Pituitary Disease Research Articles

Discordance of insulin-like growth factor-1 results and interpretation on four different platforms

ObjectiveInconsistent Insulin-like Growth Factor 1 (IGF-1) measurements among different platforms have been observed. In this study, we compared the IGF-1 assay on four different platforms. MethodsA total of 110 serum specimens were analyzed in this comparison study. IGF-1 was measured on the three different chemiluminescent automated immunoassay of Siemens Immulite 2000 XPi, DiaSorin Liaison XL, IDS iSYS and LC-MS/MS method. Results were compared with Weighted Deming regression. Bias was evaluated using the Bland-Altman method. ResultsWeighted Deming regression analysis showed approximately 36 % negative variation on Immulite, compared to Liaison (Immulite = 0.64 * DiaSorin + 2.95, r2 = 0.95); 8 % negative variation on iSYS, compared to Liaison (iSYS = 0.92 * DiaSorin + 0.51, r2 = 0.97); 17 % negative variation on LC-MS/MS, compared to Liaison (LC-MS/MS = 0.83 * DiaSorin-11.23, r2 = 0.93); 34 % positive variation on LC-MS/MS compared to Immulite (LC-MS/MS = 1.34 * Immulite-21.97, r2 = 0.96); 81 % positive variation on IDS iSYS compared to Immulite (IDS iSYS = 1.81 * Immulite-117.65, r2 = 0.83).The Bland-Altman plot showed a significant negative variation of Immulite versus DiaSorin and positive variation of IDS iSYS versus Immulite. Overall agreement between different platforms was poor, which reflected systematic difference. The variation between platforms increased as IGF-1 values increased. ConclusionsThere are wide variations between different platforms for IGF-1 measurement. The lack of standardization in IGF-1 measurement creates a challenge for clinicians to monitor IGF-1 and treat patients with pituitary disorders, when switching from one platform to another. The potential impact of the variations in IGF-1 measurement between different platforms should be taken into consideration when managing patients.

Clinical characteristics of patients with unexplainable hypothalamic disorder diagnosed by the corticotropin-releasing hormone challenge test: a retrospective study

The corticotropin-releasing hormone (CRH) challenge test can distinguish the disorders of the hypothalamus from those of the pituitary. However, the pathophysiology of hypothalamic disorder (HD) has not been fully understood. This study aimed to elucidate the clinical characteristics of patients with unexplainable HD, diagnosed by the CRH challenge test. We retrospectively reviewed patients who underwent the CRH challenge test. Patients were categorized into four groups as follows: patients with peak serum cortisol ≥18 μg/dL were assigned to the normal response (NR) group (n = 18), among patients with peak serum cortisol < 18 μg/dL and peak adrenocorticotropic hormone (ACTH) increase ≥two-fold, patients without obvious background pathology were assigned to the unexplainable-HD group (n = 18), whereas patients with obvious background pathology were assigned to the explainable-HD group (n = 38), and patients with peak serum cortisol < 18 μg/dL and peak ACTH increase <two-fold were assigned to the pituitary disorder (PD) group (n = 15). Inter-group comparisons were performed based on clinical characteristics. In the CRH challenge test, the peak plasma ACTH levels were significantly lower in the unexplainable-HD group than in the NR group, despite more than two-fold increase compared to basal levels. The increase in serum cortisol was significantly higher in the unexplainable-HD group than in the explainable-HD and PD groups. Although patients in the unexplainable-HD group showed a clear ACTH response in the insulin tolerance test, some patients had peak serum cortisol levels of < 18 μg/dL. Furthermore, attenuated diurnal variations and low normal levels of urinary free cortisol were observed. Most patients in the unexplainable-HD group were young women with chronic fatigue. However, supplementation with oral hydrocortisone at physiological doses reduced fatigue only in some patients. Patients with unexplainable HD diagnosed by the CRH challenge test had hypothalamic-pituitary-adrenal (HPA) axis dysfunction and some patients had mild central adrenal insufficiency. Hydrocortisone supplementation reduced fatigue only in some patients, suggesting that HPA axis dysfunction may be a physiological adaptation. Further investigation of these patients may help elucidate the pathophysiology of myalgic encephalitis/chronic fatigue syndrome.

Causes of hyperprolactinaemia in the primary care setting: How to optimise hyperprolactinaemia management

Background and purposeTo analyse the causes of hyperprolactinaemia in patients with symptoms compatible with hyperprolactinaemia evaluated in a primary care setting. Patients and methodsA retrospective study of all patients tested for serum prolactin levels between 2019 and 2020 in 20 primary care centres at the Hospital Ramón y Cajal in Madrid. Hyperprolactinaemia is defined as a serum prolactin>19.4ng/ml in men and >26.5ng/ml in women. Aetiology is grouped into physiological (pregnancy, lactation, inadequate venipuncture, macroprolactinaemia), pharmacological, pathological (hypothalamic and/or pituitary diseases, chronic renal failure, primary hypothyroidism), and idiopathic. ResultsIn 1630 patients tested for serum prolactin, 30.7% (n=501) had hyperprolactinaemia. Of these 501 patients, 89.6% were females. 149 patients were referred to the Endocrinology Department and 164 to the Gynaecology Department. Aetiological diagnosis of hyperprolactinaemia was achieved in 411 out of 501 cases. The most frequent cause of hyperprolactinaemia was pharmacological, in 39.1%. The second more frequent cause was idiopathic (29%) and less common were inadequate venipuncture extraction (13.4%), tumour (8.5%) and macroprolactinaemia (3.9%). Patients with tumoural hyperprolactinaemia presented higher serum prolactin levels (87.0±80.19 vs 49.7±39.62ng/ml, P=0.010). In addition, symptoms, such as galactorrhoea (33.3% vs 16.5%, P=0.018), and headache (25.7% vs 13.3%, P=0.045), were more frequent than in patients of the other aetiological groups. ConclusionHyperprolactinaemia is common among patients evaluated in a primary care setting with symptoms of hyperprolactinaemia, but more than 50% of cases are due to pharmacological treatments or improper sample extraction. It is necessary to establish referral protocols to specialised medicine to optimise healthcare resources and avoid unnecessary studies.

Pilot Findings on SARS-CoV-2 Vaccine-Induced Pituitary Diseases: A Mini Review from Diagnosis to Pathophysiology.

Since the emergence of the COVID-19 pandemic at the end of 2019, a massive vaccination campaign has been undertaken rapidly and worldwide. Like other vaccines, the COVID-19 vaccine is not devoid of side effects. Typically, the adverse side effects of vaccination include transient headache, fever, and myalgia. Endocrine organs are also affected by adverse effects. The major SARS-CoV-2 vaccine-associated endocrinopathies reported since the beginning of the vaccination campaign are thyroid and pancreas disorders. SARS-CoV-2 vaccine-induced pituitary diseases have become more frequently described in the literature. We searched PubMed/MEDLINE for commentaries, case reports, and case series articles reporting pituitary disorders following SARS-CoV-2 vaccination. The search was reiterated until September 2022, in which eight case reports were found. In all the cases, there were no personal or familial history of pituitary disease described. All the patients described had no previous SARS-CoV-2 infection prior to the vaccination episode. Regarding the type of vaccines administered, 50% of the patients received (BNT162b2; Pfizer-BioNTech) and 50% received (ChAdOx1 nCov-19; AstraZeneca). In five cases, the pituitary disorder developed after the first dose of the corresponding vaccine. Regarding the types of pituitary disorder, five were hypophysitis (variable clinical aspects ranging from pituitary lesion to pituitary stalk thickness) and three were pituitary apoplexy. The time period between vaccination and pituitary disorder ranged from one to seven days. Depending on each case's follow-up time, a complete remission was obtained in all the apoplexy cases but in only three patients with hypophysitis (persistence of the central diabetes insipidus). Both quantity and quality of the published data about pituitary inconveniences after COVID-19 vaccination are limited. Pituitary disorders, unlike thyroid disorders, occur very quickly after COVID-19 vaccination (less than seven days for pituitary disorders versus two months for thyroid disease). This is partially explained by the ease of reaching the pituitary, which is a small gland. Therefore, this gland is rapidly overspread, which explains the speed of onset of pituitary symptoms (especially ADH deficiency which is a rapid onset deficit with evocative symptoms). Accordingly, these pilot findings offer clinicians a future direction to be vigilant for possible pituitary adverse effects of vaccination. This will allow them to accurately orient patients for medical assistance when they present with remarkable symptoms, such as asthenia, polyuro-polydipsia, or severe headache, following a COVID-19 vaccination.

Long-range axonal projections of transplanted mouse embryonic stem cell-derived hypothalamic neurons into adult mouse brain.

The hypothalamus is comprised of heterogenous cell populations and includes highly complex neural circuits that regulate the autonomic nerve system. Its dysfunction therefore results in severe endocrine disorders. Although recent experiments have been conducted for in vitro organogenesis of hypothalamic neurons from embryonic stem (ES) or induced pluripotent stem (iPS) cells, whether these stem cell-derived hypothalamic neurons can be useful for regenerative medicine remains unclear. We therefore performed orthotopic transplantation of mouse ES cell (mESC)-derived hypothalamic neurons into adult mouse brains. We generated electrophysiologically functional hypothalamic neurons from mESCs and transplanted them into the supraoptic nucleus of mice. Grafts extended their axons along hypothalamic nerve bundles in host brain, and some of them even projected into the posterior pituitary (PPit), which consists of distal axons of the magnocellular neurons located in hypothalamic supraoptic and paraventricular nuclei. The axonal projections to the PPit were not observed when the mESC-derived hypothalamic neurons were ectopically transplanted into the substantia nigra reticular part. These findings suggest that our stem cell-based orthotopic transplantation approach might contribute to the establishment of regenerative medicine for hypothalamic and pituitary disorders.

ODP653 DNA Methylation Markers Detected in Liquid Biopsy Specimens Differentiate Pituitary Neuroendocrine Tumors from Other Sellar and CNS Diseases

Abstract Background DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect these molecular alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system tumors but not across PitNETs. Hypothesis PitNET-specific methylation signatures detected in liquid biopsy specimens differentiate PitNETs from other sellar diseases. Method We profiled the cfDNA methylome (EPIC array) of 44 serum and 34 plasma liquid biopsy (LB) specimens from patients with PitNETs and other CNS (craniopharyngiomas, other pituitary diseases, gliomas, meningiomas) or nontumor conditions, grouped as non-PitNET. Results Our results indicated that, despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylome captured epigenetic features reported in PitNET tissue. Using LB-derived PitNETs-specific signatures as input into a machine-learning algorithm, we generated a score that distinguished PitNETs from other pituitary and CNS diseases with high accuracy in an independent set. Conclusions Our results underpin the potential application of a methylation-based LB as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the management of patients with PitNETs. Presentation: No date and time listed

ODP358 The effect of multi-cultural inter-facility endocrine video case conferencing – A novel model of education during the COVID pandemic

Abstract Introduction Coronavirus disease 2019 (COVID-19) pandemic brought not only physical and mental health problems but also negative impacts on social, economic and educational activities. Trainees, including medical students, residents, and clinical fellows had fewer opportunities to see and discuss patients with supervisors in person. In contrast, recent advances in technology have made it possible to review cases with overseas experts through online conferences. We launched a biannual inter-facility endocrine case review meeting in a video conference format during the pandemic of COVID-19. Here we present the format of our inter-facility online case conference and its impact on trainees. Methods The conference was organized by clinical faculty members from Japan, USA and Canada. For each conference, each facility prepared one to two cases in English. Four to five cases were presented and discussed with participants and guest commentators. After completion of the 4th conference, an anonymous multiple-choice online survey was administered to all attendees, and data was collected and analyzed by the committee members. Differences in responses before and after attendance were analyzed by paired t-test. Results Four conferences were held between July/31/2020, and Dec/10/2021 (CST). The facilities participating was as follows: University of Minnesota, Hokkaido Univ., University of Alberta, and Kobe Univ. Participants included medical students, residents, endocrine fellows, and faculty. Presenters were medical students (n=1), endocrine fellows (n=15), and neurosurgery faculty (n=1). Presented topics included the following: 11 cases with pituitary disorders, 3 cases with neuroendocrine tumors, 2 cases with adrenal disorders and 1 case of thyroid disorder. Sixty-two percent of the attendees stated that 3-4 facilities are an ideal size of the collaborations in inter-facility case conference, and 82% of the attendees felt twice a year is an appropriate frequency of the conference. Ninety-seven percent of the participants indicated their willingness to continue to attend. The survey results also revealed that the conference has a positive impact on trainees’ clinical practice and career development. Furthermore, the confidence in presenting skills in English significantly increased after the conference (p&amp;lt;0. 01). Conclusion Under the COVID-19 pandemic, we launched a new format of inter-institutional case review meeting using a video conferencing system that transcends national boundaries. This represents a new educational method for trainees. A small-scale (3-4 facilities) international collaboration in a video format may provide opportunities for learning rare endocrine cases, cultural diversity of endocrine care, enhanced active learning for trainees, and the opportunity for international presentation. This may lead to the development of a novel educational system in the future. Presentation: No date and time listed

PMON312 A De Novo Heterozygous Nonsense Variant In The SEC31A Gene Associated With Pituitary Hormone Deficiency And Disorders Of Sex Development.

Abstract Introduction XYdisorders of sex development (DSD) result from variants in many different human genes but frequently have no detectable molecular cause. In approximately 25% of cases of XY DSD, the index case may have associated malformations. Genetic disorders of endoplasmic reticulum (ER) function are increasingly being recognised but have not been associated with DSD or pituitary disorders. Clinical case Three siblings (with unaffected non-consanguineous parents) were reviewed at the tertiary endocrine clinic. Child I was noted at birth to have cliteromegaly. Imaging and examination under anaesthetic revealed a normal vagina and uterus but gonads of indeterminate origin. She was 46,XY and basal endocrine investigations at the age of 4 years showed a low AMH for male but otherwise normal gonadal and thyroid function and normal IGF-1. She had a laparoscopic bilateral gonadectomy aged 5 years. Pathology demonstrated bilateral testicular tissue, with substantial fibrotic atrophic change and occasional placental alkaline phosphatase (PLAP) positive cells, suggestive of germ cell tumours. Aged 8 years she developed obesity and later hypertension. Child II was reviewed due to short stature and diagnosed with GH deficiency aged 2 years. She has normal adrenal and thyroid function and gonadotrophins. MRI demonstrated an ectopic posterior pituitary. Child III presented with perineal hypospadias, a small phallus, bilateral undescended testes and craniofacial abnormalities. Endocrine investigations revealed hypogonadotrophic hypogonadism, with no testosterone response to hCG stimulation, a low normal AMH and no response of LH or FSH on LHRH stimulation. He has panhypopituitarism with an ectopic posterior pituitary gland on MRI and is currently on treatment with GH, hydrocortisone and levothyroxine. His BP is on the 98th centile for age and height. Child I and Child III have mild developmental delay but are in mainstream school with additional educational support. High-throughput DNA sequencing revealed, in all three siblings, a heterozygous truncating variant in the SEC31A gene that encodes a component of the COPII-complex that coats the vesicles mediating ER to Golgi transport. CRISPR-Cas9 targeted knockout of the corresponding Sec31a region resulted in embryonic lethality in homozygous mice. mRNA phenotyping of ER-related genes demonstrated increased mRNA expression of ATF4 and CHOP in the affected children, genes encoding key ER stress-related proteins, associated with defective protein transport. Conclusions Dysregulation ofanterograde and retrograde COPII-coated-vesicle ER-Golgi transport is increasingly recognised to underlie human developmental disorders, including Craniolenticulosutural dysplasia (OMIM 607812) and Saul-Wilson syndrome (OMIM 618150). The de novo SEC31A nonsense variant in all three affected siblings, the ER stress response, plus reported developmental syndromes with dysfunction of this transport mechanism and evidence from the preclinical mouse model suggest that SEC31A might underlie a previously unrecognised clinical syndrome comprising DSD, endocrine abnormalities, dysmorphic features and developmental delay. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

RF09 | PSAT83 Diagnosis of Adrenal Insufficiency Based on Peak Stimulated Cortisol Levels Between 14 and 18 mcg/dL on High Dose Cosyntropin Stimulation Testing

Abstract Background Traditionally, stimulated serum cortisol &amp;lt; 18 mcg/dL at 30 or 60 minutes has been used as the cutoff for diagnosis of adrenal insufficiency (AI) during high dose cosyntropin stimulation testing (CST). Recent studies suggest that a cutoff of 14-15 mcg/dL is more accurate when using more specific monoclonal immunoassays (IAs). In February 2017, our institution switched from a polyclonal IA to a monoclonal IA. Despite this change, providers were diagnosing AI based on the 18 mcg/dL cutoff. Long term glucocorticoid use has several unwanted pleiotropic effects such as impaired glucose tolerance or diabetes mellitus (DM), hypertension (HTN), and increased risk of infection. Our study aims to evaluate patients with peak stimulated cortisol levels between 14-18 mcg/dL diagnosed with AI and placed on steroids. Methods We retrospectively reviewed charts of patients with peak cortisol levels 14-18 mcg/dL at 30 or 60 minutes on high dose CST with 250 mcg cosyntropin between February 2017 and August 2021. Cortisol levels were assessed using the monoclonal IA Roche Elecsys Cortisol II. Data regarding type and etiology of AI as well as patient demographics, comorbidities, steroid regimen, and follow up cortisol testing was collected. Worsening HTN and DM were defined as increase in blood pressure and HgbA1c respectively and/or intensification of medications between baseline at time of CST and last follow up while on steroids. Results 41 patients met inclusion criteria. 29 (71%) patients were female and mean age at CST was 52 years (range 21-86). Most patients were diagnosed with secondary (71%) or partial secondary (19%) AI by provider. Most common etiologies were pituitary disease (45%), chronic steroid use (24%), and unilateral adrenalectomy (19%). Mean follow up was 23 months (range 0.5-57). 33 (80%) patients were started or continued on glucocorticoid replacement. Remaining patients who were never started on steroids had a peak cortisol ≥ 15.6 mcg/dL. 21/33 (64%) of patients started on steroids had repeat adrenal function testing a mean of 18 months (range 2-42) after the initial CST. Based on testing or clinical judgement, 19/33 (58%) were taken off steroids. In patients treated with steroids, 64% developed weight gain, 42% worsening HTN, and 6% worsening DM. Additionally, 48% developed an infection, 24% insomnia, and 15% psychiatric illness. Conclusions The majority of patients with peak stimulated cortisol between 14-18 mcg/dL on high dose CST had secondary AI. Over 50% of patients started on steroids were later able to stop. Steroid-related complications were observed, but this may not differ significantly from the general population. This study underscores the importance of interpreting CST results in the context of the cortisol assay used and evaluating patients with secondary AI for recovery of the hypothalamic-pituitary-adrenal axis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m.

LBODP082 Thresholds For Normal In Low Dose Cortrosyn Stimulation Depends On Assay Type

Abstract Stimulation testing is used to diagnose adrenal insufficiency. The low dose stimulation test uses Cosyntropin 1 mcg to measure cortisol when pituitary disease is suspected. Protocols call for cortisol levels at baseline, 30, and 60 minutes post-administration. A passing peak cortisol threshold of 18 mcg/dl is often used. In 2019, most cortisol assays in our area shifted to more sensitive methods; these are reported to require a lower pass threshold of 12 -14 mcg/dl. We did a retrospective review on 186 consecutive patients in whom newer assays were used, to describe pass/fail rates by timepoint/threshold. Using newer assays, and cortisol cut-off of 14 mcg/dl, a significantly higher percentage pass than if one used newer assays with the older cut-off of 18 mcg/dl (84.9% vs 72%.). When a cut-off of 14 is used, a 60 min assay adds little (pass rate including only 0 and 30 min values =83.3%; pass rate if include 0, 30, and 60 min values = 84.9%). We suggest that with newer assays, interpreting with a 14 mcg/dl cut-off shows higher pass rate than with 18 mcg/dl cut-off. We also suggest that when using newer assays and cut-off of 14 mcg/dl, 60 min assays add little. Presentation: No date and time listed

RF13 | PMON83 Culture Negative Pituitary Abscesses: A Case Series

Abstract Introduction Pituitary abscesses are rare, representing less than 1% of pituitary lesions. Patients may present with pituitary hypofunction, headache, and/or vision changes, often without systemic or biochemical signs of infection, with diagnosis only made intraoperatively. Cases A 74-year-old man with history of diabetes and coronary artery disease presented with headache and left-eye ptosis. MRI revealed a 1.8 cm hypoenhancing cystic, hemorrhagic sellar mass extending into the left cavernous sinus. Pre-operative labs showed AM cortisol 1.1 ug/dL, testosterone 43 ng/dL (reference range 250-1100), FSH 15.3 mIU/mL, LH 4.5 mIU/mL consistent with adrenal insufficiency and hypogonadism. He underwent transsphenoidal pituitary resection (TSR) during which frank pus was demonstrated after incision into the dura overlying the pituitary. Surgical pathology showed necrosis and granulation-type reaction with acute inflammatory cell infiltrates. Gram stain and methenamine silver stains did not reveal definite micro-organisms while tissue bacterial cultures showed normal skin flora. He remained hemodynamically stable without fevers throughout the hospitalization and was discharged on empiric antibiotics and hydrocortisone. A 74-year-old female with history of a pituitary macroadenoma was admitted for worsening headaches. Labs were consistent with her known history of secondary adrenal insufficiency and hypogonadotropic hypogonadism. Repeat MRI showed characteristics suggestive of hemorrhage within a 1.8 cm intrasellar mass with inhomogeneous and peripheral enhancement after contrast. She underwent TSR and intraoperatively frank pus was encountered. Surgical pathology showed sinonasal mucosa with chronic inflammation. There was no growth in aerobic, fungal, or AFB cultures; anaerobic cultures grew rare commensal bacteria. She was discharged with a course of antibiotics and remains on hydrocortisone. A 42-year-old male presented with headache and was found to have a 2.5 cm sellar mass with rim enhancement elevating and compressing the optic chiasm on MRI. Labs were significant for AM cortisol 4.9 ug/dL and testosterone 8 ng/dL, FSH 0.4 mIU/mL, LH &amp;lt;0.2 mIU/mL consistent with adrenal insufficiency and hypogonadism. He underwent TSR and was found to have purulent debris in the sella. Pathology showed epithelial tissue fragments insufficient for diagnosis, and cultures grew few skin and oropharyngeal contaminants. He was discharged on hydrocortisone with a course of antibiotics. Conclusion We describe three patient cases presenting with headache and varying degrees of hypopituitarism, found to have purulent material emanating from the sella during transsphenoidal resection. None presented with clinical or biochemical systemic signs of infection. MRI imaging was variable, ranging from cystic, hemorrhagic features to peripheral enhancement. Surgical pathology and cultures were unrevealing for a definitive infectious source or other cystic lesion such as Rathke's cleft cyst. This case series demonstrates the potential nonspecific presentation of pituitary abscesses including negative cultures and pathology. It is important to keep this rare diagnosis in the differential for patients presenting with pituitary disease. Presentation: Sunday, June 12, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PSAT043 Liraglutide Ameliorates Symptoms of Cushing Syndrome in a Pediatric Patient

Abstract Background Cushing Syndrome (CS) is a rare disease characterized by hypercortisolism. Pituitary adenomas resulting in ACTH-dependent disease may be difficult to visualize radiologically, resulting in a prolonged diagnostic course and delay in definitive treatment. Adjuvant medical treatment with pharmacologic agents, including steroidogenesis inhibitors and adrenolytics, can be utilized for symptom management. However, hypercortisolemia may be refractory to medical therapy making it necessary to consider symptomatic treatments. We present a case of a pediatric patient with Cushing syndrome in whom treatment with liraglutide, a GLP-1 agonist approved for the treatment of hyperglycemia and obesity, resulted in improvement of symptoms of hypercortisolemia. Case A 13 year old Caucasian female presented with a 2 year history of linear growth arrest, accelerated weight gain and delayed puberty. Her physical examination was remarkable for overt signs of hypercortisolemia. Initial laboratory evaluation showed normal thyroid function, hyperglycemia with HbA1c 7.2% (normal &amp;lt; 5.7%), dyslipidemia and elevated midnight salivary cortisol 0.898 (normal &amp;lt; 0.112 mcg/mL). Hypercortisolemia was confirmed when morning serum cortisol was 25.6 mcg/dL after 1 mg overnight dexamethasone suppression test (DST). This along with an elevated morning ACTH level, 72.8 (7.2- 63.3 pg/mL), confirmed a diagnosis of ACTH-dependent Cushing syndrome. Magnetic Resonance Imaging of the pituitary gland with contrast showed a 4 mm non- enhancing lesion consistent with a Rathke's cleft cyst which was unlikely to be the source of excess ACTH. Results from high dose (8 mg overnight) DST, Corticotropin Releasing Hormone (CRH) stimulation test, and Inferior Petrosal Sinus Sampling for ACTH post CRH stimulation were partially inconsistent with pituitary disease. Further workup for ectopic source(s) of ACTH showed normal imaging of the neck, chest, abdomen and pelvis. A DOTATATE PET scan failed to identify an ACTH source. Adrenolytic adjuvant treatment with mitotane was started but was discontinued due to intolerable gastrointestinal effects. Treatment was changed to ketoconazole, however, hypercortisolemia remained refractory to treatment as evidenced by continued elevation of 24- hour urine free cortisol levels. Metformin was initiated for hyperglycemia treatment but was not tolerated due to persistent nausea and vomiting. The patient was switched to liraglutide and within 3 months she had 10% weight loss, normalization of fasting blood glucose levels and reduction of HbA1c to 5.7%. Additionally, the patient's energy level and baseline hidradenitis suppurativa improved. Conclusion In some pediatric patients with CS, definitive treatment of hypercortisolemia may be delayed or not feasible due to a lack of biochemical or radiological evidence showing the specific etiology for CS. Medical treatment with pharmacologic agents can be utilized for symptom management, however, hypercortisolemia may persist and even be recalcitrant to therapy. In this setting, clinicians should consider using liraglutide to ameliorate some of the cardinal symptoms of CS in pediatric patients. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PMON145 The Role of Pou3f4 in Pituitary Development and Disease

Abstract Mutations in the pituitary specific transcription factor Prophet of Pit-1 (PROP1) are the most common genetic etiology of combined pituitary hormone deficiency (CPHD), which affects 1 in 8,000 newborns worldwide. CPHD is associated with short stature, attributable to growth hormone (GH) deficiency and/or thyroid stimulating hormone (TSH) deficiency. Pathogenic lesions impair pituitary development and differentiation of endocrine cells. Prop1-mutant mice show increased expression of genes including SRY-Box Transcription Factor 21 (Sox21) and Pou Domain, Class 3, Transcription Factor 4 (Pou3f4). POU3F4 is expressed in the developing inner ear and restricts the proliferation and lineage potential of neural stem cells. Genetic defects cause non-syndromic X-linked deafness (DFNX2) in humans and mice. The function of POU3F4 in pituitary development is largely unknown and the implications of its overexpression in Prop1-mutant pituitaries remain unexplored. Therefore, we aim to address the role of Pou3f4 in pituitary development and determine the contributions of Pou3f4 upregulation to pituitary disease by utilizing Pou3f4-mutant mice as well as double mutant mice lacking both Prop1 and Pou3f4. Utilizing immunofluorescent analysis at critical timepoints during pituitary development, we have characterized the timeline for endogenous POU3F4 expression. Initial expression is detected at e11.5 in differentiating cells on the ventral side of Rathke's pouch and is restricted to the proliferating anterior lobe at e13.5, continuing postnatally, similar to previously published expression data. POU3F4 expression then decreases and becomes gradually restricted to the periluminal stem cell niche at e15.5 and p0. We further validated the upregulation of POU3F4 in histological sections of Prop1-mutant mice at e15 and p0, finding increased expression in the developing anterior lobe of mutants compared to wildtypes. Single-cell regulatory network inference and clustering (SCENIC) analyses, which utilize single-cell transcription factor co-expression with potential direct downstream targets that contain the corresponding transcription factors’ binding sequence to infer active transcription networks, predict increased activity of the Pou3f4 gene regulatory network in a subpopulation of Sox2-expressing stem cells in Prop1-mutant mice. Preliminary analyses indicate that Pou3f4 mutant have normal morphology at P1, together with grossly normal expression of Sox2 and Pou1f1. We are performing quantitative PCR to determine possible compensatory mechanisms in response to loss of Pou3f4 expression. To investigate whether any Prop1-mutant phenotypes, including dysmorphology and ectopic expression of Sox21 and Otog, are attributable to Pou3f4 upregulation, we are studying Pou3f4;Prop1 mice. We will determine the impacts of POU3F4 upregulation on cellular morphology, stem cell maintenance and endocrine cell differentiation. The mechanisms of action in the regulation of stem cell differentiation constitutes a gap in our current understanding of the pathogenesis of CPHD. These studies will provide novel insights into the mechanistic function of Pou3f4 during embryonic pituitary development and potential novel etiologies of CPHD in human patients. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP036 Cortisol Values During the Standard-Dose Cosyntropin Stimulation Test: Personal Experience with Elecsys Cortisol II Assay

Abstract Background There has been debate regarding the appropriate cortisol cutoffs during the cosyntropin stimulation test (CST) when the newer cortisol assays are used. Recent studies have recommended cortisol cutoffs lower than previously recommended. We aimed to evaluate the cortisol levels during the standard dose CST in patients evaluated for adrenal insufficiency and found to have a normal HPA axis using the Elecsys ® Cortisol II (Roche Diagnostics)assay. METHODS: This was a retrospective chart review study of adult patients who had the CST performed within an academic ambulatory setting from January 2018 to December 2020. They had ICD-10 codes of pituitary gland disorders in their problem list or diagnoses at the time of data extraction. Only patients with a normal HPA axis were included in the analysis, which was defined based on evaluation by an endocrinologist, restrictive exclusion criteria, and a lack of glucocorticoid administration for at least 6 months after CST. Exclusion criteria included oral glucocorticoid use within 6 months before the CST or 3 months for other routes, albumin &amp;lt; 2.5 g/dL, liver disease, pituitary insult within 6 weeks before the CST, estrogen and opioid use within 3 months before the CST, and pregnancy. The results are reported in the median (range). Results Out of 305 patients, 63 (20.6) met the study criteria. The median age was 54.7 (27.6-89.1) years; 32 (51%) were females, and 27 (43%) were white. The duration of follow-up after the CST was 13.9 (6.3-43.9) months. Cortisol values at 30- and 60-minutes post-CST were available for 43 (68.2%), and 61 patients (96.8%), respectively. The cortisol levels at 30- and 60-minutes after the CST were 21.7 (15.7-29.1) µg/dL and 24.4 (17.9-35.8) µg/dL, respectively. The lowest cortisol levels at 30 and 60 minutes after the CST for patients with either normal TSH or gonadal axis (n=47) or in whom both axes were normal (n=18) were similar to the entire cohort. Conclusion Our study supports using a lower cortisol cutoff value at 30 minutes after the CST using the Roche Elecsys ® Cortisol II assay. The lowest cortisol level in our cohort was 15.7 ug/dL. However, the same pass criteria cannot be used at 60 minutes. Therefore, it is essential to consider the time of cortisol draw after the CST. Presentation: No date and time listed

Use of the U.K. 100,000 genomes project to identify the genetic basis of childhood pituitary disorders within a tertiary paediatric endocrinology centre

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The effect of COVID-19 process on patients with endocrinological disease in a pandemic hospital: What happened to the others?

To evaluate the effects of the pandemic process on those with an endocrinological disease that will require close follow-up from the last visit before the pandemic. Patients of 3,903 with thyroid, calcium-bone metabolism, adrenal gland, pituitary diseases, and neuroendocrine tumor (NET) were retrospectively scanned. The remaining 855 (656 females and 199 males) patients with active disease or who still needed multidisciplinary approaches were included. The number of patients who continued the disease-related medical procedures and could complete these procedures on time in the pandemic period was determined, and medical deprivation rate (MDR) was calculated. The prepandemic period of our patients with thyroid disease (n = 594), calcium-bone metabolism disorder (n = 130), adrenal disease (n = 85), pituitary disease, and NET (n = 46) had MDRs of 85%, 56%, 81%, and 89%, respectively. For each subgroup of patients, the lowest MDR (67%) was in medullary thyroid carcinoma, the highest MDR (89%) was in differentiated thyroid carcinoma; the lowest MDR (6%) was in osteoporosis, the highest MDR (100%) was in the active Paget's disease; the lowest MDR (0%) was in primary adrenocortical insufficiency, the highest MDR (100%) was in hyperfunctional adrenal adenomas; the lowest MDR (81%) was in pituitary nonfunctional adenomas, and the highest MDR (100%) was in Cushing's disease, active prolactinoma, TSHoma, and NET, respectively. This study showed that not only those who had COVID-19 but also those who had medical deprivation due to their current endocrinological disease were not to be underestimated during the pandemic period.

Individualized Homoeopathy for Hypothyroidism: Evidence based case series

Background: Hypothyroidism is divided in two types where primary hypothyroidism is due to cause within the thyroid gland itself and Secondary Hypothyroidism is due to failure of TSH production following pituitary or hypothalamic disease.1 In this article, two cases discussed had presented with symptoms which indicates Hypothyroidism (Supported by Laboratory Investigations). Repertorial totality was obtained on the basis of individualization and Individualized homoeopathic medicines were prescribed after repertorization. Thyroid stimulating hormone ranges within the normal value after receiving individualized homoeopathic medicines with improvement of symptoms.Method: Two chronic cases of Hypothyroidism were treated with individualised homoeopathic treatment.Result: The patients were euthyroid at end of homoeopathic treatment with long followups.Interpretation: Homoeopathy is good alternative treatment to treat hormonal imbalance in the disease like Hypothyroidism where the conventional treatment has no significant effect as the medicine has to continue throughout life.Conclusion: Individulised homoeopathic medicine can treat Hypothyroidism and effect continues even after stoppage the medicines where the conventional treatment has no significant result.

Pituitary adenomas and COVID-19 related disease in pandemic time: Clinical, pathological, immunohistochemical, and ultrastructure analysis

Introduction: Methods: 47 patients were emergency operated on due to pituitary apoplexy during the pandemic time. The patients were divided into two groups according to PCR COVID-19 positive vs negative test. Histopathology all cases showed varying degrees of necrosis, microthrombi formation secondary to inflammation, and endothelial cells injuries in association with TNFa, TNFk, FVIII, DPGF, HIF1a, Il6, Il10, Il17, DPGF, CD3, CD4, CD8, CD20, CD68, CD163, ACE2, and antiCOV immunoexpression. Results: 24 women and 23 men, age ranges from 21 to 76 years (mean 42.25±13.38), 14 (36%) presented positive COVID19 tests, and 30 (64%) were covid negative. 15 were already recurrences, 4 recurrences in the same year, and 4 died during the pandemic time. 9 (30%) showed histological data of stroke, of which necrosis around &lt;25% were 8 (47%), 25-50% were 2 (12%) and &gt;50% were 8 (45%). Weak vascular changes in 4 (24%), moderate in 7 (65%) and severe in 1, moderate, and intense in 1 (6%) were observed. Conclusions: Apoplexy in a previously diagnosed macro-PAD in the setting of a recent COVID-19 infection. The patients who presented with histological features of pituitary tumor infarction alone had less severe clinical features on presentation, a longer course before presentation, and a better outcome than those presenting with hemorrhagic infarction or frank hemorrhage. Hyperactivated and dysregulated immune cells pose a substantial danger for exacerbated tissue damage. COVID-19 may increase the risk of pituitary apoplexy, and we should be vigilant for signs of this. A more insidious pathological link between COVID-19 and apoplexy may exist in addition to severe inflammatory response.

Apoplexy in Pregnancy

Headache during pregnancy is a common complaint in the emergency room. In pregnancy, pituitary disorders include both hormone active and hormone inactive tumors. Apoplexy may be the first clinical presentation of an underlying pituitary tumor. Red flag signs of presenting symptoms, to be assessed for identifying life-threatening etiology. Various pathophysiological mechanisms have been passed for pituitary apoplexy in pregnancy. Magnetic resonance imaging of the brain is the gold standard investigation. The mainstay of management is the initiation of steroids. Transnasal transsphenoidal removal of the tumor is the definitive treatment that requires a multidisciplinary approach. The indications of surgery are the presence of symptoms due to compression and endocrine abnormalities; however, gestational period should be taken into consideration. We report a case of headache in antenatal women who presented to our emergency room diagnosed with pituitary apoplexy managed with steroids and early surgery, and discharged with good clinical outcome. We recommend a methodical approach to common symptoms that assist in diagnosing forgotten etiology.

An Overview of Pituitary Incidentalomas: Diagnosis, Clinical Features, and Management.

Simple SummaryA pituitary incidentaloma is a pituitary tumor or mass that is incidentally discovered in imaging studies which have been performed for reasons other than the symptoms of pituitary lesions. The majority of pituitary incidentalomas are pituitary neuroendocrine tumors (PitNETs) and Rathke cleft cysts. PitNETs have received attention because of their distinction from pituitary adenoma in the new World Health Organization (WHO) classification. The natural history of PitNETs is partially known, and the management of pituitary incidentalomas has been determined based on this history; however, the pathology of PitNETs has significantly changed with the new WHO classification, and studies with a high level of evidence are required to consider treatment guidelines for pituitary incidentalomas.Pituitary incidentalomas are tumors or mass lesions of the pituitary gland. These are incidentally discovered during imaging studies for symptoms that are not causally related to pituitary diseases. The most common symptom that triggers an examination is headache, and the most common type of pituitary incidentalomas are pituitary neuroendocrine tumors (PitNETs) and Rathke cleft cysts. The existing treatment strategy is controversial; however, surgical resection is recommended in cases of clinically non-functioning PitNETs with optic chiasm compression. In contrast, cystic lesions, such as Rathke cleft cysts, should be followed if the patients are asymptomatic. In this case, MRI and pituitary function tests are recommended every six months to one year; if there is no change, the follow-up period should be extended. The natural history of PitNET is partially known, and the management of pituitary incidentalomas is determined by this history. However, the pathogenesis of PitNET has significantly changed with the new World Health Organization classification, and follow-up is important based on this new classification. Therefore, a high level of evidence-based research is needed to consider treatment guidelines for pituitary incidentalomas in the future.