Anterior Pituitary Dysfunction Research Articles

Complications and visual outcomes following surgical resection of pediatric optic pathway/hypothalamic gliomas: a systematic review and meta-analysis.

Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.

Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis

IntroductionWhen children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little...

"One-and-a-Half" Interdural Transcavernous Pituitary Transposition/Rotation for Protection of Hypophyseal Portal System in Adult Peripheral Retroinfundibular Craniopharyngioma.

Craniopharyngiomas originate from the pituitary stalk (PS) and extend along the pituitary-hypothalamic axis. Peripheral retroinfundibular craniopharyngiomas, particularly, may have worse surgery outcomes than other types. This study aims to investigate the advantage of using "one-and-a-half" interdural transcavernous pituitary transposition/rotation to dissect the tumor from the residual stalk and hypophyseal portal system for this subtype of craniopharyngioma. From August 2018 to February 2023, patients with peripheral retroinfundibular craniopharyngioma underwent surgical treatment. We analyzed clinical information, surgical records, imaging, and examination findings. The surgical procedure, including "one-and-a-half" interdural transcavernous pituitary transposition and rotation, was explained. Postoperative follow-up included endocrinological tests, MRI examinations, and urination surveys. Among the 52 patients diagnosed with craniopharyngioma who underwent surgical treatment, 9 were classified as peripheral retroinfundibular craniopharyngioma, and they received "one-and-a-half" interdural transcavernous pituitary transposition and stalk rotation. In 6 cases, the residual PS and most of the hypophyseal portal system were preserved. Gross total resection was achieved in 5 patients and near total resection in 1 patient. One patient had a transection of the bilateral inferior hypophyseal arteries and 5 unilaterally. None experienced permanent diabetes insipidus, but varying degrees of anterior pituitary dysfunction postoperatively required hormone replacement therapy, which gradually decreased over time. The natural anatomic corridor, "one-and-a-half" interdural transcavernous pituitary transposition, and stalk rotation provide increased working space compared with intradural or extradural pituitary transposition. Simultaneously rotating the tumor and pituitary enables a specific attack angle for lesion dissection after the anteriorly displaced residual stalk is rotated laterally. This approach preserves the residual PS and hypophyseal portal system, avoiding complications of diabetes insipidus and hypopituitarism. In most cases, only one side of the inferior hypophyseal artery needs to be sacrificed, ensuring normal pituitary function.

WITHDRAWN: Clinical observation of 19 primary pituitary abscess cases treated by transsphenoidal surgery with or without sella packing

ObjectivePituitary abscess (PA) is a rare disease in the sellar region. This study aimed to investigate a series of PA cases with two different approaches to better understand the surgical principles and underlying mechanisms. Methods19 cases of primary PA were included for a comprehensive evaluation with special attention paid to the surgical approaches and the effectiveness and safety with or without sella packing. ResultsHeadache, and visual impairment were the most frequently seen symptoms among all patients. More than half of patients exhibited anterior pituitary dysfunction including panhypopituitarism, with a considerable portion of patients found with elevated prolactin (PRL) along with a thicker stalk on MRI. 11 patients underwent transsphenoidal surgery (TSS) without sella packing for allowing continuous drainage (Non-packing group), while the remaining 8 were operated with fat-based packing following intraoperative pus irrigation (Packing group). Both groups had similarly good outcomes including the duration of antibiotics use, complications, and hospital stay, but the incidence of abscess recurrence was higher for the packing group. ConclusionTSS without sella-packing exhibited comparable safety to the packing approach for PA and may be associated with a lower incidence of recurrence, provided that cerebrospinal fluid (CSF) leakage is well prevented.

A case of hypophysitis after COVID-19 vaccination with a detection of anti-pituitary antibody, with review of literature.

COVID-19 vaccines have resulted in a remarkable reduction in both the morbidity and mortality associated with COVID-19. However, there are reports of endocrine rare clinical conditions linked to COVID-19 vaccination. In this report, we present a case of hypophysitis following COVID-19 vaccination and review the literature on this condition. This case involved a 72-year-old male with type 1 diabetes who experienced symptoms such as vomiting, appetite loss, and headaches following his fifth COVID-19 vaccine dose. He was diagnosed with secondary adrenal insufficiency; subsequent assessment revealed an enlarged pituitary gland. Unlike previous cases, our patient has partial recovery from pituitary insufficiency, and his pituitary function gradually improved over time. Anti-pituitary antibodies (APAs) against corticotrophs, thyrotrophs, gonadotrophs, and folliculo stellate cells (FSCs) were detected in serum samples taken 3 months after onset. Hypophysitis after COVID-19 vaccination is a rare clinical condition, with only eight cases reported by the end of 2023, most occurring after the initial or second vaccination. Symptoms of hypophysitis after COVID-19 vaccination are similar to those of classic pituitary dysfunction. Pituitary insufficiency is persistent, with five of the above eight patients presenting posterior pituitary dysfunction and three patients presenting only anterior pituitary dysfunction. Two of those eight patients had autoimmune diseases. Our case suggests a potential link between acquired immunity, APA production, and pituitary damage. To elucidate the etiology of hypophysitis associated with COVID-19 vaccination, detailed investigation of patients with nonspecific symptoms after vaccination against COVID-19 is necessary.

NCMP-08. TREATMENT OF PITUITARY METASTASIS: A SINGLE CENTER EXPERIENCE AND SYSTEMATIC LITERATURE REVIEW

Abstract PURPOSE To understand the natural history and optimal treatment strategy for pituitary gland metastasis. METHODS We performed both a retrospective chart review of patients treated at our institution and a scoping review of the topic. RESULTS The retrospective review identified seven patients with an average age of 59.6. Primary histologies included breast cancer (4), melanoma (1), renal carcinoma (1), and sarcoma (1). Two patients had anterior pituitary endocrine dysfunction, one of whom was the only patient with visual symptoms. All patients were treated with radiosurgery and two also underwent surgical resection. Overall survival ranged from 6.5 – 117 months. We identified 166 patients from 71 studies in our literature review. The most common primary cancer was lung (27.7%), followed by breast (18.7%) and renal (14.5%) cancer. 107 presented with endocrine dysfunction; with 41 cases of diabetes insipidus and 55 cases of hypopituitarism. 110 presented with visual compromise. 107 patients received radiotherapy, 96 underwent surgical resection and 44 received systemic chemotherapy/immunotherapy. Surgery was significantly associated with an increased likelihood of vision improvement and a decreased likelihood of endocrine normalization. Radiographic regression predicted visual improvement. Median overall survival was 9.9 months (range: 0.2 – 96). CONCLUSIONS Our scoping review showed that both radiosurgery and surgical resection have been frequently used to treat pituitary metastases with good response. Vision improvement is more likely to happen following surgical resection. Despite treatment and radiographic response, patient survival remains less than a year.

FRI327 Lymphocytic Hypophysitis Presenting As Hypoprolactinemia In A Post-partum Female

Abstract Disclosure: J. John: None. S. Graybill: None. Lymphocytic hypophysitis is the most common presentation of primary pituitary gland inflammation. It typically presents with headache, vision changes, and sequelae of hypopituitarism, including central diabetes insipidus, anterior pituitary dysfunction, and hyperprolactinemia. Lymphocytic hypophysitis has a propensity to affect women in association with pregnancy due to an unknown underlying mechanism. A 38-year-old female presented with intractable headache and peripheral vision changes 3 weeks after giving birth to twin boys. Her post-partum course was complicated by preeclampsia with severe features. She also began experiencing blurry vision during this period. Seventeen days after delivery, she developed an acute onset headache and peripheral vision loss. She also noted sudden cessation of lactation with the onset of her headache. Initial CT head demonstrated a 1.6 centimeter enhancing pituitary mass suspicious for macroadenoma, and subsequent MRI sella revealed a 2.0 x 1.7 x 1.5 cm heterogeneously enhancing mass arising from the pituitary adenohypophysis extending to the undersurface of the optic chiasm. Initial laboratory evaluation demonstrated central hypothyroidism and inappropriately normal prolactin for a recently post-partum female. Given the patient’s impending vision loss, she was taken to the operating room for resection of suspected pituitary macroadenoma. Upon gross dissection, the abnormal appearance of the suspected mass prompted biopsy and immediate frozen section evaluation demonstrated significant lymphocytic infiltration. The resection was subsequently aborted. The patient was placed on levothyroxine and prednisone 80 milligrams daily for suspected lymphocytic hypophysitis, which was confirmed on tissue pathology. The patient’s headache and vision changes improved and after six days, she was discharged on a prednisone taper. Following three months of prednisone therapy, a repeat MRI sella demonstrated a reduction in the overall size of the pituitary gland to 1.7 x 1.2 x 1.1 cm. The patient was maintained on physiologic hydrocortisone and levothyroxine while monitoring for potential pituitary function recovery. Twelve months following her initial diagnosis, the patient did not demonstrate normalization of anterior pituitary function and required ongoing treatment for hypopituitarism. While hypoprolactinemia is atypical of hypophysitis, it is imperative to consider alternative pituitary pathology such as lymphocytic hypophysitis in the post-partum female when the clinical history is suspicious. Presentation: Friday, June 16, 2023

THU110 Wrong Tissue At Wrong Place—Rare Case Of Hypopituitarism Secondary To Metastatic Renal Cell Carcinoma

Abstract Disclosure: S. Avula: None. A. Ahmed: None. M. Salim: None. H. Alameddine: None. Introduction: Metastasis to pituitary is very rare occurrence, accounting for 1-4%. Most common primary cancer that metastasis to pituitary are Breast cancer in females and Lung cancer in males. Most of the pituitary metastasis are asymptomatic with symptomatic patient account for around 7 %. Most common symptoms reported are anterior pituitary dysfunction, visual field defects, headache, diabetes insipidus. Metastasis from Renal cell carcinoma (RCC) is very rare with only 25 cases reported so far. Metastases to the pituitary from RCC cause more severe hypopituitarism and visual dysfunction in comparison to those from other primaries. We present a rare case of hypopituitarism due to metastatic RCC presenting after Clinical Case: A 59-year-old male who initially presented in 2010 with complains of abdominal pain, underwent abdominal imaging and was found to have 7 cm solid mass in the right kidney. He underwent right nephrectomy in France and pathology confirmed RCC with no lymph node involvement. Patient didn’t have any adjuvant therapy. He had 5 years of follow up surveillance scans in Palestine which didn’t show any recurrence. In 2021 patient started to notice vision changes with loss of peripheral vision loss on right side but he didn’t seek any medical attention. In 9/2022 he noticed to have excessive fatigue, low libido, low appetite, excessive thirst and worsening of his vision. He had hormonal evaluation done in Palestine which showed low testosterone, cortisol, thyroid levels and was diagnosed with panhypopituitarism and was started on Hydrocortisone, Levothyroxine, Testosterone and Desmopressin. In 9/2022 had MRI brain in Palestine and showed 2cms suprasellar enhancing mass arising in the suprasellar cistern and appears inseparable from the pituitary stalk infundibulum. In 11/2022 he came to USA for further evaluation and management. In November 2022 patient complained of hallucinations, memory loss, personality changes and bitemporal vision loss. MRI brain showed sellar and suprasellar mass, 2.1 x 2.3 x 3.8 cm, extending to the suprasellar cistern and elevates the optic chiasm with possible third ventricle involvement and had increased in size compared to previous scan. On 11/29/22 patient underwent Endoscopic Endonasal Transplanum, Transtuberculum approach for tumor removal, biopsy of sellar and suprasellar tumor which returned as metastatic RCC. Patient was discussed in tumor board and is scheduled for gamma knife. Conclusion: Metastatic RCC to pituitary is very rare and most of them are asymptomatic leading to delay in diagnosis. Treatment of pituitary metastases is not standardized and should be tailored to patients’ clinical conditions, histology, and presence of extra-pituitary metastases. We need more prospective studies to formulate guidelines for management of pituitary metastases. Presentation: Thursday, June 15, 2023

FRI334 A Case Of Delayed Onset Sheehan's Syndrome With Diabetes Insipidus

Abstract Disclosure: S. Inkollu: None. A. Estrada: None. Introduction: Sheehan's syndrome (SS) is characterized by hypopituitarism that develops due to ischemic pituitary necrosis from severe postpartum hemorrhage. The frequency of SS has declined in developed countries as the result of modern obstetric care. It may present immediately after delivery or many years later with delay up to 32 years after the inciting event.1 SS is characterized by anterior pituitary dysfunction, while diabetes insipidus (DI) is an uncommon complication with an estimated frequency of 5%.2 Here, we present a case of a 58-year-old woman with late onset SS 33 years after delivery, complicated by DI. Clinical Case: A 58-year-old female was referred to endocrine clinic for hypothyroidism with TSH 4.98 mIU/mL (0.27-4.20) and undetectable free T4 (fT4) at <0.1ng/dL (0.8-1.6). Her symptoms included fatigue, dizziness, cold intolerance, dry skin, and hair loss for the past two years. On further questioning, patient reported that she was unable to lactate or menstruate since her last childbirth 33 years ago in Thailand, but never sought evaluation since she had completed her family. She was able to breastfeed her previous 3 children. On examination, she appeared well oriented but lethargic, withdrawn and pale. Axillary and pubic hair was absent. Pituitary hormonal panel demonstrated panhypopituitarism with fT4 <0.1 ng/dL, ACTH 14.2 pg/mL (7.2-63.3), cortisol 0.5 mcg/dL (10-20), prolactin 0.9 ng/mL (4.8-23.3), insulin like growth factor-1 of 10 ng/mL (56-194) and FSH 1.2U/L (25.8-134.8 postmenopausal). MRI of the pituitary showed a partially empty sella turcica. A diagnosis of SS was made and the patient was started on prednisone and levothyroxine. Shortly after starting prednisone, she developed significant polyuria and polydipsia. Given concern for DI unmasked by steroids, she was started on desmopressin 1mcg PO daily. Workup for DI was not done due to financial stressors. She showed marked improvement in general well-being and all her symptoms with hormone replacement. Conclusion: SS is not as rare as assumed in developed countries like USA, likely due to migrant women and unawareness of physicians regarding possibility of late onset SS. DI, though uncommon, still occurs with SS and can be masked by adrenal insufficiency on initial presentation. Clinicians should be aware of this condition as early diagnosis and treatment of SS improves quality of life along with morbidity and mortality to a great extent. Reference: 1. Otsuka F, Kageyama J, Ogura T, Hattori T, Makino H. Sheehan's syndrome of more than 30 years' duration: an endocrine and MRI study of 6 cases. Endocr J. 1998 Aug;45(4):451-8. doi: 10.1507/endocrj.45.451. PMID: 9881893. 2. Keleştimur F. Sheehan's syndrome. Pituitary. 2003;6(4):181-8. doi: 10.1023/b:pitu.0000023425.20854.8e. PMID: 15237929. Presentation: Friday, June 16, 2023

SAT624 Neurosarcoidosis Presenting With Panhypopituitarism

Abstract Disclosure: E.M. Niedzialkowska: None. T. Blazin: None. K. Strubchevska: None. M. Kozyk: None. N. Saini: None. Introduction: Neurosarcoidosis is estimated to occur in approximately 5-15% patients with sarcoidosis. Pituitary involvement may be present in up to 5% of those cases and can manifest as hypothalamus, adenohypophysis dysfunction or arginine vasopressin deficiency (AVP-D) in isolated fashion or variedly combined. Clinical case: 32 year old male presented with chief complaint of worsening bilateral lower extremity weakness, urinary incontinence, polyuria and polydipsia. 9 months prior to admission the patient was diagnosed with neurosarcoidosis. At that time brain MRI showed diffuse leptomeningeal enhancement, chest CT showed hilar lymphadenopathy, lumbar puncture with CSF analysis showed protein 227 mg/dl (N<38), ACE 6 U/l (N <2.5), WBC 10 (N<5) with 88% lymphocytes. Hilar lymph node biopsy was consistent with non-caseating granuloma. The patient was diagnosed with neurosarcoidosis and started on prednisone and methotrexate. The patient was referred to our institution for further evaluation. On examination gait ataxia and gynecomastia were noted. Laboratory results showed urine specific gravity of 1.001, LH 0.4 mIU/ml (N 0.6-1.2), FSH 1.1 mIU/ml (N 1-12), ACTH <5 pg/ml (N 6-46), cortisol 2.1 ug/dl (N 2.9-19.4), prolactin 10.5 ng/ml (N 2-18), total testosterone 4 ng/dl (N 240-1080), free testosterone 0.1 ng/dl (N 4.8-19), TSH 0.58 uIU/ml (N 0.4-4.5), free ft3 1.5 pg/ml (N 1.7-3.7), free ft4 0.6 ng/dl (N 0.7-1.5), IGF-1 52 ng/ml (N 71-234), Copeptin proAVP of <2.8 pmol/l( N>13.2), urine osmolality of 72 mOsmol/kg, blood osmolality of 297 mOsmol/kg (N <295), vit D 25-OH 9 ng/ml (N 30-100), vit D 1,25-OH 57.3 pg/ml (N 19.9-79.3). MRI of the spine showed extensive nodular enhancement of the leptomeninges of the cervical, thoracic spine and lumbar cauda equina nerve roots. Brain MRI was positive for numerous small nodular enhancement involving leptomeninges and pituitary stalk. The patient was started on desmopressin with significant improvement of symptoms and increase in urine osmolality to 709 mOsmol/kg. Due to risk of hypercalcemia and normal vit D 1,25-OH vitamin D supplementation was not initiated. For neurosarcoidosis the patient was started on pulse dose methylprednisolone and infliximab infusion. Upon discharge he was transitioned to oral hydrocortisone and started on levothyroxine and testosterone replacement therapy. Conclusion: We present a case of pituitary neurosarcoidosis presenting with AVP-D, secondary hypothyroidism, secondary adrenal insufficiency, hypogonadism and growth hormone deficiency. Panhypopituitarism with complete anterior and posterior pituitary dysfunction is extremely rare and might be found in up to 13% cases of pituitary sarcoidosis. The diagnosis should be considered in patients with sarcoidosis and endocrine dysfunctions. Presentation: Saturday, June 17, 2023

Early Postoperative Serum Sodium Level and Urine Output Volume Profile after Endoscopic Endonasal Transsphenoidal Surgery in Macroadenoma Pituitary Tumor

Introduction: Surgery is still the initial treatment of choice to for the majority of date with pituitary tumors. One of the most commonly performed minimally invasive neurosurgical procedures is transsphenoidal endoscopic endonasal surgery (ETS) and microscopic transsphenoidal surgery (MTS), used commonly for the resection of pituitary tumors. Neurosurgical operations for pituitary and suprasellar tumors may result in postoperative complications due to the crucial anatomical location of these tumors. The resulting postoperative complications can manifest as anterior or posterior pituitary dysfunction, particularly sodium disturbances, due to the changes in antidiuretic hormone (ADH) secretion, which remains one of the most frequent postoperative reasons for hospital readmission. Method: The aim of this study is to describe and determine the frequency distribution of patient characteristics who underwent endoscopic endonasal transsphenoidal resection of pituitary adenoma at Universitas Sumatera Utara Hospital between 2021 and 2022. Result: The findings of this study showed the frequency distribution of patient characteristics who underwent endoscopic endonasal transsphenoidal resection and postoperative sodium serum level profile as well as postoperative urine output profile. Discussion: The discussion section briefly discusses the findings and their implications. It mentions the high prevalence of headache and visual deficits among the patients, which aligns with previous studies. It also provides an overview of normal water balance and the pathophysiology of water balance disorders after pituitary surgery.

Dilemmas in the Management of Acute TBI: A Prospective Observational Study of Anterior Pituitary Dysfunction and Its Correlation with Outcome

Abstract Background The frequency and pattern of endocrinal abnormalities among patients with traumatic brain injury occur more frequently than previously suspected. Objective The aim of this study was to assess anterior pituitary dysfunction in patients with moderate-to-severe traumatic brain injury and outcome after treatment. Material and Methods One hundred patients with moderate-to-severe head injury presenting within 48 hours of injury were enrolled. Blood samples of all patients were taken for the hormonal assay at second day, at 2 weeks, 1 month, 3 months, and 6 months. Patients were evaluated by Glasgow coma scale (GCS), Glasgow outcome score (GOS), and hormone profile. Results The median GCS score was 10/15. Forty-four patients were operated and 56 patients were managed medically. Seven operated patients expired; 30 patients had good recovery. In conservative group, 46 patients had good outcome and two patients died. Cortisol and thyroid hormone values were changed prominently, followed by prolactin and growth hormone. On univariate analysis, association of GOS with fT3, fT4, serum prolactin, and serum cortisol was seen. On multivariate analysis, strong correlation of GOS with f T4 values was seen (p = 0.008) Conclusion Most of the hormonal deficiency occurs in immediate phase. Hormonal screening should be done to improve long term outcome.

Isolated anterior pituitary dysfunction in adulthood.

Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.

Chronic Anterior Pituitary Dysfunction Following Traumatic Head Injury: Prospective Study in Hospital Sultanah Aminah Johor Bahru, Malaysia.

Hypopituitarism following traumatic brain injury (TBI) is not rare however most patients were left undiagnosed and untreated. Association of post TBI hypopituitarism causing neurobehavioural and quality of life impairment. The aim of the study is to determine the incidence of the chronic anterior pituitary deficiency in patients with traumatic brain injury. Subsequently determine the risk factor and the outcome of the patient with chronic anterior pituitary dysfunction. This is single centre cross-sectional study involved 105 traumatic head injury patients under the Neurosurgical Department Hospital Sultanah Aminah, Johor Bahru, Malaysia. The primary investigator will do an interview and the patients will be asked question to complete a questioner from SF-36 (36 questions). Subsequently, consent for participation will be taken and blood sampling will be done. Thirty-three patients were noted to have anterior pituitary dysfunction. The mean age was 36.97 ± 12.96 years old. Twenty-seven patients (32.5%) were male and six patients were female (27.3%). Chronic anterior pituitary dysfunction in patients with a severe traumatic head injury around 47.1% (23 patients), as compared to a moderate head injury (8 patients, 38.1%) and 2 sustained mild head injury (5.6%). The mean duration after the onset of trauma was 10.3 ± 1.79 months. All patient with anterior pituitary dysfunction had positive CT brain findings with 22 had subarachnoid haemorrhage (SAH) at the basal cistern and 27 patients had a base of skull fracture, where 52.1% of the patient underwent surgical intervention, 84.8% involved one axis and another 5 patients had two axes involved. Severity of the head injury (P < 0.001), prolonged duration of hospital stay (P = 0.014), radiological findings of a base of skull fracture (P < 0.001) and presence of SAH at basal cistern (P < 0.001) was significantly associated with pituitary dysfunction. The patient with anterior pituitary dysfunction has the lower 36-item Short Form Survey (SF-36) marks 56.3 ± 10.3. The prevalence of hypopituitarism was 31%. Indicators are increased TBI severity, prolonged hospitalisation and positive finding in radiological assessment. Post-traumatic chronic anterior pituitary dysfunction also related with poor quality of life as showed by low SF-36 marks.

Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.

Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease caused by mutations in WFS1 and WFS2 genes that produce wolframin, a protein involved in endoplasmic reticulum calcium homeostasis and cellular apoptosis. Its main clinical features are diabetes insipidus (DI), early-onset non-autoimmune insulin-dependent diabetes mellitus (DM), gradual loss of vision due to optic atrophy (OA) and deafness (D), hence the acronym DIDMOAD. Several other features from different systems have been reported such as urinary tract, neurological, and psychiatric abnormalities. In addition, endocrine disorders that can appear during childhood and adolescence include primary gonadal atrophy and hypergonadotropic hypogonadism in males and menstrual cycle abnormalities in females. Further, anterior pituitary dysfunction with deficient GH and/or ACTH production have been described. Despite the lack of specific treatment for the disease and its poor life expectancy, early diagnosis and supportive care is important for timely identifying and adequately managing its progressive symptoms. The current narrative review focuses on the pathophysiology and the clinical features of the disease, with a special emphasis on its endocrine abnormalities that appear during childhood and adolescence. Further, therapeutic interventions that have been proven to be effective in the management of WS1 endocrine complications are discussed.

Central diabetes insipidus from a patient's perspective: management, psychological co-morbidities, and renaming of the condition: results from an international web-based survey

Central diabetes insipidus is a rare neuroendocrine condition. Data on treatment-associated side-effects, psychological comorbidities, and incorrect management are scarce. The aim of this study was to investigate patients' perspectives on their disease. This study used a cross-sectional, web-based, anonymous survey, developed by endocrinologists and patient representatives, to collect the opinions of patients with central diabetes insipidus on management and complications of their disease, psychological comorbidities, degree of knowledge and awareness of the condition among health-care professionals, and renaming the disease to avoid confusion with diabetes mellitus (diabetes). Between Aug 23, 2021, and Feb 7, 2022, 1034 patients with central diabetes insipidus participated in the survey. 91 (9%) participants were children and adolescents (37 [41%] girls and 54 [59%] boys; median age 10 years [IQR 6-15]) and 943 (91%) were adults (757 [80%] women and 186 [20%] men]; median age 44 years [34-54]). 488 (47%) participants had isolated posterior pituitary dysfunction and 546 (53%) had combined anterior and posterior pituitary dysfunction. Main aetiologies were idiopathic (315 [30%] of 1034 participants) and tumours and cysts (pre-surgical 217 [21%]; post-surgical 254 [25%]). 260 (26%; 95% CI [0·23-0·29]) of 994 patients on desmopressin therapy had hyponatraemia leading to hospitalisation. Patients who routinely omitted or delayed desmopressin to allow intermittent aquaresis had a significantly lower prevalence of hyponatraemia compared with those not aware of this approach (odds ratio 0·55 [95% CI 0·39-0·77]; p=0·0006). Of patients who had to be hospitalised for any medical reason, 71 (13%; 95% CI 0·10-0·16) of 535 patients did not receive desmopressin while in a fasting state (nil by mouth) without intravenous fluid replacement and reported symptoms of dehydration. 660 (64%; 0·61-0·67) participants reported lower quality of life, and 369 (36%; 0·33-0·39) had psychological changes subjectively associated with their central diabetes insipidus. 823 (80%; 0·77-0·82) participants encountered a situation where central diabetes insipidus was confused with diabetes mellitus (diabetes) by health-care professionals. 884 (85%; 0·83-0·88) participants supported renaming the disease; the most favoured alternative names were vasopressin deficiency and arginine vasopressin deficiency. This is the largest survey of patients with central diabetes insipidus, reporting a high prevalence of treatment-associated side-effects, mismanagement during hospitalisation, psychological comorbidities, and a clear support for renaming the disease. Our data are the first to indicate the value of routinely omitting or delaying desmopressin. Swiss National Science Foundation, Swiss Academy of Medical Sciences, and G&J Bangerter-Rhyner-Foundation.

Central diabetes insipidus and partial anterior pituitary dysfunction in acute myeloid leukemia.

SummaryCentral diabetes insipidus (CDI) is a rare manifestation of acute myeloid leukemia (AML) with unclear etiology. When present, CDI in AML has most often been described in patients with chromosome 3 or 7 aberrations and no abnormalities on brain imaging. In this case, we present a woman with newly diagnosed AML t(12;14)(p12;q13) found to have diabetes insipidus (DI) with partial anterior pituitary dysfunction and abnormal brain imaging. While in hospital, the patient developed an elevated serum sodium of 151 mmol/L with a serum osmolality of 323 mmol/kg and urine osmolality of 154 mmol/kg. On history, she reported polyuria and polydipsia for 5 months preceding hospitalization. Based on her clinical symptoms and biochemistry, she was diagnosed with DI and treated using intravenous desmopressin with good effect; sodium improved to 144 mmol/L with a serum osmolality of 302 mmol/kg and urine osmolality of 501 mmol/kg. An MRI of the brain done for the assessment of neurologic involvement revealed symmetric high-T2 signal within the hypothalamus extending into the mamillary bodies bilaterally, a partially empty sella, and loss of the pituitary bright spot. A pituitary panel was completed which suggested partial anterior pituitary dysfunction. The patient’s robust improvement with low-dose desmopressin therapy along with her imaging findings indicated a central rather than nephrogenic cause for her DI. Given the time course of her presentation with respect to her AML diagnosis, MRI findings, and investigations excluding other causes, her CDI and partial anterior pituitary dysfunction were suspected to be secondary to hypothalamic leukemic infiltration.Learning pointsLeukemic infiltration of the pituitary gland is a rare cause of central diabetes insipidus (CDI) in patients with acute myeloid leukemia (AML).Patients with AML and CDI may compensate for polyuria and prevent hypernatremia with increased water intake.AML-associated CDI can require long-term desmopressin treatment, independent of AML response to treatment.

Nomograms to Predict Endocrinological Deficiency in Patients With Surgically Treated Craniopharyngioma.

ObjectivePostoperative hypopituitarism associated with increased risks of premature mobility and mortality is often encountered in craniopharyngioma patients. The aim of our study is to construct nomograms related to injury types of the hypothalamus–pituitary axis (HPA) to predict hypopituitarism 1 year after surgery.MethodsCraniopharyngioma patients undergoing initial endoscopic endonasal surgery between December 2012 and March 2021 in our center were retrospectively reviewed, and injury types of the HPA were categorized according to intraoperative endoscopic observation. Included patients were randomly divided into a training group and a validation group. Nomograms were established based on the results of multivariate logistic analysis. The predictive performance of the nomograms was evaluated in the training and validation groups.ResultsA total of 183 patients with craniopharyngioma were enrolled, and seven injury types of the HPA were summarized. Relative to intact HPA, exclusive hypothalamus injury significantly increased the risk of anterior (OR, 194.174; 95% CI, 21.311–1769.253; p < 0.001) and posterior pituitary dysfunction (OR, 31.393; 95% CI, 6.319–155.964; p < 0.001) 1 year after surgery, while exclusively sacrificing stalk infiltrated by tumors did not significantly increase the risk of anterior (OR, 5.633; 95% CI, 0.753–42.133; p = 0.092) and posterior pituitary dysfunction (OR, 1.580; 95% CI, 0.257–9.707; p = 0.621) 1 year after surgery. In the training group, the AUCs of nomograms predicting anterior and posterior pituitary dysfunction 1 year after surgery were 0.921 and 0.885, respectively, compared with 0.921 and 0.880 in the validation group.ConclusionsIntact hypothalamus structure is critical in maintaining pituitary function. Moreover, our preliminary study suggests that the pituitary stalk infiltrated by craniopharyngioma could be sacrificed to achieve radical resection, without substantially rendering significantly worse endocrinological efficiency 1 year after surgery. The user-friendly nomograms can be used to predict hypopituitarism 1 year after surgery.

Surgical complications of endoscopic approach to skull base: analysis of 584 consecutive patients.

Endoscopic techniques have been widely applied for challenging cranial base surgeries in recent years. In this study, we evaluated the safety and efficacy of using the endoscopic endo-nasal route for various skull base pathologies in terms of postoperative complications. A total of 584 consecutive patients who underwent endoscopic skull base surgery were studied. Peri- and post-operative complications and risk factors affecting the occurrence of these complications were evaluated. 648 endoscopic skull base surgical procedures were performed on 584 patients (47.8% females and 52.2% males) with the mean age of 41.2years. Pituitary adenoma (69.3%) was the most common pathology. Post-operative mortality was 2.0%. The rates of post-operative permanent neurological deficit (one case of 6th nerve injury, two 12th nerve injuries and one hemiparesis) and visual deterioration were 0.6% and 1.5%, respectively. Ten patients (1.7%) were complicated with meningitis and it was the cause of death in 3. Systemic complications not directly attributable to skull base surgical access occurred in 2% (11 patients) with 5 mortalities. The rate of intra-operative vascular injury was 1% and among them one patient died due to PCA injury. The most common post-operative complications were diabetes insipidus (12.5%), anterior pituitary dysfunction (10.6%) and CSF leak (3.6%), respectively. In general, reoperation, malignant lesions, and level IV of surgical complexity were associated with a higher incidence of complications. Endoscopic endo-nasal approach can be a safe and less-morbid first-line treatment of patients with various skull base lesions.

Clinical features and difficulty in diagnosis of Langerhans cell histiocytosis in the hypothalamic-pituitary region.

Langerhans cell histiocytosis (LCH) is a multi-organ disorder that rarely involves the hypothalamic-pituitary region (HPR). HPR-LCH presents with severe progressive pituitary dysfunction and its prognosis is poor. The definitive diagnosis of LCH is considerably difficult and complicated owing to the occurrence of several diseases with similar manifestations in the HPR and its location in the deepest portion of the anterior skull base, in close proximity to important normal structures, severely limiting the size of the biopsy specimen. Chemotherapy is the established treatment modality for LCH; hence, timely and accurate diagnosis of LCH is essential for early therapeutic intervention. We retrospectively reviewed clinical features and biopsy procedures in four patients with HPR-LCH (all female, 28-44 years old) from 2009 to 2020. Maximum diameter of supra-sellar lesions was 23-35 mm and 2 cases had skip lesions. All patients demonstrated central diabetes insipidus, hyper-prolactinemia, and severe anterior pituitary dysfunction. Two of the patients had progressive disease. Furthermore, four patients presented body weight gain, two visual disturbance, and two impaired consciousness. The duration from onset to diagnosis of LCH was 3 to 10 (average 7.25) years. In total, eight operations were performed until final diagnosis. The percentage of correct diagnosis by biopsy was 50% (4/8). Clinical features of HPR-LCH are very similar to those of other HPR diseases, and their symptoms are progressive and irreversible. Clinicians should consider repeated biopsy with a more aggressive approach if the lesion is refractory to steroid therapy, in order to ensure accurate diagnosis and appropriate treatment.