Amenorrhea Research Articles

SAT346 Empty Sella Syndrome And Hypopituitarism In A Childhood Cancer Survivor

Abstract Disclosure: W. Akhter: None. J.L. Gilden: None. Introduction: It has been reported that 50% of childhood cancer survivors develop an endocrinopathy and require life-long monitoring. Hypopituitarism is common in patients who have been treated with radiotherapy and is progressive and irreversible. We present the case of a young cancer survivor, referred for evaluation of secondary amenorrhea and hyperprolactinemia., who was diagnosed with empty sella syndrome and hypopituitarism. Clinical Case: A 29-year-old female with past history of right maxillary rhabdomyosarcoma at age 15, treated with chemotherapy and radiation, was referred to the endocrinology clinic for evaluation of secondary amenorrhea and hyperprolactinemia. Menarche was at age 13, and stopped when starting chemotherapy and radiation. She had not been treated with hormone replacements or dopamine agonists. Upon evaluation, she had fatigue, lethargy, generalized muscle weakness, but denied headaches, fractures, abdominal pain, galactorrhea, and vaginal dryness. Laboratory revealed hypopituitarism with low estradiol <15 (nl=30-400 pg/ml premenopausal women, <10 pg/ml postmenopausal women) with inappropriately low FSH 0.82 (nl=1.5-12.4 mIU/ml), and low LH 0.22 (nl=5-25 IU/L premenopausal female), high prolactin 41.3 (nl=non-pregnant female <25 ng/mL, pregnant female 80-400 ng/mL), negative HCG, low cortisol 3.4 (nl=5-25 mcg/dL), low ACTH 9.7 (nl= 10-60 pg/mL), normal TSH 2.446 (nl=0.27-4.20 uIU/mL) and Free T4 0.54 (nl=0.5-1.6 ng/dL), negative thyroglobulin <1 (nl=0-4 IU/mL) and thyroid peroxidase AB 0.46(n=0-9 IU/mL), normal HbA1C 5.2(nl<5.7 %). MRI pituitary with contrast done 11 yrs. earlier showed a 1.5 mm focus of relative delayed and nonenhancement between anterior and posterior pituitary gland, as well as an overall volume of the pituitary smaller than expected for age. However, recent repeat MRI of brain and sella revealed a partially empty sella without evidence of macro or microadenoma. Conclusion: Patients with childhood malignancies have a greater chance of survival, as observed in the past 30 years. It is now recognized that disorders of the hypothalamic-pituitary axis can occur at any time in patients who have undergone radiation therapy. We should be aware that empty sella syndrome, which can be caused by radiation, can also be associated with hormonal abnormalities. Studies have reported that 50 % of patients with empty sella syndrome had endocrine dysfunction, with the most common endocrine abnormality being hyperprolactinemia. Therefore, amenorrhea in our patient could be from hypopituitarism caused by radiation and empty sella, as opposed to hyperprolactinemia. When evaluating amenorrhea our focus should not be entirely on hyperprolactinemia, but a diagnosis of empty sella syndrome can be missed, thus delaying appropriate hormonal replacement therapy. Presentation: Saturday, June 17, 2023

THU440 A Case Of Osteomalacia In A Young Adult Female With Premature Ovarian Insufficiency

Abstract Disclosure: I.H. Kasimoglu: None. T. Vu: None. J.Q. Dai-Ju: None. Background: Osteomalacia is a condition due to inadequate mineralization during the bone-remodeling process. Common causes of bone demineralization include Vitamin D deficiency and low calcium intake. Consequently, the treatment often involves both Vitamin D and calcium supplementation, corresponding dietary modifications, and adequate exposure to sunlight. Clinical Case: 34-year-old female with past medical history of sickle cell disease s/p allogenic bone marrow transplant in 11/2020, brain toxoplasmosis infection 3/2021, secondary amenorrhea due to premature ovarian insufficiency diagnosed in 12/2021, was referred to endocrinology for management of osteomalacia. Dexa Scan from 11/2021 reported lower bone density than expected compared with the same age/gender group (Z-Scores: Left Hip – 0.3, Neck –1.4, and L1-L4 –3.6). Vitamin D 25-OH level was 8.3 (n>30) ng/mL and serum calcium level as low as 5.8 (n8.6-10.3) mg/dL in 3/2021, PTH-I elevated to 459 (n10-68) pg/mL, alkaline phosphatase elevated to 166 (n34-104) U/L. The patient was encouraged to increase Vitamin D3 to 4000 iu daily and calcium intake to 1200 mg daily. After discussion with patient of benefits and risks of hormone replacement, patient was started on very low dose of estradiol patch (0.025mg/day) for concern of prior history of pulmonary embolism, and progesterone 100 mg oral daily 3/2022. Vitamin D 25-OH, PTH, serum and 24 hr urine calcium have been within normal range since 9/2022. Dexa Scan from 11/2022 showed significant improvement of bone density (32.0% increase of lumbar spine, 11.2% increase of left hip). This case of osteomalacia resulting from Vitamin D deficiency and subsequent secondary hyperparathyroidism demonstrates that it is imperative to recognize and treat Vitamin D deficiency because it restores bone strength and prevents fractures while simultaneously correcting biochemical abnormalities (1). This case is also interesting as the patient still carries an increased risk of bone density loss complicated by underlying premature ovarian insufficiency and hypoestrogenic state. Thus, by providing patients with the appropriate Vitamin D and calcium supplementation recommendations along with hormone replacement therapy in young adults, it is possible to rehabilitate their overall bone health as well as reduce future risks of fractures. Conclusion: Adequate Vitamin D and calcium supplementation is important for the management of osteomalacia. In patients with premature ovarian insufficiency, it is even more imperative to promote supplementations, dietary modifications, and sunlight exposure in conjunction with traditional agents of hormonal therapy to promote overall bone health. Reference: 1) Bhan A., et al. Osteomalacia as a result of vitamin D deficiency. Endocrinol Metab Clin North Am. 2010;39(2):321–331. 10.1016/j.ecl.2010.02.001 Presentation: Thursday, June 15, 2023

SAT343 Nicotinamide Nucleotide Transhydrogenase (NNT)-related Familial Glucocorticoid Deficiency: More Than Adrenal Insufficiency

Abstract Disclosure: A. Shanker: None. H.L. Calero: None. K. DeCarlo: None. Background: Familial glucocorticoid deficiency (FGD) is a rare cause of primary adrenal insufficiency, with an estimated prevalence of fewer than 5,000 cases in the United States. Patients often present as infants with signs including hypoglycemia, failure to thrive, seizures, and recurrent infections. Clinical Case: A 25-year-old woman with a history of intellectual disability was admitted with MIS-A due to COVID-19. Her presenting symptoms were lethargy and fever for several days. Her vitals were significant for a heart rate of 122 with atrial flutter and blood pressure of 90/50. Her initial labs showed elevated TSH (24.07 mcIU/mL [0.35-4.00]), normal free T4 (0.7 ng/dL [0.6-1.7]), hyponatremia (133 mmol/L [135-145]), and low alkaline phosphatase (25 U/L [40-125). Her physical exam was notable for hyperpigmentation, macrognathia, and oral mucositis. Her parents report she has limited daily activities and recalls recurrent illnesses as a child. She has been amenorrheic for the past 5 years; menarche was at age 12. Further chart review revealed that ketotic hypoglycemic seizure was diagnosed during hospitalization at 11 months of age. . Pediatric Endocrinology diagnosed Addison’s disease, which was treated until age 12 when she was lost to follow-up. On this admission, ACTH was elevated (756.5 pg/mL [7.2 - 63.3]), 8 AM cortisol was 1.2 ug/dL, and peak cortisol obtained after high dose co-syntropin stimulation was abnormal at 1.1 ug/dL upon high dose. Primary adrenal insufficiency was confirmed, and stress-dose steroids were initiated; her clinical condition improved. She was discharged with prednisone and fludrocortisone maintenance therapy. As an outpatient, TSH was persistently elevated (17.9 mcIU/mL [0.35-4.00]) and weight-based levothyroxine was initiated. Secondary amenorrhea testing demonstrated normal FSH, LH, and estradiol levels and discussions began regarding progesterone withdrawal testing (pending given patient again lost to follow up). The nutritional screening revealed deficiencies in vitamins A, C, and D, and supplementation was initiated. A unifying diagnosis was reached with microarray and whole exome sequencing showing nicotinamide nucleotide transhydrogenase (NNT) -related FGD. Conclusions: In FGD, several causative genes have been identified. One of these, NNT is expressed in most tissues, including cardiac, renal, thyroid, gastrointestinal, and gonadal tissue. This may predispose patients to organ dysfunction outside of the prominent effect on the adrenal glands. Since NNT is widely expressed, routine screening can include nutritional, renal, and hepatic labs and patients should receive reproductive counseling due to the risk of gonadal dysfunction. Therefore, patients with NNT-related glucocorticoid FGD require significant care coordination to ensure that patients receive uninterrupted therapy and appropriate multispecialty follow-up. Presentation: Saturday, June 17, 2023

SAT369 Rare Cause of Hyperandrogenism and Elevated 17 OH Progesterone Levels - Ovarian Steroid Cell Tumor (NOS)

Abstract Disclosure: A. Shafi: None. G. Meier Surrey: None. Background:There are several causes of hyperandrogenism. We report a rare cause of hyperandrogenism and elevated 17 OH progesterone levels due to ovarian steroid cell tumor Clinical Case: A 21 yr old female presented to our clinic for evaluation of secondary amenorrhea and hirsutism for 2 years. She also endorsed deepening of voice and possible clitoromegaly. On physical exam she had hirsutism, acne with mild clitoromegaly. Labs were pertinent for normal TSH, Ft4, prolactin, DHEAS, am cortisol 14.85 ug/dl, ACTH 16 pg/ml (6-50), IGF-1 303 ng/ml (830-456), but elevated total and free testosterone 394.5 ng/dl (10-75), 70.5 pg/ml (0.2-5) respectively, elevated 17 OH progesterone 842 ng/dl (23-431 ng/dl depending on the menstrual phase). Due to testosterone >3x ULN, and significant symptoms of hirsutism/hyperandrogenism there was a concern for androgen producing tumor and therefore CT abdomen and Pelvis was obtained which showed “heterogeneously enhancing right adnexal mass measuring 6 x 5.1 x 5.4 cm causing leftward displacement of the uterus and left ovary. Right ovary was not identified and is likely inseparable from the right adnexal mass”. She underwent a laparoscopic Right salpingo oophorectomy with pelvic washings, peritoneal biopsies and omental biopsy. Pathology of ovary showed a steroid cell tumor, NOS. Pt seen 2 months post surgery pt reported that her menstrual cycles had become regular, however she continued to have acne and hirsutism for which she was referred to Dermatology. Post surgery 17 OH progesterone levels had normalized. Conclusion:Steroid cell tumors of the ovary are extremely rare, accounting for only 0.1% of all ovarian tumors. The clinical presentation may take many forms, including abdominal pain, distention, irregular menstrual cycles, and hirsutism. Labs can show elevated 17 OH progesterone levels. Therefore among other etiologies clinicians should also consider Ovarian Steroid cell tumor (NOS) as a possible cause for hypernadorgenism and elevated 17 OH progesterone levels Presentation Date: Saturday, June 17, 2023

FRI247 Case Of Metabolic Resolution Of Non-classic Congenital Adrenal Hyperplasia Post Roux-En-Y Gastric Bypass

Abstract Disclosure: K.G. Romo: None. S. Shu: None. M. Gabriel: None. S. Bhamre: None. Q.Z. Iqbal: None. A.A. Noor: None. G.I. Uwaifo: None. Background: Non-classic congenital adrenal hyperplasia (NCCAH) is an autosomal recessive disorder resulting from loss of function mutations of the 21-hydroxylase gene. It is characterized by mild cortisol deficiency, excess ACTH production, and androgen excess, often with various features of dysmetabolic syndrome. Elective bariatric surgery is one of the most effective long-term management strategies for morbid and complicated obesity. This case presents a woman with NCCAH and complicated morbid obesity who s/p Roux-en-Y Gastric Bypass (RYGB) had metabolic resolution of NCCAH and no longer required glucocorticoid (GC) therapy. Clinical Case: A 34-year-old G1P1 woman with NCCAH on glucocorticoid therapy, treated hypothyroidism with thyroid nodular disease, dyslipidemia, and morbid obesity (pre-RYGB BMI 60-69.9) initially presented to endocrinology on account of hirsutism and secondary amenorrhea attributed to PCOS. Work-up then confirmed diagnosis of NCCAH with 21-hydroxylase genetic testing showing deletion of one copy of CYP21A2 and the pathogenic variant p.V282L in the remaining copy. Outside the peripartum period, she was managed with OCP therapy, spironolactone, and metformin. She was additionally prescribed GC therapy of hydrocortisone 10mg TID following her diagnosis of NCCAH. She subsequently became pregnant unexpectedly. Post-partum course was complicated by significant weight gain, which led her to seek elective bariatric surgery for long-term weight management. At 5 months post-op, she had a weight deficit of ∼100lbs. Although she self-discontinued GC therapy due to fear of weight gain, her amenorrhea resolved, her hirsutism significantly improved, and lab testing revealed normalization of all NCCAH markers, including ACTH, 17-OHP, and androstenedione. Thus, GC therapy was not restarted. At 11 months post-op and still off GC therapy, she had a total weight deficit of ∼160lbs and continued metabolic resolution of NCCAH markers. Conclusions: This case presents a patient with NCCAH and morbid obesity who no longer required GC therapy post-RYGB. Presently, GC therapy remains the only available treatment for CAH; however, long-term GC therapy has the potential for myriad possible complications and side effects. Our case presents elective bariatric surgery as a potential and unique treatment option for patients with classic or non-classic CAH who have associated morbid obesity. The exact pathophysiologic basis for this effect and its potential role in long-term management of appropriate CAH patients requires further in-depth study. Presentation: Friday, June 16, 2023

FRI254 Unconventional Pre-operative Management Of Congenital Adrenal Hyperplasia

Abstract Disclosure: M.A. Ortiz-Rivera: None. L.N. Madera Marin: None. A. Rosado-Burgos: None. L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez-Vick: None. M. Alvarado-Santiago: None. A.J. Grana Santini: None. M. Feliciano-Emmanuelli: None. Management of classic salt-wasting congenital adrenal hyperplasia [CAH] warrants suppression of the hypothalamic-pituitary-adrenal axis through glucocorticoid and mineralocorticoid supplementation. Preferred glucocorticoid replacement is generally hydrocortisone [HC] 3 times daily but caring for these patients often involves unconventional choices of glucocorticoid preparation regimens tailored to meet patient needs. A 41-year-old female with history of long-standing poorly controlled classic salt-wasting CAH associated to secondary amenorrhea and hypothyroidism, presenting with bilateral myelolipomas was consulted to our service for pre-op optimization. She underwent evaluation by Urology due to worsening right-sided back pain for which an abdominal-pelvic CT was performed showing large bilateral adrenal gland lesions (left mass measuring 11.5 x 10.3 x 10.6 cm and right mass measuring 8.1 x 10.4 x 7.7 cm) consistent with adrenal myelolipomas. Endocrine surgeon favored adrenalectomy due to mass effect brought about by massive adrenal growth secondary to inadequate therapeutic regime. Patient had been lost to follow-up after transitioning from pediatric to adult Endocrinology and was managed by her primary care physician who kept her on an unmodified therapeutic regime. During a pharmacy shortage of HC, she was switched from HC 25 mg TID to 5 mg daily. Furthermore, use of fludrocortisone 0.1 mg daily had been inadvertently halted in the past year. There had been progressive skin hyperpigmentation since the age of 20, significant hirsutism and salt cravings which made her add soy sauce to meals. At the age of 12 a vaginoplasty was performed, with menstrual periods ceasing at age 15. Physical examination was remarkable for grave voice, broad shoulders, bronze skin and coarse terminal hairs on chin, upper lip, sides of face and upper back. Hormonal workup revealed a direct renin > 300 pg/mL (nl 3.6 – 81.6), ACTH 463 pg/mL (nl 0.00 – 46.00), androstenedione > 10 ng/mL (nl 0.6 – 3.10), total testosterone [TT] 419 ng/dL (nl 13 – 53) and 17-hydroxyprogesterone [17-OHprog] > 20 ng/mL (nl 0.20 – 2.6). Frequent increases in medication dosing, up to HC 20mg TID and fludrocortisone 0.1mcg BID, did not attain adequate hormonal control. Dexamethasone 0.25 mg was then added at bedtime and the patient was finally able to achieve restoration of menses, resolution of salt cravings and hormonal profile control with decreases in renin to 23.02 pg/mL, androstenedione to < 0.30 ng/mL, TT to 11 ng/dL and 17-OHprog to 3.15 ng/mL. Alternative treatment strategies are sometimes warranted to achieve control of CAH. In this patient with prominent androgen excess and amenorrhea who failed to meet goals on high doses of hydrocortisone and fludrocortisone, combination therapy with a small dose of long-acting glucocorticoid at bedtime achieved the desired goal. Presentation: Friday, June 16, 2023

THU201 Atypical Presentation Of Kallmann Syndrome With A Rare Genetic Mutation

Abstract Disclosure: E.L. Montgomery: None. B. Thrasher: None. S. Watson: None. Kallmann Syndrome presents as idiopathic hypogonadotropic hypogonadism with additional findings of hyposmia or anosmia and midline facial defects, including cleft lip/palate. We present a case of Kallmann Syndrome due to a rare genetic mutation with absent Mullerian structures. A 15 year, 6 month old female with history of cleft lip and palate and short stature was referred for primary amenorrhea. Clinical history was notable for limited sense of smell and no signs of puberty, including thelarche or adrenarche. Family History unknown (adopted). Significant physical exam findings include tanner 1 breast, no pubic or axillary hair, normal external female genitalia without clitoromegaly, unestrogenized vaginal introitus. Height 147cm (0.88%ile for age). Lab evaluation consisted of: LH 0.66 mIU/ml (2.4-12.6 mIU/ml), FSH 1.63 mIU/ml (3.5-12.5 mIU/ml), prolactin 11.30 ng/ml (4.79-23.30 ng/ml), BhCG negative, testosterone 8 ng/dl (2-17 ng/dl), free testosterone 1.1 pg/ml (<2.2 pg/ml), estradiol 3.0 pg/ml (9.0-249.0 pg/ml), AMH 2.46 ng/ml (1.05-12.86 ng/ml), thyroid function testing and growth factors normal. Imaging included pelvic ultrasound that showed no uterus or gonads. An MRI was obtained that confirmed these findings and also a blind-ending vaginal canal. While the presentation is suggestive of Kallmann Syndrome, the lack of Mullerian structures on imaging has not previously been described. Further evaluation included karyotype (46, XX) and hypogonadotropic hypogonadism genetic panel that identified a mutation in the FGFR1 gene with c.2172C>G (p.Asn724Lys), heterozygous, variant of uncertain significance. Estrogen replacement therapy was initiated with subsequent expected pubertal progression. Repeat imaging after seven months of treatment demonstrated presence of normal developing uterus and bilateral ovaries. Clinical Lesson/Conclusion: 1.Rare mutation with now 3 reports suggesting it is a true pathologic variant2.Unique presentation with hypoplastic Mullerian structures not detected on imaging.This patient’s particular variant has previously been described in in 2 individuals (mother/son) with features of Kallmann Syndrome (PMID: 16606836) with normal and partial puberty respectively, increasing the suspicion that this variant is pathogenic. Newly described FGFR1 variant associated with Kallmann Syndrome / hypogonadotropic hypogonadism. Kallmann Syndrome is not associated with lack of Mullerian structures, however this patient presented with features of Kallmann Syndrome and imaging that did not demonstrate presence of Mullerian structures. Since initiating estrogen therapy, she has had appropriate development of uterus and ovaries. This case demonstrates that prior to estrogen therapy, patients with Kallmann Syndrome may have underdeveloped Mullerian structures that not recognized on imaging prior to estrogen replacement therapy. Presentation: Thursday, June 15, 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 < 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

SAT422 Gender Affirming Hormone Therapy in a Non-Binary Individual with Swyer Syndrome

Abstract Disclosure: J.M. Yohannan: None. T. Reisman: None. Background: Swyer syndrome is a rare genetic disorder of sexual development. Patients with Swyer syndrome require physiologic hormone replacement congruent with their gender identity in order to prevent bone loss. It is also important to screen for complications of this condition including osteopenia and dysgerminomas. Clinical Case: A 25 year old individual with a history of Swyer syndrome (46 XY gonadal dysgenesis) presents to clinic to discuss initiation of gender affirming hormone therapy. The patient identifies as non-binary and is interested in starting testosterone for masculinization. The patient was initially diagnosed with Swyer syndrome at age 23 during an evaluation for primary amenorrhea. At that time the patient had a laparoscopic gonadectomy and was found to have a dysgerminoma. Upon diagnosis the patient was started on hormone replacement therapy with norethindrone acetate-ethinyl estradiol 1 - 0.01 mg for bone loss prevention. They had a bone mineral density scan two years prior to presentation that was reportedly normal. To avoid the deleterious effects of hypogonadism they were started on estradiol-norethindrone 0.05 - 0.25 mg patch to provide bone protection. They were also provided testosterone gel for masculinization as part of their gender affirming care. Swyer syndrome is a disorder of sex development in which individuals with XY chromosomes develop phenotypically female Mullerian structures (uterus, fallopian tubes, and vaginal canal). Individuals with Swyer syndrome typically have non-functional “streak gonads” and are diagnosed during evaluation for primary amenorrhea. While some cases may be from a novel mutation, there are case reports showing that the condition can have an autosomal dominant, autosomal recessive, or even X-linked pattern of inheritance depending on the mutated gene. Patients with Swyer syndrome require physiologic doses of hormone replacement for maturation of secondary sex characteristics and bone health. For this patient in particular it is also important to provide appropriate hormone replacement congruent with their gender identity. Additionally, approximately 30% of patients with this condition may develop a gonadal tumor, including dysgerminomas. Because of this, patients frequently have their gonads removed upon diagnosis. Conclusion: Patient’s with Swyer syndrome should be on appropriate hormone replacement as they do not make endogenous sex steroids. Additional consideration of masculinizing hormone replacement should be made for patients that have a gender identity other than cisgender female. It is also important to screen patients for gonadal tumors as there is an increased incidence in this population.

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, <2 pg/ml. Anti-Mullerian hormone was low, <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

FRI413 Hormonal Menstural Suppression For Menstrual Obstruction: A Retrospective Review Of Patients With Complex Obstructed Uterovaginal Anomalies Who Underwent Surgical Management In A Tertiary Referral Centre

Abstract Disclosure: H.I. Learner: None. S.M. Creighton: None. S.A. Clarke: None. Aims: To describe the use of hormonal menstrual suppression in patients undergoing surgery for complex utero-vaginal anomalies with menstrual obstruction. Background: Obstructed menstruation can present with painful primary amenorrhea or progressive dysmenorrhea due to unilateral obstructing duplication utero-vaginal anomalies. Menstrual suppression is essential to relieve pain during investigation and surgical planning. The off licence use of progestogens, hormonal contraception and GNRH analogues is common but there is little literature describing their best use in this context. Methods: This was a retrospective case series review of patients undergoing surgical management of complex menstrual obstruction in a tertiary referral centre between 2016-2022. Data collected on age, diagnosis, symptoms, duration of symptoms, surgery, the type of endometrial suppression used and associated side effects.Patients with partial obstruction were excluded. Results: Eighty-four patients were identified from the surgical database. The median age at time of surgery was 16 years (range 11-36). Unilateral obstruction was managed in 53/84 and complete obstruction in 31/84. Diagnoses included obstructed hemi-vagina (32/84), unicornuate uterus with functional uterine remnant (19/84), transverse vaginal septum (15/84), cervical/vaginal agenesis (9/84), and Mullerian agenesis with functional uterine remnant (5/84). Symptom duration information was available in 74/84 with a median of 10 months(0-252 months). Changes to endometrial suppression treatment were required in most patients, with 50/84 (40%) remaining on their original prescription. The average number of treatment regimes was 2 (0-7). Menstrual suppression at time of surgery was Norethisterone 35/84 (42%), Continuous combined oral contraceptive pill18/84 (21%), Medroxyprogesterone 11/84 (13%), GNRH 10/84 (12%), Desogestrel 6/84 (7%), and Depo-Provera 4/84 (5%). Tibolone was used as add-back in five patients on GNRHa for more than 6 months duration of use (4/5) or hypoestrogenic side-effects (1/5) . Conclusion Menstrual suppression for pain relief is an essential component in management for complex uterovaginal anomalies. Suppression should be started at initial presentation but there is limited guidance for clinicians as to what and how to prescribe. Our study has demonstrated that this can lead to chaotic prescribing, unnecessary pain and multiple treatment changes. Presentation: Friday, June 16, 2023

THU094 Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss To Follow Up

Abstract Disclosure: S.J. Sternlieb: None. K.G. Romo: None. R.S. Boothe: None. D. Englert: None. N. Manuel: None. Q.Z. Iqbal: None. Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss to Follow-up Sternlieb, S. J., Romo, K.G., Boothe, R., Manuel, N., Iqbal, Q.Z., Grissett, B., Englert, D. Background: MEN1 is a rare, autosomal dominant tumor disorder due to mutations in the MEN1 tumor suppressor gene. It is characterized by parathyroid, enteropancreatic and pituitary tumors. We present a young woman with MEN1 with prolactinoma, primary hyperparathyroidism and multiple pancreatic neuroendocrine tumors. Clinical Case: A 30-year-old woman with MEN1 presented with complaints of abdominal pain and GI bleeding (GIB). She was diagnosed with a prolactinoma at age 14 after presenting for primary amenorrhea and galactorrhea. She didn’t tolerate medical therapy with bromocriptine or cabergoline and required transphenoidal resection. At age 19, she presented with hypoglycemia and was found to have multiple pancreatic neuroendocrine tumors (NET) as well as a left (L) adrenal gland tumor. She underwent distal pancreatectomy and L adrenalectomy. Ten tumors in the pancreas stained variably for insulin, glucagon, gastrin and VIP. Multiple cortical adenomas were found in the adrenal gland. Post-operatively she developed a spinal cord hematoma related to placement of an epidural catheter for pain control, which led to permanent paraplegia. At age 21, she was diagnosed with primary hyperparathyroidism. She underwent left parathyroidectomy, then was lost to follow-up for 9 years. EGD showed multiple superficial duodenal ulcers. MRI brain identified a right (R) cavernous sinus mass inseparable from the R pituitary. CT abdomen showed a pancreatic head mass. Given the concern for neuroendocrine etiology, she underwent an EUS showing a pancreatic mass and a liver mass. Pancreatic mass pathology confirmed low-grade NET with Ki67 proliferation rate <1%, positive synaptophysin and chromogranin staining. After multidisciplinary discussion, the consensus was to continue PPI and sucralfate for GI ulcers, start lanreotide, and obtain somatostatin receptor scintigraphy. Surgery was not recommended unless significant GIB occurred on maximal therapy. She was referred to follow-up with GI, endocrinology, and NSGY. Since discharge, she has presented several times to other hospitals for abdominal pain, but has not adhered to follow-up. Conclusions: This case of recurrent neuroendocrine and pituitary tumors despite prior resections demonstrates the consequences of prolonged loss to follow-up with MEN1. Without routine surveillance, recurrence is likely. This patient lives in a rural area with lack of access to nearby subspecialty care, which is a barrier. More resources are needed to support patients with social barriers and progressive endocrinopathies. Key words: MEN1, prolactinoma, gastrinoma, NET, health care barriers Presentation: Thursday, June 15, 2023

An adolescent girl presenting with primary amenorrhea: A case report of complete androgen insensitivity syndrome

Abstract Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder characterized by distinct clinical features. Key diagnostic indicators include well-developed breasts, absent axillary and pubic hair growth, and unambiguous female external genitalia. Additional clues can be obtained from the patient’s medical history, such as a previous inguinal hernia and the absence of Müllerian structures. Testosterone levels in CAIS patients typically exceed the reference range for females and fall within the normal to elevated range for males in the corresponding age group. The conversion of testosterone to estrogen plays a crucial role in promoting appropriate breast development. In CAIS, the Müllerian structures are typically absent due to the secretion of the anti-Müllerian hormone, leading to their regression and the presence of a blind vaginal pouch. This case report presents the diagnosis and management of a 15-year-old girl with CAIS who initially presented with primary amenorrhea. The patient underwent bilateral laparoscopic gonadectomy, followed by hormone replacement therapy involving estradiol administration. Plans for future treatment include vaginal dilatation to facilitate penetrative intercourse. The case emphasizes the importance of conducting a thorough physical examination in patients with primary amenorrhea, as it aids in early detection and facilitates appropriate management decisions. By recognizing the clinical clues and implementing a comprehensive management approach, healthcare professionals can effectively address the challenges associated with CAIS and provide appropriate care to affected individuals.

Langerhans Cell Histiocytosis Presenting as Isolated Hypothalamic Involvement

Background: Obesity and associated primary amenorrhea are common presentations in the endocrinology outpatient department. Hypothalamic obesity is rare, and Langerhans cell histiocytosis (LCH) causing hypothalamic dysfunction is even more rare. Clinical Description: A 16-year-old girl presented with rapid weight gain over preceding 2 years, associated with headache for 2 months and primary amenorrhea. On examination, she had a weight and body mass index corroborating with obesity, while her height was age-appropriate. In addition, she had acanthosis nigricans but no Cushingoid features or intellectual disability. Systemic examination was normal. Management and Outcome: Considering a possibility of neuroendocrine cause of obesity, investigations were carried out. Bone age was delayed. Hormonal work-up revealed low estradiol, luteinizing hormone, and follicular stimulating hormone while thyroid function tests, growth hormone, and cortisol were normal, suggestive of hypogonadotropic hypogonadism. Magnetic resonance imaging of the brain revealed a mass in the hypothalamus region with a normal pituitary gland and stalk which was confirmed to be LCH on a stereotactic biopsy. Fluorodeoxyglucose-positron emission tomography showed no other sites of abnormal uptake. Thus, the child was diagnosed with a low-risk single-system LCH and treated accordingly. Conclusion: This case creates the awareness regarding the rare possibility of isolated hypothalamic involvement in LCH, causing obesity and primary amenorrhea, confirmed by biopsy.

Complete androgen insensitivity syndrome: A tale of two sisters with primary amenorrhea

Complete androgen insensitivity syndrome (CAIS) is a rare disorder that is often diagnosed in the pubertal period during the evaluation of primary amenorrhea. Diagnosis is important not only in the context of early removal of undescended testis but also in terms of the grave psychological outcome of the diagnosis on the adolescent and family members. Here, we present case reports of two sisters who presented with primary amenorrhea. It is imperative to keep CAIS as a differential during the evaluation of primary amenorrhea. CAIS may also present as a case of a childhood inguinal hernia.

Menstrual cycle characteristics, perceived impact on performance, and barriers to communication: Perspectives of high-performance adolescent athletes in Singapore.

The purpose of this study was to examine the menstrual cycle (MC) characteristics, explore the impact on performance, and identify barriers to and facilitators of MC-related communication among high-performance female adolescent athletes in Singapore. Ninety athletes (15.4 ± 1.8 years) from multiple sports completed an online questionnaire. Eighty-four athletes were postmenarcheal (menarcheal age 11.9 ± 1.3 years), including two who were using an oral contraceptive pill (OCP). Secondary amenorrhea, current or history of, was self-reported in 16% of athletes. Sixty-two percent and 67% of non-OCP athletes perceived that the MC affected their ability to train and compete, respectively. Athletes preferred speaking to a parent (85%) and a female figure (67%) about MC-related concerns. Through thematic analysis, three barriers to communication were constructed: (1) pervasive menstrual stigma, (2) constraints of the training environment, and (3) the low value placed on MC-related conversations. Two facilitators of communication were constructed: (1) respect athletes' individual experiences as menstruating girls and (2) foster a safe space for MC-related conversations. Findings demonstrated that menstrual irregularities are common in adolescent athletes and screening for MC disorders, particularly primary amenorrhea should be undertaken in this population, with clear support pathways for management including symptom mitigation. To support athletes in raising MC-related concerns when needed, structured communication pathways that consider individual preferences and involve a (female) point of contact should be established within the training environment. Improving menstrual health literacy among adolescent athletes before any misinformation or negative perceptions are firmly established may contribute to longevity in their athletic careers.

Lack of evidence that progesterone in ovulatory cycles causes breast cancer

A recent Perspective article asserted that progesterone secretion during ovulatory cycles is the cause of breast cancer. However, we challenge most of the evidence developed in this publication. First, there is a lack of evidence that progesterone is mutagenic for breast cells. Cause of a cancer should mean initiation by mutation, as opposed to promotion. Second, subclinical ovulatory disturbances occur rather frequently in normal-length menstrual cycles. Third, the authors attribute a potential carcinogenic effect to progesterone secreted during menstrual cycles but not to progesterone during pregnancy. They did not discuss breast cancer evidence from progesterone/progestin therapeutics. They argue that in genetic primary amenorrhea, a hypothetic lower risk of breast cancer could be due to the lack of progesterone, despite the progesterone/progestin in hormone replacements these women receive. Fourth, they advocate a regulatory effect of progesterone on several genes potentially involved in cancer genesis. In particular, they attribute a lower risk of breast cancer in women with Mayer–Rokitansky–Küster–Hauser syndrome to a defect in the progesterone-stimulated Wnt4 gene. However, this defect is only present in a small subset. Thus, the postulated progesterone breast cancer risk is unconvincing, which we discuss point by point in this commentary.

Clinical and Molecular Characteristics and Long-term Follow-up of Children With Pseudohypoparathyroidism Type IA.

Pseudohypoparathyroidism type IA (PHPIA) is a rare genetic disorder characterized by hormone resistance and a typical phenotype named Albright hereditary osteodystrophy. Unawareness of this rare disease leads to delays in diagnosis. The aims of this study were to describe the clinical and molecular characteristics of patients with genetically confirmed GNAS mutations and to evaluate their long-term outcomes. A retrospective search for all patients diagnosed with PHPIA in 2 referral centers in Israel was conducted. Nine children (8 females) belonging to 6 families were included in the study. Five patients had GNAS missense mutations, 2 had deletions, and 2 had frameshift mutations. Four mutations were novel. Patients were referred at a mean age of 2.4 years due to congenital hypothyroidism (5 patients), short stature (2 patients), or obesity (2 patients), with a follow-up duration of up to 20 years. Early obesity was observed in the majority of patients. Elevated parathyroid hormone was documented at a mean age of 3 years; however, hypocalcemia became evident at a mean age of 5.9 years, about 3 years later. All subjects were diagnosed with mild to moderate mental retardation. Female adult height was very short (mean -2.5 SD) and 5 females had primary or secondary amenorrhea. Long-term follow-up of newborns with a combination of congenital hypothyroidism, early-onset obesity, and minor dysmorphic features associated with PHPIA is warranted and molecular analysis is recommended since the complete clinical phenotype may develop a long time after initial presentation.

Gonadotropin Levels and Underlying Diseases in Adolescent With Secondary Amenorrhea.

To provide characteristics and hormonal profiles of secondary amenorrhea cases in adolescent patients treated at Hasan Sadikin General Hospital in Bandung. The study was retrospective in nature and involved the analysis of medical records from 2017 to 2022 for 44 adolescent patients aged 10-18 who had secondary amenorrhea. There were 44 adolescents included in this study after excluded 69 adults from 113 secondary amenorrhea cases. The majority of patients were 14-17 years old (38.63%), in senior high school (45.45%), had started menarche at 11 years old (45.45%), had normal nutritional status (65.91%), and had normal stature (65.91%). The underlying diseases found in most patients were systemic lupus erythematosus (SLE) and tuberculosis. Among the patients, 29 had FSH, LH, and estradiol levels measured. The results of hormonal assays showed a wide range of abnormal serum levels, with normal to low concentrations of FSH and low levels of LH and estradiol. The median (interquartile range) results for FSH, LH, and estradiol were 4.57 (0.64, 90.65), 1.635 (0.06, 55.76), and 24.3 (0.2, 154.71), respectively. Positive significant correlation between FSH and LH (p < 0.01) was found in children with secondary amenorrhea. Hormonal assay for FSH, LH, and Estradiol showed a wide range of abnormal serum level. Normal to low concentration levels of FSH and low LH and estradiol. The majority of secondary amenorrhea patients are associated with autoimmune disease and infection.

Swyer syndrome: a rare cause of primary amenorrhea

PurposeSwyer syndrome is one of the rare causes for disorders of sexual development.Case reportAn 18-year-old girl presented with complaints of inability to attain menarche. Physical examination revealed underdeveloped breast with absent pubic and axillary hair; however, the vagina was well canalized. Her hormonal profile was of hypergonadotropic hypogonadism. USG and MRI demonstrated hypoplastic uterus with very small ovaries. Chromosomal analysis reported 46 XY genetic makeup. Given the higher risk of malignancy in dysgenetic gonads, the patient underwent laparoscopic gonadectomy and had been put on hormone replacement therapy.ConclusionSwyer syndrome, though a very rare entity, should be kept in mind while evaluating primary amenorrhea. Gonadectomy should be performed early once diagnosis is made to avoid the risk of malignancy.