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Objectives The incidence of pituitary neuroendocrine tumors has been reported high at autopsy. This study aimed to detect many tumors in both anterior and posterior lobes to prove tumor histogenesis. Methods In total, 150 pituitary glands were studied from the University of Kansas Medical Center from 1995 to 2000. The pituitary gland was sagittally sliced from anterior to posterior into 6 to 8 sections. When H&E-stained sections revealed tumors, the tumors were immunohistochemically stained for 6 pituitary hormones. Results Among 150 autopsy cases, 38 (25.3%) harbored microadenomas, including 4 cases with double tumors. Twenty-three (54.7%) cases were negative to all pituitary hormones. Of the remaining 19 tumors, 13 (30.9%) were lactotrophs, with 4 cases being concomitantly somatotrophs and gonadotrophs, and 2 cases were corticotropes. More than 85% of pituitary neuroendocrine tumors were adjacent to the capsule. Thirteen (8.7%) granular cell pituicytomas were found in the posterior lobe. There were pituicytes transforming into granular cell tumors. Conclusions The incidence was 25.3% for pituitary neuroendocrine tumors and 8.7% for granular cell pituicytomas. Since most pituitary neuroendocrine tumors were adjacent to the pituitary capsule, the capsule appeared to be the germinal center. Both pituitary tumors belonged to the 2 different transcription factor lineages. [ABSTRACT FROM AUTHOR]

The posterior pituitary (PP) hormones oxytocin (OXT) and arginine vasopressin (AVP) are synthesized within the hypothalamic nucleus and released from the PP into systemic circulation. Hypothalamic AVP projects its axons into the external layer of median eminence (eME) and regulates anterior pituitary hormone secretion during stress responses. Although similar as PP hormones, we demonstrate distinct regulatory roles of estrogen in hypothalamic OXT and AVP dynamics. OXT dynamics in the hypothalamus exhibit sex‐dependent variations and that estrogen may influence dynamic OXT level changes, as observed in OXT‐mRFP1 transgenic rats. Estrogen was also observed to modulate dynamic changes in AVP levels in the axon terminals of eME in female AVP‐eGFP transgenic rats. Although OXT and AVP are produced within the similar hypothalamic region, both exhibit distinct dynamics within the hypothalamus. Estrogen acts on the hypothalamus, and further effects of estrogen replacement therapy can be expected. [ABSTRACT FROM AUTHOR]

This series of three articles will explore the fundamentals related to anatomy, physiology and pathophysiology in relation to three important topics: the cardiac system, the respiratory system and the endocrine system. The series is intended to provide an informative and evidence-based summary of each topic for both students and clinicians. This third and final paper explores the maternal endocrine system, outlining the key physiological adaptations in pregnancy and summarising the key pathophysiological conditions that may occur. [ABSTRACT FROM AUTHOR]

Hyperandrogenemia is associated with polycystic ovarian syndrome (PCOS) and imbalances in the pituitary hormones, luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) levels. Apelin and its receptor, APJ (class A, rhodopsin‐like G‐ protein‐coupled receptor), belongs to adipokines, and its expression has been shown in the pituitary. It is also well known that, hyperandrogenism and PCOS have deregulation of different adipokines. Whether hyperandrogenism also deregulates the apelin system in the pituitary has yet to be investigated. Thus, we have investigated the expression and localization of apelin and its receptor, APJ, in the letrozole‐induced hyperandrogenised pituitary of female mice. Our results showed that the apelin, APJ and androgen receptor (AR) expression were upregulated in the anterior pituitary. Furthermore, the immunostaining of LH exhibited increased abundance than FSH. The circulating LH was also found to be elevated compared to FSH levels. The increased LH synthesis and secretion coincides with elevated apelin system in the pituitary of hyperandrogenised mice. Recently, a direct role of apelin has also been reported in the female pituitary, where apelin inhibits LH secretion. Thus, apelin could be one of the factors for deregulated gonadotropin secretion in hyperandrogenised conditions. However, more research is needed to fully understand the complex interactions between apelin and androgen regarding gonadotropin secretion in hyperandrogenised conditions. Research Highlights: Apelin and apelin receptor are upregulated in the in hyperandrogenised pituitary.Expression of androgen receptor (AR) also upregulated in the in hyperandrogenised pituitary.The elevated luteinizing hormone/follicle‐stimulating hormone ratio in hyperandrogenised pituitary coincides with elevated apelin system and AR expression. [ABSTRACT FROM AUTHOR]

Introduction: Congenital hypopituitarism (CH) is characterized by the deficiency of pituitary hormones. Among CH patients, 85% lack a molecular diagnosis. Whole Exome Sequencing (WES) identified a homozygous variant (c.865G>A, p.Val289Ile) in the CDH2 gene, responsible for N-Cadherin production, crucial for cell-cell adhesion. Predicted to be likely pathogenic, the variant was found in a patient deficient in GH, TSH, ACTH, and LH/FSH. Its impact on cell adhesion was confirmed in L1 fibroblast cell lines. Objective: Create a cdh2 knockdown in zebrafish for investigating its role in pituitary development through growth hormone and transcription factors expression. Methods: Utilized pET28B-RfxCas13d-His plasmid for Cas13 mRNA production via in vitro transcription, guiding Cas13 to cdh2 with three RNAs. Injected the complex into single-cell embryos for analysis up to 96 hpf. Assessed gene expression of cdh2, prop1, pit1, and gh1 using RT-qPCR. Evaluated cdh2 protein expression through the western blot technique. Results: Knockdown animals displayed developmental delay. The cdh2 expression decreased by 75% within 24 hours, rebounded by 48 hours, and reached wild-type levels by 96 hpf. gh1 expression decreased at 48h but increased by 96 hpf, aligning with WT. No significant differences in prop1 and pit1 expression were observed. Conclusion: Our findings underscore cdh2's role in pituitary development and hormonal regulation, offering insights for developmental biology research. [ABSTRACT FROM AUTHOR]

This article provides an updated review of hypopituitarism (HP), an endocrine disorder characterized by a deficiency of one or more pituitary hormones. The various etiologies are reviewed, including pituitary neuroendocrine tumors (PitNETs), hypothalamic lesions, genetic mutations, and acquired factors such as head trauma, medications, neoplasms, and infiltrative diseases. It is noted that PitNETs are responsible for approximately half of the cases in adults, whereas in children the causes are predominantly congenital. Diagnosis is based on clinical evaluation and hormonal testing, with identification of the specific hormonal deficiencies essential for effective treatment. Laboratory tests present challenges and limitations that must be understood and addressed. Hormone replacement therapy is the mainstay of treatment, significantly improving patients' quality of life. It is important to know the possible interactions between hormone replacement therapies in HP. Recent advances in understanding the pathophysiology of HP and the importance of a multidisciplinary approach to the management of associated complications are discussed. This article emphasizes the need for comprehensive evaluation and continuous follow-up to optimize outcomes in patients with HP and highlights the importance of ongoing research to improve diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Superior surgical skill improves surgical outcomes in endoscopic pituitary adenoma surgery. Video-based coaching programs, pioneered in professional sports, have shown promise in surgical training. In this study, we developed and assessed a video-based coaching program using artificial intelligence (AI) assistance. An AI-assisted video-based surgical coaching was implemented over 6 months with the pituitary surgery team. The program consisted of 1) monthly random video analysis and review; and 2) quarterly 2-hour educational meetings discussing these videos and learning points. Each video was annotated for surgical phases and steps using AI, which improved video interactivity and allowed the calculation of quantitative metrics. Primary outcomes were program feasibility, acceptability, and appropriateness. Surgical performance (via modified Objective Structured Assessment of Technical Skills) and early surgical outcomes were recorded for every case during the 6-month coaching period, and a preceding 6-month control period. Beta and logistic regression were used to assess the change in modified Objective Structured Assessment of Technical Skills scores and surgical outcomes after the coaching program implementation. All participants highly rated the program's feasibility, acceptability, and appropriateness. During the coaching program, 63 endoscopic pituitary adenoma cases were included, with 41 in the control group. Surgical performance across all operative phases improved during the coaching period (P < 0.001), with a reduction in new postoperative anterior pituitary hormone deficit (P = 0.01). We have developed a novel AI-assisted video surgical coaching program for endoscopic pituitary adenoma surgery - demonstrating its viability and impact on surgical performance. Early results also suggest improvement in patient outcomes. Future studies should be multicenter and longer term. [ABSTRACT FROM AUTHOR]

Background. Incidentalomas have an increasing incidence all over the world due to a larger access to imaging assessments, and endocrine incidentalomas make no exception in this matter, including pituitary incidentalomas (PIs). Objective. Our objective was to analyse the dynamic changes amid a second computed tomography (CT) scan after adult patients were initially confirmed with a PI (non-functioning micro-adenoma). Methods. This was a multi-centric, longitudinal, retrospective study in adults (aged between 20 and 70 y) amid real-world data collection. We excluded patients who experienced baseline pituitary hormonal excess or deficiency or those with tumours larger than 1 cm. Results. A total of 117 adults were included (94.02% females) with a mean age of 43.86 ± 11.99 years, followed between 6 and 156 months with a median (M) of 40 months (Q1 Q3: 13.50, 72.00). At the time of PI diagnosis, the transverse diameter had a mean value of 0.53 ± 0.16 cm, the longitudinal mean diameter was 0.41 ± 0.13 cm, and the largest diameter was 0.55 ± 0.16 cm. No PI became functioning during follow-up, neither associated hypopituitarism nor increased >1 cm diameter. A total of 46/117 (39.32%) patients had a larger diameter during follow-up (increase group = IG) versus a non-increase group (non-IG; N = 71, 60.68%) that included the subjects with stationary or decreased diameters. IG had lower initial transverse, longitudinal, and largest diameter versus non-IG: 0.45 ± 0.12 versus 0.57 ± 0.17 (p < 0.0001), 0.36 ± 0.11 versus 0.43 ± 0.13 (p = 0.004), respectively, 0.46 ± 0.12 versus 0.6 ± 0.16 (p < 0.0001). IG versus non-IG had a larger period of surveillance: M (Q1, Q3) of 48 (24, 84) versus 32.5 (12, 72) months (p = 0.045) and showed similar age, pituitary hormone profile, and tumour lateralisation at baseline and displayed a median diameter change of +0.14 cm versus −0.03 cm (p < 0.0001). To conclude, a rather high percent of patients might experience PI diameter increase during a longer period of follow-up, including those with a smaller initial size, while the age at diagnosis does not predict the tumour growth. This might help practitioners with further long-term surveillance protocols. [ABSTRACT FROM AUTHOR]

Background: Suicide is a significant public health problem influenced by various risk factors, including dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. Zinc (Zn), essential for pituitary function in hormone synthesis and release, has been linked to suicide, with studies noting reduced serum levels and altered brain transport mechanisms. Despite Zn's crucial role in pituitary function and its involvement in suicidal behavior, information on pituitary Zn in suicide is scarce. Tumor cells modify Zn dynamics in tissues, and a previous report suggests microadenomas in the anterior pituitary as a risk factor for suicide. Methods: Histopathological analysis with hematoxylin-eosin stain and histochemical techniques to assess Zn homeostasis were carried out on anterior pituitary postmortem samples from 14 suicide completers and 9 nonsuicidal cases. Results: Pituitary microadenomas were identified in 35% of suicide cases and none in the non-suicidal cases. Furthermore, compartmentalized Zn (detected via dithizone reactivity), but not free Zn levels (detected via zinquin reactivity), was lower in the suicide cases compared to the non-suicidal group. Conclusion: This is the first report of a potential association between disrupted Zn homeostasis and microadenomas in the anterior pituitary as a feature in suicide and provides critical insights for future neuroendocrine Znrelated research. [ABSTRACT FROM AUTHOR]

Various factors may affect cognition in patients with pituitary adenoma, including size and extension of the tumor, degree of pituitary hormone deficiencies, and treatment of the tumor, most often being transsphenoidal surgery (TSS). The aim of this cross-sectional study was to evaluate cognitive function in patients with clinically significant pituitary adenoma and to identify factors influencing cognition. Sixty-eight patients with pituitary adenoma were included. Of these, 31 patients were evaluated before TSS and 37 patients 12 months following TSS. Cognitive function was evaluated by using the Repeatable Battery for the Assessment of Neuropsychological Status. Patients had lower mean scores on cognitive assessment compared to age-adjusted normative data. Variability in cognition, analyzed by linear regression analysis, was explained by sex, educational level, and self-perceived fatigue, but not by pituitary hormone deficiencies, diabetes insipidus, or surgical treatment. Our results are in line with previous findings, namely that pituitary adenoma affects cognition. To better evaluate the factors affecting cognition, longitudinal studies are recommended. Such studies would allow for within-individual comparisons, effectively controlling for the considerable influence of sex and education on test results. [ABSTRACT FROM AUTHOR]

Growth hormone deficiency (GHD) is the most frequent pituitary hormone deficiency in childhood, with an incidence of 1 in 4000–10,000 live births. GHD can be congenital (genetic or due to hypothalamic/pituitary abnormalities) or acquired and can be isolated (IGHD) or associated with other pituitary hormone deficiencies, but most cases are idiopathic. GH stimulation testing is commonly used in the diagnostic workup of GHD, except for some clinical conditions that do not require GH stimulation tests for the diagnosis. Children with GHD receive replacement therapy with daily injections of recombinant human GH (rhGH). RhGH therapy is effective in increasing short-term height gain and adult height in patients with GHD. The safety of long term GH therapy has been confirmed in many large international studies. Recently, long-acting weekly GH formulations have been introduced, showing good efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

The Snell dwarf mouse (Pit1dw/dw), an animal model of congenital combined pituitary hormone deficiency, displays skeletal muscle weakness. While enhanced responsivity to repeated exposures of muscle contractions have been documented for Snell dwarf mice, the response following single exposure to distinct contraction protocols remained uncharacterized. The purpose of this study was to investigate the muscle recovery of Snell dwarf and control littermate mice following a single exposure to two separate protocols—an intermittent slow velocity (30°/s) contraction protocol or a continuous rapid velocity (500°/s) contraction protocol. Following both protocols for control mice, torque values were 30% and 80% of pre‐protocol values at 5 min and 3 days, respectively. At 10 days, performance returned to baseline for the 30°/s protocol and were depressed for the 500°/s protocol. For Snell dwarf mice following both protocols, torques were depressed to 5% of pre‐protocol values at 5 min and returned to baseline by 3 days. Recovery following the 30°/s protocol for control mice and both protocols for Snell dwarf mice coincided with increased transcriptional output, upregulation of cytokine‐mediated signaling genes, and a distribution shift to smaller muscle fibers with reduced area per nucleus. These features represent efficacious remodeling ubiquitous across distinct contraction paradigms in the context of the Pit1 mutation. [ABSTRACT FROM AUTHOR]

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. [ABSTRACT FROM AUTHOR]

Pituitary adenoma is a benign intracranial tumor, commonly found in adults and occasionally in children. Pituitary adenoma is classified into secretory and non-secretory adenoma based on whether there is abnormal hormone secretion. The main manifestations include endocrine system abnormalities, visual disturbance and symptoms of intracranial hypertension. Although the incidence rate of pituitary adenoma in children is low, its physiological and psychological impact on children is obvious, diagnostic and therapeutic process is unique, and it has some characteristics, more complicated differential diagnosis than adults, such as more endocrine symptoms, poor paranasal sinus gasification, the impact of transnasal surgery on developing children, drug therapy and radiotherapy for children and individualization, postoperative endocrine regulation and subsequent development problems, etc.. Therefore, it is necessary to discuss pituitary adenoma in children independently from adults. This article reviews the clinical research progress of pediatric pituitary adenoma in recent years. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. Methods A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. Results A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001–1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002–1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139–1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165–1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004–1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020–1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029–1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. Conclusions Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

The evolution of classification systems of pituitary adenomas (now PitNETs) has culminated in the use of transcription factor (TF) immunohistochemistry (IHC), forming a cell lineage‐based system. However, several issues remain to be addressed, including the additional financial and logistic burden of undertaking the complete array of anterior pituitary hormones and TF IHC. To that end, several groups have suggested algorithms to minimise the number of tests performed, with varying levels of diagnostic accuracy. Although the proportion of null cell tumours has decreased following the use of TFs, “multilineage” tumours have been reported and characterised using transcriptomic signatures, most prominently the PIT1‐SF1 co‐expressing PitNETs, which do not bear a position in the present system of classification. In this review, we examine the proposed practical approaches to the diagnosis of PitNETs. We review the literature on reported PitNET types that challenge the existing classification system, such as those that express multiple TFs, with their potential clinical implications. Finally, we assess limitations in the present system, such as the lack of a standardised system for IHC interpretation, that need to be addressed in the future. [ABSTRACT FROM AUTHOR]

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the "hook effect"), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. Methods: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. Results: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001–1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002–1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139–1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165–1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004–1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020–1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029–1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. Conclusions: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE. [ABSTRACT FROM AUTHOR]

Joubert syndrome (JS) is a complex medical condition characterized by a pathognomonic midbrain-hindbrain malformation visible on brain imaging, which is known as the "molar tooth sign" (MTS). The presence of the MTS in the brain is the defining diagnostic criterion for JS. Individuals with JS commonly exhibit a developmental delay, hypotonia, and abnormal eye movements. In addition, neonatal breathing dysregulation is observed in about half of the cases. Midline brain defects associated with JS can lead to pituitary hormone abnormalities, thereby manifesting as multiple pituitary insufficiencies in the neonatal period, such as hypoglycemia and, in male patients, a micropenis with undescended testes. Although JS is a well-researched genetic condition, there is minimal information on the endocrinological aspects of JS. This manuscript aims to emphasize the spectrum of endocrinologic findings in JS through the retrospective evaluation of four cases characterized by combined pituitary dysfunctions, including secondary hypothyroidism, growth hormone deficiency, and panhypopituitarism. Highlighting these treatable aspects of JS is crucial, as continuous endocrinological monitoring can positively impact a patient's well-being, particularly in managing secondary adrenal and thyroid insufficiencies. [ABSTRACT FROM AUTHOR]

LIM homeobox 4 (LHX4) is a transcription factor crucial for anterior pituitary (AP) development. Patients with LHX4 mutation suffer from combined pituitary hormone deficiency (CPHD), short statures, reproductive and metabolic disorders and lethality in some cases. Lhx4-knockout (KO) mice fail to develop a normal AP and die shortly after birth. Here, we characterize a zebrafish lhx4-KO model to further investigate the importance of LHX4 in pituitary gland development and regulation. At the embryonic and larval stages, these fish express lower levels of tshb mRNA compared with their wildtype siblings. In adult lhx4-KO fish, the expressions of pituitary hormone-encoding transcripts, including growth hormone (gh), thyroid stimulating hormone (tshb), proopiomelanocortin (pomca) and follicle stimulating hormone (fshb), are reduced, the pomca promoter-driven expression in corticotrophs is dampened and luteinizing hormone (lhb)-producing gonadotrophs are severely depleted. In contrast to Lhx4-KO mice, Lhx4-deficient fish survive to adulthood, but with a reduced body size. Importantly, lhx4-KO males reach sexual maturity and are reproductively competent, whereas the females remain infertile with undeveloped ovaries. These phenotypes, which are reminiscent of those observed in CPHD patients, along with the advantages of the zebrafish for developmental genetics research, make this lhx4-KO fish an ideal vertebrate model to study the outcomes of LHX4 mutation. [ABSTRACT FROM AUTHOR]

Purpose: An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index. Methods: We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55). Results: IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04). Conclusions: Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies. [ABSTRACT FROM AUTHOR]

Lhx3 is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs are Japanese native dog breeds that have different body sizes. To determine whether Lhx3 plays a role in the differing body sizes of these three dog breeds, we sequenced the Lhx3 gene in the three breeds, which led to the identification of an SNP in codon 280 (S280N) associated with body size. The allele frequency at this SNP differed significantly between the large Akita and the two kinds of smaller Shiba dogs. To validate the function of this SNP on body size, we introduced this change into the Lhx3 gene of mice. Homozygous mutant mice (S279N+/+) were found to have significantly increased body lengths and weights compared to heterozygous mutant (S279N+/−) and wild-type (S279N−/−) mice several weeks after weaning. These results demonstrate that a nonsynonymous substitution in Lhx3 plays an important role in regulating body size in mammals. [ABSTRACT FROM AUTHOR]

Somatostatin inhibits endocrine and exocrine secretion in various tissues by acting on five somatostatin receptor subtypes (SSTR1–5). The clinical effects of SSTR5 antagonism remain unknown. Herein, we evaluated the effects of SCO‐240, an oral SSTR5 antagonist, in healthy individuals. This randomized, single‐center, double‐blind, placebo‐controlled, phase I study included healthy Japanese and White individuals. The effects of ascending single oral doses of SCO‐240 were evaluated in healthy individuals. The main outcome measures were safety, tolerability, pharmacokinetics, and pharmacodynamics (gallbladder contractions and levels of serum insulin and plasma glucagon‐like peptide‐1 (GLP‐1)). The levels of pituitary hormones were evaluated in our exploratory analysis. The results indicated that SCO‐240 was safe and well‐tolerated at all tested doses. Oral SCO‐240 was readily absorbed, with its systemic exposure increasing in a dose‐dependent manner. The median time to maximum concentration and mean terminal half‐life of SCO‐240 were 3–4 and 10.2–12.6 hours, respectively, in the ascending dose section. No clinically meaningful changes in SCO‐240 pharmacokinetic profiles were observed between fed and fasted or between Japanese and White individuals. No increase in gallbladder contractions or levels of insulin and GLP‐1 were detected. SCO‐240 induced robust growth hormone (GH) secretion without altering the levels of other pituitary hormones. In conclusion, the study is the first to demonstrate that SSTR5 antagonism stimulates GH secretion in humans. SCO‐240 was safe and well‐tolerated and exhibited once‐daily oral dosing potential. The robust effects of SCO‐240 on GH secretion suggest that it may be a treatment option for GH‐related disorders. [ABSTRACT FROM AUTHOR]

* Context.--Pituitary neuroendocrine tumors/adenomas are common intracranial tumors that require accurate subtyping because each tumor differs in its biologic behavior and response to treatment. Pituitary-specific transcription factors allow for improved lineage identification and diagnosis of newly introduced variants. Objective.--To assess the usefulness of transcription factors and design a limited panel of immunostains for classification of pituitary neuroendocrine tumors/adenoma. Design.--A total of 356 tumors were classified as per expression of pituitary hormones and transcription factors T-box family member TBX19 (TPIT), pituitary-specific POU-class homeodomain (PIT1), and steroidogenic factor-1 (SF-1). The resultant classification was correlated with patients' clinical and biochemical features. The performance and relevance of individual immunostains were analyzed. Results.--Reclassification of 34.8% (124 of 356) of pituitary neuroendocrine tumors/adenoma was done after application of transcription factors. The highest agreement with final diagnosis was seen using a combination of hormone and transcription factors. SF-1 had higher sensitivity, specificity, and predictive value compared with follicle-stimulating hormone and luteinizing hormone. On the other hand, TPIT and PIT1 had similar performance and Allred scores compared with their respective hormones. Conclusions.--SF-1 and PIT1 should be included in the routine panel for guiding the classification. PIT1 positivity needs to be followed by hormone immunohistochemistry, especially in nonfunctional cases. TPIT and adrenocorticotropin can be used interchangeably as per availability of the lab. (Arch Pathol Lab Med. 2024;148:178-189; doi: 10.5858/arpa.2021-0479-OA), Pituitary adenomas (PAs) or pituitary neuroendocrine tumors (pitNETs) are common intracranial tumors, third only to meningioma and gliomas. (1) Pituitary transcription factors (PTFs) play a well-established and dominant role in [...]

Objective. Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Because the etiology and clinical cognition of PSIS remain elusive, we analyzed the clinical features of PSIS in Chinese patients. Methods. A retrospective analysis was conducted on the clinical presentation, laboratory data, imaging examination, and management of 24 PSIS inpatients from our center over 10 years. Results. Among the 24 PSIS patients, there were 22 males (91.7%) and 2 females (8.3%). Growth hormone deficiency was present in all 24 cases (100%), hypogonadism in 24 cases (100%), secondary adrenal insufficiency in 22 cases (91.2%), and hypothyroidism in 21 cases (87.5%). 20 cases (83.3%) of PSIS patients exhibited deficiencies in four anterior pituitary hormones, 3 cases (12.5%) exhibited deficiencies in three anterior pituitary hormones, and 1 case (4.2%) exhibited deficiencies in two anterior pituitary hormones, with none exhibiting deficiencies in posterior pituitary hormones. Among the 24 PSIS patients, 12 had a history of growth hormone therapy before admission, and 12 had no such history. Additionally, 19 cases (79.2%) with PSIS were complicated by dyslipidemia, 15 cases (62.5%) were complicated by nonalcoholic fatty liver disease, and 9 cases (37.5%) were complicated by hyperuricemia. Conclusions. PSIS often presents with growth retardation and hypogonadotropic hypogonadism, but in some cases, short stature is not exhibited. PSIS is prone to complications such as dyslipidemia, nonalcoholic fatty liver disease, and hyperuricemia, increasing the risk of cardiovascular and cerebrovascular diseases. In clinical practice, the diagnostic ability of PSIS should be improved, and pituitary function and complications should be evaluated in a timely manner to avoid delayed treatment. [ABSTRACT FROM AUTHOR]

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion. [ABSTRACT FROM AUTHOR]

Objectives: Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript will assess the sex distribution when biases are minimised. Methods: Retrospective chart review was conducted on patients diagnosed with GHD between 3 and 16 years of age. The sex distribution of cases was ascertained according to: (1) peak GH (pGH) by groups; based on growth hormone provocative testing, (2) pituitary gland imaging results, and (3) isolated GHD (IGHD) versus multiple pituitary hormone deficiencies (MPHD). The relative frequency of each sex was compared according to these subgroups with significance evaluated at α =.05 level. Results: Of the 5880 clinic referrals for short stature, there were 3709 boys (63%) and 2171 girls (37%). Of these, 20% of boys (n = 745) and 15.3% of girls (n = 332) underwent provocative testing for GHD. Of those tested, 39.2% of boys (n = 292) and 32.2% of girls (n = 107) were diagnosed with GHD, all p <.001. There was a male predominance in GHD cases based on pGH or GHD severity. Though not significant, girls were more likely than boys to have MPHD (p =.056), even across pGH groups (p =.06). Both boys and girls had a similar distribution of imaging abnormalities. Conclusion: Stratifying by sex, we found similar percentages of pituitary imaging abnormalities (including tumours) and the number of pituitary hormone deficiencies in boys and girls as the cause of GHD. For these classifications, we did not find the historically reported male sex predominance. [ABSTRACT FROM AUTHOR]

Children with neurodisabilities are a very diverse group. Endocrine dysfunction is not always anticipated but screening for potential risk of developing hypopituitarism is important in clinical practice. Hypopituitarism in children with neurodisability can be part of an underlying congenital syndrome or acquired. Diagnosis of hypopituitarism on clinical grounds is challenging in some cases. Accurate growth monitoring is more difficult in this group due to orthopaedic factors, such as spasticity, spinal deformities such as scoliosis or joint contractures. Moreover, the signs and symptoms of hypopituitarism may mimic those associated with their neurodisability itself. These can overlap or exacerbate each other and the onset is sometimes insidious. In this review, we focus on the pituitary hormone deficiencies most commonly associated with neurodisability and offer practical advice for healthcare professionals. We explain when it is important to consider further pituitary function investigations and when and why referral to a paediatric endocrinologist is required. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the median effective dose (ED50) and 95% effective dose (ED95) of nicardipine for treating pituitrin-induced hypertension during laparoscopic myomectomy, providing guidance for the management of intraoperative blood pressure in such patients. Methods: Among the initial 40 participants assessed, 24 underwent elective laparoscopic myomectomy. A sequential up-and-down method was employed to ascertain the ED50 of nicardipine based on its antihypertensive efficacy. Nicardipine was initially administered at 6 µg/kg following the diagnosis of pituitrin-induced hypertension in the first patient. Dosing adjustments were made to achieve the desired antihypertensive effect, restoring systolic blood pressure and heart rate to within ± 20% of baseline within 120 s. The dosing increment or reduction was set at 0.5 µg/kg for effective or ineffective responses, respectively. The ED50 and ED95 of nicardipine were calculated using Probit regression by Maximum Likelihood Estimation (MLE) to establish dose-response curves and confidence intervals. Results: 24 patients were included for analysis finally. The ED50 and ED95 of nicardipine for blood pressure control after pituitrin injection were determined. The study found that the ED50 of nicardipine for treating pituitrin-induced hypertension was 4.839 µg/kg (95% CI: 4.569–5.099 µg/kg), and the ED95 was estimated at 5.308 µg/kg (95% CI: 5.065–6.496 µg/kg). Nicardipine effectively mitigated the hypertensive response caused by pituitrin without inducing significant tachycardia or hypotension. Conclusions: Nicardipine effectively controlled blood pressure after pituitrin injection during laparoscopic myomectomy, with ED50 and ED95 values established. This research highlights the potential utility of nicardipine in addressing hypertensive responses induced by pituitrin, particularly in clinical settings where pituitrin is routinely administered. [ABSTRACT FROM AUTHOR]

Pregnancy is a period in which the anatomy and physiology of the pituitary gland change significantly. Normal pituitary gland functions are necessary for fertility and the continuation of pregnancy. The presence of a pituitary disease requires management with a multidisciplinary approach to protect the health of the mother and fetus, and it is recommended that these patients become pregnant in a planned manner. Treatment should be considered before pregnancy for pituitary adenomas with a risk of growth. Non-contrast magnetic resonance imaging (MRI) may be performed safely during pregnancy, but the ideal approach is to postpone the MRI until after the birth if possible, and if it is not possible, to take it without contrast. If there are no signs of compression in pituitary adenomas, no treatment is necessary during pregnancy. However, due to increased fetal and maternal morbidity and mortality in Cushing’s disease, treatment is necessary even if there is no compression. In the presence of compression findings, dopamine agonists can be used in all types of pituitary adenomas. Surgery may be performed in the second trimester for pituitary adenomas that cause compression unresponsive to medical treatment and for Cushing’s disease. In pregnant women with pituitary insufficiency, replacement doses should be adjusted according to the gestational week. The diagnosis and treatment of pituitary diseases in this period is more complex and specific than in the nonpregnant period and require a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Gamma knife radiosurgery (GKRS) is an established treatment option for residual and recurrent nonfunctioning pituitary adenoma (NFPA). This investigation assessed hormonal and radiologic outcomes after adjuvant and primary GKRS for NFPAs. This retrospective study included 252 patients with NFPA who underwent GKRS at a single center between 2005 and 2016. GKRS was performed as adjuvant procedure in 216 (85.8%) patients and as primary procedure in 36 (14.2%) patients. Characteristics of these two groups were compared. Mean age was comparable between adjuvant and primary GKRS groups (48.3 ± 12.6 vs. 52.2 ± 13.2 years, respectively, p > 0.05). Adjuvant GKRS and primary GKRS groups were similar in terms of the mean prescribed radiation dose and tumor volume (15.1 ± 2.7 vs. 15.3 ± 1.9 Gy and 4.2 ± 3.6 vs. 3.1 ± 2.5 cm3, respectively, p > 0.05 for both). The rate of endocrine deficiency during 5-year follow-up showed similar trend in adjuvant and primary GKRS groups (3.7%, 8.7%, and 14.8% vs. 5.6%, 13.9%, and 27.8% at first, third, and fifth year time points, respectively). Tumor control rates were also similar (98.6%, 96.3%, and 93% vs. 100%, 97.3%, and 94.5% at first, third, and fifth year time points, respectively). In both groups, tumor volume >5 cm3 was associated with higher rate of hypopituitarism and tumor progression. GKRS was effective both as adjuvant and primary procedure in patients with NFPA. Radiation dose of ≤13.5 Gy was associated with lower tumor control rate and tumor volume >5 cm3 was associated with higher rates of hypopituitarism and tumor progression. [ABSTRACT FROM AUTHOR]

Introduction: It has been proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH deficiency (GHD). Only children with a monogenic cause of GHD or an identifiable combined hormonal deficiency or anatomical anomaly in the hypothalamic-pituitary axis should be considered definite GHD (dGHD). The remaining patients can be defined as a separate group of patients, "short stature unresponsive to stimulation tests" (SUS). The aim of this proof-of-concept study, was to assess whether SUS patients treated with rhGH exhibit any differences compared to GHD patients undergoing the same treatment. Methods: Retrospective analysis on 153 consecutive patients with short stature and pathological response to two GH stimulation tests. Patients with dGHD were defined as those with a clear genetic or anatomical hypothalamic-pituitary anomaly, as well as those with combined pituitary hormone deficiencies and those with a known insult to the hypothalamic-pituitary axis (i.e. total brain irradiation) (n=38, 25%); those without any of the previous anomalies were defined as SUS (n=115, 75%). Results: At diagnosis, dGHD and SUS populations did not differ significantly in sex (F 32% vs 28%, p=0.68), age (11.9 vs 12.1, p=0.45), height SDS at diagnosis (-2.2 vs. -2.0, p=0.35) and prevalence of short stature (height <-2 SDS) (56% vs 51%, p=0.45). IGF-1 SDS were significantly lower in dGHD (-2.0 vs -1.3, p<0.01). After 1 year of treatment, the prevalence of short stature was significantly reduced in both groups (31% in dGHD vs. 21% in SUS, p<0.01) without any significant differences between groups (p=0.19), while the increase in IGF-1 SDS for bone age was greater in the dGHD category (+1.9 vs. +1.5, p<0.01), with no further difference in IGF-1 SDS between groups. At the last available follow-up, 59 patients had reached the near adult height (NAH) and underwent retesting for GHD. No differences in NAH were found (-0.3 vs. -0.4 SDS, 0% vs. 4% of short stature). The prevalence of pathological retesting was higher in dGHD (60% vs. 10%, p<0.01) as well as of overweight and obesity (67% vs. 26%). Conclusion: Stimulation tests and the equivalent benefit from rhGH therapy, cannot distinguish between dGHD and SUS populations. In addition, lower IGF-1 concentrations at baseline and their higher increase during treatment in dGHD patients, and the lack of pathological retesting upon reaching NAH in SUS patients, are facts that suggest that deficient GH secretion may not be the cause of short stature in the SUS studied population. [ABSTRACT FROM AUTHOR]

Background: Lymphocytic hypophysitis is a rare autoimmune condition that usually presents during pregnancy and causes inflammation of the pituitary gland. Although the pathophysiology is not well understood, it often presents with headaches, visual disturbances, and symptoms of hypopituitarism. However, not all cases may present with hypopituitarism which can make this rare disease with an incidence of ~ 1 in 9 million much more difficult to diagnose. Case Presentation: We present a 35-year-old G4P4 woman with progressive vision loss and intermittent frontal headaches during her first trimester through 2 months postpartum. She presented with no symptoms of hypopituitarism and her hormone panel only showed elevated prolactin, possibly due to her breastfeeding. She was treated with a right pterional craniotomy with decompression of both optic nerves, partial resection of the suprasellar mass, and glucocorticoid therapy for headaches and visual disturbances. Conclusion: This case is notable for a presentation of lymphocytic hypophysitis without symptoms of hypopituitarism. This is important for outpatient providers to be aware of, especially those that care for pregnant patients so that unfavorable outcomes can be avoided. [ABSTRACT FROM AUTHOR]

To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature. [ABSTRACT FROM AUTHOR]

Introduction: Genetic forms of growth hormone deficiency (GHD) may occur as isolated GHD (IGHD) or as a component of multiple pituitary hormone deficiency (MPHD). This study aimed to present the clinical and molecular characteristics of patients with IGHD/MPHD due to the GH1 gene variants. Methods: A gene panel accommodating 25 genes associated with MPHD and short stature was used to search for small sequence variants. Multiplex ligation-dependent probe amplification was performed in patients with normal panel results to investigate gross deletion/duplications. Segregation in the family was performed by Sanger sequencing. Results: The GH1 gene variants were detected in 5 patients from four unrelated families. One patient had IGHD IA due to homozygous whole GH1 gene deletion and one had IGHD IB due to novel homozygous c.162C>G/p.(Tyr54*) variant. Two patients from a family had previously reported heterozygous c.291+1G>A/p.(?) variant in which clinical and genetic characteristics were compatible with IGHD II accompanying MPHD. One patient had clinical and laboratory characteristics of IGHD II with MPHD but the heterozygous c.468 C>T/p.(R160W) variant had conflicting results about the relationship with the phenotype. Conclusion: Expanding our knowledge of the spectrum of GH1 gene variants by apprehending clinical and molecular data of more cases, helps to identify the genotype-phenotype correlation of IGHD/MPHD and the GH1 gene variants. These patients must be regularly followed up for the occurrence of additional pituitary hormone deficiencies. [ABSTRACT FROM AUTHOR]

Objective: To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS). Methods: A retrospective analysis of confirmed cases of PSIS was performed. The development of new pituitary hormonal deficiencies and response to recombinant human growth hormone (rhGH) therapy were assessed during follow-up. Results: This study included 14 children (10 boys) of PSIS with median (range) age of 12.15 years (2 months–18 years). Short stature was the most common presentation (n = 13), and micropenis (n = 4), cleft lip (n = 1) and single central incisor (n = 1) were other midline defects. Growth hormone (GH) deficiency was present in 14 children and 7 of them also had multiple pituitary hormone deficiencies at baseline. Central hypothyroidism (n = 5), secondary adrenal deficiency (n = 4) and gonadotropin deficiencies (n = 2) were also seen. All children received rhGH. The mean height gain on follow-up was 12.78 cm in first year (n = 14), 6.5 cm in second year (n = 8) and 4.07 cm in third year (n = 7) of rhGH therapy. Four children developed additional pituitary hormone deficiency on follow-up. Conclusion: Short stature with isolated GH deficiency was the most common presentation of PSIS that showed good response to rhGH therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Tachykinin1 (tac1) gene products participate in the regulation of hormone secretion in the pituitary of Dabry's sturgeon. Two products of tac1 gene, Substance P (SP) and neurokinin A (NKA), were initially confirmed to regulate the gene expression of two gonadotropins (lh and fsh) in the Dabry's sturgeon pituitary tissue by intraperitoneal injection in vivo and co-culture of primary cells in vitro. This research presents the initial investigation into the reproductive role of SP and NKA in Dabry's sturgeon, offering a valuable insights for advancing efficient ripening techniques in artificial breeding of sturgeon. As an ancient and endangered species unique to the Yangtze River in China, the wild population of the Dabry's sturgeon has become scarce. Due to the long time till the first sexual maturity of Dabry's sturgeon, the population of artificially bred Dabry's sturgeon recovered slowly. As a member of the tachykinin family, TAC1 has been reported to have a variety of functions in mammals such as pain control, smooth muscle contraction and reproductive cycle regulation, but the function of Tac1 in fish has been rarely reported. In this study, we synthesized two tac1 gene products, Substance P (SP) and neurokinin A (NKA), and further verified the effect of two tac1 gene products on the secretion of related hormones in the pituitary of Dabry's Sturgeon by intraperitoneal injection and co-culture of primary cells. Expression studies revealed that the newly cloned tac1 were mainly distributed in the hypothalamus and pituitary tissue of the brain. In prepubertal Dabry's sturgeon, this study showed that the two gonadotropins' mRNA levels in pituitary tissue can be significantly increased by SP and NKA through intraperitoneal injection, and the LH protein level in serum was also increased. Further study showed that both NKA and SP could promote the two gonadotropins' mRNA expression in pituitary cells of Dabry's sturgeon. In addition, we explored the optimal dose and time of SP and NKA on pituitary cells is 24 h and over 10 nM. These results, as a whole, suggested that tac1 gene products play an important role in gonadotropin release and gonadal development in prepubertal Dabry's sturgeon. [ABSTRACT FROM AUTHOR]

Objective Prolactinomas are treated with dopamine agonists (DAs) as first-line therapy and transsphenoidal surgery as an alternative approach for medically failed tumors. We sought to summarize the efficacy of stereotactic radiosurgery (SRS) in the medically and surgically failed prolactinomas as well as in nonsurgical candidates with medically failed prolactinomas by systematic review and meta-analysis. Method A literature search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Results A total of 11 articles (total N = 709) met inclusion criteria. Thirty-three percent of patients were able to achieve endocrine remission at a mean follow-up of 54.2 ± 42.2 months with no association between stopping DA and endocrine remission. Sixty-two percent of patients were able to achieve endocrine control with DA therapy and 34% of patients were able to decrease the dose of DA dose when compared with pre-SRS DA dose at the end of the follow-up period. However, 54% of patients required DA at the end of the follow-up to control hyperprolactinemia. Ninety percent of patients were able to achieve radiologic control at the end of the follow-up in comparison to pre-SRS imagings. Furthermore, 26% of patients newly developed hypopituitarism (one or more pituitary hormones) post-SRS throughout the follow-up period. Conclusion This systematic review and meta-analysis demonstrates SRS as an effective adjunct therapy in medically failed nonsurgical candidates or surgically and medically recalcitrant prolactinomas with a 33% chance of achieving endocrine remission, 62% of patients achieved hormonal control with DA and GKRS (gamma knife radio-surgery), with a 34% chance of decreasing DA dose and 90% chance of achieving radiologic control. [ABSTRACT FROM AUTHOR]