bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &gt;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 (&lt;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 &gt; 3ng/ mL (goal for remission &lt; 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

Abstract
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 &lt;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&lt; 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&lt;0. 001, predominantly White and a higher proportion of patients with CCI &gt;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&lt;0. 001), increased length of stay (LOS), (5.8 vs 4.8 days, p&lt;0. 001) and increased mean hospitalization cost (THC) ($12,284 vs $10,340, p &lt;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&lt;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

Abstract

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 &lt;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

Abstract

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 &lt;=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.
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

Abstract
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&lt;0.001). Body weight was reduced with a Week 24 mean±SE change of -5.5±0.3 kg (p&lt;0.001). The change from baseline in FIQR and PSS scores were -29.1±1.1 and -20.0±0.8, respectively (both p&lt;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&lt;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

Abstract

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

Abstract
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&gt;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&gt;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.