 233 healthy children (114 girls) with repeated blood samples during the first year of life. Main Outcome Measure(s) Serum concentrations of IGF-I and IGFBP-3, length velocity, weight velocity, and PAPPA2 (rs1325598) genotype. Results Individual trajectories of length and weight velocities were sex specific. We provide detailed reference curves based on longitudinal data for IGF-I and IGFBP-3 during infancy. In both girls and boys, IGF-I decreased during infancy, whereas IGFBP-3 remained stable. IGF-I and IGFBP-3, but not PAPPA2 genotype, were positively associated with weight gain, but not with longitudinal growth. When stratified by sex, the association between weight gain and IGF-I only remained significant in girls. Conclusions Interestingly, we found a significant association between IGF-I and infant weight gain in girls, but not with longitudinal growth in the first year of life. Our findings highlight the role of IGF-I as an important anabolic hormone that is not limited to linear growth.

Pituitary gigantism is a condition caused by excessive secretion of Growth Hormone (GH). The GH is the most commonpituitary hormone-deficient in pituitary disease. Chordoma is a bone primary tumor that grows slowly and is rarely found.Hypothyroidism is a pathological condition due to thyroid hormone deficiency. Symptoms of hypogonadism arenon-specific including libido disorders, erectile dysfunction, and decreased muscle mass and no hair growth in the head orbody. A 24-year-old male came with pain in the knee. Physical examination showed increased growth of natural and bodyparts as well as the loss of body hair. Laboratory investigations revealed pancytopenia, increased prolactin; decreased GH,Insulin-Like Growth Factor-1 (IGF-1) and testosterone; increased Thyroid-Stimulating Hormone (TSH), decreased FreeTriiodothyronine (FT3) and Free Thyroxine (FT4). Ahead MRI demonstrated the presence of a mass in the clivus. In this case,the patient presented with clinical gigantism. However, laboratory examination showed decreased GH and IGF-1 whichmight be due to the suppressive effect of mass on the clivus bone to the pituitary. Further examinations were needed to clearthe suspicion of hypothyroid. Hypogonadism can result from suppression in the pituitary. Pancytopenia can be caused by adeficiency of GH or from hypothyroidism. Gigantism may occur with GH and IGF-1 deficiency due to suppressed pituitarycaused by chordoma.

The pituitary is an endocrine gland with ability to uptake diverse radiopharmaceuticals and, therefore, susceptible to be investigated by nuclear medicine diagnostic procedures. Although this topic has been scarcely scrutinized, we have data indicating that somatostatin receptor scintigraphy with111In-DTPA-D-Phe-octreotide or 99mTc-EDDA/HYNIC-TOC may be of clinical utility in the diagnosis of some pituitary adenomas (PA). Only a few studies have evaluated the diagnostic performance of 99mTc-MIBI and 99mTc (V)-DMSA scintigraphy in pituitary disease. Scintigraphy using 123I-methoxybenzamide (123I-IBZM) might be useful in macroprolactinomas expressing dopamine D2 receptors. Pituitary gland does not usually accumulate 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) and, therefore, it is not visualized on positron emission tomography (PET) imaging studies with this radiotracer. The pituitary uptake on18F-FDG PET/CT scans performed in the follow-up of oncological patients are uncommon. However, 60% of these incidental findings are due to PA, mainly non-functioning pituitary macroadenomas, and a small percentage to metastases or other pituitary lesions. Interestingly, 18F-FDG PET/CT may identify hypophysitis induced by different immunotherapeutic agents used in cancer patients. Positive 18F-FDG uptake has been reported in a high percentage of patients with PA, mainly macroadenomas and it seems that there is correlation between tumor size and SUVmax. 68Ga-DOTA-TATE PET/CT may identify functioning and non-functioning PA, although this technique is more useful in the detection of remaining normal pituitary tissue after transsphenoidal adenomectomy, and in the confirmation of recurrence of functioning PA, such as thyrotroph-secreting PA. Furthermore, 68Ga-DOTA-TATE uptake has potential therapeutic implications on molecular-targeted therapy. Lastly, other radiopharmaceuticals that have shown to be taken up in some patients with pituitary disease include 18F-DOPA (prolactinoma), 11C-methionine (residual or recurrent PA), O-(2-18F-fluoroethyl)-l-tyrosine (metastasis), 18F-choline (silent adenoma, ectopic corticotropinoma), and 13N-ammonia (hypopituitarism).

Objective: Abnormalities of water and sodium balance, including diabetes insipidus and the syndrome of inappropriate antidiuretic hormone (SIADH), are common complications of transsphenoidal surgery. Postoperative practice patterns vary among clinicians, and no consensus guidelines exist to direct their monitoring and management. We aimed to identify and compare practice patterns regarding the evaluation and management to these postoperative complications. Methods: A questionnaire was utilized to capture demographic data and practice habits in the postoperative setting. Respondents were members of the Pituitary Society, an international organization comprised of clinicians and researchers dedicated to the study of pituitary disease. Results: Eighty-six respondents completed at least part of the survey. The geographic distribution of respondents was roughly even between American and non-American practitioners. The majority of respondents practiced at academic institutions (67.4%), worked in multidisciplinary teams (88.4%), and possessed significantly greater than 10 years of clinical experience (71%). Compared to non-American practitioners, American practitioners described a shorter length of stay postoperatively (P

Objective: The inflammation of the pituitary gland is known as hypophysitis. It is a rare disease accounting for approximately 0.24%-0.88% of all pituitary diseases. The natural course of hypophysitis is variable. Main forms are histologically classified as lymphocytic, granulomatous, IgG4 related and xanthomatous. We aim to present our patients with hypophysitis and compare clinical, laboratory and radiological features. Subjects and methods: We retrospectively reviewed our database of 1.293 patients diagnosed with pituitary diseases between 2010 and 2017. Twelve patients with hypophysitis were identified. Demographical data, clinical features, endocrinological dysfunction, imaging findings, treatment courses and follow-up periods were evaluated. Results: The frequency of hypophysitis was found 0.93% in all cases of the pituitary disease. Twelve patients (nine females and three males), ages between 17-61 years, were evaluated. The characteristic features of our patients tended to be predominantly female and young. Diagnosis of hypophysitis was made after pituitary biopsy in four patients, and in eight patients after pituitary operation due to adenoma. Headache (67%) and visual problems (33%) were the most frequent nonendocrine symptoms. Anterior pituitary hormone deficiencies (63.7%) and/or diabetes insipidus (17%) were seen among patients. According to histopathological forms, four had lymphocytic, seven had granulomatous and one had xanthogranulomatous types. Contrast enhancement heterogeneous and thickened pituitary stalk were the most common radiological alterations. Conclusion: Hypophysitis should be considered in the differential diagnosis of sellar masses. It can mimic pituitary adenomas in radiological and endocrinological aspects. The different patterns of pituitary hormone deficiencies may be seen in the course of the disease.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Introduction: Heterozygous mutations or haploinsufficiency of NKX2-1 are associated with the brain-lung-thyroid syndrome incorporating primary hypothyroidism, respiratory distress, and neurological disturbances. Case Presentation: We report a patient presenting in the neonatal period with multiple pituitary hormone deficiency including central hypothyroidism and hypoadrenalism, growth hormone deficiency, undetectable gonadotrophins, and a small anterior pituitary on MRI. CGH microarray revealed haploinsufficiency for NKX2.1 and during subsequent follow-up, she has exhibited the classic triad of brain-lung-thyroid syndrome with undetectable tissue on thyroid ultrasonography. Whilst the role of NKX2-1 is well described in murine pituitary development, this report constitutes the first description of multiple pituitary dysfunction in humans associated with the syndrome and haploinsufficiency NKX2-1. Conclusion: The report highlights a potential need for pituitary screening in patients with established brain-lung-thyroid syndrome and implicates NKX2.1 in human pituitary disease.

Background Pituitary lesions are present in >10% of the population. Approximately one in 1000 people has a symptomatic pituitary tumour, which may cause clinical problems from mass effect, hormonal hypersecretion and impairment of normal pituitary function. Objective The aim of this article is to outline the potential causes of a sellar and parasellar mass, with an emphasis on the presenting clinical features and screening investigations that are applicable to doctors working in the primary care setting. Discussion There is a broad range of causes of a sellar/parasellar mass. Pituitary adenomas and Rathke's cleft cysts are the most frequently encountered. Prolactinomas are the most common functioning tumour and tend to present as macroadenomas in men, while hyperprolactinaemia is associated with 15% of secondary amenorrhoea in women. Acromegaly and Cushing's disease are rare but important diagnoses to detect. Pituitary disease is optimally managed in a specialist centre in the context of an established multidisciplinary team.

The pituitary is the master gland that conducts the endocrine orchestra of the human body. Manifestations of pituitary toxicity are usually expressed as functional and structural changes in target endocrine glands under its control. Although several drugs can affect the pituitary gland, relatively low exposure of the pituitary cells to xenobiotics as the vascular supply and concentrating ability of the gland are less than the major organs of excretion and metabolism such as the liver and the kidneys. Pituitary apoplexy, originally described as postpartum ischemic necrosis of the anterior pituitary due to spasm of the infundibular arteries, is now known to be due to several causes including drugs. Case reports in the literature are limited and include bromocriptine, chlorpromazine, leuprorelin, clomiphene, and goserelin. Other complications include CSF leakage through the nose due to shrinking of macroprolactinomas as an effect of bromocriptine therapy. Hypopituitarism or pituitary insufficiency in anterior-pituitary hormone secretion may result from pituitary disease, and manifestations may be due to deficiency of corticotrophin, gonadotropins, androgen, or growth hormone. Drugs such antineoplastics, interferon, and corticosteroids may cause hypopituitarism. Several drugs have a secondary effect on the pituitary via induction of changes in the other endocrine function.

After treatment, patients with pituitary diseases often still experience complaints or persistent morbidity (physical or psychological), which tend to impair their everyday life and limit their professional, personal, or social activities. In other words, their health-related quality of life is affected. This is especially so in Cushing's disease (in fact, in both pituitary- and adrenal-dependent Cushing's syndrome), hypopituitarism (and especially GH deficiency), and acromegaly. Surgical and/or medical therapy and control of pituitary dysfunction are usually followed by improvement of quality of life, but it is still impaired when compared with healthy matched controls. Understanding of the potential health hazards after being diagnosed with a pituitary disease through patient education and understanding by the involved health professionals help to adapt to the new situation and tend to prevent depression and anxiety. Additionally, support by family, friends, or patient associations all help to improve patients’ perception of health and outcome, improving their quality of life.

Magnetic resonance imaging is the preferred method for diagnosis and follow-up of secreting and nonfunctioning pituitary adenomas. However, the frequency and duration of serial imaging follow-up varies depending on the adenoma type, pathology, biochemical status of the pituitary disease, and other factors. Clinical practice guidelines recommend performing early follow-up imaging in patients with a new or worsening neurological deficit and patients with a suspected cerebrospinal fluid leak, postoperatively. Otherwise imaging should be performed approximately 3 months after surgery; further imaging should be guided by clinical, biochemical, and pathological data. Recent data show that some gadolinium-based contrast agents could have a potential for long-term tissue deposition; thus macrocyclic agents are preferred until definitive safety evidence of cumulative use is available. Long-term imaging follow-up should be individualized and assessed in conjunction with patient's clinical and biochemical status and pituitary adenoma pathology.

Background: Dopamine agonists (DA) are the first line therapy for prolactinoma and symptomatic hyperprolactinemia; use as an adjuvant treatment for acromegaly and Cushing's disease is rare. Some patients develop de novo psychiatric symptoms or have exacerbation of pre-existing conditions during DA therapy. A practical, clinically sensitive depression and impulse control disorders (ICD; particularly hypersexuality and gambling disorders) detection tool is important for identifying at risk patients. The Barratt Impulsivity Scale (BIS-11) and the 9-item Patient Health Questionnaire (PHQ-9) are sensitive in identifying impulsivity and depression.Objective: Detail use of the BIS-11 and PHQ-9 as screening tools for depression and ICD in patients with pituitary disease at a high-volume academic pituitary center.Methods: DA-treated and naïve patients with pituitary disease were included. Patients with a known history of depression or psychiatric disorder were excluded. PHQ-9 standardized interpretation criteria were utilized to classify depression severity. For BIS-11, threshold was established based on previous studies. Statistical analysis was with SPSS version 25.Results: Seventy-six DA-treated and 27 naïve patients were included. Moderate and moderately severe depression were more prevalent in DA-treated patients; severe depression only found in DA-treated patients. A normal BIS-11 score was noted in 76.69%; higher scores (not significant) were noted in DA-treated patients. There was a positive correlation between higher BIS-11 and PHQ-9 scores; higher in DA-treated patients (r = 0.52, p < 0.001) than DA-naïve patients. Patients with BIS-11 scores ≥60 were younger and received lower cumulative DA doses compared to patients with BIS scores

To evaluate the prevalence of differentiated thyroid cancer (DTC) in patients with non-GH secreting pituitary adenomas [NGHPA group: non-functioning (NFPA), prolactin (PRL) and corticotropin (ACTH)-secreting adenomas] compared to patients with acromegaly, a pituitary disease that has been associated with increased risk for thyroid cancer.Prospective, cross-sectional study involving consecutive outpatients followed in our institution with diagnosis of acromegaly (n = 71; 43 women, median age 57 yrs) and NGHPA (n = 57; 38 women, median age 48 yrs.; PRL (n = 35), ACTH (n = 7), NFPA (n = 15). All participants were subjected to thyroid ultrasound (US) by the same examiner, and US-guided fine needle aspiration (FNA) biopsy when indicated.Thyroid volume was higher in acromegaly than in NGHPA (median 12.5 ml vs 6.3 ml; p 0.0001), and thyroid nodules were present in 27/71 (38.0%) of acromegaly patients and in 14/57 (24.6%) of NGHPA group. FNA was indicated in 15/27 (55.5%) of acromegaly patients [Bethesda I (n = 1); II (n = 11), III (n = 1), two patients refused FNA], and in 8/14 (57.1%) of the NGHPA group [Bethesda I (n = 2); II (n = 4); V (n = 1); VI (n = 1)]. The two patients of NGHPA group with Bethesda V and VI were operated and papillary carcinoma was confirmed histologically.DTC was not detected in our acromegaly patients and its presence in patients with NGHPA suggests that DTC predisposition is not related to GH excess.

Background: Adult growth hormone deficiency (GHD) is considered a rare condition. Current guidelines state that GH provocative test is indicated in patients affected by organic hypothalamic/ pituitary disease or with a history of head injury, irradiation, hemorrhage or hypothalamic disease with multiple pituitary deficiencies. Nevertheless, the clinical picture related to GHD may be subtle. Objective: We have retrospectively evaluated the indication to GHRH+arginine test in our monocentric cohort of patients treated with hrGH in order to assess whether other conditions had been considered as a rationale for provocative testing. Methods: Ninety-six patients (51 females and 45 males), aged 19-67 years were included. The GHRH+arginine test had been performed in 29 patients with organic hypothalamic/pituitary disease and in 4 patients for Childhood onset-GHD (CoGHD). In other patients, the diagnosis was suspected for “non classical” reasons in the clinical picture suspected for GHD. Results: Classical indications included previously known primary empty sella (n=15), pituitary surgery (n=14), pituitary cyst (n=1), non-secreting pituitary tumors (n=3) but more than half of the patients (57.3%) had been studied for “non classical” indications: metabolic syndrome (n=25), asthenia (n=13), heart failure (n=4), osteoporosis (n=6), unexplained hypoglycaemia (n=1) and infertility (n=6). The latter represented a significant percentage in the male subgroup under 45 ys. IGF-1 levels were lower than 50th percentile in 63% of patients. Finally, among non-classical reasons, organic pituitary disease was discovered in 22 patients. Conclusions: Idiopathic GHD may be unrecognized due to its subtle manifestations and that an extended use of dynamic GH tests may reveal such conditions. A potential field of investigation could be to identify subsets of patients with clinical conditions caused or worsened by underlying unrecognized GHD.

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.

Pregnancy results in a significant change in both pituitary gland size and function. Due to this physiological adaptation, the diagnosis and management of pituitary diseases during pregnancy represents a particularly complex challenge. The presence of a functioning pituitary adenoma may be harmful to the health of the mother and fetus, and scientific evidence regarding the safety of drugs normally used to control hormone excess during pregnancy is scarce. In addition, pregnancy may be associated with the risk of the growth of a pre-existing pituitary adenoma. This review focuses on the diagnostic challenges in pregnant women with adenomas secreting prolactin, growth hormone, or adrenocorticotropic hormone. Some evidence-based recommendations for the treatment of these conditions during pregnancy are provided, and algorithms that could help monitor a pituitary adenoma during pregnancy are examined. Mention is also made of how hormone replacement therapy can be optimised in pregnant women with hypopituitarism. Finally, differential diagnosis between Sheehan's syndrome and lymphocytic hypophysitis, two pituitary disorders that may occur during pregnancy or delivery, is discussed.

Hypophysitis (HP) is a rare acute or chronic inflammatory condition of the pituitary gland. The greatest challenge in the management of HP is establishing a diagnosis through clinical criteria and non-invasive methods and predicting the patients’ clinical outcome. The aim of this review is to describe the neuroradiological findings of this rare disease, providing some information regarding the possible differential diagnosis in order to avoid unnecessary surgery. Gadolinium-enhanced pituitary magnetic resonance imaging (MRI) is considered the neuroradiological investigation of choice. The features suggestive for HP include an enlarged triangular- or dumbbell-shaped gland with a thickened and not obviously deviated stalk, further supported by the absence of posterior pituitary bright spot on T1weighted images, particularly in patients presenting with diabetes insipidus. Contrast enhancement pattern is quite variable; dural enhancement has been reported in some cases after intravenous contrast administration. The characterization of the unusual sellar mass is not straightforward and generally results in a wide differential. HP should be primarily differentiated from pituitary adenomas (including pituitary apoplexy), from pituitary metastases, and from other sellar and parasellar tumors, e.g., craniopharyngiomas, germinomas, gliomas, lymphomas, meningiomas, pituicytomas, chordomas, teratomas, dermoids and epidermoids, Rathke’s cleft cysts, and abscesses. In patients suspected for secondary forms related to systemic pathology, additional imaging is helpful in identifying other involved sites. Neuroradiologists need to know MRI appearance of this rare disease, as well as its typical symptoms and serological markers. A strict collaboration with endocrinologists and neurosurgeons is mandatory in order to reach a definitive diagnosis, allowing to promptly initiating an appropriate treatment.

The presence of a pituitary adenoma may affect the course of pregnancy, as the hormonal changes related to these tumors may lead to early termination of pregnancy due to failure to implant or maintain the conceptus or early embryo. The age-adjusted incidence rate of pituitary adenomas is estimated to be 3.4 cases per 100,000 inhabitants per year. They are usually benign adenomas, with a peak incidence in young women of childbearing age. The management of pituitary adenomas during pregnancy depends on its clinical presentation and should be adapted to the individual case. Most pregnant women with pituitary adenomas can be safely observed with frequent neuro-ophthalmologic assessments and MRI, if needed. Among women with pituitary adenomas, prolactin (PRL)-secreting pituitary adenomas (prolactinomas) are the most common. Dopamine agonists (DAs) are the gold standard treatment for prolactinomas; they normalize serum PRL levels, leading to tumor shrinkage in more than 80% of cases and restoration of eugonadism. In micro- and intrasellar macroprolactinomas, DA is usually withdrawn when pregnancy is confirmed. In pregnant women with acromegaly, hormonal control is often achieved in most patients, allowing the withdrawal of clinical treatment. Due to similar clinical features and changes in the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, the diagnosis of Cushing disease (CD) during gestation can be difficult. Similar to nonpregnant women, surgery is the first treatment option for CD during pregnancy, if complications develop. Overall, pregnancy in women harboring clinically nonfunctioning tumors is a rare event. Causes of hypopituitarism that are most specific to pregnancy include lymphocytic hypophysitis and postpartum pituitary infarction (Sheehan’s syndrome). During pregnancy, the priority for hormonal replacement should be glucocorticoid, followed by thyroid hormone. Doses should be adjusted throughout pregnancy based on the severity and nature of the condition. For this reason, it is necessary to follow these patients regularly and closely during pregnancy. Central or nephrogenic diabetes insipidus (DI) can also be observed during pregnancy. Therefore, a detailed medical history is essential for the differential diagnoses of DI. Primary polydipsia and head trauma should be excluded. Ingestion of drugs such as lithium, mannitol, diuretics, and anticholinergic drugs should be questioned. Management of pituitary disease during pregnancy in otherwise healthy women poses difficult challenges from various perspectives. However, a multidisciplinary approach, involving the endocrinologist, obstetrician, neurosurgeon, and anesthesiologist, will allow a better outcome for both mother and fetus during pregnancy.

Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays a key role in GH secretion. In this review, we summarize the current state of knowledge regarding the physiology and molecular machinery of VGCCs in pituitary somatotrophs. We next discuss the possible involvement of Ca2+ channelopathies in pituitary disease and the potential use of Ca2+ channel blockers to treat pituitary disease. Various types of VGCCs exist in pituitary cells. However, because L-type Ca2+ channels (LTCCs) contribute the major component to Ca2+ influx in somatotrophs, lactotrophs, and corticotrophs, we focused on these channels. An increasing number of studies in recent years have linked genetic missense mutations in LTCCs to diseases of the human cardiovascular, nervous, and endocrine systems. These disease-associated genetic mutations occur at homologous functional positions (activation gates) in LTCCs. Thus, it is plausible that similar homologous missense mutations in pituitary LTCCs can cause abnormal hormone secretion and underlying pituitary disorders. The existence of LTCCs in pituitary cells opens questions about their sensitivity to dihydropyridines, a group of selective LTCC blockers. The dihydropyridine sensitivity of pituitary cells, as with any other excitable cell, depends primarily on two parameters: the pattern of their electrical activity and the dihydropyridine sensitivity of their LTCC isoforms. These two parameters are discussed in detail in relation to somatotrophs. These discussions are also relevant to lactotrophs and corticotrophs. High dihydropyridine sensitivity may facilitate their use as drugs to treat pituitary oversecretion disorders such as acromegaly, hyperprolactinemia, and Cushing disease.

BACKGROUND Perioperative steroid protocols for patients undergoing transsphenoidal surgery (TSS) for pituitary pathology vary by institution. OBJECTIVE To assess the safety of withholding glucocorticoids in patients undergoing TSS. METHODS Patients with an intact hypothalamic-pituitary-adrenal (HPA) axis undergoing TSS for a pituitary tumor at the same academic institution between 2012 and 2015 were randomized to either receive 100 mg of intravenous hydrocortisone followed by 0.5 mg of intravenous dexamethasone every 6 h for 4 doses (STER, n = 23) or to undergo surgery without steroids (NOSTER, n = 20). Postoperative cortisol levels were then used to determine the need for glucocorticoids after surgery. Data regarding postoperative cortisol levels, hospital stay length, and complications were collected. RESULTS Mean postoperative 8 am cortisol levels were higher in the NOSTER group compared to the STER group (745 ± 359 nmol/L and 386 ± 193 nmol/L, respectively, P = .001) and more patients were discharged on glucocorticoids in the STER group (42% vs 12%, P = .07). There was no difference in the incidence of postoperative complications, including hyperglycemia, diabetes insipidus, or permanent adrenal insufficiency. Permanent adrenal insufficiency occurred in 8% of patients. CONCLUSION Perioperative steroids can be safely withheld in patients with an intact HPA axis undergoing TSS. Although administration of perioperative glucocorticoids does not appear to increase the risk of complications, it may interfere with assessment of the HPA axis after surgery.

Several different proteins regulate, directly or indirectly, the production of growth hormones from the pituitary gland, thereby complex genetics is involved. Defects in these genes are related to the deficiency of growth hormones solely, or deficiency of other hormones, secreted from the pituitary gland including growth hormones. These studies can aid clinicians to trace the pattern of the disease between the families, start early treatment and predict possible future consequences. This paper highlights some of the most common and novel genetic anomalies concerning growth hormones, which are responsible for various genetic defects in isolated growth and combined pituitary hormone deficiency disease.

BACKGROUND Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. METHODS In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. RESULTS Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). CONCLUSIONS Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

Background: Growth hormone (GH) treatment may unmask central hypothyroidism (CeH). This was first observed in children with GH deficiency (GHD), later also in adults with GHD due to acquired “organic” pituitary disease. We hypothesized that newly diagnosed CeH in children after starting GH treatment for nonacquired, apparent isolated GHD points to congenital “organic” pituitary disease. Methods: Nationwide, retrospective cohort study including all children with nonacquired GHD between 2001 and 2011 in The Netherlands. The prevalence of CeH, hypothalamic-pituitary (HP) abnormalities, and neonatal congenital hypothyroidism screening results were evaluated. Results: Twenty-three (6.3%) of 367 children with apparent isolated GHD were prescribed LT4 for presumed CeH within 2 years after starting GH treatment. Similarly to children already diagnosed with multiple pituitary hormone deficiency, 75% of these 23 had structural HP abnormalities. In children not prescribed LT4, low pre- or post-GH treatment FT4 concentrations were also associated with structural HP abnormalities. Neonatal screening results of only 4 of the 23 children could be retrieved. Conclusion: In children with nonacquired, apparent isolated GHD, a diagnosis of CeH after, or a low FT4 concentration around the start of GH treatment, is associated with congenital structural HP abnormalities, i.e., “organic” pituitary disease. Neonatal values could not be judged reliably.

Patients with growth hormone deficiency (GHD) have an increased risk of atherosclerosis and vascular mortality. Evidence suggests that endothelial dysfunction is involved in all stages of atherogenesis. This study examined the effect of growth hormone (GH) replacement therapy on diacron-reactive oxygen metabolites (d-ROMs) and endothelial function in Japanese patients with GHD, using peripheral arterial tonometry. This was an open-label, prospective, case-control study. Nine patients with GHD who had not previously received any GH replacement therapy were enrolled. The following parameters were evaluated at baseline (before treatment), and after 24 weeks of GH replacement therapy: endothelial function using the reactive hyperemia index (RHI; EndoPAT® system), d-ROMs, blood pressure, and fasting lipid levels. Plasma GH and insulin-like growth factor-1 (IGF-1) levels were measured at baseline and after 24 weeks of GH replacement therapy. We also enrolled eight controls with pituitary disease but no GH deficiency. Over 24 weeks of GH replacement therapy, the serum IGF-1 levels normalized with significant improvement in the RHI (from 1.65 ± 0.33 to 1.92 ± 0.26, p < 0.05) and decreased d-ROM levels (from 356.8 ± 64.1 to 303.1 ± 43.3 U.CARR, p < 0.05). There were no significant improvements in the RHI or d-ROM levels in controls. GH replacement therapy in Japanese patients with GHD may be mediated by the reduced oxidative stress and the d-ROMs associated with the treatment.

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.

Central nervous system (CNS) disease is an uncommon but significant complication of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and affects 3 primary areas of the CNS: the pituitary, the pachymeninges, and the CNS vasculature. Pituitary disease in uncommon, but hormonal deficiencies can be long lasting even in the face of excellent disease response. Chronic hypertrophic pachymeninigitis occurs in anti-proteinase 3-positive patients with systemic GPA and in anti-myeloperoxidase-positive patients with a milder and more limited form of the disease. Cerebral and spinal vasculitis due to GPA and MPA presents with focal and general neurologic abnormalities.

Background The use of combined positron emission tomography/computed tomography for staging in patients with cancer and the widespread use of magnetic resonance imaging has led to increased detection of incidental sellar masses. The imaging findings can be suggestive of a benign pituitary tumor, but metastasis can never be completely ruled out with noninvasive work-up. Appropriate diagnosis of sellar masses is critical, as the treatment paradigm might change in the presence of a pituitary metastasis. Definitive tissue diagnosis might prevent unnecessary radiotherapy to the skull base or the need for systemic treatment when benign pituitary disease is confirmed. Methods A retrospective chart review from 2010 to 2015 of all patients with recently diagnosed cancer and undergoing surgery for sellar region masses was performed. Results There were 9 patients (3 female and 6 male) identified. Lung cancer was the primary condition in 4 patients; the remaining 5 patients had breast cancer, follicular thyroid cancer, cutaneous melanoma, colorectal carcinoma, and renal cell carcinoma. On final pathology, the sellar mass was a benign pituitary adenoma in 5 patients, metastatic cancer in 3 patients, and a granular cell tumor in 1 patient. Conclusions Surgical resection of a sellar mass in patients with known cancer helps in the definitive diagnosis, relieves compressive symptoms, and avoids unnecessary empiric radiotherapy in cases of confirmed benign pituitary disease.

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.

The prevalence of pituitary disease is increasing mainly because of advances in modern imaging techniques and an increased awareness among the medical community. Pituitary tumours constitute 10–15% of all diagnosed intracranial neoplasms, and their clinical manifestations result from local mass effects (mostly neurological, visual, hypopituitarism) and/or hypersecretion. Pituitary adenomas are the most common pituitary tumours and are clinically classified as functioning or non-functioning. Most are sporadic, but in rare cases they can be related to hereditary syndromes. Other lesions involving the (para)sellar region include inflammatory and infiltrative diseases, cysts, primary or metastatic neoplasms, abscesses and internal carotid artery aneurysms. The clinical manifestations of hypopituitarism depend mainly on the type, number and severity of hormonal deficits. Establishing the diagnosis requires hormonal measurements (basal or after dynamic tests), and management includes relevant hormonal replacement and life-long monitoring.

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.

Pituitary adenomas (PA) occur mainly as sporadic disease, but familial syndromes are found in approximately 5% of cases. Identification of these syndromes is important in order to diagnose individuals at risk at an earlier stage. To evaluate the frequency of familial PA in a reference outpatient clinic devoted to PA treatment and to identify family members suspected to have pituitary disease. Patients with PA were interviewed with respect to the presence of family members with diagnosis of PA or with signs or symptoms suggestive of them. The family members who had a clinical picture suggestive of pituitary disease were further evaluated in an attempt to identify new PA cases. In families with familial disease, the AIP gene was sequenced. 262 patients were evaluated and familial syndrome was found in 13 (5%). Ten (3.8%) patients had familial isolated PA (FIPA) and three (1.2%) had multiple endocrine neoplasia type 1. After evaluation of family members’ symptomatology, 110 were considered suspected of having pituitary disease, but only 24 participated in the study. Of these 24, 1 was diagnosed with a corticotropinoma. AIP mutations were found in 20% of FIPA families. We found a frequency of familial PA similar to that previously described, as well as a similar frequency of AIP mutations among FIPA families. An active search of the affected family members was able to identify one case of Cushing´s disease. Patients should be aware of pituitary disease’s clinical picture to identify possibly affected family members.

Context: Cabergoline (CAB) is very effective in the treatment of macroprolactinomas, but there are few data on the CAB dose necessary to achieve and maintain normal prolactin (PRL) levels. Design and Patients: We retrospectively studied 260 patients. CAB was introduced at a mean dose of 0.83 ± 0.52 mg/wk. When the PRL level had normalized, the patient's physician chose to either maintain the CAB dose (fixed-dose group) or to taper it (de-escalation group) until the minimal effective dose required to maintain a normal PRL level was established. Results: PRL normalized in 157 patients (60.8%) during CAB treatment. CAB de-escalation was attempted in 84 (53.5%) of these 157 patients and was successful in 77 (91.7%) cases. The mean CAB dose was reduced from 1.52 ± 1.17 mg/wk to 0.56 ± 0.44 mg/wk at the last visit (P < 1 × 10−4). De-escalation was also possible in some “CAB-resistant” patients, namely those requiring ≥2 mg/wk to normalize PRL. CAB de-escalation had no negative long-term effect on tumor size. At the last visit, maximal diameter was 8.8 ± 8.8 mm in the de-escalation group and 13.4 ± 8.5 mm in the fixed-dose group (P < 0.01). Conclusion: In patients with macroprolactinomas, the CAB dosage required to maintain a normal PRL level long term is lower than the initial dosage necessary to normalize the PRL level. After PRL normalization, CAB tapering was almost always successful, even when very high initial doses were necessary. CAB tapering does not undermine tumor control and may attenuate the potential adverse effects of CAB, which appear to be dependent on the cumulative dose., Even if high doses of cabergoline were necessary to achieve normal PRL levels in patients with macroprolactinomas, it was possible to taper cabergoline to very low doses in 90% of cases.

Background Transsphenoidal surgery (TSS) was introduced into the Republic of Uzbekistan in 2005 and has been developing since then. The principal center for the management of all pituitary disease is a single site for a nation with a population of approximately 30 million. Results in surgery for Cushing disease are a marker of surgical technical skill in TSS. All previously published series come from the developed world, where sophisticated investigations and management are available. Many of these investigations are not available in Uzbekistan. Methods This mixed series of 154 patients from 2000 to 2013 presents the data from Uzbekistan. The management of Cushing disease before the introduction of TSS was with unilateral adrenalectomy, a procedure virtually unknown in the West. It reduces cortisol burden but is, in the long-term, only a temporary measure because it allows the tumor to continue to grow. The results of this procedure are presented and show that in the short-term, surprisingly reasonable remission is obtained. Results These results are contrasted with the experience with TSS, for which the impact of the input from an experienced team including an endocrinologist and neurosurgeon from the United Kingdom allowed a transformation in management and enabled outcomes to match what can be expected in the West. Conclusions TSS for Cushing's Disease achieved an early remission of 68.7% (early morning cortisol of