Isosexual Precocious Puberty Research Articles

The clinical diversity of primary hypothyroidism presenting as a spontaneous ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) usually occurs in patients undergoing assisted reproduction techniques and ovulation induction. Its variant, spontaneous ovarian hyperstimulation syndrome, a potentially life-threatening disorder, is uncommon and only a few cases have been reported in association with hypothyroidism. This study analysed five patients with untreated chronic hypothyroidism presenting with multicystic ovaries, isosexual precocious puberty, and delayed bone age; subsequently, the follow-up and regression of ovarian pathology was assessed. Two patients had presented to the emergency department with menorrhagia and hypotension, of these, one had ovarian torsion at presentation. Three patients presented to the outpatient department: one for evaluation of short stature, one for premature menarche, and another with polycystic ovaries. They were all diagnosed with long-standing, untreated chronic hypothyroidism. There was regression of the size of the cystic ovaries on subsequent follow-up. In all these patients, long-standing hypothyroidism had resulted in ovarian hyperstimulation syndrome. The potentially life-threatening complications of this syndrome may be prevented by careful screening and a strong index of clinical suspicion at the outset. Long-standing, untreated primary hypothyroidism may result in spontaneous ovarian hyperstimulation syndrome. A high index of suspicion is required for an early and accurate diagnosis. The requirement for interdepartmental collaboration between gynaecology and endocrinology departments is essential for the successful management of this life-threatening but easily treatable disorder.

Juvenile granulosa cell tumor of the ovary: A rare cause of precocious puberty in a toddler

Ovarian tumors are a rare cause of sexual precocity in female children. Functional neoplasms of the ovary are relatively infrequent, and only 5% occur before puberty. Although ovarian juvenile granulosa cell tumor (GCT) is a rare tumor described infrequently in pediatrics, the most common presentation of this tumor is precocious puberty. We report a 1⅟2 year-old girl with isosexual precocious puberty, who presented with a rapid onset of premature menarche, pubic hair, and vaginal bleeding, with an abdominal mass on clinical examination. Ultrasonography of the pelvis and abdomen showed a heterogeneously hypoechoic solid mass with cystic areas and internal vascularity. The child underwent a left oophorectomy. Microscopic features of the resected mass were characteristic of juvenile GCTs. Even though the most common cause of precocious puberty in girls is idiopathic, functional ovarian tumors must be considered, especially when the onset is at an early age and puberty is rapidly progressive. Early-stage disease has a good prognosis, and adjuvant chemotherapy is not indicated.

Van Wyk–Grumbach Syndrome

Van Wyk–Grumbach syndrome is a rare presentation of long-standing prepubertal hypothyroidism in a female characterized by bilateral polycystic ovaries, delayed skeletal growth, and isosexual precocious puberty. We report a case of juvenile primary hypothyroidism presenting as an abdominal mass due to huge bilateral ovarian cysts which responded to the thyroid hormone replacement therapy. This case report highlights that hypothyroidism and other endocrinopathies should be considered in the differential diagnosis of girls with short stature and ovarian masses to avoid unnecessary surgery in young women.

Ovarian steroid cell tumors, not otherwise specified: analysis of nine cases with a literature review

BackgroundOvarian steroid cell tumors (SCTs), not otherwise specified (NOS), are rare, with few large studies. The purpose of this study was to analyze the clinical features, prognosis, and treatment choices for these patients of different age groups.MethodsThis was a retrospective study. We identified nine cases of ovarian steroid cell tumor, not otherwise specified, confirmed by post-operative histopathological examination, and analyzed clinical features, surgical procedures, and follow up outcomes. We also reviewed cases reports of ovarian steroid cell tumors, not otherwise specified.ResultsA total of nine cases were included. The age range was 9–68 years (mean, 41.89 ± 19.72 years). Clinical features included virilization, amenorrhea, abdominal pain, vaginal bleeding, isosexual precocious puberty, Cushing’s syndrome, and abnormal weight gain with elevated testosterone levels. The follow up interval ranged 5–53 months and no recurrence was observed.ConclusionOvarian steroid cell tumors covered all age groups, with manifestations of androgen excess. Younger patients appeared to have a more favorable prognosis, which provided more opportunities for these patients to pursue treatment options that will preserve reproductive function.

Down Syndrome and Van Wyk-Grumbach Syndrome: A Rare Presentation

Van Wyk-Grumbach Syndrome (VWGS) is presented by juvenile hypothyroidism, delayed bone age and isosexual precocious puberty. All of the features will be reversed with treatment of the underlying thyroid hormone deficiency. It has been described, a 3- year-old girl with Down Syndrome who presented with per vaginal bleeding. Physical examination showed typical morphologic features of Down Syndrome and hypothyroidism. Pubertal developments in tanner stages were: breast at stage II and pubic hair at stage I. Serum TSH level was very high. Serum FSH, LH and Estrogen level were also high for her age. On radiological examination her bone age was 2 years. Her pelvic sonogram revealed enlarged uterus with ovarian cysts. These findings confirmed the diagnosis of VWGS. Treatment with Levothyroxine, her vaginal bleeding did not recur and ovarian cyst size decreased after 4 weeks and disappeared after 2 months. In conclusion, thyroid hypo-function must be investigated in children who have precocious puberty with multicystic enlarged ovaries. JAFMC Bangladesh. Vol 18, No 1 (June) 2022: 97-99

Case report: A rare case of central precocious puberty due to hypothalamic hamartoma

Precocious puberty defined by the onset of secondary sexual characteristics before 8 years in girls and 9 years in boys. It is more common in females than males and is usually sporadic. Depending on the primary source of hormonal production, precocious puberty is classified as central and peripheral. Precocious puberty in infants is very rare. While investigating a case of precocious puberty, it is essential to progress systematically, with an identification of isolated or complete precocious puberty followed by bone age estimation, relevant hormonal assays, including GnRH stimulation, as well as neuroimaging when indicated. We present a case of isosexual (central) precocious puberty in a 1 year, 3-month-old girl, who was symptomatic for 1 year of age and was diagnosed to have hypothalamic hamartoma after methodical evaluation and responded to treatment with GnRH agonists.

Updating the Landscape for Functioning Gonadotroph Tumors.

Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they cause clinical syndromes due to hypersecretion of intact gonadotropins. The clinical spectrum of endocrine dysfunction includes an exaggerated response of ovaries characterized as ovarian hyperstimulation syndrome (OHSS) in premenopausal females and adolescent girls, testicular enlargement in males, and isosexual precocious puberty in children. Transsphenoidal surgery and removal of tumor reduces hormonal hypersecretion, improves endocrine dysfunction, and provides tissue for further analysis. Medical therapies (somatostatin analogues, dopamine agonists, GnRH agonists/antagonists) are partially or totally ineffective in many cases, especially with respect to antitumor effect. This review aims to update recent literature on these rare functioning tumors and highlight their therapeutic management.

109 Juvenile granulosa cell tumor of the ovary as a cause of isosexual precocious puberty in a 3-year-old girl

Objective: The etiology of most cases of precocious puberty in girls is idiopathic and can develop due to central or peripheral causes [ [1] Cisternino M. Arrigo T. Pasquino A.M. et al. Etiology and age incidence of precocious puberty in girls: a multicentric study. J Pediatr Endocrinol Metab. 2000; 13: 695 Crossref PubMed Google Scholar ]. Juvenile granulosa cell tumor (JGCT) of the ovary can be seen as a rare cause of peripheral precocious puberty. [ 2 Young R.H. Dickersin G.R. Scully R.E. Juvenile granulosa cell tumor of the ovary. A clinicopathological analysis of 125 cases. Am J Surg Pathol. 1984; 8: 575 Crossref PubMed Scopus (370) Google Scholar , 3 Wu H. Pangas S.A. Eldin K.W. et al. Juvenile granulosa cell tumor of the ovary: a clinicopathologic study. J Pediatr Adolesc Gynecol. 2017; 30: 138-143 Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar ]. We describe a case of JGCT presented with isosexual precocious puberty in a three-year-old- girl. Case: A three-year-old- girl presented with a three-week history of vaginal bleeding. She had also started having some breast development during the past few months. Her past medical and surgical history were unremarkable. On physical examination, she had Tanner stage 2 breast and stage 1 pubic hair development. Perineal inspection revealed normal anatomy of the external genitalia and no mass or foreign body. There was also no sign of vulvovaginitis or trauma. Vaginal mucosa looked estrogenized. Transabdominal ultrasound showed a normal prepubertal uterus with increased endometrial thickness and an approximately 6-cm solid adnexal mass on the left. Laboratory investigations revealed elevated estradiol level (117 pg/mL) despite of prepubertal gonadotropin levels. Serum tumor markers included alpha-fetoprotein, beta human chorionic gonadotrophin and lactate dehydrogenase were normal, but inhibin B level was significantly elevated (1101 pg/ml). Magnetic resonance imaging (MRI) revealed a solid mass of approximately 6 cm in size in the left ovary with marked contrast enhancement and suspicious para-aortic lymph node involvement which was approximately 2 cm in size (Figure 1). Left salpingo-oophorectomy and excision of palpable paraaortic lymph nodes were performed through a lower midline incision (Figure 2). Postoperative period was uneventful. Histopathologic examination revealed FIGO stage 1A JGCT of the left ovary and reactive lymph nodes without tumor metastasis. Her estradiol level was < 5 pg/ml and inhibin level < 3.6 pg/ml at 4 weeks postoperatively. Adjuvant chemotherapy was not indicated due to early stage of the disease. Conclusion: This report highlights the importance of screening for peripheral causes of precocious puberty such as hormone-secreting tumors of the gonads or adrenal glands, especially in the presence of elevated estrogen level despite of prepubertal gonadotropin levels.

Transformation of Peripheral Sexual Precocity to Central Sexual Precocity Following Treatment of Granulosa Cell Tumor of the Ovary

Juvenile granulosa cell tumor leading to isosexual peripheral precocious puberty is a well-known association. Here, we report a rare case of central precocious puberty secondary to granulosa cell tumor of the ovary. A five-year and five-month-old girl presented with a history of progressive enlargement of bilateral breasts and intermittent vaginal spotting, associated with growth acceleration. Elevated estradiol and suppressed serum follicle-stimulating hormone were found on investigation. Additionally, abdominal and pelvic ultrasonography was suggestive of a right ovarian mass, which proved to be a juvenile granulosa cell tumor on histopathology and immunohistochemistry, leading to a diagnosis of peripheral precocious puberty secondary to granulosa cell tumor of the ovary. One and a half years after resection of the tumor, secondary sexual characteristics progressed with regression of tumor markers, and no mass was noted on ultrasonography, leading to the suspicion of central precocious puberty. Pubertal basal luteinizing hormone (LH) and elevated triptorelin-stimulated LH confirmed the diagnosis of central precocious puberty secondary to granulosa cell tumor of the ovary.

Torsion of juvenile granulosa cell ovarian tumor

Juvenile granulosa cell tumor (JGCT), which is one of the sex cord-stromal tumors of the ovary, is a rare malignancy of childhood. Juvenile type is a rare form that accounts for 5% of granulosa cell tumors. Isosexual precocious puberty is the most common presentation in prepubertal girls with juvenile granulosa cell tumors. Less frequently, they present with the complaint of a mass in the abdomen. We present an 8-year-old girl with a juvenile granulosa cell tumor who presented with sudden onset of abdominal pain and enlargement of the abdomen. She underwent exploratory laparotomy with right salpingo-oophorectomy and a complete mass resection was performed. Pathologic staging of the mass, which was diagnosed as juvenile granulosa cell tumor of the ovary, was determined as pT1c3, and our patient received four cycles of chemotherapy.

Congenital adrenal hyperplasia in men: classical form. Clinical case

Recently, in the foreign scientific literature there have been reports that boys and young men with the classic virile form of congenital adrenal hyperplasia or congenital dysfunction of the adrenal cortex as a result of inadequate glucocorticoid therapy in 21–28% of cases have testicular adrenal rest tumors, which increases under the influence of excessive production of adrenocorticotropic hormone (ACTH). This benign formation up to 2 cm in diameter and larger is detected by palpation and ultrasound. The formations can press on the testicular tissue and lead to hypogonadism. Such individuals may have low testosterone levels due to decreased Leydig cell function. Testicular adrenal rest tumors usually decrease after treatment optimization. Unreasonable surgery is sometimes performed in suspected cancer. A clinical case is presented of the classic form of congenital adrenal hyperplasia, manifested itself in isosexual precocious puberty, cryptorchidism and testicular adrenal rest tumors rare, increased under the influence of excessive ACTH production as a result of inadequate glucocorticoid replacement therapy. Formations detected during ultrasound decrease when treatment is optimized. Observation of the patient in the dynamics showed that ones of the main diagnostic hormonal tests are blood levels of ACTH and 17-hydroxyprogesterone, which at the time of disease detection were excessively high. Continuous glucocorticoid replacement therapy maintains the level of these indicators within the reference values. Timely diagnosis of the nature of the pathology, constant corrective hormone therapy ensured the patient’s ability to adapt to life and society in accordance with his status. Clinical manifestations of hypocorticism and/or hyperandrogenism in the parents of our patient were not detected, which indicates autosomal recessive inheritance of congenital adrenal hyperplasia. In the future, it is important to provide genetic counseling to expectant parents, especially with manifestations of hyperandrogenism, to assess the possible development of such pathology in their offspring.

Hormone Secreting Juvenile Granulosa Cell Tumor of the Ovary in an Infant Presenting with Massive Ascites and Precocious Pseudopuberty

Juvenile granulosa cell tumors (JGCTs), account for 4–5% of GCTs, the rare sex cord stromal tumors. Presentation of JGCTs in infants is even rarer. We present case of a 3-month-old female infant with abdominal distension, feeding intolerance and fever of 10 days' duration. The child had gross abdominal distension causing visible respiratory distress. She also had signs of isosexual precocious puberty. Radiological evaluation was suggestive of left ovarian tumor. Left oophorectomy with preservation of the fallopian tube was done after hemodynamic stabilization. Histopathology evaluation of the tumor was suggestive of JGCT, which was confirmed on immunohistochemical evaluation. On 1 year follow-up, the child is stable, has achieved age-appropriate milestones and is tumor-free. Parents have been explained importance of regular follow-up to detect tumor recurrence. This is probably the youngest case of JGCT presenting with precocious puberty reported in literature so far.

Van Wyk Grumbach Syndrome.

Van Wyk Grumbach syndrome is well known for protracted hypothyroidism, characterised by multicystic ovaries (normal size ovaries contain many follicles of various sizes), isosexual precocious puberty and delayed skeletal growth. A series of ten children with Van Wyk Grumbach syndrome is been presented with their clinical features, biochemical and radiological profile and management. Patients showed a noteworthy improvement upon thyroxine therapy. It is vital to keep this entity in consideration and; hence, should investigate for thyroid status during the evaluation of ovarian cysts. Thyroxin replacement after establishing the diagnosis early can prevent the patient from going through extensive workup and surgeries. Key Words: Hypothyrodism, Multicystic ovaries, Isosexual precocious puberty.

Pubertas Prekoks Perifer Isoseksual akibat&lt;i&gt; Juvenille Granulosa Cell Tumor&lt;/i&gt;

A 16-month-old girl with peripheral isosexual precocious puberty due to juvenile granulosa cell tumor underwent unilateral salpingo-oophorectomy procedure to stop the symptoms of precocious puberty. The diagnosis was established based on the patient’s medical history, physical findings, laboratory and other examinations which demonstrated secondary sexual characteristics according to Tanner scale M3P2, presence of abdominal mass, elevated serum estradiol, and a histological finding of juvenile granulosa cell tumor. Karyotyping results was normal. Left salpingo-oophorectomy successfully reduced estradiol concentration and stop the menstruation, while the other secondary sexual characteristics is monthly assessed at the clinic.

Juvenile granulosa cell tumor of the ovary in a 7-year-old girl: Rare case report

Ovarian granulosa cell tumor (GCT) is a rare ovarian neoplasm, which typically occurs in children and young women. More than 90% of the patients are diagnosed in Stage IA, who can be cured by unilateral oophorectomy. Meanwhile, the remaining is diagnosed in more advanced stages, wherein tumors may exhibit aggressive behavior. In this stage, surgery and adjuvant chemotherapy may be required. Isosexual precocious puberty in girls is mostly idiopathic in origin. However, this is a diagnosis of exclusion, and many differential diagnoses have to be thought of in evaluation of precocity in girls. We are presenting here a case of isosexual precocity in a 7-year-old girl due to juvenile GCT of ovary, a rare etiology of precocity.

Iso-sexual precocious puberty associated with primary hypothyroidism–Van Wyk–Grumbach syndrome: An uncommon presentation of a common disorder

Iso-sexual precocious puberty associated with primary hypothyroidism–Van Wyk–Grumbach syndrome: An uncommon presentation of a common disorder

MON-LB082 Elevated Expression of KISSR Is Associated with Secretory Function of Functioning Gonadotroph Adenomas

Background: Gonadotroph adenomas are identified as the most common histological subtype of pituitary adenomas. But overwhelming majority of them are hormonally silent and act as non-functioning pituitary adenomas that presenting only with mass effects. The rest few named functioning gonadotroph adenomas (FGAs) can secrete biologically active gonadotropins and lead to characteristic abnormities of the hypophysial-gonadal axis function, such as isosexual precocious puberty in children, ovarian hyperstimulation and menstrual irregularity in premenopausal women and testicular enlargement in men. The mechanism remains unknown why FGAs have different secretory function from the clinical non-functioning ones which are morphologically same. Kisspeptin secreted by KISS1 neurons on hypothalamus can stimulate GnRH secretion when combines with its receptor KISS1R. Objective: To investigate whether kisspeptin and KISS1R are of effect for the secretory function of FGAs. Methods: we studied 18 clinically and histologically verified pituitary adenoma tissue samples: Group I(3 FGAs including 2 females and 1 male) ,Group II(12 NFPAs with immunohistochemistry positive for FSH and/or LH)and Group III(3 NFPAs with immunohistochemistry negative for FSH and LH). The mRNA expression levels of Kisspeptin and KISS1R were measured by RT-qPCR and the protein expression of KISS1R were determined by Western bolt. We also sequenced KISS1R gene in sera of all 3 FGAs patients and 2 female FGA stissue samples. The DNA methylation analyses of KISS1R promoter region in PA tissues were also performed. Results: We found that the KISS1R mRNA level was significantly different among three groups(p<0.05): Group I was highest,which was 1.8 times as Group II and 8.5 times as Group III. But there was no difference of Kisspeptin mRNA level among the groups. Western bolt showed that the KISS1R protein level was also significantly up-regulated in FGA group than the other two groups(p<0.05). A missense change c.1091T>A in exon 5 of KISS1R gene was found in the both female FGA pituitary adenoma DNA while no mutations of this gene were found in the serum samples of 3 FGA patients. No DNA methylation differences of KISS1R promoter region were observed among the three groups. Conclusion: We speculate that the elevated expression of KISS1R could play a role in the secretion function of FGAs. The expression of KISS1R might need to achieve to a certain threshold that could bring the secretory ability of FGAs. Sources of Research Support: The National Key Research and Development Program of China” (No. 2016YFC0901501) and CAMS Innovation Fund for Medical Science (CAMS-2016-I2M-1-002) awarded to HJZ. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

65. A Case Review of a Rare Ovarian Tumor Presenting with Ovarian Torsion and Isosexual Precocious Puberty

Precocious puberty is the onset of secondary sexual characteristics prior to 8 years of age. It can be related to a central or peripheral process. In the setting of an ovarian mass the differential diagnosis includes functional ovarian cysts, McCune Albright syndrome (MAS), hypothyroidism and Sex Cord Stromal tumors (SCST) most commonly Granulosa cell tumors.

An uncommon presentation of a common disorder: Van Wyk–Grumbach syndrome

Van Wyk–Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism, delayed bone age, and isosexual precocious puberty. We report the case of a 7-year-old girl who presented with premature menarche, short stature, and isosexual precocity. She had delayed bone age and multicystic ovaries. High circulating levels of thyroid-stimulating hormone (TSH) with prepubertal luteinizing hormone confirmed the diagnosis of VWGS. High circulating levels of TSH acting directly on follicle-stimulating hormone receptors could be the mediators of precocity. VWGS syndrome is quite rare and needs to be suspected for prompt treatment and resolution and avoidance of unnecessary surgery.

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism.

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH.Learning points:Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.