Lymphocytic Hypophysitis Research Articles

Hypophysitis in COVID-19: a systematic review.

This systematic review aims to collect and examine recent research findings regarding hypophysitis in COVID-19 patients. We conducted a comprehensive literature review in English on the topic "Hypophysitis in COVID-19," using the MEDLINE (PubMed) database in July 2024. The selected articles were systematically tabulated and we have assessed in this review patient demographics, symptom presentation, imaging results, diagnosis, clinical management, and outcomes. Seven reported cases of post-COVID-19 hypophysitis were identified, comprising 4 (57%) females and 3 (43%)males, with a median age of 37 years. The interval between COVID-19 infection symptoms and the onset of hypophysitis ranged from 2 to 3 weeks. Initial symptoms included frontal headache in 4 (57%) cases and polyuria and polydipsia in 3 (43%)cases. Anterior or posterior hypopituitarism was observed in 6 (85%)patients. Radiological findings varied: 2 (28.5%) cases showed panhypophysitis, 3 (43%) cases exhibited gland enlargement with homogeneous contrast enhancement on magnetic resonance imaging (MRI), 1 case involved the loss of the posterior pituitary bright spot, and 1 case involved pituitary apoplexy/enlargement of the gland and infundibulum. No pituitary biopsies were performed. Four (57%) patients received glucocorticoid (GC) treatment. Long-term follow-up was documented in only one case, a 16-year-old female followed for 2 years reporting complete clinical and radiological resolution. Although rare, hypophysitis related to COVID-19 is documented in the literature exhibiting distinct characteristics such as a homogeneous gender prevalence, an average age of onset around 35 years, and primary symptoms of headache, polyuria, and polydipsia which are indicative of angiotensin-vasopressin deficiency. This is in contrast with primary autoimmune hypophysitis characterized by a female prevalence and typical symptoms with headache and visual impairment. Longer-term follow-up of these patients is needed to better understand the potential lasting impact on pituitary function and radiological improvement. Future research should also explore the presence of anti-pituitary antibodies and the other possible pathophysiological mechanisms potentially involved in these cases.

6530 A Case of Lymphocytic Hypophysitis Followed by Acromegaly

Abstract Disclosure: L. Medina Mora: None. S. Htoo: None. A. Sanchez Ruiz: None. M. Harshan: None. M. Liu: None. Introduction: Acromegaly, a disorder with an estimated incidence of 0.28-0.4 cases per 100,000 individuals, is characterized by overproduction of growth hormone. Features include acral enlargement, frontal bossing, macrognathia, headaches, and hyperhidrosis. Comorbidities include hypertension, sleep apnea, type 2 diabetes, and cardiomyopathies. Hypophysitis, with an incidence of 1 in 9 million individuals, is an even rarer condition that involves pituitary gland inflammation. It can often lead to hormonal dysfunction and compression of surrounding structures. It is extremely rare for both acromegaly and hypophysitis to occur in the same individual. In this case report, we present a patient who developed lymphocytic hypophysitis followed by acromegaly. Case Report: A 58-year-old woman with a history of hypertension and lymphocytic hypophysitis (discovered during a workup of headaches without hormone derangement) returned to the clinic two years after complaining of progressive enlargement of her hands and feet, fragmented sleep, insomnia, and coarsening of facial features. She was found to have elevated IGF-1 (886 ng/mL; reference range: 48-235 ng/mL) and growth hormone levels (86.9 ng/mL; reference range: 0.12-9.88 ng/mL). An MRI showed a 2.9 x 3.2 x 3.8 cm suprasellar/sellar mass causing pressure on the optic chiasm, hypothalamus, third ventricle and midbrain. The patient underwent transsphenoidal resection (TSR), which was incomplete because the tumor was located behind the pituitary gland, followed by a right craniotomy to remove the remaining tumor. The tumor specimen stained positive for GH and PIT 1, exhibiting elevated proliferative indices (>2 mitotic figures per 10HPF, Ki-67 20%) and p53 labeling (5%). After the surgery, the patient's IGF-1 and GH levels normalized. However, her postoperative course was complicated by third cranial nerve palsy, diabetes insipidus, hypothyroidism, and secondary adrenal insufficiency. Discussion: Although TSR is the first-line treatment for most patients with acromegaly, it may not always result in a complete cure, as almost 50% of patients with macroadenomas do not achieve full surgical recovery. For persistent disease, medical therapy or transcranial surgery may be required. The tumor in this case was atypically proliferative, which was likely why GH and IGF-1 levels rose rapidly, manifesting in acromegalic symptoms in our patient two years after diagnosis of lymphocytic hypophysitis. The natural history of hypophysitis typically progresses from inflammation to fibrosis and subsequently to atrophy of the pituitary cells. This atrophy may cause changes in regulatory hormones that promote tumorigenesis. Therefore, hypophysitis may stimulate adenoma formation leading to acromegaly. More research is needed to characterize the relationship between these two rare entities. Presentation: 6/2/2024

8264 An Interesting Case of Hypophysitis in a Young Woman

Abstract Disclosure: A. Garcia: None. R. Sharma: None. C.M. Knight: None. Background Hypophysitis is an uncommon disorder and presents with clinical signs and symptoms along with biochemical abnormalities. Herein, we present a case of hypophysitis that responded well to high dose steroids. Case An 18 y.o black, adopted woman presented to hospital with complaints of headache and vision disturbances. Endocrinology was consulted for pituitary macroadenoma. Symptoms started a month prior. She had extensive work-up at an outside hospital including brain imaging, CSF analysis, and bloodwork. No definitive diagnosis was made and she was sent home on topiramate. Her symptoms continued to worsen prompting her to seek another opinion. No family history as she is adopted. She has a history of depression controlled with medication. MRI Brain showed 1.8x1.1x1.6 cm T2-enhancing mass with suprasellar extension deforming the midline optic chiasm. Initially, a diagnosis of macroadenoma was made and Endocrinology and Neurosurgery services consulted. Patient denied galactorrhea, menstrual abnormality, polyuria, polydipsia, cold intolerance, orthostasis, or weight gain. Bloodwork was significant for low TSH (0.045 uIU/ml; normal 0.35-4.94), low free T4 (0.58 ng/dl; normal 0.76-1.79). Thyroid functions were normal approximately one year prior. Cortisol was very low at 1.8 mcg/dL and ACTH inappropriately low-normal at 12 pg/ml (normal 6-50). LH and estradiol were low, while FSH was low normal. Prolactin, GH, IGF-1, sodium, glucose and creatinine were normal. Endocrine reviewed the previous MRI brain done four weeks ago that was reported as normal. Discussion with previous outside hospital radiologist suggested that pituitary was indeed not normal but was fuller with convexity towards chiasm although no definitive adenoma was found. Since it is unlikely that such adenoma would develop over 4 weeks, Endocrinology reached out to our radiologist who assessed this as pituitary enlargement due to likely hypophysitis, especially when compared to imaging 4 weeks ago. Further work up showed mildly-elevated ESR, and normal ACE, dsDNA, ANA, and Sjogren’s antibody levels. Tests for pregnancy, Lyme disease, tuberculosis, EBV and syphilis were negative. SARS-CoV-2 was negative for COVID. IgG4 levels were normal. CSF analysis was normal. She was started on levothyroxine and high-dose corticosteroids with improvement in her symptoms. Repeat imaging after 5 days of corticosteroids showed about 30% decrease in pituitary size. A diagnosis of likely lymphocytic hypophysitis was made and pituitary surgery averted for time being. Conclusion We present a case of possible lymphocytic hypophysitis in a young woman who avoided pituitary surgery due to diligent history and examination, in addition to a multidisciplinary team approach. It is very important to have prompt multidisciplinary approach if there is any doubt about a diagnosis as in this case. Presentation: 6/3/2024

8110 Lymphocytic Hypophysitis secondary to a ruptured Rathke’s Cleft Cyst complicated by post surgical recurrence: A rare phenomenon

Abstract Disclosure: M.S. Maharaul: None. F. Thelmo: None. I. Ahmed: None. Introduction: Lymphocytic hypophysitis secondary to ruptured Rathke’s cleft cyst (RCC) is a rare entity. Rathke’s cleft cysts are benign fluid-filled intra-sellar cysts that originate from the remnants of Rathke’s pouch and contain mucoid material. Most are asymptomatic; some may get symptomatic during cyst expansion and rupture releasing liquid content and trigger local inflammation. Surgical resection followed by glucocorticoids is usually curative. Case: A 42-year-old female presented to the hospital with one week history of right sided frontal headache associated with blurred vision in right eye. MRI Brain showed a 15 mm complex cystic lesion in the sella with suprasellar extension associated with peripheral calcifications. On admission, endocrine laboratory investigations including pregnancy test were normal. Ophthalmic testing did not reveal any acute abnormalities. Transsphenoidal surgery was performed for tumor resection. Pathology examination revealed infiltration of massive lymphocytes, macrophages, plasma cells, and eosinophils that were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe. She was started on glucocorticoids and discharged home. Rheumatology and Infectious diseases workup were unrevealing. On follow up 3 weeks later, she had self-discontinued steroids. The following week, she presented to the emergency room again with a right sided headache and blurred vision. MRI Brain revealed a 16 mm recurrent inflammatory mass lesion in the sella. Endocrine panel demonstrated an 8 am serum cortisol level of 7.4 mcg/dl, ACTH 20 pg/ml, FSH 6.2 mIU/ml, LH 4.9 mIU/ml, free T4 1.1 ng/dl and prolactin 8 ng/ml. She underwent transsphenoidal resection of the mass again and was restarted on glucocorticoids. This time pathology examination revealed an epithelial lined cyst most compatible with Rathke’s cleft cyst. She continued to remain on a glucocorticoid taper during the follow up period. On re-evaluation, her endocrinology laboratory investigations continued to show a deficiency of gonadotropins for which she is following up with OBGYN, but the remaining pituitary hormones were all within normal limits. Conclusion: Rathke’s Cleft Cysts (RCCs) should be in the differential diagnoses for evaluation of hypophysitis. There have only been a handful of cases in the literature of hypophysitis associated with a ruptured RCC, and only one case of recurrence after surgical debulking. This case provides an insight into the clinical behavior, diagnosis, and timely management of lymphocytic hypophysitis due to a ruptured Rathke’s cleft cyst and management post-recurrence. Presentation: 6/3/2024

6937 A Rare Case of Pembrolizumab-induced Multiple Endocrinopathies Presenting with Acute Adrenal Crisis Secondary to Isolated ACTH Deficiency - A Case Report

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) that blocks programmed cell death receptor 1 (PD-1) which took a massive leap in the oncology world. However, we are still understanding more about its immune-related adverse events (irAEs). Here we report a case of adrenal crisis due to pembrolizumab-induced hypophysitis and adrenalitis. Case Description: A 74-year-old male with a history of left renal cell carcinoma post left nephrectomy 5 years ago, complicated with lung metastasis for which Pembrolizumab was started. 5 months after, patient developed hypothyroidism and was started on Levothyroxine. 3 months later, Patient presented with lethargy and hypotension. Physical exam revealed hypotension (MAP of 55), fever, and acute encephalopathy. AM cortisol 4.2 ug/dL, Patient was started on IV pressors and a stress dose of Hydrocortisone. Hemodynamics improved, and Hydrocortisone was tapered down. ACTH stimulation test revealed a subnormal response of cortisol 0.2, 1.7, and 2.7 ug/dL at 0, 30, and 60 minutes respectively in the setting of very low ACTH of < 1.5 pg/ml, other pituitary hormones were checked, revealing normal insulin-like growth factor was 116 ng/mL, LH 15.29 mIU/mL, and FSH 27.45 mIU/mL. TSH was high 15 mIU/mL and free T4 was 1.4 ng/dl, levothyroxine dose was increased, and hydrocortisone was maintained at 10 in am and 5 in pm with excellent response. Discussion:ICIs inhibit the immunological pathways that control T-cell activation, leading to multiple immune-related endocrinopathies. Thyroiditis is the most reported one (30%), though anti-PD1-induced hypophysitis is exceptionally rare (< 1%). To date, the pathophysiology of pembrolizumab-induced central AI is not clearly understood, it’s presumed that it causes lymphocytic hypophysitis often presenting with isolated ACTH deficiency. Also, Pembrolizumab-induced primary adrenal insufficiency has seldom been reported and not yet understood, interestingly, anti-steroidogenic enzyme antibodies were absent in those few most reported cases which suggests a different mechanism compared to traditional primary AI. We suggest that our patient had combined primary and secondary adrenal insufficiency based on ACTH stim test result with very low cortisol responses in the setting of very low ACTH, which we believe is what led to such severe presentation of adrenal crisis. Diagnosis of PD1-induced AI can be challenging due to the overlapping of advanced malignancy and AI presentation. A higher level of suspicion is prompted especially in patients who experienced other endocrine irAEs (as our patient who had PDL-1-induced hypothyroidism). We present this case to shed light on this rare yet potentially fatal endocrine adverse event that can be reversed by prompt diagnosis and timely management due to the increasing use of pembrolizumab. More cases are needed for a better understanding of such a rare adverse event. Presentation: 6/2/2024

7102 Pituitary Apoplexy with Eventual Complete Tumour Involution

Abstract Disclosure: A. Ng: None. R. Lai: None. Pituitary apoplexy is an endocrinological emergency resulting from infarction or haemorrhage of the pituitary gland. We present a case of pituitary apoplexy from a non-functioning pituitary macroadenoma, complicated by pituitary insufficiency and subsequent tumour involution. An 80-year-old gentleman presented to the Emergency Department with sudden severe headaches and persistent vomiting and admitted for further evaluation. Computed tomography (CT) imaging of the brain showed a prominent pituitary gland and magnetic resonance imaging (MRI) confirmed a large sellar hyperintense lesion containing blood and proteinaceous material. It measured 1.6 cm by 1.2 cm by 1 cm and indented the optic chiasm. CT angiography did not reveal any aneurysms or intracranial haemorrhage. There were no neurological or visual field deficits at presentation. There was no indication for surgery upon neurosurgical consultation. Initial evaluation of the pituitary axis was consistent with central hypocortisolism (cortisol 75 nmol/L, adrenocorticotropic hormone 1.4 pmol/L [reference range (RR) 1.6-13.9]) and hypoprolactinaemia (prolactin 56 mIU/L, RR 73-351). Luteinising hormone levels were < 1 IU/L (RR 1-9); follicle stimulating hormone levels were 3 IU/L (RR 1-19) and testosterone levels were < 1 nmol/L (RR 5 to 30) as the patient was on androgen deprivation therapy for prostate cancer. Hydrocortisone was started and he was monitored for development of frank diabetes insipidus. He did not require regular desmopressin. He later developed anti-diuretic hormone mediated hyponatraemia (serum sodium nadir of 125 mmol/L, serum osmolality 275 mmol/kg, urine osmolality 390 mmol/kg) that was managed with fluid restriction and solute loading. He also developed central hypothyroidism on day 19 of admission (free thyroxine 11 pmol/L, thyroid stimulating hormone 0.49 mIU/L, RR 0.45-4.5) and oral levothyroxine was started. He was discharged with oral hydrocortisone and levothyroxine replacement. A repeat MRI of the pituitary 2 months later showed complete resolution of the mass and resolution of the mass effects. He was kept on oral hydrocortisone and levothyroxine replacement with regular follow-up.Most pituitary macroadenomas are non-functional, and can present with complications of apoplexy, mass effects or hormonal disturbances. However, the natural history of non-functional macroadenomas is not well known as most are operated on. Spontaneous regression of the tumour can rarely occur, notably in the setting of apoplexy and lymphocytic hypophysitis. Recovery of the pituitary axis may also accompany tumour regression. As spontaneous remission of pituitary macroadenomas may occur, close observation of tumours without visual field defects or significant mass effects may be an alternative to surgery. Presentation: 6/1/2024 12:15:00 PM

7815 Pembrolizumab-Induced Autoimmune Hypophysitis with “Isolated” ACTH Deficiency: Need for Heightened Awareness and Action Among Medical Fraternity

Abstract Disclosure: S. Shankar: None. S.S. Sundar: None. M.S. Vaishnav: None. L. Lekkala: None. K. Thummala: None. S. Srikanta: None. T. Deepak: None. R.B. Vijay: None. K. Muniraj: None. V. Nath: None. C. Siddlingappa: None. P. Ravikumar: None. M.D. Chitra: None. Introduction: Autoimmune hypophysitis caused by immune checkpoint inhibitors [ICIs; anti-CTLA-4 (Ipilimumab alone 7.9%), anti-PD-1 (Pembrolizumab alone 1.7%; nivolumab alone 0%)] are being increasingly documented, with anterior hypopituitarism affecting corticotrophs more commonly than thyrotrophs and gonadotrophs (large time span of onset; different recovery patterns). Clinical Case 2021 Sep Age 65 years (type 2 diabetes, hypertension). Renal Cell Carcinoma S/P radical nephrectomy. 2023 Jul PET-CT= Metastatic pleuropulmonary nodules. Four admissions to Specialist Oncology Hospital [Four 2 weekly cycles of Inj Pembrolizumab 200 mg (with Tab Axitinib 10 mg/day)]. After first cycle: progressive fatigue, body aches, drowsiness. S Sodium= Pre-pembrolizumab= 137 mEq/L (135-145); Post-pembrolizumab= 124, 134, 132, 124; T3= 1.63 to 0.60 to 1.24 to 1.35 ng/mL (0.97-1.69); T4= 6.83 to 4.93 to 10.44 to 11.44 mcg/dL (5.53-11); TSH= 10.46 to 6.28 to 5.39 to 9.48 mIU/mL (0.46-4.68); S Cortisol 8 am= 1.54 mcg/dL (5-25); S Potassium= 4.59 mEq/dL (3.5-5.1)]. One episode of loss of consciousness; EEG= abnormal; MRI Brain= normal. During every hospital admission, oncology, medical, endocrinology and nephrology teams attributed the same to “illness” (no specific diagnosis) and provided symptomatic treatment (IV 3% saline, tolvaptan and sodium bicarbonate tablets).2023 Nov Medicine: Very severe nausea, anorexia, generalised weakness, myalgia, hiccoughs, and inability to walk. Frustrated family members sought admission in “new” General Hospital. S Sodium= 119, 120; S Potassium= 4.8; S Creatinine= 1.67 mg/dL (0.7-1.3); S Uric acid= 4.5 mg/dL (4.40-7.60); Urine spot Sodium= 84 mmol/L; ESR= 144 mm. Endocrinology: S Cortisol 8 am= 0.09 mcg/dL;S Cortisol post 250 mcg Inj Synacthen= 3.76 (>20);Plasma ACTH= 5.4 pg/ml (9-52). S T3= 1.35; S T4= 11.44; S TSH= 9.48; LH= 3.61mIU/mL (1.5-9.3); FSH= 1.4mIU/mL (1.4-18.1); PRL= 30.1 (2.6-13.3); Testosterone total= 314 ng/dL (241-827); TPO antibodies negative. MRI-Pituitary: Partial empty sella; infundibulum neurohypophysis normal; mild asymmetric enhancement (5.5 mm) left cavernous sinus. Treatment: Tab Hydrocortisone 25 mg/day, with complete clinical and biochemical response [Suggestion of gonadotroph dysfunction and partial recovery of thyrotrope dysfunction/ injury. Hence, not on thyroxine replacement]. Clinical Lessons: Mechanisms for differential cellular vulnerability for ICI induced autoimmune pathologies [thyroid (destructive versus stimulatory), islet beta cells, adrenal cortical cells, various anterior pituitary cells (corticotrophs vs thyrotrophs and gonadotrophs] need elucidation. Specific molecular and cellular immunopathogenic pathways in different autoimmune endocrinopathies appear distinct and disparate. Presentation: 6/2/2024

7480 Isolated IgG4-Related Infundibulo-Hypophysitis

Abstract Disclosure: M. Allen: None. R.T. Beck: None. N.T. Zwagerman: None. R.J. Ryzka: None. D. Coss: None. A. Fisco: None. A.G. Ioachimescu: None. Background: 130 cases of IgG4-related hypophysitis (IgG4-RH) have been reported, usually in context of multi-organ IgG4-disease (e.g., siladenitis, pancreatitis, retroperitoneal fibrosis). Among patients with IgG4-disease, up to 5% develop hypophysitis. Presentation entails mass effects, AVP-D and anterior hypopituitarism.Case report: A 72-year-old man with history of hyperlipidemia presented with gradual decrease in strength, energy, appetite, libido, and depressed moods. Laboratory tests (8 AM) indicated undetectable AM cortisol, ACTH 6.8 pg/mL (7.2-63.3), TSH 0.20 mIU/mL (0.35-4.94), free thyroxine 0.64 ng/dL (0.7—1.48), prolactin 50.9 ng/mL (3.46-19.4), IGF-1 57 ng/mL (53-222), testosterone 7 ng/dL (240-950), LH 0.16 mIU/mL (0.57-12.07), and FSH 1.5 mIU/mL (1.0-12). MRI revealed a homogenously enhancing nodular suprasellar mass adjacent to the hypothalamus (0.8x0.7x0.8 cm) and contiguous with a 0.5 cm area of infundibular thickening. Neuro-ophthalmological evaluation was normal. In absence of mass effects, patient was monitored conservatively and treated with hydrocortisone, levothyroxine and testosterone replacement. Six months later, the mass enlarged to 1.2x0.8x1.1 cm. Patient underwent a transsphenoidal biopsy which revealed a dense fibrous mass with lymphoplasmacytic infiltration. Most cells stained for CD138 and IgG4. Postoperatively, serum IgG and complement levels, inflammatory markers, hemogram, serum protein electrophoresis, amylase and lipase were normal. CT chest and abdomen and thyroid ultrasound were unremarkable. After 4 weeks of prednisone 40 mg daily, the nodular lesion significantly decreased on MRI (0.6x0.5x0.4 cm). Prednisone was gradually tapered to 5 mg daily over 3 months. After 2 months of physiologic prednisone therapy, imaging remained stable. During follow-up of 1.5 years, no systemic IgG-4 disease was apparent and patient remained on glucocorticoid, thyroid and testosterone replacement.Discussion: Suprasellar masses can be inflammatory, infiltrative, infectious or neoplastic. The possibility of IgG4-RH should be considered even in absence of IgG4 systemic disease, as it happened in our case. Primary involvement of the infundibulo-hypophysis was suggested by a retrospective review study that found isolated IgG4-RH in 41% specimens initially diagnosed as primary autoimmune hypophysitis. Our case maintained a good radiological response after prednisone taper to physiologic doses. Response to prednisone is generally good in IgG4-RH, but relapse can occur upon taper, and long-term studies are lacking. Conclusion: We present a histologically-confirmed case of isolated IgG4-RH presenting with clinical manifestations of anterior hypopituitarism. Diagnosis and management of IgG4-RH requires multidisciplinary collaboration (endocrinology, rheumatology, neurosurgery, neuropathology and neuroradiology). Presentation: 6/3/2024

Pituitary Dıseases and Care in Pregnancy

The pituitary gland causes very serious effects on the body thanks to the hormones it secretes. The main pituitary diseases are prolactinoma, acromegaly, lymphocytic hypophysitis, pituitary insufficiency (hypopituitarism), Cushing's syndrome and Sheehan's syndrome. Since pregnancy is rare in these diseases, the diagnosis is usually made in the pre-pregnancy period. A definitive diagnosis is made by means of disease-specific diagnostic tests accompanied by symptoms and findings seen in the pre-pregnancy period. Anatomical and physiological changes in the pituitary gland during pregnancy cause difficulties in the diagnosis of pituitary diseases. For this reason, the care to be given in pituitary diseases should be carried out effectively from the pre-pregnancy period. These diseases cause serious complications for both mother and foetus and require a multidisciplinary care approach. Midwives and other health professionals, who have a major role in the multidisciplinary team providing care, should be familiar with the symptoms, diagnosis and treatment methods of pituitary diseases and an individualised care management specific to the disease should be carried out.

Hypophisitis in pregnant women with persistent diabetes insipidus in the outcome

Autoimmune/lymphocytic hypophysitis is one of the rare causes of central diabetes insipidus in adults and is most common among women in the second or third trimester of pregnancy. Numerous studies have shown that lymphocytic hypophysitis is characterized by a very variable clinical signs with the development of neurological symptoms, visual disturbances and hypopituitarism with partial or complete loss of pituitary function, as well as a number of features in magnetic resonance imaging (MRI). Isolated lymphocytic indibuloneurohypophysitis occurs in fewer cases and involves the posterior lobe and stalk of the pituitary gland with a clinical presentation of diabetes insipidus. The above clinical case describes the development of hypophysitis in a pregnant woman with a predominant lesion of the posterior pituitary gland and an outcome in diabetes insipidus, which persists 6 years after pregnancy and childbirth. In the article some aspects of the differential diagnosis of diabetes insipidus in pregnant women, as well as instrumental diagnosis and treatment approaches of hypophysitis are discussed.

Maternal Death Due to Lymphocytic Hypophysitis: A Case Report

Lymphocytic hypophysitis is a rare condition characterized by lymphocyte and plasma cell infiltration, leading to fibrosis and functional impairment of the pituitary gland. Although lymphocytic hypophysitis is associated with pregnancy, its diagnosis may be challenging in pregnant women owing to unclear symptoms of pituitary dysfunction. Lymphocytic hypophysitis can lead to serious complications, including a sudden death; however, no case of maternal death has been reported in Korea. This study presents a case of maternal death after childbirth. The deceased had a history of hypertension, obesity, hypothyroidism, and gestational diabetes and died suddenly the day after the emergency cesarean section. Notably, no other pregnancy-related complications were observed. Histopathological examination of the pituitary gland confirmed lymphocytic hypophysitis. This case report emphasizes the requirement of clinical awareness and underscores the significance of examining the pituitary gland during autopsy investigations of maternal deaths.

Evaluation and follow-up of patients diagnosed with hypophysitis: a cohort study.

Primary hypophysitis might be challenging to diagnose, and there is a lack of evidence regarding optimal treatment strategies due to rarity of the disease. We aim to investigate the clinical features and compare the outcomes of different management strategies of primary hypophysitis in a large group of patients recruited on a nationwide basis. A retrospective observational study. The demographic, clinical, and radiologic features and follow-up data were collected in study protocol templates and analyzed. One hundred and thirteen patients (78.8% female, median age: 36 years) were included. Lymphocytic (46.7%) and granulomatous hypophysitis (35.6%) were the prevailing subtypes out of 45 patients diagnosed after pathologic investigations. Headache (75.8%) was the most common symptom, and central hypogonadism (49.5%) was the most common hormone insufficiency. Of the patients, 52.2% were clinically observed without interventions, 18.6% were started on glucocorticoid therapy, and 29.2% underwent surgery at presentation. Headache, suprasellar extension, and chiasmal compression were more common among glucocorticoid-treated patients than who were observed. Cox regression analysis revealed higher hormonal and radiologic improvement rates in the glucocorticoid-treated group than observation group (hazard ratio, 4.60; 95% CI, 1.62-12.84 and HR, 3.1; 95% CI, 1.40-6.68, respectively). The main indication for surgery was the inability to exclude a pituitary adenoma in the presence of compression symptoms, with a recurrence rate of 9%. The rate of spontaneous improvement might justify observation in mild cases. Glucocorticoids proved superior to observation in terms of hormonal and radiologic improvements. Surgery may not be curative and might be considered in indeterminate, treatment-resistant, or severe cases.

Arginine vasopressin deficiency onset after COVID-19 vaccination with positive anti-rabphilin-3A antibodies: a case report and literature review

BackgroundArginine vasopressin deficiency (AVP-D) can occur due to various conditions, so clarifying its cause is important for deciding treatment strategy. Although several cases of AVP-D following coronavirus disease 2019(COVID-19) infection or COVID-19 vaccination have been reported, the diagnosis of the underlying disease has not been reported in most cases.Case presentationA 75-year-old woman who presented with polydipsia and polyuria 9 weeks after contracting COVID-19 and 5 weeks after receiving the SARS-CoV-2 vaccination, leading to the final diagnosis of AVP-D 8 months after the first appearance of symptoms. Interestingly, pituitary magnetic resonance imaging (MRI) still revealed stalk enlargement frequently observed in patients with SARS-CoV-2 vaccination-induced AVP-D. Although this finding could not rule out any malignancies, we additionally measured anti-rabphilin-3A antibodies, a known marker for lymphocytic infundibulo-neurohypophysitis (LINH), and found that the results were positive, strongly suggesting LINH as the cause of this disease. Thus, we avoided pituitary biopsy. At the follow-up MRI conducted 12 months after the initial consultation, enlargement of the pituitary stalk was still observed.ConclusionWe experienced a case with LINH probably induced by SARS-CoV-2 vaccination. In SARS-CoV-2 vaccination-related LINH, unlike typical LINH, there is a possibility of persistent pituitary stalk enlargement on MRI images for an extended period, posing challenges in differential diagnosis from other conditions. Pituitary stalk enlargement and positive anti-rabphilin-3A antibodies may help in the diagnosis of AVP-D induced by SARS-CoV-2 vaccination.

Pregnancy in Autoimmune Hypophysitis: Management of a Rare Condition.

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

Pituitary Complications of Checkpoint Inhibitor Use.

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

Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology. It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress. Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.

Acquired isolated ACTH deficiency co-occurrence with breast cancer irrespective of paraneoplastic syndrome: coincidence or inevitability.

A 52-year-old female patient with breast cancer presented with a history of fatigue and malaise 1 year prior. She was diagnosed with isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) on endocrinological examination. Her pituitary gland showed normal morphology. Paraneoplastic IAD associated with breast cancer was suspected; however, immunofluorescence staining revealed no ectopic ACTH or proopiomelanocortin expression in the tumor tissue. Subsequently, the patient was diagnosed with idiopathic acquired IAD concurrent with breast cancer, ruling out paraneoplastic syndrome. Although malignancy should be considered a potential cause of IAD, not all patients with concurrent IAD and malignancy necessarily develop paraneoplastic syndrome. Several adrenal insufficiency symptoms are similar to the nonspecific symptoms associated with malignancies, and therefore, the diagnosis of IAD remains challenging, especially in patients with cancer. When we encounter a case of IAD accompanied by a malignant tumor, it is important to suspect that paraneoplastic IAD, a novel clinical condition as secondary hypophysitis, may be the etiologic agent. Although malignant tumours should be considered a potential cause of IAD, not all patients with concurrent IAD and malignancy necessarily develop paraneoplastic autoimmune hypophysitis.

Utility of F18-FDG PET/CT in the Evaluation of Pituitary Uptake

Abstract Introduction Pituitary adenoma is the most common disease that affects the gland and may be classified as functional/nonsecretory tumors. Inflammatory/infective causes may also affect the pituitary gland. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (F18-FDG PET/CT) may have an incremental value in assessing these lesions and in determining their clinical significance. Aim This article assesses the utility of F18-FDG PET/CT in detecting and determining clinical profile of pituitary lesions with abnormal uptake. Methodology Retrospective analysis of all patients who underwent F18-FDG PET/CT from January 2015 to January 2023 was done. Those with abnormal pituitary uptake (standardized uptake value [SUV] > 2.5) were included in the study. SUV value along with relevant anatomical details, biochemical parameters, histopathological details, and follow-up imaging were analyzed. Results Among 15,085 studies, a total of 36 patients (21 males/15 females, average age 47.36 years, range: 17–75 years) with pituitary uptake (0.23%) were included. Out of 36 patients, causes are primary pituitary tumor (21/36, 58%), tubercular hypophysitis (3/36, 8%), lymphocytic hypophysitis (2/36, 6%), lymphomatous involvement (2/36, 6%), autoimmune hypophysitis (1/36, 3%), questionable significance/incidental (4/36, 11%), and metastasis (3/36, 8%)—one each from neuroendocrine tumor ileum, chondrosarcoma, and adenocarcinoma lung. There was no difference in the SUV range between the different etiologies.Among 21 patients with pituitary tumor, biochemical evaluation was done in 19 patients. Two patients were lost to follow-up and did not have biochemical evaluation. Among them, 8 underwent endoscopic transsphenoidal radical excision and 1 patient had PET-CT-guided stereotactic radiosurgery alone. In another 8 patients who had prior endoscopic transsphenoidal radical excision, uptake was noted as residual lesion on PET-CT. Of them, 3 underwent subtotal excision and 5 had PET-CT-guided stereotactic radiosurgery. Biopsy was done in 14 patients, of which 11 were macroadenoma and 3 were microadenoma. Overall, magnetic resonance imaging (MRI) brain was performed in 22 of them and the findings were concordant with F18-FDG PET/CT. Conclusion F18-FDG PET/CT is a useful modality in the evaluation of pituitary uptake. It has an incremental value along with MRI brain and biochemical parameters and is useful for follow-up. Due to its high diagnostic accuracy, it is particularly useful in those with suspected residual/recurrent adenomas.

OTHR-24. CLINICAL COURSE OF ISOLATED PITUITARY STALK THICKENING IN PEDIATRIC PATIENTS AND RISK FACTOR FOR NEOPLASTIC ETIOLOGY: A SINGLE INSTITUTIONAL EXPERIENCE

Abstract BACKGROUND The incidence of pituitary stalk thickening (PST) has increased in recent years due to the increased utilization of diagnostic MRI of the brain. The etiology of PST includes germ cell tumors, Langerhans cell histiocytosis (LCH), and lymphocytic hypophysitis, among others. The clinical significance of PST, appropriate diagnostic workup, and clinical course for these patients is not well documented. We report our institutional experience with patients presenting with PST. METHODS After IRB approval, we reviewed lists of patients discussed in pediatric tumor boards from 2003-2023 to identify patients with PST. We excluded patients with other significant intracranial masses from our analysis. We followed the clinical course of these patients to collect applicable data. RESULTS A total of 20 patients were identified with PST, five patients were excluded due to additional MRI findings. The median age of diagnosis with PST was 14 years; 60% of cases were female. Seven patients had diabetes insipidus (DI), and five patients had other endocrinological abnormalities. Initial diagnostic workup included serum and CSF tumor markers (AFP, B-HCG), skeletal survey, CBC, and CMP. With this initial workup, no patients were diagnosed with neoplasm. All patients were followed with serial MRIs. Four patients (26.6%) displayed progression of PST, warranting biopsy. The median time from diagnosis to biopsy was seven months (range 4-26 months). Among four patients with biopsy, two had LCH, one had germinoma, and one inconclusive result. Among those diagnosed with neoplasm, 100% of them had DI. Three patients had complete resolution of PST during the follow-up period. Eight patients had stable PST during the median follow-up period of 19.5 months (Range 3-59 months). CONCLUSIONS Most isolated PST among pediatric patients remained stable during the follow-up period. The risk for neoplastic process was high among patients with increasing thickening of pituitary stalk and DI.

Lymphocytic hypophysitis, with diabetes insipidus

Lymphocytic hypophysitis, with diabetes insipidus