Endocrinological Examinations Research Articles

6372 Changes in Blood Steroid Hormone Profile after Switching from Metyrapone to Osilodrostat

Abstract Disclosure: K. Yokozeki: None. H. Kameda: None. A. Miya: None. H. Nomoto: None. A. Nakamura: None. S. Jin: None. K. Matoba: None. T. Atsumi: None. Background: The new steroidogenesis inhibitor osilodrostat has recently been approved for use in Cushing's syndrome. However, there are limited studies on changes in blood steroid hormone profiles after switching from existing drugs including metyrapone. Purpose: To study the changes in steroid hormone profiles with switching from metyrapone to osilodrostat in patients with Cushing's disease and to examine the differences in clinical efficacy. Case 1: A woman in her 40s underwent transsphenoidal pituitary tumor surgery (TSS) for Cushing's disease in X-12, but was not in remission and was treated with 1000 mg/day of metyrapone and oral hydrocortisone. In X-3, the patient complained of masculinization and was started pasireotide LAR 10 mg per month, which was subsequently increased to 30 mg. Despite the addition of 240 mg/day of trilostane in X-2, the patient did not show improvement. Switched the steroidogenesis inhibitors to osilodrostat 4 mg/day in year X, blood cortisol and testosterone levels decreased and the symptoms of virilization disappeared.Case 2: A woman in her 40s experienced edema in her face and limbs, increased appetite and weight gain since Y-13. After endocrinological examination, she was diagnosed with Cushing's disease. TSS was performed and she was in remission. However, she suffered a relapse in Y-4 and was started on metyrapone, which was titrated up to 4,000 mg/day. Due to gastric discomfort, metyrapone was switched to osilodrostat 52 mg/day in year Y, leading to an improvement of her gastric symptoms and stabilized blood cortisol level. Case 3: A woman in her 70s underwent TSS for Cushing's disease in Z-6, but the tumor remained and she was prescribed metyrapone 1,500 mg/day. The disease was stable and complications were under control with metyrapone. In Z-1, the patient developed elevated blood pressure and worsening leg edema, and metyrapone was switched to osilodrostat 3 mg/day in year Z, resulting decreased blood cortisol level and blood pressure. Results: Liquid chromatograph mass spectrometry (LC-MS) analysis of blood steroid hormone profiles in above three cases demonstrated a decrease in 17-OH pregnenolone, 17-OH progesterone, and 11-deoxycorticosterone after switching the steroidogenesis inhibitors. Discussion and Conclusion: It has been noted that osilodrostat lowers serum cortisol in a shorter period of time compared to metyrapone and may also decrease the number of antihypertensive medications used. Under metyrapone administration, hypertrichosis, hypertension, and hypokalemia are often observed with increased mineralocorticoid precursors, but osilodrostat may have a different clinical effect as a result of its different pattern of steroid hormone synthase inhibition. Presentation: 6/2/2024

7483 The Pharmacokinetic Profile of Lanreotide Autogel® Improved Long-Term Arrhythmia Fluctuations in Acromegalic Cardiomyopathy

Abstract Disclosure: M. Iwabuchi: None. Background: The prognosis of acromegaly is related to the status of cardiac complications. Ventricular premature contractions (VPC) are frequently observed in acromegaly, and it is very important to suppress fatal arrhythmias to improve long-term prognosis. Somatostatin analogs are widely used as pharmacotherapy for acromegaly, and they have been reported to improve cardiac prognosis. In comparison to LAR, lanreotide Autogel® has a unique property of self-aggregation under favorable conditions, leading to a stable structure of highly organized nanotubules and has a long half-life after subcutaneous injection determined by pseudo-first order kinetics. CASE: 55-year-old man visited a cardiologist for the treatment of PVCs and heart failure. Because of his acromegalic features, endocrinological and image examinations were performed, and diagnosis of acromegaly was confirmed. His GH was 7.17 ng/mL, IGF-1 566 ng/mL (Normal range: 59-215). Concerning excess of GH may cause nonischemic cardiomyopathy, administration of 20 mg of LAR once a month was started. GH and IGF-1 improved to1.52 ng/mL and 217 ng/mL respectively. The dose of LAR was increased to 30mg because of a remaining fluctuation of VPCs. Considering a possibility of the problem of bioavailability due to method of injection and the pharmacokinetics of LAR, administration of lanreotide Autogel® was started instead of LAR, with the result that an improvement of the fluctuation of the symptom was observed without remarkable change in GH and IGF-1. Arrhythmia status was assessed over time using Holter electrocardiography. Pretreatment Holter electrocardiogram showed 18% of total heart rates in PVCs. After LAR injection, the frequency of PVCs decreased to 3%, and 6 years after changing LAR to lanreotide, the frequency of PVCs decreased to 2%. Clinical Lessons: Simulated steady state pharmacokinetic profiles of LAR and lanreotide Autogel® differ significantly. During LAR treatment, serum concentrations of the drug are approximately stable, whereas the characteristic first-order kinetics of lanreotide Autogel® is superimposed on levels just before the next administration. The pharmacokinetic differences indicate that LAR can be better tailored to therapeutic levels, whereas serum levels of lanreotide must be high for part of the interval between injections to be effective in the period before the next administration. Lanreotide Autogel® has similar clinical effects compared to LAR for the treatment of cardiomyopathy of acromegaly and has the advantage of being available in a convenient pre-filled syringe and no necessity of injection by healthcare professionals. It is suggested that the pharmacokinetic profile of Lanreotide Autogel® resulted in decreased arrhythmia fluctuation in acromegalic hearts, which has been maintained for the past 6 years. Presentation: 6/3/2024

Mediterranean Diet adherence, physical activity level, and quality of life in patients affected by thyroid diseases: Comparison between pre- and post-lockdown assessment

Background: SARS-CoV-2 pandemic resulted in lifestyle change of world’s population because of the measures adopted by governments to contain the virus spread. Design and Methods: This study examined whether lockdown impacted anthropometric indices, Mediterranean Diet (MD) adherence, Physical Activity Level (PAL), and Quality of Life (SF-12) in a cohort of 116 patients (96 F, aged 57.2 ± 13.1 years) affected by thyroid disorders. Before lockdown, data were collected during the endocrinological examination; after lockdown they were collected through a tele-phone interview (via video call). Results: Data revealed an overweight condition in 59% of patients, with no significant differences between the two observations (BMI values: 26.5 ± 4.9 vs 26.6 ± 4.9 kg/m2), whereas waist circumference values significantly increased over time (93.3 ± 12.6 vs 94.4 ± 12.5 cm; p = 0.003). Moreover, a lower adherence to the MD (PREDIMED score: 7.3 ± 1.8 vs 7.0 ± 1.8; p = 0.003) and a significant increase of sitting time (6.4 ± 3.2 h/die vs 9.0 ± 4.2; p < 0.001) were observed. A not significant decrease in PAL, which revealed a sedentary condition in pre- and post-lockdown (648 and 562 METs/week respectively), was found. The SF-12 score did not show relevant changes between the two observations. Conclusion: Our study highlights that patients with thyroid diseases are often sedentary and exhibit a high prevalence of over-weight, underscoring the need for a systematic anthropometric evaluation and, at times, lifestyle interventions.

Impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors: a retrospective study.

To investigate the impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors. Between January 2020 and October 2022, patients with adrenal lesions were retrospectively screened for nonfunctional adrenal tumors at the Zhongnan Hospital of Wuhan University. All patients underwent detailed endocrinological examination and computed tomography to characterize the lesions. One year after discharge, follow-up blood pressure (BP) was assessed and compared to the blood pressure on admission. Univariate analysis and multivariate regression analysis were performed to determine factors predicting favorable hypertension outcomes after adrenalectomy. A total of 309 patients were found to be eligible, including 123 who underwent adrenalectomy. Patients who underwent adrenalectomy were stratified into two groups: (Bancos I (2022) Adrenal Incidentalomas: Insights Into Prevalence. Ann Intern Med 175:1481-1482. https://doi.org/10.7326/M22-2600 ) those with improved hypertension (n = 71), and (Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J et al. (2023) European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 189:G1-42. https://doi.org/10.1093/ejendo/lvad066 ) those without improved hypertension (n = 52). In contrast, the blood pressure levels of conservatively treated patients remained relatively stable 1 year after discharge. Univariate analysis and multivariate regression analysis showed that body mass index (BMI) and duration of hypertension were significantly different between the hypertension improvement group and the non-improvement group (p < 0.05). Adrenalectomy has been shown to be effective in improving hypertension in certain patients with nonfunctional adrenal tumors. BMI and duration of hypertension were independent factors associated with favorable hypertension outcomes after adrenalectomy.

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.

"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.

Genetic Testing of Children With Familial Tall Stature: Is it Worth Doing?

Familial tall stature (FTS) is considered to be a benign variant of growth with a presumed polygenic etiology. However, monogenic disorders with possible associated pathological features could also be hidden under the FTS phenotype. To elucidate the genetic etiology in families with FTS and to describe their phenotype in detail. Children with FTS (the life-maximum height in both the child and his/her taller parent > 2 SD for age and sex) referred to the Endocrinology center of Motol University Hospital were enrolled into the study. Their DNA was examined cytogenetically and via a next-generation sequencing panel of 786 genes associated with growth. The genetic results were evaluated by the American College of Molecular Genetics and Genomics guidelines. All of the participants underwent standard endocrinological examination followed by specialized anthropometric evaluation. In total, 34 children (19 girls) with FTS were enrolled in the study. Their median height and their taller parent's height were 3.1 SD and 2.5 SD, respectively. The genetic cause of FTS was elucidated in 11/34 (32.4%) children (47,XXX and 47,XYY karyotypes, SHOX duplication, and causative variants in NSD1 [in 2], SUZ12 [in 2], FGFR3, CHD8, GPC3, and PPP2R5D genes). Ten children had absent syndromic signs and 24 had dysmorphic features. Monogenic (and cytogenetic) etiology of FTS can be found among children with FTS. Genetic examination should be considered in all children with FTS regardless of the presence of dysmorphic features.

FRI225 Clinical Course Of Late-onset Adrenal Insufficiency Due To Treatment Of Childhood Acute Lymphoblastic Leukemia

Abstract Disclosure: M. Iwabuchi: None. Background: Some people who were treated for cancer during childhood may develop endocrine problems as because of changes in the function of endocrine system. Acute lymphoblastic leukemia is the most common type of cancer and leukemia in children and components of ALL treatment are induction, consolidation, maintenance, and central nervous system prophylaxis. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. Clinical Case: A man in his 40s was admitted with symptoms of diarrhea, low-grade fever, and drowsiness. The serum sodium level that caused his symptoms decreased to 100 mEq/L and was adequately corrected. Endocrinological examination confirmed the diagnosis of central adrenal insufficiency. Soon after starting hormonal replacement therapy with hydrocortisone, his general conditions improved. After establishing our relationship, he confessed to having a history of ALL in childhood. According to his medical records at the time, he underwent induction therapy with vincristine-prednisone in 1977, maintenance therapy with 6-mercaptopurine, and radiation therapy to the central nervous system of 25 Gy in 1983. In 2023, 40 years have passed since radiation therapy. He was able to lead a normal life on oral hydrocortisone 20 mg/day without recurrence of adrenal insufficiency. Clinical Lesson: A 40-old male survivor of ALL developed adrenal insufficiency in 30 years after cranial irradiation during childhood. Undiagnosed adrenal insufficiency is often the cause of death. We should consider childhood cancer survivors have the risk of a central adrenal insufficiency. The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (COG LTFU Guidelines) are a resource for healthcare professionals who provide ongoing care to survivors of pediatric malignancies. The screening recommendations in these guidelines are appropriate for asymptomatic survivors of childhood, adolescent, or young adult cancer presenting for routine exposure-based medical follow-up. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. This case highlights the importance of long-term follow-up of cancer survivors after irradiation and the delayed presentation of adrenal insufficiency. This is the first report of the subsequent treatment course of late-onset adrenal insufficiency that developed 30 years after irradiation for childhood central nervous system ALL. Presentation: Friday, June 16, 2023

The Scientific Knowledge of Bard and ChatGPT in Endocrinology, Diabetes, and Diabetes Technology: Multiple-Choice Questions Examination-Based Performance.

The present study aimed to investigate the knowledge level of Bard and ChatGPT in the areas of endocrinology, diabetes, and diabetes technology through a multiple-choice question (MCQ) examination format. Initially, a 100-MCQ bank was established based on MCQs in endocrinology, diabetes, and diabetes technology. The MCQs were created from physiology, medical textbooks, and academic examination pools in the areas of endocrinology, diabetes, and diabetes technology and academic examination pools. The study team members analyzed the MCQ contents to ensure that they were related to the endocrinology, diabetes, and diabetes technology. The number of MCQs from endocrinology was 50, and that from diabetes and science technology was also 50. The knowledge level of Google's Bard and ChatGPT was assessed with an MCQ-based examination. In the endocrinology examination section, ChatGPT obtained 29 marks (correct responses) of 50 (58%), and Bard obtained a similar score of 29 of 50 (58%). However, in the diabetes technology examination section, ChatGPT obtained 23 marks of 50 (46%), and Bard obtained 20 marks of 50 (40%). Overall, in the entire three-part examination, ChatGPT obtained 52 marks of 100 (52%), and Bard obtained 49 marks of 100 (49%). ChatGPT obtained slightly more marks than Bard. However, both ChatGPT and Bard did not achieve satisfactory scores in endocrinology or diabetes/technology of at least 60%. The overall MCQ-based performance of ChatGPT was slightly better than that of Google's Bard. However, both ChatGPT and Bard did not achieve appropriate scores in endocrinology and diabetes/diabetes technology. The study indicates that Bard and ChatGPT have the potential to facilitate medical students and faculty in academic medical education settings, but both artificial intelligence tools need more updated information in the fields of endocrinology, diabetes, and diabetes technology.

Results of surgical therapy of functioning pituitary adenomas.

Functioning pituitary adenomas lead to substantial morbidity and increased mortality associated with typical endocrine syndromes. Surgical therapy is an integral part of the management of these tumours. The aim of this study was to evaluate the results of surgical transnasal procedures in patients with functioning pituitary adenomas who underwent the surgery at the Department of Neurosurgery, University Hospital Olomouc. Patients with functioning pituitary adenoma (ACTH, GH, PRL) were indicated for surgery. All patients underwent preoperative and postoperative endocrinological examination and laboratory tests to assess excessive or deficient hormonal production and imaging examination. The cohort consisted of 58 patients, 33 of whom were women and 25 men. The age range was 12-77 years (mean age 47.6 years). Microadenoma was diagnosed in 58.6% of patients and macroadenoma in 41.4% of patients. The most common hypersecretory syndrome was excessive production of growth hormone (56.9%), followed by excessive production of adrenocorticotropic hormone (24.1%) and prolactin (12.1%). In the group with excessive production of ACTH, complete remission was achieved after the first surgery in 78.6% of cases (72.8% for microadenomas (8) and 100% (3) cases in macroadenomas); in the group with excessive GH production in 51.4% (63.2% (7) in microadenomas and 46.2% (12) cases in macroadenomas). In the group with excessive production of PRL, it was 57.1% (100% (2) in microadenomas and 40% (2) cases in macroadenomas). Surgical therapy in the presented cohort led to the normalisation of hormonal excessive production in 58.6% of cases. A combination of drug therapy and radiotherapeutic methods was necessary in the remaining cases to achieve hormonal remission.

Insulin Resistance in Patients with Polycystic Ovary Syndrome is a Predictor of Fibromyalgia.

This study aims to investigate the frequency of fibromyalgia and its predictors in women with polycystic ovary syndrome (PCOS) and its relationship with insulin resistance, and to assess the effect of fibromyalgia on the anxiety and depressive symptoms in PCOS patients, and how the quality of life was affected by this combination. The study was conducted with 74 women with PCOS according to the Rotterdam criteria, which applied to our tertiary care clinic between January 2021 and January 2022, and 51 controls. Endocrinologic and rheumatologic examinations, biochemical and hormonal analyses, and radiologic imaging are made. Hospital anxiety and depression scale (HADs) and Short Form 36 (SF-36) quality of life scale were applied. There was no statistical difference between patients (n = 74 (23%)) and controls (n = 51 (13.7%)) in terms of fibromyalgia frequency. This frequency was 41.4% in PCOS patients with insulin resistance. The presence of insulin resistance was significantly higher in patients with PCOS and fibromyalgia (70.4%, 12 of 17 patients with fibromyalgia for the PCOS group; 8.3%, 1 of 7 patients with fibromyalgia for the control group) (χ2 = 9.130, p=0.003). Higher HOMA-IR levels (B = 1.278, p = 0.034) and age (B = 1.134, p = 0.022) were significant predictors of fibromyalgia in PCOS patients. Physical functioning (U = 1.960, P = 0.050), bodily pain subscales (U = 2.765, p = 0.006), and physical health summary measure (U = 2.296, p = 0.022) were significantly lower, VAS pain (U = 5.145, p < 0.0001) and fatigue (U = 5.997, p < 0.0001) scale scores were higher in PCOS patients with fibromyalgia. Our results show that fibromyalgia is frequent in PCOS patients with insulin resistance.

Late effects of medulloblastoma treatment: multidisciplinary approach of survivors.

Medulloblastoma is one of the brain tumors with increased life expectancy due to improvements in treatment approaches. Besides the promising results, various undesirable effects can be encountered. This study's aim is to review long-term follow-up outcomes of our cases with medulloblastoma. Age at diagnosis, histological type of medulloblastoma, resection extension, chemotherapy and radiotherapy schemes, follow-up duration, and endocrinological, neuropsychiatric, cardiological, auditory, and visual examination results were evaluated in 20 patients diagnosed between 2007 and 2018 and followed 5 years and more. Twenty of 53 patients were included to the study. Eleven (55%) were male. Mean age at diagnosis was 6.95 years; mean age at the time of the study was 14 years. Mean follow-up time was 8.95 years. In terms of surgery, 14 (70%) were gross total, 1 (5%) was near total, and 2 (10%) were subtotal resection. In histopathological examination, 14 (70%) were classical medulloblastoma, 4 (20%) were desmoplastic medulloblastoma, and 1 (5%) was anaplastic medulloblastoma. With regard to endocrinological evaluation, 15 (75%) patients had hypothyroidism, 5 (25%) had growth hormone deficiency, 7 (35%) had clinical growth hormone deficiency, and 5 (25%) had sex hormone disorders. In neuropsychiatric examination, 11 (55%) patients had neurological sequelae, 18 (90%) patients had psychiatric issues, and 14 (70%) patients had two or more neuropsychiatric problems simultaneously. One (5%) patient had mitral valve insufficiency. Twelve patients (60%) had hearing loss. According to visual examination, 6 (30%) patients had refraction problem, 4 (20%) had cataract, and 1 (5%) had dry eye. Careful monitoring of long-term side effects is important for improving the quality of life of medulloblastoma patients. Besides endocrinological and other somatic sequelae of the disease and treatment, increased neuropsychiatric problems showed us that only cure is not the issue while treating childhood medulloblastoma.

Optical coherence tomography angiography findings in pediatric patients with graves ophthalmopathy.

The aim of this study was to evaluate peripapillary, macular microvascular structure, and retinal nerve fiber layer (RNFL) thickness profile in children with Graves Ophthalmopathy (GO). Thirty-six eyes of 18 children with GO were prospectively compared with 40 eyes of 20-age and sex-matched controls. The severity and activity of the disease were evaluated according to the criteria of the European Group on Graves' Ophthalmopathy (EUGOGO) and Clinical Activity Score (CAS). After complete ophthalmologic and endocrinologic examination, all patients underwent optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) measurements. Retinal nerve fiber layer (RNFL) thickness, macular superficial capillary plexus (SCP), deep capillary plexus (DCP), foveal avascular zone (FAZ) area, acircularity index (AI) of the FAZ and peripapillary microvascular structure were analyzed. The mean age was 12.1 ± 2.4years in the GO group and 11.2 ± 2.6years in healthy control group (p = 0.11). Duration of disease was 8.9 ± 4.2months in the GO group. All patients in GO group had mild and inactive ophthalmopathy. In temporal inferior quadrant, RNFL thickness was significantly thinner in the GO group compared to the control group (p = 0.03). No significant difference was seen between groups both peripapillary and macular microvascular structure (all p > 0.05). GO has no effect on optic nerve thickness, peripapillary and macular vascular parameters except inferior temporal RNFL in children.

Different cell compositions and a novel somatic KCNJ5 variant found in a patient with bilateral adrenocortical adenomas secreting aldosterone and cortisol.

This study aimed to explore the possible pathogenesis of a rare case of co-existing Cushing's syndrome (CS) and primary aldosteronism (PA) caused by bilateral adrenocortical adenomas secreting aldosterone and cortisol, respectively. A 41-year-old Chinese woman with severe hypertension and hypokalemia for 5 and 2 years, respectively, was referred to our hospital. She had a Cushingoid appearance. Preoperative endocrinological examinations revealed autonomous cortisol and aldosterone secretion. Computed tomography revealed bilateral adrenal adenomas. Subsequently, adrenal vein sampling and sequential left and right partial adrenalectomy indicated the presence of a left aldosterone-producing tumor and a right cortisol-producing tumor. Pathological examination included immunohistochemical analysis of the resected specimens. Secretions of aldosterone and cortisol were observed both in vivo and in vitro. Further, whole-exome sequencing was performed for DNA that was extracted from peripheral blood leukocytes and bilateral adrenal adenomas in order to determine whether the patient had relevant variants associated with PA and CS. Immunohistochemical staining revealed that the left adenoma primarily comprised clear cells expressing CYP11B2, whereas the right adenoma comprised both eosinophilic compact and clear cells expressing CYP11B1. The mRNA levels of steroidogenic enzymes (including CYP11B1 and CYP17A1) were high in the right adenoma, whereas CYP11B2 was highly expressed in the left adenoma. A novel somatic heterozygous missense variant-KCNJ5 c.503T > G (p.L168R)-was detected in the left adrenal adenoma, but no other causative variants associated with PA and CS were detected in the peripheral blood or right adrenocortical adenoma. In the primary cell culture of the resected hyperplastic adrenal adenomas, verapamil and nifedipine, which are two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol. We present an extremely rare case of bilateral adrenocortical adenomas with distinct secretion of aldosterone and cortisol. The heterogeneity of the tumor cell compositions of aldosterone- and cortisol-producing adenoma (A/CPA) and somatic mutation of KCNJ5 may have led to different hormone secretions in the bilateral adrenal adenomas.

Osteoporotic vertebral compression fractures caused by Cushing’s syndrome in young women: case report and literature review

BackgroundCushing’s syndrome is known as an important cause of secondary osteoporosis, characterized by reduction of bone mineral density and potential occurrence of fragility fractures before diagnosis in young population. Therefore, for young patients with fragility fractures, especially in young women, more attention should be paid on glucocorticoid excess caused by Cushing’s syndrome, due to relatively higher rate of misdiagnosis, distinct pathological characteristics and different treatment strategies compared with violent fractures and primary osteoporosis related fractures.Case presentationWe presented an unusual case of a 26-year-old woman with multiple vertebral compression fractures and pelvis fractures, subsequently diagnosed as Cushing’s syndrome. On admission, the radiographic results showed fresh second lumbar vertebra fracture, and old fourth lumbar vertebra and pelvic fractures. The dual energy X-ray absorptiometry of lumbar spine revealed marked osteoporosis, and her plasm cortisol was extremely high. Then, Cushing’s syndrome, caused by left adrenal adenoma, was diagnosed by further endocrinological and radiographic examinations. After receiving left adrenalectomy, her plasma ACTH and cortisol values returned to normal level. In term of OVCF, we adopted conservative treatments, including pain management, brace treatment, and anti-osteoporosis measures. Three months after discharge, the patient’s low back pain was in complete remission without new onset of pain, and returned to normal life and work. Furthermore, we reviewed the literatures on advancements in the treatment of OVCF caused by Cushing’s syndrome, and based on our experiences, proposed some additional perspectives to guide treatment.ConclusionIn term of OVCF secondary to Cushing’s syndrome without neurological damage, we prefer systematic conservative treatments, including pain management, brace treatment, and anti-osteoporosis measures, to surgical treatment. Among them, anti-osteoporosis treatment has the highest priority because of the reversibility of osteoporosis caused by Cushing’s syndrome.

PS-C21-3: URINARY FREE CORTISOL EXCRETION AS A MARKER OF DECREASED BONE DENSITY IN PATIENTS WITH ADRENAL CUSHING'S SYNDROME

Objective: Patients with adrenal Cushing's syndrome (CS) have a poor prognosis due to the autonomous hypersecretion of endogenous cortisol from the adrenal gland. Although several clinical examinations have been developed to manifest the autonomous hypersecretion of endogenous cortisol in this syndrome, it is unknown which parameter of cortisol overproduction is best associated with adrenal cortisol content and the bone and vascular complications of this syndrome. Therefore, the present study was undertaken to evaluate the parameter(s) associated with adrenal cortisol content in patients with adrenal CS, as well as to assess the associations between these parameters and the vascular and bone complications of this syndrome. Design and method: Patients with CS who were over 18 years old and had undergone adrenalectomy for this syndrome were enrolled in this study. Patients who were pregnant, had an allergy to iodine, or who were receiving medications that may interfere with the evaluation of 131I-adosterol single-photon emission computed tomography (SPECT) /computed tomography (CT) were excluded. Those taking medications that may interfere with the evaluation for the diagnosis of CS were also excluded. Relationships between office blood pressure and pulse rate, urinary examinations, blood examinations, endocrinological examinations, CT and 131I-adosterol SPECT/CT data, bone density, physiological function tests, and adrenal cortisol concentration/content were examined. In addition, relationships between the parameter associated with adrenal cortisol concentration/content and complications of CS were investigated. Results: Cardiovascular factors, except for diastolic blood pressure, failed to show an association with adrenal cortisol content. 24-h urinary free cortisol excretion (ρ = 0.893, P = 0.007) and plasma cortisol levels after the 1 mg (ρ = 0.857, P = 0.014) or 8 mg (ρ = 0.900, P = 0.037) overnight dexamethasone suppression test, but not plasma cortisol levels in the morning or at late night or indices of 131I-adosterol SPECT/CT, were significantly and positively associated with adrenal cortisol content. 24-h urinary free cortisol excretion, and not plasma cortisol levels after the 1 or 8 mg overnight dexamethasone suppression test was significantly and negatively associated with lumbar spine bone density (lumbar spine T-score, ρ = -0.883, P = 0.009; lumbar spine Z-score, ρ = -0.883, P = 0.009). Conclusions: 24-h urinary free cortisol excretion is best associated with a decrease in bone density via increased adrenal cortisol overproduction and suggested that it could be used as a marker for osteoporosis in these patients.

Late diagnosed prolactinoma in men: a case report

Endocrinologic examinations encounter hyperprolactinemia, which is the release of prolactin hormone in excess of normal amounts, more frequently than any other pathological condition. In this case , we present a case of it is explained that a 42-year-old male patient can be diagnosed with prolactinoma by deepening the anamnesis without specifics symptoms. It is aimed to raise awareness on this issue.

PS-R04-5: A CASE OF SEVERE RENAL FAILURE WITH HYPERTENSIVE EMERGENCY WHO SUCCEEDED IN HEMODIALYSIS WITHDRAWAL BY STRICT CONTROL OF BLOOD PRESSURE

Introduction: Hypertensive emergency is a condition in which progressive and irreversible organ damages occur as a result of extremely elevated blood pressure. Although the prognosis for renal outcomes has been improved by advances in antihypertensive therapy, the cases who result in maintenance dialysis are still not uncommon. We herein report a case of hypertensive emergency who was successfully withdrawn from hemodialysis by intensive treatment. Case presentation: A 55-year-old woman, whose systolic blood pressure was 150–160 mmHg constantly for at least 2 years, was seen by her primary care physician due to nocturnal cough and respiratory distress. She exhibited marked hypertension (diastolic blood pressure, 120–130 mmHg) and renal dysfunction (serum creatinine (sCr), 2.76 mg/dL, baseline 0.5 mg/dL). She was diagnosed as hypertensive emergency and was treated with antihypertensive agents immediately. Despite the treatment, her renal function did not improve, so that she was transferred to our hospital for further examination and intensive treatment. While imaging examination revealed a right adrenal tumor, for which primary aldosteronism was suspected, endocrinological examinations showed high plasma aldosterone concentration with high plasma renin activity; therefore it was assumed that the hormonal changes were secondary to hypertensive emergency. Although funduscopic findings were relatively mild (KW-IIb), the condition was considered as accelerated-malignant hypertension caused by essential hypertension. A renal biopsy revealed extensive interstitial damage with onion skin-like lesions, which led to a diagnosis of malignant nephrosclerosis. While continuing strict antihypertensive management including the renin-angiotensin system blockade, hemodialysis was started on day 17 due to progressive renal dysfunction (sCr 9.27 mg/dL). Continuous intensive treatment gradually alleviated renal dysfunction, and hemodialysis was finally withdrawn on day 38. There was no further deterioration seen, and the patient was discharged on day 55. After discharge, her renal function was kept improved and her sCr was 2.5 mg/dL 6 months after the discharge. Discussion and Conclusion: Hypertensive emergency may cause irreversible kidney damage without appropriate antihypertensive therapy. In particular, acute tubular damages have been suggested to correlate with both systolic and diastolic blood pressures. Controlling blood pressure appropriately is crucial to protect kidneys against disease progression and even reverse kidney damage upon acute renal failure with hypertensive emergency.

Extra-pseudocapsular Transnasal Transsphenoidal Resection of Pituitary Macroadenoma: Technique Note and Evaluation of Endocrine Function

In this study, we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS). Clinical data of 144 patients with pituitary macroadenomas in the same surgical group at the Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed from January 2019 to June 2021. Based on the results of the endocrinological evaluation and MRI examinations before and after surgery, the fluctuation of pituitary function and the extent of resection were analyzed. Multiple Logistic regression analysis was used to determine the predictors affecting postoperative tumor residual. Among the 144 patients with pituitary macroadenomas, 72 (50.0%) were female and 72 (50.0%) were male, the median age was 50 years, 26 (18.1%) had invasiveness grade 0, 46 (31.9%) had grade I, 57 (39.6%) had grade II, and 15 (10.4%) had grade III according to Lu's classification method. Based on observation during surgery, 37 cases (25.7%) had no pseudocapsule, 54 cases (37.5%) had incomplete pseudocapsule, and 53 cases (36.8%) had intact pseudocapsule. In addition, 91 (63.2%) patients had total resection, 39 (27.1%) had subtotal resection, and 14 (9.7%) had partial resection. As for anterior pituitary function, 13 of 19 hypothyroid patients had recovery after surgery, with a remission rate of 68.4%. Eighteen of the 26 decreased cortisol patients got back to normal, with a remission rate of 69.2%. A total of 27 of 51 patients with hypogonadism improved, with a remission rate of 52.9%. Univariate and multivariate analyses indicated that gender, tumor size, and invasiveness were predictors of postoperative residual in patients (P<0.05). The results showed that ETTS is an effective treatment modality for restoring the function of pituitary gland of the patients with macroadenomas. Tumor size and invasiveness are predictors of the extent of surgical resection and postoperative residual of macroadenomas.

ODP344 Pituitary lymphoma: A case series in a referral center in Mexico City

Abstract Malignant lymphoma of the pituitary gland is extremely rare. The most common form of CNS involvement in lymphoma is leptomeningeal metastases, but it can also affect the spine or the cerebral parenchyma. Pituitary involvement usually presents as diabetes insipidus but can also present as hypopituitarism if there is adenohypophyseal destruction and may also present as bitemporal hemianopsia. (1)We present a case series of four patients with metastatic lymphomas to the pituitary gland that presented with diabetes insipidus to a tertiary center in Mexico City. Our investigation identified 4 patients with a previous diagnosis of lymphoma (3 B cell non-Hodgkin and 1 Hodgkin lymphoma) that were admitted into the endocrinology clinic with evidence of pituitary involvement and metastases to the pituitary gland. The average age of the cases was 54.5 years. 1 of the 4 patients had a diagnosis of HIV infections prior to the diagnosis of the lymphoma. Diabetes insipidus was present in 100% of the patients, while headache (75%) and visual field defects (50%) were the most common findings at presentation. Two of the patients also had involvement of the adenohypophysis and had hypocortisolism and central hypothyroidism that required hormone replacement therapy. All cases were documented by a lesion in the contrast enhancing lesion on MRI. Lymphoma involving the pituitary gland is particularly rare. In our series, involvement of the posterior pituitary was the most common form of presentation in contrast to the reported in other series, but the clinical presentation can be heterogenous, hence, it is important to perform an extensive endocrinological examination when pituitary involvement is suspected.1. Mathiasen RA, Jarrahy R, Cha ST, et al. Pituitary lymphoma: a case report and literature review. Pituitary. 2000;2(4): 283-287. doi: 10.1023/a: 1009969417380 Presentation: No date and time listed