Case Report: Lipoma of the Tuber Cinereum Mimicking a Pituitary Gland Abnormality in a Girl With Central Precocious Puberty.

Introduction: Magnetic Resonance Imaging (MRI) is the best approach to investigate the hypothalamic-pituitary region in children with central precocious puberty (CPP). Routine scanning is controversial in girls aged 6-8 year, due to the overwhelming prevalence of idiopathic forms and unrelated incidentalomas. Cerebral lipomas are rare and accidental findings, not usually expected in CPP. We report a girl with CPP and an unusually shaped posterior pituitary gland on SE-T1w sequences. Case Description: A 7.3-year-old female was referred for breast development started at age 7. Her past medical history and physical examination were unremarkable, apart from the Tanner stage 2 breast. X-ray of the left-hand revealed a bone age 2-years ahead of her chronological age, projecting her adult height prognosis below the mid parental height. LHRH test and pelvic ultrasound were suggestive for CPP. Routine brain MRI sequences, SE T1w and TSE T2w, showed the posterior pituitary bright spot increased in size and stretched upward. The finding was considered as an anatomical variant, in an otherwise normal brain imaging. Patient was started on treatment with GnRH analogue. At a thorough revaluation, imaging overlap with adipose tissue was suspected and a new MRI scan with 3D-fat-suppression T1w-VIBE sequences demonstrated a lipoma of the tuber cinereum, bordering a perfectly normal neurohypophysis. 3D-T2w-SPACE sequences, acquired at first MRI scan, would have provided a more correct interpretation if rightly considered. Conclusion: This is the first evidence, to our knowledge, of a cerebral lipoma mimicking pituitary gland abnormalities. Our experience highlights the importance of considering suprasellar lipomas in the MRI investigation of children with CPP, despite their rarity, should the T1w sequences show an unexpected pituitary shape. 3D-T2w SPACE sequences could be integrated into standard ones, especially when performing MRI routinely, to avoid potential misinterpretations.

Routine screening by brain magnetic resonance imaging is not indicated in every girl with onset of puberty between the ages of 6 and 8 years.

CONTEXT: It is still controversial whether all girls with central precocious puberty (CPP) should undergo brain magnetic resonance imaging (MRI) for unveiling intracranial pathology. OBJECTIVES: The objectives of the study were to determine the prevalence and type of intracranial lesions in otherwise normal girls with central precocious puberty (idiopathic CPP) and to identify the clinical and biochemical predictors of brain abnormalities. DESIGN AND SETTING: This was a retrospective study conducted at the Endocrine Unit of "Bambino Gesù" Children's Hospital (Rome, Italy) from 1990 to 2012. PATIENTS: One hundred eighty-two girls were consecutively diagnosed with CPP. All girls underwent a thorough endocrine assessment and brain MRI with a detailed examination of the hypothalamic-pituitary area. None of them had a history of neurological diseases, endocrine disorders, neurofibromatosis or other genetic syndromes, or previous hormonal therapies. MAIN OUTCOME MEASURE: Prevalence of brain abnormalities at MRI scan was measured. RESULTS: Brain MRI showed no alteration in 157 (86%), incidentalomas of the hypothalamic-pituitary area unrelated to CPP in 19 (11%), and hamartomas in six girls (3%). Girls with hamartomas were younger than 6 years and had significantly higher mean baseline and stimulated LH values (P < .001), LH to FSH ratio (P < .001), serum 17ß-estradiol levels (P < .001), and uterine length (P < .05). However, all the parameters overlapped extensively in girls with or without cerebral alterations. CONCLUSIONS: Our data cast doubt on the need of routine screening by brain MRI in girls with idiopathic CPP older than 6 years. Evidence-based criteria to drive clinical decision making about the use of MRI are lacking.

Effects of environmental endocrine disruptors and phytoestrogens on the kisspeptin system.

Sex steroid hormones, most notably estradiol, play a pivotal role in the sex-specific organization and function of the kisspeptin system. Endocrine--disrupting compounds are anthropogenic or naturally occurring compounds that interact with steroid hormone signaling. Thus, these compounds have the potential to disrupt the sexually dimorphic ontogeny and function of kisspeptin signaling pathways, resulting in adverse effects on neuroendocrine physiology. This chapter reviews the small but growing body of evidence for endocrine disruption of the kisspeptin system by the exogenous estrogenic compounds bisphenol A, polychlorinated biphenyl mixtures, and the phytoestrogen genistein. Disruption is region, sex, and compound specific, and associated with shifts in the timing of pubertal onset, irregular estrous cycles, and altered sociosexual behavior. These effects highlight that disruption of kisspeptin signaling pathways could have wide ranging effects across multiple organ systems, and potentially underlies a suite of adverse human health trends including precocious female puberty, idiopathic infertility, and metabolic syndrome.

Manganese induces IGF-1 and cyclooxygenase-2 gene expressions in the basal hypothalamus during prepubertal female development.

Precocious puberty is a significant child health problem, especially in girls, because 95% of cases are idiopathic. Our earlier studies demonstrated that low-dose levels of manganese (Mn) caused precocious puberty via stimulating the secretion of luteinizing hormone-releasing hormone (LHRH). Because glial-neuronal communications are important for the activation of LHRH secretion at puberty, we investigated the effects of prepubertal Mn exposure on specific glial-derived puberty-related genes known to affect neuronal LHRH release. Animals were supplemented with MnCl(2) (10 mg/kg) or saline by gastric gavage from day 12 until day 22 or day 29, then decapitated, and brains removed. The site of LHRH release is the medial basal hypothalamus (MBH), and tissues from this area were analyzed by real-time PCR for transforming growth factor α (TGFα), insulin-like growth factor-1 (IGF-1), and cyclooxygenase-2 (COX-2) messenger RNA levels. Protein levels for IGF-1 receptor (IGF-1R) were measured by Western blot analysis. LHRH gene expression was measured in the preoptic area/anteroventral periventricular (POA/AVPV) region. In the MBH, at 22 days, IGF-1 gene expression was increased (p < 0.05) with a concomitant increase (p < 0.05) in IGF-1R protein expression. Mn also increased (p < 0.01) COX-2 gene expression. At 29 days, the upregulation of IGF-1 (p < 0.05) and COX-2 (p < 0.05) continued in the MBH. At this time, we observed increased (p < 0.05) LHRH gene expression in the POA/AVPV. Additionally, Mn stimulated prostaglandin E(2) and LHRH release from 29-day-old median eminences incubated in vitro. These results demonstrate that Mn, through the upregulation of IGF-1 and COX-2, may promote maturational events and glial-neuronal communications facilitating the increased neurosecretory activity, including that of LHRH, resulting in precocious pubertal development.

Pre- and postnatal MR imaging of hypothalamic hamartomas associated with arachnoid cysts.

We describe two cases of hypothalamic hamartoma associated with arachnoid cysts. One case was initially documented on prenatal MR images. Because of the rarity of the association and resultant distortion in regional anatomy, the solid component of the mass may be overlooked. This would certainly be true when using lower-resolution diagnostic studies such as fetal MR imaging. The lesion could also be confused with a cystic tumor such as pilocytic astrocytoma. Thorough evaluation is required in patients with precocious puberty, gelastic seizures, and the presence of a suprasellar arachnoid cyst.

Hypothalamic hamartoma: the role of surgery in a series of eight patients.

Hypothalamic hamartoma are rare lesions. We report a new series of eight patients treated for precocious puberty (six cases) or gelastic seizures (two cases). Surgical resection was total in four cases (three pediculated and one sessile). Precocious puberty was controlled by surgical treatment in all cases. Gelastic seizures were controlled by medical treatment, but the patients did not become seizure free. We observed no mortality and no endocrinological or visual morbidity. The fact that a vascular "rete mirabilis" was observed on the surface of the lesion in our surgical material is an argument favoring a vascular mechanism in precocious puberty. Coagulation of this vascular structure can help control precocious puberty. Our series confirms that the hypothalamic hamartoma can be surgically treated when patients fail to respond to medical treatment, when the length of the treatment cannot be tolerated by the chidren and their families, and when there are uncontrolled gelastic seizures

Hypothalamic hamartoma associated with an arachnoid cyst.

A hypothalamic hamartoma associated with an arachnoid cyst in an 8-year-old boy is reported herein. He presented with precocious puberty, and neuroimaging studies demonstrated a solid mass in the prepontine cistern and a huge arachnoid cyst in the left cranial fossa. The mass appeared isointense to the surrounding cerebral cortex on T1-weighted magnetic resonance images, hyperintense on T2-weighted images, and was not enhanced after administration of Gd-DTPA. The patient underwent a left frontotemporal craniotomy and a cyst-peritoneal shunt was inserted. Histological features of the cyst wall and the mass were characteristic of an arachnoid cyst and hamartoma, respectively. While a hypothalamic hamartoma associated with an arachnoid cyst is rare, such a case may help clarify the geneses of both anomalous lesions.

Hypothalamic hamartomas: with special reference to gelastic epilepsy and surgery.

This study presents six patients with hypothalamic hamartomas diagnosed on the basis of magnetic resonance imaging. Histological confirmation was performed in three patients who underwent surgery. Immunohistological assays were used to determine the neurosecretory pattern. Four patients presented with epilepsy, including gelastic seizures. Other symptoms included behavioral abnormalities in four patients and precocious puberty and visual impairment in two patients. One patient presented associated developmental defects. Good results without morbidity were achieved with surgical resectioning in two patients with large hamartomas associated with behavioral abnormalities and gelastic epilepsy that was unresponsive to conventional medical treatment and in one patient with visual impairment. We propose a classification of the hypothalamic hamartomas based on topographical and clinical data obtained from 36 selected cases in the literature and six of our own cases. This classification should help to classify the various treatment methods and the surgical risks into four subgroups (Types la, lb, lla, and llb). We conclude that the surgical approach is a realistic alternative in certain cases, including large and broad-based Type llb hamartomas associated with gelastic epilepsy and behavioral disorders.

Hamartoma of the tuber cinereum in a six-month-old boy, causing isosexual precocious puberty.

A case of hamartoma of the tuber cinereum causing isosexual precocious puberty in a six-month-old boy, in whom the lesion was successfully extirpated, is presented. Our patient was relatively young, since hamartomas causing sexual precocity most often occur between the ages of one and three years. Hamartomas are discussed from the clinical and pathological points of view. The mechanisms of initiating pubertas praecox in cases of cerebral tumours, particularly hamartomas, are reviewed.

Testicular changes in gonadotropin-independent familial male sexual precocity. Familial testotoxicosis.

A recently described form of male sexual precocity characterized by active Leydig cell differentiation and premature onset of spermatogenesis in the absence of pituitary gonadotropin stimulation has been termed familial testotoxicosis. The clinical and endocrine findings in the condition are consistent with an inherited intratesticular defect rather than central or true precocious puberty. In this report, testicular changes in biopsy specimens from a series of affected patients are presented. In all of the cases, Leydig cells demonstrated nuclear and cytoplasmic features characteristic of fully differentiated steroidogenic cells. Reinke crystals were absent. Germ cells at all stages of spermatogenesis were present, but there was evident disorganization of maturation. Spermatids exhibited a variety of structural abnormalities. Sertoli cells were characterized by complex cytoplasmic differentiation, Charcot-Böttcher crystals, and tight junction formation. The morphologic changes indicate premature differentiation of all of the major testicular cell types and are consistent with a distinctive type of intratesticular abnormality.

Identification of gonadotropin-releasing hormone in neurons of a hypothalamic hamartoma in a boy with precocious puberty.

We have studied a 3 1/12-year-old boy who presented with a hypothalamic mass and precocious puberty. His history suggested a course of isosexual precocity progressing from birth. Gelastic seizures also began at an early age. Endocrine evaluation revealed normal thyroid-stimulating hormone and growth hormone secretion, elevated basal and stimulated prolactin concentrations, and luteinizing hormone responses to sequential intravenous injections of gonadotropin-releasing hormone (GnRH) that were pubertal in pattern and magnitude. A needle biopsy of the mass recovered tissue that contained neurons histologically similar to those found in the normal hypothalamus, and the mass was characterized as a hypothalamic hamartoma. Immunohistochemical staining of this tissue with anti-GnRH antiserum demonstrated positive staining for GnRH immunoreactivity in neurons. This suggests a neurosecretory pathogenesis for the precocious puberty found in patients with hamartomas in the hypothalamic region.