bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-586 Cold-Acclimation Prevents the Onset of Glucocorticoid-Induced Adipose Dysfunction in Male Mice
Authors: Gado Manuel M , Noll Monique , Heinrich Annett , Rauner Martina , Hofbauer Lorenz C , Henneicke Holger
Published: May 2020

Glucocorticoid (GC) excess, either endogenously or exogenously, has been causally linked to the development of chronic diseases such as obesity and type-2 diabetes mellitus. Continuously elevated GC levels result in an expansion of white adipose tissue (WAT) depots and a dramatic decrease in the thermogenic capacity in brown and beige adipose tissue (BAT and BeAT, respectively). Herein we aimed to examine the interaction between GCs and the sympathetic nervous system (SNS) in the regulation of WAT, BAT, and BeAT. To this end, we utilized an altered environmental temperature as a non-invasive method for the modulation of sympathetic activity - cold is an activator of SNS-mediated non-shivering thermogenesis. Thus, during a 4-week treatment with either corticosterone or placebo, 10-week-old male C57BL/6NRj mice were maintained at two different temperature levels: 29°C (thermoneutrality) or 13°C (cold temperature). Body weight, as well as energy and water intake, were monitored throughout the study. At sacrifice, serum and adipose tissues were collected for analysis. GC-exposed mice showed a marked increase in circulating corticosterone concentrations compared to placebo controls with no appreciable difference between temperature levels. At thermoneutrality, GC-treated mice gained more weight and consumed more food than their placebo-treated littermates. This GC-induced body weight gain was accompanied by increased (visceral & subcutaneous) WAT weight as well as adipocyte hypertrophy. Interestingly, cold-acclimatized mice showed a marked reduction in GC-induced weight gain, hyperphagia, and fat accumulation. Moreover, the GC-induced rise in blood glucose and serum insulin concentrations - readily observed when mice were maintained at thermoneutrality - was absent in cold-exposed animals. In addition, GC treatment at thermoneutrality resulted in increased lipid deposition and decreased UCP1 expression in BAT, the ‘whitening’ of BAT. This GC-induced loss of thermogenic capacity was profoundly reduced in cold-adapted mice. Across all groups, UCP-1 protein levels in BAT closely correlated (r2 = 0.70, p < 0.0001) with those of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. These results indicate that cold-acclimation prevents the development of GC-induced metabolic dysfunction in mice. Thus, environmental temperature is a potent modulator of GC-induced adiposity and body weight gain, potentially via an interaction between SNS and GC signaling.
SAT-268 Thyrotropin Secreting Pituitary Adenoma Initially Misdiagnosed as Primary Hyperthyroidism in a Taiwanese Man
Authors: Lin Yu-Yi , Wang Wei-Hsin , Lai Tzong-Yoe , Hwu Chii-Min
Published: May 2020

Background:TSH (Thyrotropin) secreting pituitary adenoma (TSHoma) account for less than 1% of all causes of hyperthyroidism and 1% of all functioning pituitary tumors. Definite diagnosis and treatment of TSHoma are clinical challenges in practice. Here we report laboratory data, imaging findings, endocrine dynamic test, and treatment outcomes in a 50-year-old Taiwanese man with pituitary plurihormonal adenoma secreting TSH and LH.

Clinical case:The patient was initially diagnosed as goiter with primary hyperthyroidism and DM while medical check-up by primary care physician in 2014. He had no significant hyperthyroidism symptoms and signs except goiter and mild palpitation. He received propylthiouracil and Metformin. Two years later, he visited to Endocrinologist’s clinic for poor glycemic control. Central hyperthyroidism was diagnosed due to measurable TSH level in the presence of increased serum thyroid hormone level. Moreover sella MRI revealed left sided pituitary lesion. He was referred to Taipei Veteran General Hospital for further management. There was no family history of thyroid disease. Physical examination was not remarkable except diffuse grade 3 goiter and tachycardia (HR 100~115 bpm). Follow up laboratory data showed TSH 4.89; range 0.4~4.0 uIU/ml, free T4: 3.05; range 0.9~1.8 ng/dl, T4: 16.02; range 4.50~12.50 μg/dl, T3: 249; range 58~159 ng/dl, free T3: 8.0; range 2.3~4.3 pg/ml. Two times of TRH stimulation test showed blunted TSH response. Normal limit of thyroid autoantibodies level were found. Thyroid sonography revealed heterogenous echogenicity with increased size and vascularity of both lobes. I-131 uptake was homogenous uptake (94%). Other pituitary hormones level were within normal limit except mild elevation of testosterone 12.69 ng/ml. Sella MRI with contrast showed macroadenoma (size 10x10x7.6 mm) at left pituitary gland. Taken together, he was diagnosed as central hyperthyroidism related to left sided pituitary macroadenoma. Surgery was performed after one year of definite diagnosis due to personal reason. TSH level returned to normal ranges (0.799 uIU/ml) in 1st post operative day. Histologically, the pituitary mass was compatible with plurihormonal adenoma and immunohistochemistry showed positivity for TSH (4+) and LH (3+). Post operative condition was well. Antithyroid agent was discontinued after operation. His blood glucose became well controlled after operation.

Clinical lessons:A biochemical hallmark of TSHoma is an escape of TSH from the feedback loop that is detectable TSH levels in the presence of increased serum thyroid hormone level. Diagnosis of TSHoma was frequently unrecognized and thus much delayed despite its relatively straightforward. Physician should keep in mind that the importance interpretation of simple laboratory tests to avoid delay diagnosis and unnecessary treatments.
SUN-064 Diversity of Endocrine Function in Patients with CHARGE Association
Authors: Uehara Erika , Nagata Tomohiro , Terashita Shintaro , Matsumoto Masaaki , Yamaguchi Tomoe , Ota Tomoko , Yoshii Keisuke , Naiki Yasuhiro , Horikawa Reiko
Published: May 2020

Context: CHARGE association consists of congenital malformation of Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies and/or deafness. It is often caused by CHD7 gene mutation, which also one of the causative gene for Kallmann syndrome. The endocrine dysfunction in CHARGE association has been reported but not fully understood. Objective: To clarify the mode of growth and frequency of endocrine dysfunction in CHARGE association. Subjective: We investigated the characteristics of growth and puberty, and endocrine function in 23 children (15 males and 8 females, 0~20 years old) with CHARGE association. Results: The birthweight was from -2.74 to +1.14 SDS and the birth length was from -2.86 to +1.10 SDS. 5 children were born small for gestational age. The height below -2SDS in 18 children. GH secretion was evaluated in 11 children with short stature (-9 to -2.3SD) except for one with normal height (-0.3 SD in 6 years old girl); 5 children including one with normal stature were revealed to have GH deficiency. One short girl with GH deficiency previously showed normal GH response to provocation test at 1 year old but has developed to be GH deficient at 7 years old. Gonadotropin-releasing hormone loading tests were performed in 7 males and 3 females. Nine out of 10 children showed hypogonadotropic hypogonadism; one girl showed hypergonadotropic hypogonadism, whose ovaries were undetectable on ultrasound. Human chorionic gonadotrophin (HCG) tests were performed in 6 males with micropenis and/or cryptorchidism. Peak testosterone levels after HCG stimulation were from 0 to 6.99 ng/ml. 4 patients showed peak testosterone levels less than 1 ng/ml. Four boys showed combined gonadotropin deficiency and primary hypogonadism. Conclusions: Our data showed the diversity of endocrine function in children with CHARGE association. GH deficiency can be developed over time. Hypogonadotropic hypogonadism is common, while isolated/combined primary hypogonadism should be taken into consideration in children with CHARGE association.
OR14-07 Association Between Placental Glucose Uptake and Protein O-Glcnacylation and Birth Outcomes in Obese Non-Diabetic Mothers
Authors: Panetta Pamela , Zammit Victor A , Savvidou Makrina D , Johnson Mark R , Grammatopoulos Dimitris
Published: May 2020

Increased transport of nutrients such as glucose, across the placenta, has been linked to abnormal fetal growth and pregnancy complications in obese non-diabetic mothers (1); however, the underlying mechanisms are poorly understood. We hypothesized that in placenta, the metabolic and nutrient sensor O-GlcNAc transferase (OGT), highly sensitive to glucose flux through the hexosamine biosynthetic pathway (HBP), responds to maternal obesogenic environment by increasing O-GlcNAc post-translational modification of nucleocytoplasmic proteins in the placenta altering fetal growth trajectories. Tissue biopsies were isolated from placentas collected at term from 26 non-diabetic mothers alongside routine biochemistry and anthropometric data (maternal fasting glucose, glycated hemoglobin (HbA1c), early pregnancy body weight (BMI) and birth weight). OGT and glucose transporter 1 (GLUT1) protein expression as well as tissue levels of O-GlcNAcylation were determined by immunoblotting using specific antibodies. The BeWo choriocarcinoma cell line was also used as an in vitro model of trophoblast to test the effect of high glucose and GLUT1 silencing on the OGT activity by immunoblotting. Maternal BMI was positively correlated to birth weight centile (BWC) (p=0.0130, R2=0.231), maternal fasting glucose (p=0.0177, R2=0.221) and HbA1c levels (p= 0.0156, R2=0.229) as well as placental OGT protein expression (p=0.0294, R2=0.183). The latter was positively associated to the levels of protein O-GlcNAcylation (p=0.0023, R2=0.326). Interestingly, GLUT1 protein levels were positively correlated to BWC (p=0.0056, R2=0.279) and strongly correlated to protein O-GlcNAcylation (p<0.0001, R2=0.507), suggesting an increase in the placental flux of glucose. In agreement with findings in placenta biopsies, in BeWo cells total protein O-GlcNAcylation levels were altered by cell exposure to different glucose levels (5 mM vs 15 mM, p<0.01). This was prevented by downregulating OGT or GLUT1 expression (p<0.001) using gene silencing. In addition, OGT protein levels were negatively associated to AMP-activated protein kinase (AMPK) activation (p=0.0005, R2=0.402) in placenta biopsies identifying a novel cross-talk between two placental nutrient sensors, OGT and AMPK, previously shown in other tissues (2). Accordingly, the silencing of OGT promoted the activation of AMPK (p<0.01) and its downstream target acetyl-CoA carboxylase (ACC) (p<0.01) in BeWo cells, as demonstrated by increased phosphorylation of residues Thr172 and Ser79 for AMPK and ACC respectively. Such obesity-associated cross talk between metabolic and nutrient sensors might disrupt multiple cellular pathways involved in fetal development and growth. References: (1) Acosta et al. Am J Obstet Gynecol. 2015 Feb;212(2):227. (2) Bullen et al. J Biol Chem. 2014 Apr 11;289(15):10592-606.
MON-334 Severe Hypercalcemia Following Hip Joint Implantation of Stimulan® Calcium Sulfate Antibiotic Beads
Authors: Motevalli Mahsa , Moseley Kendall F , Buber Robert , Jha Smita , Zilbermint Mihail
Published: May 2020

Introduction: The diagnosis and management of hypercalcemia in hospitalized patients can be challenging. Hypercalcemia is often associated with significant morbidity and end-organ damage which may delay a patient’s recovery. Case report: A 63-years-old female presented for evaluation of left hip pain and was found to have an infection of the prosthetic joint. Past medical history was significant for type 2 diabetes and atrial fibrillation. No known history of malignancy or excess calcium, vitamins A or D intake. Past surgical history was significant for multiple left hip fixation surgeries and a left hip arthroplasty 4 months prior. Patient’s serum calcium on admission was 8.4 mg/dL (corrected 9.5 mg/dL, range 9.5-10.5 mg/dL), serum creatinine 1.2 mg/dL (range, 0.5 - 1.2 mg/dL). Three days later, she underwent surgical irrigation and debridement of the left hip with placement of 30 cc STIMULAN® antibiotic beads with vancomycin. On postoperative day (POD) 5, patient was found to be confused. Laboratory workup revealed serum calcium 13 mg/dL, ionized calcium 1.91 mmol/L (range, 1.12-1.32 mmol/L), serum creatinine 1.6 mg/dL, intact PTH 10 (range, 15- 65 pg/mL), PTH-rp 15 pg/mL (range, 14-27 pg/mL), 25-OH-vitamin D 18 ng/mL (range, 30-60 ng/mL), 1,25-OH2-vitamin D <8 ng/mL (range, 18-72 ng/mL). Clinical challenge: The differential diagnosis of non-PTH mediated hypercalcemia includes malignancy, granulomatosis and/or excess calcium intake. The patient’s history and laboratory data were not consistent with these etiologies. The temporal nature of the hypercalcemia in relation to implantation of antibiotic beads suggest causality of exogenous calcium sulfate and development of the patient’s hypercalcemia. Mild renal insufficiency, as well as immobilization in the setting of surgery, were likely also contributory. Treatment and outcome: This patient was first treated with aggressive intravenous saline and calcitonin. Serum calcium rose to 13.7 mg/dL and pamidronate 30 mg was administered. Hypercalcemia resolved on POD 11 with improvement in patient functional status. Discussion: Hypercalcemia due to implanted calcium sulfate antibiotic beads is not well described outside of case reports. Kallala found hypercalcemia in less than 0.01% of patients who underwent bead implantation, with all the affected patients presenting with preoperative renal failure. Conclusion: Hypercalcemia in the setting of calcium sulfate antibiotic beads implantation may contribute to a patient’s confusion and increase length-of-stay. We recommend serum calcium and creatinine to be closely monitored during the perioperative period in patients who receive calcium sulfate antibiotic beads. Risk factors for the development of hypercalcemia require additional study, though patients with pre-existing renal insufficiency may not be good candidates for the mechanism of antibiotic administration.
MON-310 Factors Associated with Remission After Surgery for Acromegaly
Authors: Cunha Clara , Ferrinho Cátia , Silva Eugénia , Saraiva Catarina , Marques Conceição , Chorão Martinha , Graça Joana , Duarte Sequeira
Published: May 2020

Background: Acromegaly is a disorder characterized by excessive growth hormone (GH) secretion, which, in most cases, is caused by a GH secreting adenoma. Surgical removal of the tumor via a transsphenoidal approach is the first choice treatment for most patients. The remission rate after an initial resection is 80 to 90 percent for microadenomas and less than 50 percent for macroadenomas.

Objective: To analyze predictive factors of remission in acromegaly patients who underwent transsphenoidal surgery for GH secreting adenoma.

Methods: From January 2006 to October 2019, 75 patients with GH secreting pituitary adenoma were evaluated at our center. Patients who had undergone medical treatment or radiotherapy as first treatment were excluded. A total of 60 patients were included in the analysis. Remission was defined as normal serum insulin-like growth factor-1 (IGF-1) age and sex adjusted and a random serum GH less than 1 ng/mL and/or nadir GH during oral glucose tolerance test <0.4 ng/mL.

Results: We evaluated 60 patients (41 females and 19 males), with a mean age at diagnosis of 49.6 (ranged from 23 to 77 years). Mean initial IGF-1 was 905.3 ng/mL (range 100-324) and mean initial GH was 25.0 ng/mL (<2.5). Macroadenomas were more common than microadenomas (48 vs 12). The average maximum tumor diameter was 15.6 mm and 21 patients were graded as Knosp 3 or 4, which indicated cavernous sinus invasion. Patients were follow for 11.8 years. Overall, the remission rate was 50.0% after surgery. Mean age of patients in surgical remission (51.6 years) was higher than those patients not in remission (47.5 years) (p=0.439). Remission rates for microadenomas and macroadenomas were 75.0% and 44.9%, respectively (p=0.04). Patients who achieved remission had smaller tumors compared with those who failed to attain remission (mean diameter 11.6mm versus 17.8 mm). Using the Knosp classification system and preoperative magnetic resonance images to determine cavernous sinus invasion, Knosp grade 3 to 4 tumors were found in 5 patients in remission and in 16 patients with persistence of disease (p=0.003). Patients who achieved remission had a significantly lower preoperative IGF-1 level (650.5 ng/mL) compared with those who did not (1211.0 ng/mL) (p=0.04). Preoperative GH levels were lower for the patients who achieved remission (18.7 ng/mL) than for those who did not (32.5 ng/mL, p=0.006).

Conclusions: In our study, predictors of biochemical remission after surgery were smaller tumor size, lower Knosp grade, and lower preoperative GH and IGF-1 levels.
SAT-560 Usefulness of Contralateral Suppression in Adrenal Venous Sampling to Define Lateralization in Primary Aldosteronism
Authors: Freitas Thaís C , Maciel Ana Alice Wolf , Vilela Leticia Assis Pereira , Rassi-Cruz Marcela , Petenuci Janaina , Pereira Maria Adelaide A , Silva Giovanio V , Abreu Andrea P , Yamauchi Fernando , Srougi Vitor , Tanno Fabio Y , Chambo Jose L , Latronico Ana Claudia , Bortolotto Luiz A , Drager Luciano , Pilan Bruna , Cavalcante Aline C B , Francisco Carnevale , Fragoso Maria Candida B v , Mendonca Berenice B , Almeida Madson Q
Published: May 2020

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA subtypes include bilateral hyperplasia and unilateral PA, typically aldosterone-producing adenomas. Adrenal venous (AV) sampling (AVS) is a key step to define PA subtype and guide PA management. According current PA guidelines, most PA patients should undergo AVS, which is a challenging procedure, especially in terms of successfully cannulating the right AV. The aim of this study was to report a single tertiary center experience with AVS in PA patients. We retrospectively evaluated 84 AVS from 1984 to 2019. Sequential AVS was performed by an experienced interventional radiologist. AV and inferior vena cava (IVC) samples were obtained under cosyntropin continuous infusion. Successful catheterization was defined by a selectivity index [SI= AV/IVC cortisol (C) concentrations] ≥5. Unilateral disease was defined by a lateralization index [LI= aldosterone (A)/C ratio in the dominant AV divided by A/C in the non-dominant AV] ≥4. The relative aldosterone secretion index (RASI= A/C ratio in AV divided by A/C in IVC) was calculated in each side. A RASI <1 was defined as contralateral suppression (CS). In patients with unsuccessful AV catheterization (mostly right AV) or undetermined LI (3-4), CS was used to indicate adrenalectomy. The biochemical cure of PA after adrenalectomy was defined as the gold standard parameter to confirm unilateral disease. Successful bilateral AV catheterization was achieved in 75% of the cases. After 2015, the use of intra-procedural rapid cortisol assay improved angiographer experience and increased AVS successful rate from 52 to 80%. LI revealed unilateral and bilateral aldosterone excess in 68 and 32% of the cases, respectively. A LI ≥4 had a sensitivity of 100% and specificity of 98% to define unilateral PA among patients with successful catheterization. In addition, RASI in the non-dominant AV was significantly lower in unilateral PA according the LI when compared to bilateral cases [0.12 (0.03 to 1.18) vs. 1.1 (0.04 to 4.56), p= 0.0001]. RASI in the non-dominant AV was inversely correlated with LI (r= -0.81, p= 0.0001). A CS index ≤0.5 had a high sensitivity (90%) and specificity (94%) to define unilateral aldosterone excess. In conclusion, the LI is the most valuable parameter in AVS for PA subtyping. Additionally, CS (cut-off of 0.5) is very useful to define lateralization and can be used in cases of borderline LI or unsuccessful AV catheterization.CAPES Grant to Freitas TC.
SAT-425 Characteristics of Hypothyroid Patients Achieving Long Term Euthyroidism on Levothyroxine Treatment
Authors: Tandeter Howard , Murad JaYanah , Alfandari Liad , Novack Victor , Fraenkel Merav
Published: May 2020

Background

Studies have shown that hypothyroid patients treated with Levothyroxine replacement therapy often experience fluctuations in TSH levels, while others remain well controlled over time.

Aim

To assess the association between pre-treatment TSH and other biochemical and clinical characteristics and long-term maintenance of normal TSH under Levothyroxine treatment.

Methods

This is a retrospective nested case-control study. Study population included patients above age 18 insured by Clalit Health Service (CHS) in the South of Israel between the years 2002-2017, diagnosed with hypothyroidism (ICD 9 code 244.9) and who had at least one TSH measurement before initiating levothyroxine therapy, purchased this medication for at least 5 consecutive years with one annual TSH measurement while on treatment. Patients with surgical, post iodine ablation or congenital hypothyroidism were excluded. Patients with a TSH level within the normal range for 5 consecutive years were defined as cases while the others served as controls. Demographic, laboratory, pregnancy status and pharmacy purchase were extracted from the computerized medical records of CHS and compared between the groups.

Results

Out of 5472 patients included in the study, 644 had a normal TSH for 5 consecutive years (11.8%, cases). Mean age at first levothyroxine purchase was 55.8±13.7 in cases and 54.10±16.2 in controls (p=0.003) and females comprised 84.8% and 81.4% respectively (p=0.035). Mean pretreatment TSH was 5.15±9.6 in cases and 10.02±29 in controls (p<0.001). Thyroid autoantibodies (anti TPO or anti thyroglobulin) were available in 40.8% and 44.8% of cases and controls respectively (P=0.63) and were positive in 36.5% and 56.7% (p<0.01). Subclinical hypothyroidism was diagnosed in 44.4% of cases and 54.6% of controls with prior to treatment. The odds ratio (OR) for having normal TSH for at least 5 consecutive years, using multivariable logistic regression was 0.99 for pretreatment mean TSH (p=0.89), 0.48 for positive thyroid antibodies (p<0.001), 0.72 for pretreatment diagnosis of subclinical hypothyroidism (p=0.032), 0.69 for use of iron supplements and 1.01 for age at first levothyroxine purchase (per year, p=0.02).

Conclusions

In our study population of adults with hypothyroidism treated with levothyroxine, only 11.8% were controlled for at least 5 consecutive years. Positive thyroid autoantibodies, pretreatment subclinical hypothyroidism and use of iron supplements lowered probability of long term TSH normalization, while age was associated with the increased rate. Further research should test whether TSH control for 5 consecutive years signals simply “good contol”, or perhaps the possibility of transient forms of hypothyroidism for which treatment discontinuation is recommended.
MON-632 The Effects of a High Intensity Glycemic Program on Weight and BMI
Authors: Guzman Heidi , O’Malley Grenye , Tamru Abigail , Levy Carol Joan , Lam David
Published: May 2020

Background:

Multiple studies have shown that intensive glycemic control leads to improved HbA1c and delays the onset of complications in diabetes.1 However, improvement in glycemic control has also been associated with weight gain.1 The High A1C (HAC) program uses a multidisciplinary team to provide intensive therapy to patients with HbA1C ≥ 10% over 3 months to improve glycemic control. The aim of this retrospective study is to examine if the HAC program is associated with a significant change in weight and BMI.

Methods:

Patients enrolled in the HAC program were scheduled for frequent visits over the course of 3 months with an Endocrinologist, nurse practitioner, or diabetes educator. Data from patients with type 2 diabetes enrolled from March 2018 to June 2019 who attended at least 2 appointments was collected. Pre-enrollment HbA1c, weight, BMI, and total daily dose (TDD) of insulin (units/kg/day) were compared to post-enrollment using t-test analysis. Use of weight-lowering anti-hyperglycemic agents such as Metformin, GLP-1 agonists (GLP1A) and SGLT-2 inhibitors (SGLT2i) was collected.

Results:

44 patients were enrolled with 39/44 (88.6%) attending at least 2 visits and 5/44 (11.3%) who were lost to follow-up. The median HbA1c improved from 11.5% (9.7-14%) to 8.4% (5.9-14%), p<0.001.There was no significant change in mean weight (195lbs (110-360) vs 192lbs (114-358), p=0.14) or BMI (31 (20-49) vs 31 (21-49) kg/m2, p=0.86). Pre-enrollment, 33/39 (84.6%) patients were on Metformin, 10/39 (25.6%) were on a GLP1A, and 3/39 (7.7%) were on a SGLT2i. At the end of the program, there were 34/39 (87%) patients on Metformin, 26/39 (66.6%) on a GLP1A, and 17/39 (43.5%) on a SGLT2i. There was no difference in the mean TDD of insulin at the start of the program of 0.63 units/kg/day (0-3.52 units/kg/day) compared to 0.60 units/kg/day (0-4.07 units/kg/day) at the end of the program (p=0.97).

Conclusions:

Patients enrolled in a high intensity glycemic control program had significant improvements in HbA1c without change in weight or BMI. Additional adjunctive non-insulin therapies and lifestyle management may be contributing factors for weight neutrality in our population. The significant improvement in HbA1c was not linked with increases in TDD of insulin.

Citation:

1.“U.K. Prospective Diabetes Study Group: Intensive blood glucose control with sulfonylureas or insulin compared with convention treatment and risk of complications in patients with Type 2 Diabetes.” Lancet, vol.353, 1998, pp.837-53.
SAT-108 Growth Hormone Deficiency in a Patient with Ectodermal Dysplasia
Authors: Alkhaled Lina , Haider Anzar
Published: May 2020

Background information:

Ectodermal dysplasia (ED) is a rare heterogeneous group of genetic disorders of ectodermal derived tissues, characterized by abnormalities in skin, teeth, hair and eccrine glands. Growth failure in these children varies depending on the genetic mutation and has not been well characterized. This clinical case report presents a 11-year-old male with a heterozygous mutation in WNT 10 A, a variant of the hypohydrotic ED gene, who was found to have growth hormone (GH) deficiency and treated with GH.

Case report:

He was born at 35 weeks gestation by C-section with a birth weight of 5 lbs. 12 oz. to a mother who had invitro fertilization with donor eggs from the maternal aunt with ocular myasthenia gravis and sperm from the father. Pregnancy was complicated by twin gestation and polyhydraminos. He had transient myasthenia gravis and treated with pyridostigmine for 3 months for feeding problems and swallowing difficulty. He also had arthrogryposis of the distal upper extremities attributed to placental transfer of the maternal aunt’s myasthenia gravis antibodies.

He was referred to the endocrine clinic for evaluation of his growth failure around the age of 8 years. His growth chart indicated that he grew along the 5thpercentile until age 5 year with a gradual decline to the 3rd percentile by age 7 year and close to 2nd percentile by age 8 year. His BMI was at 7th percentile. Mid parental height was 5’9”. There was no history of delayed adolescence in the family. His twin sister had very mild form of arthrogryposis with dental delay but steady linear growth. He also had decreased exercise tolerance. His body tended to become hot during sports activities and had to wrap his face and neck with cold soaked towels. His other problems included delayed dental development with conical incisor, thin nail, missing teeth and hearing defects that raised suspicion for ectodermal dysplasia. Genetic testing at the age of 4 years had demonstrated a heterozygous mutation in the WNT 10A gene, an important gene for tooth development. Physical examination revealed a mild facial dysmorphism with conical incisor, missing teeth and high arched palate. He had contracture of the proximal inter phalangeal joints of the hands. Investigations revealed a normal thyroid function test, IGF-1 and IGFBP-3 level, CBC, sedimentation rate, chemistry panel and celiac titer. The bone age was concordant with his chronological age of 8 years. A GH stimulation study demonstrated a peak GH level of 4.94 ng/ml. An MRI of the brain revealed a normal pituitary gland. He was started on GH therapy with 0.3 mg/kg/week at age 9 year. His height improved from 2nd percentile at age 9 year to 20th percentile by age 11 year on growth hormone therapy. His exercise capacity and stamina also improved.

Conclusion:

Growth failure and GH axis should be evaluated in children with ED. GH therapy improves growth velocity and exercise capacity in patients with ED.
SAT-038 Ambulatory Blood Pressure Increases in Hypogonadal Men Who Develop Increases in Hematocrit on Oral Testosterone Undecanoate
Authors: Dobs Adrian Sandra , White William B , Carson Culley , DelConte Anthony , Khera Mohit , Miner Martin , Shahid Muhamma , Papangkorn Kongnara , Kim Kilyoung , Chidambaram Nachiappan
Published: May 2020

There is concern that testosterone replacement therapies might increase blood pressure (BP) with chronic use. Testosterone undecanoate is a novel oral testosterone therapy under development for the treatment of male hypogonadism. We studied the effects of testosterone undecanoate (225 mg twice daily) on ambulatory blood pressure (ABP) and heart rate, in 138 men with hypogonadism (mean age, 54 years, 79% white, 48% with a history of hypertension). Ambulatory BP and heart rate and hematologic parameters were obtained at baseline and following 4 months of daily therapy. Changes from baseline in ambulatory 24-hour, awake, and sleep systolic BP of 3.8 (p=0.06), 5.2 (p=0.01), and 4.3 mmHg (p=0.07) were observed post-treatment, respectively. Smaller changes in the diastolic BP were observed (1.2 (p=0.13), 1.7 (p=0.04), and 1.7 mmHg (p=0.11) for 24-hour, awake, and sleep, respectively). Changes in the 24-hour, awake and sleep heart rates were 1.9 (p=0.07), 2.6 (p=0.02), and 0.4 (p=0.68) beats/minute respectively. There were no significant differences in changes from baseline in the 24-hour ambulatory BP for the 57 subjects who had a medical history of hypertension versus the 61 subjects who did not have hypertension: 4.5/1.5 mmHg in the hypertension subgroup versus 3.2/0.9 mmHg in the non-hypertensive subgroup (p = 0.53/0.46 between groups). Hematocrit and hemoglobin increased by 3.2% and 0.9 g/dl in all subjects after 4 months of therapy. In those men in the top quartile of changes in hematocrit (corresponding to upper / lower boundary increases of 6 and 14% with 9.3% achieving levels > 52%), the largest increases in ambulatory systolic BP (8.3 mmHg) were observed, whereas the changes in ambulatory systolic BP in the lower 3 quartiles were substantially smaller (1.6, 3.2, and 2.7 mmHg in quartiles 1, 2 and 3 of hematocrit change, respectively). In conclusion, these data demonstrate increases in ambulatory BP occurred following 4 months of oral testosterone undecanoate, particularly in those men whose hematocrit rose by > 6% or whose resultant hematocrit was 52% or higher. Hence, hematocrit maybe a useful clinical parameter that could effectively predict the risk of developing increases in BP on oral testosterone undecanoate.
MON-019 Maternal Behaviour in Mice Is Modified by a High Fat Diet in Pregnancy
Authors: Moazzam Showall , Noorjahan Noshin , Jarmasz Jessica S , Jin Yan , Siddiqui Tabrez J , Cattini Peter Andrew
Published: May 2020

Background: About a third of pregnant women of age 20-39 are obese, which carries significant risks for the mother and fetus, and adversely impacts pregnancy outcome. Specifically, women with obesity are at increased risk for peripartum depression. Maternal behaviour in mice is influenced by changes in hormone signaling in pregnancy, which is associated with effects on adult neurogenesis in the brain. Thus, we used mouse as a model system to gain further insight into the possible relationship between overeating/obesity and brain physiology and maternal behaviour. Objective: To assess the ability of a high-fat diet (HFD) versus a regular chow diet (CD), starting up to 10 weeks pre-pregnancy, to modify glucose clearance before and during pregnancy and affect maternal behaviour in the CD1 mouse. Study Design: Two groups of 3-4 week-old female CD1 mice were fed a HFD (fat=60 kcal%; carbohydrate=20 kcal%; protein=20 kcal%) or CD (fat=14 kcal%; carbohydrate=60 kcal%; protein=26 kcal%) and maintained on their respective diets throughout the study and weighed periodically. After at least 4 weeks of feeding on their diets, mice were allowed to breed. Glucose tolerance was tested using 2 g/kg of i.p. glucose at gestational day (GD) -1) after fasting (16 hours-overnight) as well as during pregnancy at GD16.5. An even number of pregnant and non-pregnant females were selected for each diet for maternal behaviour testing. Tests include an assessment of nest building at GD16.5-17 (use of nesting material and nest quality), and after birth pup retrieval at postpartum day (PD) 3, 4 and 5 (time of retrieval of each of the four pups within six minutes) using video capture. Results: The HFD led to a significant increase in weight relative to mice fed a CD. HFD impaired glucose-load clearances at GD -1 and 16.5 (p<0.05) compared to mice fed a CD. Mice fed on HFD performed poorly in the nest building task (p<0.01) as well as demonstrated a reduced completion rate on the pup retrieval test on PD3 (CD=8/10 vs. HFD 2/9 mice) but their retrieval response latency was improved by PD4 (CD=8/10 vs. HFD 8/9 mice) and PD5 (CD=7/10 vs. HFD 7/9 mice). Conclusions: Initial observations suggest that a HFD for at least 4 weeks before and during pregnancy results in overweight CD1 mice with impaired glucose clearance, and a negative effect on maternal behaviour as assessed by nest-building during pregnancy and pup retrieval postpartum; however, with regard to the latter, mice on the HFD show the ability to learn. Additional behavioural tests for locomotion, anxiety, risk avoidance and object recognition memory during or after pregnancy, as well as associated changes in hormonal signaling and adult neurogenesis are also currently under investigation.
SAT-519 Armour Thyroid and Liothyronine Combination Potentiated Thrombosis
Authors: Shin Tai Ho , Smith Pinar , Goulden Peter
Published: May 2020

Objective To describe a case presentation of multiple sinus thrombosis while on combination therapy of liothyronine and Armour Thyroid for Hashimoto’s thyroiditis with other risk factors of thrombosis. Methods A case report with medical history, diagnostic and treatment course is presented with discussion. Results A 47-year-old female with a history of Hashimoto’s thyroiditis on liothyronine and Armour Thyroid, on oral contraceptive use and cigarette smoking presented to Emergency Room with complaints of severe headache, neck pain and dizziness later developing confusion, word-finding difficulty and various left-sided neurological deficit. She was found to have superior sagittal sinus and right transverse sinus thrombosis, both with partial to complete occlusion and involved hematoma. Patient went through endovascular intervention for successful thrombectomy with recanalization, and neurosurgical intervention for decompressive evacuation of hematoma. Patient was found to have undetectably low thyroid stimulating hormone level, and her base-line level from one year ago was 0.147 milli-international units per liter while having been on liothyronine and Armour Thyroid for years. Patient was started on daily oral levothyroxine and recovered eventually from neurological deficits. Repeated thyroid function test showed improving results. Evaluation for other causes of thrombosis included positive results for prothrombin gene mutation, confirming her inherited thrombophilia condition that has been undiagnosed until this event. Discussion Primary hypothyroidism is one of the most prevalent endocrine disorders, occurring in up to 5% of the population. While synthetic thyroxine has been standard therapy for the primary hypothyroidism for many years, many alternative thyroid therapies have resurfaced recently. For instance, there has been increasing trend of using liothyronine in addition to levothyroxine with symptomatic benefit despite insufficient evidence. Armour Thyroid, which is a natural porcine derivative thyroid supplement often used as a weight loss supplement without proper monitor by physician, has repeatedly been controversial. Many studies have raised concerns for cardiovascular disease including arrhythmia with high thyroid hormone level. Also a number of case reports have shown association with hyperthyroidism and pro-thrombotic state. Although there are scarce publications associating liothyronine or Armour Thyroid and hypercoagulable thrombotic event, significant drug interactions may exist with patient who are more vulnerable with inherited condition or other risk factors.
SAT-506 Rare Case of Durvalumab-Induced Thyroiditis, Transient Secondary Adrenal Insufficiency and Autoimmune Diabetes
Authors: Gorantla Yamuna , Amblee Ambika , Lee Yee Liong , Yap Sara Elizabeth T
Published: May 2020

Introduction:

Cancer Immunotherapy (CI) is rapidly advancing field with different immune check point inhibitors (ICPi) targeting different cancers, with Durvalumab being one of the recent ICPi. Durvalumab induced endocrinopathies are common, mostly irreversible and if managed appropriately do not require cessation. Here we are presenting a patient (pt) who developed 3 different endocrinopathies simultaneously.

Case:

A 69 year old female with type 2 diabetes mellitus (T2DM), Stage III lung cancer was started on Durvalumab for unresectable cancer. 2 months later, presented to Emergency Department with fatigue, poor appetite, dizziness, palpitations, heat intolerance, polydipsia, polyuria. Labs suggestive of Thyrotoxicosis, blood glucose of 600mg/dl, AM Cortisol & ACTH consistent with central adrenal insufficiency (AI). Her previously well controlled T2DM (A1C 6.1%), suddenly became uncontrolled (A1C 9.5%), Antibodies were positive suggesting superimposition of autoimmune diabetes (AID). Pt was discharged on Methimazole (MMI), hydrocortisone (HC) and modified Insulin regimen.

After discharge patient stopped MMI and HC. TFT’s 2 weeks after stopping MMI were suggestive of hypothyroidism. AM Cortisol 10 days after stopping HC was normal, her subsequent AM cortisol remained normal. Her clinical picture with rapid conversion of thyrotoxicosis to hypothyroidism is suggestive of Thyroiditis from Durvalumab.

Discussion:

Durvalumab an ICPi is a programmed death-ligand 1(PD-L1) blocking antibody, initially approved for urothelial cancer, but was later shown to be effective in other solid tumors. Immune-related adverse events (irAE) due to Durvalumab therapy are mostly thyroid-related, AID and AI rarely reported. Pathogenesis of AID is likely related to PD-L1 blockage on autoreactive T cells that target islet cells. Ansari et al showed the development of autoimmune antibodies in a mouse model, later demonstrated in few human studies. irAE can affect more than one endocrine gland, typically occur in 10-11 weeks, can happen at same time or in succession. ICPi-induced hypophysitis should be considered prior to committing to diagnosis of primary AI. American Society of Clinical Oncology (ASCO) recommends screening for endocrine irAE with TSH/FT4 every 4-6 weeks, checking BG at baseline, every cycle for 12 weeks and then every 3 to 6 weeks. In patients with suspected type 1 DM, ASCO recommends checking antibodies, insulin, and, C-peptide levels. For AI, routine diagnostic work-up not recommended if asymptomatic.

Conclusion:

Our pt with T2DM developed AID, thyroiditis which progressed to hypothyroidism, central AI. This is a rare case where pt developed all 3 endocrinopathies secondary to durvalumab and also a rare case where AI self-resolved when pt still on durvalumab.
SAT-063 Polymicrobial Suppurative Thyroiditis Masquerading as Thyroid Storm
Authors: Finn Erin E , Tommerdahl Kalie L , Hayes Kari L , Chan Christine L
Published: May 2020

Introduction:

The thyroid gland is highly resistant to infection due to a robust blood supply, good lymphatic drainage, and high iodine concentration. Suppurative thyroiditis (ST) often presents with fever, tachycardia, leukocytosis, tenderness, and euthyroid labs. However, when ST occurs with thyrotoxicosis, it can meet criteria for thyroid storm, which presents a diagnostic dilemma.

Clinical Case:

A 17 year old female with family history of Graves’ disease presented to the ER with a sore throat. She was diagnosed with viral pharyngitis and treated with dexamethasone. Over the next 2 weeks, she developed fatigue, body aches, nausea, vomiting, and chills. She returned to the ER and was found to have tachycardia, hyperthyroidism [free T4 5.64 ng/dL (0.8 - 2.0 ng/dL), TSH <0.015 uIU/mL (0.5 - 4.5 uIU/mL)], and WBC 11 k/uL (3.5 - 11.5 k/uL). She was prescribed atenolol and referred to Endocrinology. Three days later she developed fever, diaphoresis, ear pain, vomiting, and abdominal pain. In the ER, she was febrile to 101.2°F with a heart rate (HR) of 117 BPM. Labs showed a free T4 6.14 ng/dL, TSH <0.015 uIU/mL, and WBC 20 k/uL. She was treated with methylprednisolone, propylthiouracil, and labetalol with improvement and transferred for concern of impending thyroid storm. Exam showed left-sided thyroid enlargement with tenderness. Thyroid ultrasound showed an enlarged heterogenous left thyroid lobe with 2 nodules, one 25 x 33 x 21 mm heterogenous and one 19 x 11 x 19 mm homogenous, without discrete abscess. That night she developed vomiting, hand tremors, HR in the 130’s BPM, fever to 104.1°F, and a headache. Treatment was initiated with methimazole, SSKI drops, propranolol, and dexamethasone. Symptoms improved save persistent neck tenderness and dysphagia. CT neck demonstrated a left-sided 25 x 17 x 90 mm abscess with concern for 4th branchial apparatus abnormality. She underwent incision and drainage with drain placement. Cultures grew Streptococcus anginosus and Fusobacterium necrophorum. Broad spectrum antibiotics were started and later narrowed to ampicillin-sulbactam. Betablockers and methimazole were discontinued and thyroid labs nearly normalized by discharge [T4 11.8 mcg/dL (4.5-11.5 mcg/dL), free T4 2.0 ng/dL (0.8-2 ng/dL), and total T3 78 ng/dL (100-210 ng/dL)]. Thyroid auto-antibodies were negative.

Discussion:

In patients with ST, only 11% present with hyperthyroidism. Current thyroid storm scoring systems are sensitive but not specific so an acute bacterial infection with thyrotoxicosis can easily meet criteria. While ultrasound is standard for assessing for thyroid abscesses, in the setting of high clinical suspicion, further imaging with contrasted neck CT is warranted.
SAT-487 Untreated Primary Hypothyroidism Presenting as Pica with Concurrent Hyponatremia and Rhabdomyolysis
Authors: Mirza Mehwish A , Ayala Ricky , Savage Jacqueline
Published: May 2020

Background:

Psychosis is a rare but known presentation of hypothyroidism, whereas other mental health disorders are less commonly associated. Pica, the consumption of non-nutritive, non-food substances, has not been reported to be associated with hypothyroidism. We describe a case of untreated severe hypothyroidism in which the patient presented with pica that reversed with treatment with levothyroxine.

Clinical case:

A 65-year-old female with a history of cigarette smoking and chronic marijuana use was brought to the emergency department by family after she was found attempting to eat non-food objects such as pens and a toothbrush. She reported new onset unsteady gait and having frequent falls over the past several months in addition to being increasingly forgetful. She complained of fatigue and reported recent unintentional weight loss, but denied cold intolerance, skin or hair changes, or constipation. On admission, she was noted to be hypothermic with body temperature between 94-95 degrees Fahrenheit. Physical examination was essentially unremarkable with normal thyroid size and reflexes. No pretibial edema was noted. Admission labs showed hemoglobin of 14.0 g/dL with a white cell count of 8000 cells/uL, without evidence of anemia or infection. Sodium was low at 123 mmol/l and creatinine kinase was elevated at 989 U/L which peaked at 1356 U/L during her admission. CT of the head was negative for any acute intracranial process. Further workup was significant for TSH 85.6 mIU/L (0.27-4.20 mIU/L), free T4 <0.1 ng/dL (0.80-1.90 ng/dL), total T4 0.7 mcg/dL (5.1-11.9 mcg/dL), total T3 < 25 ng/dL (76-181 ng/dL), and TPO antibody 416 IU/ml (<9 IU/ml). AM cortisol was 27.0 ug/dL (6.2-19.4 ug/dL) at 8 AM, ruling out hypocortisolemia. The patient had not seen a medical provider in 10 years, had no recent health maintenance, and had no prior known history of thyroid disease. She was given IV fluids and started on oral levothyroxine 100 mcg daily due to the severity of hypothyroidism. Her sodium improved to 130 mmol/l over the next 4-5 days. Mental status returned to baseline with improvement in memory function and in gait and balance. Creatinine kinase trended down to 688 U/L over the next 2 days. She did not exhibit any additional behavior of eating non-food objects during the hospital stay. Patient was diagnosed to have severe hypothyroidism presenting as pica along with hyponatremia and rhabdomyolysis. Patient was discharged on levothyroxine 75 mcg daily.

Clinical lessons/conclusions:

Hyponatremia, rhabdomyolysis, and psychosis are relatively uncommon but known reported complications of untreated primary hypothyroidism. Acute psychosis has been reported as a presenting feature of undiagnosed hypothyroidism, but hypothyroidism presenting as pica as seen in our patient is extremely rare. This case highlights the importance of screening for hypothyroidism in patients presenting with unexplained pica.