Are prolactin levels efficient in predicting a pituitary lesion in patients with hyperprolactinemia?

PURPOSE: Data regarding the presence of a prolactin (PRL) threshold above which a pituitary magnetic resonance imaging (MRI) is mandatory in patients with hyperprolactinemia (hyperPRL) are controversial and derived primarily from studies focused on female populations. Aim of our study was to evaluate in a cohort of patients of both sexes with confirmed hyperPRL, the possible correlation between PRL values and the presence of pituitary abnormalities. METHODS: We retrospectively analyzed data from patients who underwent serial PRL sampling at our Division between January 2015 and December 2022. Patients diagnosed with monomeric hyperPRL at serial sampling and with subsequent contrast-enhanced MRI results available for the pituitary region were included in the study. Exclusion criteria were prior pituitary disease, severe renal insufficiency, liver cirrhosis, uncompensated primary hypothyroidism and ongoing therapy with hyperprolactinemic drugs. Physiological causes of hyperPRL were also ruled out. RESULTS: Out of the 1253 patients who underwent serial PRL sampling, 139 patients (101 women and 38 men) met the inclusion criteria: 106 (76.3%) patients had some form of pituitary disease, with microlesions observed in 69.8%, macrolesions in 25.5% and other findings in 4.7% of subjects. PRL values showed a modest accuracy in predicting the presence of a pituitary abnormality and the best cut-offs identified were >25 µg/L (AUC 0.767, p = 0.003) and >44.2 µg/L (AUC 0.697, p < 0.001) in men and women, respectively; however, if only patients with PRL values > 500 µg/L were excluded from the analysis, as they were already supposed to harbor a macroprolactinoma, PRL levels were not able to predict the presence of a macrolesion neither in men nor women. CONCLUSION: Given the high prevalence of pituitary abnormalities in patients of both sexes with hyperPRL at serial sampling, performing a pituitary imaging in all cases of hyperPRL, even if mild, appears to be a cautious choice.

Neuroimaging of hypophysitis: etiologies and imaging mimics.

Hypophysitis is an inflammatory disease affecting the pituitary gland. Hypophysitis can be classified into multiple types depending on the mechanisms (primary or secondary), histology (lymphocytic, granulomatous, xanthomatous, plasmacytic/IgG4 related, necrotizing, or mixed), and anatomy (adenohypophysitis, infundibulo-neurohypophysitis, or panhypophysitis). An appropriate diagnosis is vital for managing these potentially life-threatening conditions. However, physiological morphological alterations, remnants, and neoplastic and non-neoplastic lesions may masquerade as hypophysitis, both clinically and radiologically. Neuroimaging, as well as imaging findings of other sites of the body, plays a pivotal role in diagnosis. In this article, we will review the types of hypophysitis and summarize clinical and imaging features of both hypophysitis and its mimickers.

Generating novel pituitary datasets from open-source imaging data and deep volumetric segmentation.

PURPOSE: The estimated incidence of pituitary adenomas in the general population is 10-30%, yet radiographic diagnosis remains a challenge. Diagnosis is complicated by the heterogeneity of radiographic features in both normal (e.g. complex anatomy, pregnancy) and pathologic states (e.g. primary endocrinopathy, hypophysitis). Clinical symptoms and laboratory testing are often equivocal, which can result in misdiagnosis or unnecessary specialist referrals. Computer vision models can aid in pituitary adenoma diagnosis; however, a major challenge to model development is the lack of dedicated pituitary imaging datasets. We hypothesized that deep volumetric segmentation models trained to extract the sellar and parasellar region from existing whole-brain MRI scans could be used to generate a novel dataset of pituitary imaging. METHODS: Six open-source whole-brain MRI datasets, created for research purposes, were included for model development. Deep learning-based volumetric segmentation models were trained using 318 manually annotated MRI scans from a single open-source MRI dataset. Out-of-distribution volumetric segmentation performance was then tested on 418 MRIs from five held-out research datasets. RESULTS: On our annotated images, agreement between manual and model volumetric segmentations was high. Dice scores (a measure of overlap) ranged 0.76-0.82 for both in-distribution and out-of-distribution model testing. In total, 6,755 MRIs from six data sources were included in the final generated pituitary dataset. CONCLUSIONS: We present the first and largest dataset of pituitary imaging constructed using existing MRI data and deep volumetric segmentation models trained to identify sellar and parasellar anatomy. The model generalizes well across patient populations and MRI scanner types. We hope our pituitary dataset will be an integral part of future machine learning research on pituitary pathologies.

Pituitary stalk thickening in patients under 18 years of age - the most common causes and diagnostic procedures.

INTRODUCTION: Pituitary stalk thickening (PST) is a rare abnormality in children, and it may be challenging due to its diverse clinical picture. AIM OF THE STUDY: The aim of the study is to summarize the data on the causes and diagnostic procedures of PST. MATERIAL AND METHODS: Papers were searched in the PubMed database identifying published randomized clinical trials, reviews, systematic reviews, meta-analyses, and case reports. RESULTS: The most common causes of a thickened pituitary stalk in children are germ cell tumours (GCTs), Langerhans cell histiocytosis (LCH), and lymphocytic infundibulo-neurohypophysitis (LINH). Neurosarcoidosis, pituitary tuberculosis, granulomatosis, or specific inflammations were only reported in the paediatric population as case studies. PST mainly affects teenagers and is often detected with brain magnetic resonance imaging (MRI) in patients with central diabetes insipidus (CDI). It is not possible to differentiate the causes of PST with the use of the MRI image alone. Although various biochemical and oncological markers and other imaging tests are used, the diagnosis of PST remains a significant diagnostic challenge for clinicians. The final diagnosis is made based on histopathological examination. The indications for a biopsy are not uniform. Most experts, including the authors of the 2021 British consensus, recommend biopsy in the case of PST with a stalk lesion diameter ≥ 6.5-7 mm. CONCLUSIONS: The differential diagnosis of PST is a challenge. The diagnostic and treatment strategy should be individually adapted. Patients should be diagnosed in large clinical centres with experience in this field.

Adding T2-Weighted Images to FAST1 Protocol to Evaluate the Anatomy of the Hypothalamic-Pituitary Region.

INTRODUCTION: Ectopic posterior pituitary (EPP) is a malformation of the hypothalamic-pituitary region presented as a spectrum from isolated growth hormone deficiency (GHD) to multiple pituitary hormone deficiencies (MPHDs). Our goal was to establish whether the FAST1.2 protocol, which combines the FAST1 protocol with 3D-T2 DRIVE images, could identify the pituitary stalk (PS) and the regional anatomy more accurately. METHODS: A retrospective study of 36 individuals with EPP and hypopituitarism and a control group of 78 individuals with eutopic posterior pituitary was conducted. All individuals were submitted to FAST1.2. The position and size of the pituitary lobes were described, and the presence/absence of the PS was confirmed. RESULTS: FAST1 identified the PS in 19% of individuals with EPP, while FAST1.2 identified the PS in 67% (p < 0.001). In the FAST1.2 protocol, the PS was visible in all control individuals. All EPP patients with isolated GHD had visible PS in FAST1.2, while only 58.6% of MPHD cases had visible PS. The size of the anterior lobe and the anteroposterior length of the posterior pituitary were smaller in the EPP group versus controls (p < 0.001). We noticed a reduced anterior pituitary lobe in both diameters in MPHD patients (p < 0.05). Six patients acquired new pituitary hormone deficiencies not recognized at the time of MRI; in this group, only 1 patient had a PS not visible in FAST1.2. DISCUSSION/CONCLUSION: The FAST1.2 protocol could prevent the misdiagnosis of idiopathic GHD in patients with short stature and could also be important in the progression to MPHD. The PS could be considered a predictor of hypopituitarism, but its use as an isolated indicator for the progression to MPHD is not recommended. Our results reinforce the use of the size of the anterior lobe as a predictor of hypopituitarism and a possible predictor of the degree of pituitary insufficiency. The FAST1.2 protocol could be used as an alternative to gadolinium administration, as a cheaper and faster method, while eliminating the potential risks associated with the administration of contrast media.

Differential Diagnosis and Radiographic Imaging of Pituitary Lesions: An Integrated Approach.

The sellar and parasellar region of the skull base is an area that can harbor a broad range of pathologic conditions. Formulating a differential diagnosis of a lesion in this region relies heavily on neuroimaging in addition to clinical and laboratory data. In this article, the authors briefly discuss some of the common pathologic conditions and their associated radiographic and clinical features.

Abnormal magnetic resonance imaging of the sellar region and its surroundings in patients with pituitary abscess.

Pituitary abscess is a rare disease with a high preoperative misdiagnosis rate. Magnetic resonance imaging is the primary method for confirming pituitary abscesses before surgery. We reported magnetic resonance imaging findings of four cases of pituitary abscess (three males and one female) aged from 33 to 72 years old. All four cases underwent transnasal sphenoid surgery and had a good prognosis. The findings on magnetic resonance imaging were analyzed. Three cases showed ring enhancement of the capsule wall. Four cases showed thickened pituitary stalk, with the diameter of the lower end larger than that of the upper end. The position of the pituitary stalk where it was inserted into the upper edge of the pituitary was located at the middle and posterior 1/3 junction of the upper edge of the pituitary two cases were with the enhancement of the dura mater at the bottom of the temporal lobe. Two cases were with the enhancement of the dura mater of the petroclival region, and one case was with the enhancement of the cavernous sinus. There are few articles concerning abnormal magnetic resonance imaging around the sellar region of pituitary abscess. The findings of the four cases in this article suggest that the pituitary abscess has characteristic abnormal magnetic resonance imaging of the sellar region and its surroundings.

Magnetic resonance imaging of the hypothalamo-pituitary region.

The diagnosis and management of mass lesions in the sellar and parasellar areas remain challenging. When approaching patients with possible sellar or hypothalamic masses, it is important not only to focus on imaging but also detect possible pituitary hormone deficits or excess, in order to establish an appropriate diagnosis and initiate treatment. The imaging modalities used to characterize hypothalamic and pituitary lesions have significantly evolved over the course of the past several years. Computed tomography (CT) and CT angiography play a major role in detecting various sellar lesions, especially in patients who have contraindications to magnetic resonance imaging (MRI) and can also yield important information for surgical planning. However, MRI has become the gold standard for the detection and characterization of hypothalamic and pituitary tumors, infections, cystic, or vascular lesions. Indeed, the imaging characteristics of hypothalamic and sellar lesions can help narrow down the differential diagnosis preoperatively. In addition, MRI can help establish the relationship of mass lesions to surrounding structures. A pituitary MRI examination should be obtained if there is concern for mass effect (including visual loss, ophthalmoplegia, headache) or if there is clinical suspicion and laboratory evidence of either hypopituitarism or pituitary hormone excess. The information obtained from MRI images also provides us with assistance in planning surgery. Using intraoperative MRI can be very helpful in assessing the adequacy of tumor resection. In addition, MRI images yield reliable data that allow for noninvasive monitoring of patients postoperatively.

Clinical analysis of 10 cases of pituitary stalk interruption syndrome and literature review.

OBJECTIVE: To analyze the clinical characteristics and MRI imaging of the patients with pituitary stalk interruption syndrome (PSIS) in the First Affiliated Hospital of Anhui Medical University in the past four years, and to achieve better comprehension of this disease. METHODS: Ten patients with PSIS (9 males, 1 female) in our hospital were retrospectively analyzed, regarding clinical manifestation, laboratory data and MRI imaging. RESULTS: The clinical features of 10 cases of PSIS were as follows: growth retardation, 55% of patients with hypogonadism, 45% of patients with short stature; the dystocia rate at birth is as high as 90%, of which 61% are breech presentation and 27% are foot presentation; 10 patients with PSIS, the height was between 135 cm and 180 cm, the weight was between 31 kg and 93 kg, the lower part was larger than the upper part, and the finger distance was smaller than the height; bone age is behind 3~7 years old; normal intelligence; 10 patients have clinical manifestations of hypopituitary hypofunction; no manifestations of diabetes insipidus; MRI imaging of pituitary showed that the pituitary stalks were not shown, atrophy or aplasia of anterior pituitary, posterior pituitary ectopic. CONCLUSION: The incidence of PSIS is low, and the etiology and pathogenesis are unknown. Appropriate hormonal replacement therapy is the only effective way but the timing of treatment is very important. Therefore, clinical doctors should strengthen the awareness of the disease, and master the clinical characteristics of the disease to grasp the timing of treatment.

Duplication of the Pituitary Gland (DPG)-Plus Syndrome Associated With Midline Anomalies and Precocious Puberty: A Case Report and Review of the Literature.

Duplication of the pituitary gland (DPG)-plus syndrome is a very rare developmental disorder with few cases described in the literature and characterized by multiple midline and central nervous system malformations. The hypothalamus and hypophysis involvement may be clinically associated with endocrine abnormalities. A 5.9-year-old female child was admitted to our Clinic for premature thelarche and acceleration of growth. DPG-plus syndrome with paired infundibula and pituitary glands was diagnosed after birth, when she appeared small for gestational age and she presented with lingual hypoplasia, cleft palate, right choanal stenosis, nasopharyngeal teratoma, and facial dysmorphisms. Neuroimaging revealed a duplication of the infundibula, the pituitary gland, and the dens of the epistropheus despite surgical removal of a rhino-pharyngeal mass performed at the age of two months. An array-CGH revealed a 2p12 deletion. At our evaluation, bone age assessment resulted advanced and initial pubertal activation was confirmed by Gonadotropin-Releasing Hormone stimulation test. Hormonal suppression treatment was started with satisfactory results. This case shows that DPG-plus syndrome must be considered in presence of midline and craniofacial malformations and endocrinological evaluations should be performed for the prompt and appropriate management of pubertal anomalies.

3D fat-suppressed T1-weighted volume isotropic turbo spin-echo acquisition (VISTA) imaging for the evaluation of the ectopic posterior pituitary gland.

OBJECTIVE: We evaluated the usefulness of fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) imaging for the evaluation of the ectopic posterior pituitary gland (EPPG). MATERIALS AND METHODS: This retrospective study included 9 patients with EPPG due to causes other than tumor. All underwent sagittal two-dimensional (2D) T1W-, FS 3D T1W-VISTA- (VISTA), and 3D T2W-driven equilibrium radiofrequency reset pulse (DRIVE) imaging. Two radiologists independently reviewed the 2D T1W- and VISTA images for their image quality and for visualization of the EPPG and of pituitary stalk transection. DRIVE findings were used as the reference standard for pituitary stalk transection. Interobserver and intermodality agreements were evaluated with the kappa (κ) coefficient. The mean grade assigned to the 2D T1W- and the VISTA imaging technique for visualization of the EPPG was assessed by the Mann-Whitney U test. RESULTS: Interobserver agreement for visualization of the EPPG on 2D T1W- and VISTA images was excellent (κ = 0.82 and κ = 1.00, respectively). The mean grade for EPPG visualization was significantly higher for VISTA- than 2D T1W images (p = 0.0039). CONCLUSION: FS 3D T1W-VISTA imaging is useful for the evaluation of EPPG. Conventional MRI yields insufficient information for the evaluation of the ectopic posterior pituitary gland (EPPG). The visualization of the EPPG was significantly higher for fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) than 2D T1W images. FS 3D T1W-VISTA imaging is useful for the evaluation of the EPPG.

Secondary Pituitary Abscess from Mite.

A 30-year-old woman experienced nasal stuffiness followed by a progressive headache and reduced visual acuity for 3 weeks. She underwent an endoscopic endonasal transsphenoidal approach for pituitary spindle cell oncocytoma 13 months before the present admission. Magnetic resonance imaging revealed an intrasellar cystic lesion with a suprasellar extension. After endoscopic endonasal transsphenoidal approach for tumor removal, the histologic findings of inflammatory infiltration showed a pituitary abscess. Microscopy revealed mites and fungal hyphae. Cultures from the abscess showed Staphylococcus hyicus, Stenotrophomonas maltophilia, and Aspergillus sp. The patient received a 6-week antibiotic treatment, which completely resolved the clinical symptoms and cleared the magnetic resonance imaging findings.

Prevalence and MRI findings of incidentally detected pituitary non-enhancing lesion on brain MRI in children.

OBJECTIVES: To determine the prevalence and MRI findings of incidentally detected pituitary nonenhancing lesion on brain MRI in children, and to compare the detection rates of pituitary nonenhancing lesion according to magnetic field strength and acquisition technique. METHODS: Pediatric patients (≤18 years old) who underwent brain MRI with contrast-enhancement between January 2018 and September 2019 were retrospectively included (n=365). The presence, size, and signal intensity of pituitary nonenhancing lesions were assessed by two radiologists. The prevalence of pituitary nonenhancing lesions was compared between different magnetic field strengths and MRI acquisition techniques. RESULTS: Pituitary nonenhancing lesions were identified in 76 patients (20.8%). The anteroposterior diameter of pituitary nonenhancing lesion was the smallest diameter in most patients (93.4%; mean diameter ± SD of 2.4 ± 1.5 mm; range: 0.9-9.0 mm). Sixty-seven percent of the pituitary nonenhancing lesions were hypointense on T1-weighted imaging, 44.1% were hyperintense on T2-weighted imaging, and 12.9% showed low signal intensity on susceptibility-weighted imaging. There was no diffusion restriction in any of the nonenhancing lesions. There was no significant difference in the prevalence of pituitary nonenhancing lesions according to magnetic field strength, age, gender, slice thickness, or 2D vs. 3D contrast-enhanced T1-weighted imaging sequence. CONCLUSIONS: Pituitary nonenhancing lesions were identified on contrast-enhanced brain MRI in 20.8% of pediatric patients, with no significant difference in the prevalence according to magnetic field strength, slice thickness, and 2D or 3D contrast-enhanced T1-weighted imaging.

Primary pituitary abscess in an adolescent female patient: case report, literature review, and operative video.

PURPOSE: Primary pituitary abscesses are extraordinarily rare lesions, especially in pediatric populations, with very few cases described in the literature. Here we review this rare condition and discuss its management. METHODS: We report a case of a previously healthy 12-year-old female patient who presented with vomiting and meningismus. We review the literature on pediatric patients presenting with pituitary abscesses and the described treatments. An operative video demonstrating our surgical technique is provided. RESULTS: Magnetic resonance imaging of the brain revealed a rim-enhancing, diffusion-restricting sellar lesion concerning for abscess. No sinus disease or other structural cause of intracranial infection was identified. An endoscopic transsphenoidal approach was used to visualize the endonasal structures, and microscopic guidance was used for evacuation of the abscess. Purulent material was drained immediately upon entry into the lesion. Tissue cultures grew Cutibacterium acnes. Postoperatively, the patient was hypocortisolemic but otherwise endocrinologically normal. She was discharged four days later on oral hydrocortisone and intravenous ceftriaxone without any neurologic deficit. CONCLUSION: To the best of our knowledge, this is the second report in the literature of a primary pituitary abscess due to C. acnes infection.

Associations among palatal impaction of canine, sella turcica bridging, and ponticulus posticus (atlas arcuate foramen).

INTRODUCTION: The palatal impaction of canine (PIC) can be predicted by some head and neck skeletal anomalies or variants. Since studies on this regard (especially vertebral anomalies) are scarce, this study was conducted. METHODS: This case-control study was done on 46 PIC orthodontic patients (34 females, 12 males) and 46 control orthodontic patients (36 females, 10 males). The diagnosis of PIC was done on lateral cephalographs and panoramic radiographs. On cephalographs, sella turcica bridging (occurrence and severity) and ponticulus posticus (occurrence and severity) were assessed. Associations between PIC, sella bridging, and ponticulus posticus were examined statistically (α = 0.05, ß ≤ 0.2). RESULTS: Cases' and controls' mean ages were 17.7 ± 4.0 and 17.4 ± 3.5, respectively. Of the case subjects, 22, 22, and 2 had respectively types I (normal), II, and III of sella bridging, while these numbers were 34, 12, and 0 in controls (chi-square P = 0.023 for severity, 0.010 for occurrence). Ponticulus posticus was observed in 28 cases (7 completed) and 17 controls (6 completed, P = 0.022 for occurrence, 0.056 for severity). Sella bridging was not associated with ponticulus posticus (Spearman P = 0.150). According to binary logistic regression, sella bridging can increase the odds of palatal canine impaction for OR = 2.8 times, while ponticulus posticus for OR = 2.6. Age and sex did not affect sella bridging or ponticulus posticus. CONCLUSIONS: Both sella bridging and ponticulus posticus can predict an increased rate of PIC for more than 2.5 times.

Comparison of cervical vertebral anomalies and sella turcica bridging in different growth stages with various vertical skeletal growth patterns.

PURPOSE: To compare cervical vertebral anomalies and sella turcica bridging (STB) in different growth stages in orthodontic patients with different vertical skeletal growth patterns. METHODS: Lateral cephalometric radiographs (LCR) of 270 patients in the preadolescent, adolescent, or postadolescent periods and having low angle [LA], normal angle [NA], or high-angle [HA] vertical skeletal growth patterns were evaluated retrospectively. STB was visualized using LCRs while evaluating the deficiency of ponticulus posticus (PP) and atlas posterior arch (PAA) associated with the atlas bone. The Pearson chi-square and Fisher's exact tests were used for categorical data and one-way ANOVA for numerical data. RESULTS: The prevalence of fully calcified PP and STB increased from the preadolescent (PP, 10.0%; STB, 11.1%) to the postadolescent period (PP, 24.4; STB, 21.1%); they did not differ from vertical skeletal growth patterns (p > 0.05). The prevalence of PAA deficiency is significantly higher in individuals with LA (46.7%) than with other angles (NA, 27.8%; HA, 26.7%). The vertical skeletal growth pattern was significantly related to STB in the preadolescent period and PAA in the postadolescent period. CONCLUSIONS: Different anomalies during different growth periods correlate with the vertical skeletal growth pattern. It will be useful to evaluate a different anomaly according to the relevant growth period.

Prolactin-to-Testosterone Ratio Predicts Pituitary Abnormalities in Mildly Hyperprolactinemic Men with Symptoms of Hypogonadism.

PURPOSE: We aimed to identify predictor variables associated with pituitary abnormalities in hypogonadal men with mild hyperprolactinemia. We also sought to develop a decision-making aid to select patients for evaluation with pituitary magnetic resonance imaging. MATERIALS AND METHODS: We retrospectively examined men with mild hyperprolactinemia (15.1-50.0 ng/ml) who presented with symptoms of hypogonadism and underwent pituitary magnetic resonance imaging. Demographics, laboratory values and clinical data were obtained from the electronic medical record. Selected predictor variables were included in multivariable logistic regression and partitioning models. Cost avoidance analysis was performed on models achieving sensitivities ≥90%. RESULTS: A total of 141 men were included in the study, of whom 40 (28%) displayed abnormalities on pituitary magnetic resonance imaging. Patients with pituitary abnormalities exhibited higher prolactin (p=0.01), lower testosterone (p=0.0001) and lower luteinizing hormone (p=0.03) levels than those with normal anatomy, as well as higher prolactin-to-testosterone ratios (p <0.0001) and lower luteinizing hormone-to-follicle-stimulating hormone ratios (p=0.0001). These serological variables were identified as the best performing predictor variables. The partition incorporating a prolactin-to-testosterone ratio cutoff of 0.10 and prolactin cutoff of 25 ng/ml achieved 90% sensitivity and 48% specificity, and reduced diagnostic expenses by 28%. CONCLUSIONS: Hypogonadal men presenting with mild hyperprolactinemia and pituitary abnormalities declare themselves via endocrine studies routinely ordered to evaluate these conditions. The prolactin-to-testosterone ratio is the best independent predictor of finding a pituitary abnormality on magnetic resonance imaging, although sensitivity improves by referencing additional serological parameters. Significant cost avoidance may result from screening this population prior to ordering pituitary magnetic resonance imaging.