The pituitary gland is an uncommon site of tumor metastasis and is predominantly associated with malignancies of the lung and breast. Metastatic involvement of the pituitary gland in lung cancer (LC) typically indicates advanced disease and is associated with poor prognosis and pituitary insufficiency, which often remains underdiagnosed and significantly affects quality of life and survival. We present four cases of pituitary metastasis (PM) originating from LC, characterized by distinct histological subtypes, variable timing from initial diagnosis, and diverse clinical manifestations. Clinical presentation was heterogeneous: two patients had involvement of both pituitary lobes with multiple pituitary hormone deficiencies, one had anterior lobe involvement with anterior pituitary deficiency following immune checkpoint inhibitor-associated hypophysitis, and one remained asymptomatic. Therapeutic approaches included partial surgical resection followed by radiotherapy in two patients and radiotherapy alone in the other two; all patients continued systemic antineoplastic therapy and received hormone replacement as indicated. Mean overall survival was 7.5 months. PM can occur across all histological subtypes of LC and typically signifies advanced disease with poor prognosis. Early identification and appropriate management of hypopituitarism may improve quality of life and clinical outcomes.

Neurosarcoidosis is a rare but serious manifestation of sarcoidosis involving the central nervous system. When it affects the hypothalamic-pituitary axis, it can result in panhypopituitarism and diabetes insipidus due to disruption of anterior and posterior pituitary hormone regulation. Early recognition is critical, as delayed diagnosis may lead to life-threatening complications. We report the case of a 42-year-old White man with a 12-year history of sarcoidosis who presented with abdominal pain, hypotension, hypothermia, hypernatremia, polyuria, and polydipsia. He also had widespread skin plaques, joint pain, and cartilage deformities. Notably, he had developed drug-resistant seizures 3years earlier. Laboratory investigations demonstrated hypernatremia, low urine osmolality, and hormonal deficiencies consistent with panhypopituitarism. Imaging revealed suprasellar and brainstem lesions. After excluding alternative diagnoses, neurosarcoidosis was established. The patient responded well to hormone replacement therapy with levothyroxine and desmopressin, which led to clinical improvement. This case highlights the importance of considering neurosarcoidosis in patients with sarcoidosis who develop endocrine or neurological symptoms. It underscores the value of timely diagnosis and multidisciplinary management to prevent irreversible complications and improve long-term outcomes.

Pituitary Developmental Gene Defects and Their Contribution to Growth Hormone Deficiency.

Chimeras (Holocephali) occupy a pivotal phylogenetic position, being the oldest jawed vertebrate, for understanding the evolution of hypothalamic-pituitary organization in vertebrates. However, the structural organization of the hypothalamic-pituitary axis and the anatomical relationships with the buccal lobe (BL), a unique gland thought to play a role in reproduction, remains poorly characterized. We present an anatomo-histological analysis of the chimaera Callorhinchus callorynchus using classical histology, immunohistochemistry, and RT-PCR, focus on key neuropeptides related to the control of the reproductive activity in other vertebrates: gonadotropin-releasing hormone (GnRH), secretoneurin (SN), cholecystokinin (CCK), and gonadotropic hormones. The pituitary gland displays clear regionalization into the rostral pars distalis, proximal pars distalis, and neurointermediate lobe. The BL is connected to the posterior telencephalon by paired canals containing a prominent blood vessel and bundles of neuropeptidergic fibers. Gonadotropin-releasing hormone-immunoreactive nerve cell bodies and fibers were identified in the posterior telencephalon using two antisera, with fibers projecting to the proximal pars distalis of the pituitary and the BL. Secretoneurin-immunoreactive neuronal somata and fibers were observed in the posterior telencephalon and hypothalamus, and SN-immunoreactive cells were also present within the pituitary and BL. Cholecystokinin-immunoreactive neuronal elements were detected in the hypothalamus, while CCK-immunoreactive cells were present in the pituitary, and a subset of fibers extending into the BL. RT-PCR analyses revealed the presence of Fshb and Fhb transcripts in the pituitary and BL, with a stronger apparent signal in the BL. These observations provide anatomical evidence for direct neuropeptidergic innervation of both the pituitary and BL and indicate that the BL is associated with gonadotropin subunit gene expression in C. callorynchus. This new anatomical framework of the hypothalamus-pituitary-BL axis identifies two new pathways: direct GnRH and CCK innervation, and local SN-mediated autocrine/paracrine signaling.

FOXL2 is a highly conserved transcription factor that is essential for ovarian development and female fertility. In humans, FOXL2 mutations or deletions cause Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) leading to eyelid defects and, in BPES type I, primary ovarian insufficiency. BPES is also associated with a wide range of less common phenotypes such as craniofacial features, cleft palate, or heart defects. In this study, we generated a new constitutive Foxl2-Cre mouse model using CRISPR/Cas9 editing. Crossing Foxl2-Cre mice with Rosa-tdTomato reporter confirmed robust and specific labeling of FOXL2+ cells during fetal development. We provide a detailed characterization of the permanent labeling of cells that, at any time in development, expressed Foxl2, with a particular interest on organs associated with a spectrum of features identified in BPES patients. Our model effectively targeted key reproductive tissues, such as fetal ovarian somatic cells, including granulosa, interstitium and theca-cell precursors, the anterior pituitary, and mesenchymal cells of the uterus and oviduct. We also identified Foxl2-derived cells in the supporting-like cells of the testis, as well as in the peri-urethral cells of the external genitalia. Beyond the reproductive organs, Foxl2-derived cells were identified in several other tissues relevant to BPES, including the head, palate and the outflow tract of the heart. Overall, this Foxl2-Cre model provides a new tool for reproductive organ studies, and our characterization of Foxl2-derived cell fate brings a new perspective into the potential roles of FOXL2 in the wide spectrum of clinical features associated with BPES.

The posterior lobe (PL) of the pituitary contains a specialized neurovascular junction, where neurosecretory axon terminals closely associate with fenestrated capillaries to enable efficient hormone release into the circulation. The neurosecretory axon terminals and the fenestrated capillaries are supported by an outer basement membrane (BM) and an inner BM, respectively. Although BMs are critical structural components of this junction, their molecular composition and regulatory mechanisms remain poorly understood. We previously demonstrated that COL15A1, the α1 chain of collagen XV, localizes to the BMs surrounding fenestrated capillaries in the anterior lobe of the rat pituitary. In the present study, we examined the localization and regulation of COL15A1 in the rat PL. Immunohistochemical analyses revealed that COL15A1 is localized to the inner BMs of fenestrated capillaries. Combined in situ hybridization and immunohistochemistry demonstrated that Col15a1 is predominantly expressed in NG2-positive pericytes. Water deprivation, which induces arginine vasopressin (AVP) secretion, significantly decreased Col15a1 expression in the PL, whereas AVP stimulation did not affect its expression in primary cultured posterior and intermediate lobe (PIL) cells. We also found that TGFβ2 is produced by S100β-positive pituicytes and TGFβ receptor II is localized to NG2-positive pericytes in the PL. Furthermore, TGFβ2 induces Col15a1 expression in primary cultured PIL cells via TGFβ receptor II and SMAD2 signaling. Collectively, our results identify collagen XV as a key component of the inner BMs surrounding fenestrated capillaries and demonstrate that pericytes orchestrate the structural and functional organization of the neurovascular junction in the PL.

Pituitary tumours are intracranial neoplasms that pose significant clinical challenges due to their potential for recurrence, therapeutic resistance and resultant endocrine dysfunction and mass effects. In the normal anterior pituitary, resident pituitary stem cells (PSCs) contribute to tissue homeostasis and cellular turnover. The extent to which PSCs contribute to tumourigenesis is not known, but an increasing number of studies have been aiming to address this. In this review, we summarise current evidence implicating PSCs and tumour stem-like populations in pituitary tumour biology, including potential roles in tumour initiation, maintenance and progression. We outline practical criteria for defining tumour stem cells and evaluate findings from functional studies of human tumours, emerging single-cell and spatial transcriptomic datasets and murine lineage-tracing models. We also provide a curated overview of published single-cell RNA sequencing studies of pituitary tumours, highlighting reported stem/progenitor populations and transcriptional signatures across tumour subtypes and propose a framework for future genomic analyses. Finally, we discuss the translational implications of these findings, including the potential for targeting stem-like populations and their associated signalling pathways.

Pituitary blastoma (PitB) is an exceedingly rare tumor originating from the anterior pituitary gland, first documented in 2008 in humans. It is considered pathognomonic for DICER1 syndrome, primarily affecting children, although cases in adults have been noted. Clinical manifestations vary widely, attributed to hormone hypersecretion (such as Cushing's syndrome) and mass-related effects (like visual impairment and intracranial pressure changes). Histopathologically, PitB exhibits distinct features: proliferating Rathke's epithelium with rosette formations, adenohypophyseal neuroendocrine cells expressing ACTH and occasionally GH, and primitive small blastemal cells. This report describes the first case of PitB in a dog, presenting with ACTH-dependent hypercortisolism. The canine patient exhibited clinical signs consistent with ACTH-hypersecretion related to a pituitary mass. Histologically, the pituitary mass revealed hallmark features resembling human PitB. Immunohistochemistry confirmed ACTH expression and nuclear expression of TBX19 (TPIT), supporting a corticotroph lineage. CAM 5.2 expression in tubule-forming cells suggested an immature epithelial origin, likely from Rathke's pouch. Although DICER1 mutation analysis was not performed due to technical limitations with FFPE tissue, this case raises the possibility of a similar pathogenetic mechanism in dogs. This canine case expands the known species range of PitB and highlights important clinical, morphological and immunohistochemical parallels with the human counterpart, providing new insights into comparative pituitary tumor pathology.

Rationale:Sheehan syndrome is a rare but potentially fatal cause of hypopituitarism resulting from ischemic necrosis of the anterior pituitary following severe postpartum hemorrhage. Because symptoms often develop gradually and nonspecifically, diagnosis is frequently delayed until acute illness precipitates adrenal crisis or severe hypoglycemia.Patient concerns:A 48-year-old woman presented with central chest pain, productive cough, dyspnea, intermittent fever, severe anemia, and recurrent hypoglycemia. She had a history of severe postpartum hemorrhage 20 years earlier, followed by secondary amenorrhea and agalactia.Diagnoses:Physical examination revealed basal crepitations. Laboratory investigations demonstrated microcytic hypochromic anemia, leukocytosis with neutrophilia, hyponatremia, markedly low morning cortisol (0.6 µg/dL), low FT3 and FT4, and low-normal TSH, consistent with panhypopituitarism. Based on the obstetric history and hormonal profile, a diagnosis of Sheehan syndrome was established.Interventions:The patient was treated with glucocorticoid replacement therapy, followed by levothyroxine supplementation. Supportive management for the respiratory tract infection and hypoglycemia was also provided.Outcomes:The patient showed significant clinical improvement after initiation of hormonal replacement therapy, with stabilization of blood glucose levels and improvement in systemic symptoms.Lessons:This case highlights the prolonged latency between postpartum hemorrhage and presentation of Sheehan syndrome, with acute infection acting as a trigger for adrenal insufficiency. Clinicians should maintain high suspicion for Sheehan syndrome in women with a history of complicated delivery, lactation failure, amenorrhea, and chronic endocrine symptoms, even decades after the inciting event. Early recognition and prompt hormone replacement are lifesaving.

Irisin, an adipomyokine primarily known for its role in metabolic regulation, has recently emerged as a potential regulator of reproductive function. While its ovarian actions have been partially characterised, its influence on the anterior pituitary remains largely unexplored. This study aimed to investigate the in vitro effects of irisin on the transcriptome of porcine anterior pituitary cells (APc) isolated from gilts on days 15-16 of pregnancy. Primary APc were isolated from pigs on days 15-16 of pregnancy and treated with 300 ng/mL of irisin. RNA sequencing (NovaSeq 6000, Illumina) was performed to identify differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) events. Functional annotation was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Selected transcripts were validated by polymerase chain reaction (PCR) and quantitative PCR (qPCR). Irisin treatment altered the expression of 500 genes, 747 lncRNAs, and 245 transcripts undergoing AS events. Differentially expressed genes were enriched in pathways related to hormonal signalling, angiogenesis, calcium signalling, and cell remodelling. Notably, genes encoding key regulators of these processes, such as growth hormone 1, insulin-like growth factor type 1, somatostatin, prolactin receptor, and progesterone receptor, were modulated. Pathway enrichment analysis indicated enrichment of genes assigned to Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/protein kinase B, and mitogen-activated protein kinase signalling cascades. This study provides the first comprehensive transcriptomic profiles of irisin action on porcine APc during early pregnancy. Irisin can modulate endocrine, structural, and molecular functions through both transcriptional and post-transcriptional mechanisms, positioning it as a novel modulator of pituitary adaptation in early gestation.

Bone is a highly dynamic and purposefully organized structure that remodels constantly throughout adult life. Disordered bone remodeling, in which resorption of old bone by osteoclasts exceeds new bone formation by osteoblasts, results in bone loss, which, in turn, is associated with debilitating conditions, including osteoporosis and metastatic bone disease. The past decade has revealed vital new insights into the role of the central nervous system in skeletal regulation. These studies have led to a better understanding of physiologic circuitry, enabled us to revisit disease pathophysiology, and in doing so, prompted the creation of candidate therapeutics. The central neural control of bone is exerted through two arms - an amplitude-modulated (AM) neurohormonal arm that relies on changes in circulating levels of anterior and posterior pituitary hormones, which act on bone directly, and a frequency-modulated (FM) arm that arises from changes in the firing frequency of sympathetic, parasympathetic, and sensory nerves that innervate bone. Here, we review the medical consequences arising from the dysfunction of the AM and FM arms, as well as studies that have unmasked promising therapeutic targets.

Endocrinological evaluation is essential in neurosurgery for pituitary-hypothalamic disorders and intracranial conditions, such as tumors, trauma, hemorrhagic/ischemic events, inflammatory diseases, and iatrogenic injuries. Appropriate selection and interpretation of hormonal tests influence diagnosis, treatment strategies, perioperative care, and long-term outcomes. Baseline assessments should include measurements of anterior pituitary hormones (ACTH, TSH, GH, LH/FSH, and prolactin) and their corresponding peripheral hormones (cortisol, free thyroxine, IGF-1, and sex steroids). Because adrenal insufficiency is life-threatening, the ACTH-cortisol axis must be prioritized, with thyroid hormone replacement initiated only after adrenal function is confirmed. If baseline tests are inconclusive, dynamic stimulation tests are used to evaluate each axis; however, test selection must consider safety, as some stimulation tests are associated with rare complications, such as pituitary apoplexy, in patients with large Pit-NETs. This review summarizes the practical aspects of endocrine testing that are relevant to neurosurgeons, including typical endocrine profiles in intracranial diseases, indications and pitfalls of stimulation tests, and perioperative monitoring and hormone replacement, in collaboration with endocrinologists.

Somatostatin receptor 5 (SSTR5) negatively regulates growth hormone (GH) secretion in the human pituitary. Current therapy for GH deficiency (GHD) relies on exogenous recombinant GH injections, posing a significant treatment burden. SCO-240 is a novel, oral selective SSTR5 antagonist designed to stimulate the GH/insulin-like growth factor 1 (IGF-1) axis by "releasing the brake" on endogenous GH secretion. We evaluated whether sustained SSTR5 antagonism could induce a durable IGF-1 response while maintaining endocrine selectivity and metabolic neutrality. In this randomized, double-blind, placebo-controlled phase 1 study, 32 healthy Japanese men received once-daily oral SCO-240 (3, 10, 20, or 80 mg) or placebo for 7 days. Safety, pharmacokinetics, the GH-IGF-1 axis, metabolic parameters, and anterior pituitary hormones were assessed. SCO-240 was safe and well-tolerated; all treatment-emergent adverse events were mild and resolved spontaneously. Steady-state plasma concentrations of SCO-240 were achieved by day 2. SCO-240 induced a robust, sustained increase in serum IGF-1 across all dose levels, which remained elevated above placebo from day 2 through day 8. This response was driven by enhanced GH secretion, characterized by persistent basal tone and enhanced pulsatility. Notably, SCO-240 exhibited a metabolically neutral profile, with no alterations in other pituitary axes, fasting glucose, or fasting/postprandial insulin levels. Multiple oral doses of SCO-240 elicited selective, sustained, and physiologically regulated activation of the GH-IGF-1 axis without detrimental metabolic effects. These findings highlight SSTR5 as a druggable target and support SCO-240 as a potential first-in-class oral therapy for some forms of GHD. jRCT2051240252.

The hypothalamus regulates anterior pituitary (AP) hormone release via the hypophyseal portal system by secreting specific releasing and inhibiting peptide hormones. Growth hormone (GH) secretion from pituitary somatotrophs (PS) is regulated by a cholinergic mechanism that induces calcium (Ca2+) signaling, which in turn triggers vesicular exocytosis and GH release. Given that the transient receptor potential canonical channel 3 (TRPC3) regulates vesicle exocytosis in endocrine and neuroendocrine cells, we investigated its role in GH release from somatotrophs and whether GH release could support neuronal growth in the hypothalamus. Activation of TRPC3 by the diacylglycerol analog, 1-oleoyl-2-acetyl-sn-glycerol (OAG), resulted in a rapid increase in intracellular Ca2+ ([Ca2+]i) in wild type (WT) PS, attenuated by the TRPC3 inhibitor Pyr10, or by the knockout of TRPC3. ELISA assay confirmed that OAG exposure triggered GH release in WT PS. Conditioned media from OAG-stimulated PS promoted significant neurite outgrowth in hypothalamic neuronal cultures, suggesting a role for released GH in this process. Exposure of PS to H2O2-induced oxidative damage enhanced store-operated Ca2+ entry (SOCE) compared to control cells. Electrophysiological characterization revealed that somatotrophs under increased reactive oxygen species (ROS) conditions exhibited elevated SOCE, whereas cells under more native conditions exhibited receptor-operated Ca2+ entry. Furthermore, media from oxidative-stressed PS cultures, followed by the OAG exposure, induced neurite outgrowth, suggesting TRPC3 activation may provide an alternative pathway after ROS-induced damage in GH release. These findings indicate that Ca2+ signaling activation may promote GH secretion from control and ROS-induced AP cells, potentially leading to neurite outgrowth in hypothalamic cells. This study may provide insights into restoring neuronal connectivity following brain injury.

Introduction Granulomatosis with polyangiitis (GPA) is a multisystem disease characterised by necrotising small-vessel vasculitis, primarily affecting the upper respiratory tract, lungs, and kidneys. Pituitary involvement is reported in the literature in about 1% of all GPA cases. Pituitary GPA typically presents as a pituitary mass effect, resulting in symptoms such as headaches, visual disturbances, and anterior and posterior pituitary hormone deficiencies. This report presents a rare case of pituitary GPA that was successfully treated with glucocorticosteroids (GCs) and cyclophosphamide. Case description A 22-year-old woman with a two-year history of headache, rhinitis, sinusitis, otitis media and cough. Sinus tomography revealed impaired ventilation of the middle ear, sphenoid and maxillary sinusitis. A chest computer tomography scans revealed multiple nodules. The diagnosis of GPA was confirmed by elevated anti-neutrophil cytoplasmic antibodies (c-ANCA) levels and the presence of ANCA directed to proteinase 3 antibodies. The initial treatment consisted of highdose GCs and mycophenolate mofetil (2 g/day). After 6 months, clinical symptoms subsided. However, since May 2025, the patient experienced recurrent headache, general weakness, polyuria and polydipsia. The patient also had periodic nosebleeds and menstrual disorders. Biochemical tests revealed a deficiency of vasopressin, thyroid hormones and gonadotropins. The magnetic resonance imaging of the brain showed pituitary enlargement and thickening of the pituitary stalk – a typical symptom of pituitary inflammation. Treatment with GCs and cyclophosphamide in intravenous pulses was initiated. The headache resolved, and the patient underwent hormone replacement therapy. Conclusions To date, there are no established treatment guidelines of pituitary gland involvement in GPA. Several reports presented successful treatment with GCs and cyclophosphamide or rituximab. However, in most patients, pituitary gland dysfunction persists, necessitating long-term hormone replacement therapy. It is important to be aware of the potential pituitary gland involvement in GPA, particularly in patients presenting with persistent headache and endocrine disorders.

Insulin-like growth factor 1 (IGF-1) is a crucial protein that participates in cell growth and development. The actions of growth hormone (GH) are primarily regulated by IGF-1. The anterior pituitary gland is responsible for the production of GH, which is then delivered in the bloodstream and triggers the liver for the production of IGF-1. The growth-promoting effects of IGF-1 then occur in nearly every cell of the human body, including skeletal muscle tissues, kidneys, skin, bone, cartilage, nerve tissues, bone marrow, and lungs. While the liver is responsible for secreting about 75% of the circulating IGF-1, some target tissues can produce and express IGF-1 locally through autocrine and paracrine roles. These tissues include muscle, cartilage, bone, kidneys, and brain. IGF-1 can influence cell growth and development, particularly in nerve cells, along with the synthesis of DNA within cells, in addition to its insulin-like effects. The importance of IGF-1 in cell proliferation and inhibition of cell death (apoptosis) has been demonstrated. This review article aimed to determine and present the effect of IGF-1 in murine craniofacial growth in the presence of decreased masticatory load.

Background: Triple A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder characterized by the triad of alacrima, achalasia, and adrenal insufficiency. Its clinical presentation is often variable and progressive, which may delay diagnosis. In addition to the classical triad, neurological and endocrine manifestations have also been described. Case presentation: We report the case of an 18-year-6-month-old male patient, born to first-degree consanguineous parents, referred for evaluation of severe short stature in the setting of primary adrenal insufficiency. His medical history included severe dry eye consistent with alacrima, achalasia confirmed by upper gastrointestinal endoscopy, recurrent school failure, micropenis previously treated with testosterone injections, and fungal esophagitis. On examination, he had marked short stature, low body weight, cutaneous hyperpigmentation suggestive of melanoderma, and advanced pubertal development. Hormonal investigations revealed low morning cortisol with mildly elevated ACTH, supporting the diagnosis of primary adrenal insufficiency. Growth evaluation showed delayed bone age, low IGF-1 levels, and abnormal growth hormone stimulation tests, with an inadequate response to glucagon–propranolol and a partial response to L-DOPA, suggesting impairment of the somatotropic axis. Pituitary MRI demonstrated a normal-sized anterior pituitary gland and an incidental small pineal cyst, with no other abnormalities. The association of alacrima, achalasia, and primary adrenal insufficiency strongly supported the diagnosis of Allgrove syndrome, accompanied in this case by somatotropic axis dysfunction. Hydrocortisone replacement, education on emergency steroid use, and vitamin D supplementation were initiated, and recombinant growth hormone therapy with Genotropin was started. Conclusion: This case underlines the importance of recognizing the association of alacrima, achalasia, and adrenal insufficiency in adolescents presenting with growth failure. It also suggests that somatotropic axis dysfunction may contribute to short stature in some patients with Allgrove syndrome, supporting a more comprehensive endocrine assessment in affected individuals.

Pituitary adenomas are the most prevalent pituitary pathology and originate from the neoplastic proliferation of anterior pituitary lobe cell lineages. Two primary surgical approaches are employed: microscopic transsphenoidal surgery (MTS) and endoscopic transsphenoidal surgery (ETS). Both approaches aim to optimize tumor resection while reducing the risk of complications. The objective of this review is to compare the outcomes of ETS and MTS in the treatment of pituitary adenomas. Studies from 1974 to March 20, 2026, from PubMed, ScienceDirect, and Cochrane databases were included. The inclusion criteria were patients diagnosed with pituitary adenomas and patients aged ≥18 years. The systematic review includes a total of 22 articles with a total of 4390 participants, of which 2413 underwent ETS and 1973 underwent MTS. The findings suggest that gross total resection (GTR) was more frequently reported in patients undergoing the endoscopic technique; however, considerable variability exists across studies. Postoperative complication rates were variable and showed substantial overlap between endoscopic and microscopic techniques. Although the endoscopic technique may provide some benefits, overall safety and recovery outcomes seem to be affected more by study features and the surgeon's experience than by the surgical method itself. The comparison between both surgical techniques suggests potential advantages for the endoscopic approach in terms of GTR; however, clinical outcomes, including complications, recovery, and endocrine function, are comparable between techniques and appear to be influenced more by surgical expertise, tumor characteristics, and study design than by the surgical approach alone.

Several macro-hormones have been reported to date. Among them, macroprolactinemia is a common cause of hyperprolactinemia. Growth hormone (GH) and prolactin (PRL) are anterior pituitary hormones related by structure and function. The aim of this study was to clarify the prevalence and etiology of macro-GH. We examined the sera of 185 patients with high serum GH concentrations among 1,552 females who visited an obstetrics and gynecology hospital. The presence of macro-GH was investigated via the polyethylene glycol (PEG) method and gel filtration chromatography (GFC). Experiments using several reagents to block interfering substances in the serum with immunoassays and 125I-GH tracers were performed to examine the nature of macro-GH. PEG and GFC identified five patients with potential macro-GH, but four of them were due to the interference caused by human anti-rabbit IgG antibodies. One patient had true macro-GH due to anti-human GH autoantibody. The prevalence of macro-GH was 0.54 % (1/185) in patients with high serum GH concentrations. A 125I-GH binding study revealed that this autoantibody significantly bound to human 22-kDa GH and 20-kDa GH but did not bind to the other human anterior pituitary hormones, rat GH or human chorionic gonadotropin. The affinity of the anti-GH autoantibody was 0.77×108 M-1 for 22-kDa GH and 0.71×108 M-1 for 20-kDaGH. We presented a patient with macro-GH due to anti-human GH autoantibody. The prevalence of macro-GH was extremely rare compared to that of macro-PRL.

Oxytocin, a posterior pituitary hormone known for its role in parturition and lactation, is also implicated in many physiologic functions. Intranasal oxytocin is under investigation for obesity treatment, among other indications. The interplay of anterior and posterior pituitary hormones is currently not well understood. Given the well-established role of oxytocin in reproduction, it is important to examine intranasal oxytocin effects on prolactin and the hypothalamic-pituitary-gonadal (HPG) axis. Preclinical studies indicate that regulation of oxytocin, prolactin, and sex steroids in both sexes are intertwined; however, data in humans are limited, and no studies have reported the effects of prolonged oxytocin administration on prolactin or the HPG axis OBJECTIVE: To elucidate physiology and generate preliminary data regarding reproductive safety of prolonged intranasal oxytocin, we leveraged a completed trial to investigate oxytocin effects on circulating prolactin and sex steroid levels in adults with obesity. Sixty-one adults with obesity (52% females) participated in a longitudinal randomized clinical trial data and received eight-weeks intranasal oxytocin (24 IU) four times daily or placebo. Main outcome measures were pre- and post-treatment fasting estradiol, testosterone, and prolactin; exploratory outcome measure was on-treatment menstrual cycle length. Oxytocin vs. placebo groups did not differ for effects on prolactin or sex steroid levels (p's ≥ 0.140). On-treatment mean menstrual cycle length did not differ across groups (p = 0.234). In our study, eight-weeks of intranasal oxytocin administration did not impact prolactin or sex steroid levels, or menstrual cycle length, providing preliminary support for reproductive safety of oxytocin-based therapeutics in adults with obesity.