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Canine Cushing’s syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, noninvasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as noninvasive biomarkers for canine Cushing’s syndrome.After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre-and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples).In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9×10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of < 11.These results indicate that circulating miRNAs have the potential to be noninvasive biomarkers in dogs with Cushing’s syndrome that may contribute to clinical decision-making.

The clinical course of pituitary adenoma can be highly variable. Aggressive pituitary tumours may require multimodal therapy with multiple operations. Even standard pituitary adenomas exhibit relatively high long-term recurrence rates and delayed intervention is often required. The indications for revision surgery in the endoscopic era are expanding for both functioning and nonfunctioning tumours, including access to the cavernous sinus and intracranial compartments. Although revision surgery can be challenging, it has been demonstrated to be both safe and effective. The question of the use of early radiotherapy in pituitary adenoma remains controversial. Our increasing understanding of pituitary tumour biology facilitates individualized treatment and surveillance protocols, with early intervention in high-risk adenoma subtypes. In this review, we discuss the treatment options for recurring pituitary tumours and focus on the role of revision surgery.

Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

Objective Lymphocytic hypophysitis (LYH) is a rare autoimmune inflammatory disease of the pituitary gland. In this study, we aim to characterize LYH at presentation and focus on the management and prognosis of LYH. Methods A retrospective study of patients with LYH was conducted between 2011 and 2018 at a single institute. The patients were included by pathologic conformation and strict exclusion criteria. Clinical profile, imaging, and management data were collected. Results Twenty patients with LYH (16 women and 4 men) were included. Ten patients were diagnosed histologically and the remaining 10 patients were confirmed clinically of exclusion criteria. The median age at diagnosis was 37 years (range, 16–58 years). Presenting symptoms were followed by polyuria/polydipsia (11, 55%), vision changes (10, 50%), headache (8, 40%), menstrual irregularities and amenorrhea (4, 20%), diplopia (1, 5%), or sexual dysfunction (1, 5%). Eight patients had partial anterior pituitary hormone dysfunction. The thyroid-stimulating hormone axis was most involved. Ten patients received transsphenoidal surgery, 5 patients experienced steroid pulse therapy, and observation was performed on 5 patients. Only 5 patients (25%) showed improvement of anterior pituitary dysfunction after initial management. Recovery of diabetes insipidus occurred in 2 patients (18%). The overall recurrence rate was 22.2%. Conclusions Nonoperative treatment is a better option for most patients with LYH because it is effective and noninvasive. Surgery is recommended for definitive diagnosis, severe or rapid progression of neurologic impairment, and glucocorticoid insensitivity. Periodic follow-up is mandatory in a patient's long-term management.

Sex differences in liver gene expression are determined by pituitary growth hormone secretion patterns, which regulate sex-dependent liver transcription factors and establish sex-specific chromatin states. Hypophysectomy (hypox) identifies two major classes of liver sex-biased genes, defined by their sex-dependent positive or negative responses to pituitary hormone ablation. However, the mechanisms that underlie each hypox-response class are unknown. We sought to discover candidate, regulatory, long noncoding RNAs (lncRNAs) controlling responsiveness to hypox. We characterized gene structures and expression patterns for 15,558 mouse liver-expressed lncRNAs, including many sex-specific lncRNAs regulated during postnatal development or subject to circadian regulation. Using the high natural allelic variance of Diversity Outbred (DO) mice, we discovered tightly coexpressed clusters of sex-specific protein-coding genes (gene modules) in male and female DO liver. Remarkably, many gene modules were strongly enriched for sex-specific genes within a single hypox-response class, indicating that the genetic heterogeneity of DO mice encompasses responsiveness to hypox. Moreover, several distant gene modules were enriched for gene subsets of the same hypox-response class, highlighting the complex regulation of hypox-responsiveness. Finally, we identified eight sex-specific lncRNAs with strong negative regulatory potential, as indicated by their strong negative correlation of expression across DO mouse livers with that of protein-coding gene modules enriched for genes of the opposite sex bias and inverse hypox-response class. These findings reveal an important role for genetic factors in regulating responsiveness to hypox, and present testable hypotheses for the roles of sex-biased liver lncRNAs in controlling the sex-bias of liver gene expression.

An 11-year-old castrated male Chihuahua dog was presented with complaints of polyuria, polydipsia, abdominal enlargement, and alopecia. Hyperadrenocorticism was diagnosed on the basis of clinical signs, blood tests, adrenocorticotropin-stimulation test results, and an elevated serum adrenocorticotropin concentration. Contrast-enhanced magnetic resonance imaging showed that the pituitary gland was enlarged, compatible with a pituitary macroadenoma. Pituitary-dependent hyperadrenocorticism was suspected, and transsphenoidal hypophysectomy was thus performed for complete resection of the tumor. After surgery, the serum adrenocorticotropin concentration normalized and the hyperadrenocorticism resolved. Histological and immunocytochemical analyses revealed a benign tumor composed of mature neuronal cells and glial cells, suggestive of a ganglioglioma with immunolabeling for adrenocorticotropin. Careful analysis of the resected tumor revealed no pituitary adenoma tissue. The clinical and histopathologic findings indicated that the ganglioglioma was directly responsible for the hyperadrenocorticism. This is the first case of hyperadrenocorticism caused by a ganglioglioma in a dog.

OBJECTS Cushing's disease (CD) is the most common cause of ACTH-dependent hypercortisolism in children age ≥ 7. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children. We present a case series of children with ACTH-dependent hypercortisolemia and review the literature to assess the utility of BIPSS in the diagnosis and localization of CD. METHODS We performed an IRB-approved chart review of patients aged ≤ 18 with ACTH-dependent hypercortisolism at MGH between 2000 and 2019 and collected clinical, laboratory, radiographic, BIPSS, surgical, and outcomes data. RESULTS In our cohort (n = 21), BIPSS had a sensitivity of 93% and specificity of 100% for diagnosis of CD. Compared to surgery, successful BIPSS correctly predicted adenoma laterality in 69% of cases vs. 70% by MRI. Among patients with lesions ≥ 4 mm (n = 9), BIPSS correctly lateralized in 50% vs. 100% by MRI. In patients with subtle lesions (

Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia. After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following: preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset. Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25 days postoperatively and persisted for 5.54 days. The lowest average blood sodium level was 123.9 mEq/L, which occurred at 7.49 days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative “measurable pituitary stalk”. The difference in blood sodium levels between pre-TSS and 2 days post-TSS was also an independent predictor of postoperative hyponatremia onset. DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.

Background Successful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats. Objectives To describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020. Animals Twenty-five client-owned cats with spontaneous hypersomatotropism. Methods Retrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin-like growth factor-1 (IGF-1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF-1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow-up information from owners and referring veterinarians. Results Median postoperative hospital stay was 7 days (range, 3-18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0-101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6-13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF-1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14-240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900-1794 days; range, 11-3180 days) and the overall 1-, 2-, and 3-year all-cause survival rates were 76%, 76%, and 52%, respectively. Conclusions and clinical importance This study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval anastomosis (PCA) is a model of liver damage and fibrosis. Arginine vasopressin (AVP) has been implicated as a proinflammatory-profibrotic hormone. In rats, neurointermediate pituitary lobectomy (NIL) induces a permanent drop (80%) in AVP serum levels. We hypothesized that AVP deficiency (NIL-induced) may decrease liver damage and fibrosis in a rat PCA model. Male Wistar rats were divided into intact control (IC), NIL, PCA, and PCA+NIL groups. Liver function tests, liver gene relative expressions (IL-1, IL-10, TGF-β, COLL-I, MMP-9, and MMP-13), and histopathological assessments were performed. In comparison with those in the IC and PCA groups, bilirubin, protein serum, and liver glycogen levels were restored in the PCA+NIL group. NIL in the PCA animals also decreased the gene expression levels of IL-1 and COLL-I, while increasing those of IL-10, TGF-β, and MMP-13. Histopathology of this group also showed significantly decreased signs of liver damage with lower extent of collagen deposition and fibrosis. Low AVP serum levels were not enough to fully activate the AVP receptors resulting in the decreased activation of cell signaling pathways associated with proinflammatory-profibrotic responses, while activating cell molecular signaling pathways associated with an anti-inflammatory-fibrotic state. Thus, partial reversion of liver damage and fibrosis was observed. The study supports the crucial role of AVP in the inflammatory-fibrotic processes and maintenance of immune competence. The success of the AVP deficiency strategy suggests that blocking AVP receptors may be therapeutically useful to treat inflammatory-fibrotic liver diseases.

Dynamic testing represents the mainstay in the differential diagnosis of ACTH-dependent Cushing's syndrome. However, in case of undetectable or detectable lesion 6 mm on MRI, bilateral inferior petrosal sinus sampling (BIPSS) is suggested by current guidelines. Aim of this study was to analyze the performance of CRH, desmopressin and high-dose dexamethasone suppression test (HDDST) in the differential diagnosis of ACTH-dependent Cushing's syndrome as well as the impact of invasive and noninvasive tests on surgical outcome in patients affected by Cushing's disease (CD).Retrospective analysis on 148 patients with CD and 26 patients with ectopic ACTH syndrome.Among CD patients, negative MRI/lesion 6 mm was detected in 97 patients (Group A); 29 had a 6-10 mm lesion (Group B) and 22 a macroadenoma (Group C). A positive response to CRH test, HDSST and desmopressin test was recorded in 89.4%, 91·4% and 70.1% of cases, respectively. Concordant positive response to both CRH/HDDST and CRH/desmopressin tests showed a positive predictive value of 100% for the diagnosis of CD. Among Group A patients with concordant CRH test and HDDST, no difference in surgical outcome was found between patients who performed BIPSS and those who did not (66.6% vs 70.4%, p = 0.78).CRH, desmopressin test and HDDST have high accuracy in the differential diagnosis of ACTH-dependent CS. In patients with microadenoma 6 mm or non-visible lesion, a concordant positive response to noninvasive tests seems sufficient to diagnose CD, irrespective of MRI finding. In these patients, BIPSS should be reserved to discordant tests.

Surgical or chemical hypophysectomy has historically shown good effectiveness in management of intractable pain but has often been accompanied by serious complications. In contrast, high-dose irradiation of the pituitary gland and stalk provides comparable analgesic effects and is associated with minimal morbidity. Although its physiological mechanism remains elusive, pituitary radiosurgery using the Gamma Knife has demonstrated high clinical efficacy and safety in cases of both cancer pain and noncancer pain. According to the available data, this treatment provides at least a temporary analgesic effect in >80% of patients, usually within hours to days after the procedure. Although the pain relief is most prominent and durable in cases of metastatic bone disease, it is not limited to that pathological condition or to cases of hormone-dependent cancers. Nevertheless, the low-quality studies reported to date cannot support any meaningful clinical recommendations on use of pituitary radiosurgery. Therefore, additional well-elaborated clinical and basic investigations, preferably performed in a multi-institutional and prospective fashion, are clearly needed and may bolster further developments of this highly promising treatment modality.

Long-term hormone replacement therapy due to panhypopituitarism can lead to serious complications and thus, pituitary transplantation is considered a more desirable. We investigated functional restoration after allotransplatation of the pituitary gland. We transplanted extracted pituitary gland into the omentum of an hypophysectomized rat. Two experiments were performed: (1) to confirm the hypophysectomy was successful and (2) to assess functional restoration after pituitary transplantation. Pituitary hormone level and weight change were consecutively assessed. Electron microscopic (EM) examinations were performed to identify morphological changes at 3 days after transplantation. We confirmed that pituitary gland was properly extracted from 6 rats after sacrifice. The findings showed (1) a weight loss of more than 3% or (2) a weight change of less than 2% along with a decreased growth hormone (GH) level by more than 80% at 2 weeks post-hypophysectomy. A further four rats underwent pituitary transplantation after hypophysectomy and were compared with the previously hypophysectomized rats. All showed rapid weight gain during the two weeks after transplantation. The thyroid-stimulating hormone, prolactin, and GH levels were restored at one week post-transplantation and maintained for 10 weeks. Hypophyseal tissue architecture was maintained at 3 days after transplantation, as indicated by EM. These data suggest that a transplanted pituitary gland can survive in the omentum with concomitant partial restoration of anterior pituitary hormones.

Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass ( P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases ( P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.

The theory holds that the anterior pituitary in mammals receives humoral regulation. Previous studies have reported that the pars distalis of the anterior pituitary of several mammalian species contains substance P-, calcitonin gene-related peptide (CGRP)-, and galanin-like immunoreactive nerve fibers, but the origins of these nerve fibers are unclear. Removal of the pituitary gland, also called hypophysectomy, involves methods that access the pituitary gland via the transauricular or parapharyngeal pathways. However, these methods are not applicable for viral tracer injection to investigate the innervation of the anterior pituitary. The transauricular technique leads to inaccuracies in locating the pituitary gland, while the parapharyngeal approach causes high mortality in animals. Here, we introduce a protocol that accesses the pituitary gland in the rat via the transsphenoidal pathway. This method imitates surgical manipulations such as endotracheal intubation and sphenoid bone drilling, which involve the use of custom-made devices. Using the transsphenoidal pathway greatly improves the survival rate of rats because no additional dissection of blood vessels and nerves is required. Moreover, the pituitary gland can be viewed clearly and directly during the operation, making it possible to accurately inject pseudorabies virus (PRV) 152-expressing enhanced green fluorescent protein (EGFP) into the anterior or posterior pituitary, respectively. After injecting PRV 152 into the anterior pituitary, we found no evidence of direct innervation of the anterior pituitary in the rat brain. However, PRV 152 injection into the posterior pituitary revealed retrograde transneuronal cell bodies in many brain areas, including the CA1 field of the hippocampus, the basolateral amygdaloid nucleus, posterior part (BLP), the arcuate hypothalamic nucleus (Arc), the dorsal portion of the dorsomedial hypothalamic nucleus (DMD), the suprachiasmatic nucleus (SCh), and the subfornical organ (SFO). In the present study, we provide a description of a possible model of hypophysectomy or pituitary injection, and identify brain regions involved in regulating the rat pituitary gland using transneuronal retrograde cell body labeling with PRV.

Growth hormone secreting pituitary tumor or gigantism has not been previously reported to be associated with rapid progression of scoliosis in the literature. However, there are some reports indicating scoliosis can be worsened by growth hormone therapy in children and adolescents. A 19-year-old boy was referred to our institution for the treatment of a right thoracolumbar scoliosis. The Cobb angle had worsened from 29° to 83° over two years' duration. He attained puberty at the age of 13. He had a previous history of slipped upper femoral epiphysis (SUFE), which was operated in 2015, with no clinical features of gigantism. Preoperative assessment was performed. He was diagnosed with growth hormone secreting pituitary macroadenoma by magnetic resonance imaging with a high serum level of insulin-like growth factor-I (IGF-I). Computed tomography (CT) of the pancreas showed a pancreatic endocrine tumor. The patient was later diagnosed with multiple endocrine neoplasia type 1 (MEN 1). He underwent endoscopic endonasal excision of the pituitary mass and distal pancreatectomy. This case indicates that growth hormone secreting pituitary macroadenoma could result in rapid progression of scoliosis.

ContextAlthough consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1).MethodologyRetrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients’ dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed.ResultsA microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (p = 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (p = 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4–37.7,p = 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs.ConclusionsFirst-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term.

OBJECTIVE Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. METHODS In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. RESULTS We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. CONCLUSIONS Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD.

A 57-year-old woman presented with severe lethargy, dizziness and nausea 1 week after transsphenoidal resection of a growth hormone secreting pituitary adenoma. She was found to have severe hyponatremia of 115 mmol/L. Importantly, she was neurologically intact and clinically euvolaemic. Her fluid intake was restricted and her sodium levels increased to 131 mmol/L over 4 days. She made a full recovery.She was diagnosed with isolated second-phase diabetes insipidus, a state of symptomatic hypoosmolar hyponatremia that usually occurs 7–10 days after transsphenoidal surgery. The sodium levels improve with fluid restriction.

Importance Iatrogenic olfactory dysfunction after endoscopic transsphenoidal hypophysectomy (ETSH) is an overlooked complication without elucidated risk factors. Objective To assess the independent prognostic role of demographic, comorbidity, cephalometric, intraoperative, histological, and postoperative parameters in patient-reported postoperative olfactory dysfunction, and to explore the association between anatomical measurements of the skull base and sinonasal cavity and postoperative olfactory dysfunction. Design, Setting, and Participants This retrospective cohort study in a tertiary care medical center enrolled consecutive patients with primary sellar lesions who underwent ETSH between January 1, 2015, and January 31, 2019. Patients were excluded if they underwent multiple sinonasal surgical procedures, presented with a sellar malignant neoplasm, required an expanded transsphenoidal approach, had nasal polyposis or a neurodegenerative disease, or sustained traumatic brain injury. After undergoing medical record review and telephone screening, patients were asked to participate in a 3-item telephone survey. Main Outcomes and Measures The primary outcome was the Clinical Global Impressions change in smell rating, a validated transitional patient-reported outcome measure. Patients rated their change in smell before and after ETSH on a 7-point Likert scale, with the following response options: (1) much better, (2) somewhat better, (3) slightly better, (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, or (7) much worse. Responses of slightly worse, somewhat worse, and much worse were surrogates for postoperative olfactory dysfunction status. Patient medical records, preoperative imaging scans, operative notes, and pathology reports were reviewed. Results Of the 147 patients (mean [SD] age, 54 [15] years; 79 women [54%]) who responded to the telephone survey, 42 (29%) reported olfactory dysfunction after ETSH. Median (interquartile range [IQR]) time between the ETSH completion and survey response was 31.1 (21-43) months. On multivariable analysis, abdominal fat grafting (adjusted relative risk [aRR], 2.95; 95% CI, 1.89-4.60) was associated with postoperative olfactory dysfunction, whereas smoking history (aRR, 1.54; 95% CI, 0.95-2.51) demonstrated a clinically meaningful but imprecise effect size. A more obtuse angle between the planum sphenoidale and face of the sella turcica on sagittal imaging was protective (aRR, 0.98; 95% CI, 0.96-0.99). Increased number of months after the ETSH was associated with patient-reported normosmia (aRR, 0.93; 95% CI, 0.91-0.95). In contrast, other comorbidities; intraoperative variables such as turbinate resection, nasoseptal flap, and mucosal or bone grafting; histological variables such as pathology and proliferative index; and postoperative variables such as adjuvant radiotherapy were not associated with postoperative olfactory dysfunction. Conclusions and Relevance This study found that abdominal fat grafting, acute skull base angle, and smoking history appeared to be clinically significant risk factors for patient-reported postoperative olfactory dysfunction. Increased time after ETSH may be associated with better olfactory outcomes.

Among the various ways that growth hormone (GH) underlies the growth physiology of teleost fishes, GH stimulates transport pathways that facilitate the absorption of nutrients across intestinal epithelia. The current study investigated the effects of GH on the gene expression of nutrient transporters in an omnivorous teleost, the Mozambique tilapia (Oreochromis mossambicus). We employed pituitary gland removal (hypophysectomy) and hormone replacement to assess whether GH directs the gene expression of the GH receptor (ghr2), the peptide transporters, pept1a, pept1b and pept2, the amino acid transporter, slc7a9, the Na(+)/glucose cotransporter, sglt1, the glucose transporter, glut2, and the myo-inositol transporter, smit2, in anterior, middle, and posterior intestine. ghr2 was predominantly expressed in posterior intestine, while pept1a, pept1b, slc7a9, sglt1, glut2, and smit2 exhibited the highest mRNA levels in anterior and/or middle intestine. While hypophysectomized tilapia exhibited diminished expression of ghr2, pept1a, pept1b, slc7a9, and glut2 compared with intact and sham-operated controls, only ghr2, pept1a, pept1b and glut2 levels were restored by GH replacement. Our findings indicate that GH supports growth, at least in part, by stimulating the gene expression of its cognate receptor and key nutrient transporters in the intestine.

Acromegaly is a chronic endocrine disorder caused by hypersecretion of growth hormone (GH) mostly because of pituitary adenoma. GH induces the formation of Insulin like Growth Factor1 (IGF1)from the liver. Both GH andIGF1 lead to sign and symptom of acromegaly.Aim: This study designed to identify the prevalence of thyroid dysfunction in Iraqi patients with acromegaly ,to identify the factors responsible for thyroid dysfunction in patients with acromegaly.Is the treatment modalities for acromegaly has a role in thyroid dysfunction?Study design: A cross sectional case control studyPatients and Method: seventy patients with acromegaly were enrolled from 2 different tertiary centers of endocrinology from Jan. -Dec. 2017 compared with 70 non acromeglic subjects. Their mean age 46 +/-11 years ;forty one (58.5%) males and 29(41.5%)females. Thyroid function test conducted to both patients and control groups including TSH, free T4 and total T3 in both centers. In addition to other variables.Results: Out of 70 (100%) patients with acromegaly; (51.5%) were euthyroid, (20%) had primary hypothyroidism , (15.7%)had central hypothyroidism and (12.8%) had hyperthyroidism that is significantly higher than normal population (p

Medical management is currently the most common treatment for pituitary-dependent hyperadrenocorticism and hypersomatotropism/acromegaly in veterinary medicine. Medical management does not provide a cure for either disease process, and rarely is pituitary imaging a part of initial diagnostics. Early pituitary imaging in animals with clinically functional pituitary tumors provides a baseline assessment, allows monitoring of tumor changes, and permits radiation and surgical planning. Surgery is the only treatment for pituitary tumors that has curative intent and allows for a definitive diagnosis. Surgical removal of pituitary tumors via transsphenoidal hypophysectomy is an effective treatment for clinical pituitary tumors in patients exhibiting endocrine abnormalities associated with pituitary-dependent hyperadrenocorticism and hypersomatotropism. Surgery, however, is rarely pursued until patients have failed medical management, and often not until they are showing neurologic signs, making surgical success challenging. It is well documented that dogs surgically treated when the pituitary mass is small have a lower mortality, a lower recurrence rate, and a longer survival than those with larger pituitary masses. Providing owners with the option of early pituitary imaging in addition to medical, surgical, and radiation treatment options should be the standard of care for animals diagnosed with pituitary-dependent hyperadrenocorticism or hypersomatotropism.

Background Pituicytoma is a rare; slow-growing primary tumour originating from the glial cells of the neurohypophysis. It was classed as a low-grade (grade I) central nervous system tumour by the World Health Organization in 2007. We present the case of a 71-year-old man with a previous history of sellar meningioma who underwent surgical resection of pituicytoma by transphenoidal hypophysectomy. Method We conducted a literature search using Medline EMBASE and the Cochrane Database of Systematic Reviews using the Ovid search engines. Key words searched were ‘pituitary gland’, ‘pituicytoma’, ‘neurohypophysis’. Patient records and imaging were obtained from the Royal Stoke University Hospital database. Results A 71-year-old man with a background of sellar meningioma 16 years previously was found to have a pituitary fossa tumour on surveillance magnetic resonance imaging. Differential diagnosis was pituitary adenoma. Endoscopic transphenoidal hypophysectomy was performed. Histology was consistent with pituicytoma. As a result of this histology from his initial tumour was re-examined and was amended to pituicytoma, indicating a recurrence. Conclusion Pituicytoma is a benign, slow growing lesion of the posterior pituitary. Brat et al diagnosed it as a distinct entity in 2000 and it was listed as a World Health Organization classification grade I tumour in 2007. It can be mistaken for pituitary adenoma owing to its similar clinical presentation. Complete excision of the tumour by transphenoidal hypophysectomy is an effective management for pituicytoma as demonstrated in this case.

A 31-year-old male was referred for evaluation after being diagnosed with Cushing syndrome secondary to a pituitary microadenoma. He presented with a reduced visual acuity and high intraocular pressure (IOP) of 48mmHg in both eyes. The examination with biomicroscopy showed normal anterior segment, increased cup to disc ratio, and open angle. There was a moderate-advanced involvement in the visual field. The patient was diagnosed with glaucoma secondary to endogenous corticosteroids, and medical treatment was initiated pending the removal of the adenoma. The IOP did not return to normal after the incomplete removal of the adenoma, so a trabeculectomy was performed to control the IOP. As conclusions: In the case of an ocular hypertension with pituitary tumour, secondary glaucoma to endogenous cortisone should be suspected. Early treatment of the tumour is necessary to bring the cortisone and IOP levels back to normal. Late diagnosis or incomplete treatment of these tumours may lead to not obtaining adequate IOP control.

Acromegaly is a condition caused by a pituitary somatotroph adenoma which causes an over production of somatotropin (hypersomatotropism). This can cause the patient to become insulin resist...

Hypophysectomy specimens from 16 dogs with pituitary adenoma were evaluated with periodic acid-Schiff (PAS), reticulin, and immunohistochemistry for adrenocorticotrophic hormone (ACTH), melanocyte stimulating hormone (MSH), growth hormone (GH), and Ki-67. The reticulin network was obliterated in all adenomas. One adenoma expressed ACTH and GH. Eight corticotroph adenomas were basophilic to chromophobic, and PAS- and ACTH-positive. Seven melanotroph adenomas were distinguished from corticotroph adenomas by expression of MSH. Pituitary-dependent hypercortisolism was diagnosed in 5 of 8 dogs with corticotroph and 4 of 7 with melanotroph adenoma. Pituitary height/brain area (P/B) ratio was elevated in all dogs. Previous canine hypophysectomy studies suggested that melanotroph adenomas were larger and carried a worse prognosis than corticotroph adenomas; however, in this study, corticotroph adenomas in comparison to melanotroph adenomas were larger (median P/B ratio: 1.06 versus 0.76), more proliferative (median Ki-67 index: 9.47% versus 1.99%), and associated with shorter survival (median: 300 versus 793 days). Recommended immunohistochemistry for PAS-positive pituitary adenomas includes ACTH and MSH to distinguish corticotrophs from melanotrophs and Ki-67 for proliferation index.

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system.

To determine if the consistency of pituitary adenomas can be predicted based on a preoperative MRI study and to assess the surgical outcome of firm pituitary adenomas.One hundred consecutive patients with pituitary adenomas and suprasellar extension were operated by a transsphenoidal approach from July 2003 to December 2006. In addition to the neurological examination, the patients were evaluated by ophthalmological, endocrinological and radiological workups. The signal intensity of the lesion on T2WI and other dimensions of the tumors were included in the MRI study.There were 52 male and 48 female patients with a mean age of 42.47 years. The mean diameter of the tumor was 32.97mm and the mean SSE was 14.95mm. Six out of 100 patients had firm adenomas peroperatively. Only one of the six patients had isointense SI on T2 WI. Of these 6 patients, total excision was performed in 1 patient, subtotal in 3 patients and partial excision in 2 patients. Among the six patients with firm adenomas, 4 had preoperative hypopituitarism (P0.001). There was a statistically significant correlation between consistency and the postoperative permanent hypopituitarism (P0.001). The average follow up was 43.5 months. The literature is reviewed and various aspects of pituitary adenoma consistency are discussed.With the present study, the consistency of pituitary adenomas cannot be reliably predicted based on a preoperative MRI study. Patients with firm adenomas likely to have more incidence of preoperative hypopituitarism and postoperative permanent hypopituitarism.