Abstract Disclosure: L.M. Vasquez: None. J.M. Bruder: None. M. Koops: None. J. Trejo: None. Background: Extramedullary hematopoiesis is frequently seen in non-osseous locations but not endocrine organs, this is a case of hematopoesis in a thyroid nodule. Clinical Case: A 79-year-old man with myelofibrosis diagnosed at age 66, CAD post CABG, atrial fibrillation on anticoagulation and HFrEF was referred to the endocrinology clinic due to enlarging left lobe thyroid nodule. He was diagnosed with a goiter at age 72 but denied compressive symptoms. He had no history of radiation to his neck or family history of thyroid cancer. On physical exam, the left thyroid lobe was visibly enlarged with slight right tracheal deviation without lymphadenopathy. TSH level was normal. Thyroid ultrasound demonstrated a 6.4 x 4.0 x 4.8 cm, complex cystic-solid, taller than wide nodule in the left lobe and a sub-centimeter cystic nodule in the right lobe. FNA showed hematopoietic elements, including maturing cells in three lineages of hematopoiesis. On repeat ultrasound 5 years later. The left nodule increased in size to 7.3 x 5.4 x 4.4 cm and highly suspicious (TR4 and TR3) by Ti-RADS criteria. Repeat FNA of the nodule showed many red blood cells with few hematopoietic cells, flow cytometry did not show any abnormal populations. No thyroid follicular cells were reported. Myelofibrosis was diagnosed by bone marrow biopsy many years prior. He had maintained a stable CBC without palpable spleen or hepatomegaly. Given this history without thyroid dysfunction or reported symptoms, surgery was not pursued. External beam radiation was a treatment option should the nodule cause symptoms. He continued to have mild anemia not requiring blood transfusions. He passed away 2 years later in hospice care after hospitalization for severe heart failure decompensation. Conclusion: Extramedullary hematopoiesis involving the thyroid is rare but has been reported(1). This type of extramedullary hematopoiesis. can be treated with surgery or low-dose radiation because of the radiosensitivity of hematopoietic tissue (2). This was a potential treatment modality if compressive symptoms arose, but they did not. This case illustrates a situation in which surgical intervention on highly suspicious nodules would not have been the optimal treatment choice. Reference: 1. Jan I., Weng M., Wang C., et al. Extramedullary hematopoiesis involving the thyroid: A rare cytologic finding in otherwise healthy patients and review of literature. Journal of the Formosan Medical Association. (2018) 117, 1108-1114. 2. Taher A, Vichinsky E, Musallam K et al., authors; Weatherall D, editor. Guidelines for the Management of Non-Transfusion Dependent Thalassaemia (NTDT) [Internet]. Nicosia (Cyprus): Thalassaemia International Federation; 2013. Chapter 11, EXTRAMEDULLARY HEMATOPOIESIS. Available from: https://www.ncbi.nlm.nih.gov/books/NBK190455/ Presentation Date: Saturday, June 17, 2023

Abstract Background: Although suprasellar and cavernous sinus invasion are common in giant prolactinomas, intra-orbital extension is extremely uncommon [1]. Even less reported are cases of giant prolactinomas causing cerebral ischemia or death. Clinical Case: A 51-year old woman presented to the ED with confusion, right-sided weakness and severe left eye proptosis with loss of vision. Five years prior, she underwent a partial transphenoidal resection for a macroprolactinoma due to acute vision changes with compression of the optic chiasm. Prior to surgery, prolactin level was elevated to 2,106 ng/mL (n 2.4-24.0 ng/mL). Post-operative MRI showed residual 2.7 x 3.1 x 2.6 cm mass. Thereafter she was prescribed cabergoline which she self-discontinued three years later. MRI of the brain at time of presentation demonstrated a 10.1 x 6.4 x 4.3 cm sellar/suprasellar mass extending into the left orbit causing severe proptosis and mass effect on the left frontal lobe, temporal lobe, midbrain, and basilar artery with encasement of the left cavernous internal carotid artery. A recent left striatocapsular infarct due to compression of the left middle cerebral artery was present. Prolactin level was elevated to 16,487 ng/mL. Neurosurgery was consulted and recommended medical management. Free thyroxine level was low and thyroid hormone replacement was started. Although the cosyntropin stimulation test showed an appropriate cortisol level peak of 21.5 mcg/dL, she was given stress dose glucocorticoids. Bromocriptine was initially started and titrated and later changed to cabergoline. Six weeks after discharge, she was readmitted with worsening confusion and seizure activity. On day 2 of admission, she decompensated. New hemorrhage inside the mass with increased vasogenic edema and a midline shift was discovered on a head CT. She underwent emergent craniotomy with surgical debulking of the tumor. Unfortunately, her mental status did not improve post-operatively. She was transitioned to hospice care and died 7 days after surgery. Surgical pathology showed a lactotroph adenoma with markedly elevated Ki67 proliferation index of 20-30%. Conclusion: This case demonstrates an unusually aggressive macroprolactinoma causing severe proptosis, ischemic stroke and death and adds to the very few cases previously reported [2]. References: 1. Karcioglu ZA, Aden LB, Cruz AA, Zaslow L, Saloom RJ. Orbital invasion with prolactinoma: a clinical review of four patients. Ophthalmic Plast Reconstr Surg. 2002 Jan;18(1):64-71. 2. Navarro-Bonnet J, Martínez-Anda JJ, Balderrama-Soto A, Pérez-Reyes SP, Pérez-Neri I, Portocarrero-Ortiz L. Stroke associated with pituitary apoplexy in a giant prolactinoma: a case report. Clin Neurol Neurosurg. 2014 Jan;116:101-3.

Abstract Background: Adrenal cortical carcinoma is a rare neoplasm. Adrenal cortical carcinoma has previously been reported in less than 10 cases of patients with Neurofibromatosis Type I. Clinical Case: A 44-year-old Hispanic man with Neurofibromatosis Type I (NF1) presented with progressive hypoxia, tachypnea and abdominal pain. Intubation was required with 100% FiO2. CT angiogram of the chest and abdomen showed a 9.5 cm left adrenal mass with tumor thrombus in the left adrenal vein, distal left renal vein, IVC extending into the right atrium, suggestive of an adrenocortical carcinoma. Café-au-spots, neurofibromas and Lisch nodules were seen on physical exam but no signs suggestive of a functional adrenal cortical carcinoma. Transthoracic echocardiogram demonstrated a large well circumscribed echo-dense mass filling the right atrial cavity. Hemodynamically he was unstable with labile blood pressures due to right atrium thrombus burden. He was supported pending pheochromocytoma investigation. Biochemical work up revealed an elevated 24-hour free cortisol concentration of 95.9 ug/d (<=60ug/d) with a normal 24-hour urine metanephrine and normetanephrine [140ug/d (55-320ug/d) and 448 ug/d (114-865ug/d]. Plasma free metanephrine level was normal 0.43 (0.00-0.49nmol/L) and the normetanephrine levels was increased at 2.7 (0.00-0.89nmol/L) consistent with stress response. Serum aldosterone level and renin activity with potassium and DHEA-S levels were normal. Once pheochromocytoma was ruled out, he successfully underwent a left nephrectomy, left adrenalectomy, IVC thrombectomy, right atrium thrombectomy under a multidisciplinary team of surgeons. Surgery was well tolerated and he was discharged home 11 days later. Pathology confirmed adrenal cortical carcinoma, stage 4, with involvement of endocardium and left renal vein with mitotic count greater than 20/50 high-power fields, consistent with a high-grade tumor. Summary: Patients with NF1 have a higher predilection to develop tumors including pheochromocytoma, paraganglioma, gastrointestinal stromal tumor, and pancreatic neuroendocrine tumor. NF1 association with adrenal tumors is well known, most commonly pheochromocytomas which occur in 0.1–5.7% of patients with NF1. However, based on a literature search there have been less than 10 case reports which postulate an association between NF1 and ACC. Genetic analysis of these reported cases suggest a loss of heterozygosity at the NF1 locus as a possible explanation of development of ACC in patients with NF1. Conclusion: Adrenal cortical carcinoma is rare but should be considered in a patient with NF1 and adrenal mass when plasma/urine metanephrines are not suggestive of pheochromocytoma.

Purpose This work aimed to evaluate genotype-phenotype associations in individuals carrying germline variants of transmembrane protein 127 gene (TMEM127), a poorly known gene that confers susceptibility to pheochromocytoma (PHEO) and paraganglioma (PGL). Design Data were collected from a registry of probands with TMEM127 variants, published reports, and public databases. Main Outcome Analysis Clinical, genetic, and functional associations were determined. Results The cohort comprised 110 index patients (111 variants) with a mean age of 45 years (range, 21-84 years). Females were predominant (76 vs 34, P < .001). Most patients had PHEO (n = 94; 85.5%), although PGL (n = 10; 9%) and renal cell carcinoma (RCC, n = 6; 5.4%) were also detected, either alone or in combination with PHEO. One-third of the cases had multiple tumors, and known family history was reported in 15.4%. Metastatic PHEO/PGL was rare (2.8%). Epinephrine alone, or combined with norepinephrine, accounted for 82% of the catecholamine profiles of PHEO/PGLs. Most variants (n = 63) occurred only once and 13 were recurrent (2-12 times). Although nontruncating variants were less frequent than truncating changes overall, they were predominant in non-PHEO clinical presentations (36% PHEO-only vs 69% other, P < .001) and clustered disproportionately within transmembrane regions (P < .01), underscoring the relevance of these domains for TMEM127 function. Integration of clinical and previous experimental data supported classification of variants into 4 groups based on mutation type, localization, and predicted disruption. Conclusions Patients with TMEM127 variants often resemble sporadic nonmetastatic PHEOs. PGL and RCC may also co-occur, although their causal link requires further evaluation. We propose a new classification to predict variant pathogenicity and assist with carrier surveillance.

Abstract Gender affirming hormone therapy (GAHT) is the mainstay of long-term management of transgender individuals. In transwomen, treatment with physiologic doses of estrogen alone is often insufficient to suppress testosterone to the desired level. Although GnRH agonist therapy is usually prescribed for puberty suppression in trans youth, in adult transwomen, GnRH agonist may be added. The durability of long-term GnRH agonist in lowering testosterone as well as the long-term safety is not clear. We examined the effect of leuprolide a GnRH agonist, on testosterone as well as clinical and metabolic features in transwomen Veterans. Out of 91 subjects with gender dysphoria followed at a VA Endocrinology clinic, 65 were transwomen (age 49 ± 3 years) who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol). We performed a retrospective cohort study of the 31 (48%) transwomen on Leuprolide (3.375mg q month) and 33 transwomen who were not on Leuprolide. Plasma testosterone, lipid profile, were analyzed before, 6 months, 1 year and at the last follow-up visit. The median follow-up of subjects on Leuprolide was 2.7 (1.7-3.8) years. Plasma testosterone concentration declined by 89% from 432±32 ng/dl to 47±9 ng/dl within 3-6 months after initiation of GnRH agonist treatment. Plasma testosterone remained persistently low 39±4ng/dl at 1 year and at the end of 2.7 yrs, most subjects on Leurprolide had plasma testosterone concentration <50ng/dl. Leuprolide therapy led to similar rapid decline in testosterone concentration in both younger (<40yrs) or relatively older (>50yr) transwomen. Leuprolide was in general well tolerated requiring discontinuation in just one patient due to severe fatigue. Three subjects (10%) experienced hot flashes which did not lead to discontinuation of medication. In the non-Leuprolide group, of 33 subjects, the follow-up was relatively inconsistent and only 12 subjects were regularly followed throughout a year with stable treatment. The decline in plasma testosterone was of a lower magnitude versus the leuprolide group (55% vs 89%, p <0.05). The testosterone levels declined from 393±42 to 180±44 ng/dl at 6 months. Body weight, and lipid profile: triglyceride, and plasma HDL concentration did not change significantly with or without GnRH agonist therapy. In conclusion, GnRH agonist therapy led to a sustained suppression of plasma testosterone levels in transwomen and was not associated with worsening lipid profile, was effective, and well tolerated in transwomen regardless of their age and may be considered an adjunct to the ant-androgen and estrogen therapy.

Clinical ThyroidologyVol. 32, No. 7 Case Report“An Unusual Case of Abnormal Thyroid Function Tests”Lyan Gondin, Gustavo Armaiz, Jonathan Trejo, Devjit Tripathy, Jan M. Bruder, and Maureen KoopsLyan GondinUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A.Search for more papers by this author, Gustavo ArmaizUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A.Search for more papers by this author, Jonathan TrejoUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A.Search for more papers by this author, Devjit TripathyUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A.Search for more papers by this author, Jan M. BruderUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A.Search for more papers by this author, and Maureen KoopsSouth Texas Veterans Affairs (VA) Healthcare System, Audie L. Murphy VA Hospital, San Antonio, Texas, U.S.A.Search for more papers by this authorPublished Online:9 Jul 2020https://doi.org/10.1089/ct.2020;32.351-354AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 32Issue 7Jul 2020 InformationCopyright 2020 American Thyroid Association, Inc.To cite this article:Lyan Gondin, Gustavo Armaiz, Jonathan Trejo, Devjit Tripathy, Jan M. Bruder, and Maureen Koops.“An Unusual Case of Abnormal Thyroid Function Tests”.Clinical Thyroidology.Jul 2020.351-354.http://doi.org/10.1089/ct.2020;32.351-354Published in Volume: 32 Issue 7: July 9, 2020PDF download

Abstract Recently, cluster analysis has been used to classify adult onset diabetes based on pathophysiologic profile. Using autoimmunity status, BMI, insulin resistance, and beta cell function, this classification system can predict diabetes associated complications. Individuals with primarily insulin resistant phenotype have been associated with increased incidence of nephropathy while those with insulin deficient phenotype are associated with retinopathy. Clinically, patients with severe insulin resistance can be defined as those who require high doses of insulin to achieve glycemic control, such as patients on U-500 insulin requiring more than 200 units of insulin a day. To characterize the clinical and metabolic phenotype of insulin-resistant patients from a South Texas VA diabetes clinic, we evaluated presence of macro or microvascular complications and beta-cell autoimmunity and function in this population. A retrospective cohort study was completed at the South Texas VA Diabetes Clinic. Charts were reviewed for anthropometric measurements, presence of macro and microvascular complications, anti-diabetic medication, lipid profile and HbA1c over 3 visits, autoimmunity (anti-GADab), and beta-cell function (fasting C-peptide). Patients with insulin doses >200 U/day or on U-500 insulin were categorized as “severe insulin-resistant”. Those with insulin doses < 0.5 U/kg/day were categorized as “mild insulin resistance” as a control group. Out of 120 patients, 30 met criteria for severe insulin resistance (n=30, M/F=29/1 age 61±1.6 years (yr), BMI 41±0.9 kg/m2, duration of diabetes 18.3±0.3 yr, HbA1c -8.4±0.2%, total daily insulin dose (TDD) 301±31U). 30 patients with insulin use <0.5 U/kg/day met criteria for mild insulin resistance (N=30, M/F: 28/2, age 62±2 yr, BMI 30±1 kg/m2, duration of diabetes 12±1.2 yr, HbA1c 7.2±0.2%, TDD 17±2U). Prevalence of nephropathy was higher in the insulin resistant group vs the mild insulin resistant group (76% vs 43%, p<0.05). There was no difference in prevalence of retinopathy (p=0.095) or CAD (p=0.6) between the groups. There was no difference in use of ACE-i or SGLT-2i between the groups. Insulin resistant subjects had a higher plasma triglyceride (325±0.3 vs 202±0.3 mg/dl, p=0.04). Prevalence of GAD ab was not different between the groups (3% vs 0%). Fasting C-peptide concentrations were similar in both groups (5.6±0.3 vs 5.2±0.25 ng/ml, p=0.3). HbA1c in the insulin resistant group improved between visits 1 and 3 (p<0.01). Weight increased over three visits in the severe insulin resistant group as opposed to mild weight loss in the mild insulin resistant group. Our results support the high prevalence of diabetic nephropathy in patients with severe insulin resistance, although it is unclear that insulin resistance is the etiology. Long-term follow up of these patients may provide insight into the underlying mechanisms of these complications.

Abstract Recently a cluster-based classification of disease phenotypes has been developed as a tool to aid in improved characterization and management of diabetes. The majority of these studies have been completed in European populations, but it is unclear if these are applicable to other populations. Using these cohorts, we categorized patients in a South Texas VA diabetes clinic to evaluate if these phenotypes apply to that population. A retrospective cohort study was completed from August 2019 through October 2019, in which 120 patients’ records in the Audie Murphy VA Diabetes Clinic were reviewed for presence of macro and microvascular complications, type of anti-diabetic medication, lipid profile and HbA1c levels, and fasting C-peptide and GADab status. 86 patients who had anti-GADab and C-Peptide levels measured were then stratified into diabetic phenotype cohorts as defined by Ahlqvist et al. 2018, based on presence of diabetes associated autoantibodies, fasting C-peptide level, insulin use >200 U/day, BMI, and age >65. Six subjects belonged to the Severe Autoimmune Diabetes (SAID) cohort, with average GADab 713±301IU; 66% of the cohort had nephropathy, 33% had retinopathy. The Severe Insulin Deficiency (SIDD) cohort had 9 patients, with average fasting C-peptide of 0.58±0.08ng/ml, 44% of the cohort had retinopathy, nephropathy and CAD as complications. The Severe Insulin Resistant (SIRD) cohort had 26 patients; fasting C-peptide was 4.94±0.43ng/ml, 73% had nephropathy, 38% retinopathy and 46% CAD. The Mild Obesity Related (MOD) cohort had 35 patients with average BMI of 35±0.6 kg/m2 and average A1c 7.9±0.2%. Nephropathy was the most prevalent complication, present in 49% of the cohort. The Mild Age Related (MARD) cohort had 10 patients, with average age of 71±1.0 years, with nephropathy and CAD present in 66% of the cohort. The highest gross prevalence of nephropathy was in the SIRD cohort, whereas highest prevalence of retinopathy was in the SIDD cohort, both of which are concordant with the recently reported study, although not statistically significant (p=0.28 and 0.65, respectively). There was no difference in prevalence of CAD between the different categories of diabetes. These findings in a South Texas VA diabetes clinic population reflect agreement in diabetes associated complications in clusters of diabetes based on insulin resistance and insulin deficiency. Targeted intensification of therapy based on the major underlying pathophysiologic abnormalities may delay or prevent micro and macrovascular complications. 1. Ahlqvist E, et al. Novel Subgroups of Adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Endocrinology and Diabetes. 2018;6: 361-369.

Abstract Parathyroid carcinomas have an estimated prevalence of <0.1% of all cancers and is found in <1% of patients with primary hyperparathyroidism (PHPT). While they frequently present with PTH- mediated hypercalcemia, they are often distinguished by severe hypercalcemia and markedly elevated PTH levels compared to their benign counterparts. Parathyroid cancers most often arise from existing parathyroid glands, making them identifiable with standard imaging modalities such as parathyroid sestamibi scan, thyroid ultrasound, and 4-D CT scan. There are reports of non-functioning parathyroid carcinomas, including those that are intrathyroidal. Most of the reported cases are found de novo. We present a case of an intrathyroidal parathyroid carcinoma with intermittent hypercalcemia. A 72-year-old man with a history of Graves’ disease and RAI ablation in the 1970’s was found to have hypercalcemia up to 14.1 mg/dL (8.5 - 10.1) with a PTH level of 223 pg/mL (14 - 64). He denied any constipation, bone pain, fractures, renal stones, or changes in mental status. Thyroid ultrasound demonstrated a 3.9 cm R lobe complex nodule reported as TI-RADS 4, and a hypoechoic 1.0 cm nodule in the L lobe. No definitive parathyroid adenoma was reported. A parathyroid sestamibi scan showed persistent uptake in area of the L 1.0 cm nodule favoring a PTH adenoma while the R nodule had initial radiotracer uptake with delayed washout but no technetium uptake. Laboratory evaluation demonstrated a 24-hour urinary calcium of 338 mg/24hr, low 25-OH vitamin D, and normal vitamin D 1,25 levels. Osteoporosis was diagnosed by BMD with T-score of -3.2 at the femoral neck. Repeat serum corrected calcium level was 9.7 mg/dL and PTH was 93 pg/mL. FNA cytology of the R thyroid mass was reported as benign thyroid tissue. Due to size of the R thyroid nodule, the patient underwent a R hemithyroidectomy with L parathyroidectomy. Intraoperative PTH levels decreased from 154 to 120 pg/mL after removal of L parathyroid adenoma; PTH level decreased further to 12.9 pg/mL after R hemithyroidectomy. Surgical pathology revealed 4.5 cm R parathyroid carcinoma without thyroid tissue with positive margins, and a hypercellular L parathyroid gland. PHPT resolved. After review of all aspects of the case and discussion with patient, the decision was made to monitor his calcium and PTH levels and repeat BMD 1 year from resection. This is an uncommon presentation of a rare endocrine malignancy. To our knowledge, there are few case reports of non-functional parathyroid carcinomas that were initially reported as thyroid cancer or benign thyroid tissue after biopsy. This report underscores the importance in keeping this rare diagnosis in the evaluation of PTH-mediated hypercalcemia.

Pheochromocytomas/paragangliomas (PHEOs/PGLs) are frequently heritable catecholamine-secreting, neuroendocrine tumors. More than 15 distinct genes cause PHEO/PGL predisposition, including the TMEM127 tumor suppressor gene, a transmembrane protein of unknown function. The clinical spectrum, disease severity and risk of other tumors has not been well established in TMEM127-associated disease. This information is critically important for risk assessment and follow up of probands and mutation-carrier relatives. Goal: The objective of this study is to identify clinical and genetic features of patients with germline TMEM127 mutations and begin to delineate genotype-phenotype associations of relevance for clinical and follow up surveillance. Methods: Demographic and clinical data, including tumor type and location, family history, age at diagnosis, plasma and/or urine catecholamine and/or metanephrine levels, and mutation status were obtained from medical records and/or literature of patients identified with TMEM127 gene nonsynonymous variants. Results: 97 index patients (28 males/50 females/19 unreported) were identified with a germline TMEM127 variant. The most common clinical presentation was PHEO (n=72, 74.2%), followed by PGL (n=6, 6.1%) and renal cell carcinoma (RCC n=5, 5.1%). In addition, three patients presented with both PHEO and PGL (3%), two of which were head and neck PGL, and three other patients had combined PHEO and RCC (3%). The median age at diagnosis was 43.8 years (range, 9 months to 80 years). Twenty-five patients had multicentric presentation, mostly due to bilateral pheochromocytoma (20/25 patients, 80%). Familial history of PHEO/PGL was present in 13 patients and five individuals developed metastatic PHEO. Of those with available biochemical data, tumors secreted predominantly epinephrine (n=14/26, 53.8%), although norepinephrine- (n=2) and dopamine- (n=1) secreting tumors were also detected, and one tumor was non-secreting. In total, 70 distinct variants were identified. Most had a single occurrence (n= 56/70 80%), but 14 variants were detected more than once (2-7 times). Most mutations led to a truncated product including indels, splice site or nonsense variants (56.3%), while 43.6.% were missense. Approximately half of the missense mutations occurred within transmembrane domains. Conclusion: The most common presentation of TMEM127-associated disease is a single PHEO in patients older than 40y, similar to sporadic disease, as previously suggested. However, the frequency of PGLs and malignant disease is higher, while penetrance is lower, than previously reported. This information will be relevant for clinical surveillance strategies for affected individuals and their high-risk relatives.

Background: Long-term effects of gender-affirming hormonal therapy (GAHT) on cardiovascular risk factors and metabolic syndrome (MS) is currently unclear. Particularly, the effect of GAHT on cardiovascular outcomes in older individuals (>60 years) with gender dysphoria (GD) is unknown. The aim of this study was to examine the effect of GAHT on cardiovascular risk factors, MS and the incidence of T2DM in subjects with GD. Methods: We reviewed the records of 75 subjects with GD, 54 transwomen (age 49 ± 2 years) and 21 transmen (age 37 ± 2 years), who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol) of which 55 were followed for at least 1 year. MS was defined based on ATP III criteria. As a control group, we reviewed the records of 30 subjects without GD who attended the endocrinology clinic for other hormone-related disorders. Results: The median (IR) follow-up was 22 (11-39) months for transwomen and 15 (11-21) months for transmen. In transwomen plasma testosterone levels decreased (379 ± 31 vs 71 ± 18 ng/dL), estradiol increased (40 ± 7 vs 124 ± 34 pg/mL) while the plasma testosterone levels increased in transmen (57 ± 14 vs 411 ± 79 ng/dL). At baseline, 24% of transwomen had MS and after 1 year, 16% of subjects had MS. In transmen, the prevalence of MS was similar before and 1 year after treatment (25 % vs. 24%). In transwomen, GAHT was associated with mild weight gain, BMI increased (29 ± 1 vs. 30 ± 1 kg/m2, p=0.04). There was no difference in HDL, total cholesterol and triglyceride levels before and after hormone therapy, though LDL cholesterol tended to decrease (101 ± 6 vs. 90 ± 6 mg/dL, p=0.06). There was no change in HbA1C, FPG or SBP in transwomen, though DBP decreased (77 ± 1 vs. 74 ± 1 mmHg, p=0.05). In transmen, no changes were observed in BMI, HDL, total cholesterol, triglycerides, LDL, HbA1C, FPG and blood pressure. There were no new cases of T2DM, however 1 transman developed MS, 1 transman had CABG and 1 transwoman died from laryngeal cancer. There were no new cases of myocardial infarction or stroke in subjects with and without GD. For subjects above 60 years (n=16, 13 transwomen and 3 transmen), BMI in transwomen increased (27 ± 1 vs. 29 ± 2 kg/m2, p=0.03), there was no change in HDL, LDL and total cholesterol, triglycerides, HbA1C, FPG or blood pressure. In 3 transmen older than 60 years old, only the LDL decreased (194 ± 59 vs. 141 ± 55 mg/dL, p=0.006). In the entire group as well as older individuals with GD the incidence of CV events were not different from the control group. Conclusion: GAHT for 1.5 years was not associated with worsening cardiovascular risk factors, metabolic syndrome or incidence of T2DM in both transmen and transwomen regardless of their age. Long-term studies are required to assess the definite effects of GAHT on cardiovascular outcomes.

BACKGROUND Hypercalcemia associated with chronic myeloid leukemia (CML) is an ominous sign. Although rare, several cases have been reported and multiple pathophysiologic mechanisms have been independently proposed. We present a patient case and a literature review of the clinical presentation and mechanisms of CML-associated hypercalcemia. CASE REPORT A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia. On physical examination, we observed tachycardia, altered mental status, and dehydration. Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL). His chest CT scan showed diffuse lytic lesions and bone destruction concerning for diffuse bone marrow involvement. The patient was diagnosed with hypercalcemia in the context of a CML blast phase. Treatment with hydration, calcitonin, and zoledronic acid lead to control of his symptoms and normalization of his serum calcium levels. After discharged, the patient was maintained on palliative treatment and zoledronic acid management without new episodes of hypercalcemia. However, eight months later, the patient died. CONCLUSIONS Evidence from the literature demonstrates a highly variable clinical presentation of CML-associated hypercalcemia, commonly occurring during an accelerated or a blast phase, and associated with poor survival. Multiple mechanisms could be involved and are not exclusive of each other. Better understanding of the pathophysiologic mechanisms involved in CML-associated hypercalcemia could lead to improvement in clinical and laboratory evaluation of these patients and be the foundation for the development of better management strategies and possibly target-directed therapy to positively improve prognosis.

A 55-year-old African American woman was referred for management of uncontrolled diabetes. She was diagnosed with type 2 diabetes (T2D) when she was 44 years old during a routine physical exam and initially was started on metformin. After 2 years, glyburide was added, and 4 years later, glargine insulin was initiated following hospitalization for hyperglycemia with ketosis. She was discharged home on insulin, metformin, and glyburide. She reported that her glycemic control was still poor and she experienced wide swings in her glucose values, ranging from 60 to 400 mg/dL (3.3–22.2 mmol/L). At presentation, she was on glipizide, metformin, glargine, and premeal aspart insulin. On further questioning, she revealed that she had a history of hypothyroidism and pernicious anemia. Her vitamin B12 deficiency was so severe that it led to myelopathy and permanent weakness in her lower extremities. She has been on B-12 and levothyroxine. She denied skin pigmentation or history of adrenal insufficiency. Her other medications included simvastatin and lisinopril. She had a family history of T2D in both parents, but she denied any family history of other autoimmune diseases.