Duplication of the Pituitary Gland (DPG)-Plus Syndrome Associated With Midline Anomalies and Precocious Puberty: A Case Report and Review of the Literature.

Duplication of the pituitary gland (DPG)-plus syndrome is a very rare developmental disorder with few cases described in the literature and characterized by multiple midline and central nervous system malformations. The hypothalamus and hypophysis involvement may be clinically associated with endocrine abnormalities. A 5.9-year-old female child was admitted to our Clinic for premature thelarche and acceleration of growth. DPG-plus syndrome with paired infundibula and pituitary glands was diagnosed after birth, when she appeared small for gestational age and she presented with lingual hypoplasia, cleft palate, right choanal stenosis, nasopharyngeal teratoma, and facial dysmorphisms. Neuroimaging revealed a duplication of the infundibula, the pituitary gland, and the dens of the epistropheus despite surgical removal of a rhino-pharyngeal mass performed at the age of two months. An array-CGH revealed a 2p12 deletion. At our evaluation, bone age assessment resulted advanced and initial pubertal activation was confirmed by Gonadotropin-Releasing Hormone stimulation test. Hormonal suppression treatment was started with satisfactory results. This case shows that DPG-plus syndrome must be considered in presence of midline and craniofacial malformations and endocrinological evaluations should be performed for the prompt and appropriate management of pubertal anomalies.

Is surgery effective for treating hypothalamic hamartoma causing isolated central precocious puberty? A systematic review.

The aim of this review was to determine the role of surgery in treating hypothalamic hamartoma (HH) causing isolated central precocious puberty (CPP). Literature review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Patients with isolated CPP due to HH, managed with surgical resection, were included. We found 33 studies, reporting 103 patients (76 pedunculated, 27 sessile). Patients were considered "cured" if the symptoms of PP had regressed and the hormone profile had normalized after surgery. Indications for surgery included hamartoma deemed surgically resectable (n-12), for the purpose of tissue diagnosis (n-3), partial response/failure of preoperative therapy (n-9), and unable to afford/to avoid long-term medical therapy (n-7). The extent of resection was total (TR) (n-39), near total/subtotal (NTR/STR) (n-20), partial (PR) (n-35), or unspecified (n-9). On follow-up (range: 3 months-16 years), 73.6% (56/76) of patients with pedunculated HH were cured, while 17.1% (13/76) had partial relief. Only 3/27 (11.1%) of patients with sessile HH were cured. All patients with a pedunculated hamartoma who underwent TR (n=36) improved, with 88.88% cured of the symptoms. Surgery had no effect in 17/23 (73.9%) patients with sessile HH who underwent PR. Psychological symptoms improved in 10/11 patients. There was no mortality. Permanent complications, in the form of 3rd nerve palsy, occurred in 3.7% (2/54) of the patients. To conclude, in the current era of availability of GnRH analogs, surgical resection in a subset of patients may be acceptable especially for small pedunculated hamartomas.

A Multicenter Retrospective Review of Pediatric Leydig Cell Tumor of the Testis.

Leydig cell tumors (LCTs) are rare tumors arising from testosterone-producing Leydig cells. Although LCTs are usually benign, malignancy has been reported in 10% of cases in adults, and local recurrence or metachronous tumors of the contralateral testis have been described. Radical orchiectomy is the current standard of care. We report on 12 children with LCT at 3 institutions between 2000 and 2016. Presenting symptoms included precocious puberty, palpable testicular mass, and scrotal swelling. Radical orchiectomy was performed in 9 patients. Three patients were treated with enucleation. All patients were alive at last follow-up without evidence of local recurrence or metastasis.

A 10-Month-Old Infant Presenting With Signs of Precocious Puberty Secondary to a Sclerosing Stromal Tumor of the Ovary in the Absence of Hormonal Elevation.

Precocious puberty in an infant is an alarming and infrequent finding, making the differential diagnosis difficult for practitioners. Precocious puberty secondary to a sclerosing stromal tumor (SST) of the ovary is rare. We present a case of a child that began precocious puberty at 3 months of age including development of breast buds, pubic hair, growth spurt, and menarche 5 days prior to presenting to pediatric endocrinology at 10 months. She underwent right salpingo-oophorectomy which demonstrated a soft tissue mass occupying almost the entire ovary with a tan-pink fleshy cut surface. Histological examination confirmed a variant of SST. This case represents an extremely young onset of precocious puberty secondary to a variant of SST without hormonal elevation.

Gamma Knife radiosurgery for hypothalamic hamartoma preserves endocrine functions.

Gamma Knife radiosurgery (GK) is an effective treatment for hypothalamic hamartoma. No precise data are available on the risk of endocrine side effects of this treatment. In this study, 34 patients with hypothalamic hamartoma (HH) were followed prospectively at the Department of Endocrinology, La Timone Hospital, Marseille, France, for a mean follow-up of >2 years (mean ± standard deviation [SD] 3.6 ± 2 years). Initial pre- and post-GK radiosurgery evaluations were performed, including weight, body mass index (BMI), and a complete endocrinological workup. At diagnosis, eight patients presented with central precocious puberty at a mean age of 5.4 ± 2.4 years. At the time of GK (mean age 18.2 ± 11.1 years), two patients previously treated with surgery presented with luteinizing hormone/follicle-stimulating hormone (LH/FSH) deficiency. After GK, only one patient presented with a new thyrotropin-stimulating hormone (TSH) deficiency, 2 years after the procedure. The other pituitary axes remained normal in all but two patients (who had LH/FSH deficiency prior to GK). There was no significant difference between pre- and post-GK mean BMI (26.9 vs. 25.1 kg/m2 , p = 0.59). To conclude, in this group of 34 patients, GK did not induce major endocrinologic side effects reported with all the other surgical techniques in the literature. It is, thus, a safe and effective procedure in the treatment of hypothalamic hamartoma.

Gonadotropin-dependent precocious puberty in an 8-year-old boy with leydig cell testicular tumor.

Leydig cell testicular tumors are very rare in children. They can present as gonadotropin-independent precocious puberty due to excess androgen secretion. We report the case of an 8-year-old boy with isosexual precocity whose hormonal investigation showed luteinizing hormone-independent testosterone hypersecretion. Although no palpable mass was present, scrotal ultrasound revealed a testicular tumor. Testis-sparing tumor resection was performed and the histopathology analysis showed a Leydig cell tumor. After surgery the testosterone levels remained high and further examination showed gonadotropin-dependent precocious puberty, which is believed to be likely caused by the activation of the hypothalamic-pituitary axis due to a long-term exposition to sex steroids. He is currently being treated with a long-acting gonadotropin-releasing hormone analog and the process of sexual precocity has until now been suppressed.

Precocious pseudopuberty due to an autonomous ovarian follicular cyst: case report with a review of literatures.

BACKGROUND: Small follicular cysts are commonly found in the ovaries of prepubertal girls, and in most cases, they are of no clinical importance. These cysts are usually self-limiting and resolve spontaneously. However, occasionally, these cysts may enlarge and continue to produce estrogen, resulting in signs of sexual precocity. Here, we report a case of precocious pseudopuberty associated with an autonomous ovarian follicular cyst. CASE PRESENTATION: A 5.9-year-old girl initially presented to a local clinic with vaginal bleeding and a large unilateral ovarian cyst. At 6 months after the initial acute episode, the patient visited our hospital as the ovarian cyst had persisted and increased in size. Endocrinological examination showed elevated estrogen levels and suppressed gonadotropin levels on GnRH stimulation test. Also, no skin pigmentation or bone anomaly was noted. Based on these observations, laparoscopic cystectomy was performed, and histologic analysis confirmed the diagnosis of a follicular cyst. After the laparoscopic cystectomy, the patient's hormone levels returned to normal and no ovarian cyst was detected by ultrasound. CONCLUSIONS: As autonomous ovarian cysts are usually self-limiting disorder, no treatment is necessary. Therefore, surgical management should be deferred as long as possible to avoid the risk of repeat surgery, as pseudoprecocious puberty due to autonomous ovarian cysts can resolve spontaneoulsy and frequently recurs. Precocious pseudopuberty with an ovarian cyst may be due to granulosa cell tumor or may be one symptom of the McCune-Albright Syndrome (MAS). A careful longer-term follow up of patients with autonomous ovarian cysts and/or molecular studies may be necessary in such cases.

Giant hypothalamic hamartoma: case report and literature review.

INTRODUCTION: Hypothalamic hamartomas are very rare (1:200,000) and range in size from 17.9 to 18 mm. When their dimensions exceed 30-40 mm, they are classified as giant hypothalamic hamartomas. METHODS: We present a 14-month-old boy with central precocious puberty and gelastic seizures in whom a magnetic resonance imaging scan revealed a giant hypothalamic hamartoma measuring 50 × 50 × 40 mm. RESULTS: In the 11 cases described so far, we found that in comparison to the average-size lesion, giant hypothalamic hamartomas had a lower frequency of precocious puberty, but a similar frequency of seizures. The mean age at diagnosis was younger, and males were more affected than females. Magnetic resonance imaging results were similar with the exception of mass effect. CONCLUSIONS: Giant hypothalamic hamartomas had a higher tendency to adhere to surrounding structures. Their invasiveness and cystic degeneration were frequent findings among the 11 studies. Surgical removal was ineffective in controlling refractory epilepsy and caused postoperative morbidity in all patients.

Giant multilocular sex cord tumor with annular tubules associated with precocious puberty.

We report a case of sex cord tumor with annular tubules featuring a giant multilocular cyst, grossly similar to cystadenoma, in the ovary of an 8.5 year old girl. Estrogen-related symptoms, including precocious puberty and irregular uterine bleeding, immediately improved after tumor resection.

Ashley revisited: a response to the critics.

The case of Ashley X involved a young girl with profound and permanent developmental disability who underwent growth attenuation using high-dose estrogen, a hysterectomy, and surgical removal of her breast buds. Many individuals and groups have been critical of the decisions made by Ashley's parents, physicians, and the hospital ethics committee that supported the decision. While some of the opposition has been grounded in distorted facts and misunderstandings, others have raised important concerns. The purpose of this paper is to provide a brief review of the case and the issues it raised, then address 25 distinct substantive arguments that have been proposed as reasons that Ashley's treatment might be unethical. We conclude that while some important concerns have been raised, the weight of these concerns is not sufficient to consider the interventions used in Ashley's case to be contrary to her best interests, nor are they sufficient to preclude similar use of these interventions in the future for carefully selected patients who might also benefit from them.

Non-Peutz-Jeghers syndrome associated ovarian sex cord tumor with annular tubules: a case report.

OBJECTIVE: Sex cord tumors with annular tubules (SCTAT) are a rare subtype of sex cord stromal tumor of the ovary. An evidence-based management plan with follow-up evaluations is difficult to outline because of the rarity of these tumors. We describe the case of a premenarcheal patient with a SCTAT. DESIGN: Case report. SETTING: The patient was encountered during routine patient care process. PATIENT(S): The patient presented with a pelvic mass and precocious puberty. Her condition was diagnosed as SCTAT. Her clinical presentation was consistent with an estrogen-secreting tumor, resulting in early menarche and premature breast development. Inhibin and estradiol levels were markedly elevated preoperatively and normalized 5 weeks after surgical removal of the tumor. The preoperative computed tomography scan demonstrated a 12-cm abdominopelvic mass, which appeared to be mostly cystic. INTERVENTION(S): The patient was treated surgically. She underwent laparotomy, right salpingo-oophorectomy, ipsilateral pelvic and paraaortic lymph node sampling, and partial omentectomy. Peritoneal biopsy samples were obtained from the abdomen and pelvis. MAIN OUTCOME MEASURE(S): The patient did well postoperatively. She is being observed with serial examinations and serum inhibin measurements. RESULT(S): Normalization of serum estradiol and inhibin along with cessation of menstruation were seen 5 weeks postoperatively, with persistence of morphologic signs of precocious puberty and advanced bone age at 11 months after the diagnosis. CONCLUSION(S): The diagnosis of SCTAT was established on final pathology examination based on morphologic features of the tumor microscopically and the marker expression profile on immunohistochemistry. Primary management was surgical.