bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-169 A Rare Case of Adrenocortical Carcinoma Presenting as Hyperaldosteronism Combined with Cushing’s Syndrome
Authors: Punni Emma , Lim Jonea
Published: May 2020

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Most ACC cases are hormonally functional. Commonly produced hormones are cortisol, followed by adrenal androgens. Aldosterone secretion is quite rare (< 2%) (1). Co-secretion of multiple hormones is further rare. Case Presentation: A 59 year old female presented with progressive worsening hypertension. Initial biochemical evaluation confirmed primary hyperaldosteronism. Her potassium was low at 2.9 mEq/L (N: 3.5-5.3 meq/L). Aldosterone level was elevated at 23 ng/dL (N: < or = 28 ng/mL), renin value was 0.90 ng/mL/h (N: 0.25-5.82 ng/mL/h). Aldosterone Renin Ratio was 25. CT abdomen with and without contrast showed 2 lesions within the right adrenal gland. The larger nodule was 3.7 x 2.7 x 4.9 cm with an absolute washout of 61%. A smaller nodule was 2.3x1.8 cm with an absolute washout of approximately 64%. Left adrenal gland was unremarkable.

Further biochemical workup showed plasma catecholamines and metanephrines were normal. A random cortisol value was 22.8 mcg/dL (N: 3.0-16.0 mcg/dL) with a low ACTH level of 3.3 pg/mL (N: 7.2 - 63.3 pg/mL). Given suspicion for adrenal Cushing’s syndrome, we further obtained a 24 hour free urinary cortisol which was elevated at 84.1 mcg/24 h (N: 4-50 mcg/24 h). 8 am Cortisol after an overnight 1 mg Dexamethasone failed to suppress at 17.5 mcg/dL (n<1.8 mcg/dL). DHEAS level was low at 14.1 ug/dL (N: 29.4-220.5 ug/dL). The patient eventually underwent a right adrenalectomy. Post-operatively, her cortisol was suppressed at 1.9 mcg/dL (8 am ref range: 4-22 mcg/dL), and Hydrocortisone replacement dose was initiated. Surgical pathology report was consistent with adrenocortical carcinoma. The patient continues to follow-up with the endocrinology and oncology department for treatment. Conclusion: This case is particularly interesting given the co-secretion of both aldosterone and cortisol by an adrenocortical carcinoma which has been reported in only a few cases in literature. The case highlights the importance of completing a comprehensive biochemical workup pre-operatively in patients with suspicious adrenal mass. There should especially be a low threshold for initiating workup for cortisol hypersecretion as early intervention can help avoid an adrenal crisis in the post-operative period for such patients. A low DHEAS level should raise suspicion for cortisol hypersecretion in a patient with adrenal lesions. As ACTH is the primary stimulant of DHEA, the suppression of ACTH secretion in the setting of adrenal Cushing’s syndrome can contribute to a low DHEAS level. Reference 1.Else, T et al. Adrenocortical Carcinoma. Endocr Rev. 2014; 35(2):282-326.
SAT-074 A Rare Endocrine Cause of Pseudotumor Cerebri
Authors: Gazzaz Nour , Patel Trisha , Metzger Daniel L
Published: May 2020

Introduction: Idiopathic intracranial hypertension, also known as pseudotumor cerebri, can be associated with various medications, obesity, systemic conditions, and inherited disorders. To the best of our knowledge, this is the second pediatric case of a GnRH agonist reported to cause pseudotumor cerebri.

Case presentation: Our patient, a 12 5/12-year-old transgender male (birth-assigned female), started depot leuprolide acetate to suppress puberty at 11 10/12 years of age (early Tanner 2 breast development). He received Lupron Depot® 7.5 mg intramuscularly for 4 doses, then 22.5 mg intramuscular every 13 weeks thereafter. Five months after his first injection, a routine eye examination revealed bilateral papilledema and enlarged blind spots, which was confirmed by a Pediatric Ophthalmologist. He was asymptomatic. There was no marked weight gain in the previous year with a BMI of 24.5 kg/m2 (+1.85 SD). His blood pressure was 110–123 mmHg systolic and 71–85 mmHg diastolic. Neurological examination was normal. CT head was normal. Cranial MRI showed slight flattening of the optic nerve heads, mild engorgement of optic nerve sheath fluid, and no space-occupying mass. Sedated lumbar puncture revealed elevated opening pressure of 31 cm H2O. CSF analysis, including pathology, was benign. He was managed with acetazolamide. Based on these findings, he was diagnosed with pseudotumor cerebri secondary to the GnRH agonist. Follow-up by the Ophthalmologist one month after starting acetazolamide showed significant improvement of the papilledema.

Conclusion: This case highlights that patients on GnRH agonist therapy are at risk for pseudotumor cerebri, and we recommend periodic ophthalmologic surveillance.
MON-670 An Overlooked Cause of Diabetic Pain
Authors: Arzeno Luis Enrique , Lessard Kimberly Kochersperger , Jabbour Serge A
Published: May 2020

Persistent hyperglycemia has been associated with vascular damage in patients with uncontrolled diabetes. Special emphasis has been placed on the heart, kidneys, eyes, and brain since those major organs are vital. However, little has been studied in terms of the vascular supply to the muscle and how it could be affected by high blood glucose. Here we present a 26-year-old female with a history of uncontrolled Type 1 Diabetes Mellitus treated with insulin pump who presented with muscle aches on her right lower extremity. During the evaluation at the Emergency Department (ED), the patient was noted to have diabetes ketoacidosis, intravenous fluids and insulin drip were started. As part of the workup for the muscle aches multiple blood studies were ordered including Creatinine Phosphokinase (CPK) 26 IU/L (25 - 185 IU/L), Erythrocyte Sedimentation Rate (ESR) 102 (0 - 20), C-Reactive Protein (CRP) 3.4 mg/dL (<=0.80 mg/dL), Aldolase 7.5 U/L (<=8.1 U/L), White Blood Cell (WBC) was 13.1 B/L (4.0 - 11.0 B/L). At this point, a muscle biopsy was considered given the lack of evidence to support a definite diagnosis. Before proceeding with the biopsy, a Magnetic Resonance Imaging (MRI) of the low extremities was done, showing diffuse intramuscular edema, predominantly in the right vastus intermedius, with additional patchy intramuscular edema in the right vastus lateralis, vastus medialis, and biceps femoris, as well as the left gluteus maximus, vastus lateralis which were compatible with myositis. Also, discrete areas of myonecrosis in the right vastus intermedialis (1.7 x 1.1 x 3.6 cm), left vastus lateralis (1.7 x 0.8 x 6 cm) and left gluteus maximus (2.8 x 3 cm x 6 cm). Given her previous history of uncontrolled diabetes, the clinical presentation with low CPK levels, lack of data to support another diagnosis, and MRI findings the possibility of diabetes myonecrosis was raised. The patient was managed with conservative therapy: intravenous fluids, pain control and aspirin with improvement in myalgias and muscle strength. Diabetic myonecrosis is a rare condition that appears to be related to vasculopathic changes on uncontrolled diabetics. The lack of specific diagnostic tools and the nonspecific symptoms could make this condition to be overlooked easily; leading to unnecessary studies like muscle biopsy with consequences from complications and increased health care expenditure. A high index of suspicion is essential for timely treatment, which is limited to rest, optimal glycemic control, pain control and patients who are candidates low-dose aspirin. This condition resolves spontaneously over a few weeks to months in most patients and acknowledging this condition could provide timely relief and reassurance.
SAT-098 The Impact of 17-OHP Cutoffs Determination in a Public Newborn Screening Program for Congenital Adrenal Hyperplasia in Southern Brazil: A Three Years’ Experience
Authors: Kopacek Cristiane , Wiest Paloma , de Castro Simone Martins , Spritzer Poli Mara
Published: May 2020

Congenital adrenal hyperplasia (CAH), an autosomal recessive disease, is characterized by impairment of metabolic cortisol synthesis, with or without insufficient aldosterone production. It is caused by mutations in the CYP21A2 gene in approximately 90% of all cases, leading to 21-hydroxylase deficiency and androgen precursors elevation. The main disease marker is 17-hydroxyprogesterone (17-OHP). Early diagnosis through neonatal screening (NS) allows proper treatment and reduces mortality. In Brazil, the average incidence of the classic form of CAH ranges from 1: 7,500 to 1: 18,000 live births.

Objective: To determine the 17-OHP cutoffs ​​for newborn screening to diagnose Congenital Adrenal Hyperplasia (CAH) in a Public Neonatal Screening Program in Southern Brazil.

Materials and Methods: A retrospective, descriptive, cross-sectional study was carried out for analysis of dried blood test results on the 17-OHP paper filter of 317,745 newborns screened by a public neonatal screening center from May 2014 to April 2017. CAH-C was defined as NB with elevation of 17-OHP confirmed by retest and/or clinical evaluation, followed by genotype study. False positive cases (FP) were characterized by absence of genital alterations and/or loss of salt, with normalization of 17-OHP levels on retest. For the determination of the cutoffs ​​according to the four weight groups (WG) (WG1 ≤1,500 g, WG2 1,501 to 2,000 g, WG3 2,001 to 2,500 g and WG4 ≥ 2,501 g), the percentiles 97.5, 98.5, 99.5 and 99.8 were calculated. Sensitivity, specificity, positive predictive values ​​(PPV), negative predictive values ​​(NPV) were performed for the four WG.

Results: Based on the descriptive analysis of the data, the incidence of CAH for the state of Rio Grande do Sul was 1:15,887 live births, with 20 cases of classic CAH being diagnosed during this period, and 17-OHP values ​​ranged from 32.50 ng/mL to 733.00 ng/mL in WG 2,000 g to 2,500 g and WG ≥ 2,501 g. No confirmed cases of CAH were detected for WG ≤ 1,500 g and 1,501 g at 2,000 g until the time of analysis of this study. Most (80.73%) newborns were caucasian and prematurity rate was 9.8% of the study population. The median and average (days) of first sample collection was 5 and 5.83, while for retest was 21 and 25.97 respectively. The cutoffs change from the 99th percentile to the 98.5 for the weight group between 2,001 g and 2,500 g and to the 99.8 for the other weight groups, decreasing false positive results and increasing specificity compared to current reference values ​​to identify classic CAH cases.

Conclusion: The new 17-OHP cutoffs ​​specified were, for all weight groups, higher than currently used by this screening program. The calculation of reference values ​​from local population data and the combination of percentages prove to be an important tool for proper diagnosis of CAH cases and reduction of the number of FP newborns.
MON-255 Oral Contraceptive Pills Mask an Aggressive Crooke’s Cell Pituitary Adenoma
Authors: Gnanapragasam Helen Prathiba , Idupuganti Amrutha , Karunakaran Abhijana
Published: May 2020

Background

Crooke’s cell tumors are rare and aggressive forms of pituitary adenomas. This variant of Cushing’s disease requires prompt diagnosis to avoid life-threatening complications. We report a unique case of Crooke’s cell tumor with longstanding history of irregular menstrual cycles, undiagnosed and later presented as acute unilateral ptosis and diplopia due to aggressive tumor invasion.

Clinical Case

23-year-old female presented to the ER with facial swelling, left eye droop and diplopia for 3 days. She had a past medical history of oligomenorrhea and hirsutism which was normalized by oral contraceptive pills (OCP)- a combination of ethinyl estradiol and drospirenone for the last 3 years. Years prior, workup of her oligomenorrhea showed normal androgenic profile with normal DHEA-S, testosterone and 17-OH progesterone. Current exam was also significant for elevated blood pressure 200/110mmHg, BMI 37, pigmented abdominal striae and terminal hair over her chin. Labs remarkable for hypokalemia K+ 2.7 mmol/L (3.5-5.3), elevated AM cortisol 51 mcg/dL (4-20), low TSH 0.152 mcUnit/mL (0.4-5.0), low IGF-1 170 ng/mL (222-566) and FSH 1.4 mUnit/mL (1.0-9.0), with normal prolactin 24.3 ng/mL (<0.5-25) and free T4 0.87ng/dL (0.8-1.8). MRI brain showed 2.8cm homogenous enhancing soft tissue mass involving the central skull base, sphenoid sinus, sella, suprasellar cistern, and parasellar regions; displacing the optic chiasm, and invading the cavernous sinuses bilaterally and orbital apices. Post trans-sphenoidal surgery (TSS) of the pituitary mass, her left eye ptosis and diplopia resolved. Post-op MRI showed subtotal resection of the extra-axial enhancing abnormality at the central skull base with extension to multiple other anatomic spaces. Pathology read consistent with aggressive Crooke’s cell adenoma, showing invasive biologic behavior without an elevated proliferation index with positive ACTH immunohistochemistry supportive of corticotroph cell adenoma. Post-op ACTH level 73 pg/mL (6-50) and cortisol 12.5 mcg/dL (4-20), while on dexamethasone. Repeat TSS was performed for residual adenoma. Cortisol remains elevated at 15.7mcg/dL despite high dose dexamethasone taper by the neurosurgery team for post-op development of right eye ptosis. She is currently awaiting proton beam radiation therapy.

Conclusion

Crooke’s cell tumors are an aggressive form of pituitary adenoma for which early diagnosis is crucial for its prognosis. Our case highlights the importance of maintaining a wide differential in evaluating young women with menstrual irregularities and to include screening for Cushing’s syndrome. Empiric treatment with OCPs can mask symptoms in the earlier course of Cushing’s disease as in our patient, causing recognition only after presentation with significant tumor growth. Earlier detection could have prevented adenoma invasion and potential neurological sequelae.
SAT-485 Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case Series
Authors: Atalay Hande , Mon Sann Y
Published: May 2020

Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case Series

Introduction:

Thyroid dysfunction is reported in 5 - 9.5 % of patients treated with Pembrolizumab, one of the PD-1 immune checkpoint inhibitors. However, the underlying mechanism of Pembrolizumab-induced thyroid disorders remains unclear.

We present 3 clinical cases with Pembrolizumab-induced painless thyroiditis. They initially presented with thyrotoxicosis, but later converted to hypothyroidism. The onset of thyrotoxicosis after the treatment and time course of changing in thyroid function were varied among these cases. All three cases had normal thyroid function prior to the treatment.

Case 1: 63-year-old M with bladder cancer, NSCLC and multiple brain metastases developed overt thyrotoxicosis with TSH 0.02 (0.34 - 4.82 mIU/mL) and Free T4 2.2 (0.8 - 1.5 ng/dL) at 108 days after the first cycle of Pembrolizumab. He had high TgAb (856) and TPO antibodies (196). In 14 days, he converted to hypothyroidism confirmed by TSH 14.6 and Free T4 0.8. Patient was started on Levothyroxine.

Case 2: 69-year-old M with Stage IV NSCLC presented with thyrotoxicosis (TSH 0.01, Free T4 1.9) at days 41 after starting Pembrolizumab. TPO antibodies and TgAb were negative. During 51 days of follow up, he converted to hypothyroidism (TSH 8.89 and continued to trend up above 60). He eventually required levothyroxine therapy.

Case 3: 57-year-old M with invasive verrucous squamous cell carcinoma of the perineum, urethra and prostate had normal TSH at baseline. Within 39 days after the first dose of pembrolizumab, TSH dropped to 0.013 and Total T4 increased to 14.8 (4.5 - 12.1 ug/dL), consistent with overt hyperthyroidism. In 108 days, patient developed hypothyroidism with Free T4 0.7.

Discussion:

All 3 cases we present did not have overt signs or symptoms of hyperthyroidism. Thyrotoxicosis spontaneously resolved without requiring steroid treatment. Studies suggest symptomatic treatment of beta blockers in cases of tachycardia, otherwise steroid use is not routinely recommended in PD1-induced thyroiditis.

One cohort study analyzed the dynamic course of thyroid functions in patients receiving Pembrolizumab. Among the patients who developed thyrotoxicosis while on PD-1 inhibitor therapy, median onset time was 47 days (14–447 days). The median time for transition from thyrotoxicosis to hypothyroidism was 42 days (21–169 days).

Conclusion:

Our case series highlight the variations in the time course and nature of the Pembrolizumab-induced thyroiditis. Clinicians should be aware of the relatively short period of fluctuations of thyroid functions in patients treated with PD-1 inhibitors.

References: Lee, Hyunju et al. “Characterization of Thyroid Disorders in Patients Receiving Immune Checkpoint Inhibition Therapy.” Cancer Immunology Research 5, no. 12 (2017): 1133–40. https://doi.org/10.1158/2326–6066.cir-17–0208.
SUN-267 Dissecting Type 2 CRH Receptor Signaling Characteristics in the Hypothalamic Cell Line MHYPOA-2/30
Authors: Alcantara-Alonso Viridiana , Gortari Patricia de , Dallmann Robert , Grammatopoulos Dimitris
Published: May 2020

The stress peptides coticotropin-releasing hormone (CRH) and urocortins (Ucns) exert anorectic effects acting mainly through the type 2 CRH receptor (CRH-R2) in the hypothalamus. Impairment of CRH-R2 signaling in chronically stressed rats has been linked with the development of hyperphagia (Alcantara-Alonso et al. Neuropeptides, 2017) however the exact mechanisms and molecular defects are unknown. In the present study we used the mHypoA-2/30, a hypothalamic immortalized cell line derived from adult mice (Belsham et al. FASEB J, 2009) to further explore the signaling molecules mediating the anorexigenic effect of the CRH-R2 cognate agonist urocortin 2 (Ucn2). Specifically, we investigated mRNA, protein expression and cellular localization of CRH-R2 in the mHypoA-2/30 neurons. Additionally, we examined the effects of Ucn2 on the phosphorylation of CREB and AMPK, as well as its transcriptional effects on genes of feeding-related peptides and molecules involved in modulation of circadian rhythms. Both CRH-R2 mRNA and protein expression were detected in mHypoA-2/30; indirect immunoflourescence experiments using a specific CRH-R2 antibody demonstrated widespread localization in the plasma membrane and cytoplasm. Moreover, the receptor sub-cellular localization was redistributed in response to activation by Ucn2 (100 nM), as the plasma membrane immunofluorescent signal was decreased after 4h of agonist treatment, suggesting CRH-R2 homologous internalization. We also observed a 50% increase in the phosphorylation of CREB associated with a concomitant decrease in AMPK phosphorylation after 30 min of Ucn2 treatment. Among the panel of hypothalamic genes analyzed, we identified after 24h of Ucn2 treatment increases in the gene expression of the anorexigenic peptides neurotensin and proopiomelanocortin. Interestingly, sustained CRH-R2 activation also led to an increase in the mRNA levels of Aryl Hydrocarbon Receptor Nuclear Translocator Like (ARNTL), a protein involved in the control of circadian rhythm. A luciferase reporter gene analysis of ARNTL showed that the mHypoA-2/30 cells also exhibit circadian patterns of expression and that the treatment with Ucn2 enhanced circadian amplitude of ARNTL reporter on these cells, which in turn may be involved in glucocorticoid release in circadian cycles and stimulating appetite during the activity phase of the animals. In conclusion, we found that the mHypoA-2/30 cell line expresses endogenous functional CRH-R2 that is linked to downstream regulation of anorexigenic gene expression. This cell line appears to be a useful in vitro tool to study hypothalamic CRH-R2 signaling machinery involved in central control of food intake and circadian cycles.
SUN-395 Pelvic Bone Density Is Lower Than Bone Density of Hip and Femoral Neck in Postmenopausal Women
Authors: Mohseni Mahshid , Civitelli Roberto , Stum Shannon , Toennies Bridgett , Eisen Seth
Published: May 2020

Pelvic fractures represent 7% of all fragility fractures; they account for 5% of the cost of osteoporotic fracture care, and are commonly (> 50%) associated with loss of independence in the elderly. The incidence of pelvic fractures has increased significantly over the past 3 decades. However, little is known about the relationship between bone mineral density (BMD) and pelvic fractures. We have conducted a pilot cross-sectional study to establish a method of measuring pelvic BMD and to correlate BMD of the pelvis with BMD at other skeletal sites. Postmenopausal women without a history of pelvis and hip fragility fractures were enrolled. Hip, spine, and pelvis DXA scans were obtained using a Hologic DXA machine. Pelvic BMD was calculated using Hologic Research Software from 3 areas of the pelvis (R1: public symphysis, R2: inferior pubic ramus, and R3: superior pubic ramus), corresponding to common fracture locations. Pelvis BMD was the average of the 3 pelvis sites. Pelvic BMD measurement precision error was calculated using the root mean square method (Recommended by International Society of Clinical Densitometry (ISCD)). Statistical analysis was used to compare BMD at different sites. Alpha error was set at 0.05. Of 73 postmenopausal women who were enrolled in the study (average age 64 years, average 15 years postmenopausal), 3% had chronic kidney disease, 7% had type 2 DM, 3% were on corticosteroids and none were smokers. BMD of femoral neck assessed on pelvic DXA was not significantly different from femoral neck BMD measured on standard DXA (P=0.09). To assess pelvis BMD measurement precision, 15 patients underwent 3 separate pelvic DXA images after repositioning. BMD precision error was 0.011g/cm2 which is slightly lower than the precision total hip BMD at our center (0.007 g/cm2). BMD of R1, R2, and R3 pelvic areas were measured as 0.44±0.15, 0.41± 0.15, and 0.62 ±0.19 g/cm2, respectively. Notably, BMD of R3 was significantly higher than the other 2 areas (P<0.001, ANOVA). Average BMD (0.49±0.14 g/cm2) of pelvis was significantly lower than BMD of femoral neck (0.72± 0.16 g/cm2), total hip (0.86±17 g/cm2) and spine (0.97± 19 g/cm2)(P <0.001). Average BMD of pelvis was significantly lower in participants with osteopenia and osteoporosis of the hip and femoral neck compared to participants with normal BMD in those locations. In summary, we report a precise method of measuring BMD of commonly fractured areas of the pelvis. Pelvis BMD is lower than hip, femoral neck, and spine. Bone density of the pelvis correlates with hip and femoral neck bone density. The results of this pilot study can be used for future studies looking at pelvic low bone density in patients with pelvic fragility fractures which could help identify patients at risk for pelvic fragility fractures and change how osteoporosis is defined based on DXA images.
SUN-114 Successful Long-Term Medical Management of Insulinomas
Authors: Spiro Andrew , Hoang Thanh Duc , Shakir Mohamed K M
Published: May 2020

Background: Insulinomas are usually benign, solitary tumors. Surgical resection is the treatment of choice and only method of cure. Surgical cure is not possible with unresectable metastatic disease, unlocalizable disease, or contraindications to surgery. Long-term medical management may be required. Clinical Cases: Patient 1: A 57-year-old female was diagnosed at age 42 when imaging confirmed a 2.4cm insulinoma in the pancreatic tail and two lesions in the right hepatic lobe. She underwent distal pancreatectomy with splenectomy, and hepatic wedge resection. Follow-up imaging showed two new hepatic lesions. She underwent chemoembolization with resolution of her symptoms. By age 48, her symptoms returned. Imaging showed new lesions in the liver, not amenable to embolization. She was placed on Octreotide 20mg IM monthly and her symptoms resolved soon after initiation of therapy. She has since had an unremarkable clinical course. Additional therapies have been deferred as follow-up imaging has not shown disease progression. Patient 2: A 48-year-old female was diagnosed at age 37. CT and MRI did not find a source. A DOPA-PET showed increased uptake in head and tail of the pancreas. An 8-hour ex-laparotomy with EUS and palpation of the pancreas did not localize a mass. A second surgery, with 75% removal of the distal pancreas, including the tail and body, did not relieve her symptoms. She had unsuccessful trials of verapamil, verapamil with low-dose diazoxide, and octreotide. She started diazoxide 300mg daily, but had fluid retention and tachycardia. Her dose was decreased to 200mg daily and HCTZ 25mg daily was started. Due to persistent symptoms, prednisone was started at 5mg in the morning and 2.5mg in the afternoon, which gave symptom relief. At her request it was decreased to 5mg daily. By age 42 she had self-decreased it to 2.5 mg daily, but continued her other meds. She endorsed the return of symptoms, but felt she could manage them without increasing her dose. At age 44, as part of a clinical trial, an MRI and nuclear medicine study showed a 9mm lesion in the head of the pancreas. Another exploratory surgery did not find a lesion. Currently, she is on the same medication regiment with strict diet and frequent meals. She endorses only rare hypoglycemic episodes. Conclusion: The patients have been managed with medical therapy for 15 and 11 years respectively. Long-term survival data of patients with metastatic insulinoma indicates that prolonged survival is unlikely; however, most data is from the 1990s or earlier. It does not incorporate new medical treatments, or advancements in technology and the field of medicine. Patients who are not candidates for surgical cure, may have better survival rates and undergo longer courses of medical management. Additionally, while oral prednisone is not standard therapy for insulinoma, there are cases of its use to control hypoglycemia when other treatments are exhausted.
SAT-297 Pituitary Hormonal Levels and Gonadal Histology in the Pubertal Period of the Ames Mice
Authors: Silva Juliana M , Viscardi Bruna A , Mendonca Berenice Bilharinho , Carvalho Luciani Renata Silveira
Published: May 2020

Introduction: The pituitary gland controls several mechanisms as metabolism, growth, and reproduction, in response to hypothalamic stimuli. The adequate temporal/ spatial expression of transcription factors is mandatory for a normal pituitary development. PROP1 transcription factor is widely known as a key pituitary regulator. The Ames mice is a model of congenital hypopituitarism due to a pathogenic variant in the Prop1 gene, leading to growth retardation, infertility, and hypothyroidism. Aim: To characterize the peripheral levels of pituitary hormones and correlate with gonadal histology during the pubertal period of the Ames mice. Methods: Weight and naso-anal length were measured. Peripheral blood samples were collected from 5 wild type (WT) and 5 Prop1 mutants (Mut) animals with 30 (P30), 40, (P40), and 60 (P60) days after birth. Pituitary hormone levels were measured using the kit Milliplex Map® - Mouse Pituitary Bead Panel (Merck Millipore, Massachusetts, USA). Ovaries and testis from 3 WT and 3 Mut animals from each sex were collected and fixed in 4% paraformaldehyde and embedded in paraffin. Gonadal sections of 3 μm were obtained and the slices were stained with hematoxylin and eosin. Follicles were counted and classified according to the size and cellular composition as small follicle (17μm to 28μm), developing follicle (100μm), and antral follicle (>550μm). Testis were classified using the Johnsen score, ranging from 1 to 10 according to cellular composition and spermatogenesis state. Results: All mutant mice presented decreased weight and naso-anal length at the three analyzed periods. At P30, the female mutants presented GH, LH, and TSH levels similar to wild type and decreased FSH and PRL levels, as well as the males that only differed from GH reduced levels. At P40, females and males presented GH, LH, FSH, and TSH levels similar to wild type with reduced PRL levels. At P60, it was observed decreased GH, FSH, and PRL levels for both sexes and TSH levels with no difference from WT, LH secretion was decreased in mutant females and normal in males compared to WT. There was no significant difference in follicular number and classification between mutants and wild type in all analyzed periods, despite the observation of ovarian hypoplasia in the mutants. Johnsen score was in the average of 7.5 in mutant males and 8.8 in WT, with no significant difference between periods. Conclusion: Despite the absence of PROP1 and the hypopituitary phenotype, mutant females and males were able to secrete some pituitary hormones, mainly during puberty, a pituitary high demand period. Although the ovaries and testis from mutant mice are hypoplastic, cellular morphology and classification are similar to WT.
SUN-367 Changes in Bone and Glucose Metabolism in Patients Post Solid Organ Transplant
Authors: Lo Keswick , Tarar Omer H , Yaturu Subhashini
Published: May 2020

Introduction:

Solid organ transplantation has emerged as a pivotal therapeutic option for various organ failures and has gained more popularity with newer technologies and better immunosuppressive options.

However, immunosuppressive therapies for survival of solid organ transplant is also associated with various metabolic complications with changes in bone and glucose metabolism.

The aim of our study is to review the changes in bone and glucose metabolism in post solid organ transplant recipient Veterans.

Methods:

Single center, retrospective study with subjects who had solid organ transplant conducted at William Jennings Bryan Dorn Veteran Hospital in Columbia, South Carolina. All available subjects who had solid organ transplant between January 1, 2008 till December 31st, 2017 and had at least one post-transplant followed up visit were included. Data was collected from computerized patient record system after approval by Institutional Review board (IRB) and Research and development. Collected data included age, sex, BMI, Laboratory data, Medications, Bone mineral density (BMD) by DXA, Diabetes status and medications pre and post operatively.

Results:

Data collected include 227 patients with solid organ transplants. Out of those, only 88 had BMD evaluation and only 45 had follow up BMD. Out of 88 with baseline BMD, 16 had osteoporosis, 36 had osteopenia and 36 had normal BMD. Although 51 were on Bisphosphonates, many of them did not have follow up DXA scans. 157 were receiving Vitamin D supplementation but very few had levels checked.

A total of 158 patients had Diabetes, with 95 having pre-existing diabetes and 52 were diagnosed post transplantation. The time of onset was unknown in 11 patients. Majority of patients with pre-existing diabetes required intensification of their medications for diabetes to achieve optimal glycemic control.

Discussion

A multitude of factors including type of transplant, individual pre-operative metabolic profiles, choice of immunosuppressive agents and certain infections increase the risk of these metabolic complications. Given the complex post-operative care, issues with immunosuppressive agents and other comorbidities, metabolic bone disease and other complications may go unnoticed and under recognized which may later lead to higher risk of fractures, morbidity and mortality.

Conclusion

This study highlights the importance of monitoring prudently for metabolic changes after solid organ transplantation. Early identification and aggressive management of these complications may help decrease morbidity and mortality related to fractures and sub-optimal glycemic control.
SUN-005 Hirsutism Due to Bilateral Leydig Cell Tumors
Authors: Shakir Mohamed K M , Sherin Rinsha P V , Weaver Travis , LaChance David , Hoang Thanh Duc
Published: May 2020

Severe hyperandrogenism in post-menopausal women is rare. It may be caused by either benign or malignant neoplasms of the adrenal or ovary. We report a rare case of a post-menopausal woman with hirsutism associated with virilization due to Leydig cell tumors (LCT) of both ovaries. Case report 61 yo female presented for evaluation of hirsutism. She had also been experiencing increased facial hair growth, deepening of voice, clitoromegaly, alopecia, and acne. Physical examination: normal vital signs. Patient had signs of virilization, including coarse hair along her upper lip, chin, lower abdomen and inner thigh with Ferriman-Gallwey score of 8, acne, and clitoromegaly. She had no signs of acanthosis nigricans or Cushing syndrome. Base line labs: Hemoglobin 16.2 gm/dL (ref 12.0 to 15.5), total testosterone 803 ng/dL (ref 3–41), free testosterone 20.2 pg/mL (ref 0.0–4.2), estradiol 77 pg/mL (<6.0−54.7), estrone 148 pg/mL (ref 7–40), FSH 11.5 mIU/mL (ref 25.8 - 134.8), LH 6.90 mIU/mL (ref 7.7 - 58.5), androstenedione 28 ng/dL (ref 17–99), DHEAS 99.9 mcg/dL (ref 19–205), dehydroepiandrosterone 512 ng/dL (ref 31–701), inhibin A 2.3 pg/mL (ref <5), inhibin B <7.0 pg/mL (ref 00-16.9), 17-alpha hydroxyprogesterone 187 ng/dl (ref <51). Her other serum markers such as anti -Mullerian hormone, alpha-fetoprotein, and hCG were normal. A CT scan of adrenals: normal. Similarly a transvaginal US did not show any ovarian pathology, however MRI of the pelvis showed homogeneous ovarian enhancement bilaterally and based on this information a diagnosis of ovarian hyperthecosis was considered and patient underwent laparoscopic bilateral oophorectomy. Pathology confirmed: LCT in both ovaries. Laboratory values performed 3 months later showed the following values: hemoglobin 14.2 gm/dL, total testosterone 13 ng/dL, free testosterone 1.4 pg/mL, LH 124 mIU/mL, FSH 99mIU/mL, estradiol <5.0 pg/mL. In 6 months she had significant improvement in hirsutism and virilization. Discussion Hyperandrogenism, especially serum testosterone in the male range with rapidly progressive hirsutism or virilization signs in a female indicates tumor etiology. Androgen-secreting ovarian tumors are usually small and often embedded in the ovary. Transvaginal US is useful in the diagnosis of ovarian tumors. However, in our case, transvaginal US failed while MRI scan showed bilaterally enlarged ovaries and with this information patient underwent bilateral oophorectomy. Although 5 cases of bilateral LCT are reported in the literature, LCT is unilateral 95% of the time, the pathogenesis of Leydig cell proliferation and LCT is unclear. In conclusion, androgen secreting tumors should be considered in women (especially in post-menopausal state) with hyperandrogenism and hirsutism. In fact, diffuse stromal Leydig cell hyperplasia and small Leydig cell tumors may be missed on imaging and in some cases only pathology can confirm the result.
SUN-310 Growth Hormone Deficiency and Replacement Therapy: Association with Health-Related Physical Fitness
Authors: Carvalho-Furtado Adriana Claudia Lopes , Ramari Cintia , Soares Edgard , Saint-Martin Daniel R F , Porto Luiz Guilhemme Grossi , Nogueira Montenegro Maria Luiza Ricardo , Ferro André Metzker , Rodrigues Marcelo Palmeira , Naves Luciana Ansaneli
Published: May 2020

Objective: To compare health-related physical fitness (HRPF) in patients with severe adult growth hormone deficiency (AGHD) according to the deficiency onset phase, and to evaluate the effects of a six-months human growth hormone (rhGH) replacement therapy on HRPF, in a subgroup of patients. Methods: First arm: cross-sectional observational study at baseline of naive rhGH multiple pituitary hormonal deficiency (MPHD) hypopituitarism patients - adult-onset growth hormone deficiency (AO-GHD) versus child onset growth hormone deficiency (CO-GHD). Second arm: a 6-month intervention clinical trial in a selected group of a non-randomized, non-controlled cohort. HRPF was evaluated by measuring isokinetic and isometric torque stensor strength at the knee using an isokinetic dynamometer, handgrip strength and six-minute walk test. Body composition was assessed by DXA. Results: Patients who presented AO-GHD had higher BMI than CO-GHD (28.1±3.5 x 22.4±4.8; p=0.017), but body composition (lean body mass%:57.9±7.9 x 58.9±8.6;p=0.816/fatty body mass%:39.3±6.8 x 36.0±9.1;p=0.434), stensor peak torque/body weight at 60, 90 and 180deg/s (2.18±0.6 x 2.18±0.6; p=0.580/1.99±0.5 x 2.14±0.5;p=0.546/1.52±0.4 x 1.64±0.4;p=0.547), isometric torque/body weight at the knee (2.62±0.7 x 2.91±0.6;p=0.357) and six-minute walk test (570.2±76.0cm x 554.1±91.0cm;p= 0.703) did not differ between groups. Handgrip strength test also showed significant reduction in scores for age and gender in both groups of GHD patients. After six months of rhGH, no improvement in muscular strength tests was found. There was a significant worsening in the six-minute walk test (575.1±84cm x 545.4±90.6cm; p=0.033) despite the improvement in body composition (lean body mass%:59.7±8.6 x 63.6±11.1;p=0.005/fatty body mass%:35.7±9.2 x 32.9±10.0;p=0.003). Conclusion: Despite differences in BMI, there were no other differences in HRPF between AO-GHD and CO-GHD patients. The decrease of the six-minute walking test performance after rhGH replacement therapy supports the clinical evidence that the GH regulates bioenergetics in human skeletal muscle fibers. Although the treatment had a short period, GH might have stimulated the anaerobic and suppressed the aerobic energy system.
SAT-457 The Association Between Thyroid Stimulating Hormone and Severe Depression: A Historical Cohort Study
Authors: Sundaresh Vishnu , Newman Mike , Bakian Amanda V , Abraham Devaprabu , Singh Balwinder
Published: May 2020

Introduction: Hypothyroidism is implicated in the pathophysiology and clinical course of mood disorders. This study aimed to investigate the association between TSH and severe depression.

Methods: The historical cohort included all consecutive adult patients (≥ 18 years) who had a TSH and PHQ-9 questionnaire data within 6 months of index visit, between October 2016 and July 2019, at the University of Utah Health. Data on demographics, hypothyroidism, TSH, PHQ-9, thyroid hormone replacement (THR), and antidepressant medications were extracted electronically. T-test and chi-square were used to compare continuous and categorical variables respectively. Logistic regression and one-way ANOVA were used to evaluate the association between TSH and depression severity. A sub-group analysis was performed among mood disorder patients without a diagnosis of overt hypothyroidism, comparing euthyroid patients (TSH 0.3-4) and patients with sub-clinical hypothyroidism based on TSH 4-10.

Results: The cohort included 26,722 patients, mean age 46.3 years, 79.5% Caucasian, 68% females, and mean BMI 30. Mean PHQ-9 score was 8.2, 10% patients had severe depression (PHQ-9 ≥20), and 51% were on antidepressants and 26% on mood stabilizers. Mean TSH was 2.85, 19% patients had a diagnosis of hypothyroidism, and 20% patients were on THR. Patients with severe depression were more likely to have a higher mean TSH (p=0.06), be on antidepressants (p= <0.0001), and have a higher BMI (p=0.0003). There was a positive correlation between TSH and PHQ-9 score (p= 0.04). TSH was associated with severe depression, odds ratio 1.006 (1.003-1.009), after adjusting for potential co-variates. Hypothyroid patients who were on THR had a lower mean PHQ-9 score (p= <0.0001) as compared to hypothyroid patients not on THR. Patients with TSH from 7-10 had a higher PHQ-9 score as compared to those who had a TSH from 4-7 (p= <0.003).

Conclusion: Severe depression was associated with higher TSH. Subclinical hypothyroidism with TSH above 50th percentile was associated with higher PHQ-9 scores. Future RCTs should evaluate the effect of THR in (a) patients with severe depression and (b) patients with mood disorders who have subclinical hypothyroidism.
SUN-414 Tyrosine Kinase Inhibitors Induced Thyroid Dysfunction: An Experience from a Tertiary Care Hospital
Authors: Wangnoo Subhash Kumar , Siddiqui Mohammad Asim , Pamnani Harsha , Usman Khwaja Mohammed
Published: May 2020

Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multi-targeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. TKI-induced thyroid dysfunction is recognized as a common adverse effect of treatment., but the onset of thyroid dysfunction is variable. This study analysed correlation between initiation of TKIs and the onset of thyroid dysfunction in non-thyroid cancers patients without any background thyroid dysfunction.

METHODS:

This was a retrospective cohort study to evaluate thyroid dysfunction in adult patients (n=227, M:F=153:74) with non-thyroidal cancers treated with TKIs. Patients having pre-existing thyroid disease including euthyroid goitres were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid function tests (TFTs) were done prior to initiation, at 2 months, 6 months and at 1 year. TFTs were classified as euthyroid (thyrotropin [TSH] normal), subclinical (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement).

RESULTS:

Of the 227 patients in the study, OH occurred in 57 patients (25.1%)(M:F = 19:38) and SCH occurred in 89 patients (39.2%) (M:F=39:50) with TKI therapy at the end of 12 months. 37 patients (M:F=13:24) developed OH in first 6 months after initiation of TKIs. Female patients were more likely to have OH in the first 6-month period following TKIs irrespective of type of TKI or the cancers. SCH was also more common after 2 months in female patients (n=23) (M:F=6:17) but the conversion of SCH to OH was more common in male patients at the end of 12 months. The symptoms were variable and most the patients did have any thyroid specific symptoms. After adjustment for age, sex, cancer type, cancer stage, performance status, and type of TKI, OH remained significantly associated with survival at 1-year (hazard ratio=0.461; p<0.0001), whereas SCH did not (hazard ratio=0.591; p=0.165). Analysis of hypothyroid patients (SCH and OH) with TSH >5 and <10 mIU/L stratified by hormone replacement status showed improved survival associated with hormone replacement, although 1 year follow-up is too short to comment on overall survival rates.

CONCLUSIONS:

New onset hypothyroidism, both OH and SCH is common in non-thyroidal cancer patients treated with TKI. SCH is more common after 2 months and OH after 6 months following TKI initiation. Female sex is more predisposed to develop thyroid dysfunction irrespective of underlying cancer or type of TKI used but male patients progressed to OH at the end of 12 months.
SAT-158 New Data on High Prevalence and Time of Occurrence of New Onset Hypothyroidism Associated with Mitotane Therapy in a Cohort of Adrenocortical Cancer
Authors: Poirier Jonathan , Lacroix André , Olney Harold J , Bourdeau Isabelle
Published: May 2020

Context. Mitotane is a steroidogenesis inhibitor and an adrenocorticolytic drug used to treat adrenocortical cancer (ACC). Central hypothyroidism is recognized in mitotane-treated patients and recent data suggested that mitotane could have an inhibitory effect on TSH-secreting cells in the pituitary gland. Moreover, mitotane may lead to induction of thyroid hormone metabolism. Clinical data on hypothyroidism related to mitotane such as prevalence and time of occurrence was described in a limited number of patients.

Objective. To better characterize clinically secondary hypothyroidism in patients with ACC treated with mitotane therapy.

Methods. We reviewed retrospectively paper charts and electronic records from patients with histologically confirmed diagnosis of ACC evaluated at our center from 1995-2019. We analysed the pattern of TSH and thyroid function, but also mitotane timing and levels at baseline and during treatment of patients under mitotane therapy. Thyroid hormone assessment including TSH, FT4 and FT3 was performed at least every 3 months during follow-up.

Results. Our cohort of 104 patients with ACC includes 84 patients that received mitotane therapy. Among them, thyroid function data was incomplete for 39 cases. Complete data was retrieved from 45 patients. Ten out of 45 (22.2%) patients were already known for primary hypothyroidism and were receiving L-T4 replacement before the initiation of mitotane. Two of 45 (4.4%) patients maintained a normal thyroid function during complete follow up (4.5 years) and 33/45 (73.3%) had new onset hypothyroidism requiring levothyroxine treatment. Of these 33 patients, 22 were females and 11 were males, ranging from 22-74 yo with a median of 46 yo. The number of patients with ENSAT stage I, II, III and IV of disease were 1, 8, 11 and 13 respectively. Thyroid profiles were compatible with central hypothyroidism (low T4 with low or inappropriately normal TSH) in 22/33 patients (66.7%). Interestingly, 6/33 patients (18.2%) developed a TSH elevation with a normal lower-limit or low T4 level. The timeline distribution of the occurrence of hypothyroidism was 21.2% (n:7) at <3 months, 15.2% (n:5) between 3-6 months, 21.2% (n:7) between 6-9 months and 15.2% (n:5) between 9-12 months. 9.1% (n:3) occurred within the second year of treatment (between 12-24 months). However, in 5/33 (15.2%) cases, the exact time of new hypothyroidism onset was undetermined.

Conclusion. Mitotane therapy is frequently associated with new onset hypothyroidism with a prevalence of 73% in our cohort of exposed patients and is most likely of central etiology. 72.7% of cases occur in the first year of treatment while 9.1% occur in the second year. This study supports the importance of monitoring thyroid function (including a free T4 level) during the complete course of mitotane therapy.
SUN-692 Comprehensive and Structured Care Program for Patients with Type 2 Diabetes Mellitus: A Preliminary Report from Raipur, Chhattisgarh State of India
Authors: Dash Kalpana , Tippisetty Surekha , Rao Samba Siva , Kolukula Vamsi Krishna
Published: May 2020

Aim: To assess the glycemic outcomes of T2DM patients enrolled in comprehensive structured care program at the outpatient clinic of Apollo Sugar at Raipur, India. Methods: This is a preliminary, prospective, single-center, observational study on T2DM patients from Jan 2018 to December 2018. Uncontrolled diabetes or patients with comorbid conditions with the duration of disease for more than one year and age ≥18 years and who gave consent to enroll in the program were included in the study. The structured care program is a 6 months program where patients were continuously engaged by counseling them on diabetes management- diet and exercise, self-monitoring of blood glucose, health interactions with the remote health coach through a mobile app. Baseline demographics and clinical data were collected at the time of enrollment and were followed up for 6 months. HbA1c reduction is the target measurement of this program. Descriptive statistics were used to analyze and report the data. A paired t-test is used to check the significant reduction in HbA1c from baseline to follow up Results: Total 102 patients were included in this study. Mean (SD) age was 50.7 (10.5) years, males were 78 (76%) and females were 24 (24%). The mean (SD) duration of diabetes and BMI were 7.9 (7.0) years and 27.5 (4.5) kg/m2 respectively. At the time of enrollment, patients were at mean HbA1c of 9.0(2.1)%, fasting (F) and post-prandial (PP) blood (BG) glucose was 194(68) mg/dL and 247(94) mg/dL respectively. Among these patients 38% had neuropathy and 15% had retinopathy as their complications. These patients were regularly followed up over the phone call to counsel on diabetes management with a healthy diet, exercise, self-monitoring of blood glucose, and medication compliance. After 6 months followup the HbA1c, FBG, and PPBG were 7.6 (1.5) %, 139 (50) mg/dL, and 196 (75) mg/dL, respectively with a significant mean reduction of 1.4%, 56 mg/dL, and 51 mg/dL (p <0.001). Further analysis of glycemic outcomes between these patients on oral hypoglycemic agents (OHAs) and OHAs+insulin, the reduction in HbA1c (1.5%) was not significant. Conclusion: Our study demonstrates that a structured care program might bring a clinically significant glycemic control through tight adherence to SMBG, diet, exercise, and medication. To establish these results a study in large sample is in progress.