MRI Radiomics Features of Adenohypophysis Determine the Activation of Hypothalamic-Pituitary-Gonadal Axis in Peri-Puberty Children.

BACKGROUND: The status of the hypothalamic-pituitary-gonadal (HPG) axis is important for assessing the onset of physiological or pathological puberty. The reference standard gonadotropin-releasing hormone (GnRH) stimulation test requires hospital admission and repeated blood samples. A simple noninvasive method would be beneficial. OBJECTIVES: To explore a noninvasive method for evaluating HPG axis activation in children using an MRI radiomics model. STUDY TYPE: Retrospective. POPULATION: Two hundred thirty-nine children (83 male; 3.6-14.6 years) with hypophysial MRI and GnRH stimulation tests, randomly divided a training set (168 children) and a test set (71 children). FIELD STRENGTH/SEQUENCE: 3.0 T, 3D isotropic fast spin echo (CUBE) T1-weighted imaging (T1WI) sequences. ASSESSMENT: Radiomics features were extracted from sagittal 3D CUBE T1WI, and imaging signatures were generated using the least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation. Diagnostic performance for differential diagnosis of HPG status was compared between a radiomics model and MRI features (adenohypophyseal height [aPH] and volume [aPV]). STATISTICAL TESTS: Receiver operating characteristic (ROC) and decision curve analysis (DCA). A P value <0.05 was considered statistically significant. RESULTS: Eight hundred fifty-one radiomics features were extracted and reduced to 10 by the LASSO method in the training cohort. The radiomics model based on CUBE T1WI showed good performance in assessment of HPG axis activation with an area under the ROC curve (AUC) of 0.81 (95% CI: 0.71, 0.91) in the test set. The AUC of the radiomics model was significantly higher than that of aPH (0.81 vs. 0.65) but there was no significant difference compared to aPV (0.81 vs. 0.78, P = 0.58). In DCA analysis, the radiomics signature showed higher net benefit over the aPV and aPH models. DATA CONCLUSIONS: The MRI radiomics model has potential to assess HPG axis activation status noninvasively, potentially providing valuable information in the diagnosis of patients with pathological puberty onset. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Diagnostic value of adenohypophyseal MRI features in female children with precocious puberty.

AIM: To evaluate the diagnostic value of adenohypophyseal magnetic resonance imaging (MRI) features for precocious puberty (PP) in female children and also to establish a non-invasive diagnostic approach in clinics. MATERIALS AND METHODS: A total of 126 female children (37, 57, and 32 female children clinically diagnosed with central PP [CPP], incomplete PP [IPP], and controls, respectively) were enrolled in this study. Data were collected and analysed using analysis of variance. Pearson correlation and stepwise multivariate linear regression analysis were used to examine the association and build prediction models. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy. RESULTS: The values of adenohypophysis volume (aPV), adenohypophysis height (aPH), and signal-intensity ratio (SIR), height, weight, and seven laboratory testing characteristics were correlated closely with the activation status of the hypothalamic-pituitary-gonad axis in the different groups (all p<0.05). Model 1 including aPV, weight, and aPH and Model 2 including SIR, aPV, and height were built to obtain predicted luteinising hormone (LH; R2 = 0.271) and LH/follicle stimulating hormone (FSH; R2 = 0.311). ROC analysis showed the predicted LH, predicted LH/FSH, and aPV were the top 3 best predictors in distinguishing CPP from controls (AUC = 0.969, 0.949, and 0.938) while predicted LH/FSH was the best predictor in distinguishing CPP from IPP and controls (AUC = 0.829 and 0.828). CONCLUSION: The adenohypophysis volume itself and the prediction models including main adenohypophyseal MRI features increased diagnostic efficiency for PP and offered a non-invasive and credible diagnostic method.

Insight into the Characteristics of Novel Desmin-Immunopositive Perivascular Cells of the Anterior Pituitary Gland Using Transmission and Focused Ion Beam Scanning Electron Microscopy.

Recently, another new cell type was found in the perivascular space called a novel desmin-immunopositive perivascular (DIP) cell. However, the differences between this novel cell type and other nonhormone-producing cells have not been clarified. Therefore, we introduced several microscopic techniques to gain insight into the morphological characteristics of this novel DIP cell. We succeeded in identifying novel DIP cells under light microscopy using desmin immunocryosection, combining resin embedding blocks and immunoelectron microscopy. In conventional transmission electron microscopy, folliculostellate cells, capsular fibroblasts, macrophages, and pericytes presented a flat cisternae of rough endoplasmic reticulum, whereas those of novel DIP cells had a dilated pattern. The number of novel DIP cells was greatest in the intact rats, though nearly disappeared under prolactinoma conditions. Additionally, focused ion beam scanning electron microscopy showed that these novel DIP cells had multidirectional processes and some processes reached the capillary, but these processes did not tightly wrap the vessel, as is the case with pericytes. Interestingly, we found that the rough endoplasmic reticulum was globular and dispersed throughout the cytoplasmic processes after three-dimensional reconstruction. This study clearly confirms that novel DIP cells are a new cell type in the rat anterior pituitary gland, with unique characteristics.

Growth hormone deficiency in a child with branchio-oto-renal spectrum disorder: Clinical evidence of EYA1 in pituitary development and a recommendation for pituitary function surveillance.

Branchio-oto-renal spectrum disorder (BORSD) is a rare autosomal dominant condition characterized by ear abnormalities with hard of hearing/deafness, second branchial arch malformations and renal anomalies. Pathogenic variations in EYA1 gene are found in the majority of clinically diagnosed individuals with BORSD. We describe an infant with BORSD related to a paternally inherited heterozygous pathogenic variation in EYA1 gene presenting with poor growth and hypoglycemia due to growth hormone deficiency. Magnetic resonance imaging revealed a diminutive pituitary gland and morphologically abnormal sella. Upon initiation of growth hormone therapy, the hypoglycemia resolved and catch up growth ensued. Pituitary abnormalities have not been reported previously in patients with BORSD. The zebrafish ortholog of eya1 is important for the development of adenohypophysis, suggesting that this patient's growth hormone deficiency and pituitary abnormality are part of BORSD. Inclusion of screening for pituitary hormone deficiency and pituitary imaging should be considered as a part of surveillance in patients with BORSD.

Anterior pituitary gland T1 signal intensity is influenced by time delay after injection of gadodiamide.

To test the hypothesis of washout from the anterior pituitary (AP) gland after serial injections of gadodiamide. We included 59 patients with history of at least 5 injections of gadodiamide. Values of mean signal intensity of the AP and of the central pons were measured on unenhanced sagittal T1-weighted images. AP-to-pons signal intensity ratios were calculated dividing the values of the AP by those of the pons. The measurements were performed using MR images acquired at four different time points including baseline (prior to any gadodiamide injection), minimum post-injection time delay, maximum post-injection time delay, and last available MR scans. Normalized ratios (i.e. ratios divided total volume of injected gadodiamide) were also calculated. To assess the difference between ratios, non-parametric Wilcoxon signed-rank test was applied. The correlations were tested with non-parametric Spearman correlation coefficient. A p-value < 0.05 was considered as statistically significant. A statistically significant increase of AP signal intensity was found by comparing the baseline scans with both the minimum time delay (p = 0.003) and maximum time delay scans (p = 0.005). We found significant higher normalized ratios for minimum post-injection time delay with respect to maximum post-injection time delay (p < 0.001). The normalized ratios demonstrated a statistically significant negative correlation with the post-injection time delay (r = - 0.31; p = 0.006). The findings of this study suggest that washout phenomena of retained/deposited gadolinium from the AP are influenced by the total injected volume and post-injection time delay.

Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions.

CONTEXT: Association of central diabetes insipidus (CDI) and pituitary stalk thickening (PST) may have several etiologies (including malignancies) and differential diagnosis remains often difficult. OBJECTIVE: The purpose of this study was to identify which clinical, biochemical or radiological features could help clinicians to make an etiological diagnosis, especially distinguishing neoplastic from non-neoplastic pituitary stalk lesions. DESIGNS AND METHODS: We retrospectively analyzed clinical, biochemical, radiological and histological data of 38 adult patients diagnosed with CDI and PST of proven etiology. RESULTS: Of the 38 pituitary stalk lesions included, 11 (29%) were neoplastic. A histopathological diagnosis was obtained in 22/38 (58%) patients. The three most frequently observed etiologies of PST were neuroinfundibulitis (34%), germinoma (21%) and histiocytosis (18%). Pituitary stalk thickness was larger for neoplastic lesions, particularly germinomas. Male gender and a very young age were statistically associated with a risk of germinoma. At least one anterior pituitary deficit was observed in nearly 60% of patients. Patients with neoplastic PST were more affected by multiple anterior pituitary dysfunction than patients with benign PST. A high serum prolactin level was individually the best predictor of a neoplastic origin (90% sensitivity and 60% specificity for a serum prolactin level 1.27-fold above the normal upper limit (ULN)). CONCLUSION: We confirm a relatively high risk of malignancy in adult patients presenting with the association of CDI and PST. Young age, male gender, a very large thickening of the stalk, multiple anterior pituitary deficits and prolactin above 1.3× ULN increase the likelihood of a neoplastic origin.

Increased T1 Signal Intensity of the Anterior Pituitary Gland on Unenhanced Magnetic Resonance Images After Chronic Exposure to Gadodiamide.

OBJECTIVE: The aim of this study was to assess the signal intensity of the anterior pituitary (AP) gland on unenhanced T1-weighted images in patients with history of serial intravenous injections of gadodiamide and normal renal function. MATERIALS AND METHODS: We included 53 patients who had undergone at least 5 injections of gadodiamide and a control group of 15 subjects who underwent at least 5 brain magnetic resonance imaging without gadolinium-based contrast agents. Using unenhanced sagittal T1-weighted images, values of mean signal intensity of the AP and of the central pons were obtained. Anterior pituitary-to-pons signal intensity ratios were calculated dividing the values of the AP by those of the pons. Then, the ratios were compared between the first and the last magnetic resonance imaging scans for all the subjects. To assess the difference between the first and the last ratios, nonparametric Wilcoxon signed-rank test with Monte Carlo resampling was applied. A P value less than 0.05 was considered as statistically significant. RESULTS: The comparison between the first and the last scan revealed a statistically significant increase of AP-to-pons ratio in the last scan for the gadolinium-exposed group (P < 0.001), whereas nonsignificant results were found for the control group (P = nonsignificant). CONCLUSIONS: We found an increased signal intensity of the AP on unenhanced T1-weighted images in patients with history of serial intravenous injections of gadodiamide and normal renal function, suggesting gadolinium deposition or long-term retention within the AP gland. Our findings need to be confirmed by further histochemical analysis of AP gland tissue samples.

Sellar Xanthogranuloma: A Quest Based on Nine Cases Assessed with an Anterior Pituitary Provocation Test.

BACKGROUND: Xanthogranuloma is a chronic inflammatory mass characterized by cholesterol crystal deposition, which is rarely seen in the sellar region. The objective of this study is to identify the clinical features and cause of sellar xanthogranulomas. METHODS: We retrospectively analyzed manifestation, radiographic, and endocrinologic presentation in 9 patients (7 women and 2 men) whom we had previously treated. RESULTS: The patients were between 26 and 73 years of age (median, 56 years). The chief symptoms were visual symptoms in 3, polyuria in 3, headache in 4, and tiredness in 4 patients. Perimetry found visual field deficit in 6 patients. Anterior pituitary provocation tests disclosed impairment of ≥1 hormone in all patients: growth hormone in 8 patients and adrenocorticotropic hormone-cortisol axis in 8 patients. The lesions were suprasellar in 2 patients, intrasellar in 2 patients, and intrasuprasellar region in 5 patients. Three of the lesions were solid and 6 were single cystic to multicystic. Very low intensity area on T2-weighted magnetic resonance imaging was observed in 4 lesions. Postcontrast study performed in 7 lesions showed enhancement in solid parts or cyst walls. Surgical decompression improved visual disturbance in half of the patients but rarely improved hormonal deficits. Follow-up (median, 47 months) found no recurrence of the lesion. In addition to these 9 cases, we found 2 xanthogranulomatous lesions pathologically associated with ciliated epithelia, which also presented with severe hypopituitarism. CONCLUSIONS: Xanthogranuloma seems to be the last stage of the chronic inflammation affecting Rathke cleft cyst or craniopharyngioma presenting with severe anterior pituitary insufficiency.

Combined Pituitary Hormone Deficiency Caused by a Synonymous HESX1 Gene Mutation.

CONTEXT: Mutations in the HESX1 gene can give rise to complex phenotypes that involve variable pituitary hormone deficiencies and other developmental defects. CASE DESCRIPTION: A 14-year-old boy presented with short stature and delayed puberty and received a diagnosis of GH deficiency, central hypothyroidism, hypogonadotropic hypogonadism, and secondary adrenal insufficiency. He had anterior pituitary hypoplasia, ectopic posterior pituitary, and an interrupted pituitary stalk. Genetic studies uncovered a heterozygous variant in exon 2 of the HESX1 gene (c.219C>T; p.Ser73Ser). This single base change was predicted to be synonymous at the translational level but was shown to cause skipping of exon 2 in the RNA transcript. CONCLUSIONS: This study of a patient with combined pituitary hormone deficiency revealed an unusual synonymous mutation of the HESX1 gene leading to abnormal RNA processing and indicates the importance of investigating silent variants that at first glance appear to be benign.

Clinical and Pathological Aspects of Silent Pituitary Adenomas.

CONTEXT: Silent pituitary adenomas are anterior pituitary tumors with hormone synthesis but without signs or symptoms of hormone hypersecretion. They have been increasingly recognized and represent challenging diagnostic issues. EVIDENCE ACQUISITION: A comprehensive literature search was performed using MEDLINE and EMBASE databases from January 2000 to March 2018 with the following key words: (i) pituitary adenoma/tumor and nonfunctioning; or (ii) pituitary adenoma/tumor and silent. All titles and abstracts of the retrieved articles were reviewed, and recent advances in the field of silent pituitary adenomas were summarized. EVIDENCE SYNTHESIS: The clinical and biochemical picture of pituitary adenomas reflects a continuum between functional and silent adenomas. Although some adenomas are truly silent, others will show some evidence of biochemical hypersecretion or could have subtle clinical signs and, therefore, can be referred to as clinically silent or "whispering" adenomas. Silent tumors seem to be more aggressive than their secreting counterparts, with a greater recurrence rate. Transcription factors for pituitary cell lineages have been introduced into the 2017 World Health Organization guidelines: steroidogenic factor 1 staining for gonadotroph lineage; PIT1 (pituitary-specific positive transcription factor 1) for growth hormone, prolactin, and TSH lineage, and TPIT for the corticotroph lineage. Prospective studies applying these criteria will establish the value of the new classification. CONCLUSIONS: A concise review of the clinical and pathological aspects of silent pituitary adenomas was conducted in view of the new World Health Organization classification of pituitary adenomas. New classifications, novel prognostics markers, and emerging imaging and therapeutic approaches need to be evaluated to better serve this unique group of patients.

Hipopituitarismo. Una causa poco frecuente de retraso psicomotor / Hypopituitarism: An uncommon cause of developmental delay

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Ganglioglioma of the adenohypophysis mimicking pituitary adenoma: A case report and review of the literature.

INTRODUCTION: Ganglioglioma is a generally benign tumor, mostly occurring in patients <30 years old. Temporal lobe is most frequently involved. Up to now, only 3 cases were reported of ganglioglioma in the pituitary gland, all being confined to the neurohypophysis. Here, we are the first to report an adenohypophysis ganglioglioma. CASE PRESENTATION: A 43-year-old woman presented with chronic headache was referred to our hospital. Magnetic resonance imaging (MRI) indicated pituitary adenoma. Endoscopic transnasal transsphenoidal surgery was performed. The tumor was rich in blood supply, with tough texture, therefore only subtotal resection was conducted. Pathology analysis revealed an adenohypophysial tumor composed of dysplastic ganglion cells and neoplastic glial cells collided with nonspecific hyperplasia of pituitary cells. Immunohistochemistry revealed positive staining of synaptophysin, glial-fibrillary acidic protein, and CD34. The results were consistent with the diagnosis of ganglioglioma. After the surgery the patient recovered well except developing cerebrospinal fluid rhinorrhea, which was controlled by lumbar drainage. MRI 6 months later did not show any sign of progression. CONCLUSION: According to the findings of our case, concerns should be raised considering ganglioglioma as a differential diagnosis of mass located in the sellar region. Furthermore, an ideal management strategy for pituitary ganglioglioma is not known; therefore, more cases and long-term follow-up are needed to enrich our knowledge of the diagnosis, treatment, and prognosis of this rare intracranial lesion.

Image analysis for TSH mRNA in situ hybridization in pituitary glands from rats with thyroid follicular cell hypertrophy after treatment with three different test compounds.

The goal of this in situ hybridization and image analysis technique is to study the effects of new pharmacological/chemical entities on the thyroid and pituitary gland in rats, reveal the pathogenesis of thyroid follicular cell hypertrophy and to retrospectively exclude the risk of thyroid tumor development in humans. In the present study, we describe the increase of thyroid-stimulating hormone- (TSH-) beta subunit mRNA in the pars distalis of the pituitary gland and the quantitative measurement of TSH mRNA positive cells from rats of three 4-week toxicity studies treated with three different test compounds inducing thyroid follicular cell and hepatocellular hypertrophy in rats. Compared to immunohistochemistry (IHC), in situ hybridization (ISH) for TSH was found to be more sensitive. With this technique we are able to exclude a direct effect of the test compound on the thyroid gland by showing the activation of thyrotrope cells from the pituitary gland and therefore this technique retrospectively enables us to exclude a possible risk for humans at an early stage of drug development. Also in case blood serum samples for evaluation of TSH are not available anymore or hepatocellular hypertrophy is not present (close metabolic relationship between thyroid gland and liver in rodents), the described method allows retrospective investigations on thyroid follicular cell hypertrophy or hyperplasia. This can be of high relevance in human safety assessment for certain drugs in order to exclude a primary effect on the thyroid gland especially when it comes to thyroid neoplasia in rodents as previously described.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions.

INTRODUCTION: plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. OBJECTIVE: To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. MATERIALS AND METHODS: We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. RESULTS: We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). CONCLUSION: Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment.

Spindle cell oncocytoma: Report of two cases with massive bleeding and review of the literature.

Spindle cell oncocytoma (SCO) is a rare pituitary tumor, classified as a WHO grade I neoplasm. Due to its rarity, SCO is often preoperatively misdiagnosed as a pituitary macroadenoma. In the present study we report two recent cases of SCO, a 61-year-old male and a 65-year-old female presenting at Treviso General Hospital between March 2014 and April 2015. Tumor resection was achieved by endoscopic transsphenoidal approach but massive hemorrhagic events hampered surgery, endangering the patient's life in both cases. Both tumors featured fascicles of spindle cells with eosiniphilic cytoplasm expressing vimentin, S-100 and thyroid transcription factor-1 (TTF-1). The diagnosis of SCO was confirmed by second opinion in both cases. Extensive review of available literature, about 30 cases from 2002 to 2015, provided valuable clinical data for preoperative diagnosis and surgical removal of SCO tumors.

Pituitary Antibodies in an Adolescent with Secondary Adrenal Insufficiency and Turner Syndrome.

BACKGROUND/AIMS: Autoimmune hypophysitis (AH) is a rare inflammatory disease of the pituitary gland causing varying degrees of hypopituitarism and/or sellar compression. Cranial MRI remains the best noninvasive tool to diagnose AH, although a diagnosis of certainty requires pituitary biopsy. The objective of this study was to assess the utility of detecting pituitary antibodies for the diagnosis of AH. METHODS: A 15-year-old female with Turner syndrome (TS), hypothyroidism, and ovarian failure presented acutely with hypocortisolism. Laboratory studies revealed secondary adrenal insufficiency. MRI showed a hypotrophic pituitary gland and loss of the posterior pituitary bright spot. To establish an autoimmune basis for the adrenal insufficiency, serum was analyzed by double indirect immunofluorescence for the presence of pituitary autoantibodies. RESULTS: The patient's serum contained autoantibodies that recognized 36% of the adrenocorticotropic hormone-secreting cells, suggesting that these adenohypophyseal cells were targeted by autoimmunity. The serum contained antibodies that identified the majority of the gonadotropin-secreting cells (FSH 77%, LH 65%). No recognition of GH-, prolactin-, and TSH-secreting cells was found. Preabsorption experiments showed that antigenic targets of autoantibodies were not anterior pituitary hormones themselves. CONCLUSION: Demonstration of circulating pituitary antibodies expands the diagnostic options for AH. In this adolescent with TS, positive and cell-specific pituitary antibodies suggested that AH was the cause of her secondary adrenal insufficiency.

Copper, zinc and calcium: imaging and quantification in anterior pituitary secretory granules.

The anterior pituitary is specialized for the synthesis, storage and release of peptide hormones. The activation of inactive peptide hormone precursors requires a specific set of proteases and other post-translational processing enzymes. High levels of peptidylglycine α-amidating monooxygenase (PAM), an essential peptide processing enzyme, occur in the anterior pituitary. PAM, which converts glycine-extended peptides into amidated products, requires copper and zinc to support its two catalytic activities and calcium for structure. We used X-ray fluorescence microscopy on rat pituitary sections and inductively coupled plasma mass spectrometry on subcellular fractions prepared from rat anterior pituitary to localize and quantify copper, zinc and calcium. X-ray fluorescence microscopy indicated that the calcium concentration in pituitary tissue was about 2.5 mM, 10-times more than zinc and 50-times more than copper. Although no higher than cytosolic levels, secretory granule levels of copper exceeded PAM levels by a factor of 10. Atp7a, which transports copper into the lumen of the secretory pathway, was enriched in endosomes and Golgi, not in secretory granules. If Atp7a transfers copper directly to PAM, this pH-dependent process is likely to occur in Golgi and endosomes.

Case of pituitary stalk transection syndrome ascertained after breech delivery.

Pituitary stalk transection syndrome (PSTS) is a rare complication that can accompany breech delivery. Early diagnosis of this syndrome is difficult, and it may cause a serious delay in the diagnosis. We present a case of PSTS ascertained after breech delivery. A 20-year-old woman presented with primary amenorrhea. The patient was born by breech delivery and had a history of treatment for pituitary dwarfism. Her laboratory findings showed pituitary hypothyroidism, and hormone replacement therapy was initiated. At 28 years old, she became pregnant and had a normal delivery at 38 weeks' gestation. One year after delivery, her thyroid hormone level changed. Laboratory test showed adrenocortical insufficiency, and magnetic resonance imaging of the pituitary gland showed transection of the pituitary stalk and development of an ectopic posterior lobe. These findings were compatible with PSTS. When a patient who has been born by breech delivery presents with symptoms of pituitary deficiency, PSTS should be considered in the differential diagnosis.

Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation.

BACKGROUND: Patients with pituitary stalk interruption syndrome (PSIS) are initially referred for hypoglycemia during the neonatal period or growth retardation during childhood. PSIS is either isolated (nonsyndromic) or associated with extra-pituitary malformations (syndromic). OBJECTIVE: To compare baseline characteristics and long-term evolution in patients with PSIS according to the initial presentation. STUDY DESIGN: Sixty-seven patients with PSIS were included. Data from subgroups were compared: neonates (n = 10) versus growth retardation patients (n = 47), and syndromic (n = 32) versus nonsyndromic patients (n = 35). RESULTS: Neonates displayed a more severe hormonal and radiological phenotype than children referred for growth retardation, with a higher incidence of multiple hormonal deficiencies (100% versus 34%; P = 0.0005) and a nonvisible anterior pituitary lobe (33% versus 2%; P = 0.0017). Regular follow-up of growth might have allowed earlier diagnosis in the children with growth retardation, as decreased growth velocity and growth retardation were present respectively 3 and 2 years before referral. We documented a progressive worsening of endocrine impairment throughout childhood in these patients. Presence of extra-pituitary malformations (found in 48%) was not associated with more severe hormonal and radiological characteristics. Growth under GH treatment was similar in the patient groups and did not vary according to the pituitary MRI findings. CONCLUSIONS: PSIS diagnosed in the neonatal period has a particularly severe hormonal and radiological phenotype. The progressive worsening of endocrine impairment throughout childhood justifies periodic follow-up to check for additional hormonal deficiencies.

Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited.

CONTEXT: Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings. OBJECTIVE: The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS. METHODS: This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared. RESULTS: Of the 74 patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups. CONCLUSIONS: The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS.