bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-444 Long-Term Effect of Neutering on Plasma Luteinizing Hormone Concentrations in Cats: A Potential Role in the Pathogenesis of Feline Hyperthyroidism
Authors: Aguiar Joana , Crossley Victoria , Davison Lucy , Fowkes Robert C , Syme Harriet Merlin
Published: May 2020

Feline hyperthyroidism remains a major area of interest within the veterinary field given its high prevalence, affecting nearly 10% of geriatric cats, and that causal factors leading to this disease are not completely understood.1,2 Feline hyperthyroidism shares clinical and histopathological similarities with Toxic Multinodular Goitre in humans and therefore the discovery of driving cellular mechanisms behind the pathogenesis of this feline disease may bring translational insight into the pathogenesis of the later.3,4 Gonadotropin hormones such as LH are structurally related to other glycoproteins including TSH and cross-reactivity between these and their receptors has been demonstrated.5 It is hypothesized that increased concentrations of gonadotropins in neutered cats might be implicated in the pathogenesis of hyperthyroidism. This study aimed to determine the long-term effect of neutering on plasma LH concentrations in cats. Stored plasma samples from client-owned cats were used for measurement of LH and TSH concentrations. Clinical data, including age, sex, neutering age and medical history were reviewed. Two study populations were included in this study: (1) a geriatric cat population (≥ 9 years old): 18 entire and 18 neutered cats matched for age, sex and date of sample collection; (2) an adult cat population (2-8 years old): 45 neutered cats. LH concentrations were measured using a feline ELISA and TSH concentrations were measured by the Immulite canine TSH assay. Geriatric neutered cats have higher plasma LH concentrations (median, 0.25 ng/ml [25th percentile, 0.25; 75th percentile, 2.1]) than age matched entire cats (0.25 ng/ml [0.25, 0.25], P < 0 .001). Cats neutered between 6-9 months of age have higher LH concentrations than cats neutered before or after that period (P = 0.004). No correlation was found between plasma LH and TSH concentrations (P = 0.422). In conclusion, neutering causes significant long-term increase in LH concentrations in cats. Further research to determine whether this results in activation of the TSH receptor and ultimately in thyrocyte hyperplasia and/or hyperfunction is warranted.

References:

1. Mooney CT. Pathogenesis of feline hyperthyroidism. J Feline Med Surg 2002;4:167-169.

2. Peterson M. Hyperthyroidism in cats: what’s causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 2012;14:804-818.

3. Krohn K, Fuhrer D, Bayer Y, et al. Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr Rev 2005;26:504-524.

4. Gunn-Moore D. Feline endocrinopathies. Vet Clin North Am Small Anim Pract 2005;35:171-210, vii.

5. Jiang X, Dias JA, He X. Structural biology of glycoprotein hormones and their receptors: insights to signaling. Mol Cell Endocrinol 2014;382:424-451.
MON-715 How Heterogeneous Are Pituitary Thyrotropes?
Authors: Dudley Lindsey Anne , Daley Alexandre Zacharie , Mortensen Amanda Helen , Sridhar Rachna , Brinkmeier Michelle , Cheung Leonard , Camper Sally Ann
Published: May 2020

Many transcription factors have been identified that are important for specification and differentiation of the hormone-producing cells of the pituitary gland. For example, POU1F1 is essential for differentiation of thyrotropes, somatotropes, and lactotropes. GATA2 is important for differentiation of both thyrotropes and gonadotropes, and NR5A1 drives gonadotrope differentiation. It is not known whether additional transcription factors are involved in thyrotrope specification. A few POU1F1-independent thyrotropes arise during development at the rostral tip of the pituitary gland, but the majority of thyrotropes are POU1F1-dependent and arise in the caudo-medial area of the anterior pituitary gland. Pou1f1-deficient mice lack this major, critical type of thyrotropes and are severely hypothyroid. Several pieces of evidence suggest that the caudo-medial population of thyrotropes is heterogeneous. First, NR5A1-positive cells exist that express both TSH and FSH during pituitary development. Second, Pou1f1 mRNA is detected in only about half of pituitary cells immuno-positive for TSH. Third, the transcription factor ISL1 is only detected in a fraction of developing thyrotropes. The Helix-Loop-Helix transcription factor ASCL1 is critical for zebrafish pituitary development, but there are conflicting data about its role in pituitary thyrotrope specification in mice. To quantify the role of ASCL1 in thyrotrope development we carried out immunostaining for TSH in pituitaries of Ascl1 deficient mice in late gestation. We did not detect any reduction in TSH immuno-reactive cells at this time, suggesting there are species-specific differences in the requirement of ASCL1 in the developing pituitary. To systematically assess and quantify the heterogeneity of thyrotropes for transcription factor expression, we performed co-immunostaining for TSH and various transcription factors in pituitaries of newborn mice. We found that approximately 75% of TSH-positive cells in the caudo-medial region of the pituitary express POU1F1, and the majority express GATA2. We detected a small portion of cells co-expressing NR5A1 and TSH at this time. To confirm our immunostaining results, we analyzed data from single cell RNA sequencing of postnatal thyrotropes. Three robust clusters of thyrotropes were identified. Approximately 80% expressed Gata2, 85% expressed Pou1f1, and roughly 15% expressed Nr5a1. Taken together, the protein and RNA analysis support that thyrotrope heterogeneity exists during development. The functional significance of this heterogeneity and its variation during development will be the subject of future investigation.
SAT-128 An Uncommon Case of Squamous Cell Carcinoma of the Vulva with Metastasis to the Thyroid Gland
Authors: Munshi Laishiya , Pulipati Vishnu Priya , Mascarell Susana
Published: May 2020

Background: Distant metastasis from Squamous Cell Carcinoma (SCC) of the Vulva is very rare and typically associated with poor outcomes. In the literature, there have been no reported cases of vulvar SCC with metastasis to the thyroid, which augments the uniqueness of the case we are presenting.

Clinical Case: A 29-year-old female was hospitalized for abdominal pain & altered mental status. Labs showed calcium 21 (RR 8.5-10.5 mg/dL) with iPTH 4.3 (RR 12-88 pg/mL). Imaging revealed an 8.6 x 7.2 cm right thyroid mass (solid with cystic internal components, hyperechoic to isoechoic, wider than tall, lobulated margins, punctate echogenic foci occupying nearly the entire right lobe, minimal vascularity), mildly effacing the trachea. There were also extensive lesions consistent with systemic metastasis involving the left hilar lymph nodes, pre-tracheal lymph nodes, right hepatic lobe, head of pancreas, retroperitoneal lymph nodes, right inferior pubic ramus, proximal right humerus, left humerus, proximal femur & frontal lobe of the brain. Hypercalcemia of malignancy from an unknown cancer was diagnosed. FNA biopsy of the thyroid mass was consistent with atypia of undetermined significance. Liver biopsy showed evidence of high grade carcinoma with non-calcitonin producing neuroendocrine differentiation. Labs showed serum serotonin 11 (RR 56-244 ng/mL), CA 19-9 < 0.8 (RR 0-35 U/mL), alpha-fetoprotein 2.12 (RR 0-9 ng/mL), CEA 20.97 (RR 0-2.9 ng/mL), PTHrP 33 (RR 14-27 pg/mL), 1,25OH Vit D 18 (RR 18-72 pg/mL), chromogranin A 189 (RR 25-140 pg/mL), & calcitonin < 2 (RR < 5 pg/mL). A vaginal lesion was discovered on exam & biopsy showed squamous cells with cytopathic effect of Herpes Simplex Virus (confirmed with immunohistochemical stain). Subsequent biopsy of the brain & core needle biopsy of the thyroid showed morphology similar to a concurrent biopsy of a vulvar lesion also found on exam: poorly differentiated SCC. The patient was diagnosed with vulvar SCC with extensive metastasis. Her hospital course was complicated by atrial fibrillation, acute respiratory failure, & sepsis. She, unfortunately, passed away from her severe morbidities.

Discussion: Metastasis to the thyroid is an infrequent occurrence. It is commonly encountered in breast, lung & renal cell carcinomas. It can occur due to direct spread from adjacent tissues or by lymphatic or hematogenous spread. Thyroid gland metastasis is more commonly seen in patients with aggressive or widespread carcinomas, especially by hematogenous route, due to the thyroid’s extensive vascularity.

Conclusion: Thyroid gland metastasis, particularly due to vulvar SCC, is a rare entity with a poor prognosis. In patients with extensive poorly differentiated carcinoma such as our patient, it is of utmost importance to identify suspicious thyroid nodules and perform comprehensive diagnostic testing to facilitate timely intervention for improved outcomes.
MON-691 Association of Serum Level of Omentin-1, Hs-CRP and Atherosclerosis in Patients with Type 2 Diabetes
Authors: Amara Mohamed Fahmy
Published: May 2020

Omentin-1 has been identified as an interesting novel adipokine that may modulate the action of insulin. Serum omentin-1 levels were associated with endothelial dysfunction and cardiovascular diseases, which highly contribute to morbidity and mortality of patients with diabetes, however its exact biological function is still unclear. The aim of this study was to assess the level of circulating plasma Omentin-1 level in patients with type 2 diabetes compared to control subjects, and to investigate the relationship of circulating Omentin-1levels with HOMA, BMI, lipid profile, epicardial fat, visceral fat and subcutaneous fat in early stages of atherosclerosis measured by carotid intima media thickness (CIMT). This is a cross-sectional observational study which included 45 patients with type 2 DM (not previously diagnosed as ACVD patients) and 30 (age and sex)-matched healthy control subjects. Patients with a history of recent acute infection, malignancy, metabolic or endocrinal diseases, cardiac failure, renal and hepatic impairment were excluded. Participants were subjected to measurement of FPG, HbA1c, lipid profile, calculation of HOMA2, hs CRP, serum omentin-1, CIMT, estimation of visceral, epicardial and subcutaneous fat through CAT scanning. There was no statistically significant difference between both groups in the mean circulating omentin-1 level, a mean of (793.86 ± 195.81) ng/ml in type 2 diabetes Vs (804.93 ± 205.76) ng/ml in the control group,(p=0.654). However, there was a highly statistically significant difference in hs-CRP between both groups, mean hs CRP is (4.29 ± 4.87 mg/l) vs (0.92 ± 0.53 mg/l) respectively. There was a statistically significant negative correlation between omentin-1 and hs CRP (r= -0.278, p= 0.016).There were no statistically significant correlations between omentin-1 with BMI, HbA1c, HOMA, lipid profile or adiposity. These findings may denote the anti-inflammatory effects of omentin-1 which maybe unrelated to insulin resistance and dyslipidemia. Further studies are required to confirm the cardioprotective role of omentin-1 in patients with type 2 diabetes, focusing on its local anti-inflammatory role.

Nothing to disclose: MA, NA, NK

No Sources of Research Support
SUN-271 Langerhans Cell Histiocytosis: A Difficult Diagnosis in Cranial Diabetes Insipidus
Authors: Ng Ivy Hoi Yee , Cheung Elaine Yun Ning , Kam Grace Yee Wai
Published: May 2020

Background

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder that is rare in adults, with a reported incidence of 1-2 cases per million per year. Cranial diabetes insipidus (CDI) is the most common and often the first endocrine manifestation of LCH, when histiocytes infiltrate the pituitary. Anterior pituitary dysfunction, when present, usually develops after onset of CDI. Unlike most other etiologies of CDI, multisystem involvement is frequent in LCH, especially the bones, skin, and lungs.

Case

A 23-year-old man of good past health presented with 3 months of polyuria and polydipsia in 2015. CDI was confirmed by water deprivation test, and his symptoms resolved with DDAVP treatment. There were no anterior pituitary hormone deficiencies on presentation. Pituitary MRI showed loss of the posterior bright spot and a contrast enhancing pituitary stalk thickening (PST) of 5 mm, with no compression on the optic chiasm. Lumbar puncture showed no evidence of CNS infection or neoplastic cells. Beta HCG, AFP, IgG4, ANA, and chest Xray were unremarkable. Three months later he developed central hypogonadism, and was treated with testosterone after sperm banking. A repeat MRI showed persistent PST of 5 mm, and biopsy of the pituitary suggested lymphocytic infundibulo-hypophysitis (LIH). Unfortunately the biopsy was complicated with irreversible focal visual field defect.

It was then noted that a bone scan had been arranged earlier for intermittent left hip pain, which revealed a 3.5 cm osteolytic lesion over the left ilium. The concomitant pituitary and bone lesions thus make LCH the more likely diagnosis. However bone biopsy showed nonspecific fibrosis only. The pathologist was then contacted for further immunohistochemical analysis. This identifies clusters of Langerhans cells with positive stain for S100, CD1a, and Langerin (LCH cell markers) in the pituitary tissue, and BRAF V600E mutation was detected by PCR, compatible with the diagnosis of LCH. Systemic chemotherapy was proposed due to multisystemic disease, but was declined by patient. At 4 years of follow-up, the PST spontaneously regressed to 2 mm but the CDI and central hypogonadism persisted.

Conclusion

Our case illustrates the diagnostic challenge in a patient presenting with CDI, given a pituitary biopsy with histological features mimicking LIH and an inconclusive bone biopsy. However, a diagnosis of LIH would not explain for the unusual bone lesion in a young man, and bone biopsies can be prone to crush artifacts limiting analysis. The importance of actively looking for and biopsying extracranial lesions before biopsying the pituitary cannot be understated as the latter entails risks of hypopituitarism and visual defect, as had happened to our patient. When clinical and pathologic findings do not match, communication with the pathologist for histological review had been essential in establishing the diagnosis of LCH.
SUN-351 Sex Is a Strong Variable in the Mineral Metabolism Defects and Endocrine Dysfunction Associated with the Murine Adenine Diet Model of Chronic Kidney Disease (CKD)
Authors: Liesen Michael P , Noonan Megan L , Clinkenbeard Erica , Ni Pu , Agoro Rafiou , Tippen Samantha P , Hum Julia , White Kenneth E
Published: May 2020

The adenine diet is widely used in animal models to produce a tubulointerstitial fibrosis and inflammation that mimics human CKD in many aspects. These include the biochemical manifestations hyperphosphatemia and anemia, as well as endocrine dysfunction with elevated FGF23 and hyperparathyroidism. Male rodents are known to be less tolerant of adenine diet regimen than females, however the underlying mechanisms driving the sex differences remain unclear. Additionally, much of the data for adenine studies arises from rats, whereas mice are more commonly used in laboratory settings and are far easier to manipulate genetically. To this end, as part of a larger study to test the effects of iron-handling in CKD, we assessed the biochemical, molecular, and physical differences between male and female mice receiving an adenine diet to induce CKD. Flox-Fgf23 mice (8 weeks of age, n=4-6/group; mice were Cre negative, thus phenotypically wild type) were placed on a 0.2% adenine-containing diet (CKD); a matching casein-based diet served as control. After 6 weeks, mice were euthanized, and blood and tissues were collected for analysis. As expected, body weight at baseline was initially higher in males than in females, however males lost significantly more weight. Serum BUN was also elevated in both sexes receiving adenine, although males were higher (1.2 fold; p<0.01). Males also had elevated creatinine and lower total serum iron from baseline whereas females had no significant changes. FGF23 was elevated in all mice, with no significant differences between sexes. Kidney fibrosis and inflammation markers were elevated in the CKD mice, with males having higher expression of Col1a1 and -3a1 versus females (3.5/1.5 fold; p<0.001) and TNFα mRNA (2 fold; p<0.001). Renal expression of the anabolic vitamin D metabolizing enzyme Cyp27b1 (1α-hydroyxlase) and early growth response 1 (Egr1) were increased in CKD mice, with males having higher expression over females. Conversely, CKD males had lower kidney Klotho mRNA expression, and both sexes fed adenine expressed significantly lower NPT2a (sodium- phosphate co-transporter2a) mRNA. Liver expression of ferritin (Fth1) was elevated in male CKD mice compared to diet controls, whereas female mice had no differences. Elevated FGF23 has been linked to ventricular hypertrophy, and CKD males had significantly higher heart weight to femur ratio at completion of the study. Our results support that male mice succumb more rapidly than females to adenine diet mediated CKD phenotypes, potentially enhanced by fibrosis and inflammation. It remains to be determined whether the more rapid onset of defects in iron handling parameters accelerate the severe male CKD phenotype.
SUN-135 Characterization of Transcription Factor Immunostaining and Null Cell Adenoma Status in Hormone Negative Pituitary Adenomas
Authors: Baertsch Hans C , Pangal Dhiraj J , Garrett Trey , Brunswick Andrew , Rutkowski Martin , Hurth Kyle , Michael John D , Zada Gabriel
Published: May 2020

Introduction: Since the 2017 W.H.O. classification of pituitary adenomas redefined null cell adenomas (NCAs) as negative for all adenohypophyseal hormones and the transcription factors (TFs) SF-1, PIT-1, and T-PIT, limited data exist characterizing these tumors1. We characterize NCAs in comparison to hormone negative adenomas (HNAs), which demonstrate negative hormone immunostaining in the context of positive TF immunoreactivity.

Methods: Retrospective review of 22 patients with HNAs between 2011-2019. Samples were stained for PIT-1 and SF-1. Negative ACTH staining served as a proxy for T-PIT given demonstrated prior concordance of these stains2. Demographics, tumor characteristics, preoperative symptoms, and postoperative outcomes were assessed.

Results: Fifteen samples (68%) stained negative for both PIT-1 and SF-1 and were classified as NCAs. Seven were positive for SF-1 (n=3), PIT-1 (n=3), or both (n=1) and were classified as HNAs. NCA patients were predominantly female (80%), while those with HNAs were predominantly male (57%). All tumors were macroadenomas, with mean maximal tumor diameter of 28mm in NCAs vs 23mm in HNAs (p=0.2705). NCAs were more likely to demonstrate suprasellar invasion (100% vs. 71%, p=0.0325), and although not statistically significant, cavernous sinus invasion (53% vs. 43%, p=0.6695), and higher MIB-1 proliferative index (2.271 vs. 1.971, p=0.733). The most common preoperative symptoms were headache (73% NCA, 71% HNA) and vision loss (53%, 40%). Postoperative improvements in headache (60% NCA, 71% HNA) and vision (53%, 50%) were comparable. Sixty-four percent of NCAs underwent gross total resection vs. 43% of HNAs (p=.3712). There were no recurrences or progressions in either group over 24mo. Few comparisons reached significance, potentially due to limited sample size.

Conclusion: A majority of HNAs demonstrated negative TF immunostaining and met criteria for NCAs. NCAs may be more common in females and demonstrate more suprasellar invasion than HNAs, but otherwise, do not vary significantly. TF staining may be of limited clinical utility in identifying high-risk pathology, however future studies with larger cohorts are warranted.

References:

1. Osamura RY, Lopes MBS, Grossman A, Matsuno A, Korbonits M, Trouillas J, Kovacs K (2017) Pituitary adenoma. In: Lloyd RV, Osamura RY, Klöppel G, Rosai J (eds) World health organization classification of tumours of endocrine organs, 4th edn. IARC, Lyon, pp 14-18.

2. Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, Takeshita A, Fukuhara N, Yamaguchi-Okadad M, Takeuchi Y, Yamada S (2015) The Complementary Role of Transcription Factors in the Accurate Diagnosis of Clinically Nonfunctioning Pituitary Adenomas. Endocr Path 26(4):249-55.
SAT-472 An Atypical Presentation of Severe Hypothyroidism, a Case of Large Posterior Pericardial Effusion Without Hemodynamic Compromise
Authors: Garay Paola Andrea Sanchez , Restifo Daniele , Rao Swathi , Espinoza Diana , Ionescu Madalina Liliana , Lichtenberg Robert
Published: May 2020

BACKGROUND We are reporting a case of a Hispanic female who presented with a pericardial effusion as a complication of hypothyroidism, untreated due to lack of medical care, which demonstrates health disparities in chronic diseases. CLINICAL CASE The patient is a 48 year-old Hispanic female with PMHx of hypothyroidism, non-compliant with medical therapy, who presented to the ED with fatigue and dyspnea. Despite progressively worsening symptoms for the past 4 months, she had refused to be seen by a physician because she was uninsured. Her physical exam was notable for generalized pallor and bradycardia, with otherwise normal cardiopulmonary exam. Her initial laboratory data showed hemoglobin of 5.5 g/dl. CXR demonstrated an enlarged cardiac silhouette, which on CT was found to represent a large pericardial effusion. On admission her laboratory data demonstrated low ferritin, TSH of 94 mIU/L and T4 of 1.4 mcg/dl. m. Cortisol was 9 mcg/dl at 11 am. Repeat hemoglobin post-transfusion was 9 g/dl The patient was started on IV levothyroxine and hydrocortisone. Echocardiogram showed a large posterior wall pericardial effusion without evidence of RV strain. Pericardiocentesis was attempted but was unsuccessful because of difficult access to the fluid location. She was discharged on levothyroxine 88mcg QD and recommended to follow up with endocrinology and cardiology as an outpatient. It is well known that the United States spends a disproportionate amount of money in healthcare in comparison to developing countries (1). Underinvestment in social services and high prices set by pharmaceutical companies are likely contributing factors (1). Unfortunately, the resulting outcomes do not necessarily reflect the spending. Minorities are well known to have a higher morbidity and mortality as well as to present more frequently with dramatic manifestations of chronic diseases. This can often be attributed to a lack of access to medical care and poor follow up. Our patient was diagnosed with pericardial effusion as a complication of untreated hypothyroidism, a condition that is underdiagnosed despite a high incidence (3-37%). This pericardial effusion was initially concerning due to its large volume. The fact that she was hemodynamically stable reflects its chronicity, but it could have led to a fatal complication if she continued without appropriate therapy for a longer period of time. CONCLUSION A case such as this should make us question what more we can do to improve healthcare outcomes for minorities in the USA. REFERENCES (1). Papanicolas, Irene, Liana R. Woskie, and Ashish K. Jha. “Health care spending in the United States and other high-income countries.” Jama 319.10 (2018): 1024-1039.
MON-704 Tear Glands and the Diabetic Patient: Is It a Biomarker?
Authors: Momen Donia , Wu Gloria , Luu Shannon , Leung Brian
Published: May 2020

Background: Tear glands in the eyelids, meibomian glands, play a role in tear film production and tear film stabilization. Diabetic patients often complain of dry eye and eye pain. Recently, there are new infrared (820nm) photography techniques to image meibomian glands easily in patients.

Purpose: To study meibomian glands in diabetic patients with dry eye.

Methods: A retrospective chart review (2017-2019) of Type 2 Diabetes Mellitus (T2DM) patients and non-diabetic patients with the diagnosis of “dry eye” in EHR (eClinicalworks, Westborough, MA) was performed. Infrared eyelid imaging (820 nm wavelength, Heidelberg Spectralis, Heidelberg, Germany) was taken. T2DM: Inclusion criteria: 1) HbA1c of > 5.7% who also had infrared eyelid imaging performed + 4 weeks of their HbA1c lab test results; 2) the percentage loss of meibomian glands for each eye, then averaged, for each patient. Control: Inclusion criteria: 1) non-diabetic patients; 2) HbA1c lab test results; 3) infrared eyelid imaging was performed; 4) percentage loss of meibomian glands was calculated for each eye, then averaged per patient. Exclusion criteria for both T2DM and Controls: younger than the age of 18 years old, older than 90 years old, no glaucoma topical medications, no eyelid surgery, no corneal surgery, no conjunctival surgery.

Results: n=120 patients, Avg Age=69.6 years (sd=15.1, range 23-89 years). Diabetic patients: n=60 patients, Male=30, Female=30, Avg Age=65.1 years (sd=11.50, med=65.5, range 36-85 years). Controls: n=60 patients, Male=37, Female=23, Avg Age=54.1 years (sd=16.4, med=56.5, range 23-89 years). Meibomian gland loss: Diabetics=51.54%, Controls=11.29% (p<0.0001, t-test). Of the 60 DM patients: 35/37pts with HbA1c > 6.6% had greater loss of meibomian glands (>40%), compared to 12/23 DM patients with HbA1c < 6.5%, p=0.0001.

Discussion: Loss of meibomian glands in diabetic patients have been recently investigated; however, its relationship to HbA1c as a possible biomarker has not been widely discussed in literature. In this small study, loss of meibomian glands occur more frequently with elevated HbA1c, perhaps due to microischemia of the eyelids, thereby resulting in loss of meibomian glands.

Conclusion: Loss of meibomian glands may suggest a need for HbA1c testing and further monitoring of the patient’s diabetic condition. Infrared imaging of the eyelid may be useful in characterizing dry eye in diabetic patients.
SUN-079 Baseline Body Satisfaction in Gender-Diverse Youth
Authors: Gohil Anisha , Donahue Kelly , Eugster Erica A
Published: May 2020

Background: Body dissatisfaction often contributes to the distress experienced by transgender and nonbinary individuals. However, limited data exist regarding body image in the pediatric age range.

Objective: To establish baseline ratings of body satisfaction among gender-diverse youth prior to puberty blocking medication.

Methods: Subjects were recruited from the gender health clinic at Riley Hospital for Children beginning in January 2018. Eligible subjects met clinical criteria for a puberty blocker, were treatment naïve, and were anticipated to be on a blocker alone for ≥ 1 year. We assessed self-reported body satisfaction at baseline using the Body Image Scale-Gender Spectrum. Subjects rated various body parts on a scale of 1 (very satisfied) to 5 (very dissatisfied). For analysis, body parts were grouped into gendered features (primary sex, secondary sex, & neutral characteristics) and also body areas (appearance/hair/voice, head & neck, musculoskeletal, hips, chest, & genitals/gonads).1

Results: Twenty subjects (mean age 12.0, range 8.4-14.0) were enrolled of whom 13 were transmasculine (TM) and 7 were transfeminine (TF). TM subjects had a mean BMI percentile of 73.7% and height z-score of 0.50, with breast Tanner stage (TS) of II (n=2), III (n= 3), IV (n=3) and V (n=4). Estradiol levels ranged from <20-120 pg/mL and testosterone levels ranged from <10-38 ng/dL. TF subjects had a mean BMI percentile of 65.3% and height Z-score of 0.58, with testicular volumes of 5 cc (n=1), 6 cc (n=2), 9 cc (n=1), 10 cc (n=1) and 15 cc (n=1). Testosterone levels ranged from <10-215 ng/dL and estradiol levels ranged from <5-31 pg/mL. Among all subjects, mean satisfaction ratings for gendered features were 4.45 (primary sex characteristics), 3.21 (secondary sex characteristics), and 2.61 (neutral characteristics). Mean satisfaction ratings for body areas were 4.45 (genitals/gonads), 3.85 (chest), 3.23 (appearance/hair/voice), 3.03 (hips), 2.83 (musculoskeletal), and 2.55 (head & neck). The only significant between-group difference in satisfaction was for the chest region, with TM subjects reporting higher dissatisfaction (4.35 vs 2.93, p <0.004).

Conclusion: The gender-diverse youth in our study reported high degrees of dissatisfaction with their genitals/gonads and, for TM subjects, their chest. In contrast, they reported generally neutral feelings toward many of their other body parts. To the best of our knowledge this is the youngest cohort of gender-diverse youth in whom body satisfaction has been explored. Further studies of the effects of endocrine treatment on body image in gender-diverse youth are warranted, specifically as they relate to other measures of well-being.

References: 1. van de Grift TC et al. Body satisfaction and physical appearance in gender dysphoria. Archives of sexual behavior. 2016;45(3):575-585.
SAT-449 Factors Associated with Reduced Thyroid Hormones in Cushing Syndrome Patients Before and After Surgical Cure
Authors: Shekhar Skand , McGlotten Raven , Nieman Lynnette K
Published: May 2020

Background: Hypercortisolemia adversely affects thyroid hormone secretion. We previously described the temporal pattern of thyroid function recovery in 23 patients (1). However, the factors leading to suppression and recovery of the hypothalamic-pituitary-thyroid (HPT) axis in Cushing’s syndrome (CS) are not fully understood. We performed two separate studies to investigate these factors. Methods: In study 1, we examined patients (pts, n=62) with CS who underwent curative surgery and recorded their serum morning and evening cortisol, ACTH, tumor volume and duration of symptoms and 24-hour urine free cortisol (UFC) at baseline and the morning serum free T4, TSH and T3 at six-month intervals after cure. Data were log-transformed and Pearson correlations were performed. Linear mixed models were used to study factors that predict recovery of thyroid function. In study 2, we examined the diurnal variation of TSH by performing hourly TSH measurement between 3—7 PM and 12—4 AM on a cohort of pts (n=45) before surgery. Wilcoxon Signed-Rank method was used for comparisons of mean TSH across time and Pearson correlations were performed on log-transformed data. P values <.05 were considered significant. Results: Study 1: In this larger cohort, we confirmed previous findings of suppressed or low normal fT4 and TSH values with active hypercortisolism, with normalization after cure that reflected changes in the T3:TSH, fT4:TSH and T3:fT4 ratios. There were inverse linear correlations between log10 UFC, serum AM and PM cortisol; and log10 TT3, fT4 and TSH before surgery. Independent negative prognosticators of circulating fT4 recovery included UFC greater than 1000mcg/day (nl: 3.5—45mcg/day), duration of symptoms of less than one year, and ACTH levels greater than 60pg/mL(nl: 5—45pg/mL) Study 2: The nocturnal (12 - 4AM) TSH surge was reduced, so that the difference in day and night TSH values was not statistically significant; this contrasts with the 30—50% nocturnal TSH increase above daytime values seen in healthy subjects. There was an inverse relationship between UFC and nocturnal TSH, daytime TSH and TBG values, but there was no direct relationship between UFC and percent changes in nocturnal TSH values. Conclusions: Our findings suggest that a deficit in TSH stimulation of the thyroid gland may explain the reduction in T3 and T4 levels. There is a dose-response relationship between various measures of hypercortisolemia and both thyroid hormones and the pattern of TSH secretion. Finally, the severity of hypercortisolism correlates with a longer time to recovery of the HPT axis in pts with CS after curative surgery. 1. Shekhar S et al. HPG and HPT Axes in Cushing Syndrome. J Endocr Soc, 3 S1, April May 2019
SUN-202 Is a “Failed” Adrenal Venous Sampling Useful for Surgical Decision Making in Primary Hyperaldosteronism?
Authors: El Mais Rania , Acharya Runa
Published: May 2020

Background

Adrenal venous sampling (AVS) is important in differentiating unilateral vs bilateral primary hyperaldosteronism. A limitation is the difficult cannulation of the right adrenal vein (RAV).

A study in 2016(1) investigated the usefulness of AVS with failed right sided cannulation. The investigators calculated the ratios of plasma aldosterone and cortisol in the periphery (IVC) and in the left adrenal vein (LAV), then corrected the aldosterone/cortisol ratio of the LAV for that of the IVC with the following equation: LAV/ IVC = [aldosterone in LAV/cortisol in LAV] / [aldosterone in IVC/ cortisol in IVC]. A LAV/IVC ratio ≥5.5 and ≤0.5 predicted unilateral aldosterone hypersecretion on left and right side respectively with a 100% specificity and positive predictive value.

Clinical case

We present a case of a 51-year-old patient with primary hyperaldosteronism and a failed right sided cannulation. Patient presented with uncontrolled hypertension of 10 years and hypokalemia. His blood pressure (BP) was 190/100 on amlodipine, lisinopril, atenolol, hydralazine and spironolactone.

Screening labs obtained off spironolactone and atenolol showed:

Aldosterone 18.5ng/dl(0-30), renin 0.215ng/ml(0.167-5.738), plasma aldosterone concentration (PAC)/ plasma renin concentration (PRC) 86.

CT abdomen showed a 1.2cmX1cm left adrenal adenoma.

A 24-hour urine collection without salt loading showed an aldosterone of 43.46 microg/L (0-19). He underwent an AVS with a failed RAV cannulation with the following results:

IVC: cortisol=17.2 microg/dl, aldosterone= 8.9ng/dl, aldosterone/cortisol= 0.52

LAV: cortisol=420, aldosterone=2860, aldosterone/cortisol=6.8.

Partial left adrenalectomy was performed. Pathology showed a benign adenoma.

Although his BP initially improved, over several weeks, his BP was high again, and he had a recurrence of hypokalemia. A repeat PAC/PRC of 80 confirmed persistent hyperaldosteronism.

He refused further interventions. Eplerenone was added resulting in BP control.

Conclusion

Based on the above study, his LAV/IVC of 13 predicts the source to be the left adrenal gland. However, this ratio did not apply in our patient and should be utilized carefully.

References:

1.Pasternak JD, Epelboym I, Seiser N, Wingo M, Herman M, Cowan V, et al. Diagnostic utility of data from adrenal venous sampling for primary aldosteronism despite failed cannulation of the right adrenal vein. Surgery. 2016;159(1):267-73.
SUN-282 Transient Infundibulohypophysitis in a Child with Central Diabetes Insipidus
Authors: Puthanpurayil Shabana Kalladi , Uddin Ahsan , Gerrits Peter Matthew
Published: May 2020

Case Description

A 7-year-old previously healthy female presented with a 1-month history of tiredness, excessive thirst and increased urinary frequency. Initial studies showed an elevated serum osmolality with relatively dilute urine. She underwent a water deprivation study which confirmed central diabetes insipidus (CDI). An MRI of the brain was obtained which showed markedly thickened and homogeneously enhancing pituitary stalk thickening (17mm craniocaudal x10 mm anteroposterior diameter). Workup did not reveal any signs suggestive of Langerhan’s cell histiocytosis; a skin biopsy and bone survey were normal. A pituitary stalk biopsy was scheduled, however direct endoscopic visualization of the pituitary stalk was normal, so the procedure was aborted. A repeat MRI 7 weeks later showed complete resolution of the stalk thickening. An MRI done 4 months later again showed normal anterior pituitary and normal pituitary stalk, with persistent absent posterior bright spot. She remains on desmopressin, and anterior pituitary functions have been normal to date.

Discussion

CDI in children can be due to infectious, neoplastic, traumatic or genetic processes that disrupt the hypothalamus or pituitary stalk. One third of children with CDI present with pituitary stalk thickening (PST) on initial evaluation with MRI. There are wide variations in the degree of PST. Previous studies have shown that the degree of PST is different depending on the underlying etiology. Furthermore, regression of PST has been observed in many cases of CDI with PST which has been attributed to idiopathic or autoimmune process (infundibulohypophysitis). Most studies have demonstrated that PST > 4 mm is unlikely to regress and may be more likely to progress with eventual diagnosis of a neoplastic process such as germinoma or Langerhan’s cell histiocytosis. Based on review of the literature, the earliest resolution of PST was in 3 months in a patient who received steroid therapy at diagnosis. [1]

Conclusion

Our case illustrates that in children with central diabetes insipidus, isolated pituitary stalk thickening may resolve in as short a period as 7 weeks. While ongoing evaluation is warranted with serial pituitary imaging, unnecessary invasive procedures may be avoided in patients without evidence of other underlying anatomic pathology. Anterior pituitary function requires initial and continued surveillance.

References

1. Shaefers J et al. Clinical presentation and outcome of children with central diabetes insipidus associated with a self-limited or transient pituitary stalk thickening, diagnosed as infundibuloneurohypophysitis. Clin Endocrinol (Oxf). 2017 Aug;87(2):171-176. doi: 10.1111/cen.13362. Epub 2017 Jun 5.
MON-100 Prevalence of Goitre and Thyroid Disorders in Healthy School Children of Kashmir Valley. A Multistage Cross-Sectional Survey
Authors: Sood Mona , Masoodi Shariq Rashid , VASUDEVAN Vishnu , Bhat Moomin Hussain
Published: May 2020

Background There has been a gradual transition among pattern and prevalence of thyroid dysfunctions among paediatric population post iodisation phase making it imperative to look into it with periodic surveys. Objective To comprehend the existent thyroid disease burden along with goitre prevalence in healthy paediatric population of Kashmir Valley. Design It was a cross sectional survey including 666 healthy school children of Kashmir valley of the age 6-18 years out of which 421 were girls and 245 were boys. Goitre was graded as per WHO grading system. Thyroid function test (TFT-TSH, TT4, TT3) were measured in all study subjects. Urinary iodine excretion UIE was measured in 40 subsampled children. Results The overall prevalence of thyroid dysfunction (goiter and or abnormal TFT) among children was 7.8% (CI 5.9-10.1%) with a prevalence of 9.3% in females (CI 2.9-8.9%) and 5.3% (CI 6.7-12.4%) in males. The overall prevalence of goitre was 2.4% with a significant difference observed in boys and girls as all 16 children with goitre were girls. UIE ranged from 71 to 558ug/gm of creatinine (median,150). TFT results were available in 563 children with abnormal results observed in 6.6% (n=37) subjects. Most common TFT abnormality was subclinical hypothyroidism (SCH) with total of 4.3% while 1.6% subjects had overt hypothyroidism and 0.7% had subclinical thyrotoxicosis. Children with subclinical disease were observed and those with overt hypothyroidism were treated accordingly. Conclusions Total goitre prevalence has decreased in Kashmir Valley post iodisation and continues to decrease further when we compared with previous prevalence study by Masoodi et al 2013*. However, there is a need for periodic large-scale cross-sectional surveys to know the thyroid status of our population. The most frequent thyroid function abnormality in our survey was SCH which needs judicious management as treating these children strain out stretched health resources.

*Masoodi S R et al. Goitre and urinary iodine excretion survey in schoolchildren of Kashmir Valley. Clin Endocrinol (Oxf) 2014;80(1):141–7.
SAT-257 Coexisting Craniopharyngioma and Acromegaly
Authors: Yang Almira , Engel Ashley , Maas Diana
Published: May 2020

Background: Craniopharyngioma has a bimodal age distribution with adults having more pronounced hormone deficiencies.1 Studies indicate hormone deficiencies in >80% of cases, most commonly growth hormone (GH) deficiency.2 Comparatively, acromegaly is due to excess GH primarily from a pituitary adenoma.3 Coexistence of a craniopharyngioma and a secretory pituitary adenoma is extremely rare,4 and here we present a case with both. Clinical Case: A 59-year-old woman presented with a two-month history of acutely worsening headache and a week of vision change. A computerized tomography (CT) head scan revealed a 2.2 cm partially solid and cystic sellar mass compressing the optic chiasm. The patient underwent emergent resection. Pre-operational biochemical studies demonstrated normal hypothalamus-pituitary axes except a mildly elevated insulin-like growth factor 1 (IGF-1). Pathology revealed an adamantinomatous craniopharyngioma. Although decreased, IGF-1 remained elevated post-operatively and magnetic resonance imaging (MRI) showed a small non-enhancing area within the pituitary. The patient recalled a gradual increase in shoe and glove size, coarser facial features, weight gain, bilateral carpal tunnel, and mild fluid retention in ankles over the past few years. The GH remained unsuppressed in a glucose suppression test. Conclusion: We present a case of pathology proven craniopharyngioma and concurrent GH excess. The patient presented with a sellar mass with mass effect prompting emergent pituitary resection. Although findings of combined solid and cystic with calcification on MRI point to craniopharyngioma diagnosis,1 it is difficult to discern a concurrent GH-secreting tumor as it tends to be smaller and hypointense on T2-weighted MRI.5 While most craniopharyngioma patients demonstrate hormone deficiency, comprehensive hormonal evaluation and close follow-up are warranted, as in rare cases, patients can have co-existing secretory pituitary adenoma and craniopharyngioma. Early diagnosis and intervention can help prevent detrimental complications related to excess growth hormone. References: 1. Müller HL. Craniopharyngioma. Handb Clin Neurol. 2014;124:235-53. 2. Zoicas F, Schöfl C. Craniopharyngioma in adults. Front Endocrinol. 2012;3:46. 3. Gadelha, M. et al. Complications of Acromegaly and the Impact of the Current Treatment Landscape: An Update. Endocrine Reviews. 2019;40(1):268-332. 4. Fountas A, Chai ST, Ayuk J, Gittoes N, Chavda S, Karavitaki N. A rare challenging case of co-existent craniopharyngioma, acromegaly and squamous cell lung cancer. Endocrinol Diabetes Metab Case Rep. 2018;2018:18-0018. 5. Potorac I, et al. Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences. Endocrine Related Cancer. 2015;22:169-77.
MON-299 Risk Factors of Re-Growth of Non-Functional Pituitary Adenomas
Authors: Khalimova Zamira Yusufovna , Urmanova Yulduz Mahkhakamovna
Published: May 2020

The aim of investigation to determine clinical aggressiveness diagnostic markers in patients with non-functional pituitary adenomas (NFPA) in the formation of gravity neuroendocrine disease symptoms. Material and Methods: We observed in 87 patients (including man - 44 women -43) of which have a verified diagnosis of NFPA after surgery - 31 which were subjected transnasal adenomectomy of the pituitary (TAG). Further analysis was performed on these patients, who were followed from 1 to 3 years. Results. After the analysis of the frequency of remission and relapse NFPA data selectively in patients we studied the correlation between various parameters and the frequency of relapses. NFPA developed the scale of aggressiveness allowed to identify the risk factors of markers on the 3rd degrees, allowing to create a set of measures of tumor growth relapse prevention. According to MRI data of the brain and pituitary gland, in 15 patients an endosellar tumor was found, in 16 - an endo-extrasellar tumor. In an MRI study, the structure of the NFPA had a predominantly soft tissue (n = 16) and cystic (n = 11) structure. In 4 cases (13%), the structure of the NFPA was represented by a hemorrhagic component, and in 2 (6.4%) of them, both cystic and hemorrhagic components were present. In 18 patients, microadenoma was revealed, in 12 - pituitary macroadenoma and in 1 - a giant pituitary adenoma. The developed scale of aggression markers of NFPA allowed identifying factors by 3 degrees, which allows developing a complex of measures for the prevention of tumor growth recurrence. Conclusions. 1) According to our data, the number of patients with large-cell chromophobic pituitary adenoma predominated - 24 (77.5%). In 2nd place were patients with small cell NFPA - 6 cases (19.3%). And only in 1 case was observed (3.2%) a giant malignant pituitary macroadenoma with recurrence of growth and metastasis in the brain of a teenage girl, in which dark-cell pituitary adenoma was histologically determined, 2) According to our preliminary data, the markers of aggressiveness of the course of NFPA are: young patient age, first symptoms of the disease manifest, large tumor size, asymmetry and deformation of the pituitary gland, signs of tumor invasion into adjacent tissues / arteries / cavernous sinus, presence of small cell and / or dark extracellular chromophobic adenomas, STH hypopituitarism, panhypopituitarism.
SAT-648 Flash Glucose Monitoring Helps Achieve Better Glycemic Control Than Conventional Self-Monitoring of Blood Glucose in Non-Insulin-Treated Type 2 Diabetes: A Randomized Controlled Trial
Authors: Wada Eri , Onoue Takeshi , Kobayashi Tomoko , Handa Tomoko , Hayase Ayaka , Ito Masaaki , Furukawa Mariko , Okuji Takayuki , Okada Norio , Iwama Shintaro , Sugiyama Mariko , Tsunekawa Taku , Takagi Hiroshi , Hagiwara Daisuke , Ito Yoshihiro , Suga Hidetaka , Banno Ryoichi , Kuwatsuka Yachiyo , Ando Masahiko , Goto Motomitsu , Arima Hiroshi
Published: May 2020

Background and aims: Flash glucose monitoring (FGM) is a novel system with which glucose levels are monitored and has been reported to improve glucose variability and glycemic control in type 1 and type 2 diabetes patients treated with insulin. The present study aimed to evaluate the effects of FGM and conventional self-monitoring of blood glucose (SMBG) on glycemic control in patients with non-insulin-treated type 2 diabetes. Reseach design and Methods: In this 24-week, multicenter, open-label, randomized (1:1), parallel group study, non-insulin-treated type 2 diabetic patients at 5 hospitals in Japan were randomly assigned to the FGM (n = 49) or SMBG (n = 51) groups and were provided FGM or SMBG devices for 12 weeks. The primary outcome was change in glycated hemoglobin (HbA1c) level. This trial is registered with UMIN-CTR (UMIN000026452). Results: Forty-eight participants in the FGM group and 45 in the SMBG group completed the study. The mean HbA1c levels were 7·83% (SD 0·25) in the FGM group and 7·84% (SD 0·27) in the SMBG group at baseline, and the values were reduced in both FGM (−0·43%; 95% confidence interval [CI], −0·57 to −0·28; p < 0·0001) and SMBG groups (−0·30%; 95% CI −0·48 to −0·13; p = 0·001) at 12 weeks. On the other hand, HbA1c was significantly decreased from baseline values in the FGM group, but not in the SMBG group at 24 weeks (FGM: −0·46%, 95% CI −0·59 to −0·32, p < 0·0001; SMBG: −0·17%, 95% CI −0·05 to 0·11, p = 0·124); a significant between-group difference was also observed (difference −0·29%, 95% CI −0·54 to −0·05; p = 0·022). Diabetes Treatment Satisfaction Questionnaire score was significantly improved, and the mean glucose levels, standard deviation of glucose, mean amplitude of glycemic excursions, and duration of hyperglycemia were significantly decreased in the FGM group compared with the SMBG group. Conclusions: Glycemic control was better with FGM than with SMBG after cessation of glucose monitoring in non-insulin-treated type 2 diabetic patients.