Secondary Sexual Characteristics Research Articles

A rare case of ovarian torsion in premenarcheal age- Case report and review of literature

Ovarian torsion in childhood and adolescence is rare gynecological emergency. We report a case of ovarian torsion in eleven-year-old pre-menarcheal girl who presented with acute lower left abdominal pain and vomiting. On examination her vital signs were stable, secondary sexual characters were absent, abdomen was scaphoid with tenderness in left iliac fossa. Ultrasonography with doppler study showed a heterogenous mass measuring about 58x31mm in left adnexal region close to uterus with minimal vascularity. MRI findings were consistent with ovarian torsion. Patient underwent emergency laparoscopy and left ovary was found to be enlarged, blue-black with hemorrhagic cyst with two twists along Infundibulo-pelvic ligament. Ovarian Sparing Surgery involving de-torsion of torsed ovary with drainage of hemorrhagic cyst was performed. Right ovary was found to be normal in size with multicystic appearance. Bilateral oophoropexy using sandwich technique was done in order to prevent future recurrences. This case report emphasizes on importance of immediate diagnosis with ultrasound and MRI. Surgical management in form of laparoscopy with ovarian sparing surgery in young patients is important to preserve their fertility.

Facing the Challenge: Hormonal hurdles, Olfaction Obstacles in Kallmann Syndrome

Kallmann syndrome (KS) is an uncommon disorder that was first defined in 1856 and designed by Kallmann in 1944. It is also referred to as olfactogenital dysplasia and is characterized by hypogonadism and the agenesis of the olfactory bulb. The prevalence of KS is not well understood, with the incidence in males ranging from 1 in 8000 to 1 in 10,000 and being less common in females. Kallmann syndrome exhibits genetic heterogeneity, with the inheritance of the trait occurring in an autosomal recessive, autosomal dominant, or X-linked manner. Over 24 genes have been determined to be responsible for Kallmann syndrome, which is thought to be caused by mutations that inhibit the formation of cell markers necessary for the migration of olfactory and GnRH (gonadotropin-releasing hormone) neurons to the forebrain during foetal development. Kallmann syndrome is characterised by hypogonadotropic hypogonadism and hyposmia or anosmia. Other less common symptoms include osteoporosis, cleft lip and palate, cryptorchidism, unilateral renal agenesis, and cardiovascular problems. Magnetic resonance imaging (MRI) can help detect anomalies in the olfactory system and other forebrain regions, as well as pituitary disorders. The treatment for Kallmann syndrome typically involves hormone replacement therapy (HRT) with both testosterone and gonadotropin-releasing hormone (GnRH) analogues to stimulate puberty and promote secondary sexual characteristics.

Abstract 18991: Effect of Sex Steroids on Lipid Profile in Female to Male Transgender Patients: A Systematic Review and Meta-Analysis

Background The medical transition of transgender individuals involves the administration of exogenous sex steroids to induce desired changes in secondary sexual characteristics. In the case of female-to-male (FtM) transgender individuals, the use of testosterone therapy is common. The impact of testosterone on lipid metabolism and dyslipidemia in this specific population is not well understood. Our study combines all the previous studies to study the impact of sex steroids in FtM transgender population. Aim To assess the effects of sex steroids on lipid profile in FtM transgender patients. Methods: PubMed, Cochrane, and Embase were searched from inception till May 2023 for all randomized control trials (RCTs) and observational studies. Primary outcomes were changes in basal metabolic profile (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride levels (TG), HDL, and LDL. All the baseline values before and after utilization of sex steroids were studied. A meta-cont module was used along with Inverse-variance method to calculate the pooled standard mean difference (SMD) for continuous outcomes with a probability value of p < 0.05 considered to be statistically significant. Results: A total of 21 studies with 1208 FtM transgender patients were included. Sex steroids resulted in statistically significant elevation in LDL-C (SMD 0.2850 [0.1169; 0.4531] p < 0.0009), TG (SMD 0.4312 [0.2522; 0.6101] p < 0.0001), TC (SMD 0.1754 [0.0536; 0.2972] p < 0.0048), and BMI (SMD: 0.2429 [0.0983; 0.3875] p < 0.0010) while HDL levels were significantly reduced from the baseline. However, no significant relationship between SBP and DBP was studied (Figure 1). Conclusion: In conclusion, sex steroids increase lipid levels in transgender patients, potentially contributing to dyslipidemia and cardiovascular risk.

Systematic evidence mapping informs a class-based approach to assessing personal care products and pubertal timing

BackgroundPersonal care products (PCPs) contain many different compounds and are a source of exposure to endocrine disrupting chemicals (EDCs), including phthalates and phenols. Early-life exposure to EDCs commonly found in PCPs has been linked to earlier onset of puberty. ObjectiveTo characterize the human and animal evidence on the association between puberty-related outcomes and exposure to PCPs and their chemical constituents and, if there is sufficient evidence, identify groups of chemicals and outcomes to support a systematic review for a class-based hazard or risk assessment. MethodsWe followed the OHAT systematic review framework to characterize the human and animal evidence on the association between puberty-related health outcomes and exposure to PCPs and their chemical constituents. ResultsNinety-eight human and 299 animal studies that evaluated a total of 96 different chemicals were identified and mapped by key concepts including chemical class, data stream, and puberty-related health outcome. Among these studies, phthalates and phenols were the most well-studied chemical classes. Most of the phthalate and phenol studies examined secondary sex characteristics and changes in estradiol and testosterone levels. Studies evaluating PCP use and other chemical classes (e.g., parabens) had less data. ConclusionsThis systematic evidence map identified and mapped the published research evaluating the association between exposure to PCPs and their chemical constituents and puberty-related health outcomes. The resulting interactive visualization allows researchers to make evidence-based decisions on the available research by enabling them to search, sort, and filter the literature base of puberty-related studies by key concepts. This map can be used by researchers and regulators to prioritize and target future research and funding to reduce uncertainties and address data gaps. It also provides information to inform a class-based hazard or risk assessment on the association between phthalate and phenol exposures and puberty-related health outcomes.

A clinical case of hypothalamic syndrome combined with Klinefelter syndrome

the article describes a clinical case of a hypothalamic syndrome associated with a congenital disease - Klinefelter syndrome in a 21-year-old patient. Dysmetabolic complications were studied against the background of endocrine and genetic pathologies. Klinefelter syndrome was diagnosed in the patient at the age of 10, mosaic variant of karyotype 47XXY/46XY was detected. Against the background of a rare genetic pathology, signs of a hypothalamic puberty syndrome began to appear at the age of 15: acne, pink stretch marks on the lateral areas of the abdomen and breasts, gynecomastia, and excess weight. General clinical laboratory studies, carbohydrate metabolism indicators, sexual and thyroid hormones did not differ from reference values. The cortisol level in the blood was 23.4 mcg/dL, slightly exceeding the upper limit of the reference values (4.30-22.4 mcg/dL), indicating a state of mild hypercorticism. Manifestations of dysmetabolic cardiomyopathy were noted in the cardiovascular system, complicated by stable stage II arterial hypertension. The peculiarity of the clinical case is the combination of endocrine pathology with genetic pathology, which determines the specific appearance of the patient, and the presence of dysmetabolic complications without disturbances of carbohydrate metabolism in stage III obesity. The acceleration of puberty, which often occurs with the hypothalamic syndrome, did not occur due to the concomitant hypoandrogenic effect of Klinefelter syndrome. In the presence of hypothalamic syndrome in the patient, the late development of secondary sexual characteristics was noted, which is more characteristic of Klinefelter syndrome, but normal mental activity was preserved, which is rarely observed with the mosaic form of this genetic pathology. Another clinical feature is the absence of typical manifestations of hypogonadism in the post-pubertal period, which is confirmed by a normal level of male and female sex hormones in the blood, which is atypical. Due to the peculiarity of this clinical case, the patient's fertility can be preserved. In addition to the existing dysmetabolic complications in the patient and metabolic syndrome, there is a high risk of developing type 2 diabetes, atherosclerosis, osteoporosis, and breast cancer, because Klinefelter syndrome andhypothalamic syndrome complicate each other. Therefore, it is important to study the issue of the combination of these two pathologies, possible consequences, and ways to overcome them to improve thepatient's clinical prognosis and quality of life.

A Comparative Study of the Modified Baumann's Angle Between the Dominant and Non-Dominant Sides in a North Indian Pediatric Population.

Background The literature points towards the fact that paediatric elbow fractures happen more frequently and have greater variability when contrasted with adults. Between 65%-75% of pediatric fractures involve the upper extremity, and supracondylar humerus is the most common of them all. To know the exact site of injury and to estimate the degree of reduction after manipulation, the modified Baumann's angle, the Baumann's angle, the Humero-condylar angle, the Anterior humeral line, and the Radio-capitellar line are the parameters most commonly used. This study was carried out to compare the modified Baumann's angle between both upper limbs in the paediatric population. Methodology This cross-sectional study was conducted in a tertiary health care centre in Northern India for one year from September 1, 2021, to August 31, 2022. We included pediatric patients in the age group of 3-16 years. Age, sex, weight, height, BMI, secondary sexual characters, and handedness were noted in all the children enrolled in our study. In both the dominant and non-dominant sides, the mean arm length, the forearm length, the inter-epicondylar distance, the clinical carrying angle, the radiological carrying angle, and the modified Baumann's angle were calculated. Results A total of 113 children were enrolled in the study. The majority of children (71.7%) had dominance on the right side. In both the dominant side and non-dominant side, mean arm length, forearm length, inter-epicondylar distance, clinical carrying angle, radiological carrying angle, and modified Baumann's angle values were calculated. On evaluating the data statistically, a significant difference between the two sides was observed for all the parameters (p<0.05), except forearm length (p-value -0.954). Multivariate analysis showed that only BMI was significantly negatively associated with modified Baumann's angle (p=0.016), and only age (0.019) and BMI (<0.001) were found to be significantly associated with the difference in modified Baumann's angle. Conclusions The findings of this study will be helpful in the management of elbow disorders and their reconstruction following trauma. A significant difference was found in the modified Baumann's angle between dominant and non-dominant sides, and it also showed a negative significant correlation with arm length, forearm length,and the presence of secondary sexual characteristics. The equations derived in this study will be helpful in the simple derivation of the modified Baumann's angle and its differencefrom simple measurements of the upper limb parameters.

Precocious Puberty: Types, Pathogenesis and Updated Management.

Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls by the enlargement of the breasts (thelarche) in girls and in boys by the enlargement of the testes in either volume or length (testicular volume = 4 mL, testicular length = 25 mm, or both). Two types of PP are recognized - namely central PP (CPP) and peripheral PP (PPP). This paper aims to describe the clinical findings and laboratory workup of PP and to illustrate the new trends in the management of precocious sexual maturation. Gonadotropin-releasing hormone (GnRH)-independent type (PPP) refers to the development of early pubertal maturation not related to the central activation of the hypothalamic-pituitary-gonadal (HPG) axis. It is classified into genetic or acquired disorders. The most common forms of congenital or genetic causes involve McCune-Albright syndrome (MAS), familial male-limited PP, and congenital adrenal hyperplasia. The acquired causes include exogenous exposure to androgens, functioning tumors or cysts, and the pseudo-PP of profound primary hypothyroidism. On the other hand, CPP is the most common and it is a gonadotropin-dependent form. It is due to premature maturation of the HPG axis. CPP may occur as genetic alterations, such asMKRN3, DLK1, or KISS1;as a part of mutations in theepigenetic factors that regulate the HPG axis, such as Lin28b and let-7; or as a part of syndromes, central lesions such as hypothalamic hamartoma, and others. A full, detailed history and physical examination should be taken. Furthermore, several investigations should be conducted for both types of PP, including the estimation of serum gonadotropins such as luteinizing and follicle-stimulating hormones and sex steroids, in addition to a radiographic workup and thyroid function tests. Treatment depends on the type of PP: Long-acting GnRHa, either intramuscularly or implanted, is the norm of care for CPP management, while in PPP, especially in congenital adrenal hyperplasia, the goal of management is to suppress adrenal androgen secretion by glucocorticoids. In addition, anastrozole and letrozole - third-generation aromatase inhibitors - are more potent for MAS.

THE RELATIONSHIP BETWEEN KNOWLEDGE OF HIV/AIDS AND THE RISK OF TRANSMISSION OF HIV/AIDS IN ADOLESCENTS AT SENIOR HIGH SCHOOL 22 BEKASI CITY IN 2023

Background: Adolescence is the transition period from childhood to adulthood, secondary sexual characteristics begin to appear, there is a growth spurt, fertility is achieved, and cognitive and psychological changes occur. Adolescence is actually between childhood and adulthood, so the emotional state is unstable and the desire to try new things is very high, so adolescence is often referred to as a time of self-discovery. One aspect of the development of identity-seeking adolescents is the role of sexuality in developing relationships with peers. Adolescents sexual maturity results in adolescents becoming interested in the physical anatomy of their body. In addition to being attracted to oneself, there is also attraction to the opposite sex. This condition makses adolescents, including students, vulnerable to risky behavior problems, such as premarital sex that leads to unwanted pregnancies and substance abuse. (Prabasari et al., 2019). Research Objective: To determinate the relationship between knowledge about HIV/AIDS and the risk of HIV/AIDS transmission in adolescents at SMAN 22 Bekasi City 2023. Research Method: The research method carried out by researchers is quantitative. The research design in this study used observational analytics with a cross sectional design. Cross sectional is an analytical research design that aims to determine the relationship between variable where independent variables and dependent variables are identified at one time. Research Results: Based on statistical analysis with a significant level of 95% or a value of α 5% (0,05) obtained p value (0,000) α value (0,05), so that it can be concluded from these results H0 rejected means that there is a relationship between knowledge about HIV/AIDS and the risk of HIV/AIDS transmission in adolescents at SMAN 22 Bekasi City in 2023. Conclusion: H0 rejected means that there is a relationship between knowledge about HIV/AIDS and the risk of HIV/AIDS transmission in adolescents at SMAN 22 Bekasi City.

Analysis of mRNA and MicroRNA Expression Profiles of Nervous Tissues and Reproductive Tissues in Male Procambarus clarkii After Silencing IAG.

The insulin-like androgenic gland hormone gene (IAG), primarily expressed in the androgenic gland (AG), plays a crucial role in controlling male sex differentiation and maintaining male secondary sexual characteristics in decapods. In this study, we investigated the mRNA and microRNA expression profiles of male Procambarus clarkii to understand the transcriptomic regulatory mechanism of IAG after the injection of an efficient siRNA (GsiRNA) designed based on IAG. The results revealed that several differentially expressed genes were enriched in reproduction-related pathways, such as the wnt signaling pathway, MAPK signaling pathway, and GnRH signaling pathway. In the testis (Te), the injection of GsiRNA led to the up-regulation of many ovary-related genes and down-regulation of testis-related genes. Moreover, the brain (Br) and abdominal nerve cord (AN) appeared to be involved in the regulation of IAG, with numerous differentially expressed genes found in Br and AN. Notably, the expression of five neuropeptide genes, Crustacean hyperglycemic hormone, pigment-dispersing hormone, red pigment concentrating hormone precursor, corazonin, and gonadotropin-releasing hormone II receptor isoform X1 in Br/AN, was significantly changed. Additionally, three ovary-related miRNAs (miR-263a, miR-263b, miR-133) highly expressed in Te/AG showed significant up-regulation after GsiRNA injection. Furthermore, the long-term interference of GsiRNA was found to inhibit the development of male external sexual characteristics during the juvenile stage and delay it during the adult stage. This research provides valuable insights into the molecular regulatory mechanism and function of IAG in P. clarkii.

A toddler with testosterone: where did it come from?

Precocious development of secondary sexual characters not involving pulsatile gonadotropin secretion is known as gonadotropin independent precocious puberty or peripheral precocious puberty (PPP). This form of sexual precocity in males can occur due to gonadal, adrenal, or other testosterone secreting tumors (teratomas, hepatomas, and choriocarcinomas), untreated congenital adrenal hyperplasia, testotoxicosis, and familial male limited precocious puberty. We report a case of a 2-year-old boy with PPP caused due to hepatoblastoma. Complete surgical resection of the tumor was done, and the child received cisplatin chemotherapy.

Clinical Management and Therapy of Precocious Puberty in the Sapienza University Pediatrics Hospital of Rome, Italy.

Puberty identifies the transition from childhood to adulthood. Precocious puberty is the onset of signs of pubertal development before age eight in girls and before age nine in boys, it has an incidence of 1/5000-1/10,000 with an F:M ratio ranging from 3:1 to 20:1. Precocious puberty can be divided into central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also recognized as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual features, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas, as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analog therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

Ectopic Kidney as a Clinical Manifestation of Type II MRKH Syndrome Patient: A Case Report

Introduction: Mayer-Rokitansky-Kuster-Hauser Syndrome is a reproductive system disorder that occurs due to failure in the development of the Müllerian ducts. This disorder is characterized by the absence of the uterus and upper part of the vagina. MRKH syndrome is divided into type I and type II where type II is accompanied by non-gynecological disorders. The most common non-gynecological disorder is renal abnormality. Objectives: This study aims to describe one of the rare clinical manifestations of type II MRKH syndrome. Case Presentation: We reported a case of a sexually inactive woman in her early 20s presenting with primary amenorrhea. The patient had normal secondary female sexual characteristics. In the examination, we found the patient had vaginal agenesis, uterine dysgenesis, normal ovaries, normal right kidney, and left ectopic kidney located in the lower abdomen. Laparoscopic Davydov procedure was done to create a neovagina. Discussion: In our case, the patient was diagnosed with MRKH Syndrome, a syndrome of abnormal uterine and vaginal formation with normal ovarian function. The presence of ectopic kidney in the patient showed the MRKH Syndrome type II, which required comprehensive management. The patient was treated with Davydov procedure, which is a simple, fast and safest surgical procedure in managing MRKH syndrome. Conclusion: A thorough examination is needed in MRKH patients to find other possible non- gynecological disorders, such as renal, vertebral, and hearing disorders, in order to carry out comprehensive management.

FRI490 Association Between TSH Levels And Early Development Of Secondary Sexual Characteristics Among Children With Congenital Hypothyroidism

Abstract Disclosure: M.M. Nunez Stosic: None. T. Seeherunvong: None. Although hypothyroidism typically delays puberty, early pubertal development in patients with hypothyroidism and markedly elevated TSH levels has been reported. Recent studies investigated the association between thyroid function and timing of puberty among normal children. Jung et al. reported an association between serum TSH and LH levels in girls with central precocious puberty. By contrast Wilken et al. found an association between serum T4 level and onset of pubarche but not thelarche among female subjects. We investigated the association between serum TSH levels and onset of secondary sexual characteristics among patients with congenital hypothyroidism. A retrospective study was conducted including girls and boys aged ≥6 years and ≤ 18 years with confirmed primary congenital hypothyroidism who were seen in our pediatric endocrinology clinic at University of Miami, between May 2012 and May 2022. Age of onset of secondary sexual characteristics (SSC) such as body odor, acne, axillary hair, pubic hair, breast/testicular development was recorded. Early onset of SSC was defined by its presence in girls younger than 8 years and in boys younger than 9 years. Onset of SSC was considered early normal if it occurred between 8-9.5 years in girls and between 9-10.5 years in boys. A third group of patients were those with onset of SSC after 9.5 years in girls and after 10.5 years in boys. We recorded the serum TSH levels from age 6-8 years in girls and from 7-9 years in boys. We determined the average TSH levels and the proportion of the serum TSH level above normal range. IBM SPSS Statistics software version 28.0.0.0(190) was used for data analysis. Fifty-seven subjects with a history of congenital hypothyroidism, 36 girls (63.2%) and 21 boys (36.8%) were included in the study. Seventeen patients (29.8%) had early or early normal onset of SSC. The prevalence was more frequent among girls than boys, 14% and 3% respectively (p value= 0.046). Among all 57 subjects, only 9 had normal serum TSH. The mean proportion of TSH levels above normal limit was 62.4% in patients with early or normal early onset of SSC. By contrast, the mean proportion of serum TSH level above normal limit was 53.7% in those patients who had neither early nor early normal onset of SSC (p value=0.044). In summary, early and early normal onset of SSC was associated with higher TSH levels in children with congenital hypothyroidism. Further studies with a larger number of subjects will be needed to define further the specific SSC most associated with an abnormally elevated TSH. Presentation: Friday, June 16, 2023

FRI245 Non-classic CAH Presenting As Bilateral Adrenal Incidentalomas

Abstract Disclosure: Y.A. Chin: None. T. Puar: None. T. King: None. Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disorder. Non-classic CAH usually presents in late childhood or asymptomatic may remain undiagnosed. Adrenal incidentalomas have been reported as a presentation of CAH. Clinical Case: A 56-year-old man presented with a 4-day history of epigastric pain associated with chest discomfort and diaphoresis. There was no postural giddiness, vomiting, paroxysm or constitutional symptoms. He was a smoker, his parents were non-consanguineous and he had fathered 2 children. He was tachycardic at 114 bpm, but normotensive (129/89 mmHg) with no postural hypotension and no abnormal pigmentation. He had evidence of heart failure with bibasal crepitations and pedal oedema. Secondary sexual characteristics were normal and testicular volume was 15 mls bilaterally with no palpable mass. CT abdomen showed grossly enlarged bilateral adrenal glands with heterogenous nodular appearance with several focal hypodense cystic components, with absolute washout &amp;lt;60%. Biochemistry was consistent with primary adrenal insufficiency (PAI); 8am serum cortisol 188 nmol/L, with peak cortisol post 250mcg synacthen of 195 nmol/L. Serum ACTH was elevated at 254.6 ng/L, aldosterone and renin were normal and 24hr urinary normetanephrine was mildly elevated at 1982 nmol/d (NR 600-1900 nmol/d). Echocardiography revealed severe global hypokinesia (EF 20%) but myocardial perfusion imaging was negative for ischemia. In view of suspicion for tuberculosis, malignancy or infiltrative disease, CT guided adrenal biopsy was performed. Histology showed hyperplastic adrenal cortex with lipofuscin pigments, focal lymphohistiocytic infiltrates. No lymphoplasmacytic infiltrate with IgG 4 plasma cells, granuloma, malignant cells or amyloid deposits were seen. Serum 17-OHP level later came back elevated at 39.7 nmol/L (NR 1.8-10.4 nmol/L). DNA sequencing of CYP21 revealed compound heterozygous mutations in c.292+1G&amp;gt;A and c.518T&amp;gt;A, both of which have been reported to be causative of CAH. He was transitioned from stress dose to physiological glucocorticoid replacement and ACTH normalised on subsequent outpatient visits. Follow up imaging after 6 months and 2 1/2 years revealed no change in size or morphology of the adrenal glands. Follow up echocardiography showed no improvement in ejection fraction despite intensive heart failure treatment. Conclusion: Nodular adrenal hyperplasia is well described among CAH individuals, especially in those with inadequate glucocorticoid replacement and chronically elevated ACTH levels. There was no change in size of the adrenal lesions despite adequate glucocorticoid replacement. Improvement of cardiac function with glucocorticoid replacement has been reported in paediatric patients with CAH, but our case did not show any improvement on serial echocardiography. Presentation: Friday, June 16, 2023

FRI325 Pituitary Stalk Interruption Syndrome Presenting As Short Stature: A Case Report

Abstract Disclosure: S. Ravindra: None. S. Tirupati: None. Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital pituitary anatomical defect that leads to a variable degree of pituitary hormone deficiency. The classic neuroimaging findings of this condition include thin or interrupted stalk, absent or ectopic posterior pituitary, and hypoplastic anterior pituitary gland. The reported incidence of PSIS is 0.5 per 1,00,000 live births. The exact pathophysiology of this syndrome is not fully understood, but chromosomal microdeletions and perinatal asphyxia have some established roles in the literature as primary miscreants. Here we report a case of an adolescent male child who presented with complaints of short stature and absent secondary sexual characters development, diagnosed with PSIS following an MRI. Clinical Case: A 16-year-old male child was referred to the endocrinology department for the evaluation of short stature and delayed secondary sexual character development. This patient was born out of a non-consanguinous marriage and delivered at term by the vaginal route, with no other significant perinatal or family history. Psychomotor milestones were attained appropriately as per age but had poor linear growth. On examination, he had short stature - height 146cms (-2.7 SDS), weight: 53.5kg BMI: 23.5 Kg/m2 with normal vitals. Head-to-toe examination revealed immature facies, deep-seated eyes, broad nasal bridge, bilateral lipomastia, high-pitched voice, Tanner stage: A1P1, SPL:4cms, the testicular volume of 3cc bilaterally, with rest of the system-wise examinations being normal. Routine laboratory investigations (CBC, RFT, LFT, Electrolytes) were within normal limits. Bone age: 13years. The hormonal assessment showed central hypothyroidism, hypocortisolemia, and GH insufficiency, with pre-pubertal gonadotropin levels- suggestive of pan-hypopituitarism (Table 1). MRI pituitary showed anterior pituitary hypoplasia with interrupted stalk, and ectopic posterior pituitary, with no other brain anomalies which is consistent with the diagnosis of PSIS. The patient was initiated on hormone replacement therapy, currently taking hydrocortisone, growth hormone, levothyroxine, and testosterone. Conclusion: PSIS is a rare condition, that can present with various spectrum of clinical features. Signs and symptoms may not be evident in the neonatal and infancy period, therefore diagnosis is often delayed. Early diagnosis and treatment are crucial for preventing adverse effects of long-term hormonal deficiencies and improving the quality of life. Presentation: Friday, June 16, 2023

THU198 Peripheral Precocious Puberty In Girls Due To Ovarian Cyst

Abstract Disclosure: H. Lee: None. J. Hwang: None. Y. Shim: None. S. Heo: None. Objective: Peripheral precocious puberty (PPP) is precocious development of secondary sexual characteristics caused by mechanisms that do not involve activation of pulsatile GnRH secretion. PPP in girl is less frequent than central precocious puberty (CPP). it is caused by various disease such as gonadal and adrenal tumors, ovarian cysts, hypothyroidism and exposure to exogenous sex steroids. In particular, discordant pubertal development with vaginal bleeding within one year of breast development suggests hyperestrogenic state, and may be caused by autonomous ovarian cysts, McCune-Albright syndrome (MAS) and hypothyroidism. We aimed to investigate clinical characteristics and long-term clinical course of PPP in girls with ovarian cyst. Methods: This study was conducted through a retrospective medical record analysis. We studied 12 patients who were diagnosed with PPP due to ovarian cyst after pelvic sonography from January 2003 to May 2022. Patients were examined for pelvic sonography when there was vaginal bleeding and/or nipple pigmentation in PPP. pelvic sonography findings, clinical characteristics, management and prognosis of patients with ovarian cysts were investigated. Results: Ten out of 12 cases had vaginal bleeding and the 3 cases had nipple pigmentation. E2 was elevated to median value 36 pg/mL ([IQR], 19-61). There was a total of 18 episodes of ovarian cyst including recurrence. The median size of cyst was 28 mm ([IQR], 24- 34). Surgical management was performed in one patient with large cyst of 70 mm. Aromatase inhibitor was used in three cases. Follow-up pelvic sonography was performed to confirm regression of ovarian cyst. Median time to regression of ovarian cyst was 6 months ([IQR], 3-9). Five cases were diagnosed with MAS. Later, In 4 out of 12 cases were progressed to CPP and cyst was recurred more than 2 episodes in 3 cases. Median total follow-up duration of cases was 2.5 years ([IQR], 0.9-5.3). Conclusion: Most of ovarian cysts in PPP disappear spontaneously. However, It may appear as a one of findings with MAS or can progress to CPP in recurrent case. Therefore, careful follow-up is necessary in ovarian cysts of PPP. Presentation: Thursday, June 15, 2023

FRI453 Genetic Heterogeneity of Hypothalamic Hypogonadism DIsorders

Abstract Disclosure: C. Bheeman: None. O. Astapova: None. Title: Genetic Heterogeneity of Hypothalamic Hypogonadism disorders. Introduction: Hypothalamic hypogonadism (HH) can be defined as having inappropriately low serum concentrations of gonadotropins in the presence of low circulating concentrations of sex steroids. It represents a group of genetically and clinically heterogeneous disorders. Case A 32-year-old female who presented to the endocrine clinic for evaluation of infertility. Patient had menarche at age 12 but became amenorrhoeic at age 14. Her physical exam was notable for normal female secondary sexual characteristics and intact sense of smell. She had no history of bone fracture or menopausal symptoms. The patient had failed the progesterone withdrawal test twice, but had withdrawal bleeding with the birth control pill or with hormonal replacement therapy. She had failed ovulation induction with clomiphene citrate, but was able to conceive 3 pregnancies through in vitro fertilization. Patient’s labs off of hormonal replacement and birth control were: LH &amp;lt;0.3. FSH 0.6, Estradiol &amp;lt;5, Progesterone 0.4. Her prolactin level was within normal limits at 6.6 and her TSH was 1.08. MRI of the brain showed no abnormalities in the pituitary gland. Genetic testing showed that the patient was heterozygous for a duplication mutation in the ANOS1 gene. Conclusion The genotypic and phenotypic heterogeneity that can be seen in HH disorders is due to the numerous genes involved in hypothalamic hypogonadism and their intricate interactions. Mutations contributing to HH can be involved in either the neurodevelopmental or neuroendocrine pathways of the hypothalamic pituitary gonadal axis or in both. There are mutations that can be inactivating variants while some can play the role of the modifier genes. The later may be able to explain the incomplete penetrance and variable expressivity sometimes seen in HH. It is important to note that though &amp;gt; 60 genes have been implicated in HH 50% of the cases remain genetically undiagnosed. This case is particularly interesting as this patient is a female with a heterozygous mutation on the ANOS1 gene, the primary gene associated with Kallmann syndrome. Kallmann syndrome is a X-linked recessive disorder and therefore the patient having phenotypical expression of the mutation is unexpected. Through the presentation of this case we aim to explore different modes of genetic expression and the different mechanisms that could have led to this patient hypothalamic hypogonadism. Presentation Date: Friday, June 16, 2023

FRI412 A Case of 46,XX Gonadal Dysgenesis With Mayer-Rokitansky-Küster-Hauser Syndrome And Primary Hypothyroidism

Abstract Disclosure: S. Al Allawi: None. R. Osman: None. Introduction: The association between Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and gonadal dysgenesis is rarely reported in the literature. Coexistence of hypothyroidism with this condition is scarce and clinical correlation remains unclear. We describe a case of this rare clinical entity in conjunction with primary hypothyroidism. Clinical case: A 27-year-old Female with a medical history of primary hypothyroidism was referred to our clinic for evaluation of primary amenorrhea. She was born with a female phenotype. Growth was appropriate, but puberty was delayed with self-reported late pubarche at age 19. She never had a menstrual cycle, and had received hormonal replacement therapy (HRT) for a few months but failed to trigger menarche. However due to financial constraints, treatment was not continued. She was diagnosed with hypothyroidism since birth, for which she is currently maintained on levothyroxine 225 mcg daily. On physical exam, blood pressure was 126/72 mmHg, pulse rate 83 BPM, height 5’9”, BMI 34 kg/m2. No facial dysmorphisms or skeletal deformity were apparent. She had normal pubic and axillary hair distribution, breast budding consistent with Tanner Stage II. Genital examination revealed normal external genitalia and a blind vaginal pouch. Hormonal workup revealed hypergonadotrophic hypogonadism with estradiol &amp;lt; 0.5 pg/mL and post-menopausal range follicle-stimulating hormone (FSH) 36.7 mIU/mL. Thyroid stimulating hormone (TSH) 2.19 uIU/ml (nl 0.45-4.5 uIU/mL) and anti-TPO antibodies 10 IU/mL (nl 0-34 IU/mL). Prior thyroid ultrasound reported a small thyroid gland. Fluorescence in situ hybridization (FISH) analysis revealed 46XX karyotype. Abdominal and pelvic ultrasound showed normal kidneys with a non-visualized uterus and ovaries. Pelvic MRI confirmed the absence of both and showed a blind end vaginal pouch, leading to the conclusion of the coexistence of gonadal dysgenesis with MRKH. She was then placed on transdermal estradioltherapy. Conclusion: The association between gonadal dysgenesis (the most common cause of primary amenorrhea) and MRKH syndrome (the second most common cause) is infrequent. HRT remains the only therapeutic option. It aims to trigger the development of secondary sexual characteristics and prevent osteoporosis by allowing appropriate bone mineral accrual. Unfortunately, infertility remains the most significant consequential issue; hence the availability of good caring and psychological counseling should not be underestimated. The co-existence of likely non-immune primary hypothyroidism is even less frequent. To our knowledge, our case is the second reported case of this trilogy. Given the paucity of data, the association of this condition with primary hypothyroidism cannot be well established and can be coincidental. More studies are needed to determine if this condition has a higher prevalence of hypothyroidism. Presentation: Friday, June 16, 2023

FRI193 Early Presentation Of Pediatric Oncocytic Adrenal Tumor Associated With Germline TP53 Pathogenic Variant—Report Of Three Cases

Abstract Disclosure: R.R. Oppenheimer: None. L.P. Lins: None. C.P. Oliveira: None. I.P. Magalhaes: None. A. Latronico: None. B.B. Mendonca: None. M.Q. Almeida: None. A.W. Kuhn: None. H. Charchar: None. M.C. Fragoso: None. Oncocytic adrenal tumors (OAT) are uncommon and usually nonfunctional. In the pediatric age group, OAT are extremely rare and less than 20 cases have been reported. Herein we report the clinical presentation and follow up of 3 non-related children with Li-Fraumeni syndrome with a germline TP53 pathogenic variant (PV) (p.R337H) who developed secreting OAT. Case 1. A 19 month old male presented with moon face, weight gain, irritability and pubic hair (Tanner stage P3) for over 4 months. He had no family history of neoplasms and his parents were unrelated to each other. Hormonal data revealed serum cortisol 33 mcg/dL with a suppressed ACTH. Testosterone was elevated (242 ng/dL - RR &amp;lt;12 ng/dL) with low plasma gonadotropins. Androstenedione 3,08 (RR&amp;lt;0,5ng/mL). Abdominal CT revealed a left adrenal tumor (5.0 x 4.4 x 4.0cm). He underwent a left laparoscopic adrenalectomy and histopathologic analysis confirmed OAT Wieneke score 2/9. Immunohistochemistry was positive for inhibin, p53 and Ki67 (10-15%). The postoperative clinical course was uneventful. The TP53 p.R337H PV was inherited from his father. He is now prepubertal and there is no evidence of relapse in 14 months of monitoring. Case 2. An 18 month old female presented with acne, clitoromegaly, pubic hair (Tanner stage 2), axillary odor, axillary hair and weight gain. Hormonal study showed elevated total testosterone of 624.7 ng/dL, androstenedione, DHEA-S and prepubertal gonadotropins. 17OHP and cortisol were normal. Abdominal CT confirmed a heterogeneous solid nodule of 5.5 x 4.5 x 3.7 cm in the right adrenal topography. The patient underwent a right adrenalectomy and OAT was identified by histopathology (Wieneke score 3/9). Immunohistochemistry was positive for p53, inhibin and Ki67 (30%). The TP53 p.R337H PV was inherited from her mother. She had remission of secondary sexual characteristics and he is now prepubertal. Case 3. A 2 years and 8 months old girl was referred with precocious pubarche and clitoromegaly (2,6cm). She had a right flank palpable mass and tanner 1 breasts. Hormonal studies showed elevated testosterone (70ng/dL), androstenedione (3.81ng/mL) and DHEA-S (13490ng/mL), with LH 0.3IU/L and FSH 3.4IU/L. The cortisol after DST was 5.8mcg/dL and ACTH was suppressed. Abdominal MRI revealed a 5 cm tumor at the right adrenal gland. She underwent laparoscopic adrenalectomy. The histopathologic analysis revealed an OAT Wieneke score 1/9. Immunohistochemistry was positive for p53 and Ki67 (13%). The TP53 p.R337H PV was inherited from her father. Conclusion: Although rare, functional OATs have been reported in children. Herein we describe the first patients with the TP53 p.R337H PV to present with OATs. These are the youngest cases of OAT published so far. The clinical presentation, hormonal data and follow-up were not different from those of other pediatric adrenal tumors. So far there is no evidence of disease relapse during follow-up. Presentation: Friday, June 16, 2023

FRI556 Thyroid Autoimmunity Leading To Premature Ovarian Insufficiency (POI) In A Euthyroid Young Woman

Abstract Disclosure: P. rimal: None. M. Moeed: None. C. Musurakis: None. A. Ojha: None. W. Akhtar: None. C.P. Barsano: None. M.F. Siddiqui: None. Introduction: Premature Ovarian Insufficiency is rare in young women and affects only 0.1% before the age of 30. The causes of POI in most cases remain unidentified, with autoimmunity being responsible for 4-30% of the cases. We present the case of a young euthyroid woman who presented for the evaluation of primary amenorrhea and diagnosed with POI associated with thyroid autoimmunity. Clinical Case: A 28-year-old Afghani woman with no known co-morbidities was referred to endocrinology clinic for the work up of primary amenorrhea. She was a goitrous and had normal secondary sexual characteristics and a history of withdrawal bleeding with OCP. There was no known personal or family history of autoimmune disease. Work up revealed hypergonadotropic hypogonadism with high FSH, 55 mIU/ml[Ref range for postmenopausal woman 16.7-113], high LH, 20.28 mIU/ml [Ref range for postmenopausal woman 10.8-58.69] and low estradiol, &amp;lt;2 pg/ml. Anti-Mullerian hormone was low, &amp;lt;0.08ng/ml [RefRange 0.69-13.39] signifying inadequate ovarian reserves and pelvic ultrasound confirmed atrophic ovaries. Etiological work up revealed normal female karyotype, 46XX, and negative FMR gene mutation testing for Fragile X syndrome. Thyroid functions were normal TSH, 3.3 mIU/L (0.27-4.2) and Free T4, 1.29 ng/dl[Ref Range 0.70-2.7]. Autoimmune work up was negative for adrenal 21-OH antibody and anti-ovarian antibodies. However, patient had strongly positive thyroid peroxidase (TPO) antibodies, 613.77 mIU/L[Ref range 0.0-9.0] consistent with thyroid autoimmunity. DXA scan revealed osteopenia. Thus, the diagnosis of POI associated with thyroid autoimmunity was established. HRT with estradiol patch and progesterone was initiated. Calcium, Vitamin D supplements and fertility counseling were provided. Conclusion: Thyroid disease is the most common autoimmune disease associated with POI. Studies have shown higher risk of POI and infertility in patients with Hashimoto’s and Graves’ diseases with co-existing high titers of TPO or anti-thyroglobulin antibodies. Ovaries are subject to autoimmune attack that leads to diminished ovarian reserves. However, until now the association of isolated elevation of TPO antibodies with POI has not been established. A Study by Osuka et al. did not find any significant difference in AMH levels between TPO and non-TPO positive euthyroid women and concluded that unlike hypothyroid women, thyroid autoantibodies were not likely to influence ovarian reserves in euthyroid women. Our case is unique where POI is associated with isolated elevation of TPO antibodies in the absence of clinical thyroid disease. This signifies the possibility that ovarian failure may precede the onset of thyroid disease in patients with thyroid autoimmunity and should be suspected and treated at an early stage, before ovarian reserves are diminished. Presentation: Friday, June 16, 2023