bluuebunny/crossref_metadata_2025 huggingface dataset:
PMON75 Unilateral Galactorrhea in an Elderly Male
Authors: Monsour Elio , Amole Morolake , Xhikola Majlinda , Kadiyala Sushma
Published: November 2022

Introduction/Background

Galactorrhea in men is rare, with a reported prevalence of 5.5%. It tends to occur bilaterally rather than unilaterally. Among the etiologies of galactorrhea, pharmacologic agents, pituitary tumors, and hypothalamic and pituitary-stalk lesions tend to account for most cases. Here we describe a rare cause of unilateral galactorrhea due to previous herpes zoster in the T4 dermatome.

Clinical Case

A 76-year-old male with history of hypertension, Crohn's disease, and chronic migraine headaches presented to the Endocrine clinic for evaluation of intermittent unilateral galactorrhea, which had been ongoing for the past 5 years. The patient had no known precipitating events, but he had noticed that galactorrhea was more pronounced in the spring-summer seasons, during which time he used to work outdoors more. No history of cancer, hypothalamic-pituitary disease, or other endocrinopathies. The patient was a former smoker and denied marijuana or alcohol use. He reported a family history of breast cancer in his maternal grandmother. He had no biological children. Active medications included sumatriptan as needed for migraines. Physical examination was notable for gynecomastia that was more prominent on the left. Tenderness to palpation was noticed over the left breast with no exudate expressed from the nipples. Genital exam revealed decreased testicular volume at approximately 10 ml each.

Laboratory evaluation revealed normal renal function, prolactin, estradiol, β-HCG, TSH, and normal male karyotype. Testosterone level was low with elevated LH and FSH, suggesting primary hypogonadism. Mammogram and US of the breast were not concerning for malignancy. MRI brain was without pituitary abnormalities. After a detailed discussion on a subsequent follow-up visit, the patient recalled an episode of herpes zoster infection over his left breast about 5 years ago and since had been experiencing left breast pain and nipple discharge.

Discussion and conclusion

We present a unique case of post-herpetic galactorrhea in an elderly male patient. In the literature, there are case reports that describe galactorrhea in patients post chest wall injuries or chest surgeries, and there was one case report of galactorrhea in a postmenopausal female post zoster infection. A possible mechanism of galactorrhea is thought to be stimulation of the lactational neural arch, and in our case, possibly stimulated by the zoster infection. Prior herpes zoster infection and post-herpetic neuralgia are likely causes for underlying intermittent unilateral galactorrhea. Albeit rare, clinicians should be aware of this etiology when comprehensively evaluating for galactorrhea.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON79 Supraphysiologic vasopressin-induced receptor desensitization; a case report
Authors: Rabiei Samaneh , Jaffa Matthew , Kantorovich Vitaly
Published: November 2022

Background

Arginine vasopressin (AVP) is a nonapeptide released from the neurohypophysis in response to increases in plasma osmolality, hypovolemia, hypotension, and angiotensin II. V2 receptors, expressed on the basolateral membrane of the renal collecting ducts coupled to the adenylyl cyclase-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway. PKA increases the synthesis and shuttling of aquaporin 2 water channel containing vesicles (AQMCV) from cytoplasmic vesicles to the luminal surface of the renal collecting ducts (and inhibits the endocytosis of the vesicles), where they are inserted into the apical cell membrane. As a result, AVP increases free water reabsorption from the filtrate and decreases serum osmolality.

There are different protocols for CDI management in post neurosurgical patient, including IV or SQ injections as well as continuous vasopressin drip. Here we discussed a case where prolonged IV drip could probably have caused loss of response to IV DDAVP injections.

Case

Patient is a 46-year-old male admitted with AMS with imaging revealed ruptured anterior communicating artery aneurysm associated with subarachnoid and intra parenchymal hemorrhage. The patient underwent emergent aneurysm coiling and EVD placed. The patient was subsequently started on heparin infusion due to a large frontal lobe clot which was found on cerebral angiogram. The next day, the patient developed acute diabetes insipidus with hypernatremia and polyuria. Repeat head CT demonstrated increased cerebral edema around the frontal clot. The patient underwent right frontal craniotomy for clot evacuation. He patient was subsequently started on vasopressin infusion (ranging from 0.5-6 units/hour) by neurosurgery team for urinary output less than 200 mL/hour. ​Urinary output and sodium level improved and remained stable on infusion. When endocrinology attempted transition to DDAVP IV injections patient responded with severe polyuria to initial 0.5 mcg injection. Eventually patient required 1 mcg IV every 4 hours dosing to maintain normal urine output and required a slow wean off to the standard dose of 0.5 mcg every 8 hours over 14 days.

Discussion

we are presenting a case of CDI associated to SAH who was started on IV infusion of vasopressin, required slow weaning. phenomenon called for slow re-sensitization of the receptors with gradual decreasing of DDAVP dosing. Animal studies have shown that V1 and V2 receptors levels are sensitive to hormone-induced downregulation of hormone receptors. Hypervasopressinemia in rats whose blood vasopressin concentration was experimentally elevated by IV infusion to extraphysiologic levels caused significant desensitization of kidney vasopressin receptors. In another study, IM injection of DDAVP to rats led to a total loss of kidney V receptors. Thus, it is likely that administration of high dose DDAVP IV in this patient induced downregulation of kidney V2 receptors.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON96 A Curious Case of Isolated Oculomotor Nerve Palsy From a Non-Functional Gonadotroph Adenoma
Authors: Iqbal Qasim Zafar , Moran Heberth , Harmson Jeremy , Grissett Bryan , Dendy Jared
Published: November 2022

Introduction

Pituitary adenoma typically presents with signs and symptoms of hormone hypersecretion and only 30% of cases present clinically as nonfunctioning adenomas. Furthermore, amongst these less than 5% are associated with ocular nerve palsies. We report a rare case of isolated, unilateral oculomotor nerve palsy due to a non-functional gonadotroph adenoma expanding into the left cavernous sinus.

Case

48 years old male with a pertinent medical history of Type 2 Diabetes Mellitus presented to the ER with 3 days of intractable generalized headache associated with double vision, nausea, and increased lethargy. On initial examination, he had findings of oculomotor nerve palsy on the left eye (ptosis, the eye being down and out, and non-reactive pupil to direct or consensual light stimulation) while the rest of his examination was normal. His initial blood work was non-revealing and normal. He underwent extensive imaging including an initial CT scan showing a pituitary macroadenoma, followed by a pituitary-focused MRI brain revealing a hyperplastic pituitary lesion measuring 17.8 mm×22.5 mm in axial axis and 16.4 mm×14.4 mm in sagittal axis with extension into the left cavernous sinus. Biochemical workup was done to evaluate the pituitary function and it revealed a low total testosterone level (95 ng/ml) with a suppressed LH (2.1IU/l) and FSH (1.76 mIU/ml), a low fT4 (0.58 ng/dl) with a suppressed TSH (0.68 mIU/l), low cortisol (1.2 mcg/dl) with a suppressed ACTH of < 5 pg/ml and normal IGF-1 and prolactin levels. He was given stress dose steroids and underwent transsphenoidal resection of the pituitary mass. Pathology of the specimen showed immunoreactivity for SF1 and ASU which was suggestive of a gonadotroph adenoma. The patient showed no signs or symptoms of diabetes insipidus post-operatively, however, was managed for secondary adrenal insufficiency, hypothyroidism, and hypogonadism. He was discharged home on hydrocortisone, levothyroxine, and metformin. He followed up at the Neuroendocrine clinic within a week of discharge and maintained a regular outpatient follow-up where he showed gradual improvement in his symptoms.

Conclusion

Visual impairment from a non-secreting pituitary adenoma is usually from chiasmal compression. Very rarely, pituitary macroadenoma expands laterally into the cavernous sinus and compresses the oculomotor nerve causing signs and symptoms of third nerve palsy. This case highlights the importance of recognizing different presentations of nonfunctional pituitary adenoma early as this could improve both the morbidity and mortality associated with them.

Reference

Choong, K., Lee, S L. Pituitary Macroadenoma with invasion into the cavernous sinus, cranial nerve palsies (Endocrine Today)

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON99 A Rare Case of an Intrasellar Epidermoid Cyst And Panhypopituitarism
Authors: Azmath Misbah , Rivera Luisa Bernacet , Bulsara Ketan , Madhavan Parvathy , Tendler Beatriz
Published: November 2022

Introduction

Epidermoid cysts are rare intracranially occurring mainly in subarachnoid spaces such as parasellar cisterns, middle fossa and cerebellopontine angle. Only few cases of infundibular/sellar epidermoid cysts have been described. We present the case of a large sellar epidermoid cyst resulting in panhypopituitarism.

Case

49 year old male with history of obesity and hypertension presented to the emergency department with acute onset progressively worsening headaches. He denied vision changes, nausea, vomiting or dizziness. Examination showed stable vital signs and ophthalmologic exam did not reveal any visual deficits. Further, he did not have any signs of pituitary hormone excess including hypercortisolemia or acromegaly. Brain MRI with and without IV contrast revealed a peripherally enhancing multilobulated cystic pituitary mass measuring 19.5 mm×17 mm×20.5 mm deviating the infundibulum to the left causing compression of the caudal aspect of the optic chiasm. Initial endocrinology work-up revealed noon time cortisol of 10.7 mcg/dL (range 7-23), 7 pm ACTH of 34.6 pg/mL (range 7.2-63.3), TSH of 1.71 mIU/mL (range 0.35- 4.94), free T4 of 0.93 ng/dL (range 0.5-1.39), FSH of 4.45 mIU/mL (range 1.27-19.26), LH 5.51 mIU/mL (range 1.24-8.62), IGF-1 level of 199 ng/mL (range 68-225), prolactin <0.60 ng/mL (range 2.64-13.13), and testosterone level of 186 ng/dL (range 175-800). A presumed diagnosis of non- functioning pituitary macroadenoma with compression of chiasm was made and he underwent transsphenoidal hypophysectomy after evaluation by a multi-disciplinary team including neurosurgery, ENT and endocrinology. Post-operative course was uneventful, he was started on empiric steroids which were tapered slowly. Final pathology of surgical specimen demonstrated epidermoid cyst, focal necrosis, lymphocytes and macrophages infiltration consistent with reactive granulation tissue. On subsequent laboratory evaluation, he was found to have hypogonadotropic hypogonadism with an undetectable testosterone. FT4 was also low at 0.61 ng/dL (range 0.5-1.39). He is closely following with endocrinology for management of hypogonadotropic hypogonadism and hypothyroidism.

Conclusion

Intracranial epidermoid cysts are uncommon benign congenital lesions arising from trapped surface of ectodermal elements. Very rarely, they are found in the sellar region. Sellar epidermoid cysts tend to present late and often after significant growth and mass effects. Complete resection is challenging and recurrence is a feared complication. Our patient presented with acute symptoms from expansion of a large epidermoid sellar cyst mimicking a pituitary macroadenoma. It also resulted in hypopituitarism. Although, a rare entity, early recognition and prompt management of such lesions is key.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF25 | PMON179 Role of Apparent Strong Ion Difference in the Differential Diagnosis of Thiazide Associated Hyponatremia
Authors: Monnerat Sophie , Potasso Laura , Refardt Julie , Winzeler Bettina , Christ-Crain Mirjam
Published: November 2022

Background

Differential diagnosis of hyponatremia is challenging, particularly for thiazide associated hyponatremia (TAH), as patients might have either volume depletion in need for fluid substitution or syndrome of inappropriate antidiuresis (SIAD)-like presentation requiring fluid restriction. Urine indices are of little utility, because they are influenced by thiazide therapy. Apparent strong ion difference (aSID) describes the relation between sodium, potassium and chloride in serum and is used in evaluation of acid-base disorders according to Stewart model. aSID could help in the differential diagnosis of TAH because a value >40 identifies patients with contraction alkalosis due to relative hypochloremia, and hypochloremic alkalosis is a well-known possible adverse effect of thiazide diuretics.

Material and Methods

This was a post-hoc analysis of prospectively collected data of hospitalized patients with hypotonic hyponatremia <125 mmol/l. TAH patients were divided according to treatment response in patients needing intravenous fluid substitution or fluid restriction. Treatment response was defined as a sodium increase of at least 4 mmol/l/die or >130 mmol/l based on chart review. aSID at baseline was calculated with the formula serum sodium plus potassium minus chloride and a value >40 was used to identify volume-depleted TAH patients. Descriptive analysis was carried out to find differences between volume-depleted and SIAD-like TAH patients, and patients with SIAD without thiazide use. Logistic regression and ROC curves were computed to investigate the role of aSID>40 for differential diagnosis of hyponatremia in TAH patients, in addition to known factors for identifying SIAD patients as body mass index (BMI) and fractioned uric acid excretion (FUA) with the previous described cut-off of 12%.

Results

Out of 303 hyponatremia patients, 131 (43.2%) had a TAH and 75 (24.8%) SIAD without thiazide use. Among TAH patients, 81 (61.8%) were successfully treated with fluid substitution and 31 (23.7%) with fluid restriction. 19 patients (14.5%) were excluded as they received no treatment, or needed to switch treatment during hospitalization. No differences in baseline characteristics were seen between patients with SIAD and SIAD-like TAH patients, except for BMI, lower in SIAD patients (mean(SD) 23.5(5.1) vs 27.0(5.7) kg/m2, p=0.003). A higher BMI and a FUA<12% had a sensitivity of 84% with a specificity of 60% in identifying volume-depleted TAH patients. Adding aSID>40 improved the specificity to 74% maintaining a sensitivity to 82%.

Conclusion

In hospitalized patients with TAH, calculation of aSID may help differentiating patients with volume depletion in need of fluid substitution from SIAD-like manifestation requiring fluid restriction.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:37 p.m. - 12:42 p.m.
ODP379 Brain MRIs may be value in children with isolated growth hormone deficiency whose peak GH level below 5 ng/mL in two growth hormone provocation test
Authors: Park So Yun , Kang Seok-Jin
Published: November 2022

Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormonedeficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7–10 ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations. In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed. MRIs findings were categorized as normal, incidental, of uncertain significance, or pathogenic pituitary hypoplasia, small stalk and/or ectopic posterior pituitary and tumors. Of the 379 patients with GHD, 60.4% had normal MRIs. 22.4% had incidental findings, 3.2% had pathogenic findings including ectopic pituitary gland, pituitary hypoplasia, and pituitary stalk interruption syndrome. Patient with peak GH level <5 ng/mL had a significantly higher prevalence of pathogenic findings.

Presentation: No date and time listed
ODP388 Hypernatremia in a Male Adolescent Leading to Diagnosis of Septo-optic Dysplasia
Authors: Currais Carolina , Gomez Patricia
Published: November 2022

Introduction

Septo-optic dysplasia (SOD) is a rare, heterogeneous condition defined by any combination of optic nerve hypoplasia, midline radiologic abnormalities and pituitary hypoplasia. The majority of cases are sporadic, but a number of familial cases have been described. Mutations in genes such as HESX1, SOX2 and SOX3 have been identified. Typically, SOD is diagnosed in newborns and infants with a reported incidence of 1: 10,000 live births. The diagnosis can be made when two or more features of the classic triad are present. If familial, genetic testing can be obtained to confirm the diagnosis.

Clinical Case

A 17 year and 7-month-old male patient with a history of cerebral palsy, paraplegia and obesity was admitted for management of a right arm osteomyelitis. We were initially consulted for incidentally discovered pre-diabetes (HbA1c: 6.4%), likely secondary to unhealthy eating patterns (negative pancreatic antibodies). He was made NPO prior to surgery and subsequently developed hypernatremia (161 mmol/L), which was initially thought to be iatrogenic due to large volume of normal saline received. Despite discontinuation of normal saline and replacement of free water, hypernatremia persisted (159-172 mmol/L). He had an elevated serum osmolality (321 mOsm/kg) with a low urine osmolality (240 mOsm/kg) and low specific gravity (<1. 005). He was also polyuric (urine output 4.7 mL/kg/hr). With mentioned findings and a Copetin level of 2mol/L, a diagnosis of compensated central DI was established. He initially required a vasopressin drip in addition to slow replacement of free water in order to normalize his sodium level. After his sodium was stabilized, he was started on treatment with oral desmopressin. An MRI obtained was remarkable for small optic nerves and a small optic chiasm. Ophthalmology evaluation confirmed small, hypoplastic optic nerves. Constellation of findings were indicative of septo-optic dysplasia, presenting with central diabetes insipidus. Other than an IGF-1 on the low side (155 ng/L, z-score: -2.7), there was no evidence of additional pituitary hormone deficiencies.

Conclusion

The presence of cerebral palsy and central diabetes insipidus generated suspicion of midbrain defects, which may be associated with SOD. SOD is typically diagnosed in the newborn period, but this case points to the possibility of a more delayed presentation and diagnosis. SOD is a rare, highly heterogeneous condition. Both the age of presentation and which pituitary hormone deficiencies are present are variable. With early diagnosis, hormonal deficiencies can be monitored and replaced as required. A high index of suspicion is essential if features of the classic triad are present, regardless of age of presentation.

Presentation: No date and time listed
ODP047 Intramuscular ACTH stimulation test in a patient with liver disease
Authors: Khurram Daniyeh , Dadlani Apaar , Krishnasamy Sathya
Published: November 2022

Introduction

High dose (250 mcg) ACTH stimulation test is the gold standard dynamic testing to diagnose primary adrenal insufficiency (PAI). While the current guidelines do not elaborate on the preferable route of administration of corticotropin (intravenous or intramuscular), most published studies have been conducted on healthy people using the intravenous route. We present a patient with non-alcoholic steatohepatitis cirrhosis and hypotension who was thought to have suboptimal response with intramuscular ACTH stimulation test.

Case

62-year-old male with cirrhosis, presented with dizziness, and was found to be hypotensive. Lab tests showed normal cell counts, electrolytes, renal function and lactic acid. His albumin was 2.6 g/dL. His blood pressure did not improve with intravenous fluids. Workup initiated for adrenal insufficiency showed 8 am cortisol level of 7. 0 mcg/dL, and ACTH level of 26 pg/mL. He underwent ACTH stimulation test with 250 mcg intramuscular cosyntropin, after which the 30-minute cortisol level was 13.7 mcg/dL and the 60-minute level was 15.1 mcg/dL (level immediately before the test 7.2 mcg/dL). Due to the patient not having signs of adrenal insufficiency and low albumin level due to liver disease, the cortisol response was considered adequate.

Discussion

Per the current Endocrine Society Clinical Practice Guidelines, the standard method of performing the ACTH stimulation test involves measuring baseline cortisol level, administration of 250 mcg of cosyntropin, and then measuring cortisol level 30 and 60 minutes post administration. Traditionally, an appropriate response is characterized by peak cortisol level above 18 mcg/dL, with lower values indicative of AI. While the responses can vary due to multitude of factors including time of testing etc., the individual response to the intravenous versus intramuscular injections is similar. However, the cut-off points between the two administration methods may differ. In a study on 64 healthy adult men who were administered 250 mcg cosyntropin intramuscularly, Longui et al. demonstrated lower cut-off values of 12.6 mcg/dL and 16.3 mcg/dL at 30 and 60 minutes respectively. In addition, with the introduction of newer monoclonal antibody and LC-MS/MS assays having greater specificity for cortisol, a study by Jarvosky et. al. recommends a new lower cut-off of 14-15 mcg/dL. Furthermore, several studies have shown higher prevalence of low total cortisol levels in cirrhosis and other liver disease leading to overdiagnosis of PAI, due to deficiency of cortisol binding globulin and albumin. In our patient, we hypothesize that the combination of all these factors could have caused a falsely low cortisol peak level without any underlying PAI. Our case highlights the need for additional studies on patients with underlying liver disease and hypoalbuminemia who undergo testing with intramuscular cosyntropin administration, and analysis with the new assays available.

Presentation: No date and time listed
PMON187 Worsening Hypertriglyceridemia in an Adolescent Female with Type 1 Diabetes Mellitus despite Improvement in Glucose Control
Authors: Figueredo Veronica , Sanchez Janine
Published: November 2022

Background

Chylomicronemia syndrome with severe hypertriglyceridemia may be the result of genetic abnormalities, aggravating factors or a combination of both.

Clinical case

The patient is a 17-year-old overweight female (BMI of 90th percentile) with a history of type 1 diabetes mellitus (T1D) for eleven years, PCOS, vitamin D deficiency and hypertriglyceridemia. Her father has a history of hypertriglyceridemia that improves with dietary modifications. Her mother and younger sister (who also has T1D) have normal serum lipid levels. Although the patient has a history of poor compliance (HbA1c ranging between 9-11%), glucose control had been improving (HbA1c most recently between 8.1-8.6%). Her serum triglyceride level had been slightly abnormal for the past few years (200-300 mg/dL; normal range: < 90 mg/dL) and had increased to 413 mg/dL, despite the improvement in glucose control. She subsequently started taking omega-3, 1000 mg daily. At that time, she also began treatment with combined oral contraceptives (COCs) for PCOS. The serum triglyceride level three months later increased to 1,322 mg/dL. She consistently denied alcohol or recreational drug use. The omega-3 dose was increased to 4 gm daily. Atorvastatin 10 mg daily was also started and COCs were discontinued. Three weeks later, a repeat triglyceride level was found to be 2,813 mg/dL. Fenofibrate 160 mg daily was added. Atorvastatin was discontinued and she began a low-fat diet. After further questioning, patient admitted to heavy alcohol intake during the weekends. She reported specifically drinking grain alcohols to avoid carbohydrates. Three weeks after cessation of alcohol, her triglyceride level declined to 302 mg/dL.

Clinical lesson: This patient had multiple risk factors for chylomicronemia syndrome including poorly controlled T1D, overweight and estrogen containing contraceptive therapy. Although alcohol abuse was a problem at the time hypertriglyceridemia worsened, the history of excessive alcohol consumption was not given until many other treatments had been initiated.

This case highlights the importance of screening for alcohol abuse in patients with hypertriglyceridemia who do not respond to standard therapies, especially in adolescent patients who may be reticent about discussing alcohol abuse with their physicians.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON331 The Natural History of Pituitary Cysts in Patients with Growth Hormone Deficiency and Idiopathic Short Stature
Authors: Krasnow Matthew , McGuirk Liam , Krasnow Nicholas , Patale Tara , Manely Sarah , Sayegh Emily , Epstein Benjamin , Tenner Michael , Mehta Shilpa , Schefflein Javin , Mehta Hasit , Noto Richard
Published: November 2022

Background

Pituitary cysts may be implicated in short stature and affect growth hormone secretion. The natural history of cysts is not known in patients with GHD and ISS.

Objective

To characterize the progression of cyst volume (CV) and percentage of the gland occupied by the cyst (POGO) over time in GHD and ISS patients.

Subjects and Methods

A pediatric health system's database was queried for patients diagnosed with short stature and a cyst with at least one follow up MRI between 2007-21. Data up to 7 years after first follow up was included in this study. The mean and median follow up time were 1.32±1.24 and 1.00. Cysts with a POGO≤15% were considered small, while a POGO>15% were considered large.

Results

The mean and median %ΔCV for all patients for all their follow up MRIs were 38.27%±179.14 and 0%. The mean and median %ΔPOGO for all patients were 38.32%±219.85 and -5.79%. The mean and median %ΔCV for patients with a small cyst (SC) (n=34) were 61.49%±215.60 and 0%. The mean and median %ΔPOGO for patients with a SC were 61.62%±267.25 and -2.89%. The mean and median %ΔCV for patients with a large cyst(LC)(n=14) were -0.4% ±-79.25 and 0%. The mean and median %ΔPOGO for patients with a LC were -1.08%±90.50 and -15.67%. 5 of the 35(14.3%) SCs grew into LCs and stayed large while 6 of the 14 LCs shrunk into SCs. 4 cysts fluctuated between large and small: 3 started large and 1 started small. CV of patients with LCs has a significant negative correlation with time (-0.37, p=0.01). The slope of the regression line is -0.01 mm3/month. The CV of patients with SCs does not show any change in time (-0.02, p=0.84). There is no significant difference in POGO (p=0.86) or in CV (p=0.96) in GHD and ISS patients. In GHD and ISS patients, the difference in POGO is different in each group at each MRI date (p=0.02), but not in CV (p=0.38). GHD patients had an average ΔPOGO of -1.05, while ISS patients had an average ΔPOGO of 1.26.

Conclusion

POGO can change greatly over time. LCs tend to take up less of the gland over time. SCs tend not to change significantly over time, but a minority can still enlarge and need to be monitored. So far, there have been no significant clinical consequences related to these cysts.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PSAT116 Perceived Facilitators and Barriers Using Telemedicine for Gender-Affirming Care in Youth: A Qualitative Study
Authors: Inwards-Breland David , Yeh Debra , Richardson T , Marinkovic Maja , Marino-Kibbee Bixby , Rhee Kay
Published: November 2022

Background

Multi-disciplinary gender-affirming care centers (GACC) are seeing increasing numbers of transgender and non-binary (TNB) youth seeking medical care. In the wake of the COVID pandemic, telemedicine use in clinical settings, including GACC, have increased. There is a paucity of research in the provision of care by telemedicine for gender care as well as TNB youth's perspectives on its use.

Objective

To explore perspectives of TNB youth in the use of telemedicine for gender-affirming care.

Methods

Participants aged 13-21 years, who identified as TNB, were recruited from gender center at a large academic center to participate in a semi-structured interview and demographics survey. Interviews were audio-recorded and transcribed verbatim. Survey results were analyzed using descriptive statistics. Two independent coders reviewed the transcripts, developed a preliminary coding scheme, and reached consensus on discrepancies. ATLAS.ti® was used for thematic analysis.

Results

TNB youth (n=30) had a mean age of 17 years; 30% identified as female/trans female, 47% as male/trans male, and 23% as non-binary or gender fluid. Overall, participants favored in-person visits over telemedicine because of connection with their provider. Patients also had a lack of perceived knowledge about telemedicine despite having good working knowledge of technology. They had mixed feelings regarding clinic staff's role in telemedicine (some felt it was a waste of time, others found it helpful to orient and offer future visits). There were minimal concerns around confidentiality and having a secure line. Advantages to telemedicine included convenience (no travel time or missing school), and discussion of hormone therapy, medication changes, and lab results. However, it was not optimal for full assessment of treatment progress because there was no physical exam.

Conclusions

Despite participants’ preference for in-person visits, telemedicine is a viable option for TNB youth in receiving gender-affirming medical care because of convenience and perceived confidentiality. Efforts to increase telemedicine use could center on providers and clinic staff providing education on the technical aspects of telemedicine use and promoting its availability for discussion-based visits.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF14 | LBMON195 Once-weekly Somapacitan Is Effective And Well Tolerated In Children With GH Deficiency: A Randomized Phase 3 Trial
Authors: Miller Bradley , Blair Joanne C , Højby Rasmussen Michael , Böttcher Volker , Juul Kildemoes Rasmus , Maniatis Aristides , Beck Bang Rikke , Mori Jun , Polak Michel , Stagi Stefano , Horikawa Reiko ,   on behalf of the REAL4 study group
Published: November 2022

Growth hormone (GH) replacement therapy usually requires daily subcutaneous (s.c.) injections that can be burdensome for patients and their caregivers. Somapacitan, a long-acting reversible albumin-binding GH derivative, is in development for once-weekly s.c. administration in children with GH deficiency (GHD). REAL4 is a randomised, multi-national, open labelled, and active-controlled parallel group phase 3 trial, comprising a 52-week main phase and three-year extension period (NCT03811535). Two-hundred GH-treatment-naïve, prepubertal children with GHD (74.5% male) were randomly assigned in a 2: 1 ratio to receive 0.16 mg/kg/week s.c. somapacitan (n=132) or daily s.c. GH (0.034 mg/kg/day Norditropin®; n=68). The 52-week main trial results are presented here. The primary endpoint was annualized height velocity (HV) after 52 weeks of treatment. At week 52, the estimated mean HV was 11.2 cm/year for somapacitan compared to 11.7 cm/year for daily GH. The estimated treatment difference was -0.5 [95% CI -1.1 to 0.2] cm/year, confirming non-inferiority (non-inferiority threshold: -1.8 cm/year). Secondary height-related endpoints supported the primary endpoint. Insulin-like growth factor-I standard deviation score (IGF-I SDS) showed consistent increases for both somapacitan and daily GH over the 52 weeks, with change differences from baseline not statistically significant between treatment groups. At week 52, mean IGF-I SDS levels were similar between somapacitan (+0.28) and daily GH (+0.10) and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or local tolerability issues identified. There were no clinically relevant findings with respect to changes in glucose metabolism, no neutralizing anti-somapacitan or anti-GH antibodies were detected, and a low number of patients reported injection-site reactions, with similar proportions for somapacitan (5.3%) and daily GH (5.9%). In both treatment groups, 1.5% of patients reported injection site pain. Adherence was high for both treatments. The mean and median adherence for somapacitan treatment were 95.8% and 100%, respectively. The mean and median adherence for the daily GH group were 88.3% and 96.9%, respectively. In conclusion, once-weekly somapacitan has a similar efficacy and safety profile as daily GH with similar mean IGF-I levels in treatment-naïve children with GHD.

Presentation: Sunday, June 12, 2022 1:06 p.m. - 1:11 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF26 | PMON335 Once-Weekly Somapacitan Versus Daily Growth Hormone in Children Born Small for Gestational Age: Results From a Randomized Phase 2 Trial
Authors: Juul Anders , Backeljauw Philippe , Højby Michael , Kawai Masanobu , Kildemoes Rasmus Juul , Linglart Agnès , Zuckerman-Levin Nehama , Horikawa Reiko
Published: November 2022

Treatment of persistent short stature in children born small for gestational age (SGA) requires daily growth hormone (GH) injections that can be burdensome for patients and caregivers. Once-weekly somapacitan is a long-acting GH currently in phase 3 development for replacement therapy in children with GH deficiency. We report the 26-week results of the first phase 2, multinational, randomized, open-label, controlled, dose-finding trial (NCT03878446) investigating the efficacy and safety of somapacitan as treatment for short stature in children born SGA compared with daily GH (Norditropin®, Novo Nordisk A/S). A total of 62 (35.5% female) GH-treatment-naïve, prepubertal children received 0.16, 0.20 or 0.24 mg/kg/week subcutaneous (s.c.) somapacitan, or 0.035 or 0.067 mg/kg/day s.c. daily GH for 26 weeks (main phase). All children are subsequently included in an extension to this trial.

The primary outcome was annualized height velocity (HV). At week 26, the estimated mean HV was: 8.9, 11.0 and 11.3 cm/year for 0.16 mg/kg/week (n=12), 0.20 mg/kg/week (n=13) and 0.24 mg/kg/week (n=12) somapacitan, respectively, versus 10.3 and 11.9 cm/year for 0.035 mg/kg/day (n=12) and 0.067 mg/kg/day (n=13) daily GH, respectively. A dose-dependent response in the estimated mean HV was observed with both somapacitan and daily GH. The effect of somapacitan on HV was not statistically significantly different compared with daily GH. A similar pattern was observed for change from baseline in height standard deviation score (SDS) and change from baseline in HV SDS. Consistent dose-dependent increases were observed in insulin-like growth factor-I (IGF-I) SDS with both somapacitan and daily GH. Exposure-response modeling of somapacitan exposure versus HV and IGF-I SDS vs. HV indicated an exposure-dependent increase in HV for both these parameters.

Somapacitan was well tolerated at all doses investigated, with no safety or local tolerability issues identified. There were no clinically relevant findings with respect to glucose metabolism, and no detection of anti-drug antibodies in any of the dose groups.

In conclusion, all investigated doses of weekly somapacitan were efficacious and well tolerated throughout the study period. Based on the totality of data on improvements in height-based parameters combined with exposure-response analyses, a somapacitan dose of 0.24 mg/kg/week appears as the most efficacious dose, providing similar efficacy, safety and tolerability to daily GH 0.067 mg/kg/day after 26 weeks of treatment.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:51 p.m. - 12:56 p.m.
OR25-2 RBFOX2 Copy Number Variation Disrupts Urethral Development Causing Hypospadias
Authors: O'Neill Marisol , Ruiz Rojano Fredi , Ruthig Victor , White Jeffrey , Lamb Dolores
Published: November 2022

Despite the frequency of hypospadias (1: 125 live male births) often the etiology is not known. The Lamb Laboratory previously determined that RNA Binding Fox-1 Homolog 2 (RBFOX2) copy number variation (CNV) is associated with clinical cases of upper and lower tract genitourinary (GU) anomalies, including hypospadias. RBFOX2 encodes a RNA binding protein that regulates mRNA splicing. The hypothesis was tested that altered RBFOX2 gene dosage impacts the developing penis transcriptome via mRNA splicing, specifically the mesenchymal to epithelial transition critical for penile urethra formation, resulting in hypospadias.Searches, in publically available and local clinical databases, centered on hypospadias occurance with gene CNV: identified the RBFOX2 locus as a gene dosage sensitve region. To identify developmental pathways regulated by RBFOX2 in the GU system, Rbfox2 haploinsufficient and null mouse models were developed, and penises were collected for RNA-seq, in situ hybridization, and micro-CT analysis of urethral development. In situ hybridization together with re-analysis of published scRNA-seq datasets were employed to define the anatomical regions of Rbfox2-specific expression in the developing mouse penis [Amato & Yao, PNAS 118(25): e2103856118, 2021; Armfield & Cohn, Dev Biol 477: 145-154.2021].Publicly available clinical data identified 17 patients (0.068% n=24,896) with pathogenic RBFOX2 CNVs: 4 were noted to have hypospadias. Results from our cohort of non-syndromic GU birth defect patient samples identified 11 patients (2.4% n=450) with RBFOX2 CNVs: 21% of whom have hypospadias. RNA immunoprecipitation agianst RBFOX2 in human kidney cells validated mRNA transcipt targets previously identified in cardiac cells [Verma 2016]. Micro-CT analysis on fetal Rbfox2-haploinsufficient mice validated the modeled clinical phenotype. Combined in situhybridization and scRNA-seq spatial analysis on mouse samples revealed, after penile sex determination (E15.5), Rbfox2 expression becomes restricted to the penile urethral mesenchyme. Differential gene expression and transcript usage analysis on the Rbfox2-loss mouse penis transcriptome identified mis-expression of gene products associated the estrogen signalling pathway.Alterations in RBFOX2 gene dosage clinically correlate with upper and lower tract genitourinary anomalies, specifically hypospadias. Data from human cell lines and mouse models seemingly indicate the phenotype seems is partially the product of an RBFOX2 role in directing the mesenchymal to epithelial transition. Specifically our data support the a direct role of RBFOX2 in balancing the competing male and female pathways at the level of estrogen and androgen signaling pathways. We are currently using immunofluorescence experiments to define the changes in androgen-receptor, estrogen-receptor, and RBFOX2 patterning throughout perinatal penis development.

Presentation: Monday, June 13, 2022 11:15 a.m. - 11:30 a.m.
OR25-6 In Men on Testosterone Therapy, Baseline Testosterone Level of <264 ng/dL is Associated with Greater Improvement in Body Composition, While Level of ≥264 ng/dL Favors Improvement in Metabolic Profile
Authors: Aguirre Lina , Armamento-Villarea Reina , Ballato Elliot , Chen Rui , Colleluori Georgia , Qualls Clifford , Villareal Dennis T , Deepika Fnu
Published: November 2022

Context

Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dL is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study investigating whether baseline T levels also influences body composition and metabolic response to T therapy.

Objective

To determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with baseline T level of < 264 ng/dL compared to those with levels ≥264ng/dL Methods: Secondary analysis of single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011-2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dL, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of < 264 ng/dL (N=43) and those with ≥264 ng/dL (N=57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, sclerostin), adiponectin, and leptin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD, and body composition by dual-energy x-ray absorptiometry (DXA).

Results

Men with T < 264 ng/dL showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dL (4.2±4.1 vs 2.7±3.8%; p=0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7±11.5 vs 4.4±4.3%, 7.3±11.6 vs 2.4±6.8%; p=0.033 and p=0.043, respectively). Men with T ≥ 264 ng/dL showed significant decreases in HbA1c at 12 months (-3.1±9.2 vs 3.2±13.9%; p=0.005), fasting glucose at 18 months (-4.2±31.9 vs 13.0±57.3%; p=0.040), LDL at 6 months (-6.4±27.5 vs 12.8±44.1%; p=0.034), leptin at 18 months (-40.2±35.1 vs -27.6±31.0%; p=0.034) compared to those with T < 264 ng/dL. No significant differences in BMD and bone turnover markers were observed.

Conclusion

T therapy results in improvement in body composition irrespective of baseline T levels but T <264 ng/dL is associated with greater improvement in FFM, whereas T level of ≥264 ng/dL favors improvement in metabolic profile.

Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.
ODP063 Development and Validation of Model for Sparing Adrenal Venous Sampling in Diagnosing Unilateral Primary Aldosteronism
Authors: Hu Jinbo , Song Ying , Li Qifu , Yang Shumin
Published: November 2022

Context

Current guidelines recommend adrenal venous sampling (AVS) to identify unilateral primary aldosteronism (UPA) before offering adrenalectomy. However, AVS is costly and technically challenging, limiting its use to expert centres.

Objective

To establish a model to predict UPA and therefore bypass the need for AVS prior to surgery. Design and Setting: The model was developed in a Chinese cohort and validated in an Australian cohort. Previously published prediction models of UPA were also tested. Participants: PA patients with a definite subtyping diagnosis based on AVS and/or surgery. Main Outcome Measure: Diagnostic value of the model.

Results

In the development cohort (268 UPA and 88 bilateral PA), combinations of different levels of low serum potassium (≤3. 0 or 3.5mmol/L), high PAC (≥15-30ng/dL), low PRC (≤2.5-10μIU/mL) and presence of unilateral nodule on adrenal CT (>8-15mm in diameter) showedspecificity of 1. 00 and sensitivity of 0.16-0.52. The model of serum potassium≤3.5mmol/l, PAC≥20 ng/dL, PRC≤5μIU/mL plus a unilateral nodule≥10mmhad the highest sensitivity of 0.52(0.45-0.58) and specificity of 1. 00(0.96-1. 00). In the validation cohort (84 UPA and 117 bilateral PA), the sensitivity and specificity of the model were 0.13(0. 07-0.22) and 1. 00(0.97-1. 00), respectively. Ten previous models were tested, and only one had a specificity of 1. 00 in our cohorts, but with a very low sensitivity [0. 07(0. 04-0.10) and 0. 01(0. 00-0. 06) in our development and validation cohorts, respectively].

Conclusions

A combination of high PAC, low PRC, low serum potassium and unilateral adrenal nodule could accurately determine PA subtype in 13-52% of patients with UPA and obviate the need for AVS before surgery.

Presentation: No date and time listed
PMON268 A Multicenter, Open Label, Variable Dose, Two-Arm, Pilot Paediatric Phase 1 Pk Study To Evaluate 4.5% Testosterone Nasal Gel In Hypogonadal Boys
Authors: Lucas-Herald Angela , Hawcutt Daniel , Thankamony Ajay , Faisal Ahmed S
Published: November 2022

Introduction

Testosterone treatment is regularly required by adolescent boys with hypogonadism.

Aim

To evaluate the pharmacokinetics of a nasal testosterone gel, which is available for adult men with hypogonadism, in adolescents.

Methods

Open-label, variable-dose, non-randomized, 3-treatment crossover study of testosterone nasal gel 4.5% w/w (Natesto™). Subjects were hypogonadal adolescent boys between the ages of 12.0–17.9 years. Biochemical analyses were performed by Acerus Pharma.

Summary and Conclusions

Testosterone nasal gel 4.5% w/w (Natesto™) represents a safe and acceptable method of administering testosterone to hypogonadal adolescents. Based on feedback from both patients and investigators, the nasal gel was well tolerated by patients, and it was felt that children would be able to administer this independently.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF03 | PMON288 Determining Mechanisms of Farnesoid×Receptor Regulation of Heme Biosynthesis and Ductular Reaction
Authors: Dean Angela , Jungwirth Emilian , Bailey Keith , Panzitt Katrin , Wagner Martin , Anakk Sayeepriyadarshini
Published: November 2022

Bile acids are increasingly becoming recognized as hormones, and their main endogenous receptor is the farnesoid X receptor (FXR). In order to investigate whether FXR is necessary to maintain proliferation of the bile ducts in response to injury, we challenged male and female wild-type (WT) and Fxr knockout (FxrKO) mice with 0.1% 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinediacarboxylic acid diethyl ester (DDC) in the diet for two weeks. DDC is an inhibitor of ferrochelatase, the final enzyme of heme biosynthesis, resulting in a buildup of bile plugs in the liver causing an inflammatory response called ductular reaction. We found that deletion of Fxr led to a dramatic reduction in the ductular reaction independent of the sex. Then we tested if the inhibition of ferrochelatase was compensated for in FxrKO mice by analyzing the expression of genes in the heme biosynthesis pathway. Although we find a decrease in basal Alad gene expression in FxrKO mice in both sexes, upon DDC treatment, expression does not decrease as much as seen in the WT mice. Intriguingly, we also noted sex-specific changes. Cpox expression was increased in male FxrKO mice, but FxrKO mice showed reduced suppression of Cpox expression when treated with DDC. Conversely, Ppox expression was reduced in male FxrKO mice compared to WT mice, and both male WT and FxrKO mice had a comparable reduction in Ppox expression upon DDC treatment. Female FxrKO mice showed a significant decrease in Fech expression basally that did not change with DDC treatment. These results suggest that FXR may contribute towards regulating expression of genes in the heme biosynthesis pathway. However, these observations do not explain the lack of ductular reaction. Since PGC1α was previously shown to control heme biosynthesis through its downstream targets, FOXO1 and NRF1, we examined their transcript expression in our study to determine if the pathway is playing a role in our observations. We examined this pathway and observed a significant decrease in Foxo1 expression in both sexes of WT and FxrKO mice basally but only a reduction in Nrf1 expression upon DDC treatment. We are currently investigating other potential regulators of heme biosynthesis and ductular reaction, such as Klf1 which regulates erythropoiesis and plays a role in ductular reaction and the nuclear receptors Rev-Erbα/β that use heme as a ligand, to determine how FXR is regulating heme biosynthesis.

Presentation: Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.