The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels.

OBJECTIVE: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. METHODS: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. RESULTS: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. CONCLUSIONS: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

Transgender medicine- transitioning transgender children to adulthood.

There has been an increasing prevalence of individuals presenting for treatment of gender dysphoria over the past several years. This growing population includes transgender children referred to pediatric clinics. Transgender children meeting diagnostic criteria for gender dysphoria, with supportive mental health care, may be treated with gonadotropin releasing hormone (GnRH) agonists and cross sex hormones. The treatment for these children requires ongoing maintenance and monitoring and therefore follow-up in the adult care setting. As is the case with other conditions that require long term treatment, these youth need a formal transition from pediatric to adult clinical care. The period of transition of care is critical and if not executed properly exposes the adolescent to risks of complications, and loss of follow-up. The proper clinical transfer is especially important for transgender youth in the setting of increased psychosocial and mental health issues. The transition of care for transgender adolescents has not been formally studied but given a growing population seeking treatment for gender dysphoria, it will need to be systematically assessed to determine the best outcomes to measure.

Community healthcare delivery post-Hurricane Sandy: lessons from a mobile health unit.

In the aftermath of Hurricane Sandy the North Shore LIJ Health System (NS-LIJ HS) organized and launched its first mobile health unit (MHU) operation to some of New York's hardest hit communities including Queens County and Long Island, NY. This document describes the initiation, operational strategies, outcomes and challenges of the NS-LIJ HS community relief effort using a MHU. The operation was divided into four phases: (1) community needs assessment, (2) MHU preparation, (3) staff recruitment and (4) program evaluation and feedback. From November 16th through March 21st, 2013 the Health System launched the MHU over 64 days serving 1,160 individuals with an age range of 3 months to 91 years. Vaccination requests were the most commonly encountered issue, and the most common complaint was upper respiratory illness. The MHU is an effective resource for delivering healthcare to displaced individuals in the aftermath of natural disaster. Future directions include the provision of psychosocial services, evaluating strategies for timely retreat of the unit and methods for effective transitions of care.

Prolonged Adrenal Insufficiency After Osilodrostat Exposure With Eventual Recovery of Adrenal Function.

Osilodrostat is an 11ß-hydroxylase inhibitor used in the treatment of adult patients with Cushing disease. Prolonged adrenal insufficiency (AI) after osilodrostat use is a rare but significant adverse effect. We present the case of a 41-year-old woman treated with osilodrostat for persistent hypercortisolism following pituitary surgery and Gamma Knife radiosurgery. After 11 months of osilodrostat therapy, she reported AI symptoms, and biochemical testing revealed low serum cortisol following cosyntropin stimulation as well as high plasma adrenocorticotropic hormone (ACTH). The patient was started on physiologic replacement dose of hydrocortisone, which was discontinued 23 months after last osilodrostat exposure when laboratory testing revealed recovery of endogenous cortisol production. The mechanism responsible for the prolonged AI noted with osilodrostat use is unclear and unexpected, given the short half-life of the drug. Although prolonged AI after osilodrostat use is not well understood, providers should be aware of this potential adverse effect and have a low threshold to test for AI in patients reporting AI-related symptoms.

Internal Carotid Artery Aneurysm Disguised as Pituitary Macroadenoma.

Hypopituitarism due to an internal carotid artery (ICA) aneurysm is rare. We present a case of hypopituitarism and hyperprolactinemia due to a giant right ICA aneurysm. A 56-year-old woman with a history of primary hypothyroidism presented with fatigue, right-sided headache, and blurred vision. Magnetic resonance (MR) of the brain revealed a sellar mass measuring 3.5 × 2.2 cm involving the right cavernous sinus. Initial neurologic examination was unremarkable, and her biochemical evaluation revealed secondary adrenal insufficiency, central hypogonadism, low serum free thyroxine, and mildly elevated serum prolactin, consistent with stalk effect. Hydrocortisone therapy was started for secondary adrenal insufficiency and her levothyroxine dose was adjusted. The patient was referred to neurosurgery for surgical management of her sellar lesion. Preoperative computed tomography angiography (CTA) of the brain revealed a right ICA aneurysm that contacted the optic chiasm and displaced the pituitary gland. The aneurysm was embolized and diverting stents were placed. Repeat laboratory tests showed resolution of the patient's secondary adrenal insufficiency, normalization of serum prolactin, and an increase in serum gonadotropin concentrations to the postmenopausal range. This case highlights that not all sellar lesions are pituitary adenomas, and CTA should be performed in the evaluation of large cavernous sinus lesions to exclude ICA aneurysm.

Initial Assessment of VECTRA Three-Dimensional Imaging to Accurately Simulate Breast Volume Changes in Transfeminine Patients: A Mannequin Study.

Background: Methods that aim to accurately measure and predict breast development can be utilized in gender-affirming treatment planning, patient education, and research. Objectives: The authors sought to evaluate whether three-dimensional (3D) stereophotogrammetry accurately measures transfeminine breast volume changes on a masculine frame when simulating anticipated changes in soft tissue after gender-affirming surgical therapy. Then, we describe the innovative application of this imaging modality in a transgender patient to illustrate the potential role of 3D imaging in gender-affirming surgical care. Methods: A 3D VECTRA scanner (Canfield, Fairfield, NJ) was used to measure anthropometric breast measurements. Postoperative changes in breast volume were simulated on a cardiopulmonary resuscitation mannequin using 450 cc MENTOR breast implants (Mentor Worldwide LLC, Irvine, CA). To demonstrate the ability of the VECTRA to accurately simulate transfeminizing augmentation in practice, we describe its use in a 30-year-old transgender female with a 2-year history of gender-affirming hormone therapy, presenting for gender-affirming surgical care. Results: In the mannequin, mean breast volumes were 382 cc on the right (range 375-388 cc), and 360 cc on the left (range 351-366 cc). The average calculated difference in volume between the 2 sides was 22 cc (range 17-31 cc). There were no instances where the left side was calculated to be larger than the right or where the calculated size was smaller than the actual implant size. Conclusions: The VECTRA 3D camera is a reliable and reproducible tool for preoperative assessment, surgical planning, and simulating breast volume changes after gender-affirming surgery.

Dual treatment of acromegaly and hormone-receptor-positive breast cancer with tamoxifen: a case report.

BACKGROUND: Adjuvant endocrine therapy is recommended for the treatment of hormone-receptor-positive breast cancer. Aromatase inhibitors are associated with significant musculoskeletal adverse effects, likely through growth hormone/insulin-like growth factor 1 modulation, while tamoxifen reduces insulin-like growth factor 1 production. We describe the case of a patient who was treated successfully with tamoxifen for her hormone-receptor-positive breast cancer and acromegaly. CASE PRESENTATION: A 57-year old White female with hormone-receptor-positive breast cancer was diagnosed with acromegaly. She received adjuvant endocrine therapy with anastrozole but could not tolerate this medication because of severe arthralgia, so she was switched to tamoxifen. Shortly after starting tamoxifen, the patient's musculoskeletal symptoms resolved and her insulin-like growth factor 1 levels normalized. She has remained in remission of her acromegaly and breast cancer since initiating tamoxifen. CONCLUSION: This case highlights the dual benefit of tamoxifen therapy in the treatment of hormone-receptor-positive breast cancer and acromegaly. Unlike anastrozole, tamoxifen has the benefit of lowering insulin-like growth factor 1 levels, which underscores its advantage in reducing adverse musculoskeletal symptoms during the treatment of hormone-receptor-positive breast cancer. We offer the first reported use of tamoxifen monotherapy for the successful treatment of acromegaly and hormone-receptor-positive breast cancer. While tamoxifen may offer an additional, oral option for acromegaly patients who do not respond to or tolerate conventional growth-hormone-lowering therapy, additional studies are necessary.

Pasireotide: A Novel Treatment for Tumor-Induced Hypoglycemia Due to Insulinoma and Non-Islet Cell Tumor Hypoglycemia.

Tumor-induced hypoglycemia is a serious disorder most commonly caused by insulinoma or non-islet cell tumor hypoglycemia (NICTH). The hypoglycemia can be severe and refractory to conventional therapy, leading to significant morbidity and mortality. The objective of this work is to describe a series of challenging cases in which refractory, tumor-induced hypoglycemia was shown to respond to the use of pasireotide, a second-generation somatostatin receptor ligand. We describe the clinical and biochemical features of 3 patients with tumor-induced hypoglycemia due to an occult insulinoma, malignant insulinoma, and non-islet cell tumor hypoglycemia. In these 3 individuals, the hypoglycemia remained refractory to guideline-recommended medical therapy, such as diazoxide, nonpasireotide somatostatin analogues, and glucocorticoids. Pasireotide was substituted to attenuate the refractory hypoglycemia for each patient. The addition of pasireotide led to prompt improvement in the frequency and severity of hypoglycemic episodes for each tumor-induced hypoglycemia patient. We demonstrate the successful treatment of 3 individuals with refractory, tumor-induced hypoglycemia with pasireotide. We offer the first reported use of pasireotide for the successful treatment of nonmalignant insulinoma and non-islet cell tumor hypoglycemia.

HYPERPROLACTINEMIA IN A TRANSGENDER MALE.

OBJECTIVE: We present a case of hyperprolactinemia in a transgender male. We discuss the various etiologies for hyperprolactinemia in this population of patients and discuss management options. METHODS: We present a case report and review of the literature. A 29-year-old transgender male treated with gender-affirming hormone therapy with testosterone presented with hyperprolactinemia. RESULTS: Labs revealed an elevated prolactin level. The patient completed further laboratory evaluation as well as imaging with a pituitary magnetic resonance imaging which all revealed normal results. He was wearing a tightly fitted breast binder while awaiting bilateral mastectomy. After bilateral mastectomy prolactin normalized, suggesting breast binding as the cause of the elevated prolactin. CONCLUSION: This is the only case in the literature which highlights breast binding as a possible cause of an elevated prolactin level. Our case report illustrates the various etiologies associated with an elevated prolactin level and highlights the importance of considering unique etiologies in populations such as transgender males.

Prolonged Steroid Dependence in Adult Patients With Glioma.

BACKGROUND/AIM: Prolonged use of glucocorticoids (GC) in glioma treatment can lead to adrenal insufficiency (AI) and subsequent steroid dependence due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis. This is challenging to diagnose due to its nonspecific clinical symptoms erroneously ascribed to treatment. This study aimed to evaluate the risk factors predisposing patients with gliomas to develop AI. PATIENTS AND METHODS: Charts in the neuro-oncology clinic from July 2018 to March 2019 were reviewed. Inclusion criteria included >18 y/o with WHO Grade II-IV gliomas, and secondary AI. Demographic profile, tumor characteristics, and treatment profile were compared. RESULTS: The majority of patients were started on high dose dexamethasone at >8 mg daily, and were on dexamethasone for 4-8 months. The minimum dose needed to prevent symptoms was 0.5 mg to 2 mg daily. The majority received standard radiation doses ranging from 54-60 Gy. Most patients had radiation exposure to the HPA axis within the prescription isodose levels. CONCLUSION: Prolonged steroid dependency can result from chronic GC use in patients with glioma. Dose and duration of GC are risk factors for its development. Radiation exposure to the HPA axis may also be a contributing factor.

Hormone Therapy in Children and Adolescents.

For children and adolescents with gender dysphoria, an interdisciplinary care team is essential for proper diagnosis and appropriate treatment. For children who present with gender dysphoria, once puberty begins, they can be treated with gonadotropin-releasing hormone analogs to stop pubertal progression. This allows for further gender exploration, relief of dysphoria, and better cosmetic outcomes by avoiding the physical changes associated with puberty of the gender assigned at birth. After pubertal suppression, the individual may opt to proceed with puberty or start treatment with gender-affirming hormones.

Hormonal Management for Transfeminine Individuals.

Transfeminine individuals are treated with estradiol and anti-androgen agents to transition to a more feminine appearance. The physical changes that occur with estradiol therapy include breast development, body fat redistribution, and decreased muscle mass. Transfeminine treatment regimens require monitoring and dose adjustments to achieve appropriate physiologic targets to enhance feminization and decrease risk of adverse outcomes. Adverse effects associated with estradiol use include thromboembolic disease, macroprolactinoma, breast cancer, coronary artery disease, cerebrovascular disease, cholelithiasis, and hypertriglyceridemia. Benefits of hormonal treatment may include both an improvement in quality of life and a decrease in gender dysphoria.

Two-temperature LATE-PCR endpoint genotyping.

BACKGROUND: In conventional PCR, total amplicon yield becomes independent of starting template number as amplification reaches plateau and varies significantly among replicate reactions. This paper describes a strategy for reconfiguring PCR so that the signal intensity of a single fluorescent detection probe after PCR thermal cycling reflects genomic composition. The resulting method corrects for product yield variations among replicate amplification reactions, permits resolution of homozygous and heterozygous genotypes based on endpoint fluorescence signal intensities, and readily identifies imbalanced allele ratios equivalent to those arising from gene/chromosomal duplications. Furthermore, the use of only a single colored probe for genotyping enhances the multiplex detection capacity of the assay. RESULTS: Two-Temperature LATE-PCR endpoint genotyping combines Linear-After-The-Exponential (LATE)-PCR (an advanced form of asymmetric PCR that efficiently generates single-stranded DNA) and mismatch-tolerant probes capable of detecting allele-specific targets at high temperature and total single-stranded amplicons at a lower temperature in the same reaction. The method is demonstrated here for genotyping single-nucleotide alleles of the human HEXA gene responsible for Tay-Sachs disease and for genotyping SNP alleles near the human p53 tumor suppressor gene. In each case, the final probe signals were normalized against total single-stranded DNA generated in the same reaction. Normalization reduces the coefficient of variation among replicates from 17.22% to as little as 2.78% and permits endpoint genotyping with >99.7% accuracy. These assays are robust because they are consistent over a wide range of input DNA concentrations and give the same results regardless of how many cycles of linear amplification have elapsed. The method is also sufficiently powerful to distinguish between samples with a 1:1 ratio of two alleles from samples comprised of 2:1 and 1:2 ratios of the same alleles. CONCLUSION: SNP genotyping via Two-Temperature LATE-PCR takes place in a homogeneous closed-tube format and uses a single hybridization probe per SNP site. These assays are convenient, rely on endpoint analysis, improve the options for construction of multiplex assays, and are suitable for SNP genotyping, mutation scanning, and detection of DNA duplication or deletions.

Osteoporosis as the sole manifestation of systemic mastocytosis in a young man.

OBJECTIVE: To highlight the difficulty involved in making a diagnosis of systemic mastocytosis (SM) when it manifests solely as osteoporosis. METHODS: We present a detailed case report and review the literature regarding the work-up of secondary osteoporosis and the diagnosis and treatment of SM. Other cases of SM presenting as osteoporosis in male patients are also described. RESULTS: A 35-year-old man presented with back pain after weight lifting and was diagnosed with a T7 vertebral compression fracture. A dual-energy x-ray absorptiometry scan resulted in a T-score of -3.2 in the spine and of -1.9 and -2.4 in the hip and femoral neck areas, respectively. Results of standard tests for secondary osteoporosis including calcium, phosphorus, 25-hydroxyvitamin D, kidney and liver function, thyroid function, testosterone level, and midnight salivary cortisol were normal. Further testing revealed a high serum tryptase level of 26.8 µg/L (reference range, <11.4) and elevated urinary histamine at 39.1 µg/g creatinine (reference range, <35). Bone marrow biopsy confirmed the diagnosis of mastocytosis. CONCLUSION: The rare diagnosis of SM is difficult when there is little clinical suspicion and remains a challenge to endocrinologists and other physicians. The condition should be suspected in young male patients with no other obvious cause of osteoporosis.