Myostatin in the pituitary-muscle axis: Roles in health and disease.

Pancreatic islet remodeling in horses with hyperinsulinemia and pituitary dysfunction.

ObjectiveDopaminergic medications are commonly prescribed for Parkinson's disease (PD), restless legs syndrome, pituitary and psychotic disorders. Accumulating evidence indicates that dopaminergic treatment triggers impulsive-compulsive behaviors (ICBs), yet systematic synthesis of clinical evidence remains limited.MethodThis scoping review summarizes original research directly clinically relevant to ICBs under dopaminergic treatment, selected through systematic searches of MEDLINE PubMed, Web of Science, Embase and PsycInfo.ResultsOf 349 included studies, most focused on PD, with limited evidence from other populations. Reported ICB prevalences ranged between 15 and 35%. ICBs were associated with impaired daily functioning, depression, anxiety and significant family and financial burden. Younger age, male sex and dopamine agonist treatment, especially with pramipexole and ropinirole, were ICB risk factors. Management mainly involved tapering or discontinuing dopamine agonist treatment.ConclusionICBs in PD patients are well characterized, but under-recognition in health care and limited treatment strategies persist. Iatrogenic ICBs in other patient populations remain poorly studied.

Emerging applications of human iPSCs in pituitary diseases.

Hyperprolactinemia is mainly due to pituitary disorders including prolactinomas but other causes including adverse drug reactions exist. This study aimed to assess the frequency and pattern of serum prolactin measurements in a population-wide cohort in Central Region Denmark (1.32 mill inhabitants) from 2011 to 2022. Using the Central Denmark Region’s data warehouse, we identified all individuals who had at least one prolactin measurement in the study period. We identified 84,145 individuals who had at least one measurement of prolactin. Among these, 17,008 (20.3%) had at least one measurement of elevated prolactin corresponding to an incidence of 107 per 100.000 person-years. Hyperprolactinemia, defined by at least two elevated prolactin concentrations, occurred in 5,810 individuals (73.9% female), with an incidence of 36.7 per 100.000 person-years. Only 12.7% of individuals with hyperprolactinemia were treated with dopamine agonists. We found a substantial number of repeated prolactin measurements, many of which did not seem to lead to clinical action. The findings support the need for guidelines for management of hyperprolactinemia to ensure proper utilization of health resources.

Endoscopic transsphenoidal surgery has been the most commonly performed neuroendoscopic procedure in Japan since its reimbursement category was introduced in 2012. Although the surgical technique is now largely standardized, perioperative management and operating room setup still vary among institutions. At our center, patients are positioned in a semi-Fowler's posture with the head elevated to reduce venous bleeding from the cavernous sinus, while carefully monitoring the risk of venous air embolism. A slight vertex-up angle facilitates a natural instrument trajectory and is adjusted according to lesion location. Surgery is performed using a four-hand technique, with the assistant controlling the endoscope and coordinating movements with the surgeon, adapting to anatomical constraints and the use of straight or angled endoscopes. We also describe our approach to perioperative glucocorticoid supplementation, postoperative endocrine management for pituitary disorders, and the prevention and treatment of delayed postoperative hyponatremia. Collaboration with otolaryngologists is preferred for postoperative nasal care. These strategies aim to enhance surgical safety, infection control, endocrine stability, and patient comfort while supporting continued advances in endoscopic skull base surgery.

Background/Objectives: The purpose of this study was to compare the prevalence of sarcopenia and frailty in patients with acromegaly and hypopituitarism to healthy controls. Methods: This descriptive, comparative study included 32 patients with acromegaly, 24 patients with hypopituitarism, and 28 healthy volunteers who had undergone abdominal computed tomography (CT) within a month of their presentation at the endocrinology outpatient clinic between October 2023 and October 2024. The Tilburg Frailty Indicator was used to measure frailty. Sarcopenia was assessed using a dynamometer to measure handgrip strength and a CT-derived skeletal muscle index (SMI) at the L3 spinal level to measure muscle mass. Results: Both the hypopituitarism (7.5 ± 2.8) and acromegaly (7 ± 2.7) groups had substantially greater frailty ratings than the controls (4.8 ± 2.9) (p = 0.015). Frailty prevalence was 43% in the control group, 75% in acromegaly, and 83% in hypopituitarism (p = 0.019). The hypopituitarism group's muscle strength (20.8 ± 7.4 kg) was substantially lower than that of the acromegaly (37.5 ± 14.3 kg) and control groups (36.4 ± 9.6 kg) (p < 0.001). Patients with hypopituitarism had substantially lower SMI values (45.1 ± 11.3 cm2/m2) than those with acromegaly (53 ± 8.9 cm2/m2) (p = 0.04). A total of 50% of the control group, 9% of those with acromegaly, and 54% of those with hypopituitarism had probable or confirmed sarcopenia (p < 0.001). Conclusions: This study shows that frailty is more prevalent in patients with acromegaly and hypopituitarism than in healthy controls, with sarcopenia being especially noticeable in hypopituitarism. After adjusting for age and sex, the association with frailty remained significant for hypopituitarism (OR = 5.24, p = 0.021) while acromegaly showed a borderline trend (OR = 3.00, p = 0.076). These results imply that pituitary hormones might contribute to maintaining the functional ability and integrity of the musculoskeletal system. Further research in prospective studies using population-based controls is necessary to examine screening for frailty and sarcopenia in patients with pituitary diseases.

Incretin-based therapies in patients with pituitary disorders: clinical opportunity or premature enthusiasm? A balanced perspective.

Cushing's disease is caused by corticotroph tumors of the pituitary gland, resulting in adrenocorticotropic hormone hypersecretion and cortisol excess. The majority of the tumors are microadenomas. Magnetic resonance imaging (MRI) imaging is able to detect up to 70% of the corticotroph tumors. In the remaining patients, no tumor is detectable on MRI or there are equivocal changes without a clear demarcation of a tumor. Hence, the cure rates following transsphenoidal pituitary surgery are far from being satisfactory, with around 60% to 90% short-term remission in expert centers. Positron emission tomography (PET) has recently emerged as a potent method for the localization of small corticotroph adenomas and corticotroph adenomas without demarcation on the MRI. This review analyzes the radiopharmaceuticals most commonly used in evaluating pituitary disorders and explores the potential utilization of new PET tracers for personalized management of patients with Cushing's disease. Especially 11C-methionine and 18F-fluorethyltyrosine PET have recently been reported to be highly sensitive methods to detect MRI-undetectable corticotropinomas in 80% to 100% of patients. If confirmed in randomized controlled trials, PET imaging could be a major break-through towards targeted, individualized surgical therapy.

A rare case of spinal epidural lipomatosis secondary to pituitary Cushing disease presenting with progressive paraparesis

According to current guidelines, a morning serum cortisol < 30 µg/L confirms central adrenal insufficiency (CAI), whereas a value > 150 µg/L rules it out. However, these thresholds are based on older assays, and intermediate values require further testing. Newer, specific monoclonal antibody immunoassays may have lower diagnostic thresholds. This study aimed to identify morning cortisol cut-offs with ≥ 95% specificity or sensitivity (SP/SE) to determine which patients may safely avoid ACTH stimulation testing, using a second-generation immunoassay. We retrospectively evaluated 435 adults (236 males; overall median age 58.5 [IQR 20.3] years) with pituitary disorders. Based on the 1 µg ACTH test, patients were classified as having or not having CAI using a peak cortisol cut-off of 180 µg/L (guideline) or 127 µg/L (Roche Elecsys® Cortisol II–based studies). With the 180 µg/L threshold, a morning cortisol ≤ 80.8 µg/L best predicted CAI (SE 37.1%, SP 95.2%), while > 144.0 µg/L best excluded it (SE 95.2%, SP 29.1%). Using the 127 µg/L threshold, a value ≤ 60.9 µg/L best predicted CAI (SE 54.7%, SP 96.3%), whereas > 141 µg/L (SE 96.2%, SP 21.2%) best ruled it out. We identified updated morning cortisol thresholds, specific to a second-generation immunoassay, that accurately predict ACTH test results and may streamline the diagnostic workup of suspected CAI. Based on these data, we propose a refined diagnostic algorithm.

Treatment of skeletal fragility in patients with pituitary diseases is challenging. Denosumab, an antiresorptive bone active drug, increased bone mineral density (BMD) and reduced incidence and risk of fractures in primary osteoporosis. This study aimed to evaluate the efficacy of denosumab in patients with pituitary disease-driven osteoporosis. This retrospective study investigated the frequency of fragility fractures (FF) and the percent BMD changes at 1-, 2-, 5-, and 10-years of treatment with denosumab, in patients with osteoporosis due to secreting pituitary adenoma. Seventeen patients were included: 5 patients (29.4%) were affected by hyperprolactinemia due to PRL-secreting pituitary adenoma (PAs), six patients (35.3%) were affected by acromegaly and six patients (35.3%) by Cushing's disease. Four patients carried prevalent-FF (23.5%). A single patient with acromegaly developed FF at 2 and at 5years of treatment with denosumab. Femoral neck BMD increased in 11 patients (64.7%) at 1year of treatment, in 9 patients (52.9%) at 2years of treatment, in 8 patients (47.1%) at 5years of treatment and in 2 patients (66.7%) at 10years of treatment. Lumbar spine BMD improved in all patients at 1year of treatment (100%), in 16 patients at 2years of treatment (100%), in 11 patients at 5years of treatment (100%), and in 2 patients at 10years of treatment (66.7%). No drug related adverse events occurred. This study demonstrated for the first time that long-term treatment with denosumab is effective and safe in patients with osteoporosis due to secreting pituitary adenoma.

Patients living with pituitary neuroendocrine tumours (PitNETs) present with a spectrum of clinical manifestations and often follow a circuitous route to diagnosis, resulting in diagnostic delays. The objective of this study is to identify and report the various sources of referrals for patients who underwent pituitary resection for PitNETs in a tertiary referral centre for pituitary disease. Retrospective population-based cohort study. Patients undergoing a first surgery for management of PitNET in Northern Ireland between 01/01/2000-19/07/2019. Demographics, referral sources, incidentaloma rates, apoplexy rates, symptoms, age at diagnosis and diagnostic delay according to referral source. Data were retrospectively analysed for 520 patients in whom the referral source leading to diagnosis was known. Fifty-seven percent of patients were male. Median age at diagnosis was 54 years (range 18-85). Patients were referred from 29 different sources. The majority of referrals came from general practice (23%), ophthalmology (14%), emergency medicine (9%), optician/optometry (9%) and internists (8%). Twenty-nine patients were referred following radiological discovery of an incidentaloma. Twenty-seven patients were referred with an initial presentation of pituitary apoplexy, with emergency medicine accounting for 70% of these referrals. Visual disturbance and headache were the most frequently documented symptoms. Median diagnostic delay was 2 years (range 0-25 years). Patients with PitNETs encounter a range of clinical services in their journey to pituitary surgery. Raising awareness of these tumours and educating healthcare professionals across all disciplines could reduce diagnostic delays, thereby minimising the adverse sequelae of delayed diagnosis.

Purpose: To report a rare case of pituitary macroadenoma in pregnancy. Pituitary macroadenomas are benign tumors of the pituitary gland. Routine presentation may include endocrine abnormalities or visual field defects. The prevalence of pituitary macroadenomas in the general population is approximately 40.67 per 100,000 individuals. In pregnancy, the occurrence is even more rare, and diagnosis and management require a multidisciplinary approach to minimize potential complications. This case highlights the diagnostic process, management considerations, and potential impact on pregnancy outcomes. Method: Case Report Results: A 38-year-old G8P3043 female at 26+2 weeks of gestation presented with intractable headache. The patient stated she choked while drinking juice the night before, which led to a coughing spell. She reported that the headache began soon after the coughing spell. The headache was persistent, dull, and diffuse in nature and associated with photophobia, phonophobia, and two episodes of vomiting. She denied visual changes, dizziness, or weakness. The patient was administered a pain cocktail with minimal relief. Computed tomography (CT) and magnetic resonance imaging (MRI) of the head showed a 2.6 x 1.3 x 1.8 cm expansile mass in the sella with suprasellar extension, elevating and compressing the optic chiasm. The primary diagnosis was a pituitary macroadenoma. Neurology was consulted, and the patient was evaluated. Neurological physical exam was unremarkable, including cranial nerves, motor, sensation, coordination, and higher integrative functions. Neurology concluded there was no need for further neurological workup at this time and to follow up with the neurologist in 2 months. Her pregnancy has been complicated by fetal growth restriction (FGR), abnormal non-invasive prenatal testing (NIPT) with high suspicion for Trisomy 21, chronic hypertension, and advanced maternal age. Past medical history includes chronic hypertension on labetalol 100 mg twice a day and occasional migraines. She was never evaluated by a neurologist for the migraines because she reported only a few episodes a year. The patient was receiving twice weekly fetal testing for FGR with follow up ultrasounds every 3 weeks to assess fetal growth in the setting of highly suspected Trisomy 21. The patient remained asymptomatic throughout this time and did not require pain medication. The patient expressed a desire for a vaginal delivery. Due to the findings of pituitary adenoma and concerns for labor, an anesthesia referral was requested to determine if she was an appropriate candidate for regional anesthesia. She was evaluated by anesthesia, and they deemed her an appropriate candidate. At her 2 month follow-up visit with neurology, she denied any complaints, including headache or visual changes. Neurology referred her to neurosurgery for further evaluation. Neurology plans to follow up with her in 6 months. The team plans for delivery at 38 weeks pending continued normal antenatal testing. Conclusion: Pregnancy is a physiological state that induces significant changes in the endocrine system, particularly affecting the pituitary gland. These anatomical and functional changes make the management of pituitary disease more complex compared to the non-pregnant state. Due to hyperplasia and hypertrophy of lactotroph cells, the pituitary gland may increase in size by up to 40% in the second trimester and up to 70% in the third trimester, reaching two to three times its normal size. A pituitary adenoma greater than 10 mm in diameter, classified as a macroadenoma, has a 15-36 % chance of increasing in size during pregnancy. This growth risk necessitates close monitoring for symptoms such as headaches or visual disturbances, which may indicate tumor progression and could require neurosurgical evaluation. The treatment and surveillance of macroadenomas during pregnancy should be individualized. Patients should undergo close clinical follow-up with visual field testing during each trimester. In cases of non-functioning adenomas or hormone-secreting adenomas, surgery may be considered when there is significant visual impairment or life-threatening endocrine dysfunction. The second trimester is typically considered the safest period for surgical intervention, as it is associated with lower risks of congenital anomalies and preterm birth. The majority of women with macroprolactinomas or non-functioning adenomas experience favorable pregnancy outcomes. The primary goal of management is to ensure maternal and fetal safety while effectively controlling the tumor. Although rare, pituitary apoplexy, which involves infarction or hemorrhage within the pituitary gland often in the context of a pre-existing adenoma, can occur and may require emergency intervention. A collaborative, multidisciplinary approach involving obstetrics, endocrinology, neurology, neurosurgery, and maternal-fetal medicine is essential to optimize outcomes for both the mother and the fetus.

Structural variants (SVs) that disrupt topologically associating domains can cause disease by rewiring enhancer-promoter interactions. Duplications involving GPR101 are known to cause X-linked acrogigantism (X-LAG) through ectopic GPR101 expression, but not all of these duplications are pathogenic. This presents a diagnostic challenge, especially in the prenatal setting. We evaluated POSTRE, a tool that predicts the regulatory impact of SVs, to distinguish pathogenic from benign GPR101 duplications. We analyzed seven non-pathogenic duplications and 27 known X-LAG-associated duplications. To enable predictions in an X-LAG-relevant tissue, enhancer maps built using H3K27ac ChIP-seq, ATAC-seq, and RNA-seq data derived from human anterior pituitary samples (NIH research protocol 97-CH-0076, Clinicaltrials.gov Identifier NCT00001595, submitted on 11 March 1999) were integrated into POSTRE. POSTRE correctly classified all 34 duplications as benign or pathogenic. In addition, one X-LAG case with mild clinical features (i.e. severe growth hormone hypersecretion without pituitary tumorigenesis) was found to include only 2/5 VGLL1 enhancers, whereas all typical X-LAG cases had ≥4 enhancers duplicated. This suggests that partial enhancer hijacking at VGLL1 could explain the different clinical features in this individual. These findings support the utility of POSTRE to support diagnostic pipelines when interpreting SVs affecting chromatin architecture in pituitary disease and highlight its potential to reduce uncertainty in genetic counseling without requiring chromatin conformation capture assays.

Patients with adult growth hormone deficiency (AGHD) show accelerated atherosclerosis. While growth hormone replacement therapy (GHRT) may help mitigate this process, the mechanisms driving atherosclerosis progression in GHRT-treated patients with AGHD remain unclear. Thirty-one patients with AGHD on daily GHRT for ≥5 years were assessed in this crosssectional study. Carotid intima-media thickness (cIMT) was evaluated by ultrasound. Reactive hyperemia index (RHI) was measured using peripheral arterial tonometry. Associations between vascular measures and clinical, pituitary, treatment, body composition, and laboratory parameters were evaluated. cIMT correlated with body mass index (r=0.584, p=0.001) and visceral adipose tissue area (r=0.791, p<0.001), while demonstrating nominally significant associations with triglyceride levels, insulin resistance index, smoking history, and arterial hypertension. Neither the current nor the 5-year mean insulin-like growth factor 1 standard deviation score directly correlated with vascular parameters. Median cIMT was higher in adult-onset compared with child-onset AGHD (0.70 vs. 0.58 mm; p=0.020), while median RHI was lower in genetic than structural etiology (1.58 vs. 2.18; p=0.010); however, both associations were nominally significant. Several of the identified cardiovascular risk factors associated with cIMT are unlikely to be sufficiently controlled through GHRT. Pituitary disease characteristics may play a role in atherogenesis; however, the subgroups defined by disease onset timing and etiology were small and not fully comparable. In long-term GHRT-treated patients, cIMT is linked to well-established cardiovascular risk factors rather than features of the pituitary disorder and its management, highlighting the need for targeted cardiovascular risk management alongside GHRT in AGHD.

Clinical CaseIn 2015, a 35-year-old male was referred for preoperative evaluation of pituitary surgery after MRI revealed a 25×25×19 mm macroadenoma compressing the optic chiasm. Initial prolactin was ∼2000 µg/L and IGF-1 was markedly elevated (623 µg/L). During assessment, severe hypercalcemia (>14 mg/dL) was noted with PTH also significantly elevated (up to 623 pg/mL). After correction, subtotal (3.5 gland) parathyroidectomy was performed, confirming multiglandular adenoma. Postoperatively, permanent hypoparathyroidism developed, requiring lifelong calcium and calcitriol. Despite residual macroadenoma, the patient declined pituitary surgery; cabergoline was selected, normalizing prolactin and IGF-1 with radiologic regression.The patient also initially refused thymic surgery despite a mediastinal mass, but underwent thymectomy in 2020. Histopathology revealed a well-differentiated thymic NET, Grade 2, Ki-67 3–4%, with pleural metastases. Laboratory results showed marked hypergastrinemia (417 ng/L), normal glucagon (173 pg/mL), elevated Chromogranin A (850 µg/L) and neuron-specific enolase. Ga-68 PET/CT demonstrated pancreatic, pleural, and mediastinal metastases. MEN1 genetic testing confirmed a pathogenic mutation.The patient underwent thymectomy and subtotal parathyroidectomy. Cabergoline achieved biochemical remission of pituitary disease. Sandostatin LAR (30 mg IM every 28 days) was initiated for hormonal and antiproliferative effects. Calcium and calcitriol continue for hypoparathyroidism. Multidisciplinary follow-up is ongoing.ConclusionThis case illustrates an aggressive MEN1 variant with multihormonal secretion and metastatic thymic NET. Thymic involvement is rare but prognostically significant. Somatostatin analogs are valuable for hormonal and tumor control. In case of non-response, alternative systemic treatment options may also be used. Close, multidisciplinary surveillance is essential for high-risk MEN1 patients.

Oxytocin (OXT) is a neuropeptide hormone that plays a central role in numerous physiological and socio-emotional processes. Similar to arginine vasopressin (AVP), it is synthesized in the supraoptic and paraventricular hypothalamic nuclei and released both centrally and peripherally. Peripherally, OXT regulates uterine contractions during childbirth and milk ejection during lactation, metabolism, bone health, and cardiovascular functions. Centrally, it modulates social behavior, influencing trust, empathy, stress regulation, and emotional processing. Despite its close connection to AVP, the clinical significance of OXTDeficiency has only recently gained attention, particularly in patients with hypothalamic or pituitary damage with concomitant AVP-Deficiency. OXT-Deficiency may contribute to various neuropsychological symptoms seen in these patients, including social dysfunction, anxiety disorders, and reduced quality of life. However, a major challenge lies in accurately measuring OXT and thereby diagnosing a potential OXT-Deficiency. Basal plasma levels are unreliable, and most studied provocation tests only stimulate to a limited degree; hence, stronger provocation tests (e.g., using MDMA) and new surrogate parameters such as neurophysin I (NP-I) are gaining traction. Preliminary evidence from case reports and one small study suggests that intranasal OXT administration in patients with hypothalamic disorders may have beneficial effects on social behavior and emotion recognition. However, there is a clear need for larger, well-designed clinical trials, and several trials are currently underway to investigate the therapeutic potential of OXT in patients with AVP-Deficiency. OXT is also being explored as a possible treatment option in psychiatric conditions such as autism spectrum disorder, borderline personality disorder, and social anxiety disorder, with controversial results so far.

To synthesize and analyze the current available evidence on the development of new-onset endocrine disorders associated with coronavirus disease 2019 (COVID-19) vaccination. We performed a systematic review of literature by searching PubMed, Scopus, Embase and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied, the Joanna Briggs Institute tool and New Castle-Ottawa score were used to assess the risk of bias and quality. SPSS 25.0 software was used for statistical analysis. A total of 245 patients were reported from the selected studies. The most frequently reported endocrine disorders associated with COVID-19 vaccination were thyroid conditions (70.6%), primarily subacute thyroiditis (69.9%) and Graves' disease (28.9%). Cases of type 1 diabetes mellitus (10.2%), adrenal disorders (9.8%), and pituitary disorders (9.4%) were also identified. Most cases occurred in women (64%) and following the first vaccine dose (50.6%). Messenger ribonucleic acid-based vaccines primarily Pfizer-BioNTech and Moderna were the most reported (56.7%). Additionally, studies on fertility found no significant adverse effects on ovarian reserve or semen quality. Clinical outcomes were favorable in most cases (82%), with no significant mortality reported. Overall, although cases of endocrine disorders following COVID-19 vaccination have been reported, a causal relationship has not been definitively established. The benefits of vaccination significantly outweigh the potential risks of endocrinological complications at both the individual and population levels. Nevertheless, clinicians should remain alert to the possibility of endocrine manifestations following vaccination. PROSPERO identifier: CRD42024512710.

Prolactin is a key hormone that plays significant roles in reproduction, extending far beyond its well-known function in mammalian lactation. It is vital for reproductive success across diverse taxa, including birds, fish, reptiles, and amphibians, where it regulates critical reproductive behaviors and physiological processes like parental care, pregnancy maintenance, embryonic diapause, immunity, osmoregulation, metamorphosis, and molting. Environmental cues often fine-tune its actions to ensure reproduction occurs under optimal conditions. Conversely, dysregulation of prolactin can severely impact reproduction. While hyperprolactinemia is the most common pituitary disorder affecting fertility in women and other species, including elephants, hypoprolactinemia can lead to inadequate parental care due to poor milk production or inadequate brooding. Environmental stressors such as pollution and climate change can further disrupt prolactin levels, compounding reproductive failures. Its sensitivity to social and environmental stressors has led to its increasing recognition as a valuable biomarker for animal welfare assessment. Elucidating prolactin's multifaceted functions can substantially advance our comprehension of reproductive strategies across diverse taxa. These insights could potentially inform and enhance conservation efforts for threatened species ex situ and in situ, contributing to more effective wildlife management and preservation strategies. Here, we review the role of prolactin in reproduction, health, and welfare across species, with a particular emphasis on elephants. Nearly three decades of elephant studies, facilitated by accessible blood sampling, have yielded valuable insights into its physiological roles and association with reproductive dysfunction. While many prolactin mechanisms in elephants have similarities to those observed in other species and humans, there are notable differences that warrant further study to enhance our understanding of its role in physiology and behavior and contribute to our broader knowledge of reproductive endocrinology across species.