To describe our Center's 8-year experience with subcutaneous testosterone (SC-T) as gender-affirming hormone therapy (GAHT) in transmasculine and gender-diverse (TM/GD) youth. Methods: An Institutional Review Board (IRB)-approved retrospective study for 119 TM/GD subjects who started SC-T at age 13-19 and received SC-T for > 6 months between 2012 and 2020. Results: SC-T was typically started at 25-50 mg biweekly and dose was escalated at provider's discretion. Over 96% of subjects were on 100-320 mg monthly (divided weekly or biweekly) at last follow-up. There was an overall increase in mean total and free testosterone (T) over the dose range ( p = 0.003), with mean total and free T levels of 460 ng/dL and 92 pg/mL, respectively, at a monthly SC-T dose of 200 mg. For subjects on SC-T without additional menstrual suppression, 54% had cessation of menses at 140 mg monthly and 97% at 200 mg monthly. On average, menses stopped 4.7 (standard deviation 3.0) months after starting SC-T. There was a decrease in high-density lipoprotein and increase in hematocrit from baseline to follow-up. Body mass index Z-scores did not change significantly with treatment. Mild acne was common; severe acne and significant injection site reactions were uncommon. Sustained hypertension, transaminitis, and dyslipidemia were infrequent. Conclusions: SC-T is well tolerated and effective in reaching recommended T levels and stopping menses in TM/GD youth. Occurrence of serious adverse effects is low and inability to tolerate injections is very uncommon. SC-T is a safe and effective alternative to intramuscular testosterone in initiation and maintenance of GAHT in TM/GD youth.

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Neonatal diabetes mellitus (NDM) is a rare condition that presents with diabetes in the first few months of life. The treatment of NDM may differ depending on the genetic etiology, with numerous studies showing the benefit of sulfonylurea therapy in cases caused by mutations in KCNJ11 or ABCC8 . Mutations in the insulin gene ( INS ) have also been identified as causes of NDM; these cases are generally best treated with insulin alone. We report a case of a female infant born small for gestational age (SGA) at late preterm diagnosed with NDM at 7 wk of life who was found by rapid whole-genome sequencing to harbor a novel de novo c.26C>G (p.Pro9Arg) variant in the INS gene. She presented with diabetic ketoacidosis, which responded to insulin therapy. She did not respond to empiric trial of sulfonylurea therapy early in her hospital course, and it was discontinued once a genetic diagnosis was made. Early genetic evaluation in patients presenting with NDM is essential to optimize therapeutic decision-making.

Background: IGSF1 deficiency syndrome, also known as X-linked central hypothyroidism and testicular enlargement (CHTE) syndrome, is caused by mutations in the immunoglobulin superfamily, member 1 gene. Recently recognized as the most common genetic cause of isolated central hypothyroidism (CH), its cardinal features include CH and adult macroorchidism. We describe a boy with CH and epiphyseal dysplasia found to have a novel IGSF1 variant. Clinical case: A male with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, obsessive compulsive disorder and obesity was evaluated at age 9y for high total and LDL cholesterol and low T4 with normal TSH. He had short stature for family, high BMI, high sitting height ratio, and short arm span. Laboratory investigation revealed persistently mildly high total and LDL cholesterol, low T4, normal cortisol response to low-dose Cortrosyn stimulation, and normal IGF-1 and IGF-BP3. Bone age at 9y1m chronological age was 8y0m. Skeletal survey showed abnormal epiphyses of the femoral heads, knees, and humeral capitella suggesting primary epiphyseal dysplasia; he was referred to genetics. Growth improved after starting levothyroxine for CH. Multiple epiphyseal dysplasia gene panel (with reflex to clinical exome) did not find any variants known to be pathogenic for his condition. He was found to be a carrier of autosomal recessive Bartter syndrome. Heterozygous variants of unknown significance were found in RMRP, FGFR1, CDT1 and APOB. Whole exome sequencing showed hemizygosity for the p.Q743X (c.2227C>T) variant in IGSF1. Discussion: The p.Q743X IGSF1 variant has not been reported in the literature and is not present in population databases. It is predicted to cause loss of normal protein function and is considered pathogenic. CH is found in all males with IGSF1 deficiency syndrome. Macroorchidism, another defining feature, develops in adulthood; age of testicular growth onset is normal, but pubertal testosterone rise is delayed. Our patient remains prepubertal at age 11y. Other features sometimes present include hypoprolactinemia (which was found in this child) and transient partial GHD (not seen in this case). Overweight and the metabolic syndrome are common; this child’s cholesterol abnormalities may be due to weight and/or APOB variant found on genetic testing. ADHD has been seen in some patients with this syndrome; this child also has extensive psychiatric/behavioral problems, which have not been described. The skeletal findings in this case have not been previously noted in IGSF1 deficiency syndrome; whether this is a rare feature of IGSF1 deficiency syndrome or a separate entity is unclear. This case adds to the growing list of disease-causing variants in IGSF1. Endocrinologists should consider IGSF1 deficiency syndrome when diagnosing isolated CH in boys, as the characteristic macroorchidism is not present in childhood.

Takayasu arteritis (TAK) is a rare, chronic large-vessel vasculitis affecting primarily the aorta and its branches. It is uncommon in children and non-Asian ethnic groups. Co-incidence of TAK and type 1 diabetes (T1DM) is rare. We present a case of a 19-year-old Hispanic woman with longstanding T1DM and autoimmune thyroiditis who was diagnosed with TAK. She presented with T1DM and subclinical autoimmune thyroiditis at age 9. She was poorly adherent to diabetes care plan and admitted multiple times for DKA due to insulin omission. HbA1C average over 10 yrs was approximately 11%. At age 18 she presented to an outside hospital with severe abdominal pain and was diagnosed with appendicitis. Appendectomy was complicated by identification of an ischemic segment of small bowel, which was resected, and also for finding a thrombosis in the superior mesenteric artery (SMA). The SMA thrombosis was initially felt to be related to the prothrombotic state of poorly controlled DM1; she had a high atypical p-ANCA titer but erythrocyte sedimentation rate (ESR) had been normal. Her clinical course was complicated by severe cachexia resulting in multiple readmissions to address chronic abdominal complaints, malnutrition and diarrhea. She was also admitted for an episode of pyelonephritis during which she developed severe liver dysfunction of unclear cause. Diabetes remained poorly controlled. At age 19 she was admitted for DKA and weight loss. An abdominal bruit was identified on exam. There was no hypertension. Labs demonstrated a significant elevation of ESR of 101 mm/hr. A diagnostic evaluation was initiated. Imaging (CT and MR angiography) revealed chronic occlusion of the proximal SMA as well as vasculitis of the infrarenal aorta and inferior mesenteric artery. Conventional angiogram did not show vasculitis distal to the origin of the aortic vessels. Based on the constellation of findings including constitutional and gastrointestinal symptoms, the arterial bruit on exam, the high ESR, and findings on imaging, a diagnosis of large-vessel vasculitis (TAK) was made. She was treated with azathioprine and a taper of oral prednisone. Weight increased and ESR decreased initially down to 20 mm/hr, but ESR again increased (up to 40 mm/hr) with imaging evidence of ongoing vasculitis when steroids were weaned. This case adds to the sparse literature describing the association between TAK and T1DM. It highlights that TAK may occur in very young adults of non-Asian descent. It also showcases the difficulty in diagnosis of TAK, which may have a subacute and nonspecific presentation, in an individual with poorly controlled DM1 as well as SMA thrombosis, which has been described as an acute complication of DKA in case reports. The use of systemic glucocorticoids as a mainstay of TAK therapy may present additional challenges in an individual with DM1. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until...