Pituitary Hormone Research Articles

Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase.

Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.

P-46 A CASE OF PITUITARY APOPLEXY PRESENTING WITH OPHTHALMOPLEGIA

Abstract Introduction Pituitary apoplexy is a rare endocrinological emergency that may be life-threatening due to pituitary hormone deficiency or compression effect, if not treated appropriately. It usually develops secondary to acute ischemia or hemorrhage in the pituitary gland and presents with headache, vomiting, ophthalmoplegia, vision loss. In this case, we aim to present a case of pituitary apoplexy who applied to the emergency service with a complaint of vomiting, and developed ophthalmoplegia while hospitalized. Clinical Case A 76-year-old male patient applied to the emergency department with complaints of nausea and vomiting that had been continuing for the last week. At admission, physical examination, blood pressure and neurologic examination were normal. The laboratory tests were as follows: Glu:141 mg/dl, Cre:0,7 mg/dl, AST:25 U/L, ALT:13 IU/L, Na:118 mmol/L, K:3.0 mmol/L. He was admitted to the service in order to investigate hyponatremia and hypokalemia. On the first day of his hospitalization, restriction of upward sight in the right eye and ptosis developed. Cranial imaging with computerized tomography revealed a contrast-enhancing mass at the level of pituitary gland. A well-frameworked, 20 mm in diameter, hyperintens at T1-weighted images, with heterogeneous contrast enhancing lesion was reported in the contrast-enhanced pituitary MRI. Preliminary diagnosis were considered to be a bleeding cyst or pituitary apoplexy. Pituitary hormone tests were as follows: TSH:0.5 mIU/L (0.27-4.8), sT4: 1,38 ng/dL (0,79-1,59), sT3: 2.1 ng/L (2,04-4,4), FSH: 2.6 IU/L (1,5-12,4), LH: 0.87 IU/L (1,7-8,6), Total Testosterone: 0.4 ng/ml (2,8-8), PRL: 1 µg/dl (4,6-21,4), ACTH: 1,5 ng/L (7-63,2), Cortisol: 1.8 µg/dl (6-19), İGF-1: 53 mg/L (50-184). Hormone replacement with methylprednisolone 2x20 mg intravenous was started with the diagnosis of anterior pituitary insufficiency. The patient underwent to transphenoidal pituitary surgery for decompression, under a steroid cover. Hemodynamics remained stable following surgical intervention. Postop urinary output was also normal. But, right side ptosis continued after surgery. The patient was discharged with oral prednisolone 5 mg 1*1. Steroid was discontinued at the second week following surgery. The entire pituitary axis was determined to be intact at the first month. Pathology was reported as a large hemorrhagic infarction of the pituitary gland compatible with pituitary apoplexy. Consultations with Neurology and ophthalmology departments were done because of the persistence of right ptosis. No additional intervention was planned, follow-up was recommended. A significant improvement of ptosis was observed after a two months period. Conclusion Although the neurological signs and symptoms of pituitary apoplexy usually improves following accurate medical or surgical interventions in majority of patients, it should be kept in mind that it may take time for ptosis to recover after surgical decompression as in our case.Figure 1:Improvement in ptosis in the second month after surgery

A novel X-linked variant c.1772delG (p.G591fs*20) in IRS4 in two related patients with central hypothyroidism

Introduction: Central hypothyroidism (CeH) is characterized by thyroid hormone deficiency due to impairment of pituitary thyroid stimulating hormone (TSH) or hypothalamic TRH biosynthesis. It is extremely rare and affects approximately 1:16,000-100,000 individuals. Diagnosis, especially of isolated CeH, may be challenging. CeH is often seen as a part of multiple pituitary hormone deficiencies, but it can also be seen as isolated CeH. To date, some variants that can cause CeH have been identified; although in a number of patients the cause has not been clarified. Recently, variants of the insulin receptor substrate 4 (IRS4) gene have been reported to be the cause of isolated CeH. Herein, we report two related patients and their family with carriers with a novel X-linked frameshift variant in the IRS4 gene. It has also been shown that thyroid function may be slightly affected in the heterozygous female carriers in our study. Case Presentation: Herein, we reported two Turkish male patients with CeH due to a hemizygous variant in IRS4. The index case was a 15-year-and-2-month male who presented with a low serum free thyroxin level, which was incidentally detected. Conclusion: Isolated CeH should kept in mind in insistent low fT4 levels without an increase in TSH levels. Genetic testing can aid in identifying the underlying cause of CeH in such cases. This report demonstrates the significance of providing comprehensive laboratory and molecular features of the patients and carriers with the IRS4 variants.

P-70 THYMIC HYPERPLASIA AND GRAVES' DISEASE: IS THERE A HIDDEN AUTOIMMUNE DISORDER?

Abstract Introduction Thymic hyperplasia is reported in 10-38% of patients with Graves' disease. Clinical Case We present a case of a 45-year-old female with Graves' disease and thymic hyperplasia, exhibiting non-specific symptoms. The patient was diagnosed with Graves' disease at age 42 and treated with thiamazole. While she was taking thiamazol she was felt muscle pain, spasms, and pulsations. Her pituitary and adrenal hormones were within normal limits. Three months after diagnosis, she was hospitalized for recurrent transient ischemic attacks. Myasthenia gravis was suspected, but acetylcholine receptor antibody tests, though initially elevated, were later normal. The patient also experienced flushing, and neck and facial redness without a clear diagnosis. She developed erythematous changes on her thighs, arms, and cleavage. Mastocytosis was suspected, but skin biopsy and serum tryptase tests were negative. She also reported frequent nocturnal bowel movements. Tumor markers such as chromogranin A and glucagon were slightly elevated, but a Ga-68 Dotatoc PET CT scan showed no evidence of neuroendocrine tumors. After six months of remission, the patient discontinued thiamazole, leading to symptom resolution and normalization of anti-TRAb levels. However, her TSH receptor antibodies increased seasonally, from February to August, over the next two years, resulting in hyperthyroidism. Thyroid ultrasound revealed changes consistent with autoimmune thyroid disease. The patient declined thymectomy and thyroidectomy. Due to adverse reactions to thiamazole and propranolol, possibly linked to Myasthenia gravis, she was switched to propylthiouracil with a good response. The etiology of symptoms atypical for hyperthyroidism or thymic hyperplasia, such as facial muscle tingling, spasms, pulsations, and erythematous rash, may be related to other autoimmune or neurological conditions, including Stiff Person syndrome and Myastenia gravis. Additionally, the seasonal recurrence, from February to August, of Graves' disease over three consecutive years is notable. Given the high prevalence of thymic hyperplasia in Graves' disease, ruling out neurological autoimmune diseases is advisable, as specific symptoms can affect the quality of life and may be exacerbated by antithyroid therapy.

P-51 A RARE CASE IN WHICH ACROMEGALY IS PROVEN CLINICALLY AND BIOCHEMICALLY DESPITE NEGATIVE GH IMMUNOHISTOCHEMICAL STAINING

Abstract Introduction The diagnosis of acromegaly is confirmed by high IGF-1 and GH levels. When a GH-secreting pitNET is resected, immunocytochemistry with GH staining typically supports the diagnosis. It is very rare for these tumors to stain negatively for GH in the presence of clinical and biochemical acromegaly. We are presenting a case of growth hormone (GH)-secreting PitNET with negative immunostaining for GH. Clinical Case 50-year-old male with history of headache and visual disturbances was found to have a pituitary macroadenoma. Years before the presentation, he noticed his shoe size had increased. Physical exam was notable for enlarged nose, thick lips, mandibular prognathism, and enlarged hands and feet. Blood pressure was 140/90 mmHg. Pre-operative laboratory results were remarkable for elevated GH 5.6 ng/ml (0.03-2.47) and IGF-1 816 ng/ml (80.6-207) levels. OGTT suppressed GH nadir 3.95 ng/ml. Pituitary MRI revealed an invasive macroadenoma measuring 37x31x40 mm (Figure 1). The patient underwent transsphenoidal surgery. Although GH and IGF-1 levels decreased after surgery, they did not return to the normal range. Visual field loss improved. Surprisingly, in the histopathological examination, no immunohistochemical staining was detected with GH and other anterior pituitary hormones, and Ki-67 was found to be 2%. Due to disease activity (IGF-1:278 ng/ml; 1.3XULN), medical treatment was started first with dopamine agonist and then continued with somatostatin receptor agonist (IGF-1:322 (1.6xULN). The remaining tumor tissue remained stable under treatment. Conclusion Silent somatotrophinomas detected by immunohistochemical staining have been reported in the literature. Conversely, endocrinologists should keep in mind that there may be rare cases in which immunohistochemical GH staining is negative but clinical and hormonal acromegaly is evidenced.Figure 1Magnetic resonance imaging (MRI) revealed a pituitary macroadenoma 37x31x40 mm in size, with Knosp grade 4 on the right and grade 1 on the left

P-67 TWO RARE GENETIC DISORDERS IN ONE CASE ‘’ALLAN-HERNDON-DUDLEY-SYNDROME’’ AND’ “TREACHER COLLINS SYNDROME’’:A CASE REPORT

Abstract Introduction Resistance to thyroid hormone syndrome (RTH), also named Refetoff Syndrome is an autosomal dominant or recessive rare genetic disease. It’s incidence is approximately 1:50.000 in newborns. Increasing awareness and knowledge about RTH will increase the diagnosis rate. So that other genetic diseases that accompany can be detected with early genetic consultation. Clinical Case A 45-year-old female patient was consulted to the endocrinology department for abnormal thyroid function tests. In her medical history, she had no known disease and no medication she used regularly. Her TSH level was 1,26 mıU/L(0,45-4,31), fT4:1,94ng/dl(0,85-1,70 ng/dl), fT3:5,73 ng/L(2-4,4). Thyroid autoantibodies were negative. In pituitary MRI, nodular formations that were hypointense compared to normal tissue were observed on the right and left sides of the pituitary (microadenoma?). Anterior pituitary hormones within the normal range. Heterophile antibody was negative. RTH or TSHoma was considered. She was admitted to the service for further examinations. Alpha subunit level could not measured. Basal TSH was found to be 1,49mU/L (0,54-4,31). A TRH stimulation test was performed on the patient and end of the test TSH was found to be 14.6 mıU/L. T3 supression test was performed. End of the test TSH was <0,1 mıU/L. Thyroid hormone resistance was considered. During the patient’s medical history there were no signs of hyperthyroidism other than fatigue. In patient's genetic analysis heterozygous c.401A>C:p variant detected in the THRB gene. NM_006517.5:C.401A>C:p.(Glu134Ala) missense variant heterozygous was detected in SLC16A2 gene and was associated with the ‘’Allan-Herndon-Dudley Syndrome’’ phenotype. The NM__001371623.1;C.2998G>A:p(Glu1000Lys)rs755763024 missense variant was observed heterozygous in the TCOF1 gene and was associated with the ‘’Treacher Collins Syndrome 1’’phenotype. Thyroid function tests were performed to the daughter and sons of the patient (table2). Genetic counseling was recommended to the patient and her family. There in no phenotypic features of ‘’Allan-Herndon-Dudley Syndrome ‘’ and Treacher Collins Syndrome ‘’ detected in the patient. Ophthalmology, otorhinolaryngology and cardiology examination was normal. The patient was diagnosed as RTH. She was clinically asymptomatic and discharged with plans to remain under medication-free monitoring. Conclusion As far as the literature is examined there is no previous case of the coexistence of TCS with RTH and other thyroid function test abnormalities. More case reports are needed to determine whether the coexistence of these two rare diseases is coincidental or related. According to previous literature information AHDS is usually clinically asymptomatic in women. But it is with RTH in the female patient in this case. As in the case, it is important to perform genetic screening and provide genetic counseling to the patients and family members.Table 1:Thyroid Function Tests of the Patient Table 2:Family Members Thyroid Function Test Results (1 daughter and 3 son of the patient)

P-41 THYROTROPHS HYPERPLASIA IN SEVER UNTREATED PRIMARY HYPOTHYROIDISM A RARE CAUSE OF MISLEADING PITUITARY ENLARGEMENT

Abstract Introduction Pituitary gland hyperplasia (PGH) due to primary hypothyroidism (PH) still underdiagnosed. It is reversible with proper thyroxine therapy. Unfortunately, patients may be referred to unnecessary pituitary surgery without thyroid function test (TFT) assessment. We present a case of a 13 years old female scheduled for pituitary surgery for macro adenoma diagnosed by PMRI but fortunately, endocrine assessment revealed intense PH, proper treatment produced dramatic resolution in PGH. Increase number of Pituitary gland (PG) cells causes PGH leads to abnormally enlarged PG on pituitary MRI (PMRI) (1). There is hypercellularity, polymorphism with large acini and intact reticulum (2). Firstly described at 1851 in cretins (3). It could be physiological in pregnancy or pathological due to primary hypothyroidism (PH), primary hypoadrenalism or primary gonadal insufficiency (4). Typical PMRI showed diffuse, regular, isointense enlargement of PG with homogenous uptake of gadolinium (5). Clinical Case We present a 13 years old female scheduled for PG surgery due to large mass, fortunately referred for endocrinological evaluation which showed very high TSH and low free T4 with normal other endocrine & vision assessment. Diagnosis of PH established and thyroxine therapy started with monitoring response to treatment by TSH and repeat the PMRI after 7 months which showed dramatic reduction in PG size and TSH normalized. At presentation TSH was > 100 mIU/L (0.27-4.2), while Free T4 was 0.08 ng/dL (0.93-1.70 ng/dL). Thyroxine 50 mcg had been started and increased gradually according to TSH level every 6 weeks. After 7months, TSH level became 3 mIU/L and new PMRI showed significant reduction in size of PG. Low thyroid hormones caused thyrotrophic hyperactivity resulting in PGH (6). Although thyrotrophs form 5-10% of anterior PG, trans conversion of somatotrophs to thyrotrophs with multiplication of thyrotrophs increase cells producing TSH (7). Hyperprolactinemia may occur in about 75% of cases and features of hypothyroidism are usual presentations in children and young patients rather than features due to sellar expansion (8). Thyroxine treatment reduces size of the PG in 85% of cases of PGH (9). Surgery may be indicated to decompress the optic chiasma or to confirm diagnosis when size not reduced or worsened with treatment (10). Although it is difficult to differentiate between tumor and PGH, prominent midline with smooth outlines suggests PGH (11). In PGH, there is a uniform hyperplasia causing homogenous enlargement on unenhanced T1,T2 images and post contrast there is an equal enhancement of hyperplastic PG (12). Biochemical, clinical and radiological follow up is indicated to check response and pick up early complications (13). Conclusion Prolonged, intense PH one of causes of PGH and should be kept in mind in every case of homogenously enlarged PG necessitating thyroid function and other pituitary hormones assessment before surgery.Figure 1:MRI picture before and after thyroxine therapyDramatic reduction in the size of pituitary gland after 7 month treatment with thyroxine.

Effects, Mechanisms of Action and Application of Vitex agnus-castus for Improvement of Health and Female Reproduction.

This narrative review describes the provenance and chemical composition of Vitex agnus-castus, as well as the currently available knowledge concerning its action. To search the related articles, Cochrane Library, PubMed, Web of Science, SCOPUS databases between the years 1995 and 2024, and the keywords "Vitex," "review," "fertility," "ovarian" and "mechanisms" were used in various combinations. The data listed in this review demonstrate that Vitex agnus-castus and its constituents (isoflavones and essential oils) affect a number of physiological actions via multiple extra- and intracellular mechanisms of action. This makes it an efficient drug in both traditional and modern medicine for the treatment of a number of illnesses. The main described target of Vitex agnus-castus is female reproduction. It can up-regulate ovarian cycle and fecundity via a wide spectrum of mediators from hypothalamic, pituitary and ovarian hormones up to intracellular regulators of proliferation, apoptosis, oxidation and dopamine receptors. These effects determine its potential action as protector and medicine against a number of female reproductive disorders and reproduction-related health problems including menstrual disorders, premenstrual syndrome, cyclic mastalgia, corpus luteum insufficiency, abnormal production of progesterone and prolactin, low fertility and infertility, hyperandrogenism and polycystic ovarian syndrome. Nevertheless, further high-quality studies are needed to firmly establish the biological and clinical efficacy of this plant.

Hypopituitarism Screening in Patients with Traumatic Brain Injury in the Primary Care Setting at the Minneapolis Veterans Affairs Health Care System.

Traumatic brain injury (TBI) is a significant health issue among veterans and poses a substantial risk for pituitary injury. Consensus guidelines recommend that patients who have sustained a TBI should undergo a baseline pituitary hormonal evaluation after the primary brain insult. Patients with abnormal screening test results or with symptoms of hypopituitarism should be referred to endocrinology for a full assessment. Currently, there are no reported data on the screening rates of hypopituitarism in veterans with TBI. This pilot study was conducted to determine the frequency of screening for hypopituitarism in veterans with TBI in a primary care clinic setting. We conducted a single-center retrospective cohort study of patients with a diagnosis of TBI who were seen by their primary care physicians at the Minneapolis Veteran Affairs Health Care System over a 1-year period. A random sample was generated using computerized random generator software of patient data, including demographics, TBI-related information, and pituitary hormone levels, which were collected from the panel of primary care providers. We used 2 sets of screening criteria, one by Ghigo etal. published in 2005, and the second by Tan etal. published in 2017, to define hypopituitarism screening adequacy in our cohort of TBI patients. Institutional Review Board approval was obtained. None of the 50 patients who met the criteria for screening based on the 2005 recommendations were screened for hypopituitarism. Only 2 of the 26 patients who met the criteria for screening based on the more recent 2017 recommendations were screened for hypopituitarism. We report that the screening rate for hypopituitarism in TBI patients is exceedingly low in the primary care setting, even with the less rigorous newer screening recommendations. Measures should be taken to improve screening of hypopituitarism to decrease morbidity and improve the quality of life in patients with a history of TBI.

On the Role of Epigenetic Modifications of HPA Axis in Post Traumatic Stress Disorder (PTSD) and Resilience.

Stress is a fundamental adaptive response mediated by the amygdala and Hypothalamus-Pituitary-Adrenal (HPA) axis. Extreme or chronic stress, however, can result in a multitude of neuropsychiatric disorders, including anxiety, paranoia, bipolar disorder (BP), major depressive disorder (MDD), and Post-Traumatic Stress Disorder (PTSD). Despite widespread exposure to trauma (70.4%), the incidence of PTSD is relatively low (6.8%), suggesting that either individual susceptibility or adaptability driven by epigenetic and genetic mechanisms are likely at play. PTSD takes hold from exposure to traumatic events, such as death threats or severe abuse, with its severity being impacted by the magnitude of trauma, it's frequency, and the nature. This comprehensive review examines how traumatic experiences and epigenetic modifications in hypothalamic pituitary axis (HPA), such as DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling, are transmitted across generations, and impact genes like FKBP5, NR3C1, BDNF, and SLC6A4. It also provides a comprehensive overview on trauma reversal, resilience mechanisms, and pro-resilience factors such as HATs/HDACs ratio, DHEA/Cortisol ratio, testosterone levels, and neuropeptide Y, thus highlighting potential therapeutic approaches for trauma-related disorders. The studies highlighted here underscore the narrative, for the first time, that the examination and treatment of PTSD and other depressive disorders must invoke a multitude of approaches to seek out the most effective and personalized strategies. We also hope that the discussion emanating from this review will also inform government policies directed towards intergenerational trauma and PTSD.

A retrospective analysis of 338 surgically treated pituitary adenomas.

To summarize the clinical characteristics, pituitary function assessment, postoperative pathological features, and postoperative recurrence of surgically treated pituitary adenomas (PAs). We retrospectively reviewed the data of 338 patients (169 women; average age: 50.01 ± 12.47 years) who underwent surgical PA resection at our hospital during 2016-2020. Pathological PA classification was based on postoperative immunohistochemical staining for pituitary hormones. The clinical, imaging, laboratory, and follow-up data of the patients were statistically analyzed using SPSS v25.0. The main complaints of PA patients were compressive symptoms, followed by endocrine symptoms; 23 tumors were incidentalomas. Compared with the 93 patients with functioning PAs, the 245 patients with non-functioning PAs were older, and had greater tumor diameters and rates of cavernous sinus invasion and pituitary apoplexy (P < 0.05). Postoperative hormonal staining most commonly revealed ACTH (27.4%) and FSH/LH positivity (20.6%); 23.1% of non-functioning tumors stained negative for pituitary hormones. Preoperative anterior hypopituitarism commonly involved the gonadal and thyroid axes, and was correlated with male sex and tumor diameter (P < 0.05). The optimal cut-off for tumor diameter was 1.95 cm for predicting preoperative hypopituitarism in patients with non-functioning PAs. The number of operations and preoperative hypopituitarism were correlated with postoperative pituitary dysfunction (P < 0.05). In the non-functioning PA group, tumor diameter was a risk factor for postoperative recurrence (optimal cutoff: 2.75 cm). The management of patients with surgically treated PAs is limited by deficiencies in pathological classification, assessment of hypopituitarism, and detection of recurrence.

The Prevalence of Septo-Optic Dysplasia in Neonates with Absent Cavum Septi Pellucidi Identified During Routine Prenatal Imaging.

To determine the prevalence of septo-optic-dysplasia (SOD) in patients with prenatally identified absent cavum septi pellucidi (CSP), agenesis of the corpus callosum (ACC) or dysgenesis of the corpus callosum (DCC). This retrospective chart review investigated neonates prenatally diagnosed with an absent CSP, ACC, or DCC who were admitted to a single quaternary academic medical center in the Pacific Northwest between 2016-2023. This prenatal diagnosis prompted a routine and protocolized postnatal workup for SOD including laboratory evaluation, imaging, and specialty consultation. Sociodemographic and clinical data were collected for eligible neonates and their birthing person. The prevalence of SOD in patients with midline callososeptal anomalies was calculated. Of the 86 patients prenatally diagnosed with absent CSP, ACC and/or DCC, 36.0% (n=31) were diagnosed postnatally with SOD. Of those diagnosed with SOD, 71.0% (n=22) had isolated optic nerve hypoplasia, 9.7% (n=3) had pituitary hormone abnormalities, and 19.4% (n=6) had both. Seven patients required maintenance hydrocortisone, one required thyroid hormone replacement, and one required thyroid and growth hormones. Of the 26 patients with SOD who underwent genetic testing, 9 (34.6%) had one or more genetic differences detected. SOD was diagnosed in 36.0% of cases of prenatally-diagnosed midline callososeptal anomalies. For patients with prenatally-diagnosed midline callososeptal anomalies, a standardized, postnatal SOD evaluation allows timely diagnosis and prompts early intervention and hormone replacement, thus avoiding the consequences of a delayed diagnosis.

Intra-infundibular Epidermoid Cysts- A Distinct and Rare Entity.

Epidermoid cyst (EC) located completely within the pituitary infundibulum is a rare entity with only seven reported cases. In this study, we have described our experience with resection of intra-infundibular epidermoid cysts (IECs) and reviewed the existing literature highlighting its distinguishing features and operative nuances. Three consecutive cases of IEC operated at our institute was retrospectively studied. PubMed and EMBASE databases were searched, and seven case reports of IEC were found. Relevant clinical, radiological, operative data of ten cases were analyzed. The median age at diagnosis was 53.5 years and six cases were males. Preoperatively, although the average tumor size was only 1.62 cm3, 80% of patients had visual disturbance, and 78% of patients had deficiency in pituitary hormones. Five patients had preoperative diabetes insipidus. Mild diffusion restriction was noted in four out of five cases that mentioned it. The most common differential diagnosis considered was Rathke's cleft cyst and craniopharyngioma. Adhesion of the cyst wall to the stalk and/or the hypothalamus was a common occurrence resulting in residual wall being left behind in 50% cases. Expanded endoscopic endonasal approach was utilized in nine cases and one case underwent fronto-temporal craniotomy with resection via pretemporal approach. Postoperative chemical meningitis was demonstrated in two cases and sterile abscess was noted in another case. IECs are rare tumors that are often misdiagnosed preoperatively. They have different postoperative morbidity profiles compared to other cystic lesions in the infundibulum. This makes it important to recognize this distinct entity.

Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.

Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. In this work, we report a functional role for myostatin as an endocrine hormone that directly promotes pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function in mice. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor-β family, the activins. Our results both challenge activin's eponymous role in FSH synthesis and establish an unexpected endocrine axis between skeletal muscle and the pituitary gland. Our data also suggest that efforts to antagonize myostatin to increase muscle mass may have unintended consequences on fertility.

Ontogeny of adenohypophyseal cells, pituitary gland development, and structure in adults of Astyanax lacustris (Teleostei, Characiformes): an emerging Neotropical model fish species.

Pituitary gland morphogenesis and the ontogeny of the adenohypophyseal (AH) cells of Astyanax lacustris are presented herein. This Characiformes species shows great ecological and commercial importance, and it has been increasingly used as animal model. For this study, A. lacustris specimens were collected from 0.5 to 120days after hatching (dah) (adults). The entire animal or its head was appropriately fixed, and after histological processing, the sections were subjected to histochemical and immunohistochemical reactions, using homologous and heterologous antibodies. The first AH cells of A. lacustris were detected at 1 dah by the immunostaining of prolactin (PRL)-producing cells. The morphology of the gland presented changes in shape throughout the development, starting with elongation but more oval at the end. The neurohypophysis was differentiated at 3 dah, along with the identification of adrenocorticotropic hormone (ACTH), melanotropic hormone (MSH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH)-producing cells. Identification of the immunoreactive cells to anti-luteinizing hormone (LH), anti-somatolactin (SL), and anti-growth hormone (GH) antibodies occurred at 5 dah. At 20 dah, an increase in pituitary proportions and the presence of the pituitary stalk were observed. At 60 dah, the pituitary gland already had the same shape and distribution of AH cells seen in the adult. The ontogeny of adenohypophyseal cells in A. lacustris corroborates the heterogeneity in the appearance of these cell types in teleosts and suggests that these hormones actively participate during the post-hatching development of this species, even before the establishment of all endocrine axes. Our findings contribute to understanding the morphogenesis of the hypothalamic-pituitary axis in South American teleosts, providing essential data for the development of future studies related to pituitary gland morphophysiology under normal or experimental conditions.

Exploring the Complex Relationship Between Psychosocial Stress and the Gut Microbiome: Implications for Inflammation and Immune Modulation.

There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a pro-inflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor. However, chronic stress in susceptible individuals could cause sustained activation of HPA and SNS, leading to immune dysregulation consisting of redistribution of NK cells in the bloodstream, decreased function of T and B cells, and elevation of proinflammatory cytokines such as IL-1, IL-6, TNF-ɑ, IFN-γ. It also leads to disruption of the GIM composition and increased intestinal barrier permeability, contributing to GIM dysbiosis. The GIM dysbiosis and elevated cytokines can lead to reciprocal effects and further stimulate the HPA and SNS, creating a positive feedback loop that results in a pro-inflammatory state underlying the pathogenesis and progression of stress-associated cardiovascular, gastrointestinal, autoimmune, and psychiatric disorders. Understanding these relationships is critical for developing new strategies for managing stress-related health disorders.

Central Adrenal Insufficiency: Etiology and Diagnostic Approach

Central adrenal insufficiency (CAI) occurs due to a pituitary gland disorder (secondary AI) or hypothalamic dysfunction (tertiary AI). It is a potentially life-threatening condition that has many congenital and acquired causes. Adrenocorticotropic hormone deficiency may be isolated or more commonly it can be accompanied by other pituitary hormone deficiencies or midline defects. The signs and symptoms of CAI are associated with glucocorticoid deficiency. A three-step diagnostic approach including dynamic stimulation tests is recommended in the evaluation of patients with suspected CAI. Here, members of the ‘Adrenal Working Group’ of ‘The Turkish Society for Pediatric Endocrinology and Diabetes’ present an evidence-based review with good practice points and recommendations for etiology and diagnostic approach in children and adolescents with CAI.

Evidence Suggesting That Alzheimer's Disease May Be a Transmissible Disorder.

Alzheimer's disease (AD) is characterised by progressive neurodegeneration with the formation of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain parenchyma. The causes of AD have been attributed to a combination of age-related changes within the brain as well as genetic, environmental and lifestyle factors. However, a recent study by Banerjee et al. highlights the possibility that AD may be a transmissible disease and that iatrogenic AD could be environmentally acquired, similar to iatrogenic Creutzfeldt-Jakob disease (iCJD). The study reports that contaminated Aβ in cadaver-derived pituitary growth hormone (c-hGH) therapy, which patients received during childhood inoculation, may accidentally transmit into their brains, triggering neurodegeneration and AD onset in older age. Furthermore, corroborating evidence from various animal model studies and human case reports suggests that AD can be potentially transmissible.

Cholecystokinin (CCK) Is a Mediator Between Nutritional Intake and Gonadal Development in Teleosts.

Nutritional intake is closely linked to gonadal development, although the mechanisms by which food intake affects gonadal development are not fully understood. Cholecystokinin (CCK) is a satiety neuropeptide derived from the hypothalamus, and the present study observed that hypothalamic CCK expression is significantly influenced by food intake, which is mediated through blood glucose levels. Interestingly, CCK and its receptors were observed to exhibit a high expression in the hypothalamus-pituitary-gonad (HPG) axis of grass carp (Ctenopharyngodon idellus), suggesting that CCK is potentially involved in regulating fish reproduction through the HPG axis. Further investigations revealed that CCK could significantly stimulate the expression of gonadotropin-releasing hormone-3 (GnRH3) in the hypothalamus. In addition, single-cell RNA sequencing showed that cckrb was highly enriched in pituitary follicle-stimulating hormone (FSH) cells. Further study confirmed that CCK can significantly induce FSH synthesis and secretion in primary cultured pituitary cells. Additionally, with primary cultured ovary cells as a model, the in vitro experiment demonstrated that CCK directly induces the expression of lhr, fshr, and cyp19a1a mRNA. This indicates that hypothalamic CCK may act as a nutrient sensor involved in regulating gonadal development in teleosts.

Clinical and genetic features of childhood-onset congenital combined pituitary hormone deficiency: a retrospective, single-center cohort study.

To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients. We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing. Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%). Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.