Enlargement Of Pituitary Gland Research Articles

PMON322 Gigantism in 13-Year-Old Male With Pituitary Tumor

Abstract Background Pituitary gigantism is caused by excess growth hormone [GH] secretion from the pituitary gland when the growth plates are open leading to excessive linear growth and tall stature in the pediatric population. It is extremely rare with a reported incidence of 8 cases per million person-years. Clinical Case The patient is a 13-year-old male who presented with concerns of accelerated growth rate and tall stature. His father noticed the patient's tall stature when he passed his own height the last year. The patient was seen by his PCP who referred the family to pediatric endocrinology. His symptoms included snoring and bi-weekly headaches, but no vision changes. Review of his growth charts showed linear growth tracking at greater than the 95th percentile since the age of 9 years. His clinical features included large hands, large feet, prominent jaw, testicular volume >25 ml, tall stature [Ht > 99%, Z= +4.59 SD]. The patient's mid-parental height is 69.1 inches [175.5 cm] and the patient measured 76.6 inches [194.5 cm]. His predicted height was 7 feet 1.5 inches [217.2 cm] based on his bone age. His clinical features were strongly concerning for Gigantism. Initial labs showed IGF-1 of 924 ng/mL [168–576], prolactin of 20.1 ng/mL [2.8–11.0], and IGF-BP3 8.7 mg/L [3.1–9.5]. Cortisol, ACTH, TSH, FT4, LH, FSH, Testosterone were within normal limits. Bone age was concordant with chronological age. MRI showed enlarged pituitary gland measuring 1.3 cm in height, suspicious for macroadenoma. Cardiac evaluation including echocardiogram came back normal. GH suppression test resulted in a 2-hour GH level of 27.3 ng/mL [<1] and he was diagnosed with Gigantism due to GH-secreting pituitary tumor. The parents decided to consult neurosurgery team at a different facility, where transsphenoidal resection of the pituitary tumor was performed. He did not develop any postoperative complications, including Diabetes insipidus or any pituitary hormone deficiencies, and was discharged home shortly after. Follow-up MRI of the pituitary showed no evidence of residual tumor. Pathology of the macroadenoma expressed GH and prolactin on immunohistochemical stains and was negative for TSH, LH/FSH, and ACTH. Genetic studies obtained were negative, lowering the likelihood of inherited predisposition to endocrine neoplasms. The patient has remained well post-operatively and has been able to continue school and play basketball without issues. Conclusion Pituitary gigantism occurs in the pediatric population prior to skeletal epiphyseal closure and is caused by GH excess. Initial screening tests should evaluate for pituitary function including IGF-1 and prolactin levels. The gold standard for diagnosing GH excess is the GH suppression test. Even though rare, it is important for clinicians to keep a high level of suspicion for quick recognition and management of overgrowth syndromes. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

OR08-5 Associations Between Signal Transducer and Activator of Transcription (STAT) Mutations and Galactorrhea

Abstract Background Prolactin (PRL) is responsible for the development of mammary glands and milk production. STAT1 and STAT3 are genes that express transcription factors that mediate PRL's intracellular signaling, but an association between their function and galactorrhea has not yet been identified. Here we describe three patients with somatic STAT mutations and galactorrhea. A 27-year-old woman with hyper-IgE syndrome (Job's Syndrome) due to a STAT3 deletion mutation (p.Val463del) associated with recurrent infections reported thin, white, bilateral discharge with breast manipulation beginning in adolescence. She did not have spontaneous leakage or pain. At presentation, PRL was slightly elevated to 27.9 (ref. 2.0-25.0 mcg/L) with otherwise normal levels of anterior pituitary hormones. She was not on any drugs known to cause hyperprolactinemia. MRI showed a 5×4 mm microadenoma without any mass effect. A 32-year-old woman also with Job's syndrome due to a heterozygous loss-of-function STAT3 mutation (p.R382Q) associated with recurrent infections and papillary thyroid cancer described unilateral, chronic, thin, white nipple discharge with light touch of her right breast for "as long as she could remember." She had a history of breast abscesses, but at presentation there was no evidence of abscess or infection. PRL was 15.1 mcg/L, and other anterior pituitary hormones were normal. MRI showed a structurally normal pituitary. A 22-year-old woman with a STAT1 activating mutation (p.E235A) associated with recurrent infections, autoimmune hypothyroidism, T1DM, and hypogonadotropic hypogonadism requiring pubertal induction at age 12y reported bilateral galactorrhea starting at age 18y. A white, milky discharge could be expressed with light manipulation, but no discharge was produced spontaneously. PRL was 16.2 mcg/L with serial dilution and has consistently been in the reference range. Anterior pituitary evaluation was normal except for elevated TSH of 12.5 (ref. 0.27-4.2) consistent with autoimmune hypothyroidism. MRI revealed a diffusely enlarged pituitary gland (12mm in the cranio-caudal dimension) without focal hypo-enhancement. Conclusions It is known that PRL signaling involves the JAK/STAT pathway, and an analysis of human milk cells showed upregulated STAT3 and downregulated STAT1 during lactation (PMID 26909879). These three cases provide clinical evidence for a mechanistic connection between STAT signaling and galactorrhea and suggest that STAT3 and STAT1 function in opposite directions to regulate lactation. In our cases, increased STAT1 or decreased STAT3 activity are associated with normal-PRL, inducible galactorrhea. Beyond understanding the specific intracellular signaling pathways leading to galactorrhea, these observations may be utilized for developing therapies for those with impaired lactation. Presentation: Saturday, June 11, 2022 12:30 p.m. - 12:45 p.m.

ODP292 A Xanthomatous Hypophysitis: Always Think Twice Before Pituitary Resection.

Abstract Background A xanthomatous hypophysitis is a rare form of primary hypophysitis common in females. Clinical case: A 47-year-old male was referred for pituitary adenoma resection. The patient presented with low libido and facial and body hair loss for 3 years. He reported increased thirst and nocturia for 2 years. 24-hr fluid intake showed 4,800 ml intake and 6,700 ml output. Physical examination revealed tanner 5 pubic hair with testicle size 12 ml bilaterally. He had a normal visual field. Laboratory testing revealed low morning total testosterone level of 108 ng/dL (241-872), low LH 0.39 mIU/mL (1.14-8.75) and low FSH 1.28 mIU/mL (1.37-13.58). Other pituitary hormones showed normal TSH 0.634 uIU/ml (0.35-4.9) with low free T4 0.64 (0.7-1.48), IGF-1 107 ng/mL (74-196), prolactin 10.92 mcg/mL (3.46-19.4), morning cortisol 8.9 mcg/dL (3.7-19.4). A 1 mcg ACTH stimulation test showed an inappropriate increase in cortisol level of 16.1 mcg/dL with baseline ACTH 28 pg/mL (0-46). Regarding polyuria, biochemical testing showed serum Na 148 mmol/L (136-145), Uosm 307 mOsm/Kg (50-1300), and Sosm 307 mOsm/kg (275-290). After the therapeutic trial with oral DDAVP, urine output significantly decreased. Subsequent tests showed serum Na 144 mmol/L, Uosm of 295 mOsm/kg, and Sosm of 278 mOsm/kg. The final diagnosis was hypopituitarism and central diabetes insipidus. MRI showed an enlarged pituitary gland with 2 decreased enhancing nodules in the post-contrast study of the anterior lobe measuring 4.2 and 6.7 mm in diameter. No stalk thickening was detected. There was no compression on adjacent organs. Since the pituitary lesions could not explain the hypopituitarism and DI. The surgery was postponed, and he underwent an endoscopic transsphenoidal biopsy. The procedure yielded a milky fluid content, and a circumferential dissection of a soft-yellow capsule was done. Pathology examination revealed a chronic hypophysitis with clusters of foamy macrophages. Immunohistochemistry showed positive for CD3, CD20, and CD138. A CD68 was positive in multiple clusters of foamy macrophages, while an IgG4 was negative. The final diagnosis is xanthomatous hypophysitis. The patient was treated with hormonal replacement therapy of levothyroxine, prednisolone, testosterone, and DDAVP. Until now, there are 36 cases in the literature reporting xanthomatous hypophysitis. The prevalences of hormonal deficits are 36.1% adrenal insufficiency, 42.4% central hypothyroidism, 54.6% central DI, 36.4% hypogonadism, 63.6% GH deficiency, and 54.6% hyperprolactinemia. The common MRI characteristic is a cystic mass with a ring or peripheral enhancement. Pituitary stalk thickening is shown in 50% of cases. Conclusion This clinical case demonstrated the rare entity of xanthomatous hypophysitis presenting with secondary AI, hypogonadotropic hypogonadism, central hypothyroidism, and DI. The discrepancy between clinical history and the MRI findings was a clue for pituitary biopsy leading to the final diagnosis and avoidance of unnecessary surgery. Presentation: No date and time listed

PMON80 Case of Cushing's Disease That Presented as Diabetic Ketoacidosis and Successfully Treated With Stereotactic Radiosurgery During the COVID-19 Pandemic

Abstract Background Although Cushing's disease is known to impair glucose metabolism, diabetic ketoacidosis (DKA) as its initial presentation has been reported in only a few case reports. The first-line treatment for Cushing's disease is transsphenoidal surgery, but safety concerns during the COVID-19 pandemic has led to the utilization of other treatment options. We present a case of Cushing's disease that presented initially as DKA and was successfully treated with stereotactic radiosurgery. Case Presentation Our patient was a 36-year-old female known to have diabetes mellitus and hypertriglyceridemia for one year. She presented with one-week history of generalized weakness, blurring of vision, and elevated blood pressure. Her blood glucose level was high at 523 mg/dL, associated with ketosis and metabolic acidosis. She was diagnosed with diabetic ketoacidosis which resolved after hydration and intravenous insulin administration. Further history revealed that she has been experiencing progressive weight gain and infertility for the past five years. She had cushingoid features including obesity, scalp hair thinning, moon facies, acne, hirsutism, and buffalo hump. Midnight salivary cortisol was high at 9.34 ng/mL (0.20-4. 00 ng/mL). Low dose dexamethasone suppression test showed an unsuppressed serum cortisol level at 31.2 mcg/dL (<1.8 mcg/dL). Adrenocorticotropic hormone (ACTH) level was high at 88.5 pg/mL (<46 pg/mL) and pituitary magnetic resonance imaging (MRI) showed an enlarged pituitary gland measuring 13.4 mm in the craniocaudal dimension with leftward displacement of the pituitary stalk. She was diagnosed with Cushing's disease and was initially advised transsphenoidal surgery. Due to concerns of COVID-19 transmission, the team and the patient decided to do stereotactic radiosurgery (SRS). The procedure was performed without complication. At 2 months follow-up, there was noted improvement of blurring of vision, normalization of cortisol level to 20.72 mcg/dL (4.30-22.40 mcg/dL), and a decreased ACTH level at 62.19 pg/mL. There was a 4 mm decrease in the craniocaudal dimension of the pituitary gland on repeat pituitary MRI. Thyroid stimulating hormone (TSH) level normalized from 0.209 to 0.647 uIU/mL (0.55-4.78 uIU/mL), and the glycohemoglobin decreased from 11.5% to 6.3%. Hypertension was controlled on one medication. Conclusion Stereotactic radiosurgery is usually reserved as a secondary option to transsphenoidal surgery. On average, normalization of cortisol levels after SRS takes 14 months. In our patient, the serum cortisol decreased to within normal levels at only 2 months after SRS. While a longer follow-up is desirable in order to assess the durability of control of hypercortisolemia, our case demonstrates that stereotactic radiosurgery is a safe and effective treatment option for Cushing's disease during the COVID-19 pandemic, when safety protocols and decreased hospital and patient resources might hinder the performance of transsphenoidal surgery. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Hypophysitis induced by anti-programmed cell death protein 1 immunotherapy in non-small cell lung cancer: Three case reports

Hypophysitis induced by programmed cell death 1 protein (PD-1) immune checkpoint inhibitors is rare and poorly described. We report three patients with non-small cell lung cancer who developed hypophysitis after anti-PD-1 immunotherapy. Both case 1 and case 2 presented with common symptoms of fatigue, nausea, and vomiting. However, case 3 showed rare acute severe symptoms such as hoarse voice, bucking, and difficulty in breathing even when sitting. Following two cycles of immunotherapy in case 3, the above severe symptoms and pituitary gland enlargement were found on magnetic resonance imaging at the onset of hypophysitis. These symptoms were relieved after 10 d of steroid treatment. Case 3 was the first patient with these specific symptoms, which provided a new insight into the diagnosis of hypophysitis. In addition, we found that the clinical prognosis of patients with hypophysitis was related to the dose of steroid therapy. Case 3 was treated with high-dose hormone therapy and her pituitary-corticotropic axis dysfunction returned to normal after more than 6 mo of steroid treatment. Cases 1 and 2 were treated with the low-dose hormone, and dysfunction of the pituitary-corticotropic axis was still present after up to 7 mo of steroid treatment. The clinical symptoms described in this study provide a valuable reference for the diagnosis and treatment of immune-related hypophysitis.

The Efficacy and Safety of Lumbar Accessed Catheter-Assisted Epidural Blood Patch in Cervical and Thoracic Cerebrospinal Fluid Leakage

To evaluate the clinical and radiological results of lumbar accessed catheter-assisted epidural blood patch (LACA-EBP) technique in treatment of spontaneous intracranial hypotension secondary to cervicothoracic cerebrospinal fluid leakage. Patients presenting with spontaneous intracranial hypotension where magnetic resonance imaging cisternography confirmed and localized the cerebrospinal fluid leakage at cervicothoracic levels were treated with LACA-EBP. Visual analog scale (VAS) score for headache at baseline, third day after treatment, and during long-term follow-up was used to assess the treatment response. Posttreatment VAS score ≤3 on the third day defined treatment success, and VAS score ≥4 indicated treatment failure. LACA-EBP was performed in 10 patients (7 females, 3 males) with a mean age of 38.4 ± 10.5 years. Orthostatic headache was the most common presenting symptom (10/10; 100%) followed by nausea (5/10; 50%). Pituitary gland enlargement was the most commonly observed finding on pretreatment cranial magnetic resonance imaging (9/10; 90%). On magnetic resonance imaging cisternography, 8 patients had cervical and/or thoracic fistulas, whereas 2 patients had multiple-level fistulas. LACA-EBP was successful in all patients with no complications. All patients showed a treatment response with a 72-hour VAS score ≤3. Follow-up VAS scores were available for 8 patients with a clinical follow-up duration of 1-74 months (median 7.5 months). During clinical follow-up, headache recurred in 2 patients. In our study cohort, LACA-EBP was a safe and efficacious technique in treatment of cerebrospinal fluid leakage at cervical and thoracic levels.

Pituitary Apoplexy: Risk Factors and Underlying Molecular Mechanisms.

Pituitary apoplexy is a rare syndrome, graded from asymptomatic subclinical apoplexy to a life-threatening condition due to pituitary ischemia or haemorrhage of an enlarged pituitary gland. The risk factors and the molecular underlying mechanisms are yet to be elucidated. We provide an overview of the general concepts, the potential factors associated with pituitary adenoma susceptibility for apoplectic events and the molecular mechanisms that could be involved such as HIF-1α/VEGF pathways and metalloproteinases activation, among others. The knowledge of the molecular mechanisms that could participate in the pathogenesis of pituitary apoplexy is crucial to advancement in the identification of future diagnostic tools and therapeutic targets in this rare but sometimes fatal condition.

Adult-onset Langerhans cell histiocytosis changing CNS lesion from pituitary to suprasellar extension.

SummaryLangerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of abnormal Langerhans cells in various tissues and organs, including bone, skin, the lungs, and the pituitary gland. Hypothalamic–pituitary lesions in LCH often cause central diabetes insipidus (CDI), but the natural course of LCH in the CNS remains to be elucidated. In this study, we report an interesting case of altered LCH lesions in the CNS from the pituitary to the hypothalamus in a 45-year-old woman. She developed symptoms of polyuria and was diagnosed with CDI with lymphocytic hypophysitis due to an enlarged pituitary gland with stalk thickening shown on MRI. Short-term glucocorticoid therapy cured pituitary enlargement, but serum prolactin levels gradually increased. Six years later, the immunohistological findings of a skin biopsy revealed positive for leukocyte common antigen, S-100, and CD1a expression, indicating a diagnosis of LCH. MRI revealed a new lesion in the hypothalamus without pituitary involvement, likely due to LCH. Chemotherapy improved LCH lesions both in the skin and hypothalamus, but therapy was stopped on the patient’s request. Although adult-onset LCH is rare, it should be considered as a differential diagnosis in cases of CDI as the primary disease. The clinical course in the present case indicated that LCH lesion was altered from pituitary to suprasellar extension; where such changes were observed, the possibility of LCH should be considered.Learning pointsDiagnosing the primary disease of CDI is challenging; therefore, careful observation is necessary in pathologically unknown cases.Enhanced MRI should be performed in cases with suspected hypothalamic lesions, such as elevated serum prolactin.Although adult-onset LCH is rare, it should be considered a differential diagnosis in cases of CDI as the primary disease.The direction of changing CNS lesion from pituitary to suprasellar extension might be a unique MRI finding in LCH.

Diferenciální diagnostika zvětšení hypofýzy

Enlargement of the pituitary gland is heterogenous in the etiology. Common causes of pituitary enlargement are physiological hypertrophy during pregnancy, primary and secondary tumors, autoimmune hypophysitis including side effects of anticancer therapy with check-point inhibitors. Terms like hypertrophy, hyperplasia, sellar expansion and hypophysitis are commonly used to describe enlargement of the pituitary gland on MR scan regardless its etiology. The most common pathology causing pituitary gland enlargement is pituitary adenoma. Magnetic resonance imaging can differentiate pituitary tumors from diffuse enlargement due to hypophysitis in most but not all cases. Changes on imaging during time or response to pharmacotherapy might help determine the final diagnosis in uncertain cases. We present a case report of a young woman with sellar expansion due to prolonged untreated peripheral hypothyroidism mimicking pituitary adenoma. Interdisciplinary cooperation of endocrinologist, radiologist and neurosurgeon is crucial in determining the diagnosis.

Cushing’s Disease of Unknown Etiology: A Clinical Case Report

Cushing’s disease (CD) remains a diagnostic and therapeutic challenge. Different subtypes may be recognized that will offer insight in this complex situation. We describe an atypical case that we assume is a common variation albeit with no previous formal description. A young female patient presented with minimal clinical features of CD, but increased adrenocorticotropic hormone (ACTH) and cortisol levels, with maintained circadian rhythm that was not suppressed either after the rapid dexamethasone or the prolonged low-dose dexamethasone tests, but suppressed with the prolonged high-dose dexamethasone test and presented a flat ACTH and cortisol response after the corticotropin-releasing hormone (CRH) test. A diffuse enlarged pituitary gland with thickened pituitary stalk was present and a mixed corticotroph adenoma was removed. CD persisted despite now normal pituitary morphology, except for pituitary stalk widening. Plasma levels of CRH were low and no abnormalities were found in the coding region or flanking introns of glucocorticoid receptor (GCR) gene ( NR3C1 ). Somatostatin receptors were not present in the octreoscan, and treatment with cabergoline or somatostatin analogs was ineffective. Morbidity and mortality are increased in CD even in patients successfully treated and in remission. Despite early success in over 80% of the patients, in the long term CD recurs in almost 50% of the patients. Defining subtypes of CD may help elucidate mechanisms of the disease. We propose a new variant that we assume is common. Furthermore adaptation to chronic hypercortisolism is present. J Endocrinol Metab. 2022;12(1):40-48 doi: https://doi.org/10.14740/jem784

Magnetic resonance imaging findings of intracranial hypotension.

This study aims to evaluate the differences in the sizes and configurations of various structures on brain MRIs of patients with intracranial hypotension (ICH) compared to normal individuals. The present study consisted of two study groups as 21 patients with intracranial hypotension and 21 healthy individuals. Cranial MRI findings of patients with intracranial hypotension were compared retrospectively with MRI findings of patients without any pathology. Pachymeningeal enhancement, mamillopontine distance, venous sinus diameters, transverse and straight sinus distension, pituitary gland enlargement, tonsillar herniation, bleeding (subdural, epidural), pontomesencephalic angle, lateral ventricular angle, and pituitary infundibular angle were evaluated on MRI. Intracranial hypotension developed spontaneously in 6 cases and secondary in 15 patients. Diffuse pachymeningeal enhancement was observed in all intracranial hypotension cases. In addition, transverse sinus distension was observed in 19 cases, straight sinus distension in 17 cases, subdural effusion in 7 cases, spinal epidural effusion in 3 cases, tonsillar herniation in 2 cases, and thrombosis in dural sinuses in 2 cases. The intracranial hypotension group vs control group had dominant transverse sinus diameter 10 ± 1.75 vs 7.52 ± 1.2mm, straight sinus diameter 4.76 ± 0.92 vs 3.69 ± 0.57mm, superior sagittal sinus diameter 8.35 ± 1.57 vs 6.37 ± 0.71mm, pontomesencephalic angle 46.67 ± 9.73° vs 56.27° ± 8.9°, mamillopontine distance 5.83 ± 1.5 vs 6.85 ± 1.1mm, lateral ventricular angle 131.13° ± 6.17° vs 135.19° ± 5.28°, pituitary infundibular angle 44.42° ± 12.09° vs 63.3° ± 11.56°, and pituitary gland height 8.5 ± 1.83 vs 5.5 ± 1.27mm, respectively. In cases with clinically suspected intracranial hypotension, MRI findings may contribute to the diagnosis of intracranial hypotension with quantitative evaluations.

Abstract 10800: Pituitary Apoplexy Induced Takotsubo Cardiomyopathy

Introduction: Takotsubo Cardiomyopathy (TTC), defined by transient myocardial dysfunction with patterns of regional hyperkinesis, commonly arises after an emotional or physical stressor and hypokinesis. Here, we report a TTC case in the setting of pituitary apoplexy. Case: An 82-year-old Male with a history of hypertension, hyperlipidemia, pituitary adenoma, and complete heart block (status post permanent pacemaker) was admitted to the ED after one week of malaise, nausea, and vomiting. The day prior, he developed a severe frontal pressure headache and intermittent blurry vision. He had no chest pain and initially stable vitals, but later became lethargic and febrile to 101.6F with nonsustained ventricular tachyarrhythmias. EKG showed deep T-wave inversions in V2-V4 concerning for pathologic central nervous system T-waves (Fig. 1A). An echocardiogram revealed reduced left ventricular ejection fraction (LVEF) of 20% and akinesis of all mid-myocardial apical segments (Fig. 1B-D). Labs included flat troponin trend, lactate 5 mmol/L, and electrolyte derangements of magnesium 1.5 mEq/L, phosphorous 1.0 mEq/L, and potassium 3.2 mEq/L. In the cardiac care unit, his pacemaker settings were increased from 60 to 80 bpm due to QT prolongation and torsades de pointes on telemetry (Fig. 1E). Given his history of pituitary adenoma, an MRI Sella was performed and was notable for pituitary apoplexy and interval gland enlargement (Fig. 1F). Further labs revealed low cortisol, TSH, and testosterone. Stress dose steroids and levothyroxine were initiated and he underwent transphenoidal resection. Following these interventions, he was afebrile and no longer experienced his chief complaints. Repeat EKG and echocardiogram showed T-wave resolution in V2-V4 (Fig. 1G) and LVEF 50-55%, respectively. Conclusion: Neuroendocrine disorders should be considered as possible stressors in TTC. Early recognition and treatment can ensure favorable outcomes with pituitary apoplexy.

The time sequence of brain MRI findings in spontaneous intracranial hypotension.

To investigate the time sequence of brain magnetic resonance imaging findings of spontaneous intracranial hypotension. We retrospectively reviewed the medical records and brain magnetic resonance imaging findings of consecutive patients with spontaneous intracranial hypotension hospitalized between January 2007 and December 2017. Patients were divided into quartiles based on intervals between initial spontaneous intracranial hypotension symptom onset and brain magnetic resonance imaging scan. Six categorical and five continuous brain magnetic resonance imaging findings were assessed, including venous distension sign, enlarged pituitary gland, diffuse pachymeningeal enhancement, mid-brain pons deformity, subdural fluid collection, flattening of pons, midbrain-pons angle, descent of cerebral aqueduct, mamillopontine distance, distance of suprasellar cistern, and distance of prepontine cistern. In addition, we also calculated the neuroimaging scores with a score ≥5 classified as 'high probability of spontaneous intracranial hypotension' and a score ≥3 as 'intermediate-to-high probability.' Then, we analyzed the linkage between the onset-neuroimaging interval and brain magnetic resonance imaging findings, as well as different neuroimaging scores. A total of 173 patients (57 males and 116 females) were included in the analysis, and the range of onset-neuroimaging interval was 1 to 89 days (median [interquartile range] = 17 [7 to 30 days]). We divided the patients into quartiles based on their onset-neuroimaging interval (the first quartile: 0-6 days; the second quartile: 7-16 days; the third quartile: 17-29 days; the fourth quartile: ≥30 days). Among brain magnetic resonance imaging findings, the incidence of venous distension sign was high (>75%), with no difference among quartiles (p = 0.876). The incidence of diffuse pachymeningeal enhancement (p = 0.001), severe midbrain-pons deformity (p = 0.001), and subdural fluid collection (<0.001) followed a significant stepwise increase from the first quartile to fourth quartile. Patients with shorter onset-neuroimaging intervals were less likely to have neuroimaging scores ≥5 (<17 vs. ≥17 days: 72.9% vs. 86.4%; odds ratio = 2.3 [95% CI 1.1-5.1], p = 0.028), but not neuroimaging scores ≥3 (<17 vs. ≥17 days: 92.9% vs. 92.0%, p = 0.824). The emergence of brain magnetic resonance imaging findings of spontaneous intracranial hypotension depended on disease duration and appeared sequentially. When using brain magnetic resonance imaging findings or neuroimaging scores for diagnostic purposes, the onset-neuroimaging interval should be considered.

Primary pituitary granulomatosis with polyangiitis and the role of pituitary biopsy, case report and literature review

Background Pituitary dysfunction (PD) in granulomatosis with polyangiitis (GPA) is a rare manifestation of the disease with an incidence of 2% and tends to occur as the disease progresses. On very rare occasions, PD can be the initial presentation of GPA. From our literature review, only 6 such cases were documented. Case Presentation We present a rare case of GPA in a 57-year-old female who primarily presented with PD and visual disturbance without any other systemic features of GPA. Her initial ANCA screen was negative and her MRI scan showed an enlarged pituitary gland with cystic changes. A pituitary biopsy confirmed the diagnosis and she was started on immunosuppressants. After completing her immunotherapy, her diabetic insipidus subsided and her vision markedly improved. Literature Review A literature search on Pubmed, Cochrane, Open Grey, and SciELO with keywords ‘granulomatosis’, ‘polyangiitis’, and ‘pituitary’ was performed. A total of 72 articles were reviewed. 6 articles were identified where PD was the presenting complaint of GPA without other systemic involvement. Discussion Secondary hypophysitis in GPA indicates pituitary inflammation resulting from systemic disease or pituitary near-lying lesions. PD in GPA tends to occur with concomitant active disease at other sites. Headache seemed to be a common presenting feature with diabetic insipidus being the most common type of PD. Tissue biopsy is essential to confirm diagnosis. Pituitary biopsy is rarely required as other organ involvement is available for safer tissue sampling. However, in our case, pituitary biopsy had a role in confirming diagnosis and avoiding treatment delay. Conclusion PD as a primary manifestation in GPA without systemic involvement is very rare and poses a diagnostic challenge. Pituitary biopsy can aid in diagnosis, allowing prompt treatment and prevention of long-term complications of untreated GPA such as permanent pituitary dysfunction. Nevertheless, the risk and benefit of pituitary surgery in each case should be weighted.

Sheehan’s Syndrome Presenting as Postpartum Psychosis

Sheehan’s syndrome is characterized by hypopituitarism following ischemic necrosis of the pituitary gland caused by postpartum hemorrhage and impaired blood supply to the enlarged pituitary gland during pregnancy. The worldwide prevalence has since decreased due to improvements in obstetric care. Behavioral change is a rare presentation and is often misdiagnosed and managed as psychosis. We report a 42-year-old woman presenting with behavioral changes associated with postpartum failure of lactation and amenorrhea. Hormonal work-up revealed panhypopituitarism; serum cortisol, 98.93 (NV: 138–690 nmol/L); free T4, less than 5.15 (NV: 11.5–23.00 pmol/L); free T3, less than 2.30 (NV: 2.89–4.88 pmol/L); FSH, 3.63 (NV: 30–135 mIU/mL); LH, 3.88 (NV: 13–80 mIU/mL); serum estradiol, 3.89 (NV: 10.41–35.0 pg/mL); IGF-1, 13.13 (NV: 56–194 ng/mL); and serum prolactin, 1.8 (NV: 2.6–24.8 ng/mL). Cranial MRI with contrast revealed an atrophic pituitary gland consistent with Sheehan's syndrome. The symptoms improved substantially upon replacement with steroids and thyroid hormones and she was able to resume her routine activities. The psychiatric features of hypopituitarism can be attributed to a combination of hypothyroidism, hypoglycemia, and hypocortisolism and have been shown to reverse with adequate hormone replacement.

Ectopic Relapse of Anti-neutrophil Cytoplasmic Antibody-associated Pituitary Vasculitis with No Elevation of Anti-neutrophil Cytoplasmic Antibodies after Renal Remission.

The relationship between anti-neutrophil cytoplasmic antibody (ANCA) titer levels and relapse risk in patients with ANCA-associated vasculitis (AAV) following clinical remission remains controversial. We herein report a case showing ectopic relapse of AAV in the pituitary with no ANCA elevation after renal remission. Magnetic resonance imaging revealed an enlarged pituitary gland. A pituitary biopsy showed geographic necrosis with multinucleated giant cells. We diagnosed this case as relapse of AAV in the pituitary. One month after rituximab therapy, the pituitary gland volume had decreased. The intensification of therapy due to the possibility of vasculitis relapse may facilitate better control of AAV.

Skin during pregnancy

During pregnancy, many systemic changes may occur, them being haematological, car-diac, renal, respiratory, gastro-intestinal, endocrine or metabolic. Some other modifica-tions may target the cutaneous layers. It seems logical that during pregnancy, hormonal or other less well-explained pathways may influence one or more of the skin cell types. Pigmentary changes, such as melasma, but also vascular or structural modifications may affect the skin of pregnant women. Among the latter, striae distensae are probably the most common. Hair disorders featuring hair loss are frequently of concern during this pe-riod. Endocrine changes will often affect the skin glands, especially sebaceous ones, provoking acne. By contrast, some specific diseases originating in the skin may also oc-cur during the course of the gestation. Most of them present pruritic symptoms and for this reason affect the quality of life of pregnant women. Cutaneous infections such are vari-cella zoster virus, genital warts, infestation by Candida, Lyme disease or scabies may be observed during the period of gestation. Skin is modified during pregnancy and/or postpartum. These changes are usually only physiologi-cal, expressing changes in hormones or other factors secreted though the placenta, ovaries or en-larged pituitary gland. However, various dermatoses may specifically develop during this period and may influence the foetal outcome or, more rarely, the mother’s health. Therefore, being able to di-agnose and manage them is of high importance. Further, the increasing demand about cosmetic procedures, even during pregnancy, makes necessary to adapt our knowledge about their safety during this period.In this review, cutaneous modifications will be classified as physiological changes, spe-cific dermatoses of pregnancy, cutaneous infections that may modify the prognosis of pregnancy, miscellaneous skin diseases that may be affected by pregnancy and finally the safety of cosmetic dermatologic procedures during pregnancy will be overviewed, in order to offer to the dermatologists updated information permitting them to bring accurate assistance to their pregnant patien

SUN-304 Hypophisitis in Patients with and Without Autoimmune Rheumatological Disease

Background: Hypophysitis is an inflammatory process of the pituitary gland with different origins. Infundibulum may be also involved, called infundibulum-hypophysitis. Sometimes, enlargement of pituitary gland causes mass effect and anterior or posterior hormonal dysfunction, including hypopituitarism, and diabetes insipidus (DI), respectively. Hypophysitis is a rare autoimmune disease, however, the number of cases have been recently increasing due to higher detection related with more magnetic resonance imaging (MRI) studies. In addition, hypophysitis may be related with autoimmune rheumatologic disease (ARD) such as generalized lupus erythematosus (GLE), granulomatosis with polyangeitis (GPA), IgG4-related disease, and rheumatoid arthritis (RA). Aim: to compare the clinical and biochemical findings among patients with hypophysitis grouped depending on the presence of coexistent ARD activity. Methodology: it is a comparative and cross-sectional study. We registered all data from cases followed-up in Neuroendocrinology and Rheumatology units, from January 1987 to July 2019. Results: 24 patients showed confirmed diagnosis of hypophysitis. Majority of them (n=17, 71%) do not have coexistent diagnosis of ARD. However, 7 cases (29%) presented pituitary involvement with coexistent activity of GPA (n=4, 17%), GLE (n=1, 4%), RA (n=1, 4%) and IgG4-related disease (n=1, 4%). Female gender predominate in hypophysitis cases with and without ARD (p=0.9). Interestingly, age of hypophysitis diagnosis was significantly younger in cases without (38±14) vs. with (49±5) ARD (p=0.01). MRI results showed similar and typical findings related with hypophysitis independently of the presence of ARD. Hypopituitarism was present in the majority of cases, however, none of cases with hypophysitis and ARD showed hypogonadism (p=0.02). DI was present in 15 patients (63%), three of them with ARD (all with GPA). All cases received only medical therapy (i.e., glucocorticoids, rituximab, or azathioprine). Surgery or radiotherapy was not necessary in any case. Conclusions: Almost a 30% of cases with hypophysitis may have coexistent ARD. Pituitary function should be evaluated in cases with previous ARD diagnosis. However, hypogonadism was not present in cases with ARD and hypophysitis. Patients with ARD presented hypophysitis at older age. The remaining clinical and radiological data were similar between groups.

MON-245 Brain Fog: An Important Cue to Neurosarcoidosis and Its Flare-Up?

Introduction:Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating granulomas in various organ systems, mainly the lung and lymphatic system. Neurosarcoidosis (NS) involving central or peripheral nervous system is uncommon and Hypothalamic-pituitary (HP) NS is rarer.Case:A 45-years-old African American man presented with a few days’ history of cognitive slowness (brain fog) and a sense of loss of direction. He was discharged a few months ago from another hospital after being admitted for shortness of breath and hypercalcemia of 13 mg/dl, which improved after hydration. CXR showed mediastinal and bilateral hilar enlargement. He was discharged home with outpatient pulmonary appointment but was readmitted to our hospital with altered mental status. Calcium level on this admission was 11.5 mg/dl. CT brain showed a sellar/suprasellar lesion, which was better visualized on MRI as enlargement and enhancement of pituitary gland, pituitary stalk, optic chiasm, left and right optic tract and nerves, and hypothalamus. He had left hemi-temporal field defect. Work up revealed inappropriately high normal 1,25 vitamin D, low PTH, PTrp and vitamin D. He has anterior hypopituitarism and mildly elevated prolactin. EBUS with mediastinal lymph node biopsy was non-diagnostic, however, excisional biopsy of mediastinal node showed non-caseating granuloma. ACE level, flow cytometry, infectious work up and serum IgG4 were normal.Discussion:NS may present as cranial nerve palsy, chronic headache with incidental HP mass and endocrine dysfunction such as diabetes insipidus, hyperprolactinemia, and anterior hypopituitarism. Visual deficits from optic atrophy or neuropathy; or change in vision from anterior uveitis are present in 41% of patients. Other non-specific presentations of NS include fatigue, cognitive difficulties (brain fog), such as impaired memory, slowed thinking, diminished attention and concentration. Hypercalcemia in sarcoidosis is due to increased intestinal absorption of calcium from increased 1,25 OH vitamin D. Though definitive diagnosis of NS is based on evidence of non-caseating granulomas from neural tissue, probable diagnosis can be made from clinical and radiologic characteristics, non-caseating granulomas at an extraneural site with no evidence of alternative disease. Steroid is the mainstay of treatment in NS and requires slow tapering. Other immunomodulators can be considered in worsening disease or patients with steroid adverse effect.Conclusion:Diagnosis of NS is challenging due to its rarity and difficult access to neural tissue for diagnosis. Though brain fog may not be specific for NS or its flare-up, additional neurological test or imaging should be considered especially in African American patients with hilar lymphadenopathy as 20% of NS patients may simply present with non-specific cognitive or behavioral complaints. ​

SUN-298 Spectrum of Imaging in Immune Checkpoint Inhibitor Induced Hypophysitis

Background: Hypophysitis (HP) is a known immune related adverse event of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and rarely with PD-1/PD-L1 inhibitors. Prior studies of MRIs at HP diagnosis noted pituitary enlargement with resolution within a few weeks. In this study, we examine MRI changes in patients with CPI-induced HP. Methods: Subjects with biochemical evidence of central hypothyroidism or central adrenal insufficiency and MRIs were reviewed by endocrinology and neuroradiology. MRIs were classified relative to HP diagnosis: baseline (at least 21 days prior), diagnosis (within 21 days), and follow up (over 21 days). Patient characteristics included age at CPI initiation, sex, race/ethnicity, personal and family history of autoimmunity, type of cancer and CPI. Results: Twenty-six subjects met the inclusion criteria. The mean age was 59 years; 62% were male and 86% were non-Hispanic white. Nineteen percent had a personal history and 31% a family history of autoimmunity. Fifty percent had melanoma. At HP diagnosis, 46% were on PD-1/PD-L1 inhibitors, 42% were on combination PD-1/CTLA-4 inhibitors and 12% were on CTLA-4 inhibitors.Median time from CPI initiation to HP diagnosis was 95 days. Time to HP was shorter on a CTLA-4 inhibitor combination or monotherapy (median 82 days) compared to a PD-1/PD-L1 inhibitor monotherapy (median 220 days; Wilcoxon rank sum, p <0.01). Central adrenal insufficiency was present in all patients not yet on steroids. Central hypothyroidism was common (10/19) in those without primary thyroid disease and was not associated with type of CPI (Fisher’s exact, p=0.18).Thirteen subjects had baseline MRIs, 18 had MRIs at HP diagnosis and 13 had MRIs in the follow up period. Baseline MRIs were normal in 12/13; one subject had an enlarged pituitary. At diagnosis, 10 had an enlarged pituitary, 7 a normal pituitary and 1 a partially empty sella. CTLA-4 inhibitor exposure was associated with pituitary enlargement at diagnosis: 9/11 compared to 1/7 on PD-1/PD-L1 inhibitor (Fisher’s exact, p <0.04). Of the subjects who had follow-up MRIs, 3 had an enlarged pituitary, 7 a normal pituitary and 3 a partially empty sella. Follow up imaging did not differ between treatment types (Fisher’s exact, p >0.05). Timing of MRI was significantly associated with pituitary appearance (Fisher’s exact, p <0.01). Conclusion: The MRI appearance of HP presents as a spectrum, from a partially empty sella, normal pituitary to an enlarged pituitary. HP diagnosed in the setting of CTLA-4 inhibitor treatment occurs earlier and is more likely to induce an enlarged pituitary gland compared to PD-1/PD-L1 monotherapy, which occurs later and is associated with a normal appearing MRI at diagnosis. This suggests that the pathogenesis of HP following CPI exposure may vary depending on the type of CPI.