Adenomas In Childhood Research Articles

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part1, general recommendations.

Tumours of the anterior part of the pituitary gland represent just 1% of all childhood (aged <15 years) intracranial neoplasms, yet they can confer high morbidity and little evidence and guidance is in place for their management. Between 2014 and 2022, a multidisciplinary expert group systematically developed the first comprehensive clinical practice consensus guideline for children and young people under the age 19 years (hereafter referred to as CYP) presenting with a suspected pituitary adenoma to inform specialist care and improve health outcomes. Through robust literature searches and a Delphi consensus exercise with an international Delphi consensus panel of experts, the available scientific evidence and expert opinions were consolidated into 74 recommendations. Part 1 of this consensus guideline includes 17 pragmatic management recommendations related to clinical care, neuroimaging, visual assessment, histopathology, genetics, pituitary surgery and radiotherapy. While in many aspects the care for CYP is similar to that of adults, key differences exist, particularly in aetiology and presentation. CYP with suspected pituitary adenomas require careful clinical examination, appropriate hormonal work-up, dedicated pituitary imaging and visual assessment. Consideration should be given to the potential for syndromic disease and genetic assessment. Multidisciplinary discussion at both the local and national levels can be key for management. Surgery should be performed in specialist centres. The collection of outcome data on novel modalities of medical treatment, surgical intervention and radiotherapy is essential for optimal future treatment.

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases.

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing.

ACROMEGALY COMBINED WITH GIGANTISM ASSOCIATED WITH THE AIP-GENE MUTATION: A CLINICAL CASE

Pituitary gigantism is an extremely rare disorder: the incidence of pituitary tumors in children is approximately 0.1 in one million, and only about 1 to 10% of the pituitary tumors secrete the GH in childhood. Gigantism should be suspected if the patient's height is 3 standard deviations above the normal average height or 2 standard deviations above the corrected height of parents. When pituitary gigantism is suspected, the clinician should consider the presence of disorders, known to be associated with the GH-secreting pituitary tumors, including the McCune Albright syndrome (MAS), Carney complex (CNC), multiple endocrine neoplasia, types 1 and 4 (MEN 1, MEN 4), Familial isolated pituitary adenoma (FIPA), the paraganglioma, pheochromocytoma and pituitary adenoma association (PAA) due to succinate dehydrogenase defects, and X-linked acrogigantism (X-LAG). The molecular genetics of the AIP-associated FIPA, MAS, CNC, and MEN 1 has been extensively studied and reviewed, especially in children and young adults. The GH-secreting adenomas seem to be more invasive and aggressive in childhood than in adulthood. Data on a rare disease — gigantism combined with phenotypic signs of acromegaly in a young patient are presented. Clinical and laboratory parameters, data of histological and genetic analysis are described. Genetic analysis performed by AIP gene by Sequencing, proved a rare mutation in the locus of exons 1-6 of the AIP gene. The presented clinical case describes a rare fact of the AIP-gene mutation in the p.Cys238Tyr locus, which is associated with the occurrence of a giant pituitary adenoma in childhood. Aggressive growths of the pituitary tumor, its high proliferative and hormonal activity, clinical manifestations of gigantism in combination with severe phenotypic signs of acromegaly have also been noticed. Resistance to the therapy with somatostatin analogs has been revealed in this case. Considering the absence of genetic predisposition to a pituitary adenoma in the patient, this case can be regarded as a sporadic pituitary adenoma variant due to the abnormal AIP-gene expression and the disturbance of regulation during tumorigenesis.

Obesity is common at diagnosis of childhood pituitary adenoma and may persist following successful treatment.

There is a paucity of data describing long-term outcomes of paediatric patients with pituitary adenoma. In this report, we describe clinical features, treatment and outcomes of a paediatric cohort. Retrospective cohort study. Twenty-four white Caucasian patients aged <16years from a single tertiary care centre in the United Kingdom at diagnosis followed for (median, range) 3.3, 0.7-8.4years. Clinical and radiological data at diagnosis and follow-up. Thirteen patients had prolactinomas (54.1%, age: 15.2years, 13.2-15.8years; all females), including ten macroadenomas (11.0-35.0mm). Patients presented with menstrual disorders (91%), headache (46%), galactorrhoea (46%) and obesity (body mass index [BMI] SDS>2):(38%).Ten patients with prolactinomawere treated with dopamine agonist alone, 3 also required surgery and 2 patients, cabergoline, surgery plus radiotherapy. Five patients had Cushing's disease (20.8%, age: 14.0, 4.0-15.7years; 2 female), including one macroadenoma (24mm). Patients presented with obesity (100%), short stature (60%) and headache (40%). Transsphenoidal resection resulted in biochemical cure (09.00 cortisol<50nmol/L). Two patients relapsed 3- and 6years following surgery, requiring radiotherapy. One patient also required bilateral adrenalectomy. Six patients had nonfunctioning pituitary adenoma (25.0%, age: 15.8, 12.5-16.0years; 2 female), including two macroadenomas (20.0-53.0mm). Patients presented with obesity (67%), visual field defects (50%) and headache (50%). Four required surgical resections; two recurred following surgery and required radiotherapy. On latest follow-up; 13 (54.1%) patients were obese (BMI 3.09 SDS; range: 2.05-3.73 SDS). Obesity is common at diagnosis of pituitary adenoma in childhood and may persist despite successful treatment. Adenomas were larger, more resistant to treatment, and more likely to recur than in adult populations.

Start low, go slowly - mental abnormalities in young prolactinoma patients under cabergoline therapy.

Background Prolactin-secreting pituitary adenomas in childhood and adolescence are rare. First-line therapy consists of dopamine agonists (DAs) like cabergoline. Experience in treating prolactinomas in paediatric and adolescent patients is limited. Methods This study was a retrospective analysis of clinical data, laboratory data, radiological findings and medical treatment of paediatric and adolescent patients with prolactinomas between 2009 and 2018. Results Our cohort of nine patients had a median age at diagnosis of 13 years (range 5-17). Main presenting symptoms were weight gain, disorders of the pituitary-gonadal axis and headache. Treatment with cabergoline resulted in a marked reduction in prolactin concentration in all nine patients. Tumour mass reduction was confirmed by magnetic resonance imaging (MRI) scan in seven patients. Noteworthy is that cabergoline therapy triggered frequent adverse effects in a total of eight patients - seven of whom suffered from mental disorders, five of whom had neurological symptoms and five of whom had gastrointestinal problems. The adverse effects occurred at a median dose of only 0.5 mg/week (range 0.25-2.0). Most symptoms were alleviated after the cabergoline dose was lowered. Therapy discontinuation was not necessary in any patient. Conclusions Cabergoline effectively lowers prolactin levels and may reduce tumour mass in paediatric and adolescent patients with prolactinomas. Potential adverse effects may include mental disorders and behavioural problems even at low cabergoline doses. Low starting doses and careful individual dose adjustments are required to enable therapy adherence.

Pituitary adenomas in childhood and the transition period - clinical and genetic characterization of 49 patients at one tertiary care endocrine institution in Romania

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Growth hormone-producing pituitary adenomas in childhood and young adulthood: clinical features and outcomes.

Growth hormone (GH)-producing pituitary adenomas (PAs) in childhood or young adulthood are rare, and the details surrounding these tumors remain enigmatic. We present the clinical, pathological and genetic features of this disease. We identified 25 patients aged 20years or younger with GH-producing PAs who underwent surgery between 2003 and 2016 at Toranomon Hospital in Tokyo. We retrospectively reviewed the clinical data, treatment outcomes and pathological features of these patients to shed light on childhood acromegaly. The cohort comprised 14 male and 11 female patients whose average age at the time of surgery was 17.3years. Germline AIP mutations were present in 5 of 13 patients examined, and Carney complex was identified in 2 of 25 patients. The mean maximum tumor diameter was 26.7mm, and total resection assessed during surgery was achieved in 17 patients. Based on their respective pathological findings, patients were divided into the following 4 groups: sparsely granulated adenomas (5), densely granulated (DG) adenomas (6), plurihormonal adenomas (9), and silent subtype 3 (SS3) adenomas (5). During the mean follow-up period of 50.3 months, complete endocrinological remission was achieved in 14 of 25 patients (56%) by surgery alone and in 19 patients (76%) after postoperative adjuvant therapy. GH-producing PAs in young patients are intriguing and difficult to treat due to their distinct tumor characteristics, including a lower incidence of the DG subtype and a higher incidence of SS3 adenomas and genetic abnormalities. Therefore, multi-modal therapies are essential to achieve optimal clinical outcomes.

Surgical treatment of pituitary adenomas in childhood and adolescence

Objective: To investigate the clinical characteristics and treatment of pituitary adenomas of childhood and adolescence. Methods: Thisarticle was a retrospective study of 140 pituitary adenomas of childhood and adolescence that was admitted into Peking Union Medical College Hospital from December 1987 to December 2014, whose clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-ups were studied. Results: A total of 58 (41.4%) males and 82 females (58.6%) were included, whose mean age was 12.5 years old (age range from 7 to 18). As for the type of tumors, ACTH adenoma, PRL adenoma, GH adenoma, non-functional adenoma and multiple-secreting adenoma accounted for 35.7%, 25.7%, 12.2%, 25.7% and 0.7%, respectively. Microadenoma accounted for 33.6% of total patients, while macroadenoma and giant adenoma accounted for 60.0% and 6.4% respectively. 19.3% of adenomas in our study wereinvasive. Transsphenoidal approach surgery was commonly used and accounted for 97.9% of cases in our study, 2 of which used intraoperative navigation assistance. Total resection was achieved in 93.6% of patients, and the rest achieved subtotal resection. 108 (77.1%) patients got full term follow-up until 1 year after surgery, and tumor recurred in 14 patients (13.0%). Conclusions: ACTH-secreting adenoma is the most common pituitary adenoma in childhood and adolescence which need surgical treatment. Transsphenoidal approach surgery is the most commonly used surgical procedure. The recurrence rate is about 13%, and the patients need regular examination of pituitary hormones and image study to confirm the recurrence.

Pediatric Pituitary Adenomas at the Mayo Clinic, 1975 through 2014

As an update to the publication, Pituitary adenomas in childhood and adolescence, (J Neurosurg 80:209–216, 1994) which looked at 36 pediatric pituitary adenoma surgical resections at the Mayo Clinic between 1975 and 1988: since 1975 to 2014, a total of 197 patients had pituitary adenomas were resected that were diagnosed when they were 21 years of age and under at the Mayo Clinic. 130 (66%) of these patients were diagnosed between 18 and 21 years of age. Complete pathological, laboratory and clinical data were available for retrospective review for 79 of these patients for surgeries performed between 1997 and 2014.

Pituitary adenomas in childhood and adolescence with a focus on intratumoral hemorrhage

Pituitary adenomas in childhood and adolescence are relatively rare. In the present study we investigated intratumoral hemorrhage in pituitary adenomas and examined cases of intratumoral hemorrhage using adult patients for comparison. From 1975 to 2012, 38 consecutive patients operated for pituitary adenoma and one patient treated with medication alone, were enrolled in this study. Their ages were less than 18years old at the initial diagnosis (mean age 15.3±2.9years). The comparison group consisted of 209 consecutive adult patients (>18years old). The incidence and characteristics of intratumoral hemorrhage in pituitary adenomas were evaluated, based on magnetic resonance imaging (MRI) findings (28 cases) and on operative findings. The incidence of pituitary adenomas in childhood and adolescence was 38/1,073 (3.5%) patients operated. Functioning pituitary adenomas (82.1%) were common and non-functioning pituitary adenomas (17.9%) were rare. Although no significant difference in tumor size was found and Knosp grade did not differ between young (≤18years old) and adult (>18years old) patients, indications of intratumoral hemorrhage on MRI was common in young patients (42.9%). Based on both MRI and operative findings, intratumoral hemorrhage was significantly more likely to occur in young patients, compared with adult patients.

Pituitary adenomas in childhood, adolescence and young adulthood: presentation, management, endocrine and metabolic outcomes

To elucidate the long-term outcomes of pituitary adenomas diagnosed in childhood and adolescence, knowledge of which remains sparse. A retrospective review of patients aged ≤21 years at diagnosis of pituitary adenoma, attending a neuroendocrine service in Liverpool, UK, between 1984-2009. There were 41 patients (33 female), mean age at diagnosis 17.3 years (range 11-21) and mean follow-up 9.6 years; 29 patients had prolactinomas (15 macroprolactinomas), 6 non-functioning pituitary adenomas (NFPAs), 5 Cushing's disease (CD) and 1 acromegaly. All prolactinoma patients received dopamine agonists (DAs) and three also underwent pituitary surgery. Furthermore, ten patients underwent surgery: five with CD, one with acromegaly and four with NFPA. Four received radiotherapy after surgery. Another ten patients received hormone replacement: nine hydrocortisone, five thyroxine, seven sex steroids and five GH; another seven had severe asymptomatic GH deficiency. Three female patients were treated for infertility (two successfully). Thirteen patients gained significant weight (body mass index (BMI) increase >2 kg/m(2)) since diagnosis and 16 in total are now obese (BMI>30 kg/m(2)). Five were treated with orlistat and one attended a weight management service. Two received antihypertensive medications, two had type 2 diabetes and four were treated for dyslipidaemia. This is one of the largest reviews of patients aged 21 or younger at diagnosis of pituitary adenoma followed up by a single service. Two-thirds had prolactinomas, all were treated with DAs and three underwent surgery. Increased cardiovascular risk factors (obesity and dyslipidaemia) and infertility are important sequelae and active identification and treatment are necessary.

Advances in the Diagnosis, Treatment and Molecular Genetics of Pituitary Adenomas in Childhood

The pituitary gland has an essential role in the maintenance of homeostasis, normal growth and reproductive function. Although pituitary tumours are rare in childhood and adolescence and are typically histologically benign, significant morbidity may result due to their location, mass effect and/or interference with normal pituitary hormone functions.1The early identification of pituitary tumours in children is necessary to avoid serious adverse effects on both physiological and cognitive outcomes as a result of pituitary hormone dysregulation during the critical periods of growth in childhood and adolescence. In this report, we review recent findings on the diagnosis, evaluation, treatment and molecular genetics of pituitary adenomas presenting in childhood.

Advances in the Diagnosis, Treatment, and Molecular Genetics of Pituitary Adenomas in Childhood.

Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2-6% of surgically treated pituitary tumors occur in children, with some variation attributed to a lack of consensus for a pediatric age range and whether age at surgery or age at onset of symptoms was used. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Pituitary adenomas produce a variety of hormonal conditions such as hyperprolactinemia, acromegaly or gigantism, or Cushing disease. Sporadic lesions comprise the majority of pituitary tumors in children and there is sparse information about genetic causes. However, in children more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as Carney complex, McCune-Albright syndrome, multiple endocrine neoplasia type 1 (MEN 1), and familial isolated pituitary adenoma (FIPA). The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. Molecular understanding of pituitary adenoma formation is essential for the development of medical therapies and the treatment of post-operative recurrences. In general, mutations in genes involved in genetic syndromes associated with pituitary tumors are not a common finding in sporadic lesions. In contrast MEN1 and AIP mutations may be more frequent among specific subgroups of patients, such as in children and young adults with growth hormone-producing adenomas. In this presentation, we review the most recent data on clinical diagnosis and outcomes, as well as in the molecular pathogenesis of pituitary adenomas and discuss some of the most recent findings from our laboratory. Guidelines for genetic screening and clinical counseling of patients with pituitary tumors are provided.

Pituitary adenomas in childhood.

Pituitary adenomas are common tumors composed of adenohypophysial cells. Although they usually arise in the sella turcica, they may occasionally be ectopic. Pituitary adenomas are rarely diagnosed in childhood and adolescence, but their mass effect and endocrine abnormalities can compromise both quality and length of life. Many signs or symptoms of pituitary adenoma, complained of in adulthood, not became evident during adolescence, suggesting true prevalence of this tumor in teenagers is higher than expected. Pititury adenoma occuring during adolescence are associated with features or therapeutic needs sometimes different from those occuring in adulthood. At the onset of disease, delay in growth was rarely observed in teenagers with pituitary adenomas. Many girls complain of oligoamenorrhoea and galactorrhoea, while headache and delay in pubertal development are the most commons features in boys. Hypopituitarism is occasionally encountered in adolescence. Early diagnosis and appropriate choice of therapy are necessary to avoid permanent endocrine complications of disease and its treatment.

Pleomorphic adenoma of the parotid in childhood

Introduction: Pleomorphic adenoma is a benign growth that most often appears in the parotid gland where it is the most frequent type of tumour. Its appearance in childhood is rare and there are no large series available in this age group for comparison with its presentation in adults. Surgical treatment is similar in children and in adults; whilst the prognosis is good, they may become malignant and metastasize. Material and Method: In this study, we present seven parotid pleomorphic adenomas in childhood treated in our Department and a review of the literature. The following data were evaluated: sex, age, affected side, clinical symptoms and period of evolution of the symptoms, surgical technique applied and complications observed. Results: The mean age at presentation was 12.4 years. All patients were males with the right side affected in five patients. The treatment was conservative superficial parotidectomy in five patients, conservative total parotidectomy in one, and an enucleation including a wide safety margin in the last case. None of the patients exhibited any permanent postoperative complication. The mean follow-up was 41.3 months (26–58 months). Copyright 2002 European Association for Cranio-Maxillofacial Surgery. Published by Elsevier Science Ltd. All rights reserved.

Transnasal surgery for prolactin-secreting pituitary adenomas in childhood and adolescence

BACKGROUND Prolactin (PRL)-secreting pituitary adenomas (prolactinomas) are rare in childhood and adolescence; there are only a few published series of patients who were surgically treated. We discuss the gender-dependent differences, and the surgical indications and results for 14 patients with prolactinomas under 18 years of age at surgery. METHODS We reviewed the data for 14 patients (10 girls and 4 boys) treated surgically for prolactinomas between 1980 and 1996. Surgery was chosen because of intolerance and/or resistance to dopamine agonist (DA) in 9 patients, the patient’s decision in 3, rhinorrhea in 1, and pituitary apoplexy in 1 during DA therapy. All patients underwent direct transnasal explorations. Since 1988, intraoperative PRL measurements were performed. The follow-up period was at least 6 years. RESULTS Nine of the 10 girls had primary or secondary amenorrhea, and 3 of the 4 boys had visual field defects. The boys and girls were the same age at the onset of symptoms and had the same preoperative duration of symptoms. Boys had larger, more invasive tumors and higher preoperative and postoperative plasma PRL levels than girls. Two boys demonstrated significant extrasellar extension at the time of diagnosis. Two patients required drilling of the incompletely pneumatized sphenoid sinus to reach the sella. Radical tumor resection was achieved in seven girls and in none of the four boys. In 12 of the 14 patients, normal pituitary function was preserved by transnasal surgery. There was no severe surgical morbidity or mortality. Endocrinological remission by surgery alone was achieved for seven girls, and was achieved in 4 of the 5 patients (80%) with microadenomas. In patients with preoperative mean PRL levels of less than 200 μg/L, the surgical cure rate was 75%. CONCLUSIONS Prolactinomas in childhood and adolescence differ in their biology in boys and girls. Transnasal surgery is as safe in childhood patients as it is in adult patients, and it may be an effective alternative to long-term medical therapy for selected patients with prolactinomas. Successful surgical outcomes were achieved in patients with microadenomas and preoperative serum PRL levels of less than 200 μg/L.

Recurrence in pituitary adenomas in childhood and adolescence.

Pediatric pituitary adenomas are thought to behave more aggressively than their adult counterparts, and the ability to predict the degree of such behavior remains elusive. Proliferation marker Ki-67 and tumor suppressor gene p53 mutations have been used in adults to assist in the evaluation of invasiveness and recurrence; however, their use in childhood and adolescence remains anecdotal. Our study evaluates the proliferative potential in pituitary adenomas of five patients and its relationship with recurrence or persistence of endocrinologic or clinical abnormalities. For such assessment, tissues were stained with monoclonal antibodies BP53-12 forp53 tumor suppressor gene mutation and MIB-1, which binds to cell cycle-specific nuclear antigen Ki-67. In our series, one patient with recurrent adenoma demonstrated the highest (50%) p53 immunoreactivity. Ki-67-stained nuclei ranged from 0 to 2%, failing to identify the recurrent tumor. Therefore, p53 immunoreactivity, rather than Ki-67 nuclear stain, may be useful for identification of recurrent pituitary adenomas in childhood and adolescence.

Recurrence in Pituitary Adenomas in Childhood and Adolescence

Recurrence in Pituitary Adenomas in Childhood and Adolescence

Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery.

Pituitary tumors causing gigantism are rare in childhood and adolescence. In a review of 2367 patients with pituitary adenomas who were treated between 1970 and 1997, we found 15 cases (0.63%, 9 male and 6 female patients) of growth hormone-secreting pituitary adenomas in patients who were less than 20 years of age at the time of surgery, and we compared their characteristics with those of adenomas in an adult group. Patients were grouped according to their ages at the first operation, with five patients (33.3%) in the prepubescent group (0-11 yr), eight (53.3%) in the pubescent group (12-17 yr), and two (13.3%) in the postpubescent group (18-19 yr). All 15 patients exhibited the typical symptoms of growth hormone oversecretion. The incidence of hyperprolactinemia among patients with prepubescent onset was 66.7%. Radiological examinations demonstrated microadenomas in 4 patients (26.7%) and macroadenomas in 11 patients (73.3%). The mean follow-up period was 73.5 months. Direct transnasal explorations were performed for all patients. Tumor invasion into the cavernous sinus was observed in six patients (40%). Radical tumor resection was performed for four patients (80%) in the prepubescent group, for five patients (62.5%) in the pubescent group, and for neither patient in the postpubescent group. Surgical morbidity was caused by permanent diabetes insipidus in three patients (20%). Rapid growth was postoperatively improved in 80% of the prepubescent age group. The recurrence rate was 13.3% (2 of 15 patients). Transnasal pituitary surgery was found to be as safe in pediatric patients with gigantism as in adults. Growth hormone-secreting pituitary adenomas in childhood and adolescence were more likely to be invasive or aggressive than were those in adulthood. The clinical biological characteristics for children were different from those for adults.

Growth Hormone-secreting Pituitary Adenomas in Childhood and Adolescence: Features and Results of Transnasal Surgery

Growth Hormone-secreting Pituitary Adenomas in Childhood and Adolescence: Features and Results of Transnasal Surgery