AVP Deficiency Research Articles

Desmopressin dosing in children using real-world data and pharmacokinetic/pharmacodynamic model simulations.

Variability in pediatric dosing of desmopressin (ddAVP) in AVP-deficiency (AVP-D) is well-documented but dosing recommendations are limited. This study evaluates and optimizes ddAVP dosing regimens in children with AVP-D using pharmacokinetic and pharmacodynamic (PK/PD) simulations. Retrospective electronic health record review was done to identify children (<18 years) with AVP-D on ddAVP evaluated in the outpatient setting using ICD 9 and 10 codes. A previously developed PK/PD model from Michelet et al was used to simulate ddAVP concentrations and urine rates based on a child's age and ddAVP dose. The effects of demographic characteristics (age, weight, etc.) on dose and urine rate were investigated through simulations to optimize doses of ddAVP for children who were wet overnight. A total of 276 dosing records were identified among 53 children with AVP-D. Simulations indicated that in children under 5 years of age who were wet overnight, increasing the outpatient dose to 50 mcg was predicted to decrease urine rate to a pattern similar to those who remained dry. An initial outpatient dose of at least 50 mcg for children between 1 and 5 years of age would improve efficacy of ddAVP. 50 mcg is likely a safe initial outpatient dose of oral desmopressin tablet for young children 1-5 yrs of age with central Diabetes Insipidus/AVP-Deficiency. We confirmed that desmopressin doses vary greatly in children with central Diabetes Insipidus/AVP-deficiency. Real-world clinical data can be leveraged to improve medication dosing in rare diseases.

8301 A Rare Case of IgG4-Related Hypophysitis

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: IgG4-related disease (IgG4-RD) is an immune-mediated condition that presents as systemic inflammation and fibrosis of tissues, often affecting multiple organs. Isolated IgG4-related Hypophysitis is rare and characterized by lymphoplasmacytic infiltration of the pituitary gland by IgG4-positive plasma cells. A combination of clinical, serologic, radiologic, and histopathologic findings is used for diagnosis of IgG4-RD and approximately two-thirds of all patients have elevated serum IgG4 levels. We report a case of isolated IgG4-related Hypophysitis in a middle-aged woman serologically negative for IgG4-related disease. Case Report: A 52 year old female with history of steroid dependent severe persistent asthma, allergic rhinitis, and chronic sinusitis presented with one month of headache, polyuria, and polydipsia. MRI Brain demonstrated an enlarged, rounded pituitary gland 16 x 11 x 9 mm, with homogeneous enhancement, extension into the suprasellar cistern, and mild thickening of the infundibulum suspected to represent a pituitary adenoma. Lab evaluation revealed mild hyperprolactinemia (prolactin 83.2, normal 4.8-23.3 ng/mL) and secondary adrenal insufficiency based on an abnormal high-dose cosyntropin stimulation test in the setting of a low adrenocorticotrophic hormone (ACTH) level (&amp;lt;2.0 pg/mL). Remaining pituitary hormone levels were normal. Inpatient work-up for polyuria and polydipsia showed a low urine specific gravity of 1.003. An overnight water deprivation test was performed. Baseline urine osmolality (UOsm) was 95 mOsm/kg and serum sodium was 144 mmol/L; after 3 hours of water deprivation, serum Osm increased to 301 mOsm/kg (275-300 mOsm/kg) and UOsm only to 215 mOsm/kg, while her sodium increased to 145 mmol/L. Results were felt to be consistent with AVP deficiency (Central Diabetes Insipidus) and the patient was started on desmopressin. Because of the presence of AVP deficiency, further work-up was done to evaluate for an infiltrative process or malignancy. ANA, RPR, ESR, CRP, CBC, ACE level, T-SPOT, and IgG subclasses were unremarkable. Further imaging studies yielded a negative nuclear bone scan and PET/CT scan. For diagnostic purposes, the patient underwent biopsy via an endoscopic endonasal transsphenoidal approach. Pathology showed the presence of &amp;gt;10 IgG4+ plasma cells in a single high-power field, consistent with a diagnosis of IgG4-related Hypophysitis. Conclusion: Isolated IgG4-related Hypophysitis is the least common clinical presentation of IgG4-RD, which is itself a rare and relatively newly recognized condition. IgG4-related Hypophysitis should be suspected in patients presenting with AVP deficiency and pituitary stalk enlargement with an otherwise negative work up. Presentation: 6/2/2024

6626 Fertility considerations in Klinefelter Syndrome complicated by hypogonadotrophic hypogonadism

Abstract Disclosure: M. Govinna: None. S. Sarlos: None. C.A. Allan: None. R. Giri: None. Background: Klinefelter syndrome (KS) remains underdiagnosed with less than 50% of men ever diagnosed and &amp;gt;90% of diagnoses only occurring when fertility is sought. MicroTESE (microscopic testicular sperm extraction) is now successful in 47-69% [1]. Optimal timing of the procedure is uncertain. Case: A 14-year-old male student with a history of renal stones (normal genitourinary tract anatomy) and anxiety presented with a six-day history of new onset headaches and transient visual blurring. MRI scan showed a 2.1cm pituitary lesion with local mass effect and minimal compression of the optic chiasm. Pre-operative pituitary panel: FSH 29.8 IU/L (1.2 - 5.2 IU/L); LH 8.8 IU/L (2.0 - 8.0 IU/L); testosterone 10.9 nmol/L (0.7 - 17.6 nmol/L). Remainder of anterior pituitary function was normal; no AVP deficiency. On examination, Tanner stage P4 G4, testicular volumes 5-6ml (right) and 6-8ml (left) (expected range 15-20ml). Height 175cm (75th centile) and weight 60.1kg (63rd centile). Transsphenoidal resection (TSS) of the pituitary lesion was performed. Intraoperative appearances were suggestive of craniopharyngioma adherent to the pituitary stalk, with stalk transection to achieve complete resection. Post-operatively AVP-deficiency, hypocortisolism and secondary hypothyroidism required replacement therapy. Histopathology was subsequently consistent with Rathke’s cleft cyst. Karyotype testing confirmed 47 XXY genotype (Klinefelter syndrome). Post-TSS FSH and LH levels were 0.7IU/L (1.2 - 5.2 IU/L) and 0.3 IU/L (2.0 - 8.0 IU/L); with testosterone &amp;lt;0.1 nmol/L (0.7 - 17.6 nmol/L), consistent with hypogonadotrophic hypogonadism superimposed on a background of primary hypogonadism. Testosterone replacement therapy was commenced following discussion regarding potential future fertility options. Discussion: This diagnosis of KS highlights the importance of thorough assessment of pubertal development and testicular examination. Small testes with hypergonadotrophic hypogonadism in the context of pituitary pathology should trigger further assessment. Fertility preservation procedures in prepubertal and adolescent boys with KS remain controversial [2]. This patient represents a unique scenario whereby he is LH and FSH deficient post TSS. Whilst prior treatment with hCG does not increase sperm retrieval in non-mosaic KS [3] there may be a role for gonadotrophin therapy prior to undertaking microTESE in our patient. To date, there are no reported cases.

6626 Fertility considerations in Klinefelter Syndrome complicated by hypogonadotrophic hypogonadism

Abstract Disclosure: M. Govinna: None. S. Sarlos: None. C.A. Allan: None. R. Giri: None. Background: Klinefelter syndrome (KS) remains underdiagnosed with less than 50% of men ever diagnosed and &amp;gt;90% of diagnoses only occurring when fertility is sought. MicroTESE (microscopic testicular sperm extraction) is now successful in 47-69% [1]. Optimal timing of the procedure is uncertain. Case: A 14-year-old male student with a history of renal stones (normal genitourinary tract anatomy) and anxiety presented with a six-day history of new onset headaches and transient visual blurring. MRI scan showed a 2.1cm pituitary lesion with local mass effect and minimal compression of the optic chiasm. Pre-operative pituitary panel: FSH 29.8 IU/L (1.2 - 5.2 IU/L); LH 8.8 IU/L (2.0 - 8.0 IU/L); testosterone 10.9 nmol/L (0.7 - 17.6 nmol/L). Remainder of anterior pituitary function was normal; no AVP deficiency. On examination, Tanner stage P4 G4, testicular volumes 5-6ml (right) and 6-8ml (left) (expected range 15-20ml). Height 175cm (75th centile) and weight 60.1kg (63rd centile). Transsphenoidal resection (TSS) of the pituitary lesion was performed. Intraoperative appearances were suggestive of craniopharyngioma adherent to the pituitary stalk, with stalk transection to achieve complete resection. Post-operatively AVP-deficiency, hypocortisolism and secondary hypothyroidism required replacement therapy. Histopathology was subsequently consistent with Rathke’s cleft cyst. Karyotype testing confirmed 47 XXY genotype (Klinefelter syndrome). Post-TSS FSH and LH levels were 0.7IU/L (1.2 - 5.2 IU/L) and 0.3 IU/L (2.0 - 8.0 IU/L); with testosterone &amp;lt;0.1 nmol/L (0.7 - 17.6 nmol/L), consistent with hypogonadotrophic hypogonadism superimposed on a background of primary hypogonadism. Testosterone replacement therapy was commenced following discussion regarding potential future fertility options. Discussion: This diagnosis of KS highlights the importance of thorough assessment of pubertal development and testicular examination. Small testes with hypergonadotrophic hypogonadism in the context of pituitary pathology should trigger further assessment. Fertility preservation procedures in prepubertal and adolescent boys with KS remain controversial [2]. This patient represents a unique scenario whereby he is LH and FSH deficient post TSS. Whilst prior treatment with hCG does not increase sperm retrieval in non-mosaic KS [3] there may be a role for gonadotrophin therapy prior to undertaking microTESE in our patient. To date, there are no reported cases.

8800 A Case of Hypopituitarism Due to Sheehan Syndrome

Abstract Disclosure: N. Akabogu: None. S. Dejhansathit: None. F. Marium: None. B. Stanley: None. E.M. Bazuaye: None. L.S. Krusniak: None. L.G. Kurukulasuriya: None. U.Z. Khan: None. Background: Sheehan syndrome, which is also known as postpartum pituitary infarction, refers to the necrosis of the anterior pituitary gland due to postpartum hypovolemia, hemorrhage, shock, resulting in various degrees of hypopituitarism. The pituitary gland enlarges during pregnancy due to estrogen stimulation and becomes hyper-vascular, making it prone to infarction with postpartum hemorrhage. The initial symptoms include hyponatremia, weakness, weight loss, but the most prominent specific symptoms are inability to nurse and postpartum amenorrhea. Depending on the severity of hypopituitarism, symptoms may develop within the first few days to weeks after delivery or may take months to years to develop. Case presentation: 35year-old Caucasian female with a medical history of gestational diabetes, hyperlipidemia, and hypertension, who presented to the hospital with flu-like symptoms, leg pain, abdominal pain, and proximal muscle weakness. The evaluating hospitalist observed that patient appeared sluggish and spoke with a deep coarse voice, which concerned him for hypothyroidism. Thyroid function test revealed undetectable free T4 with inappropriately normal TSH of 1.38 – consistent with secondary hypothyroidism. Additional history from patient uncovered 9 months history of constant fatigue, weight gain, dry skin, hair loss, cold intolerance, and intermittent ankle swelling. There is no history of brain irradiation or head trauma. She has 4 biological children, and her last childbirth 3years ago was complicated by severe bleeding from her incision site, requiring transfusion of 6 units of blood. She has been amenorrheic since and is neither on birth control nor had hysterectomy. Physical exam showed mildly enlarged tongue, diffuse pallor, dry scaly skin on upper arms, scanty eyebrows, and slowed speech. Further work-up for pituitary insufficiency showed secondary adrenal insufficiency, secondary hypogonadism, low prolactin, and growth hormone deficiency. There was no evidence of AVP deficiency. Other lab and clinical findings were hypoglycemia, hyperlipidemia, elevated CK, elevated Cr, pericardial effusion, and diastolic hypertension. Pituitary MRI showed markedly attenuated and flattened pituitary gland with no focal mass. Patient was given stress dose hydrocortisone and thyroid hormone replacement, initially IV then oral. Following hydrocortisone and thyroid hormone replacement, her diastolic BP, hypoglycemia, CK, and Cr improved. Further management plans include initiating estrogen (plus progesterone) for bone health. Conclusion: Although Sheehan syndrome is rare in developed countries, it does occur. This case emphasizes the importance of detailed history taking, to discover the root of patients’ presentation. Even though TSH is the screening test for thyroid disease, when pituitary etiology is suspected, it is important to also check a free T4. Presentation: 6/1/2024

6379 Clonidin does not stimulate copeptin release

Abstract Disclosure: G. Binder: None. K. Weber: None. A. Peter: None. R. Schweizer: None. Background: Copeptin is secreted in isomolar amounts along with arginine vasopressin peptide from the posterior pituitary. Its stability makes it a perfect candidate for a biomarker of AVP deficiency. In children, the infusion of arginine and bolus of insulin stimulate copeptin; the respective stimulation test could be an alternative to the water deprivation test. Here, we retrospectively studied the effect of clonidine on copeptin release. Design and patients: This is a monocentric retrospective analysis of donated residual serum samples from 42 children with suspected of GH deficiency who underwent clonidine stimulation between 2020 and 2023. Measurements: Copeptin was measured in baseline, 30-, 60-, 90- and 120-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. GH was measured using an in-house RIA calibrated against the WHO International Reference Preparation 98/574. Results: According to the test results (clonidine and arginine test), there were 20 patients with GHD and 16 without GHD. No patient had polyuria-polydipsia syndrome. Median age was 6.7 years (quartiles; 5.6-7.8), the median height was -2.92 SDS (-3.42- -2.34), and the median BMI was-0.29 SDS (-1,32 - +0,16). The median baseline level of copeptin was 5,6 pmol/l (3.4-9.6). Median copeptin mildly decreased to 4.5 pmol/l (3.0-10.0) after 30 min; this change was not significant (P=0.45). Thereafter, median values remained low at 4.6, 4.6 and 4.6 pmol/l (60, 90 and 120 min). There was no correlation between baseline copeptin levels and the diagnosis of GHD. Conclusion: The clonidine stimulation test does not stimulate copeptin release and is therefore not suitable for the assessment of AVP deficiency in children. Presentation: 6/2/2024

Factors Associated with 30-Day Readmissions after Transsphenoidal Pituitary Surgery

PurposeDetermine the association between clinical and demographic factors and 30-day readmission risk after pituitary surgery. MethodsPatients undergoing pituitary surgery between January 2018 and December 2022 were retrospectively reviewed. Cases were extracted from a converged electronic health record that included surgeries performed at the Midwest, Southeast, and Southwest campuses of the same healthcare Enterprise. Variables were compared between patients with 30-day readmission following discharge after pituitary surgery (N=83) and a randomly sampled patient cohort with pituitary surgery but no readmission within 30 days (N=174). ResultsIn a multivariable regression model looking at the relationship between patient characteristics and readmission risk, every increase in the Medicare Severity Diagnosis Related Group score resulted in a nearly 2.3-fold increase in the risk of readmission (OR=2.335, 95% CI 1.050, 5.562, p=0.045). The presence of AVP deficiency increased the odds of readmission by more than 2-fold (OR=2.784, 95% CI 1.118, 7.124, p=0.029). The Midwest site was observed to have a nearly 67% decrease in readmission risk compared to the Southwest site (OR=0.334, 95% CI 0.134, 0.813, p=0.016), with the Southeast site being comparable to the Southwest. ConclusionOur study identifies postoperative AVP deficiency, greater co-morbidities, and geographic location as risk factors for 30-day readmission after pituitary surgery. Further investigation is required to determine how site-specific care processes can be adopted to lower readmission risk at other locations in the same healthcare enterprise.

Childhood craniopharyngioma: a retrospective study of children followed in Hôpital Universitaire de Bruxelles.

Craniopharyngiomas (CPs) are benign brain tumors accounting for 5 - 11% of intracranial tumors in children. These tumors often recur and can cause severe morbidity. Postoperative radiotherapy efficiently controls and prevents progression and recurrence. Despite advancements in neurosurgery, endocrinological, visual, and neuropsychological complications are common and significantly lower the quality of life of patients. We performed a retrospective study, including all patients younger than sixteen diagnosed with CP between July 1989 and August 2022 and followed up in Hôpital Universitaire de Bruxelles. Nineteen children with CP were included, with median age of 7 years at first symptoms and 7.5 at diagnosis. Common symptoms at diagnosis were increased intracranial pressure (63%), visual impairment (47%), growth failure (26%), polyuria/polydipsia (16%), and weight gain (10.5%). As clinical signs at diagnosis, growth failure was observed in 11/18 patients, starting with a median lag of 1 year and 4 months before diagnosis. On ophthalmological examination, 27% of patients had papillary edema and 79% had visual impairment. When visual disturbances were found, the average preoperative volume was higher (p=0.039). Only 6/19 patients had gross total surgical resection. After the first neurosurgery, 83% experienced tumor recurrence or progression at a median time of 22 months. Eleven patients (73%) underwent postsurgical radiotherapy. At diagnosis, growth hormone deficiency (GHD) was the most frequent endocrine deficit (8/17) and one year post surgery, AVP deficiency was the most frequent deficit (14/17). Obesity was present in 13% of patients at diagnosis, and in 40% six months after surgery. There was no significant change in body mass index over time (p=0.273) after the first six months post-surgery. CP is a challenging brain tumor that requires multimodal therapy and lifelong multidisciplinary follow-up including hormonal substitution therapy. Early recognition of symptoms is crucial for prompt surgical management. The management of long-term sequelae and morbidity are crucial parts of the clinical path of the patients. The results of this study highlight the fundamental importance of carrying out a complete assessment (ophthalmological, endocrinological, neurocognitive) at the time of diagnosis and during follow-up so that patients can benefit from the best possible care.

A rare case of AVP deficiency secondary to Chloroma

A rare case of AVP deficiency secondary to Chloroma

Normocytic anaemia: The clue to a brewing diagnosis of craniopharyngioma and the unmasking of AVP deficiency post-steroid replacement

Normocytic anaemia: The clue to a brewing diagnosis of craniopharyngioma and the unmasking of AVP deficiency post-steroid replacement

A rare case of AVP deficiency secondary to chloroma

A rare case of AVP deficiency secondary to chloroma

Partial central AVP deficiency

Partial central AVP deficiency

Metastatic pulmonary neuroendocrine carcinoma associated with AVP deficiency and panhypopituitarism due to a hypothalamic metastasis

Metastatic pulmonary neuroendocrine carcinoma associated with AVP deficiency and panhypopituitarism due to a hypothalamic metastasis

Copeptin Stimulation by Combined Intravenous Arginine and Oral LevoDopa/Carbidopa in Healthy Short Children and Children with the Polyuria-Polydipsia Syndrome

Introduction: Stimulated copeptin may provide an alternative to water deprivation testing (WDT) in the evaluation of polyuria-polydipsia syndrome (PPS). Though best studied, arginine stimulation alone produces a modest copeptin response in children. We investigated the effectiveness of the arginine + LevoDopa/Carbidopa stimulation test (ALD-ST) for copeptin. Methods: 47 healthy short children (controls), 10 children with primary polydipsia, and 10 children with AVP deficiency received arginine hydrochloride (500 mg/kg intravenously over 30 min) and Levodopa/carbidopa (10:1 ratio; 175 mg of l-Dopa/m2 BSA) orally. Serum copeptin was measured at 0, 60, 90, and 120 min. Results: In controls, ALD-ST increased copeptin from a median of 7.0 pmol/L (IQR 5.0–10.0) to a peak of 44.0 pmol/L (IQR 21.4–181.0) between 60 and 120 min (p < 0.001). Copeptin peak was higher in subjects who experienced nausea or vomiting (57%) than in those who did not (131.0 pmol/L [IQR 42.5–193.8] vs. 22.7 pmol/L [IQR 16.0–33.7], p < 0.001). While subjects with primary polydipsia had similar baseline (8.5 pmol/L [IQR 8.0–11.0]) and stimulated (125.2 pmol/L [IQR 87.6–174.0]) copeptin levels as controls, subjects with AVP deficiency had lower baseline (2.5 pmol/L [IQR 2.0–3.1]) and peak levels (4.6 pmol/L [IQR 2.4–6.0]). A peak copeptin of ≥9.3 pmol/L best predicted absence of complete or partial AVP deficiency with a sensitivity of 100% and specificity of 80%. Conclusions: ALD-ST induced a robust peak copeptin in healthy short children and children with primary polydipsia. Nausea/vomiting, a side effect of ALD-ST, amplified the copeptin response. The ALD-ST may be a suitable initial screening test in children with PPS.

ARGININE VASOPRESSIN DEFICIENCY INDUCES DECREASED CARDIAC FIBROSIS RATE AND MEAN ARTERIAL BLOOD PRESSURE IN RATS WITH EXPERIMENTAL ABDOMINAL AORTIC STENOSIS

Cardiac fibrosis (CF) involves the accumulation of extracellular matrix proteins in the interstitial space, often seen in various cardiac pathologies. Each year, cardiovascular diseases claim the lives of 17.9 million people worldwide. Cardiac fibroblasts and myofibroblasts, equipped with vasopressin receptors (AVP), play a crucial role in regulating cell signaling pathways associated with CF development. AVP, an immunomodulatory hormone, influences immune responses, and its deficiency results in a decrease in immune activity. Abdominal aortic stenosis (AS) serves as an experimental model for left cardiac overload hypertension and CF. Neurointermediate pituitary lobectomy (NIL) induces a permanent decrease in circulating AVP levels, showcasing regression of hepatic fibrosis in liver damage models. The quest for effective alternative treatments for cardiac fibrosis poses a substantial challenge for researchers. In this experiment, groups of male Wistar rats weighing approximately 250 g (8/group) were categorized into: 1) Intact Control (IC), 2) Abdominal Aortic Stenosis (AS), 3) Neurointermediate pituitary lobectomy (NIL), and 4) AS+NIL. The AS and AS+NIL groups underwent abdominal aortic stenosis surgery on day one of the experiment. By week 5, the NIL and NIL+AS groups underwent NIL surgery. Prior to sacrifice at week 10, intracarotid mean blood pressure (MBP) was assessed in all groups. Following sacrifice, the hearts were removed, fixed in neutral formalin, and processed in paraffn for histopathological examination using H-E, Masson's trichrome, and Sirius red staining. Results revealed an elevated MBP in the AS group (156 ± 27.1 vs. 114 ± 30 mmHg in the IC), normalized in the AS+NIL group (110 ± 40.9 mmHg), and a mild decrease in the NIL group (87 ± 7.6 mmHg). The evaluation of CF in histological slides concurred with the MBP findings; a significant increase in CF occurred in the AS group compared to the IC, NIL, and AS+NIL groups, with almost complete reversion of CF observed in the AS+NIL group. In summary, this study demonstrates that AVP deficiency induces arterial hypotension, and in the AS+NIL group, AVP deficiency led to: 1) a decrease in blood pressure to normal levels and 2) reversion of cardiac fibrosis. Further experiments are warranted to determine if the decrease in blood pressure and cardiac overload are suffcient to inhibit profibrogenic mechanisms and/or activate antifibrogenic mechanisms. Additionally, investigations are needed to explore whether AVP deficiency, beyond inhibiting the inflammatory process, promotes the activation of antifibrogenic mechanisms. The present results offer new avenues for a deeper understanding of the molecular and cellular mechanisms through which AVP deficiency or the use of AVP receptor antagonists significantly influences fibrosis regulation in organ fibrotic diseases. Funding by Autonomous University of Aguascalientes (PIFF22-1). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A rare diagnosis of Langerhans cell histiocytosis made on thyroid histology with coexisting papillary thyroid cancer and AVP deficiency.

A 48-year-old Asian male, presented to the hospital for an elective total thyroidectomy in the context of 6.3 cm thyroid nodule. The fine needle aspiration cytology of the nodule confirmed papillary thyroid cancer (PTC) with some atypical histiocytes. He has a history of idiopathic arginine vasopressin deficiency (AVP-D) and has been taking oral DDAVP 100 µg daily, self-adjusting the dose based on thirst and polyuria. Additionally, he also has a history of recurrent spontaneous pneumothorax. His total thyroidectomy was aborted due to significant intraoperative bleeding, and his admission was further complicated by post-operative hyponatraemic seizure. Thyroid histology revealed the diagnosis of Langerhans cell histiocytosis (LCH), and further investigation with contrast CT demonstrated multi-organ involvement of the thyroid, lungs, and bones. Langerhans cell histiocytosis (LCH) is a condition that can affect one or more organ systems, including the pituitary, where it can present as AVP deficiency. Strict monitoring of fluid balance, as well as serial monitoring of serum sodium, is essential in all patients with AVP-D in the perioperative setting. Iatrogenic hyponatraemic seizure is an uncommon but serious complication of DDAVP treatment in hospitalised patients with AVP-D. DDAVP dosing must be carefully monitored. LCH with multisystem involvement is an important mimic for metastatic conditions, and histological diagnosis is essential to guide treatment and prognosis. Although LCH without bone marrow involvement is unlikely to increase the risk of bleeding, its effect on tissue integrity may make surgery more challenging. BRAF-V600E mutation is an important driver mutation and a potential therapeutic target in the treatment of LCH.

SAT619 Post-operative Fluid Restriction Prevents Hyponatremia And Readmissions After Pituitary Surgery

Abstract Disclosure: J.J. Chang: None. D. Veruttipong: None. O. Chu: None. W. Erin: None. V. Gates-Bazarbay: None. S. Kling: None. K. Vinluan: None. S. Chittum: None. M. Alhadha: None. J. Fernandez-Miranda: None. Background: Delayed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion is the most common cause of readmission after pituitary transsphenoidal surgery (TSS). Post-operative fluid restriction (FR) after discharge may effectively reduce hyponatremia and related readmissions. Methods: Our aim was to assess the effectiveness of FR after TTS. We compared post-operative day (POD) 8 hyponatremia and related readmission rates pre- and post- FR protocol implementation at our institution. Pre-FR (July 1, 2018-March 15, 2020) post-TSS patients were instructed to drink ad lib or to thirst on discharge. Post-FR (March 16, 2020-December 31, 2020), post-TSS patients were routinely provided education and documentation on the outpatient protocol that recommended 1 liter/day FR from POD 3-5 to POD 8-10. Serum sodium was assessed at POD-8 for all patients. Patients hospitalized for more than 5 days after surgery, had untreated adrenal insufficiency, or had pre-existing AVP deficiency were excluded. Results: The average POD-8 sodium level was lower in the 115 patients in the pre-FR cohort than the 216 patients in the post-FR cohort (135.8±6.7 vs. 138.1±4.4 mEq/L; Wilcoxon-Mann-Whitney test p=0.0081). POD-8 hyponatremia (Na ≤134 mEq/L) occurred in a lower proportion of patients post-FR (15.0%; 32/214) than pre-FR (28.9%; 30/104) (Chi-Square test p=0.0033). Similarly, severe hyponatremia (Na ≤124 mEq/L) occurred in a lower proportion of patients post-FR (1.4%; 3/214) than pre-FR (8.7%; 9/104) (Fisher test p= 0.01). Only 1.4% (3/216) of patients were readmitted post-FR compared to the 8.7% (10/115) pre-FR (Fisher test p=0.0020). Conclusions: Our retrospective evaluation showed that implementation of post-TSS FR protocol significantly decreased hyponatremia by nearly 50% and readmissions by over 80% compared to the prior standard of care of drink ad lib or to thirst. FR should be considered standard-of-care for eligible patients without ongoing AVP deficiency to reduce hyponatremia and readmission burden to both patient and healthcare system. Presentation: Saturday, June 17, 2023

Effects of pituitary hormones deficiency from the specific pituitary lobes on learning, memory and survival behavior in the Wistar rat

The role of the different adenohypophyseal hormones (GH, PRL, ACTH, TSH, LH and FSH) and neurohypophyseal (AVP and OXY) hormones on animal behavior, memory and learning have been stablished, however the role of lobe‐specific hormones on these cerebral functions has been not completely dilucidated. Here we study the specific pituitary hormone deficiencies in hypophysectomized (HYPOX), with anterior lobectomized (AL) and neurointermediate lobectomized (NIL) rats, subject to novel object recognition (NOR), forced swim (FS) and prepulse inhibition (PPI) tests. For comparisons the intact control (IC) and sham operated (SHAM) groups were also included. The NOR test that evaluate different phases of learning and memory in rodents, showed that memory discrimination index (DI) significantly increased in the NIL group, indicating that AVP and OXY deficiency negatively affect the ability of short and medium‐term memory. The FS test assess survival and motivation behavior; results showed that AL, NIL and HYPOX groups induced a loss in motivation and will to survive (increased immobility time); these observations may be partially explained by: 1) the significant deficiency of metabolic hormones (GH, ACTH‐corticosterone, TSH‐thyroid hormones and LH‐FSH‐testosterone hormones) whose decrease also induced significant loss in both mass muscle and body weight in AL and HYPOX groups and, 2) the decreased survival and motivational behavior induced by the AVP and OXY deficiency (NIL‐induced), thus supporting the view of the motivational and survival role of these hormones. The IPP test evaluates the rat ability to respond to potentially harmful acoustic stimuli and long‐term memory; results showed that AL animals did not show any sign of learning (expressed as very low inhibition percentage), whereas, interestingly, the HYPOX group (without any pituitary hormones) the long‐term memory was not significantly affected. In conclusion these results support the important role of the several pituitary hormones mainly neurohypophyseal hormones (AVP and OXY) controlling important brain functions necessary for learning, memory, and survival. These experimental models will allow in the future to study specifically the role of each pituitary hormone on the different aspects of animal behavior such as memory, motivation, generosity, adaptation, among others.

Pituitary Macroadenoma: A Case of Balanced Deficiencies

Abstract Introduction: Diabetes insipidus (DI) rarely occurs in pituitary tumors although some patients may develop DI following pituitary tumor resection. However DI is known to occur in patients with tumors metastatic to the pituitary or in infiltrative disorders of the pituitary gland. We are reporting a patient with a 2 cm pituitary macroadenoma whose DI was unmasked by glucocorticoid therapy. Case Presentation: A 61-year-old male with a history of non-functioning pituitary macroadenoma, incidentally discovered on imaging in 2015 and stable at 1.6cm for 4 years, was referred to endocrinology for interval enlargement of his macroadenoma. He had presented to primary care due to new headache during extreme physical exertion, but otherwise denied any symptoms such as vision loss, fatigue, decreased libido, weight loss, or urinary frequency. Repeat MRI indicated growth to 2.1cm in the suprasellar component, no cavernous sinus involvement, and abutting the optic chiasm. Laboratory results revealed new onset central hypothyroidism (FT4 0.21 ng/dL (ref 0.78-2.19) with triiodothyronine 68 ng/dL (ref 80-200) and TSH 1.61 mIU/L (ref 0.47-4.68), central hypogonadism (Testosterone Free 1.3 pg/mL (ref 6.6-18.1)) and concern for adrenal insufficiency with a cortisol of 4.4 mcg/dL. He was empirically started on hydrocortisone replacement until an ACTH stimulation test could be completed, and after 3 days instructed to begin low dose levothyroxine replacement. At close followup, patient revealed that he developed new hourly nocturia causing significant distress. An overnight water deprivation test yielded a serum sodium 152 mmol/L with a urine osmolality 191 mOsm/kg, both rapidly improving with intravenous desmopressin. Copeptin was 4.6 pmol/L. Discussion Diabetes insipidus occurring in pituitary tumors including macroadenomas is extremely rare. Secretion of AVP occurs in the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, and the superior portion of the supraopticohypophyseal tract. AVP deficiency is most commonly due to damage to these areas either through neurosurgery or trauma, and more rarely tumors or infiltrative disease. However, glucocorticoid and thyroid replacement each may precipitate the development of diabetes insipidus. Well described in literature, glucocorticoid deficiency and hypothyroidism each independently impairs free water excretion. Low cortisol stimulates release of antidiuretic hormone, but this secretion is then inhibited by exogenous steroid replacement. Cortisol interferes with AVP signaling through unclear mechanisms either at the V2 receptor or post-receptor level, decreasing translocation of type 2 aquaporins and therefore reducing free water reabsorption. It is important to recognize that CDI can be unmasked after glucocorticoid or thyroid hormone replacement.

Effects of Vasopressin (AVP) Deficiency and Conivaptan (an AVP Receptors Antagonist) on Liver Physiology and Fibrosis in Rats with Protracted Portacaval Anastomosis

Liver fibrosis is due to the over deposition of collagens on the extracellular matrix, causing fibrotic septa and liver failure. Portocaval anastomosis (PCA) is a model of liver disease. Fibrogenesis is stimulated by AVP. We have described the healthy effect of the AVP deficiency, induced by neurointermediate pituitary lobectomy (NIL), on liver functions and cirrhosis. We hypothesize that blocking the AVP receptors with the V1a-V2 AVP receptor antagonist conivaptan (CV) will induce the same healthy effects of NIL on liver fibrosis. Male Wistar rats were divided in 6 groups (8-10 each): Sham surgery (SHAM), PCA, NIL, PCA+NIL, CV and PCA+CV. SHAM, NIL and the 4 groups with PCA were operated at week 0, whereas NIL surgery in the PCA+NIL group was done at week 8. CV treatments (30 mg/day/im/8 weeks) in the CV group started at week 0, whereas in the PCA+CV group started at week 8. NIL and CV groups were sacrificed at week 8, whereas SHAM, PCA, PCA+NIL and PCA+CV groups were sacrificed at week 16. At sacrifice, serum levels of ALT, AST, bilirubin, NH4, urea, albumin and glucose were assessed. Livers were weighed and samples were processed for glycogen content and the other processed for light microscopy analysis (slide tissues stained with H-E, Masson and Sirius red). Results are summarized in Table 1. Table 1. Comparative effects of sham surgery (SHAM), portocaval anastomosis (PCA), neurointermediate pituitary lobectomy (NIL), PCA+NIL, conivaptan (CV) and PCA+CV on body weight, liver weight, glycogen liver content and serum biochemical parameters of liver functions GROUPS SHAM PCA NIL PCA+NIL CV PCA+CV (Basal values) Body weight = ↓ (-29%) ↓ (-22%) (- ↓(-29%) = ↓ (23%) (g) NS vs SHAM NS vs SHAM NS vs SHAM NS vs SHAM Liver weight = ↓ (-54%) = = = ↓ (-22%) (g) p<0.05 vsSHAM NS vsSHAM ALT(U/L) = ↑↑↑ ↑↑↑ = = = AST(U/L) = ↑↑↑ ↑↑↑ ↑↑ = = Total bilirubin (mg/dL) = ↑↑↑ = = = = Unconjugated bilirubin (mg/dL) = ↑↑↑ = = = = Albumin(g/dL) = = = = = = Glucose (mg/dL) = = = = = ↓↓↓ NH4(µg/dL) = ↑↑↑ = = = ↑↑↑ Urea(mg/dL) = ↓↓↓ = = = = Liver glycogen(mg/gr of tissue) = ↓↓↓ = = = = Liver histopathology. In the PCA group, mainly in the periportal areas, small inflammatory infiltrates and big deposits of collagen were developed. Compared with the PCA, PCA+NIL and PCA+CV groups showed less inflammatory areas and much less collagen deposits. Conclusions, all results showed that: 1) AVP deficiency restores to normality the liver physiology and histology in the protracted liver disease, 2) Except the alterations in glycemia and NH4 metabolism, similar restored effects in liver histophysiology were induced by CV, suggesting that similar cellular mechanisms are involved, 3) Results strongly support that AVP is an important role in the pathophysiology of the liver fibrosis and possibly other fibrotic diseases.