Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women

Objective: Suppression of testosterone secretion and/or action in transgender women using cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) is achieved through various mechanisms. Our objective was to characterize possible differential effects of these compounds on metabolic and endocrine variables.Methods: We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naïve patients and a cross-sectional analysis of the whole cohort at the last visit was carried out.Results: Among 126 transgender women (75 treatment-naïve), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naïve, the increase in serum prolactin levels over baseline was greater at 3 months following CPA initiation (mean change 397 ± 335 mIU/L) than following spironolactone (20.1 ± 87 mIU/L) or GA initiation (64.6 ± 268 mIU/L; P = .0002). Prolactin levels remained higher in the CPA-treated group throughout follow-up, irrespective of estradiol levels, which were similar between the groups. A worse metabolic profile was associated with treatment with CPA than with spironolactone or GA. In the CPA compared to the spironolactone and GA groups, high-density lipoprotein-cholesterol levels were lower (47.1 ± 10.4, 54.4 ± 12.2, and 60.3 ± 13, respectively; P = .0076), while body mass index levels (24.3 ± 5, 21.7 ± 2.3, and 20.7 ± 3.1 kg/m²; P = .03), and systolic (117 ± 12.1, 109 ± 12.2, and 105 ± 13.3 mm Hg; P = .01) and diastolic (74 ± 9, 65.6 ± 5.5, and 65.4 ± 11 mm Hg; P = .0008) blood pressure levels were higher at the last visit.Conclusion: Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA.Abbreviations: BMI = body mass index; CPA = cyproterone acetate; E2 = estradiol; FSH = follicle-stimulating hormone; GA = gonadotropin-releasing hormone analogues; LH = luteinizing hormone     

EXOGENOUS TESTOSTERONE DOES NOT INDUCE OR EXACERBATE THE METABOLIC FEATURES ASSOCIATED WITH PCOS AMONG TRANSGENDER MEN

Objective: Polycystic ovary syndrome (PCOS) is a complex condition which can include menstrual irregularity, metabolic derangement, and increased androgen levels. The mechanism of PCOS is unknown. Some suggest that excess production of androgens by the ovaries may cause or exacerbate the metabolic findings. The purpose of this study was to assess the role of increased testosterone on metabolic parameters for individuals presumed to be chromosomally female by examination of these parameters in hormone-treated transgender men.Methods: In 2015 and 2016, we asked all transgender men who visited the Endocrinology Clinic at Boston Medical Center treated with testosterone for consent for a retrospective anonymous chart review. Of the 36 men, 34 agreed (94%). Serum metabolic factors and body mass index (BMI) levels for each patient were graphed over time, from initiation of therapy through 6 years of treatment. Bivariate analyses were conducted to analyze the impact of added testosterone.Results: Regressions measuring the impact of testosterone demonstrated no significant changes in levels of glycated hemoglobin (HbA1c), triglycerides, or low-density-lipoprotein cholesterol. There was a statistically significant decrease in BMI with increasing testosterone. There was also a statistically significant decrease in high-density lipoprotein levels upon initiation of testosterone therapy.Conclusion: Testosterone therapy in transgender men across a wide range of doses and over many years did not result in the dyslipidemia or abnormalities in HbA1c seen with PCOS. Instead, treatment of transgender men with testosterone resulted only in a shift of metabolic biomarkers toward the average physiologic male body.Abbreviations: BMI = body mass index; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; PCOS = polycystic ovary syndrome     

Prolactin Levels Do Not Rise Among Transgender Women Treated With Estradiol and Spironolactone

Objective: Existing transgender treatment guidelines suggest that there is a need to monitor prolactin levels in patients receiving transfeminine hormone treatment. Also, recent studies suggest that use of cyproterone acetate as an adjunctive anti-androgen during transgender hormone treatment may elevate serum prolactin. We sought to determine whether the reported relationship between transfeminine estradiol treatment and hyperprolactinemia would be evident when the regimen used spironolactone as the adjunctive anti-androgen.Methods: Estradiol levels, testosterone levels, prolactin levels, body mass index (BMI), and prescribed spironolactone dosage were extracted from the electronic medical records of 98 de-identified transgender women treated with estrogen therapy at the Endocrinology Clinic at Boston Medical Center (BMC). Up to 6 years of data were available for some patients.Results: We found no statistically significant relationship between prolactin and any of the other measures. No estrogen dose-associated elevations in prolactin were found. None of the patients were diagnosed with prolactinoma.Conclusion: Our data suggest that there may be no significant rise in prolactin when transgender women are treated with estrogen along with spironolactone as the adjunct anti-androgen. It may be unnecessary to monitor prolactin in patients on this treatment combination.Abbreviations: BMI = body mass index; BMC = Boston Medical Center; HT = hormone therapy     

Transgender Transitioning and Change of Self-Reported Sexual Orientation

Objective

Sexual orientation is usually considered to be determined in early life and stable in the course of adulthood. In contrast, some transgender individuals report a change in sexual orientation. A common reason for this phenomenon is not known.

Methods

We included 115 transsexual persons (70 male-to-female “MtF” and 45 female-to-male “FtM”) patients from our endocrine outpatient clinic, who completed a questionnaire, retrospectively evaluating the history of their gender transition phase. The questionnaire focused on sexual orientation and recalled time points of changes in sexual orientation in the context of transition. Participants were further asked to provide a personal concept for a potential change in sexual orientation.

Results

In total, 32.9% (n =  23) MtF reported a change in sexual orientation in contrast to 22.2% (n =  10) FtM transsexual persons (p =  0.132). Out of these patients, 39.1% (MtF) and 60% (FtM) reported a change in sexual orientation before having undergone any sex reassignment surgery. FtM that had initially been sexually oriented towards males ( = androphilic), were significantly more likely to report on a change in sexual orientation than gynephilic, analloerotic or bisexual FtM (p  =  0.012). Similarly, gynephilic MtF reported a change in sexual orientation more frequently than androphilic, analloerotic or bisexual MtF transsexual persons (p  =  0.05).

Conclusion

In line with earlier reports, we reveal that a change in self-reported sexual orientation is frequent and does not solely occur in the context of particular transition events. Transsexual persons that are attracted by individuals of the opposite biological sex are more likely to change sexual orientation. Qualitative reports suggest that the individual''s biography, autogynephilic and autoandrophilic sexual arousal, confusion before and after transitioning, social and self-acceptance, as well as concept of sexual orientation itself may explain this phenomenon.     

Evidence-Based Curricular Content Improves Student Knowledge and Changes Attitudes towards Transgender Medicine

Objective: Previous studies have demonstrated that the addition of transgender medicine content to a medical school curriculum increased students' comfort and willingness to treat transgender patients. We aimed to demonstrate that (1) evidence-based curricular content would improve knowledge of and change attitudes towards transgender medicine, and (2) students would consider cross-sex hormone therapy a legitimate treatment option for transgender patients.Methods: Curricular content with a focus on the biologic evidence for the durability of gender identity was added to the first-year medical program at Boston University School of Medicine. Immediately before and after exposure to the content, students were presented with an assessment of their knowledge of the etiology of gender identity.Results: Immediately following exposure to the content, a significant number of students changed their answer regarding the etiology of gender identity so that the number of correct responses increased from 63% (n = 56) to 93% (n = 121) (P<.001). For transgender treatment, the number of correct responses increased from 20% (n = 56) before exposure to the content to 50% (n = 121) following exposure (P<.001).Conclusion: The addition of transgender medicine content to a medical school curriculum with a focus on the biologic evidence for a durable gender identity is an effective means of educating students about the etiology of gender identity and the appropriateness of cross-sex hormone therapy as a treatment for transgender patients.     

Testosterone Levels Achieved by Medically Treated Transgender Women in a United States Endocrinology Clinic Cohort

Objective: Most transgender women depend on medical treatment alone to lower testosterone levels in order to align physical appearance with gender identity. The medical regimen in the United States typically includes spironolactone and estrogens. The purpose of this cross-sectional study was to assess the testosterone suppression achieved among transgender women treated with spironolactone and estrogens.Methods: Testosterone and estradiol levels were extracted from the electronic medical records of 98 anonymized transgender women treated with oral spironolactone and oral estrogen therapy at the Endocrinology Clinic at Boston Medical Center.Results: Patients starting therapy required about 9 months to reach a steady-state testosterone, with significant heterogeneity of levels achieved among patients. Patients with normal body mass index (BMI) had higher testosterone levels, whereas patients with obese BMI had lower testosterone levels throughout treatment. Stratification of patients by age or spironolactone dosage revealed no significant difference in testosterone levels achieved. At steady state, patients in the highest suppressing quartile were able to achieve testosterone levels of 27 ng/dL, with a standard deviation of 21 ng/dL. Measured serum estradiol levels did not change over time and did not correlate with dosage of estradiol administered.Conclusion: Among a cohort of transgender women treated with spironolactone and estrogen, the highest suppressing quartile could reliably achieve testosterone levels in the female range at virtually all times. The second highest suppressing quartile could not achieve female levels but remained below the male range virtually all of the time. One quartile was unable to achieve any significant suppression.Abbreviations:BMC = Boston Medical CenterBMI = body mass indexCPY = cyproterone acetateLC-MS/MS = liquid chromatography–tandem mass spectrometryQ = quartile     

Meta-Analysis Shows Associations Of Digit Ratio (2D:4D) And Transgender Identity Are Small At Best

Abbreviations: 2D:4D = digit ratio; CI = confidence interval; F = female; FtM = female-to-male transgender; M = male; MtF = male-to-female transgender; TGI = transgender identity     

A Simple Intervention Raised Resident-Physician Willingness to Assist Transgender Patients Seeking Hormone Therapy

Objective: Lack of physician knowledge about transgender medicine is a barrier to care. An intervention with medical students changed attitudes about providing transgender medical care, but it is unknown whether at the level of postgraduate education an intervention could have a similar effect. We conducted such an intervention with resident-physicians.Methods: An intervention on transgender medicine covering the durability of gender identity and hormonal treatment regimens was added to the curriculum for residents. An anonymous survey assessed the residents' knowledge and willingness to assist with hormonal therapy before and after the lecture.Results: The percent of residents who agreed that they felt sufficiently knowledgeable to assist with hormonal therapy for a female-to-male patient increased significantly, from 5% before to 76% following the lecture (χ², 24.7; degrees of freedom, 1; P<.001). The percent of residents who reported that they felt sufficiently knowledgeable to assist with hormonal therapy for a male-to-female patient increased significantly, from 5% before to 71% following the lecture (χ², 24.0; degrees of freedom, 1; P<.001). The intervention increased resident knowledge about hormonal therapy for hypogonadal men (χ², 11.4; degrees of freedom, 1; P<.001) and women (χ², 9.4; degrees of freedom, 1; P = .002). The intervention made more residents agree that gender identity has a biologic basis that remains constant (P<.001) and that hormonal and surgical therapies should be offered (P = .047).Conclusion: The lecture significantly increased residents' knowledge and willingness to assist with hormonal therapy for transgender patients.Abbreviation: PGY = postgraduate year     

Endocrinology Fellows' Perception of Their Confidence and Skill Level in Providing Transgender Healthcare

Objective: Both educational content and hours devoted to transgender health training of endocrinology fellows are suboptimal. The objective of this study was to assess the perspectives of endocrinology fellows on their training in transgender health.Methods: We evaluated the state of comfort and knowledge of transgender healthcare among endocrinology fellows attending Endocrine University. Surveys were administered to fellows before and after their participation in a case-based session on transgender health.Results: The majority of fellows felt that training in transgender health is important (95.9%, 189/197); however, only 58.9% reported inclusion of dedicated transgender content in their training programs. Fellows who had received transgender healthcare education, and those who had seen more transgender patients in their training, were more likely to be confident in treating patients with hormone therapy (P<.001 and P<.0001, respectively). Following the case-based session, 62.4 % of fellows reported that they would change their practice, 72.8% felt that their comfort level with transgender care had improved, and 91% felt that transgender content such as that provided in the educational session should be mandatory in endocrinology training programs. Methods most desired by fellows to improve their education included lectures from visiting professors (70.3%), participation in elective rotations (62.1%), online training modules (57.9%), and attendance at meetings with transgender topics (57.4%).Conclusion: Transgender health education of U.S. endocrinology fellows is suboptimal. Participation in a case-based session significantly increased the comfort level of endocrinology fellows in key areas of transgender health.Abbreviation: ACGME = Accreditation Council for Graduate Medical Education     

Children and Adolescents with Gender Dysphoria in Israel: Increasing Referral and Fertility Preservation Rates

Objective: To describe patient characteristics at presentation, management, and fertility preservation rates among a cohort of Israeli children and adolescents with gender dysphoria (GD).Methods: We performed a retrospective chart review of 106 consecutive children and adolescents with GD (<18 years) referred to and followed at the multidisciplinary Israeli Pediatric Gender Dysphoria Clinic from March 2013 through December 2018.Results: Of the 106 patients, 10 were prepubertal (9 prepubertal transgender females), and 96 were pubertal (38 pubertal transgender females). The GD population increased 11-fold since the establishment of our clinic in 2013. The subject's median age at referral was 15.5 years (range, 4.6 to 18 years). At the time of referral, 91 (95%) of the pubertal group had completed sexual maturation in their assigned gender at birth. Thirteen (13.5%) patients had attempted suicide, and 11 (11.5%) reported having had suicidal thoughts. Fourteen (45%) pubertal transgender females and 3 (6.5%) pubertal transgender males completed fertility preservation. Gonadotropin-releasing hormone analog treatment was prescribed in 77 (80%) patients at a mean age of 15.9 ± 1.6 years. Gender-affirming hormones were prescribed in 61 (64%) patients at a mean age of 16.5 ± 1.3 years. No severe side effects were recorded. Two (2%) of the pubertal group expressed regret about medical treatment.Conclusion: Children and adolescents with GD are presenting for medical attention at increasing rates. Israeli adolescents with GD have high fertility preservation rates, perhaps attributable to cultural perspectives. Taking advantage of the option to preserve fertility can be achieved when proper counseling is both available and promoted by medical personnel.Abbreviations: GAH = gender-affirming hormone; GD = gender dysphoria; GnRHa = gonadotropin-releasing hormone analog; MHP = mental health professional     

Psychopathological Profiles in Transsexuals and the Challenge of Their Special Status among the Sexes

Objective

Investigating psychopathological profiles of transsexuals raises a very basic methodological question: are control groups, which represent the biological or the phenotypic sex, most suited for an optimal evaluation of psychopathology of transsexuals?

Method

Male-to-female (MtF) (n=52) and female-to-male transsexuals (FtM) (n=32), receiving cross-sex hormone treatment, were compared with age matched healthy subjects of the same genetic sex (n=178) and with the same phenotypic sex (n=178) by means of the Symptom Check List-90-Revisited instrument (SCL-90-R). We performed analyses of covariance (ANCOVA) to test for group and sex effects. Furthermore, we used a profile analysis to determine if psychopathological symptom profiles of transsexuals more closely resemble genotypic sex or phenotypic sex controls.

Results

Transsexual patients reported more symptoms of psychopathological distress than did healthy control subjects in all subscales of the SCL-90-R (all p<0.001), regardless of whether they were compared with phenotype or genotype matched controls. Depressive symptoms were more pronounced in MtF than in FtM (SCL-90-R score 0.85 vs. 0.45, p = 0.001). We could demonstrate that FtM primarily reflect the psychopathological profile of biological males rather than that of biological females (r = 0.945), while MtF showed a slightly higher profile similarity with biological females than with biological males (r = 0.698 vs. r = 0.685).

Conclusion

Our findings suggest that phenotypic sex matched controls are potentially more appropriate for comparison with the psychopathology of transsexual patients than are genetic sex matched controls.     

Longitudinal course of eating disorders after transsexual treatment: a report of two cases

Background

Several reports have been published on patients with gender dysphoria and eating disorders. However, there have been few reports on the longitudinal course of eating disorders after gender reassignment surgery (GRS)/gender confirmation surgery (GCS).

Case presentation

We report two Japanese cases of transsexual persons with eating disorders who underwent GRS/GCS, one male-to-female (MtF) and one female-to-male (FtM). Case 1 was a 35-year MtF person who had a 14-year-course of bulimia nervosa that developed after GRS. Case 2 was a 35-year FtM person with anorexia nervosa who underwent GCS 9 years before.

Conclusions

We found that the treatment of our transsexual patients influenced the course of their eating disorders for a long period, which could be attributable partly to the cultural situation in Japan, an East Asian country. It is possible that many gender identity problems and identity problems in general persist even after surgery and treatment; therefore, continual clinical support should be provided for patients with gender dysphoria and eating disorders even after hormonal therapy or GRS/GCS.

     

Estrogen Levels Do Not Rise With Testosterone Treatment For Transgender Men

Objective: Existing transgender treatment guidelines suggest that for transmasculine treatment, there is a possible need for estrogen-lowering strategies adjunct to testosterone therapy. Further, guidelines advocate consideration of prophylactic female reproductive tissue surgeries for transgender men to avoid the possibility of estrogen-related health risks. Despite the paucity of objective data, some transgender men seek conversion inhibitors. We sought to determine estradiol levels in transgender men treated with testosterone therapy and the change in those levels with treatment, if any.Methods: Estradiol levels were extracted from the electronic medical records of 34 anonymized transgender men treated with testosterone therapy at the Endocrinology Clinic at Boston Medical Center. Data were sufficient to observe 6 years of follow-up.Results: With increased testosterone levels in trans-gender men, a significant decrease in estradiol levels was noted. There was a significant negative correlation between testosterone levels and body mass index, which may serve to explain part of the mechanism for the fall in estradiol levels. Even though the fall in estradiol levels was significant statistically, the actual levels remained within the normal male range, even with 6 years of follow-up.Conclusion: These data suggest that when exogenous testosterone is used to achieve normal serum male testosterone levels for transgender men, it is converted to normal male levels of estradiol, with some decline in those estradiol levels that might be attributable to a fall in fat mass. There appears to be no role for aromatase conversion inhibitors or other estrogen-reducing strategies in trans-gender men.Abbreviation: BMI = body mass index     

Endocrine Dysfunction and Follow-Up Outcomes in Patients With Pituitary Abscess

Objective: Endocrine dysfunction caused by pituitary abscess (PA) and its outcomes have not been fully studied. This study aims to investigate endocrine dysfunction and outcomes in patients with PA.Methods: Eight patients (3 males and 5 females) with PA were identified for collecting clinical, hormone, and therapeutic data before and after long-term follow-up lasting 12 to 116 months (median, 25 months) since the first hospitalization, which was regarded as the baseline time. All patients' pituitary and respective target gland functions were evaluated. Six patients had acute onset (less than 1 month), and the other 2 patients had chronic onset (more than 6 months). Five patients underwent surgical therapy, and the other 3 patients underwent conservative therapy. The factors associated with endocrine outcome were analyzed as well.Results: At baseline, the release of 91.7% (22 of 24 total) of pituitary tropic hormones was impaired, but 59.1% (13 of 22) had normalized by the last follow-up. Male gender, acute onset mode, and normal baseline prolactin level seemed to be the factors that favored tropic hormone normalization, whereas surgical operation was not. Two patients received provocative test suggesting decreased reserves of both somatotrophin and prolactin or only somatotrophin. Only 1 patient suffered from permanent diabetes insipidus.Conclusion: The production of almost all pituitary tropic hormones was impaired with PA in the present study, but production of nearly 60% percent of the hormones normalized during follow-up of >1 year. A chronic abscess state may be the most important factor associated with permanent hormone deficiency.Abbreviations: ACTH = adrenocorticotropic hormone GnH = gonadotrophin MRI = magnetic resonance imaging PA = pituitary abscess TSH = thyroid-stimulating hormone     

Endocrine Outcomes of Transsphenoidal Surgery for Pituitary Apoplexy Versus Elective Surgery for Pituitary Adenoma

Objective: To determine the rate of hormone replacement therapy (HRT) after transsphenoidal surgery (TSS) for pituitary apoplexy (PA) versus elective resection of a null cell (NC) macroadenoma.Methods: A retrospective cohort study was performed. Data was collected on all consecutive patients who underwent TSS from December 31, 2000 to December 31, 2016. Patients were split into two groups: (1) patients that presented with PA, and (2) patients that underwent elective TSS for NC macroadenoma. Postoperative pituitary function was determined by examining HRT, hormone lab values, and an evaluation by an endocrinologist for each patient. The odds ratio (OR) was calculated to determine if there was an association between PA and the need for HRT after surgery when compared to elective resection of a NC macroadenoma.Results: The need for HRT was significantly higher following surgery for PA compared to resection of a NC macroadenoma (14.7% versus 2.9%, OR = 5.690; 95% confidence interval (CI) = 1.439 to 22.500; P = .013).Conclusion: There is an increased need for hormone replacement therapy after surgery in patients with PA versus patients undergoing elective resection of a NC macroadenoma. Further studies are warranted to strengthen this data and help determine further predictors of the need for HRT.Abbreviations: BNP = brain natriuretic peptide; CI = confidence interval; DDAVP = desmopressin acetate; GH = growth hormone; HRT = hormone replacement therapy; MRI = magnetic resonance imaging; NC = null cell (adenoma); OR = odds ratio; PA = pituitary apoplexy; TSS = transsphenoidal surgery     

American Association of Clinical Endocrinology Disease State Clinical Review on the Evaluation and Management of Adrenocortical Carcinoma in an Adult: a Practical Approach

Objective: The aim of this Disease State Clinical Review is to provide a practical approach to patients with newly diagnosed adrenocortical carcinoma, as well as to follow-up and management of patients with persistent or recurrent disease.Methods: This is a case-based clinical review. The provided recommendations are based on evidence available from randomized prospective clinical studies, cohort studies, cross-sectional and case-based studies, and expert opinions.Results: Adrenocortical carcinoma is a rare malignancy, often with poor outcomes. For any patient with an adrenal mass suspicious for adrenocortical carcinoma, the approach should include prompt evaluation with detailed history and physical exam, imaging, and biochemical adrenal hormone assessment. In addition to adrenal-focused imaging, patients should be evaluated with chest-abdomen-pelvis cross-sectional imaging to define the initial therapy plan. Patients with potentially resectable disease limited to the adrenal gland should undergo en bloc open surgery by an expert surgeon. For patients presenting with advanced or recurrent disease, a multidisciplinary approach considering curative repeat surgery, local control with surgery, radiation therapy or radiofrequency ablation, or systemic therapy with mitotane and/or cytotoxic chemotherapy is recommended.Conclusion: As most health care providers will rarely encounter a patient with adrenocortical carcinoma, we recommend that patients with suspected adrenocortical carcinoma be evaluated by an expert multidisciplinary team which includes clinicians with expertise in adrenal tumors, including endocrinologists, oncologists, surgeons, radiation oncologists, pathologists, geneticists, and radiologists. We recommend that patients in remote locations be followed by the local health care provider in collaboration with a multidisciplinary team at an expert adrenal tumor program.Abbreviations: ACC = adrenocortical carcinoma; ACTH = adrenocorticotropic hormone; BRACC = borderline resectable adrenocortical carcinoma; CT = computed tomography; DHEAS = dehydroepiandrosterone sulfate; EDP = etoposide, doxorubicin, cisplatin; FDG = ¹⁸F-fluorodeoxyglucose; FNA = fine-needle aspiration; HU = Hounsfield units; IVC = inferior vena cava; LFS = Li-Fraumeni syndrome; MEN1 = multiple endocrine neoplasia type 1; MRI = magnetic resonance imaging; OAC = oncocytic adrenocortical carcinoma; PC = palliative care; PET = positron emission tomography     

The Effect of Gender-Affirming Hormone Therapy on Serum Creatinine in Transgender Individuals

ObjectiveTo describe the changes in serum creatinine (Cr) levels after the initiation of gender-affirming hormone therapy (GAHT) in transgender individuals to better understand the expected changes and interpretation of laboratory values in this population.MethodsA retrospective chart review of all adult transgender patients initiated on GAHT at Mayo Clinic from January 2011 to October 2019 was completed. Laboratory values were obtained prior to initiating GAHT and at 3, 6, and 12 months after initiating GAHT. Baseline Cr values were compared with Cr values at 3, 6, and 12 months after initiating GAHT in transgender men (TM) on testosterone and transgender women (TW) on estradiol and antiandrogens.ResultsA total of 84 TW (median age of 30 years) and 24 TM (median age of 23 years) were included for analysis. Following a matched pair analysis of TW, Cr values were found to be significantly decreased by ?0.03 at 3 months (P = .04), ?0.10 at 6 months (P < .01), and ?0.07 at 12 months (P < .01) compared with baseline values. Following a matched pair analysis of TM, Cr values were found to be significantly increased, on average, by 0.14 at 3 months (P = .04), 0.21 at 6 months (P = .016), and 0.15 at 12 months (P = .003) compared with baseline values.ConclusionIn TW and TM, a change in Cr level was seen as early as 3 months toward their affirmed gender after initiating GAHT. Clinicians can use Cr levels established at 6 months as new baseline values, as these changes continue to persist up to 12 months.     

Observed Deficiencies in Medical Student Knowledge of Transgender and Intersex Health

Objective: Lesbian, gay, bisexual, transgender, and intersex (LGBTI) patients face many well-documented disparities in care which among transgender and intersex people can often be traced to providers' lack of knowledge.Methods: We administered surveys to examine the self-assessed knowledge and attitudes of all medical students at Boston University regarding different LGBTI subpopulations. Survey questions were based on a Likert scale from 1 to 5; analysis was conducted with Wilcoxon rank sum tests.Results: Overall there was a response rate of 24%, with the number of responses varying by class. Three of the 4 surveyed classes reported lower knowledge about transgender health than LGB health. Every class reported significantly lower knowledge of intersex health in comparison to LGB. Comfort with transgender or with intersex patients was lower than with LGB patients for all surveyed classes. Students across all self-identified groups (LGBTI, ally, not an ally) reported significantly lower average responses for knowledge and comfort regarding transgender or intersex health in comparison to that of LGB. Students in their preclinical years reported lower levels of knowledge in comparison with students in their clinical years. Students who identified as LGBTI reported significantly higher knowledge and comfort with only LGB and transgender health when compared with students who didn't identify as LGBTI. Respondents more frequently requested additional learning opportunities in transgender and intersex health than in LGB health.Conclusion: Self-reported knowledge of transgender and intersex health lags behind knowledge of LGB health, though these deficits appear partially responsive to targeted educational intervention.Abbreviations: BUSM = Boston University School of Medicine LGB = lesbian, gay, and bisexual LGBT = lesbian, gay, bisexual, and transgender LGBTI = lesbian, gay, bisexual, transgender, and intersex M1 = first-year medical student class M2 = second-year medical student class M3 = third-year medical student class M4 = fourth-year medical student class     

Renal Function and Plasma Renin activity as Potential Factors Causing Hyperkalemia in Patients with Thyroid Carcinoma Undergoing Thyroid Hormone Withdrawal For Radioactive Iodine Therapy

Objective: Hypothyroidism is not commonly considered a cause of hyperkalemia. We previously reported that hyperkalemia was observed mainly in elderly patients treated with renin-angiotensin-aldosterone system (RAS) inhibitors when levothyroxine treatment was withdrawn for the thyroidectomized patients with thyroid carcinoma to undergo radioactive iodine treatment. Here, we investigated whether acute hypothyroidism causes hyperkalemia in patients who were not treated with RAS inhibitors. We also investigated factors influencing potassium metabolism in hypothyroid patients.Methods: We conducted a single-center, prospective cohort study of 46 Japanese patients with thyroid carcinoma undergoing levothyroxine withdrawal prior to radioiodine therapy. All patients were normokalemic before levothyroxine withdrawal. Blood samples were analyzed 3 times: before, and at 3 and 4 weeks after levothyroxine withdrawal. We investigated factors that may be associated with the elevation of serum potassium levels from a euthyroid state to a hypothyroid state.Results: None of the patients developed symptomatic hyperkalemia. The mean serum potassium level was significantly higher at 4 weeks after levothyroxine withdrawal compared to baseline. The serum sodium levels, the estimated glomerular filtration rate (eGFR), and the plasma renin activity (PRA) decreased significantly as hypothyroidism advanced. In contrast, the plasma levels of adrenocorticotropic hormone, cortisol, aldosterone, and antidiuretic hormone were not changed, while serum thyroid hormone decreased. At 4 weeks after their levothyroxine withdrawal, the patients' serum potassium values were significantly correlated with the eGFR and the PRA.Conclusion: Acute hypothyroidism can cause a significant increase in the serum potassium level, which may be associated with a decreased eGFR and decreased circulating RAS.Abbreviations: ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ATPase = adenosine triphosphatase; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; K⁺ = potassium; Na⁺ = sodium; PRA = plasma renin activity; RAS = renin-angiotensin-aldosterone system; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Historical and Current Perspective in the Use of Thyroid Extracts for the Treatment of Hypothyroidism

Objective: To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies.Methods: A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature.Results: A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products.Conclusion: The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.Abbreviations: AACE = American Association of Clinical Endocrinologists ATA = American Thyroid Association BMR = basal metabolic rate FDA = Food and Drug Administration FT4 = free thyroxine 131-I = radioactive iodine 131 LT3 = liothyronine LT4= levothyroxine NDA = new drug application PBI = proteinbound iodine T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone TT3 = total triiodothyronine USP = U.S. Pharmacopeia