Hematologic Malignancies: Two Cases of a Rare Cause of Hypopituitarism.

Hematologic malignancies are rare causes of sellar masses and hypopituitarism. We report 2 cases of hypopituitarism due to sellar masses from hematologic malignancies. The first patient was found to have hypopituitarism but initial non-gadolinium-enhanced magnetic resonance imaging (MRI) sella did not demonstrate a mass. Subsequent gadolinium-enhanced MRI and transsphenoidal biopsy confirmed a diagnosis of intravascular lymphoma. Treatment with systemic chemotherapy resulted in resolution of abnormalities on MRI. The second patient had a known diagnosis of chronic lymphocytic leukemia, and sellar involvement contributing to hypopituitarism was confirmed on biopsy. Treatment with ibrutinib, acalabrutinib, and stereotactic radiosurgery resulted in resolution of abnormalities on MRI. Both patients were treated with hormone replacement for hypopituitarism. These cases highlight that hematologic malignancies should be suspected as causes of sellar masses/hypopituitarism in patients with concurrent symptoms atypical for a pituitary adenoma (eg, constitutional symptoms), known diagnoses of hematologic malignancies, or rapid tumor growth and invasion on imaging. Gadolinium-enhanced MRI should be pursued if nonenhanced MRI is nondiagnostic. Transsphenoidal biopsy can be considered for diagnosis. Malignancy-directed systemic therapy may improve hypopituitarism and radiographic abnormalities on MRI.

Skeletal fragility in pituitary disease: how can we predict fracture risk?

Pituitary hormones play a crucial role in regulating skeletal physiology, and skeletal fragility is a frequent complication of pituitary diseases. The ability to predict the risk of fracture events is crucial for guiding therapeutic decisions; however, in patients with pituitary diseases, fracture risk estimation is particularly challenging. Compared to primary osteoporosis, the evaluation of bone mineral density by dual X-ray absorptiometry is much less informative about fracture risk. Moreover, the reliability of standard fracture risk calculators does not have strong validations in this setting. Morphometric vertebral assessment is currently the cornerstone in the assessment of skeletal fragility in patients with pituitary diseases, as prevalent fractures remain the strongest predictor of future fracture events. In recent years, new tools for evaluating bone quality have shown promising results in assessing bone impairment in patients with pituitary diseases, but most available data are cross-sectional, and evidence regarding the prediction of incident fractures is still scarce. Of note, apart from measures of bone density and bone quality, the estimation of fracture risk in the context of pituitary hyperfunction or hypofunction cannot ignore the evaluation of factors related to the underlying disease, such as its severity and duration, as well as the specific therapies implemented for its treatment. Aim of this review is to provide an up-to-date overview of all major evidence regarding fracture risk prediction in patients with pituitary disease, highlighting the need for a tailored approach that critically integrates all clinical, biochemical, and instrumental data according to the specificities of each disease.

Long COVID and pituitary dysfunctions: a bidirectional relationship?

Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome.

Trio-based whole exome sequencing in patients with ectopic posterior pituitary.

Introduction: Ectopic posterior pituitary (EPP) is a rare congenital abnormality, sometimes associated with other midline defects, such as pituitary stalk interruption syndrome (PSIS), in which thin or absent pituitary stalk and anterior pituitary hypoplasia are combined to EPP. Most cases are sporadic, with few reports of familial cases, and many congenital hypopituitarism (CH) cases remain unsolved. Objective: To search for candidate genes associated with this condition, we performed trio-based whole-exome sequencing (WES) on patients with EPP, including two familial cases. Methods: This study included subjects with EPP and PSIS diagnosed by a simple MRI protocol (FAST1.2). We performed two distinct analyses in the trio-based WES. We looked for previously described genes associated with pituitary development. Next, we investigated the whole exome for variants inherited in a pattern consistent with a monogenic etiology. Results: Ten families were evaluated; eight were composed of a child with EPP and healthy parents, one has two affected siblings, and one family has a son and mother with EPP. When analyzing the previously described candidate variants associated with pituitary development, we found variants in GLI2 and FGFR1 in three families. We also found six other variants of interest in three patients: KMT2A, GALR3, RTN4R, SEMA3A, NIPBL, and DSCAML1. Conclusion: The analysis allowed us to find previously reported and not reported GLI2 variants, all inherited from healthy parents, which reinforces the incomplete penetrance pattern of GLI2 variants in the development of EPP and draws attention to possible future functional studies of those variants that have a recurrent expression in CH. We also found novel FGFR1 and SEMA3A variants that suggest an oligogenic mechanism in PSIS and EPP, as seen in patients with hypogonadotropic hypogonadism. We report the first case of a patient with Wiedemann-Steiner syndrome and PSIS, suggesting that the KMT2A gene may be related to pituitary development. Furthermore, the trios' analysis allowed us to find five other variants of interest. Future investigations may clarify the roles of these variants in the etiology of EPP and PSIS.

Effects of glucocorticoid replacement therapy in patients with pituitary disease: A new perspective for personalized replacement therapy.

Secondary adrenal insufficiency (SAI) is an endocrine disorder due to impaired secretion of ACTH resulting from any disease affecting the pituitary gland. Glucocorticoid replacement therapy is mandatory to ensure patient survival, haemodynamic stability, and quality of life. In fact, a correct dose adjustement is mandatory due to the fact that inappropriately low doses expose patients to hypoadrenal crisis, while inappropriately high doses contribute to glucose metabolic and cardiovascular deterioration. This review analyses the current evidence from available publications on the epidemiology and aetiology of SAI and examines the association between glucocorticoid replacement therapy and glucometabolic and cardiovascular effects.

A Diagnosis of Sheehan's Syndrome: Better Late Than Never.

A middle-aged woman presented with history of fatigue, low mood, swelling of limbs, and facial puffiness. On detailed history taking, she also complained of salt craving, secondary amenorrhea, and loss of libido for almost a decade. Investigations revealed pan-hypopituitarism. She was started on appropriate hormonal therapy which saw a rapid resolution of symptoms within 2 weeks. Sheehan's syndrome may have an acute presentation or chronic. The symptoms may be subtle like fatigue or overt like hypotension and syncope. A high degree of suspicion of Sheehan's syndrome is essential for its timely management, and goes a long way in preserving the quality of life.

Cardiovascular Risk Factors in Sheehan's Syndrome: A Case-Control Study.

Introduction: Obesity, dyslipidaemia and insulin resistance are associated with hypopituitarism. The association between these conditions and Sheehan's syndrome (SS) caused by post-partum pituitary gland necrosis is poorly understood. This study aimed to assess cardiovascular risk surrogate markers in SS patients, and we compared clinical, biochemical and radiological testing with healthy controls. Methods: In this cross-sectional study, we studied 45 patients with SS on standard replacement therapy and compared them with healthy controls. All subjects underwent anthropometric, inflammatory marker and hormonal measurement (adrenocorticotropic hormone (ACTH), stimulated cortisol, insulin-like growth factor-1 (IGF-1), thyroxine (T4), follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E2), prolactin (Prl), insulin, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP)). Carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) and echocardiography were also performed. Results: The mean age and body mass index (BMI) of SS patients were 48.1 ± 10.0 years and 24.3 ± 4.3 kg/m2, respectively, while those of controls were 44.6 ± 12.0 years and 24.6 ± 3.2 kg/m2, respectively. Systolic blood pressure was significantly higher in SS (124.6 ± 20.8 vs. 117.0 ± 18.6 mm of Hg, P < 0.05). All SS patients were hypothyroid, and all except one were hypocortisolaemic. Triglyceride (TG) levels were significantly higher in SS patients (165.6 ± 83.3 vs. 117.2 ± 56.1, P < 0.01), but no difference in the prevalence of metabolic syndrome (MetS) was found. hs-CRP (9.1 (5.2-18.5) vs. 1.5 (0.6-2.8), P < 0.001) and IL-6 (4.9 (3.7-7.3) vs. 3.1 (2.0-4.2), P < 0.001) were significantly higher in SS patients. CIMT was significantly increased in SS patients, but no difference in FMD was found. Echocardiography revealed no significant difference in left ventricular (LV) dimensions, interventricular thickness, posterior wall thickness, ejection fraction, LV mass and diastolic function. Conclusion: SS patients show increased cardiovascular risk with hypertension, dyslipidaemia and increased atherosclerotic and inflammatory markers.

Pituitary Involvement in Langerhans Cell Histiocytosis: A Challenging Case.

Langerhans cell histiocytosis (LCH) is a rare disorder involving an abnormal clonal proliferation of precursor cells of the mononuclear phagocytic system. The hypothalamic-pituitary axis is commonly affected by central nervous system (CNS) involvement, with central diabetes insipidus being the most common endocrine abnormality observed. We report the case of a 55-year-old female presenting with vision changes and found to have a hypothalamic mass that was responsive to high-dose steroids. After an initial diagnostic dilemma, the surgical pathology eventually confirmed the diagnosis of LCH. She is being treated with hormone supplementation for panhypopituitarism and intensity-modulated radiation therapy (IMRT) for the LCH. Our case highlights that LCH can present as isolated hypothalamic-pituitary involvement. Early diagnosis is critical to prevent extensive progression of the disease, ultimately leading to permanent physical and endocrine abnormalities. More studies are required to develop specific guidelines and approaches for patients with isolated hypothalamic-pituitary involvement due to LCH.

Neurosarcoidosis With Panhypopituitarism: Two Cases and Literature Review.

Neurosarcoidosis (NS) with hypothalamic-pituitary (HP) involvement (HP-NS) is a rare clinical condition, conferring variable hormonal deficits that are typically irreversible. Here, we present 2 cases of NS with panhypopituitarism. The first patient presented with cauda equina syndrome and arginine vasopressin deficiency, while the second developed recurrent optic neuritis and vision loss in the setting of a sellar mass. In the first case, neurological symptoms resolved after therapy with high-dose glucocorticoids, infliximab, and methotrexate; while in the second, visual restoration followed resection of the granulomatous tissue and immunosuppressive therapy. In both cases, pituitary dysfunction persisted despite neurological improvement. We contextualized the presentations and outcomes through a literature review of HP-NS case reports and case series. This revealed high rates of extraneurologic sarcoidosis in HP-NS patients with panhypopituitarism, while underscoring the need for hormonal replacement-as endocrinopathies rarely respond to sarcoidosis-directed immunosuppression.

Hypopituitarism after gamma knife radiosurgery for pituitary adenomas: long-term results from a single-center experience.

OBJECTIVE: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center. METHODS: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7-297.6) months. RESULTS: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5-141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm3) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708-6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032-12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found. CONCLUSION: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism after a single GKRS.

Cardiovascular risk and glucocorticoids: a Dutch National Registry of growth hormone treatment in adults with growth hormone deficiency analysis.

PURPOSE: Patients with hypopituitarism are at increased cardiovascular risk, in part because of growth hormone deficiency (GHD), but probably also because of the overuse of glucocorticosteroids in concomitant adrenal insufficiency (AI). We hypothesized that patients with hypopituitarism that were on glucocorticosteroid replacement therapy for concomitant AI would have worse cardiovascular outcomes than those without. METHODS: Retrospective nationwide cohort study. GHD patients from the Dutch National Registry of Growth Hormone Treatment in adults were grouped by the presence (AI; N = 1836) or absence (non-AI; N = 750) of concomitant AI, and differences between groups were analyzed for baseline characteristics and cardiovascular risk, at baseline and during GHRT. RESULTS: At baseline, AI patients had higher levels of total and LDL cholesterol (both p < 0.01). During GHRT, AI patients were more likely to use cardiovascular drugs (p ≤ 0.01), but we did not find worse outcomes for blood pressure, body composition, lipid and glucose metabolism. The risk of developing peripheral arterial disease (HR 2.22 [1.06-4.65]) and non-fatal cerebrovascular events (HR 3.47 [1.60-7.52]) was higher in AI patients, but these differences disappeared in the models adjusted for baseline differences. CONCLUSION: We found no clear evidence to support our hypothesis that patients with hypopituitarism and concomitant AI have worse cardiovascular outcomes than non-AI patients. This suggests that glucocorticoid replacement therapy in AI may be safer than previously thought. However, cardiovascular burden, events and medication use at baseline and during GHRT (in unadjusted models) were higher in AI; so the lack of power, the important role of (adjusting for) other risk factors, and the inability to distinguish between glucocorticoid treatment regimens may have influenced the outcomes.

An Overview of Cardiovascular Risk in Pituitary Disorders.

Cardiovascular comorbidities owing to hormonal excess or deficiency are the main cause of mortality in patients with pituitary disorders. In patients with Cushing's Disease, there is an increased prevalence of cardiovascular diseases and/or risk factors including visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia, hypercoagulability as well as structural and functional changes in the heart, like cardiac hypertrophy and left ventricle (LV) dysfunction. Notably, these demonstrate limited reversibility even after remission. Furthermore, patients with acromegaly may manifest insulin resistance but also structural and functional heart changes, also known as "acromegalic cardiomyopathy". Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism as well as endothelial dysfunction. Hypopituitarism and conventional hormonal replacement therapy may also contribute to an unhealthy metabolic status, which promotes atherosclerosis and may lead to premature mortality. This review discusses the literature on cardiovascular risk in patients with pituitary disorders to increase physician awareness regarding this aspect of management in patients with pituitary disorders.

From Hypothalamic Obesity to Metabolic Dysfunction-Associated Steatotic Liver Disease: Physiology Meets the Clinics via Metabolomics.

Metabolic health is tightly regulated by neuro-hormonal control, and systemic metabolic dysfunction may arise from altered function of the hypothalamic-anterior pituitary axis (HAPA). Ancient experimental observations of hypothalamic obesity (HO) and liver cirrhosis occurring among animals subjected to hypothalamic injury can now be explained using the more recent concepts of lipotoxicity and metabolic dysfunction-associated steatotic liver disease (MASLD). Lipotoxicity, the range of abnormalities resulting from the harmful effects of fatty acids accumulated in organs outside of adipose tissue, is the common pathogenic factor underlying closely related conditions like hypothalamic syndrome, HO, and MASLD. The hormonal deficits and the array of metabolic and metabolomic disturbances that occur in cases of HO are discussed, along with the cellular and molecular mechanisms that lead, within the MASLD spectrum, from uncomplicated steatotic liver disease to steatohepatitis and cirrhosis. Emphasis is placed on knowledge gaps and how they can be addressed through novel studies. Future investigations should adopt precision medicine approaches by precisely defining the hormonal imbalances and metabolic dysfunctions involved in each individual patient with HO, thus paving the way for tailored management of MASLD that develops in the context of altered HAPA.

Pituitary deficiencies related to optic nerve hypoplasia and visual acuity.

OBJECTIVE: Optic nerve hypoplasia (ONH), the congenital underdevelopment of the optic nerve, is an increasing cause of visual impairment and is associated with pituitary dysfunction. Past studies have focused on the relationship between ONH, pituitary deficiencies, and brain imaging. However, recent studies have demonstrated the true risk for hypopituitarism lies with the presence or absence of ONH, irrespective of midline brain findings. This study reviewed the relationship between the health of the optic nerve (visual acuity) and pituitary gland (number and age of development of pituitary deficiencies) as a way to stratify risk, regardless of imaging findings. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective chart review of 197 patients seen at a single center from 2013 to 2022. Visual assessment was defined by distance acuity, and the presence of nystagmus or afferent pupillary defect. Pituitary deficiencies were diagnosed per Endocrine Society guidelines. RESULTS: In children with bilateral ONH (bONH), profound visual impairment was associated with more pituitary deficiencies between 0 and 15 years of age. The odds of having any pituitary deficiency were 4.9 times higher (95% confidence interval [95% CI]: 2.4-10.1) for patients with bONH versus unilateral ONH (uONH). Central hypothyroidism was the most common first presenting pituitary deficiency followed by growth hormone across all patients. CONCLUSION: This study shows a significant association between severity of visual impairment and increased probability of pituitary deficiencies in children with bONH versus uONH. Children with ONH require urgent endocrine evaluation due to risk of pituitary deficiencies, but risk stratification may also be based on severity of visual impairment.

Anterior Pituitary Dysfunction After Traumatic Brain Injury: A Prospective Study.

OBJECTIVE: Anterior pituitary dysfunction is one of the major causes of disability and morbidity in patients suffering from traumatic brain injury (TBI). The present study was undertaken to evaluate the incidence of anterior pituitary dysfunction in cases of moderate and severe TBI, its value in long-term prognostication, and the factors that predispose to a higher incidence of anterior pituitary dysfunction in acute and chronic phases. METHODS: This was a prospective cohort study wherein 216 patients with moderate and severe TBI were evaluated within 72 hours of TBI (acute phase) and at 6 months (chronic phase). RESULTS: At 6 months, out of the 216 patients, 95 patients had expired and 35 patients were lost to follow-up. The remaining 86 patients were evaluated at 6 months. In the acute phase, hypopituitarism was seen in 82.4% patients, thyroid axis deficiency was seen in 57.4% patients, gonadal axis deficiency in 54.2% patients, and adrenal axis deficiency in 13.8% patients. In the chronic phase, hypopituitarism was seen in 59.3% patients, thyroid axis deficiency was seen in 24.4% patients, gonadal axis deficiency in 32.6% patients, and adrenal axis deficiency in 23.3% patients. Patients with thyroid axis deficiency at admission had significant association with a bad modified Rankin Scale score at 6 months. CONCLUSIONS: Thyroid and gonadotropin axes were most commonly affected and deficiency of at least 1 axis was found in 82.4% patients in the acute phase and 59.3% in the chronic phase. Thyroid axis deficiency had a negative impact on prognosis in post-TBI patients.

Could low prolactin levels after radiotherapy predict the onset of hypopituitarism?

Both local and external cranial radiotherapy (RT) can induce neurotoxicity and vascular damage of the hypothalamic-pituitary area, which can promote neuroendocrine alterations. While anterior pituitary insufficiency after RT has been extensively characterized, data on the effect of RT on prolactin (PRL) secretion are limited and heterogeneous, with different patterns of PRL behavior described in the literature. A progressive decline in PRL levels, reflecting a time-dependent, slowly evolving radiation-induced damage to the pituitary lactotroph cells has been reported. To date, the association between hypopituitarism and hypoprolactinemia in patients undergoing RT has not yet been fully investigated. The few available data suggest that lower PRL levels can predict an extent damage of the pituitary tissue and a higher degree of hypothalamic dysfunction. However, most studies on the effect of RT on pituitary function do not properly assess PRL secretion, as PRL deficiency is usually detected as part of hypopituitarism and not systematically investigated as an isolated disorder, which may lead to an underestimation of hypoprolactinemia after RT. In addition, the often-inadequate follow-up over a long period of time may contribute to the non-recognition of PRL deficiency after RT. Considering that hypoprolactinemia is associated with various metabolic complications, there is a need to define appropriate diagnostic and management criteria. Therefore, hypoprolactinemia should enter in the clinical investigation of patients at risk for hypopituitarism, mainly in those patients who underwent RT.

Hyponatremia due to preserved non-osmotic arginine vasopressin secretion in adipsic diabetes insipidus: a case report with review of literature.

Adipsic diabetes insipidus (ADI) is characterized by central diabetes insipidus and an impaired thirst response to hyperosmolality, leading to hypernatremia. Hyponatremia observed in patients with ADI has been considered a complication of desmopressin therapy. Herein, we present a case of impaired thirst sensation and arginine vasopressin (AVP) secretion without desmopressin therapy, in which hyponatremia developed due to preserved non-osmotic AVP secretion. A 53-year-old woman with hypopituitarism, receiving hydrocortisone and levothyroxine, experienced hyponatremia three times over 5 months without desmopressin treatment. The first hyponatremic episode (120 mEq/L) was complicated by a urinary tract infection with a plasma AVP level of 33.8 pg/mL. Subsequent hyponatremia episodes occurred after administration of antipsychotic (124 mEq/L) and spontaneously (125 mEq/L) with unsuppressed plasma AVP levels (1.3 and 1.8 pg/mL, respectively). Hypertonic saline infusion did not affect AVP or copeptin levels. Regulating water intake using a sliding scale based on body weight prevented the recurrence of hyponatremia without the use of desmopressin. Except during infection, plasma AVP levels (1.3 ± 0.4 pg/mL) were not significantly correlated with serum sodium levels (rs = -0.04, p = 0.85). In conclusion, we present a unique case of impaired thirst sensation and AVP secretion in which hyponatremia developed without desmopressin therapy. Preserved non-osmotic AVP secretion, possibly stimulated by glucocorticoid deficiency, may contribute to the development of hyponatremia in patients with ADI.

Pregnancy in Autoimmune Hypophysitis: Management of a Rare Condition.

INTRODUCTION: Hypophysitis is an inflammatory disorder of the pituitary gland. It can manifest variously, with endocrinological and neuro-ophthalmologic symptoms and signs, due to the compression of sellar and parasellar structures. CASE REPRESENTATION: Although hypophysitis is rare, this pituitary disease can occur during pregnancy or in the postpartum period. In this report, we describe the case of a woman with partial hypopituitarism secondary to autoimmune hypophysitis who, five years after the diagnosis and the immunosuppressive treatment, had an uneventful pregnancy and successfully delivered a healthy infant at term. CONCLUSION: We reported the clinical history of the patient and the evolution of the disease and also reviewed the management and treatment of autoimmune hypophysitis during pregnancy.

Pituitary Apoplexy and the Current Understanding of Its Management: A Meta-Analysis of 908 Patients.

BACKGROUND: Pituitary apoplexy (PA) is characterized by acute hemorrhage or infarction of the pituitary gland. Management can be either conservative or surgical. Evidence favoring either is still limited to observational studies. This meta-analysis evaluates the effectiveness of both approaches on patient outcomes. METHODS: A systematic search was performed until February 2024. We included cohort studies of patients with PA. Patients were divided into 2 groups: a conservative management group and a surgery group, including early and late surgery. Outcomes of interest were assessed categorically using risk ratio (RR) and Mantel-Haenszel's random effects model. RESULTS: Of the 273 published articles, 15 cohort studies comprising 908 patients were included. There was no statistically significant difference between groups in recovery of ophthalmoplegia (RR=1.09, confidence interval [CI]=1.00-1.18, P=0.05), visual field (RR=1.09, CI=0.91-1.3, P=0.35), visual acuity (RR=1.05, CI=0.87-1.26, P=0.61), hypopituitarism (RR=1.37, CI=0.81-2.32, P=0.25), and tumor recurrence (RR=0.74, CI=0.34-1.61, P=0.45). This was similar for conservative management versus early surgery in recovery of visual field (RR=0.92, CI=0.62-1.37, P=0.68), visual acuity (RR=1.01, CI=0.81-1.26, P=0.93), and ophthalmoplegia (RR=0.92, CI=0.53-1.61, P=0.77). CONCLUSIONS: Both interventions provide comparable outcomes. These findings, though, are drawn from observational studies, and more severe cases typically undergo surgery. Larger studies are necessary to provide conclusive evidence.

Pituitary Complications of Checkpoint Inhibitor Use.

Immune checkpoint inhibitors have revolutionized cancer therapy but are associated with a risk of endocrine immune-related adverse events, including pituitary complications. Autoimmune hypophysitis, traditionally a rare diagnosis, has become a more frequently encountered clinical entity with the emergence of antitumor immunotherapy. This mini-review aims to consolidate current knowledge, encompassing the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of pituitary complications of immune checkpoint inhibitor use.