Pituitary adenomas in childhood: development and diagnosis

Pituitary adenomas account for approximately 2.7% of all supratentorial tumors in the pediatric age range, and children are more likely than adults to develop a functioning adenoma. X chromosome inactivation studies indicate that pituitary adenomas arise from the clonal expression of a single mutated cell, and various intracellular mechanisms contribute to tumoral transformation. Functional pituitary tumors in childhood result in physical and biochemical effects of excess production of the oversecreted hormone, such as ACTH, prolactin, human growth hormone, TSH, LH, or FSH. In the clinical approach to pituitary adenomas, it is important to establish the presence of hormonal excess prior to undertaking imaging studies.     

Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland

We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.     

Teenagers born at extremely low birth weight

Adolescence constitutes a major transition for extremely low birth weight (ELBW) teenagers. Recent studies of ELBW teenagers born in the 1980s have provided information about the growth and developmental characteristics of these individuals in adolescence and in early adulthood. ELBW teenagers are shorter and lighter than their full-term peers, and have a smaller head circumference. Cognitive and academic vulnerabilities documented during the school years, particularly difficulties with nonverbal intelligence and arithmetic, persist into late adolescence. Many ELBW children struggle in school and have lower academic achievement levels. The self-concept of ELBW teenagers is generally similar to that of their full-term peers, but their parents perceive them to be more vulnerable over a wide range of behavioural and psychosocial dimensions, particularly depression and attention. ELBW teenagers perceive themselves as needing more assistance in job seeking than do their peers. Physical activity levels and fitness in late adolescence are significantly lower in ELBW teenagers than in their full-term peers, constituting a potential additional health hazard in later life. The outcomes of ELBW teenagers are significantly influenced by socioeconomic, family and parenting factors.     

Pituitary adenoma and unexpected sudden infant death: A case report

Pituitary adenomas can cause sudden death in adults, but they are quite rare during infancy. Herein we present an unusual case of sudden infant death associated with a pituitary adenoma. The clinical presentations were ?quietness”? complained of by the parents and probable gigantism with accelerated growth rate during the first 2 months of life. The female infants had been in good health until one day when, at the age of 3 months, she was found immobile in bed. Microscopic examination showed that the cells of the entire pituitary gland were replaced by bizarre undifferentiated tumor cells. There were no invasive lesions in the surrounding brain tissue. It was also found that the cortex of the adrenal glands was atrophic. No metastatic lesions were observed in any organ. While the mechanism leading our infant to death is both controversial and unknown, we speculated that insufficient secretion of steroid hormones might have caused cardiovascular collapse. © 1994 Wiley-Liss, Inc.     

Pituitary non-secreting macroadenoma apoplexy in an adolescent. patient report and review of the literature

Pituitary macroadenomas are rare in children and adolescents, and when encountered are usually hormone secreting. Symptomatic pituitary non-secreting macroadenoma apoplexy in an adolescent is rare and potentially life-threatening. A 15 year-old patient is described, hospitalized due to headache, fever and photophobia 4 days prior to admission. A meningeal syndrome was postulated, based on clinical examination and cerebrospinal fluid testing. However, clinical examination and hormone testing revealed partial failure of the anterior pituitary. Computed tomography of the brain demonstrated a space-occupying lesion of the pituitary. Magnetic nuclear resonance imaging suggested the presence of a pituitary macroadenoma. Hypophysectomy was performed. Histological examination revealed an extensive infarction of a pituitary adenoma. Hormonal substitution with thyroxine and corticosteroids was administered. This report emphasizes that pituitary non-secreting macroadenoma apoplexy may rarely be the cause of headache and fever in an adolescent, thus causing difficulties in differential diagnosis from acute meningitis.     

Hypoplastic optic nerves and pituitary dysfunction. A spectrum of anatomical and endocrine abnormalities.

Fourteen children with optic nerve hypoplasia associated with either mid-brain abnormalities or pituitary dysfunction, or both, are described. All patients were either partially sighted or blind. One case is reported in detail. The importance of hypoglycaemia in the neonatal period and later in childhood is emphasised in relation to diagnosis and developmental delay. Pituitary dysfunction is variable and may be progressive. Forty percent of the patients had a septum pellucidum and its presence or absence cannot be used as a radiological marker for the condition. Long term endocrine follow up of these patients is required.     

Pituitary apoplexy in adolescence: case report

Pituitary apoplexy is an uncommon, life-threatening clinical syndrome, characterized by sudden-onset headaches, visual impairment, and ophthalmoplegia. It is seen in 0.6–12.3 % of patients with pituitary adenoma, and the age at presentation ranges from 37.7 to 52 years [1]. Pituitary adenoma occurs infrequently in children, comprising 2-10% of pediatric intracranial neoplasms [2]. As a result, pituitary apoplexy is extremely rare in children [2, 3]. We report a surgically proven case of pituitary apoplexy in an adolescent, with characteristic CT and MR appearance.

     

MRI of the hypothalamic-pituitary axis in children

In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults.     

Diagnosis,treatment and long-term outcome in Cushing's disease

Cushing's disease is uncommon in childhood. It is usually caused by the oversecretion of adrenocorticotrophic hormone (ACTH) by a pituitary corticotroph adenoma. Clinical abnormality is often undetected for long periods of time. The principal clinical features are growth retardation and obesity. We present four patients who were diagnosed with Cushing's disease in a tertiary hospital from January 1995 to December 2002. There were two boys and two girls, aged 10-15 years. The main clinical features at presentation were growth failure and excessive weight gain. The interval between onset of symptoms and diagnosis ranged from 2.5 to 5 years. All patients presented moon face and increased fat around the neck. In all patients, 24-hour urinary free cortisol was high and loss of normal serum cortisol circadian rhythm (3/3) and suppression of cortisol to less than 50 % of the basal level with high-dose but not with low-dose dexamethasone (2/2) were observed. Pituitary microadenoma was detected by magnetic resonance imaging in three patients; no tumor was detected in the fourth patient and inferior petrosal sinus sampling was performed, showing left lateralization of ACTH central secretion. Therapy consisted of transsphenoidal surgery in all patients. Two patients are in remission, one patient presented disease recurrence requiring total hypophysectomy because the tumor could not be completely removed and one patient had persistent disease after a second intervention and required pituitary radiotherapy. Two patients showed pituitary hormone deficiency after therapy.     

Les dangers des jeux vidéo : diagnostic et conduite à tenir

Videogames accompany teenagers from childhood to adulthood, because they are the stage of their fantasies and hopes. But they are dangerous when teenagers are insecure, when they have lived early sufferings, or when they have a bad self-esteem. Doctor must in the same time advice the parents, and appreciate the gravity.     

Gender role across development in adults with 46,XY disorders of sex development including perineoscrotal hypospadias and small phallus raised male or female

Self-rated degree of femininity and masculinity across development were evaluated for 40 adults affected by 46,XY disorders of sex development (DSDs) who presented at birth with a small phallus and perineoscrotal hypospadias, raised either male (n = 22) or female (n = 18). Most participants were confirmed or presumed to be affected by partial androgen insensitivity syndrome (n = 14), partial gonadal dysgenesis (n = 11), or were considered to have a poorly defined case of 46,XY DSD including ambiguous external genitalia (n = 15). Participants retrospectively evaluated their degree of masculinity and femininity during their childhood, adolescence, adulthood, and in the past 12 months of filling out a questionnaire pertaining to their psychosexual development. Participants raised male reported more masculinity than those raised female due to an increase in masculinization during adolescence and adulthood. Participants raised male also reported less femininity than those raised female throughout development. Participants raised female reported more femininity than those raised male due to an increase in feminization during adolescence and adulthood. Participants raised female also reported less masculinity than those raised male throughout development. These data support the proposition that some aspects of gender role (GR), such as masculinity and femininity, are capable of proceeding along female- or male-typic patterns depending on sex of rearing among individuals affected by specific types of 46,XY DSD. Furthermore, regardless of male or female rearing, GR increasingly corresponds with assigned sex as individuals proceed through sexual maturity and into adulthood. These results are consistent with the idea that socialization/learning contributes to GR development in humans in addition to data from others demonstrating endocrine influences.     

Two cases presenting with pubertal delay and diagnosed as Celiac disease

Pubertal delay may be due to underlying chronic diseases and primary endocrine diseases. Celiac disease, one of the common malabsorption disorders of childhood, may progress silently in some cases, and the cases diagnosed late present with growth failure or disturbance of pubertal development. Currently, due to the changing face of celiac disease, patients are being diagnosed in adolescence with atypical symptoms and findings. This study describes 2 patients aged 13 and 16 years who presented with pubertal delay and who were diagnosed with celiac disease, concluding that routine screening of celiac disease in the differential diagnosis of delayed puberty should be recommended.     

Organ- and non-organ-specific auto-antibodies in children with hypopituitarism on growth hormone therapy

Serum non-organ-specific antibodies (NOSA) against nuclear, mitochondrial (AMA), smooth muscle, liver/kidney microsomal (LKM), reticulin, ribosomal, and organ-specific antibodies (OSA) against pituitary gland, gonads (testis, ovary) adrenal cortex, thyroid (thyroglobulin and microsomal), pancreas islet cells, gastric parietal cells and intestinal epithelial cells were evaluated in 45 patients with hypopituitarism (mean age 12.4±4.0 years). In 22 of them, 9 with isolated growth hormone (GH) deficiency (IGHD) and 13 with multiple pituitary hormone deficiency, MRI showed anterior pituitary hypoplasia with structural stalk abnormality and ectopic posterior pituitary. Twelve had isolated small anterior pituitary and IGHD and 11 had normal morphology of pituitary gland and IGHD. Controls were healthy age-sex-matched subjects. Thyroid antibodies were detected by a passive haemagglutination test while indirect immunofluorescence was used for the others. The auto-antibodies were found in 7/45 asymptomatic patients, a frequency not significantly different from that in controls; 5 were type NOSA and 2 type OSA. Pituitary antibodies were positive in 1 girl with IGHD and normal pituitary morphology. One girl developed hyperthyroidism during the follow up. Autoantibodies were equally distributed between the three groups and the frequency was not dissimilar from that in controls; this suggests that these patients are not at a higher risk of developing auto-immune disease, at least during the first two decades.Conclusion Pituitary insufficiency in children with different MRI features seems unlikely to be secondary to an auto-immune process.     

The late endocrine effects of childhood cancer treatment

Whilst many children diagnosed with cancer can now realistically hope for long term survival, the consequences of cancer treatment can be particularly devastating as they enter adolescence and adulthood. Disruption of the endocrine system can result from such treatment, including growth hormone deficiency, problems in normal pubertal progression and thyroid dysfunction. Fertility can also be affected by cancer treatment received as a child, which can have a devastating impact as the patient enters adulthood. In addition, these children may encounter disorders of growth and bone metabolism due to both their initial disease and aspects of its treatment, resulting in further morbidity in later life. The aetiology and diagnosis of these problems are discussed in this review, along with therapeutic options in order to reduce their impact. Long term follow up and clinical vigilance in this patient group is vital. We must continue to strive towards improved survival from childhood cancer, but equally we must remain aware of the adverse effects of treatment, particularly in the long term, and must aim to reduce the impact of these effects as children enter adolescence and adult life.     

Primary hyperparathyroidism in children

Primary hyperparathyroidism is an uncommon condition in childhood that is easily amenable to surgical treatment with excellent results. Pathologically, the parathyroid glands may show generalized hyperplasia or, more commonly, adenoma formation, the latter frequently being seen in adolescence. Two girls with solitary parathyroid adenomas and predominantly skeletal manifestations resembling rickets are reported, underlining the need to suspect and appropriately investigate these children. The literature on the subject is reviewed.     

Castleman's disease (angiofollicular hyperplasia) in children

This unusual clinicopathologic entity was first recognized by Castleman. Onset is usually in adolescence or early adulthood, occasionally childhood. A single, large mass with no tendency to compress develops, usually in the mediastinum, occasionally at other lymph node sites (superficial, retroperitoneal, abdominal), and exceptionally in extranodal locations. A variety of systemic manifestations may be found, including fever, anemia, hypergammaglobulinemia, and a broad spectrum of inflammatory and autoimmune disorders, presumably associated with specific humoral factors produced by the tumor. Histologic examination shows the characteristic features of angiofollicular lymph node hyperplasia. Two variants have been described, i.e., the plasma cell type (active stage) associated with systemic manifestations, and the hyaline vascular type (quiescent stage). Surgical removal of the tumor ensures permanent (local and systemic) recovery in the overwhelming majority of cases. A role of microorganisms in the etiology of this condition has been suggested. Identical histologic changes can be found in adults with immune dysfunction syndromes. The etiology, pathogenesis and nosology of this very benign disease are still poorly known.     

Hypopituitarism and neurodevelopmental abnormalities in relation to central nervous system structural defects in children with optic nerve hypoplasia

OBJECTIVE: Optic nerve hypoplasia (ONH) is a heterogeneous disease with variable findings of pituitary insufficiency, CNS and neurodevelopmental abnormalities. We characterized the spectrum of endocrinopathy in a cohort of children with ONH and attempted to correlate the presence of different midline CNS findings with the degree of hypopituitarism. The correlation of variable CNS abnormalities with the presence of a seizure disorder and neurodevelopmental delay was also examined. METHODS: Charts of 56 patients with ONH referred to our endocrine clinics between 1990 and 2000 were reviewed. Neurodevelopmental assessment was based on questionnaires sent to families during the study period. RESULTS: Forty-six patients (82%) had hypopituitarism, with growth hormone deficiency being the most common endocrinopathy. All patients with diabetes insipidus, hypocortisolism, and hypogonadotropin hypogonadism also had combined pituitary hormone deficiency. Evolving pituitary hormone deficiency was observed in two of 37 patients diagnosed with hypopituitarism in the first 3 years of life. No single midline CNS finding correlated with the presence of hypopituitarism or a seizure disorder. However, hydrocephalus or a seizure disorder was more commonly seen in patients with developmental delay. CONCLUSION: ONH is a heterogeneous disorder with possible multifactorial etiologies. All patients with this diagnosis deserve a comprehensive endocrine and neurodevelopmental evaluation.     

Narcolepsy with cataplexy in early childhood

Narcolepsy is a rare neurologic sleep disorder with morbidity associated with functional impairment and frequent delay in diagnosis. Symptoms typically manifest in adolescence or early adulthood, but diagnosis of narcolepsy has been reported in early childhood. Diagnosis rates are as low as 50% of the total population of patients with narcolepsy and are delayed as much as 10 years after disease onset due to inadequate patient-physician communication and/or misdiagnosis. I present the complexity of diagnosing narcolepsy in early childhood in a patient with cataplexy that started soon after independent ambulation at age 10 months.     

Multifocal Nephrogenic Adenoma – A Mimicker of Malignancy

The authors report a multifocal nephrogenic adenoma of urinary bladder in an 11-y-old girl. Nephrogenic adenomas occur almost exclusively in the urinary bladder in children and are rarely multifocal. Less than 30 cases of nephrogenic adenomas have been reported in children and very few of these are multifocal. This report aims at drawing attention to this rare entity in children.     

Diagnosis of Cushing's disease in children: A challenge for the radiologist

Cushing's disease is the most common cause of Cushing's syndrome in children and is almost always related to over secretion of ACTH by the pituitary gland. It is important to identify a secreting adenoma prior to surgery. Seven cases studied with MRI are reviewed. In five cases the MRI findings suggested adenoma. Three secreting adenomas were confirmed at surgery. One case was in fact a cyst of the pars intermedia, and nothing could be found in the last case. Two patients presented with apparently normal findings on MRI, which was confirmed. There is a close correlation between identifying an adenoma and the success of surgery.Presented at the 31st Congress of the European Society of Pediatric Radiology, June 1–3, 1994, Brussels, Belgium and selected for publication by an International Group of the ESPR