bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP314 Gynecomastia as the Initial Presentation of Acromegaly.
Authors: Lim Frederick , Rao Ambika
Published: November 2022

Acromegaly is caused by persistent hypersecretion of growth hormone. In the US, its prevalence is less 20,000 per year. It is noted that co-secretion of growth hormone and prolactin from a single pituitary adenoma is common. Prolactin is co-secreted in about 25% of patients with acromegaly. We present a case of middle-age man who initially presented to our clinic for evaluation of bilateral gynecomastia with hypogonadism and found to have growth hormone secreting pituitary macroadenoma with co-secretion of prolactin. A 50 year-old Caucasian male veteran with past medical history of hypertension, hyperlipidemia, pre-diabetes, carpal tunnel syndrome, obstructive sleep apnea was referred to our clinic for evaluation and management of 5 months history of bilateral gynecomastia. He also reported chronic fatigue and erectile dysfunction. He denied headache, vision changes, change in shoes or ring size. He had gynecomastia with a larger left breast with some tenderness to palpation with no nipple discharge. He has short stature with large hands and feet. Some skin tags were also noted on physical examination. He was found to have elevated prolactin of 49.3 ng/ml (2.64-13.13ng/ml) with normal thyroid function test. His morning total testosterone was also low at 186 ng/dl (250-1100 ng/dl) with LH of 2.81 mIU/ml (1.24-8.26 mIU/ml), FSH of 5.98 mIU/ml (1.27-19.26 mIU/ml). Since his prolactin was elevated, MRI brain was done that showed 2.3 cm pituitary macroadenoma close to cavernous sinuses with no optic chiasm compression. Other pituitary function tests showed an elevated IGF-1 of 585 ng/ml (52-328 ng/ml). His morning cortisol and ACTH were normal. Oral glucose tolerance test revealed that growth hormone was not suppressed (GH > 2.4ng/ml post OGGT) confirming growth hormone excess/Acromegaly. He was given a trial of octreotide but did not tolerate the medication. He underwent transsphenoidal hypophysectomy and developed transient post-operative diabetes insipidus requiring Desmopressin. His prolactin, IGF-1 and testosterone level had returned to normal after surgery and gynecomastia completely resolved. Repeat MRI in 6 months after surgery showed postoperative changes and OGTT showed that GH suppressed appropriately (GH < 0.1 ng/ml post OGTT) and IGF-1 was149 ng/ml. Prolactin and testosterone had remained in the normal range. Acromegaly presents organomegaly with coarse physical features, enlarged hands and feet but some early symptoms are hyperhidrosis and extremity swelling with arthritis. We describe a case of acromegaly that initially presented with gynecomastia and secondary hypogonadism with hyperprolactinemia that lead to the diagnosis of acromegaly. The gynecomastia resolved completely with treatment. We hope that our case report is for the clinicians to be aware that acromegaly can present with metabolic syndrome, hypogonadism with gynecomastia and hyperprolactinemia and include screening tests to help diagnose and treat these patients at the early stages of the disease.

Presentation: No date and time listed
ODP337 Neurenteric Cyst Apoplexy with Post-Operative Diabetes Insipidus in a 14-year-old Male
Authors: Patterson Mary
Published: November 2022

Background

Apoplexy of benign neurenteric cysts can present with acute onset of a severe headache. Pituitary dysfunction, such as hypothyroidism and diabetes insipidus, can occur after transsphenoidal resection of these cysts.

Clinical Case

A 14-year-old male presented to the ED with acute onset of a severe headache, nausea and emesis. He denied recent vision changes, weight changes, temperature intolerance, diarrhea, constipation, skin changes, polyuria, or polydipsia. He reported starting puberty by 13 years of age. He was treated with Zofran, Tylenol, and Dexamethasone which led to headache resolution. His MRI showed a trans-sellar structure measuring 12 by 16 mm and demonstrating internal intrinsic T1 hyper-intensity, deep T2 hypo-intensity, and mildly thickened peripheral enhancement. The lesion abuts the undersurface of the optic chiasm and the stalk enhances normally. The neurohypophysis is not well identified. The optic nerves are unremarkable, and the optic chasm is slightly bowed superiorly. His initial labs were significant for: Na 136 mmol/L, K 4 mmol/L, TSH 1.15 uIU/mL, FT4 0.81 ng/dL, IGF-1 286 ng/mL, cortisol <1 ug/dL (drawn in the PM), FSH 6.23 mIU/mL, LH 2. 01 mIU/mL, PRL 7.8 ng/mL, testosterone 187 ng/dL. He was taken to surgery where a transsphenoidal resection with a mucosal graft for sellar reconstruction was completed. Pathology results showed evidence of a neurenteric cyst with glandular elements within the cyst wall. He was noted to have an increase in water intake and urine output post-operatively with intake of 6200 mL and output of 6768 mL over 24 hours (3.5 mL/kg/hr). His Na was 141 mmol/L with urine SG of 1. 002, and urine osmolality of 75 mosm/kg. He was discharged on a DDAVP dose of 0.2 mg tid. His thyroid function was reassuring post-op with a T4 of 8.4 ug/dL. He had a normal morning cortisol of 14.6 ug/dL. One month post-op, he required treatment with a DDAVP dose of 0.1 mg bid. The rest of his pituitary function appeared intact one month post-op with labs significant for LH 2.56 mIU/mL, FSH 5 mIU/mL, testosterone 261 ng/dL, PRL 7.8 ng/mL, TSH 2. 09 uIU/mL, and FT4 1 ng/dL.

Conclusion

This case demonstrates that neurenteric cyst apoplexy can occur in teenagers who present with the acute onset of a severe headache with associated nausea and emesis. This case demonstrates the importance of thoroughly investigating the patient's pituitary function at baseline and post-operatively since pituitary deficiencies, such as DI, can occur.

Presentation: No date and time listed
ODP357 The Effect of Hyperbetacarotenaemia on Pituitary Homeostasis – A Case Series
Authors: Dhatariya Ketan , Rogers Rebecca
Published: November 2022

Betacarotene is an antioxidant pigment found in red, orange and yellow coloured leafy fruits and vegetables. Recent studies have found that beta carotene is involved in cell cycle arrest with apoptotic effects in ACTH secreting pituitary cells. It may have desirable anti-tumorigenic effects. Hyperbetacarotenaemia is commonly caused by excess intake of carotene rich food. However, correlating the clinical picture with liver, thyroid and lipid profiling, vitamin A concentrations and exclusion of nephrotic syndrome is necessary to underpin the causative mechanism. We present two cases of hyperbetacarotenaemia with clinical manifestations of hypopituitarism.

Case 1

– A 55 year old lady presented with partial hypopituitarism. She had a history of restrictive eating disorder and excessive exercise regime. She cycled 140 miles a week and ate 4lbs of leafy vegetables a day. Her pituitary profile reflected partial hypopituitarism with inappropriately undetectable LH/FSG, low IGF-1 and central hypothyroidism. Her cortisol response to tetracosactide testing was normal. Betacarotene reached a peak of 2.7umol/L (upper reference range 1.58umol/L).

Case 2

– A 29 year old lady was diagnosed and treated for a 4mm microprolactinoma, which subsequently regressed and prolactin levels returned to normal. Despite this, she continued to experience menstrual irregularities and found to have elevated serum beta carotene levels. On direct questioning she admitted to drinking 1.5L of Lucozade® per day. Betacarotene reached a peak of 3.81umol/L. These cases illustrate the importance of taking a detailed dietary history when considering the causes of pituitary dysfunction.

Presentation: No date and time listed
ODP024 Adrenocortical Carcinoma Identified in a Patient With Familial Adenomatous Polyposis Syndrome
Authors: Park Eujean , Prasad Heranmaye
Published: November 2022

Background

Numerous extracolonic manifestations are associated with familial adenomatous polyposis (FAP), including benign thyroid and adrenal nodules, less commonly thyroid and adrenal cancers. We describe a case of a patient with history of FAP who was found to have malignant lesions both in the thyroid and adrenal glands.

Clinical Case

A 54 year-old female with familial adenomatous polyposis (FAP) underwent partial colectomy at age 16. Known extracolonic manifestation at initial presentation was limited to a dermoid tumor of the right breast. Upon evaluation by endocrinology, she was found to have a dominant thyroid nodule in the right lobe that eventually doubled in size and was positive for papillary thyroid cancer with a BRAF V600E mutation. Successful total thyroidectomy with central neck lymph node dissection was completed, and she is now undergoing routine surveillance for ATA low risk PTC. She maintained annual endoscopic surveillance with gastroenterology and underwent serial abdominal imaging studies for complaints of abdominal discomfort. Right adrenal adenoma was first identified in August 2017 and screening for functionality, to include pheochromocytoma, was negative. Repeat abdominal imaging in 2020 showed the lesion increased in size by 30%. CT imaging identified the nodule as indeterminate based on the washout characteristics (HU 27 pre-contrast, absolute washout = 13% and relative washout = 8%). A 2cm left adrenal mass was also noted with radiographic features consistent with a lipid poor, benign, adenoma (HU 33 pre-contrast, absolute washout = 58%, relative washout = 39%). PET-CT was performed to further characterize the right sided lesion, which was vividly FDG avid at 8.7 SUV (high probability of malignancy). The left adrenal nodule was mildly FDG avid with an SUV of 2.4. CT-guided biopsy of the right adrenal gland was performed and immunohistochemistry did not stain for chromogranin, inhibin, pankeratin or calretinin. Positive staining for MART-1 was seen, which is a typically associated with adrenal cortical cells. There was a high index of suspicion for malignancy given her hereditary cancer syndrome, and the decision was made to proceed with right adrenalectomy. Final surgical pathology confirmed a low grade adrenocortical carcinoma with two nodular lesions, both staining CD10 positive with the mitotic marker (Ki-67) 2-3% positive. The patient's left adrenal gland remains functionally intact, and there were no indications to pursue postoperative treatment or adjuvant therapy.

Conclusion

The patient presented here is representative of incidentally discovered nonfunctional adrenocortical carcinoma in the setting of a hereditary cancer syndrome. The available literature suggests that adrenocortical tumors should be considered FAP tumors, and sporadic mutations leading to adrenocortical carcinoma are less likely related to germline APC gene mutations

Presentation: No date and time listed
ODP363 Growth hormone and prolactin co-secretion in acromegaly: a case study and review of the literature
Authors: Hasan Farhad , Mittal Ashima
Published: November 2022

Introduction

Growth hormone (GH) and prolactin co-secreting pituitary adenoma is the most common type of pleuri-hormonal adenomas. We present a case of GH and prolactin co-secreting macroadenoma with somato-mammotroph (SMT) histopathology.

Case

A 48-year-old female presented with complaints of chronic headaches and coarsening of facial features for >5 years. Associated symptoms included chronic fatigue, joint pain, heat intolerance, diaphoresis, and 20 lbs weight gain. She noted acral enlargement and ill-fitting dentures. She also reported snoring and witnessed apneic spells. She denied peripheral vision loss, galactorrhea, or breast tenderness. Past medical history included prediabetes, bilateral carpal tunnel surgery, and uterine ablation. On examination, her weight was 269 lbs, height 5'8", and BP 148/92 mmHg. She had acromegalic features including frontal bossing with coarse facial features, prominent jaw, and large hands with sausage-like fingers and sweaty palms. Her oropharynx was crowded with Mallampati grade 4. Laboratory data showed elevated IGF-1 level of 981 ng/mL (77- 220) and prolactin level – 189 ng/mL (4.8–23.3). The fasting GH level was 5.1 ng/mL (<7.1). Fasting blood sugar was 145 mg/ dl with an HbA1C of 6.4%. Repeat testing confirmed elevated IGF-1–803 ng/mL with a Z score of 4.5 and prolactin– 130.2 ng/mL. Prolactin levels were higher than expected for stalk effect, hence GH and prolactin co-secretion was suspected. The patient had secondary hypogonadism with normal cortisol and thyroid axes. MRI pituitary showed a 2.6×1.8×1.9 cm pituitary macroadenoma with erosion of sellar floor, extension into the right sphenoid sinus, and possible involvement of the left cavernous sinus. The patient underwent transsphenoidal hypophysectomy, which was complicated by transient diabetes insipidus. Postoperative GH levels remained elevated > 3ng/ mL (goal for remission < 1 ng/ ml). Surgical pathology showed SMT type pituitary adenoma, with tumor cells staining both for GH and prolactin. The patient will have repeat pituitary MRI and biochemical testing 2 months following surgery to assess the presence and extent of residual disease.

Discussion

The WHO's 2017 classification divides GH and prolactin co-secreting tumors to 1) SMT cell adenomas where monomorphous cells co-secrete both GH and prolactin; 2) mixed GH cell and prolactin cell adenomas, bimorphous tumors where 2 different cell types secrete GH and prolactin; and 3) acidophil cell tumors. SMT adenomas are morphologically similar to densely granulated adenomas. These are usually slow growing and rarely invade surrounding structures. They have low intensity on T2-weighted MR imaging. In a study of 94 acromegaly cases, SMT adenomas were the smallest in size, with minimal cavernous sinus invasion, and had a higher chance of complete tumor resection. In contrast, our patient had a relatively large and invasive SMT adenoma.

Presentation: No date and time listed
ODP371 A Nationwide Analysis of Hospitalization trends of Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) with comorbid Atrial Fibrillation
Authors: Batth Jaspreet , Kalangi Sreevastav , Kichloo Asim , Shaka Hafeez
Published: November 2022

Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) is a disease of unsuppressed secretion of anti-diuretic hormone (ADH) and its continued action on the Vasopressin (V2) receptors. It is characterized by hyponatremia in a setting of hypervolemia or euvolemia. In this study, we aimed to identify and compare demographic characteristics, adverse outcomes, and complications of SIADH hospitalizations with and without comorbid atrial fibrillation (AF). We analyzed the Nationwide Inpatient Sample (NIS) for 2019 to identify all adult (≥18 years) hospitalizations with a principal diagnosis of SIADH using the ICD-10-CM code (E22.2). Patients <18 years of age were excluded from the analysis. The study cohort was further divided based on the presence of absence of AF. Demographic and hospitalization characteristics were highlighted. Using a multivariate regression analysis adjusting for age, sex, race, primary payer, median household income by zip code, Carlson Comorbidity Index (CCI), hospital location, bed-size, and teaching status, inpatient outcomes such as inpatient mortality, rates of septic shock, acute myocardial infarction (AMI), acute respiratory failure (ARF), acute renal failure (AKI), and acute pulmonary edema (APE) were determined. All p-values< 0. 05 were considered statistically significant. In 2019, of the 39,110 hospitalizations for SIADH, 18.5% of the patients had comorbid AF. SIADH hospitalizations with AF were older (80.4 vs 70.1 years, p<0. 001, predominantly White and a higher proportion of patients with CCI >2 compared to the non-AF cohort. Although there was a higher proportion of females in the AF cohort (61.4% vs 63.1%, p=0.252), we did not find a statistically significant difference for gender between the two subgroups. SIADH hospitalizations with AF were associated with higher adjusted odds ratio (aOR) of inpatient mortality (2.1 vs 0.9%, aOR: 2.45, p<0. 001), increased length of stay (LOS), (5.8 vs 4.8 days, p<0. 001) and increased mean hospitalization cost (THC) ($12,284 vs $10,340, p <0. 001) compared to the non-AF cohort. Furthermore, compared to the non-AF cohort, we noted higher odds of septic shock (0.6 vs 0.3%, aOR: 3.35, p=0. 007) and ARF (11.2 vs 6.5%, aOR: 1.88, p<0. 001) for the AF cohort; however, we did not find a statistically significant difference in the odds of CVA, AKI or AMI between the two groups. Patients hospitalized with SIADH, and comorbid AF had higher inpatient mortality, LOS, THC, which may be secondary to multiple electrolyte abnormalities and fluid imbalances associated with SIADH leading to a worsening of the AF. Furthermore, these patients had higher odds of septic shock and ARF. Hence, it is vital to appropriately manage AF in patients with SIADH to prevent adverse outcomes and decrease the burden on the United States healthcare system.

Presentation: No date and time listed
OR27-6 Effects of the SGLT2-Inhibitor Empagliflozin in Patients With Chronic Syndrome of Inadequate Antidiuresis (SIAD) - Results of a Double-Blind, Randomized, Placebo-Controlled, Crossover Trial
Authors: Berres Manfred , Bridenbaugh Stephanie , Christ-crain Mirjam , Haslbauer Aaron , Imber Cornelia , Monnerat Sophie , Nobbenhuis Rianne , Refardt Julie , Sailer Clara , Vogt Deborah , Winzeler Bettina , Atila Cihan
Published: November 2022

Introduction

Hyponatremia is the most common electrolyte disorder and the syndrome of inappropriate antidiuresis (SIAD) is one of its main causes. However, treatment options for chronic SIAD-induced hyponatremia are inadequate. This is problematic because hyponatremia has been associated with neurocognitive deficits, although there is little data on its reversibility.We previously showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin is a promising short-term treatment option for hospitalized patients with SIAD-induced hyponatremia, promoting osmotic diuresis via urinary glucose excretion. However, there are no data on long-term treatment in outpatients nor its effect on neurocognitive function.

Material and Methods

In this double-blind, randomized, placebo-controlled, crossover trial we compared 4-week treatment with empagliflozin 25mg/day to placebo in addition to fluid restriction of ≤1.5L/24h in outpatients with chronic SIAD-induced hyponatremia (serum sodium <135mmol/L). At baseline and after both treatment cycles, patients underwent neurocognitive testing (Montreal Cognitive Assessment (MoCA) test). There was a 2-week wash-out period between the two treatment cycles, and a follow-up visit was scheduled 30 days after completion of the treatment phase.The primary endpoint was the difference in serum sodium levels (mmol/L) after 4 weeks of treatment with empagliflozin or placebo, calculated using a linear mixed-effects model.

Results

14 patients, 50% female, with a median (IQR) age of 72 years (65-77) completed the trial.Median (IQR) serum sodium level at baseline was 131mmol/L (130-132). Under treatment with empagliflozin, median (IQR) serum sodium level increased to 134mmol/L (132-136), while no notable change was seen under placebo (130mmol/L (128-132)). This resulted in a 4.1 mmol/L (95% CI 1.7-6.5) higher serum sodium level after 4 weeks of empagliflozin treatment compared to placebo (p=0.004). This effect was independent of severity of SIAD.In addition, treatment with empagliflozin led to improved neurocognitive function, as shown by an increase of 1.2 points (SE 0.5) in the MoCA test (p=0.042).Treatment with empagliflozin was generally well tolerated, no serious adverse events occurred during the observation period.

Conclusion

This trial shows that the SGLT-2 inhibitor empagliflozin is a promising new treatment option for outpatients with chronic SIAD-induced hyponatremia. Furthermore, hyponatremia treatment led to an improvement of neurocognitive function.

Presentation: Tuesday, June 14, 2022 11:00 a.m. - 11:15 a.m.
PMON39 A Perfect Storm – Multiple Causes of Hyponatremia in Patient With Pituitary Macroadenoma
Authors: Faisal Sobia , Ibrahim Waleed , Kantorovich Vitaly
Published: November 2022

Introduction

Adrenal insufficiency is a life threatening condition, and prompt diagnosis and treatment are necessary. Here we present a case of hyponatremia which was thought to be multifactorial due to secondary adrenal insufficiency in the setting of a pituitary macro-adenoma, central hypothyroidism, SIADH in the setting of nausea as well as analgesic use.

Case presentation

A 23 y.o female patient presented to the hospital with headaches. MRI of the head revealed a 2.2 cm pituitary mass abutting the optic chiasm with no edema and no need for urgent neurosurgical intervention. Outpatient endocrine workup demonstrated following labs: Na 135 mmol/l (ref range 135 - 145), afternoon cortisol 9.3 mcg/dl (ref range 5.0 - 23.0), ACTH 19 pg/ml (ref range 7.2-63), GH 3.8 ng/ml (ref range <=7.1), Prolactin 16.0 ng/ml (ref range 4.8 - 23.3). Due to persistent headaches, she was taking high doses of Naproxen, which resulted in nausea and vomiting, and led to another ED visit. At this time, she was found to have Na 117 mmol/l, Serum osmolality 246 mOsm/kg (re range 285–295), Urine osmolality 554 mOsm/kg (ref range 40 - 1,400), Urine Na 146 mmol/L. TSH was 0.16 mIU/ml (ref range 0.27 - 4.20) and free T4 was 0.49 ng/dl (ref range 0.80 - 1.90).

Endocrine was consulted and the pathogenesis for hyponatremia was thought to be multifactorial including central adrenal insufficiency masked by central hypothyroidism. Her cortisol levels as detailed above were done early afternoon and could not exclude at least some degree of central adrenal insufficiency. Additionally, hypothyroid state can significantly decrease metabolism of cortisol thus preventing acute drop in cortisol levels. She also seemed to have concomitant syndrome of inappropriate antidiuretic hormone secretion (SIADH), driven by both the pituitary tumor as well as nausea and vomiting. On top of that for her severe progressive headaches she was treated with non-steroidal anti-inflammatory agents and tramadol, both known to associate with hyponatremia.

She was started on intravenous hydrocortisone, and subsequently oral levothyroxine. She had improvement in her sodium levels and did not require Tolvaptan. She was discharged on hydrocortisone and levothyroxine with outpatient endocrine and neurosurgery follow up. She is currently awaiting neurosurgical intervention.

Discussion

Secondary adrenal insufficiency is more common than primary adrenal insufficiency. Establishing the diagnosis of secondary adrenal insufficiency is challenging as it is not typically associated with classical signs and symptoms of adrenal insufficiency. Clinical manifestations tend to be more indolent as they result from glucocorticoid deficiency only and there is preservation of the aldosterone and adrenal androgen axis. What makes our patient interesting is the several factors as mentioned above which contributed to her severe hyponatremia.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON52 Use of PDE5 Inhibitors as Potential Treatment for Isolated Growth Hormone Deficiency Caused by Alternate Splicing of GH1 Gene
Authors: Pandey Amit V , Velazquez Maria Natalia Rojas
Published: November 2022

Mutations in the GH1 gene cause isolated growth hormone deficiency (IGHD) by affecting production, secretion, and stability of growth hormone as well as its binding to GHR. Genetic mutations resulting from splicing errors are known to increase the production of a small 17.5 kD isoform of human growth hormone. This smaller isoform of GH1 is inactive and is linked to IGHD. While studying the impact of small GH isoform on GH production and secretion, we noticed that cells transfect with sequences carrying the mutated GH gene that resulted in splicing defects produce the short 17.5 kD version of GH, looked very different from the control cells with WT GH gene. We found that production of short GH isoform distorts the cell morphology, contributing to detrimental effects seen in the patients with mutations in GH1 gene causing alternate splicing. We hypothesized that cellular distortion caused by small GH isoform and overall GH secretion can be a target and a tool to experimental approaches for reversing the damaging effects of small GH protein, thereby providing potential treatments for IGHD caused by splicing errors. It is known for some time that increasing cAMP enhances 26S proteasome activity and the degradation of cell proteins, including the selective breakdown of misfolded proteins, and recently increase in cGMP levels has also been shown to regulate protein degradation. Inhibitors of phosphodiesterase 5 (PDE5; e.g., Viagra (sildenafil)), which raise cGMP by inhibiting its hydrolysis to GMP, are widely used for the treatment of erectile dysfunction and pulmonary hypertension, and stimulators of soluble guanylyl cyclases (riociguat), which stimulate cGMP synthesis, are used as treatments for pulmonary hypertension and heart failure. Using our model of cellular morphology changes, have investigated the impact of chemicals that enhance cGMP levels by inhibiting PDE5 or activating guanyl cyclases. The cells expressing small isoform of GH consistently show distorted rounded morphology. Treatment with BAY 41-2272, a cGMP inducer slightly improved the cell morphology in small isoform GH expressing cells. BAY 41-2272 did not show any adverse effects of normal and WT GH expressing cells. Treatment of sildenafil to cells expressing 17.5 kD isoform of GH markedly improved the cell morphology compared to untreated cells, especially after 48h when a larger percentage of cells that were distorted (rounder shapes) regained the shape of normal cells expressing WT GH and no damage to cells expressing WT-GH was observed. Another PDE5 inhibitor tadalafil also caused a marked improvement in cell morphology caused by expression of small GH isoform. Overall, it seems the strategy to regulate the cGMP levels in cells transfected in small GH isoform worked and needs further investigation. A detailed analysis of the impact of PDE5 inhibitors on GH expression and secretion will be presented.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON68 Effect of an Amino-Acid Based Blend on Human Growth Hormone (hGH) and Fibromyalgia (FM) Symptoms
Authors: Beres Adam , Kelly Colleen , Romans Jennifer , Pekarovics Susan , Billes Sonja K , Heaton Amy L , Greenway Frank L
Published: November 2022

Fibromyalgia is a chronic pain sensitivity disorder that affects approximately 3-8% of the general population with symptoms that include fatigue and widespread musculoskeletal pain. Psychological and physical stressors are frequent drivers of fibromyalgia, and additional lockdown-associated stressors may worsen symptoms. Reduced production of human growth hormone (hGH) is evident in approximately 30% of individuals with fibromyalgia, which is hypothesized to contribute to common fibromyalgia symptoms. An orally administered amino acid supplement has been previously shown to improve endogenous hGH status in adults. We investigated if daily administration of the supplement would increase levels of endogenous insulin-like growth factor 1 (IGF-1), a surrogate marker of the body's hGH levels, and improve symptoms related to low-normal hGH production in a cohort of 84 individuals being treated for fibromyalgia. This is the full-cohort analysis of an open-label, single-arm study that investigated the effects of 24 weeks of daily oral administration of the supplement in individuals with low-normal hGH production. The primary endpoint was the change from baseline to endpoint (Week 24) in serum IGF-1. Additional endpoints included the change in body weight, clinical symptoms (assessed with the Revised Fibromyalgia Impact Questionnaire [FIQR], range 0-100, and Perceived Stress Scale [PSS], range 0-40), fasting cardiometabolic markers, tolerability, and safety. Participants continued to receive standard care. The study enrolled 84 fibromyalgia patients with low-normal age-adjusted IGF-1 serum levels. High mean±SD baseline FIQR and PSS scores of 76±16 and 32±5, respectively, indicated poor to moderate symptom management with standard care. All individuals completed 24 weeks of treatment. Serum IGF-1 levels increased with a Week 24 mean±SE change of 28.4±3.0 ng/mL (paired t-test p<0.001). Body weight was reduced with a Week 24 mean±SE change of -5.5±0.3 kg (p<0.001). The change from baseline in FIQR and PSS scores were -29.1±1.1 and -20.0±0.8, respectively (both p<0.001), indicating a substantial improvement. Statistically significant improvements from baseline were also observed for systolic and diastolic blood pressure, HbA1c, LDL and HDL cholesterol, and triglycerides (all p<0.001). The supplement was well tolerated; no adverse events were reported. Sustained augmentation of IGF-1 with the supplement may represent a unique method of improving clinical symptoms of fibromyalgia in individuals with low-normal hGH production.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PSUN346 TSHoma: A Rare Cause of Pituitary Adenoma
Authors: Malik Maham , Sharma Brihant , Sood Ayushi , Syed Omar , Khattar Khyati , Jameson Brian
Published: November 2022

Introduction

The TSH-producing adenoma (TSHoma) prevalence in the general population is 1 to 2 cases per million, accounting for less than 2% of all pituitary adenomas. Plurihormonal tumors account for about 30% of these cases, with the most common co-secreted hormone being GH. We present the case of a patient diagnosed with TSH adenoma many years after presentation.

Case Presentation

A 58 year old male with a history of incidentally diagnosed pituitary microadenoma on MRI in 2007, presented in 2014 following abnormal thyroid function testing (TFT), only reported symptoms being occasional headaches. TFT was significant for elevated TSH and FT4 (TSH 4.87—Ref range: 0.27-4.2. Free T4: 1.98–Ref range 0.7-1.7). Pituitary hormone profile was remarkable for a low IGF-1 and a borderline high Alpha subunit of glycoprotein hormone. A sellar MRI confirmed a 12mm pituitary macroadenoma. He was managed conservatively on beta blockers and low dose Methimazole, owing to a stable adenoma size and poor surgical candidacy with multiple comorbidities (e. g. Atrial fibrillation). Repeat labs in 2018 showed increasing TSH (12.85), with persistent elevations of FT3, FT4 and Thyroglobulin. He had follow up TFT monitoring and surveillance MRIs until 2021 when his lesion progressed to 14 mm with mass effect on right pre chiasmatic optic nerve and adjacent internal carotid artery. The patient underwent trans sphenoidal biopsy with debulking in 2021. The biopsy showed a plurihormonal adenoma (prolactin, GH and TSH secreting). Interestingly, prolactin, GH or IGF-1 were never elevated. Following surgery, MRI showed residual 13.2×9.7 mm tumor with no mass effect. His most recent labs showed a TSH: 2.5 and FT4: 1.7.

Discussion

The diagnosis of a TSHoma should be considered in all centrally hyperthyroid patients, to avoid complications and undue thyroid ablation. A TSHoma must be differentiated from Resistance to Thyroid Hormone (RTH)-beta, which occurs due to mutations in the Thyroid Hormone Receptor Beta gene. Serum a-subunit concentration and Sex Hormone Binding Globulin (SHBG) concentrations are normal in RTH-beta with no TSH suppression following somatostatin analog administration. The presence of a high TSH, FT3 and FT4, in the setting of an elevated a-subunit and pituitary macroadenoma on MRI is strongly suggestive of a TSHoma. Beta blockers are recommended for symptomatic individuals however anti thyroid drug therapy is not advisable for there is risk of thyroid hormone suppression with concomitant tumor overgrowth. Definitive therapy includes trans sphenoidal tumor resection with somatostatin analog therapy to achieve euthyroidism prior to surgery. Patients should be followed up with frequent monitoring of TFT's, along with MRIs every 2-3 years. For patients with residual disease following surgery, treatment with somatostatin analogs such as Octreotide or Lanreotide is favorable as opposed to pituitary irradiation.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF13 | PMON133 A novel variant in an intron consensus sequence associated with familial growth hormone deficiency
Authors: Jee Youn Hee , Gangat Mariam , Hauser Benjamin , Mancuso Bethany , Miller Jennifer , Radovick Sally
Published: November 2022

Splicing variants in the exon-intron boundaries of the GH1 gene have been reported to cause autosomal dominant growth hormone deficiency (GHD type 2). However, whether variants in the intron consensus sequence (XGGG repeats) have an important role in GH1 gene splicing has not been established. Two siblings (proband 1 and 2) were diagnosed with growth hormone deficiency due to poor linear growth at age 4 years (height SDS -2.2 and – 1.6, respectively). Peak serum GH levels with provocative testing were 4.39 ng/ml and 2.77 ng/ml, respectively. They had no other pituitary hormone deficiencies and their pituitary MRIs were normal. Both children are being treated with recombinant human GH (rhGH) with excellent responses in linear growth. Their mother also had a history of GHD in childhood and received rhGH from ages 4 to 13 years. After GH treatment, she reached a normal adult height. The remainder of her pituitary function was normal. Exome sequencing was performed on the probands, their affected mother, and unaffected maternal grandparents to identify the underlying genetic cause. Exome sequencing revealed that the affected mother carried a de novo variant in intron 3 of the GH1 gene (c.291+34G>A, NM_000515.5), and the intronic variant was passed on to the two probands. The variant is not found in the general population according to gnomAD. No other variants in GH1 or other genes were detected to cosegregate with GHD in this family. The intronic variant was located in one of the two intron consensus regions in intron 3 and was predicted by ESEfinder to create a new splicing enhancer (SF2/ASF) binding site. Because intron consensus sequence repeats are important for spliceosome assembly, the variant is predicted to cause aberrant pre-mRNA splicing but not affecting the donor or acceptor site. Previously, a variant in the intron consensus sequence, c.291+28G>A, was found to cause exon 3 skipping, presumably generating a small amount of 22 kDa GH but a large amount of 17 kDa GH. Small deletions in intron 3 (c.291+28_45del and c.291+56_77del) have also been reported to cause exon 3 skipping, categorized as GHD type 2. In vitro studies with the new variant will be required to confirm exon 3 skipping as the mechanism of GHD in this family. This novel intronic variant which creates a new splicing enhancer-binding site supports the previous finding that the intron consensus sequence plays a significant role in the splicing of GH1 pre-mRNA and results in autosomal dominant GHD. As other variants in intron consensus sequence sites may cause GHD type 2, we recommend genetic testing in patients with GHD include the intron consensus sequence regions.

Presentation: Sunday, June 12, 2022 12:48 p.m. - 12:53 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON311 45,X/46,XY mixed gonadal dysgenesis: a case report from Saudi Arabia
Authors: Aljasser Abdullah , Alsaleh Norah
Published: November 2022

Introduction

Mixed gonadal dysgenesis is a sex developmental disorder where the gonads are abnormal from there being some cells with XY chromosomes and some with just asingle X, known as chromosome Y mosaicism. This results in a wide range of male/female genitalia that are not typically, or clearly, male or female

The case: 3 years old Saudi boy was born term to 35 year old G5P5 Normal anti natal and history of consanguinity. Birth weight 2 kilogram and found to have genital ambiguity in the form of short phallus structure and hypospiadius testis were felt at the right inguinal canal. his investigation showed abnormal chromosomes 45×46XY musiac . Mother chromosomes were 46XX normal female karyotype.

normal siblings and Wes WES: CNV DESCRIPTION*: seq[GRCh37] Yp11.31q11.23 (mosaic∼50% of the cells) SIZE (KB):

∼26Mb, GENE COUNT**: 116, INTERPRETATION***: Pathogenic.

RELATED DISORDER: 45,X/46,XY mixed gonadal dysgenesis

The radiological investigations showed small oval shaped mass over the right inguinal canal 0.8/0.6/0.8 cm in size .the left testis couldn't be seen . And Genetogram showed presence of vagina and small uterus.

his laboratory investigations showed at age of 2.5 years LH: less than o.3 and his Testosterone basal was less than 0.09 and Testosterone post HCG 8.29 which should excellent response to HCG.. the case was discussed with the paediatric urologist and the decision was as per the anatomical finding and results of the stimulated Testosterone to give Testosterone injections and asses the response. The child respond very well to the testosterone treatment which leads to improvement in the size and length of the phallus.

Discussion

mixed gonadal dysgenesis is one of the causes of DSD .45, X/ 46, XY mosaic: At birth around 90 per cent of babies with 45,X/46,XY have normal-appearing external male genitals, five per cent have normal-appearing female genitals and in five percent the external reproductive organs are neither fully male nor fully female. They may find one or two gonads that are very inadequate testes, possibly with some ovary-like tubules present. They may find one streak gonad and one immature, dysgenetic or normal testis. They may find an internal vagina, cervix and uterus, although these are usually quite small compared to a normal female. Some people with a 45,X/46,XY karyotype have reduced fertility and some are infertile. No judgment can be made about fertility until well after puberty in the apparently normal males. Children with a 45,X/46,XY karyotype can have any of the medical conditions that are more common among girls with Turner syndrome (who have a 45,X karyotype), which includes heart and disorders, autoimmune disorders and short stature.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF14 | PMON320 Ovarian Malignancy, Familial Multinodular Goiter Associated with DICER1 Mutation
Authors: Broussard Julia R
Published: November 2022

Background

DICER1 syndrome, a rare autosomal dominant disorder, places affected individuals at risk for benign and malignant tumors of multiple organs, including thyroid, ovaries, lungs, kidneys, CNS. These tumors occur in childhood and usually before 40 years of age.

Clinical Case

A 15-year old female presented with worsening abdominal pain and vomiting. She noted a "hard spot" on her abdomen and reported secondary amenorrhea with worsening acne and development of hirsutism over the previous 12 months. Imaging evaluation showed a 9 cm×19 cm×13 cm right ovarian mass with no enlarged lymph nodes. Initially, tumor markers and hormone levels were elevated: Alpha Fetoprotein 424 ng/mL [0-7], Testosterone 208 ng/dL [12-60], Free Testosterone 6.03 ng/dL [0.04-1.09], Inhibin A 129 pg/mL [97.5], Inhibin B 817 pg/mL [< 136], LDH 742 unit/L [370-645]. Patient underwent right salpingo-oophorectomy, lymph node and omentum biopsy; pathologic exam showed Stage 1C Sertoli-Leydig tumor of the right ovary (intermediate to poorly differentiated). She received chemotherapy with Cisplatin, Etoposide, Bleomycin. Genetic analysis revealed that she is heterozygous for a likely pathogenic variant, c.343del (p.Thr115Leufs*13) in DICER1, consistent with a diagnosis of autosomal dominant DICER1-associated disease. After therapy ended, her tumor markers and hormone levels normalized. Patient was found to have a multinodular goiter with benign pathology; her thyroid function remained normal. A 2 mm right middle lobe pulmonary nodule, stable, has been present on chest CT. Family history is significant for an euthyroid multinodular goiter with benign nodules in her 2-year older brother who has the same DICER1 pathogenic variant. Their mother and maternal grandmother also had total thyroidectomy for multinodular goiter.

Conclusion

A cluster of certain tumors in family members involving successive generations, should prompt evaluation for a genetic cause, as early diagnosis, management and appropriate surveillance improve patients’ quality of life.

Presentation: Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP537 A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities
Authors: DeLorenzo Frank , Gruntmanis Ugis
Published: November 2022

A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities Background: Leydig Cell Tumors can present with marked virilization and yet may evade detection with common imaging modalities. This is a case of a patient with hyperandrogenism due to a 1.6cm ovarian Leydig cell tumor that could not be detected on transvaginal ultrasound, contrast enhanced CT or MRI with contrast. Clinical Case: A 61-year woman presented with virilization. She had a history of a right-sided borderline serous ovarian tumor status post right oophorectomy 23 years prior to presentation and a hysterectomy 16 years prior to presentation. She followed up with gynecologic-oncology for several years but eventually stopped as her condition was stable. On re-presenting to establish care with a gynecologist she complained of increased hair growth on her face, abdomen and buttocks as well as hair loss on the front and top of her scalp. On exam, she was noted to have clitoromegaly with no palpable adnexal masses. Labs revealed total testosterone 398ng/dL (8-60ng/dL), free testosterone 9.15ng/dL (0. 06–0.87ng/dL), 17-hydroxyprogesterone 204ng/dL (<51ng/dL) CA-125 of 6.2U/mL (<=38.1U/mL) and DHEAS 23.1mcg/dL (18.9 – 205mcg/dL). Transvaginal ultrasound showed a left ovary of 3cc with no mass or abnormality. She was referred to endocrinology and a CT abdomen and pelvis with contrast was obtained that again showed no adnexal mass but was notable for a 7mm isoattenuating nodule in the left adrenal gland. Additional labs were obtained including 24 hour urinary cortisol and metanephrines, late night salivary cortisol and serum aldosterone and renin activity, all of which were within normal limits. Suspicion remained high for an ovarian source of the hyperandrogenism so a pelvic MRI with and without contrast was performed which showed a normal appearing left ovary measuring 2.3cm×4.2cm×1.8cm. She was referred to gynecologic-oncology and it was decided to proceed with a left oophorectomy. This was performed and the pathology revealed a 1.6cm Leydig cell tumor in the left ovary. Testosterone and 17-hydroxyprogesterone subsequently normalized when checked seven weeks post-op.

Conclusion

Leydig cell tumors are rare ovarian tumors often presenting with hyperandrogenism in postmenopausal patients and can be difficult to identify on imaging. A review of published case reports revealed 8 cases in which Leydig cell tumors ranging from 1.2cm to 4.6cm could be detected using one of the imaging modalities employed in this case. There were 9 reports of tumors ranging from 0.8cm to 2cm that evaded detection on imaging. When significant hyperandrogenism is present in a postmenopausal patient a strong suspicion for an ovarian source should be maintained even when imaging is apparently normal.

Presentation: No date and time listed
ODP642 Differences in hormonal profiles and vitamin D status depending on the insulin sensitivity status in women with polycystic ovary syndrome (PCOS).
Authors: Ozga-Piszczek Katarzyna , Krzyczkowska-Sendrakowska Magdalena , Piszczek Piotr , Ratajczak Maciej , Ratajczak Magdalena , Chaykivska-Agafonova Zlata
Published: November 2022

Background

Depending on metabolic profile, two different PCOS phenotypes may be distinguished- the metabolic phenotype related to insulin resistance (IR) and the reproductive one, with persistent insulin sensitivity. Hyperandrogenemia, the main feature of PCOS, leads to increased visceral fat and muscle masses and thus to lower insulin sensitivity. In turn, IR leads to metabolic consequences and hormonal imbalance. Moreover, vitamin D deficiency, which is common in PCOS patients, is also associated with insulin resistance.

Aim

To compare the hormonal profiles and vitamin D status in women with PCOS depending on insulin sensitivity status.

Materials and methods

One thousand three hundred women with PCOS, aged 18 to 40, were recruited. The patients were divided into two groups depending on their insulin sensitivity status. Metabolic and hormonal parameters were assessed in subjects from each group. Blood samples were collected between the second and the sixth day of the menstrual cycle (follicular phase)for the quantification of hormonal parameters using the electrochemiluminescence immunoassay (ECLIA) methods or colorimetry.

Results

Patients with insulin resistance have a significantly higher concentration of DHEAS and TSH, higher Free Androgen Index, and significantly lower vitamin D concentration. Moreover, cortisol and estradiol concentrations are higher and prolactin is lower in patients with IR, but the differences are not statistically significant. There are no significant differences in the prevalence of Hashimoto disease between patients with IR and patients with persistent insulin sensitivity.

Conclusions

Metabolic phenotype of PCOS is associated with higher androgen concentration and higher TSH concentration compared to reproductive phenotype. Moreover, patients with PCOS and IR often have vitamin D deficiency compared to patients with persistent insulin sensitivity. Therefore the supplementation of vitamin D and regular TSH measurements are important in patients with metabolic PCOS phenotype.

Presentation: No date and time listed