bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-218 Metastatic Non Seminomatous Germ Cell Tumor Masquerading as Bilateral Adrenal Masses
Authors: Baral Neelam , Bansal Rashika , Basyal Binaya , Lee Wen , Kantorovich Vitaly , Sharma Meeta B
Published: May 2020

Context: Adrenal incidentalomas are commonly nonfunctional and can be diagnosed with imaging and biochemical testing. However, detection of rare causes of adrenal incidentalomas like metastatic adrenal tumors can makes its’ diagnosis very challenging due to vast majority of uncommon primary tumors. Consideration of biopsy for diagnosis and the awareness of rare primary tumors that can metastasize to adrenals is essential to prevent unnecessary adrenalectomies. Our case illustrates one such rare case where bilateral adrenal mass was the initial presentation of obscure retroperitoneal primary NSGCT (Non seminomatous germ cell tumor). Case Description: We present a case of a 34-year-old male with acute abdominal pain found to have huge bilateral adrenal masses. The left adrenal gland was markedly enlarged to 11 x 9 x 5 cm and the right adrenal gland was 6.5 x 3.4 x 7.7 cm. Multiple enlarged and centrally necrotic retroperitoneal lymph nodes (maximum 2.6 x 4.2 x 5.4 cm) along with iliac and inguinal lymphadenopathy were noted. The incidentalomas were proven to be biochemically nonfunctional and extensive imaging and further lab work up ruled out lymphoma, mycobacterial or fungal infection, infiltrative diseases. He then underwent a core biopsy of the left adrenal mass which showed predominantly necrotic tissue, acute inflammatory cells with histiocytes, and rare atypical cells without evidence of malignancy. Repeat core biopsy of left adrenal mass was unrevealing. He finally underwent a core biopsy of a large 4cm retroperitoneal lymph node which ultimately revealed NSGCT. Scrotal ultrasound showed testicular microlithiasis without any testicular mass. He had a very low testosterone level of 21 (241-827 ng/dL) and an a mildly elevated b-hCG (beta human chorionic gonadotropin) of 134 (0-1mIU/ml). A retroperitoneal primary NSGCT with metastasis to the adrenal glands was the most likely diagnosis (visceral metastasis) - Stage III (pTxN3M1S1). He was started on bleomycin, etoposide and cisplatin (BEP) chemotherapy. Conclusion: Rapidly progressing adrenal masses in young males should prompt consideration for metastatic germ cell tumors as a possible cause, even with near normal tumor markers such as alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (B-HCG). Confirmation of the metastatic tumor, via histopathology, is required to avoid unnecessary adrenalectomy.
SUN-034 Combined CNV, Haplotyping and Whole Exome Sequencing Implicates Inherited Novel SRY Mutations Not Account for Familial 46,XY Sex Reversal
Authors: Qiao Jie , Wang Nan , Zhu Wenjiao , Han Bing , Zhao Shuangxia , Song Huai-Dong
Published: May 2020

SRY is one of the important genes involved in the process of human sex determination. The disturbed sex determination caused by SRY mutation accounts for 10-15% cases with complete gonadal dysplasia (CGD), also known as 46, XY sex reversal. Recently, three distal enhancers are disclosed in the upstream of SOX9 gene. In an inherited 46, XY sex reversal pedigree with 5 patients, p.Arg76Leu mutation of SRY and p.G212S mutation of NR5A1were identified from the proband who present with primary amenorrhea and lack of puberty development. The missense mutation of NR5A1was found to be derived from the mother. Interestingly, the paternal inherited p.Arg76Leu mutation of SRY was revealed from other 2 CGD patients, as well as from apparent normal male family members with fertility. P.Arg76Leu variation was found have no effect to the transcriptional activity of target gene SOX9, neither alteration of the nuclear translocation of SRY. Whole exome sequencing also found SRY mutation, FGF10 mutation, GJB4 gene mutation, etc. with no segregation in the family, which suggested SNVs are not main cause of the disease in this pedigree. By copy number variation and SNP haplotype analysis, SOX9 gene far upstream deletion of 68kb was disclosed from the 3 patients in this family, containing one of the enhancers of SOX9. Real-time PCR confirmed that the heterozygous deletion of the region result in loss of SR-XY, but not eSR-B and eALDI. Therefore, single nucleotide variation (SNV) of SRY and NR5A1 are not main causes of severe phenotype of CGD, the enhancers of SOX9 should be investigated carefully in such patients.
MON-352 When Osteoporosis Does Not Make Sense: Tumor-Induced Osteomalacia
Authors: Techathaveewat Pawarid , Elshimy Ghada , Tran Kelvin , Vinales Karyne L , Correa Ricardo R
Published: May 2020

Background: Tumor-induced Osteomalacia (TIO) is a rare paraneoplastic disorder that relates to excess FGF-23 secretion from mesenchymal tumors. Typical presentations include weakness, severe bone pain, but more importantly; multiple false or true fractures. Severe Hypophosphatemia with hyperphosphaturia is one of the pathognomonic findings due to FGF-23 action on renal tubules as phosphaturic agent. Multiple imaging modalities usually required as tumor can be in any size and anywhere in the body.

Case: 58 yo male with past medical history of multiple fractures: bilateral rib cage, and metatarsal, dextroscoliosis who present to endocrine clinic due to low bone mineral density (BMD). On initial visit, screening bloodwork done was unremarkable except for mild elevation of Alkaline Phosphatase and extremely low phosphorus (1.2). 24 Urine phosphorus ordered which was elevated but it was thought to be nutrition related thus phosphorus replacement was prescribed (4 times per day). On follow up, repeat labs noted again with severe hypophosphatemia with elevated FePhos. DEXA was also performed which noted with T score -4.0 of lumbar spine. During that appointment, he informed also that currently in the process of evaluating right lung mass with biopsy resulted with benign mesenchymal tumor which he was happy to hear. TIO was then suspicious to be the cause of decrease BMD along with history of multiple fractures and height loss. Subsequently, FGF-23 staining was then made to the biopsy sample which was positive thus confirming the diagnosis. Patient then underwent surgical resection of the tumor which post-surgery, patient experienced overall symptoms improvement, resolution of phosphatemia, as well as significant improvement of BMD without additional therapy besides calcium and vitamin D.

Discussion: Osteomalacia is a pathological bone disease involving poor mineralization of existing bone during remodeling phrase. It is commonly involved with chronic hypophosphatemia and/or hypocalcemia. Persistent decrease in calcium-phosphate product leads to reduction in bone mineralization activity and bone stiffness with Bowing deformities of the long bone being one of the common findings as well as false fracture.In TIO, FGF-23 is excessively secreted by mesenchymal tumor that is usually difficult to locate due to its small size. When FGF-Receptor is activated, NaPi-2a transcription is reduced in proximal tubule cells which leads to Phosphate excretion and wasting.TIO is a curable disease once tumor is located and surgically removed thus it is important for providers to be aware of it and pursue diagnostic work up when high suspicious. One of the most common reason for misdiagnosis is due to standard metabolic panel on its own does not include phosphorus level which is crucial. TIO has to be distinguish from osteoporosis as Bisphosphonates is not indicated as treatment which is first line for the latter.
MON-469 Rapidly Expanding Thyroid Goiter as the First Manifestation of Systemic Amyloidosis
Authors: Khil Jaclyn , Baer David , Lo Joan Chia-Mei , Arzumanyan Hasmik
Published: May 2020

INTRODUCTION

Amyloidosis is a condition manifesting with extracellular tissue deposition of fibrils of low molecular weight proteins. In Ig light chain amyloidosis (AL), the deposition of Ig light chains can cause organ dysfunction, and patients can have involvement of a range of organs including kidney (70%), liver (70%), heart (60%), peripheral nerves (20%), the tongue, skin, and the coagulation system (1). We describe a unique case of AL amyloidosis, which first presented with thyroid involvement.

CLINICAL CASE

A 78 year old female patient with hx of small lymphocytic lymphoma and normal thyroid function presented with an expanding symptomatic goiter and compressive symptoms (positive Pemberton sign) for which a total thyroidectomy was performed. Pathology showed Congo red-birefringent amyloid deposition. SPEP showed a small amount of M protein, with circulating monoclonal free lambda light chain on immunofixation. The free kappa lambda light chain ratio was low (0.04) with an elevated serum free lambda light chain (283.93). Mass spectrometry confirmed AL light chain amyloidosis - lambda type. A work up was initiated to assess other organ involvement. Echocardiogram showed mild thickening of left ventricle with a preserved EF and EKG showed low voltage in limb leads. Creatinine (1.05) was minimally elevated from baseline with minimal proteinuria (396 mg/24 hours). Alkaline phosphatase, APTT, and PT were normal. The patient described tongue enlargement and scalloping of the tongue from tooth impingement was seen. Biopsies of tongue and bone marrow also showed amyloidosis thereby securing the diagnosis of systemic amyloidosis, and chemotherapy was initiated.

CONCLUSION

This case illustrates the importance of considering amyloid goiter in the differential for a rapidly enlarging thyroid, even when there is no history of amyloidosis. Although extremely uncommon, a few case reports have described amyloid goiter. In our case, thyroid AL was the initial presentation of systemic amyloidosis. Because disease can be localized or systemic, work up should include an assessment for the presence of a monoclonal gammopathy and an assessment for amyloid mediated organ dysfunction. Tissue should be sent for amyloid typing – there are 35 different proteins known to form amyloid fibrils and prognosis and treatment depends on amyloid type (2). Typing using Liquid Chromatography-Tandem Mass Spectrometry, is the most sensitive and specific methodology, though, in experienced hands, typing by immune histochemistry is an option.

REFERENCES

1. Rajkumar, S.V., Dispenzieri, A. Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis. Uptodate. 2019.

2. Winter, M., Tholey, A., Kristen, A., Röcken, C. MALDI Mass Spectrometry Imaging: A Novel Tool for the Identification and Classification of Amyloidosis. Proteomics 2017, 17, 1700236.
SUN-919 Ectopic ACTH Syndrome: An Aggressive Presentation Due to Metastatic Liver Cancer of Unknown Primary
Authors: Serrano Ivan Alexander , Ahmad Sara , Dadu Ramona , Graham Paul , Weitzman Steven
Published: May 2020

Background: Ectopic Cushing’s Syndrome is a rare but often aggressive condition caused by ACTH-hypersecretion from non-pituitary tumors. In patients with metastatic cancer, as well as those with occult tumors, the diagnosis and management can be extremely challenging. Clinical Case: A 25-year old woman recently diagnosed with poorly differentiated metastatic liver carcinoma of unknown primary was admitted for lower extremity edema and worsening fatigue for the preceding month. Since being diagnosed with liver cancer, she developed uncontrolled hypertension, persistent severe hypokalemia and facial “puffiness”. Physical exam was remarkable for moon facies and truncal obesity but no evidence of striae. An overnight 1-mg dexamethasone suppression test resulted in an elevated morning cortisol level of 93.4 mcg/dL and elevated ACTH of 299 pg/mL. A 24-hour urine cortisol was significantly elevated at 4,448 mcg/24 hours. These findings were consistent with hypercortisolism due to hypersecretion of ACTH. An MRI of the sella revealed no pituitary abnormality. A high-dose dexamethasone suppresion test (single 8 mg dose) was performed and her morning cortisol level remained elevated at 98.6 mcg/dL, consistent with ectopic ACTH secretion. She was treated for the underlying malignancy with carboplatin and paclitaxel. After a thorough discussion of therapeutic options, she was prescribed Ketoconazole with the plan to medically control the hypercortisolism potentially followed by bilateral adrenalectomy. Ketoconazole was up-titrated and Spironolactone was added resulting in significant improvement of hypokalemia and hypertension. Unfortunately, one week after discharge she was re-admitted due to worsening performance status, watery diarrhea and abdominal pain. A serum cortisol level was elevated at 124 mcg/dL and Metyrapone was added to her regimen. Unfortunately, her performance status continued to decline due to progression of cancer and uncontrolled hypercortisolism. As a result, she was deemed a poor surgical candidate for bilateral adrenalectomy. The patient’s condition rapidly deteriorated and she developed malignant ascites as well as altered mental status. In accordance with her wishes, a DNR order was placed and she passed away shortly thereafter. Conclusion: Ectopic ACTH-syndrome is the etiology of 10–20% of cases of Cushing’s syndrome. Clinical presentation is often sudden and rapidly progressive. Severe hypertension and hypokalemia are seen more commonly than in Cushing’s disease. Cases secondary to occult tumors or metastatic cancer can be particularly challenging to treat when it is not possible to eliminate the source of ACTH hypersecretion via surgical or medical treatment. In patients such as this, early bilateral adrenalectomy should be considered after starting medical therapy in order to reduce morbidity and mortality due to hypercortisolism.
MON-064 Persistent Progressive Clitoromegaly Is Not Always Hormonal: When One Disease Fits All
Authors: Gupta Meenal , Horne Vincent , Seth Abhishek , Tu Duong , Adeyemi-Fowode Yemi , Karaviti Lefkothea P
Published: May 2020

Introduction: Clitoromegaly presenting in childhood can be congenital or acquired. The most common cause is exposure to excess androgens in fetal or neonatal life. However, non-hormonal causes like neurofibromatosis type 1 (NF-1), epidermoid cysts, tumor syndromes have been reported. An asymmetric or irregular appearing clitoris is usually caused by a non-hormonal process.

Clinical Case: A 6-year-old female with NF-1 and right-sided hemihypertrophy was referred to endocrinology due to progressive clitoromegaly since birth. NF-1 features included café-au-lait spots, bilateral optic nerve gliomas, plexiform neurofibroma, Lisch nodule, first degree relatives with NF-1 (sister and mother). At age 1.5, a hormonal work up was negative for hyperandrogenism. At age 2, patient was seen by genetics, and by urology for removal of a bladder neurofibroma, but did not return to these specialties for follow up. Lumbar spine MRI, obtained for back pain, revealed a large sciatic plexiform neurofibroma. She followed with oncology for cancer surveillance and due to parental concern for progressive clitoromegaly was referred to endocrinology at age 6. At the endocrinology visit, parents denied breast development, vaginal discharge or bleeding, axillary or pubic hair, body odor or acne. Her genital exam revealed a clitoris 3 x 1.5 cm in size, Tanner 1 pubic hair, no palpable gonads, no labial fusion but asymmetric labial sizes (right>left). A hormonal workup was normal including 41 ng/dL 17-hydroxyprogesterone (n ≤137 ng/dL), 20 ng/dL androstenedione (n ≤ 45 ng/dl), 42 ng/dL unconjugated DHEA (n ≤ 487 ng/dL), 11 mcg/dL DHEA Sulfate (n ≤ 34 mcg/dL), 3 ng/dL total testosterone (n ≤ 21 ng/dL) and pre-pubertal LH, FSH and estradiol levels. Patient was referred to a multi-disciplinary DSD (Disorders of Sexual Differentiation) clinic for further evaluation and potential surgical options. A pelvic ultrasound and subsequent pelvic MRI revealed that the large sciatic plexiform neurofibroma, detected on the prior MRI, had now extended into the clitoris and right labia. Uterus and ovaries were pre-pubertal in size. Surgical options were discussed in a multi-disciplinary approach. Since clitoral enlargement was contiguous with posterior bladder mass and vital organ functions were not affected, resection was not recommended. Clitoral reduction for cosmetic reasons had a potential risk of recurrence. Since benefits did not outweigh the risks, family chose to not pursue any surgical intervention.

Conclusions: NF-1 is a rare but potential non-hormonal cause of clitoromegaly. In the absence of clinical evidence of hyperandrogenism, clitoromegaly in a patient with NF-1 does not warrant an extensive hormonal work up. Pelvic imaging should be pursued first, to search for local neurofibromas. Decision for surgical interventions requires a multi-disciplinary approach with detailed discussion of benefits vs. risks.
MON-459 Bilateral Killian-Jamieson Diverticulum Mimicking Thyroid Nodules
Authors: Lin Yu-Yi , Wang Hsin-Kai , Chen Harn-Shen , Kwok Ching-Fai
Published: May 2020

Background

In recent years, incidence and prevalence of thyroid and extrathyroid lesion is increasing in the worldwide due to increase awareness of medical check-up, and widespread use of imaging techniques. A Killian Jamieson diverticulum (KJD), a rare type of hypopharyngeal pulsion diverticulum outpouching from the lateral wall of the proximal cervical esophagus, was incidentally detected and likely to be misinterpreted as a thyroid nodule while performing thyroid sonography. Clearly differentiate between those lesions is essential to avoid unnecessary invasive procedure. Here we report a typical case of bilateral Killian Jamieson diverticulum mimicking thyroid nodules.

Clinical case

A 57-year-old Taiwanese man was referred to our endocrine outpatient department for further evaluation of thyroid nodules. The lesions were discovered while sonographic examination performed in the clinic for routine medical check-up. He denied having dysphagia, epigastric pain, odynophagia, halitosis, chronic cough or acid regurgitation, body weight loss, fever and dyspnea. He had no previous systemic disease and no prior radiation therapy. He lives in Nangang District, Taipei city. His body weight was 70 kg and BMI was 25. An examination of head and neck was unremarkable. Laboratory data revealed normal thyroid function (TSH: 0.67 uIU/ml; range 0.4~4.0, free T4: 0.83 ng/dl; range 0.9~1.8 and aTPO <1.0 IU/ml; range <5). Thyroid ultrasonography demonstrated oval, hypoechoic nodule-like lesions containing bright foci with acoustic shadow in the posterior aspect of the both lobes of thyroid gland. The rest of thyroid glands were normal appearance. An esophagography was performed and showed two contrast-filling anterior outpouching lesions at both sides of the cervical esophagus, around C7 level and both lesions were showing anterior outpouching appearance, consider Killian-Jamieson diverticulum. Taken together, he was diagnosed as KJD and clinical follow-up alone is suggested.

Clinical lessons

KJD is usually incidentally detected and misdiagnosed as a thyroid nodule containing punctuate microcalcification foci as found in papillary thyroid carcinoma. To differentiate these nodules, real time sonographic examination is important. Although rare, non-thyroid lesions originating from the esophagus should be considered in the differential diagnosis of the thyroid nodules to avoid unnecessary invasive fine needle aspiration of thyroid gland.
MON-689 Diabetes Mellitus---Hypoglycemic Response---Empyema
Authors: Chen Yaning
Published: May 2020

Diabetes mellitus---hypoglycemic response---empyema

Case report

A 65-year-old woman was admitted to our department due to high blood glucose for two days on February 29, 2016. Fasting blood glucose was 12.53mmol/L on February 28 without polydipsia, polyuria, polyphagia and weight loss.

In the past medical history, she started to cough in January 2016. On February 2, the routine blood examination showed that white blood cells and neutrophils were higher than normal. Chest X-ray was normal. Moxifloxacin was given and symptoms were relieved slightly.

On examination, the temperature was 36.9℃. Auscultation of the chest was normal. On the evening of admission, body temperature rose to 37.8 C. On March 1st, white cell, neutrophil, erythrocyte sedimentation rate and C-reactive protein were increased. FBG was 10.5mmol/L, and HbA1c was 10.5%. Chest CT was normal. Piperacillin Tazobactam Sodium and Moxifloxacin were given, and insulin was used to lower blood glucose.

On March 2, body temperature was normal. And palpitation, tremor, sweating, fatigue and cold extremities appeared several times. Blood glucose test ruled out hypoglycemia. The above symptoms appeared again at around 4 pm, more serious than before. Gas analysis at 5:12pm showed PH 7.403 and lactic acid 19.27mmol/L. At 6:00pm, blood pressure started to drop. Vasoactive drug was given. In gas analysis at 6:27pm, PH was 7.237, lactic acid 21.05mmol/L. 5% NaHCO3 solution was given to buffer acidosis. Cardiac and respiratory arrested during transferring to ICU. Undergoing cardiopulmonary resuscitation, vasoactive drugs and ventilator-assisted breathing were applied. Hemodialysis was used to counteract lactate acidosis. The bedside chest radiograph showed that the transmittance of left lung was decreased. On March 3, the transmittance of left lung was lower. Doctors prescribed Tylenol and Vancomycin. On March 4, left thoracic puncture and catheterization were performed. The pus was drained out and bacterial cultures were made. Klebsiella pneumoniae was cultured. Sensitive antibiotics therapy was chosen according to pleural cultures. On March 9, left empyema was removed and pericardial fenestration was performed by thoracoscope under general anesthesia. Nutritional support had been given. The patient gradually recovered and was discharged on April 9.

Discussion

Palpitation, tremor, sweating and fatigue were the first manifestations of the condition change in this diabetic patient. The condition rapidly developed into septic shock and empyema. After active treatment, she was cured and discharged from hospital. Besides hypoglycemia, other diseases such as septic shock also may cause the symptoms of sympathetic excitation, which should be considered in order to avoid delaying the time of treatment. Furthermore, diabetic patients complicating with infection should be actively treated with effective antibiotics.
MON-030 Intermediate Hyperglycemia and Type 2 Diabetes in Women with Polycystic Ovary Syndrome: Findings from Large Caucasian Cohort
Authors: Livadas Sarantis , Bothou Christina , Kuliczkowska-Płaksej Justyna , Androulakis Ioannis , Robeva Ralitsa , Vryonidou Andromahi , Macut Jelica Bjekic , Mouslech Zadalla , Milewicz Andrzej Jan , Panidis Dimitrios , Macut Djuro P
Published: May 2020

Background: Insulin secretory defects and insulin resistance exists in women with polycystic ovary syndrome (PCOS) and are prerequisites for the development of type 2 diabetes (T2D). Objective: To determine the prevalence of T2D, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), as well as the factors associated with these dysglycemic conditions. Participants: 1614 women with PCOS of Caucasian origin (Rotterdam criteria) with a mean age 25.14±5.56 years and BMI 27.34±7.09 kg/m2 comprised the study group, whereas 359 normally ovulating, not hyperandrogenic women of comparable age and BMI, served as controls. Design: Observational study. Setting: Outpatient clinics of tertiary hospitals. Main Outcome and Measures: Clinical, biochemical, hormonal and ovarian ultrasound as well oral glucose tolerance test were performed in all subjects participating in the study. Diabetes and intermediate hypeglycemia was categorised according to WHO criteria and PCOS subgroups was based on the Rotterdam criteria. Results: In the PCOS group 2.2%, 9.5% and 12,4% of subjects had T2D, IGT and IFG, respectively. In control group 1,11%, 7.5% and 8.9% had T2D, IGT and IFG, respectively. When the existence of T2D was stratified according to age and BMI, no difference was found among age and BMI subgroups or PCOS subgroups. Namely in patients aged 17-22 years, T2D was detected in 3 lean and 2 obese subjects. The corresponding distribution for patients aged 22-30 years was 4 lean, one overweight and 2 obese, whereas in those older than 31 years, 2 overweight and 5 obese suffered from T2D. Free Androgen Index (FAI), waist to hip ratio (WHR) and LDL levels were significantly higher in T2D subjects in comparison to PCOS women with normal glucose metabolism. Diagnosis of T2D was significantly associated with Free Androgen Index (r: 0.469, p<0.05), while subjects with either IFG and IGT had positive association with BMI, WHR, FAI and HOMA-IR. In controls, T2D, IGT and IFG were positively associated with BMI and androgen concentrations. Conclusions: The prevalence of T2D and IGT is significantly higher in our large cohort of PCOS women in comparison to controls. The existence of T2D is irrespective of age and BMI, and seems to be inherent for PCOS women. Hence, the evaluation of glycemic status in women with PCOS using OGTT is supported.
MON-300 AIP Gene Germline Mutations in Non-Selected Patients with Apparently Sporadic Pituitary Macrodenomas
Authors: Trofimiuk-Muldner Malgorzata , Domagała Bartosz , Sokolowski Grzegorz , Skalniak Anna , Piatkowski Jakub , Hubalewska-Dydejczyk Alicja
Published: May 2020

Up to 5% of all pituitary tumors are hereditary (e.g. due to menin or AIP genes germline mutations). AIP gene mutations are more common in subjects with acromegaly, less than 30 years old at the onset of disease, and with FIPA family history.

The study was aimed at the assessment of the frequency and characteristics of AIP-mutation related tumors in non-selected patients with pituitary macroadenomas.

Material and methods. The study included subsequent 131 patients (57 males, 74 females; median age 42 years (IQR 25 years) diagnosed with pituitary macroadenomas, and with a negative family history of FIPA or MEN1 syndromes. The following tumors were identified: 11 ACTH-secreting, 49 GH-secreting (including 7 pluri-hormonal ones), 6 gonadotropinomas, 23 prolactinomas, 1 TSH-oma, and 43 non-secreting adenomas. Sanger sequencing was used for the assessment of AIP gene variants. The study was approved by the Ethics Board of JUMC.

Results. An AIP mutation was identified in five of 131 included subjects (3.8%): one diagnosed with Cushing’s disease, two with acromegaly, and two with non-secreting adenomas. In two patients, the identified mutation usually predisposes to ACTH-secreting adenomas, in two patients - mutations of unknown clinical significance were found (usually connected with pituitary adenomas), and the mutation detected in one patient was described as benign. Patients harboring hereditary AIP gene variations did not differ from the rest of the study group in median age at diagnosis (41 vs. 42.5 years, p=0.8), median largest tumor diameter (25 vs. 24 mm, p=0.6), gender distribution (60% of females vs. 56.3%, p=0.8), secreting tumor frequency (60% vs. 67.5%, p=0.7), or acromegaly diagnosis frequency (40% vs.37.3%, p=0.9). 2 of the 5 patients with identified AIP gene mutations agreed for their families to be offered AIP genetic testing: (1) An AIP mutation was found in the asymptomatic mother of one acromegalic female patient. (2) The AIP mutation of unknown clinical significance was detected in the son of a male acromegalic patient with acromegaly, clinically unscreened yet.

Conclusions. In our series of apparently sporadic pituitary macroadenomas, AIP gene mutation carriers did not differ substantially from patients with negative genetic testing. A risk factor-centered approach to AIP genetic screening may result in missing germline mutations, therefore, there is a need to establish if such a situation negatively impacts a patient’s and his/her family outcomes.
SUN-291 Presence of Aberrant Adrenocorticotropic Hormone Precursors in Two Cases of McCune- Albright Syndrome
Authors: Yamagata Satoshi , Takayasu Shinobu , Makita Koshi , Kageyama Kazunori , Okawa Yuta , Oki Yutaka , Asari Yuko , Terui Ken , Daimon Makoto
Published: May 2020

Background: McCune-Albright syndrome (MAS) is a rare disorder. MAS is caused by an activating postzygotic somatic mutation in the GNAS, and, is classically defined by the occurrence of fibrous dysplasia (FD), café-au-lait skin macules, and precocious puberty. Autonomous GH and/or PRL production in MAS has been reported. However, there have been no reports of ACTH excess in MAS. Method: Plasma ACTH and serum cortisol (F) levels were assessed using electrochemiluminescence immunoassays (Eclusys ACTHTM and Eclusys Cortisol IITM, respectively; Roche Diagnostics K.K., Tokyo, Japan).Clinical Cases: Case1; 42-year-old man showed craniofacial deformities and suffered from multiple bone fractures. He was diagnosed with FD at the age of 23 years. Café-au-lait macules were found on his back. He had slightly acromegaloid features. He showed no cushingoid features. Pituitary adenoma or hyperplasia was not detected by MRI. The diagnosis of GH excess was confirmed by no suppression of serum GH levels by a 75-g oral glucose tolerance test (nadir GH: 2.34 ng/mL) and an elevated serum IGF-I level (307 ng/mL; normal range: 92-257 ng/mL). The patient was treated with monthly subcutaneous lanreotide injection and then GH excess was well controlled. Basal ACTH and F levels in blood were 40.6-63.4 pg/mL and 8.0-10.5 μg/dL, respectively. The urinary free cortisol (UFC) level was 53 μg/day. Autonomous F excess was excluded by the level of midnight F (1.2 μg/dL) and the level of F (0.2 μg/dL) after a low-dose (1 mg) dexamethasone suppression test (DST). Case2; A 32-year-old man was diagnosed with MAS and gigantism at the Pediatrics Department at the age of 5 years. Treatment of GH excess was well controlled by monthly octreotide depot. He had no acromegaloid features and no cushingoid features. Café-au-lait macules were observed from the left flank to the back. Pituitary adenoma or hyperplasia was not detected by MRI. Basal ACTH and F levels in blood were 35.5-73.1 pg/mL and 7.0-11.7 μg/dL, respectively. The UFC level was 61 μg/day. Autonomous F excess was excluded by the level of F (<0.2 μg/dL) after a low-dose (0.5 mg) DST.Possibility of primary adrenal insufficiency was excluded by ACTH stimulation test and/or insulin tolerance test in both cases. The involvement of 11β-HSD1 by GH excess and PC1/3 deficiency were also excluded. Gel exclusion chromatography was then performed. POMC and pro-ACTH were detected and the aberrant ACTH/normal ACTH ratio was 42% in both cases. Conclusion: This is the first report of the presence of aberrant ACTH precursors, particularly POMC, in MAS. A high ratio of circulating ACTH to F may suggest secretion of inactive ACTH precursors in MAS. Further investigations are required to determine whether GNAS mutations or other mechanisms are involved in the presence of aberrant ACTH precursors in MAS.
SUN-274 Pituitary Macroadenoma Treated with Peptide Receptor Radionuclide Therapy in a Patient with Common Variable Immunodeficiency - Case Report
Authors: Brodowska-Kania Dorota , Saracyn Marek , Kolodziej Maciej , Kowalski Lukasz , Kaminski Grzegorz
Published: May 2020

Background: Nonfunctional adenomas comprise 25-35% of all pituitary tumors, 70-90% of these are gonadatroph cell adenomas. While ‘silent’ adenoma is the most common type of pituitary macroadenoma. The incidence of silent adenomas is estimated at 22/100000. Common Variable Immune Deficiency (CVID) is the most common primary immune disorder which is associated with neoplasia, mostly of the lymphatic or digestive system. We present probably the first case report of gonadotropinoma in a patient with CVID, treated with PRRT.

Clinical Case:

A 45-year-old man has been a patient at the Endocrinology Clinic for 12 years. Aged 33 years, he was diagnosed with a common variable immunodeficiency. The human immunoglobulin treatment was included. He also suffered from severe, spreading headaches. MRI of the head was performed. A 45mm tumor was found in the sella turcica, spreading to the sphenoid sinus. The tumor was slipped into the epidural reservois and both cavernous sinuses, causing compression of the internal carotid arteries and compressed the optic chiasm. Laboratory tests were as follows: TSH 2.18uIU/ml, LH 4.26mIU/ml, FSH 9.76 mIU/ml, ACTH 25.88pg/ml, PRL 18.34 ng/ml, HGH 3.9uU/ml, normal plasma and urine osmolality. So, the silent pituitary macroadenoma was diagnosed. Endoscopic transsphenoidal incomplete tumor resection was performed. The operation was complicated by massive parenchymal bleeding. Histopatological examination confirmed presence of pituitary adenoma, and immunohistochemical positive staining also of FSH (+), subunit alpha (+), TSH (+/-). A Ki67 proliferation index was 1%. After 12 months endoscopic reoperation was performed. The extent of operation was larger but not total. After 12 month the tumor mass increased (50x50x45mm). Imaging of somatostatin receptors by SPECT-CT was performed. It showed a heterogeneous radiolabel accumulation in the pituitary tumor. In 2010, 2 doses of 200mCi 90-Y-DOTATATE were administered with good effect. Tumor size was reduced to 20x23x25mm. The patient has had no headache for that time. Since 2011 he has also been treated with octreotide30 mg/month, with good therapy tolerance.

Conclusion:

This is probably the first description of a 12-year history of complicated but successful treatment of pituitary silent macroadenoma. It was also probably the first use of PRRT in the pituitary tumor with excellent effect. The patient remains in a very good condition, without neurological symptoms and no disorders of pituitary function.
MON-240 Histologically Proven Lymphocytic Hypophysitis with Marked Improvement on Glucocorticoid Therapy
Authors: Mathias Priyanka , Tabatabaie Vafa
Published: May 2020

Background: Lymphocytic hypophysitis (LH) is a rare autoimmune disorder characterized by lymphocytic infiltration of the pituitary gland. The disease predominantly affects women, with >50% of cases presenting during pregnancy or postpartum.1 LH is often associated with other autoimmune conditions, primarily thyroiditis, and adrenalitis.2

Clinical case: A 27-year-old female presented with secondary amenorrhea for eight months. Workup revealed hyperprolactinemia (PRL 65 ng/mL) and a heterogenous pituitary mass measuring 3.3 cm in the largest dimension. Cabergoline was initiated for a presumed prolactinoma. Laboratory evaluation was significant for hypogonadotropic hypogonadism (estradiol <50 pg/mL, progesterone <1 ng/mL, FSH 2.9 mIU/mL, LH 0.45 mIU/mL) despite normalization in prolactin. She was also found to have Hashimoto’s thyroiditis (FT4 0.7 ng/dL, TSH 8.2 uU/mL with positive TPO antibodies) and was started on levothyroxine.

Repeat imaging demonstrated a 2.4 cm heterogenous expanding sellar mass with soft tissue extension to the dorsum sella concerning for a meningioma. Visual field testing was intact without evidence of chiasmal compression. She underwent trans-sphenoidal pituitary decompression surgery which was terminated prematurely due to the presence of extensive fibrous tissue in the sella. Pathology was consistent with LH. Immunohistochemical staining was positive for lymphocytic markers CD3 and CD20, confirming marked infiltration of inflammatory B-cells and T-cells. Her postoperative course was notable for panhypopituitarism. In view of the pathological findings of LH, she was started on a high dose of 40mg of prednisone daily. Within two months, sellar magnetic resonance imaging revealed a homogenous normal-appearing pituitary with a reduction in soft tissue mass in the sellar and suprasellar region. Oral contraceptive therapy was initiated for sex hormone replacement with the resumption of menses. Prednisone was gradually tapered to 5mg/day, and she was subsequently transitioned to maintenance hydrocortisone for central adrenal insufficiency.

Discussion: LH is a rare chronic inflammatory disease that should be considered in the differential diagnosis of a non-secreting pituitary mass, especially if occurring in young women presenting during pregnancy or postpartum. The condition is associated with preferential destruction of corticotroph and thyrotroph cells.3 Appropriate management remains controversial. High dose glucocorticoid therapy, to which our patient responded to dramatically, has been shown to be beneficial in reducing mass effect. Optimal treatment involves surgical resection of the pituitary mass to decompress surrounding structures.3

References:

1. JCEM, Volume 100, Issue 10, October 2015, Pages 3841-3849

2. JCEM, Volume 80, Issue 8, August 1995, Pages 2302-2311

3. Horm Res, 2007;68 Supplement 5:145-50
SUN-185 Severe Hyponatremia and Type 4 Renal Tubular Acidosis (Functional Hypoaldosteronism) Secondary to Trimethoprim
Authors: Koh Yun Qing , Hoe Kian Ming Jeremy , Quek Timothy Peng Lim
Published: May 2020

Introduction:

Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. We present a case of severe hyponatremia and Type 4 renal tubular acidosis (functional hypoaldosteronism) in a patient treated with TMP-SMX.

Clinical Case:

A 62 year old gentleman with hypertension, dyslipidemia and a surgically repaired abdominal aortic aneurysm developed an aortic graft infection. He was admitted to hospital for acute right lower limb ischemia with embolic phenomena, and underwent surgical graft explantation. He required multiple courses of antibiotics post operatively.

He was initially referred to Endocrinology for severe hyponatremia, deemed likely to be from a salt losing nephropathy secondary to polymyxin. Thyroid function and morning cortisol levels were normal. He was managed with intravenous hypertonic saline and oral salt tablets. The hyponatraemia resolved a week after polymyxin was stopped.

Intravenous TMP-SMX was commenced the next day at 240 mg BD. A week later, the hyponatremia recurred, with concomitant hyperkalemia and a normal anion gap metabolic acidosis.

The serum sodium was 126 mmol/L (reference interval (RI) 135-145) and the serum osmolality 275 mmol/kg (RI 275- 305). Urine studies showed a high urinary sodium (154 mmol/L) and osmolality (481 mmol/kg), consistent with renal salt wasting. The serum potassium rose to a peak of 6.1 mmol/L (RI 3.5 - 5.0), with a normal anion gap metabolic acidosis (bicarbonate 17 mmol/L (RI 21 – 31)). A paired urine pH of 8 pointed to an inability to acidify the urine.

Given the clinical course and laboratory investigations, the diagnosis of TMP-associated hyponatremia and Type 4 RTA was made. Oral resonium was started to correct hyperkalemia, with a combination of oral sodium chloride and sodium bicarbonate used to treat the hyponatremia and metabolic acidosis. Fludrocortisone was not used given the concerns of causing hypertension in a patient with a diseased aortic graft.

The dose of TMP-SMX was gradually reduced with improvement of the acid-base and electrolyte abnormalities, lending weight to our diagnosis. After the dose of the TMP-SMX was reduced to 80 mg BD, the hyperkalemia and metabolic acidosis resolved. The oral sodium chloride and sodium bicarbonate were gradually tailed off and stopped after cessation of the TMP-SMX.

Clinical Lesson:

Trimethoprim blocks the epithelial sodium channel (ENaC) of the principal cells in the terminal portion of the nephron, similar to potassium sparing diuretics like amiloride and triampterene. The resulting hyponatremia, hyperkalemia and metabolic acidosis can be life threatening. Therefore, monitoring of electrolytes and acid base status is important, particularly in susceptible patients or in those where a high dose of trimethoprim is required.
OR33-04 The Effect of Adiposity on the Fasting Serum Proteome in Normal Weight and Obese Men
Authors: Harshman Stephanie Geris , McCormack Shana Erin , Zhang Zhe , Maso Ana Aulinas , Lawson Elizabeth Austen
Published: May 2020

In many individuals with obesity, adipose tissue is not only increased in mass but also exhibits altered function. Disordered adipokine secretion contributes to a pro-inflammatory milieu that may lead to obesity-related co-morbidities. Hypothesis-generating, high-throughput techniques can generate novel insights. Our objective was to identify proteome-wide alterations in serum proteins related to adiposity. We evaluated the fasting serum proteome in 25 men [13 normal weight (mean±SD body mass index (BMI 21.2±1.4 kg/m2) and 12 with obesity (BMI 31.5±4.8 kg/m2)]. Blood was drawn at 0, 15, 30, and 55 minutes for proteomic analysis after an overnight fast (SOMAScan, SomaLogic, Inc.). The number of proteins and pathways that significantly differed between the two groups was determined across all time points during the fasting period. Normalized protein levels were compared between adiposity groups using rank product testing. Overrepresentation of protein constituents of established biological pathways was evaluated by hypergeometric test. P-values were adjusted using the Benjamini-Hockberg method, and those with an associated false discovery rate (FDR) of <0.05 were considered statistically significant. A total of 4,785 protein isoforms were robustly identified in serum of normal weight and men with obesity, of which 226 protein isoforms were significantly higher in obesity (vs. normal weight), and 178 were significantly lower in obesity (vs. normal weight). Higher levels of leptin and lower levels of IGFBP1 and IGFBP2 were observed in individuals with obesity during fasting (all FDR < 0.019). Functional annotation using Gene Ontology indicated that the following pathways differed most between obese vs. normal weight men: complement and coagulation cascade activation, amine metabolism, phosphatase activity, cellular response to nutrients (lipids, alcohol, and vitamin D), organic acid catabolism, and regulation of inflammatory responses. The protein isoforms identified in serum likely reflect systemic tissue-level changes in metabolism that may yield insights into the pathogenesis of obesity-related comorbidities and rational targets for intervention.
SUN-012 Role of Leptin-Receptor Expressing Cells in the Pathogenesis of Polycystic Ovary Syndrome (PCOS)
Authors: Cara Alexandra , Burger Laura Lynn , Myers Martin Grosvenor , Gendt Karel De , Moenter Sue , Elias Carol F
Published: May 2020

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, and is characterized by hyperandrogenism, oligo/anovulation, and/or polycystic ovaries. Many women with PCOS also suffer from adverse metabolic phenotypes, including central adiposity, insulin resistance, and glucose intolerance, which can exacerbate reproductive dysfunction. Androgens can act upon androgen receptors (AR), which are expressed in many reproductive and metabolic tissues, and contribute to the pathogenesis of PCOS. AR are highly expressed in the neuroendocrine hypothalamus in areas which regulate the hypothalamic-pituitary-gonadal axis and contribute to the central regulation of metabolism. Many phenotypes of PCOS can be modelled in rodents by administration of the non-aromatizable androgen dihydrotestosterone (DHT) during critical periods of development. Neuronal AR is key in the development of PCOS, as female mice with neuronal AR deletion who are exposed to androgen excess are protected against development of anovulation, polycystic ovaries, and metabolic abnormalities. Yet it is not known which populations of neurons confers this protection. We hypothesize that leptin-receptor (LepR) neurons participate in the pathogenesis of PCOS, as sub-populations of LepR neurons co-express AR in the hypothalamus, and LepR neurons are critical in the central regulation of energy homeostasis, and exert permissive actions on puberty and fertility. We have pre-natally androgenized (PNA) a mouse model of AR deletion specifically in LepR cells (LepRΔAR) and are conducting reproductive and metabolic phenotyping. As previously demonstrated, control PNA females show long periods of acyclicity, whereas LepRΔAR PNA female mice show a similar number of days in each stage of the estrous cycle, number of cycles, and cycle length as vehicle treated LepRΔAR females. Our findings indicate that a subpopulation of AR/LepR cells mediate the effects of prenatal androgen excess on female estrous cycles in a mouse model of PCOS-like phenotype.
MON-081 Mathematical Modeling of Residual Endogenous FT4 Synthesis and Exogenous L-Thyroxine Administration over the First 2 Years of Life in Infants with Congenital Hypothyroidism
Authors: Leroux Stéphanie , Marc Pfister , Welzel Tatjana , Gächter Pascal , Konrad Daniel , L’Allemand Dagmar , Szinnai Gabor , Koch Gilbert
Published: May 2020

L-Thyroxine (L-T4) is the treatment of choice of congenital hypothyroidism (CH). Longitudinal measurements of free T4 (FT4) serum concentrations were collected over the first two years of life with oral L-T4 treatment in infants with CH. Purpose of this study was to develop an integrated mathematical model to characterize the kinetics of exogenous L-Thyroxine (L-T4) after multiple dosing in infants with CH, and the dynamics of residual endogenous FT4 synthesis under treatment in the context of severe, moderate and mild disease.

A total of 200 FT4 concentrations from 30 patients were available for analysis. At start of treatment, mean (standard deviation [SD]) postnatal age and weight of the population were 11 (8) days and 3.9 (1.3) kg. Mean (SD) pretreatment FT4 concentration was 11.3 (7.4) pmol/L. Measured FT4 concentrations were modelled as sum of residual endogenous FT4 and exogenously administered FT4 (L-T4). The integrated mathematical model consists of an absorption compartment for the exogenous FT4 administration, and a central compartment for measured FT4 with linear elimination. Hence, for residual endogenous and exogenous FT4 the same elimination rate constant was assumed. For the residual endogenous synthesis, different approaches were tested: a constant production and typical time-dependent production functions. FT4 data were analyzed using nonlinear mixed-effects modeling.

The integrated mathematical model with a time-dependent non-linear Emax function describing a decreasing residual endogenous FT4 synthesis for increasing time provided the best data fit in terms of Akaike value and various goodness-of-fit plots. This is in line with the expected progressive suppression of the thyroid stimulating hormone by the exogenous FT4, and the subsequent decrease of residual FT4 endogenous synthesis. The developed mathematical model allows simulation of FT4 pharmacokinetic profiles for different disease severities and different dosing regimens.