Primary Hyperparathyroidism due to Parathyroid Adenoma in Children and Adolescents.

OBJECTIVE: In contrast to adults, primary hyperparathyroidism (PHPT) in children and adolescents is a rare endocrine disorder. METHODS: A retrospective review of PHPT cases between 2005 and 2022 from a single tertiary university medical center, including clinical signs and symptoms, laboratory findings, radiological evaluation, treatment, and postoperative complications. RESULTS: Ten children (mean age at diagnosis 16.3 ± 1.3 years) were diagnosed with PHPT. All patients were in late pubertal stages without sex predominance and 8 were symptomatic. Mean calcium level was 13.6 ± 2.5 mg/dL, and mean parathyroid hormone levels were 204.8 ± 163.1 pg/mL. Parathyroid adenoma was confirmed by the postsurgical pathology results. CONCLUSIONS: PHPT in children and adolescents is often symptomatic and more severe than adults. The main cause is single parathyroid adenoma. Associated hypercalcemic syndromes were not found. Patients were cured after surgical removal of the adenoma without significant postoperative complications and no recurrence during 10.4 ± 5.9 years follow-up.

Uncommon side effects of common drugs in patients with familial dysautonomia.

PURPOSE: Patients with the autosomal recessive disorder of familial dysautonomia typically exhibit exacerbated adverse side effects to many common drugs. We aimed to catalog these adverse effects - with a focus on common drugs that are frequently administered to FD patients and compare their incidences to those within the general population. METHODS: We used data of 595 FD patients from an international database with information on drugs received and adverse effects. To investigate the molecular causes of reported differences in drug responses in FD patients, we used expression microarrays to compare the mRNA expression profiles in peripheral blood leukocytes of FD patients (n = 12) and healthy individuals (n = 10). RESULTS: Several drug classes, including cholinergics, anti-cholinergics, anti-convulsants, methylxanthines, SSRIs, and antibiotics caused either unreported symptoms or elevated rates of adverse events in FD patients. FD patients experienced different or more frequent adverse side effects than the general population in 31/123 drugs. These side effects included blood cell dyscrasias, amenorrhea, gastrointestinal bleeding, and bronchospasm. New findings include enhanced reaction of FD patients to H2 antagonist agents and to serotonin receptor agonists. We also detected eight genes differentially expressed between FD patients and healthy individuals that may underlie the differential drug responses of FD patients. CONCLUSION: We provide evidence that suggests the use of several common drugs should be discontinued or reduced in FD patients.

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.

Late cardiac assessment in children diagnosed with post-streptococcal reactive arthritis: a long term study.

OBJECTIVES: Unlike rheumatic fever (RF), the association of post-streptococcal reactive arthritis (PSRA) and carditis is controversial. The American Heart Association recommends anti-streptococcal prophylaxis for PSRA for one year, repeating echocardiogram and discontinuation of prophylaxis if normal. In this study the possibility of late cardiac involvement was investigated in a cohort of children with PSRA. METHODS: Children diagnosed with PSRA and followed at the Paediatric Rheumatology Units at two medical centres in Israel had echocardiography carried out by a paediatric cardiologist, at least 1 year following diagnosis. RESULTS: 146 patients with PSRA met the study criteria. Of these, 69 had undergone echocardiography 1-6.9 years (mean 3.6 years ± 1.5 years) after diagnosis. All had normal major parameters. Twenty (29.0%) patients had minimal cardiac findings, including 5 (7.2%) mild mitral insufficiency, 12 (17.4%) minimal mitral insufficiency, 2 (2.9%) mild tricuspid insufficiency and one patient (1.4%) had very mild, aortic insufficiency. Of the 77 patients who did not have echocardiography, 31 were randomly excluded from the initial study list, 26 refused to undergo echocardiography, and 20 were lost to follow-up. All were asymptomatic according to their medical record or telephone questionnaire. There were no significant differences in clinical or demographic data between those with or without echocardiography. CONCLUSIONS: No late cardiac involvement was found in our paediatric PSRA patients. Therefore, different approaches to antibiotic prophylaxis for PSRA and ARF are probably suggested. A prospective, controlled study is needed to definitively assess the necessity of prophylaxis in PSRA.

Body Composition and Metabolic Syndrome Components in Transgender/Gender Diverse Adolescents and Young Adults.

Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.

Adolescent Transgender Females Present Impaired Semen Quality That Is Suitable for Intracytoplasmic Sperm Injection Even Before Initiating Gender-Affirming Hormone Treatment.

The present study aimed to determine the semen quality and cryopreservation outcomes among adolescent transgender females at the time of fertility preservation (FP) before initiating gender-affirming hormone (GAH) treatment. This retrospective cohort study included 26 adolescent transgender females who underwent FP in our Fertility Institute between 06/2013 and 10/2020. Pre-freezing semen parameters were compared to WHO 2010 reference values. Post-thaw semen parameters were used to determine the adequate assisted reproductive technology (ART). A multivariate linear regression analysis was performed to assess the impact of medical and lifestyle factors on semen quality. The mean age at which adolescent transgender females underwent FP was 16.2 ± 1.38 years. The median values of all semen parameters in our study group were significantly lower compared to the WHO data, including volume (1.46 mL vs 3.2 mL, respectively, P = 0.001 ), sperm concentration (28 × 106/mL vs 64 × 106/mL, P < 0.001), total sperm number (28.2 × 106 vs 196 × 106, P < 0.001), total motility (51.6% vs 62%, P < 0.001), and normal morphology (2% vs 14%, P < 0.001). The frequency of semen abnormalities was teratozoospermia 72%, hypospermia 52%, oligozoospermia 28%, and azoospermia 4%. The median post-thaw total motile count was 0.17 × 106/vial, and the quality was adequate only for ICSI in 87.7% of the thawed semen samples. No correlation was found between selected medical and lifestyle factors and poor semen parameters. Semen quality is strongly reduced among adolescent transgender females before hormone therapy and their stored sperm samples are suitable for intracytoplasmic sperm injection (ICSI) rather than conventional IVF/intrauterine insemination (IUI).

Hypothyroidism predicts worsened prognosis in patients undergoing percutaneous coronary intervention.

Background: The link between thyroid dysfunction and cardiovascular disease is well established. Hypothyroidism has been significantly associated with increased risk of dyslipidemia, atherosclerosis and heart failure. However, little is known regarding its effect on patients undergoing percutaneous coronary intervention (PCI). Aim: The aim of study was to examine the impact of concomitant hypothyroidism on mortality and major adverse cardiac event (MACE) in patients undergoing PCI. Methods: The Rabin Medical Center PCI registry includes all consecutive patients who have undergone PCI between 2004 and 2020. We identified patients with prior diagnosis of hypothyroidism, and compared rates of mortality and MACE (comprising death, myocardial infarction, target vessel revascularization and/or coronary bypass surgery). Results: Among 28,274 patients, 1,922 (6.8%) were found to have hypothryoidism. These patients were older (70.3 ± 10.4 vs. 66.0 ± 11.8 y.o, P < 0.001) and more likely to be women (34.2% vs. 26.1%, P < 0.001). They had a higher prevalence of atrial fibrillation (10.8% vs. 7.7%, P < 0.001), chronic renal dysfunction (25.1% vs. 18.7%, P = 0.04) and dementia (2.9% vs. 1.8%, P = 0.004). PCI was performed on ACS setting in 52-54% of patients in both groups (p = 0.569). Unadjusted 5-year rates of all-cause mortality (26.9% vs. 20.3%, P < 0.001) and MACE (40.3% vs. 29.4%, P < 0.001) were higher for hypothyroid patients. A propensity match score was able to form 672 matched pairs of HT and control patients, showing similar results. Moreover, following multivariate analysis, TSH as a continuous parameter was associated with a higher risk of mortality and MACE (HR, 1.06 per additional 1 mIU/L; CI, 1.02-1.11; P < 0.001 and HR, 1.07; CI, 1.02-1.12; P < 0.001, respectively) at 5-year follow up. Conclusion: In our study, hypothyroidism confers worse outcomes in patients undergoing PCI. Further research is needed to establish effective ways to mitigate this augmented risk.

Effects of the COVID19 Pandemic on Transgender and Gender Non-Conforming Adolescents' Mental Health.

We assessed the effects of the COVID19 lockdown on the mental health of transgender and gender non-conforming (TGN) youth (n = 18) vs cisgender youth (29 males; 29 females). Coronavirus Health Impact Survey (CRISIS) and Emotion Regulation Questionnaire were used in an online study. No group differences were found in demographic variables and exposure to COVID19. Negative emotions/feeling increased for all groups. Cisgender youth reported using more adaptive emotion regulation strategies than TGN youth. While the lockdown similarly affected TGN and cisgender youth, the former showed elevated levels of symptomatology and fewer adaptive emotional regulation strategies.

Blood pressure dynamics after pubertal suppression with gonadotropin-releasing hormone analogs followed by estradiol treatment in transgender female adolescents: a pilot study.

OBJECTIVES: The benefits of gonadotropin-releasing hormone analogues (GnRHa) in the treatment of central precocious puberty are well established, and their use is regarded as both safe and effective. Possible adverse effects on blood pressure (BP) and cardiac outcomes, body composition, bone health and brain development, however, continue to be of some concern. The aim of this study was to analyze BP changes in transgender female adolescents before and after receiving GnRHa and after adding estrogen treatment. METHODS: This was a retrospective pilot study. We analyzed systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding estrogen. RESULTS: Nineteen transgender female adolescents received GnRHa and 15 continued to estrogen treatment. Their baseline SBP and DBP percentiles did not change significantly after either GnRHa or the addition of estrogen treatment. CONCLUSIONS: Blood pressure is apparently not affected by GnRHa or GnRHa + estrogen treatment in transgender female adolescents. Further larger studies are indicated to confirm these findings.

Blood Pressure Dynamics After Pubertal Suppression with Gonadotropin-Releasing Hormone Analogs Followed by Testosterone Treatment in Transgender Male Adolescents: A Pilot Study.

Purpose: We analyzed blood pressure (BP) changes in transgender male adolescents treated with gonadotropin-releasing hormone analogs (GnRHa) and after adding testosterone treatment. Methods: This was a retrospective pilot study. Outcome measures included systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding testosterone. Results: Fifteen transgender male adolescents received GnRHa. DBP percentiles increased significantly after GnRHa treatment (from 55.9% ± 26.4 to 73.6% ± 9.4, p = 0.019). BP levels did not meet criteria for hypertension. DBP percentiles were restored after adding testosterone. Conclusion: GnRHa may increase DBP in transgender male adolescents, and testosterone treatment may restore it. Further larger studies are indicated.

Final adult height of patients with childhood-onset systemic lupus erythematosus: a cross sectional analysis.

BACKGROUND: To compare final height to mid-parental target height among adults with childhood-onset systemic lupus erythematosus (cSLE) versus adult-onset SLE (aSLE), and to evaluate the impact of age at SLE onset on final height. METHODS: Data derived from the Lupus Outcomes Study, a longitudinal cohort of adults with SLE, was used for this cross-sectional analysis (N = 728). Participants aged 18-63 years with complete height data were included (N = 566) and were classified as cSLE if age at diagnosis was < 18 years (N = 72). The Tanner formula was used to calculate mid-parental target height. Multivariate linear regression was used to determine mean difference between final height and target height. Multivariate logistic regression was used to compare odds of substantially reduced final height, defined as > 2 SD below target height. Separate analyses were conducted for females and males to account for differences in timing of the pubertal growth spurt for each sex. RESULTS: Participants with cSLE were, on average, 2.4 cm shorter than their target height (95% CI -4, - 0.7). The adjusted odds ratio (OR) for substantially reduced final height was 3.9 (95% CI + 2.0, + 7.2, p < 0.001) as compared to participants with aSLE. Females diagnosed between 11 and 13 years were at greatest risk for substantially reduced final height, with adjusted OR of 11.2 (95% CI + 3.4, + 36.3) as compared to participants with aSLE (p < 0.001). CONCLUSIONS: cSLE is associated with shorter-than-expected final height. Onset of SLE in the pubertal period, near the time of maximum linear growth, may have a particularly significant impact on final height.

Post-streptococcal reactive arthritis in children: a distinct entity from acute rheumatic fever.

There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, genetic and treatment characteristics of PSRA differ from ARF. We review diagnostic criteria and regression formulas that attempt to classify patients with PSRA as opposed to ARF. The important implication of these findings may relate to the issue of prophylactic antibiotics after PSRA. However, future trials will be necessary to conclusively answer that question.