Consensus guidelines for the management of craniopharyngioma in low- and middle-income countries.

Craniopharyngiomas are benign, extra-axial epithelial tumours originating from the pituitary stalk, impacting areas such as the hypothalamus, optic chiasm, and various cranial nerves. These tumours present unique surgical challenges due to their proximity to critical neurovascular structures. Management typically involves maximal safe resection as the primary approach. However, in low- and middle-income countries (LMICs), factors like late presentation, higher risks of endocrine and visual complications, frequent recurrence, and potential for incomplete resection complicate treatment. These challenges are exacerbated by limited access to specialised expertise and surgical equipment, increasing the risk of damage during surgery compared to High- Income Countries. This manuscript outlines management guidelines tailored for LMICs, emphasizing that a combination of surgical resection and chemoradiation therapy, as advised by a neuro-oncology tumour board, often yields the best outcomes.

Extraconal orbital craniopharyngioma.

A female, in her 60s, presented with pain and swelling of the right eye for 3 years. The radiological work-up revealed an extraconal solid-cystic orbital tumour suggestive of an epidermoid cyst. The patient underwent supraorbital craniotomy with a gross total excision of the tumour. An intraoperative diagnosis was sought, which on both squash smear and frozen section showed features of craniopharyngioma (CP), later confirmed on paraffin sections and immunohistochemistry. The orbit is a very rare site for ectopic CP, with only two cases reported in the literature. Many theories have been proposed to explain the occurrence of CP at ectopic sites. This report aims to provide insight into the different hypotheses of the pathogenesis of ectopic CP through a review of the literature.

Head circumferences measured during developmental monitoring visits before diagnosis of childhood-onset craniopharyngioma.

BACKGROUND: Craniopharyngiomas (CP) are histologically benign (WHO grade 1), embryonal malformations which are related to remnants of the Rathke's pouch and are located in the (peri)sellar region. Already before CP diagnosis, many patients show a reduced growth velocity and tend to present with weight gain. However, it is unknown whether patients with CP develop an increased head circumference (HC) before CP diagnosis, which could be a useful early diagnostic indicator. PATIENTS AND METHODS: For a cohort of 83 patients recruited in the multicenter studies KRANIOPHARYNGEOM 2000 and HIT-ENDO data on HC could be analyzed, based on medical records assessed in developmental monitoring visits performed at defined time points before CP diagnosis. RESULTS: When comparing HC standard deviation scores (SDS) before CP diagnosis in 83 patients at defined time points between birth and 4 years of age, all HC were in the upper normal range. However, CP patients diagnosed at an age ≤4 years with initial hypothalamic involvement presented with a tendency towards an increased HC SDS early before CP diagnosis at routine medical examinations during the first 7 months of life. CONCLUSIONS: We conclude that monitoring of growth and weight development including HC can lead to early CP diagnosis and treatment. This might prevent higher grades of hypothalamic involvement and lead to an improvement of quality of life after CP. Further studies on the specific value of HC as a diagnostic marker are warranted.

A 55-Year-Old Woman Presenting with a Second Diagnosis of Craniopharyngioma Following Diagnosis and Successful Treatment of Craniopharyngioma as a 5-Year-Old Child.

BACKGROUND Craniopharyngioma is a rare, partly cystic embryonic malformation of the sellar and parasellar region and is usually benign. This report is of a 55-year-old woman presenting with a second diagnosis of craniopharyngioma following diagnosis and successful treatment of craniopharyngioma as a 5-year-old child. CASE REPORT Our patient was diagnosed with craniopharyngioma at age 5 when she presented with headaches accompanied by nausea and vomiting, decreased visual acuity, polyurea, and polydipsia for 6 months. She was found to have diplopia and grade II papilledema. A skull X-ray showed separation of the sutures and a calcified mass in the suprasellar region. A pneumoencephalogram showed extension of the tumor into the third ventricle. Surgery was performed via transcallosal approach followed by radiotherapy at 5000 rays. She was followed up clinically and radiologically and had been disease-free until age 55, when she presented with headache and facial numbness. On examination, she had right-eye Horner syndrome, decreased sensation in the right side of the face, diplopia, and grade 2 facial palsy. An MRI revealed interval significant recurrence of the craniopharyngioma at the sellar/suprasellar mass with extension to the right Meckel's cave and the right posterior fossa. On April 6, 2023, she underwent surgical resection through a right-sided craniotomy and Kawase approach. This was followed by CyberKnife radiation therapy. CONCLUSIONS This report has presented a rare recurrence of craniopharyngioma with a 50-year interval and has highlighted the challenges in the diagnosis and the multidisciplinary approach to patient diagnosis and management.

Rathke's Cleft Cyst and Craniopharyngioma: A Continuum of the Same Spectrum? Insights from an Interesting Case and Previous Literature.

Rathke's Cleft Cysts (RCCs) and Craniopharyngiomas (CPs) may represent disease entities on the same etio-pathological spectrum. We report the case of a 36-year-old female presenting with vision loss and menstrual irregularities, imaging shows a predominantly cystic lesion in the sellar region with suprasellar extension. She underwent a microscopic transnasal resection of the lesion. She later presented with recurrent symptoms and increased residual lesion size on imaging, a transcranial excision of the lesion was performed. Histopathology from the initial operative specimen revealed RCC with squamous metaplasia which was BRAF negative, while the specimen from the second surgery revealed BRAF positive papillary stratified squamous architecture suggestive of Papillary CP. This case adds to the evidence that both RCCs and papillary CPs may be the spectrum of the same disease. Further, papillary CPs may be an evolution from the RCCs.

Diagnostic support in pediatric craniopharyngioma using deep learning.

PURPOSE: We studied a pediatric group of patients with sellar-suprasellar tumors, aiming to develop a convolutional deep learning algorithm for radiological assistance to classify them into their respective cohort. METHODS: T1w and T2w preoperative magnetic resonance images of 226 Chilean patients were collected at the Institute of Neurosurgery Dr. Alfonso Asenjo (INCA), which were divided into three classes: healthy control (68 subjects), craniopharyngioma (58 subjects) and differential sellar/suprasellar tumors (100 subjects). RESULTS: The PPV among classes was 0.828±0.039, and the NPV was 0.919±0.063. Also explainable artificial intelligence (XAI) was used, finding that structures that are relevant during diagnosis and radiological evaluation highly influence the decision-making process of the machine. CONCLUSION: This is the first experience of this kind of study in our institution, and it led to promising results on the task of radiological diagnostic support based on explainable artificial intelligence (AI) and deep learning models.

Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma.

OPINION STATEMENT: The integration of targeted therapy into the multimodal management of craniopharyngiomas represents a significant advancement in the field of neuro-oncology. Historically, the management of these tumors has been challenging due to their proximity to vital brain structures, necessitating a delicate balance between tumor control and the preservation of neurological function. Traditional treatment modalities, such as surgical resection and radiation, while effective, carry their own set of risks, including potential damage to surrounding healthy tissues and the potential for long-term side effects. Recent insights into the molecular biology of craniopharyngiomas, particularly the discovery of the BRAF V600E mutation in nearly all papillary craniopharyngiomas, have paved the way for a targeted systemic treatment approach. However, advances have been limited for adamantinomatous craniopharyngiomas. The success of BRAF/MEK inhibitors in clinical trials underscores the potential of these targeted therapies not only to control tumor growth but also to reduce the need for more invasive treatments, potentially minimizing treatment-related complications. However, the introduction of these novel therapies also brings forth new challenges, such as determining the optimal timing, sequencing, and duration of targeted treatments. Furthermore, there are open questions regarding which specific BRAF/MEK inhibitors to use, the potential need for combination therapy, and the strategies for managing intolerable adverse events. Finally, ensuring equitable access to these therapies, especially in healthcare systems with limited resources, is crucial to prevent widening healthcare disparities. In conclusion, targeted therapy with BRAF/MEK inhibitors holds great promise for improving outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. However, additional research is needed to address the questions that remain about its optimal use and integration into comprehensive treatment plans.

[Chinese expert consensus on diagnosis and treatment of craniopharyngioma (2024)].

Craniopharyngioma is a sellar tumor with benign pathology and malignant clinical manifestations. Partial resection plus radiotherapy, internal radiation therapy and chemotherapy are the conventional treatment strategies forcraniopharyngioma in most hospitals, which cause many patients to lose the best time to cure and make reoperation more difficult after recurrence. Therefore, the Pediatric Group of Chinese Society of Neurosurgery, Chinese Medical Association organized domestic experts from Pediatrics, Pediatric Neurosurgery, Genetics and Endocrinology to reach a consensus on the following topics: pathological and molecular genetic classification of craniopharyngioma, basic principles of curing tumors, surgical classification of tumors, surgical approach, perioperative and long-term treatment plan. This is expected to improve the quality of life and prognosis of patients, and further standardize the diagnosis and treatment of craniopharyngioma.

Global pediatric craniopharyngioma management modalities and outcomes.

INTRODUCTION: Pediatric craniopharyngioma is a complex pathology, with optimal management involving a multidisciplinary approach and thoughtful care coordination. To date, no studies have compared various treatment modalities and outcomes described in different global regions. We conducted a comprehensive systematic review to compare demographics, clinical presentation, treatment approach and outcomes of children diagnosed with craniopharyngioma globally. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms included "craniopharyngioma" and country-specific terms. Inclusion criteria included full-text studies published between 2000-2022, primarily examining pediatric patients 18-years old or younger diagnosed with craniopharyngioma, and reporting management and outcomes of interest. Data extracted included country of origin, demographical data, initial presentation and treatment modality, and outcomes. Descriptive statistics and between-group comparisons based on country of origin were performed. RESULTS: Of 797 search results, 35 articles were included, mostly originating from high-income countries (HIC) (n = 25, 71.4%). No studies originated from low-income countries (LIC). When comparing HIC to middle-income countries (MIC), no differences in patient demographics were observed. No differences in symptomatology at initial presentation, tumor type, surgical approach or extent of surgical resection were observed. HIC patients undergoing intracystic therapy were more likely to receive bleomycin (n = 48, 85.7%), while the majority of MIC patients received interferon therapy (n = 10, 62.5%). All MIC patients undergoing radiation therapy underwent photon therapy (n = 102). No statistically significant differences were observed in postoperative complications or mean follow-up duration between HIC and MIC (78.1 ± 32.2 vs. 58.5 ± 32.1 months, p = 0.241). CONCLUSION: Pediatric craniopharyngioma presents and is managed similarly across the globe. However, no studies originating from LICs and resource-poor regions examine presentation and management to date, representing a significant knowledge gap that must be addressed to complete the global picture of pediatric craniopharyngioma burden and management.

Pediatric craniopharyngioma: a 20-year study on epidemiological features, clinical presentation, and survival outcomes in a tertiary care center from LMIC.

INTRODUCTION: Craniopharyngioma constitutes approximately 10% of primary brain tumors in children. It can cause considerable morbidity and mortality due to the local aggressiveness of the tumor itself or its management affecting the hypothalamus-pituitary axis and optic pathway involvement. There is very scarce data available from LMIC which makes the management controversial where multidisciplinary teams are already not available in most of the centers. This is a single-center cross-sectional retrospective review of 20-year record of 49 patients with craniopharyngioma treated between 2001 and 2020 at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan. METHODS: We have assessed the epidemiological data of children presenting with the diagnosis of craniopharyngioma, treatment modalities used, and neurological, endocrine, and hypothalamic complications in these patients. The assessment involved a retrospective review of medical records and medical follow-up. RESULTS: Out of a total of 49 patients, 26 (53%) were male, and 23 (46.9%) were female. The mean age was 9.5 years (SD ± 4.5 years). Most common symptoms at initial presentation were headache 41 (83.6%), visual deficit 40 (81.6%), nausea and vomiting 26 (53%), and endocrine abnormalities 16 (32%). Treatment modalities used at our center include gross total resection 11 (22%) and subtotal resection 38 (77%) out of total, while 6 (12.2%) patients received intracystic interferon. Histopathologic findings of the majority of patients (40 (81%)) revealed an adamantinomatous type of tumor. Only 23 (46.9%) children followed in clinic post-op. Median follow-up after craniopharyngioma presentation was 5 years (± 2.1 SD, range: 2-10 years). Pituitary hormone deficiencies (98%) and visual disturbances (75%) were the most common long-term health conditions observed. CONCLUSIONS: Since pituitary hormone deficiencies and visual disturbance were the most common long-term health conditions observed in our study, these patients require a multidisciplinary team follow-up to improve their quality of life.

National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

Craniopharyngioma in Pediatrics and Adults.

Craniopharyngiomas are rare malignancies of dysembryogenic origin, involving the sellar and parasellar areas. These low-grade, epithelial tumors account for two main histological patterns (adamantinomatous craniopharyngioma and papillary craniopharyngioma), which differ in epidemiology, pathogenesis, and histomorphological appearance. Adamantinomatous craniopharyngiomas typically show a bimodal age distribution (5-15 years and 45-60 years), while papillary craniopharyngiomas are limited to adult patients, especially in the fifth and sixth decades of life. Recently, craniopharyngioma histological subtypes have been demonstrated to harbor distinct biomolecular signatures. Somatic mutations in CTNNB1 gene encoding ß-catenin have been exclusively detected in adamantinomatous craniopharyngiomas, which predominantly manifest as cystic lesions, while papillary craniopharyngiomas are driven by BRAF V600E mutations in up to 95% of cases and are typically solid masses. Despite the benign histological nature (grade I according to the World Health Organization classification), craniopharyngiomas may heavily affect long-term survival and quality of life, due to their growth pattern in a critical region for the presence of eloquent neurovascular structures and possible neurological sequelae following their treatment. Clinical manifestations are mostly related to the involvement of hypothalamic-pituitary axis, optic pathways, ventricular system, and major blood vessels of the circle of Willis. Symptoms and signs referable to intracranial hypertension, visual disturbance, and endocrine deficiencies should promptly raise the clinical suspicion for sellar and suprasellar pathologies, advocating further neuroimaging investigations, especially brain MRI. The optimal therapeutic management of craniopharyngiomas is still a matter of debate. Over the last decades, the surgical strategy for craniopharyngiomas, especially in younger patients, has shifted from the aggressive attempt of radical resection to a more conservative and individualized approach via a planned subtotal resection followed by adjuvant radiotherapy, aimed at preserving functional outcomes and minimizing surgery-related morbidity. Whenever gross total removal is not safely feasible, adjuvant radiotherapy (RT) and stereotactic radiosurgery (SRS) have gained an increasingly important role to manage tumor residual or recurrence. The role of intracavitary therapies, including antineoplastic drugs or sealed radioactive sources, is predominantly limited to monocystic craniopharyngiomas as secondary therapeutic option. Novel findings in genetic profiling of craniopharyngiomas have unfold new scenarios in the development of targeted therapies based on brand-new biomolecular markers, advancing the hypothesis of introducing neoadjuvant chemotherapy regimens in order to reduce tumor burden prior to resection. Indeed, the rarity of these neoplasms requires a multispecialty approach involving an expert team of endocrinologists, neurosurgeons, neuro-ophthalmologists, neuroradiologists, radiotherapists, and neuro-oncologists, in order to pursue a significant impact on postoperative outcomes and long-term prognosis.

[Etiology, Genetic Features and Clinical Presentations in Craniopharyngiomas].

Craniopharyngiomas are among the most challenging intracranial tumors for neurosurgeons. Their management is complicated due to growth patterns such as infiltration into the pituitary stalk, chiasma, and hypothalamus. Therefore, patients may present with various conditions such as endocrine disorders, visual disturbances, or hypothalamic dysfunction in the first medical examination. Moreover, surgical management is challenging because of the high risk of recurrence. Two well-known histological subtypes include adamantinomatous and papillary craniopharyngiomas, and recent advances in genetic analysis have provided significant findings about these subtypes. The adamantinomatous subtype can be distinguished by mutations in CTNNB1, whereas the V600E mutation of the BRAF gene characterizes the papillary subtype. This review describes the etiology, genetic features, and clinical presentations of craniopharyngiomas.

Single-cell RNA sequencing highlights intratumor heterogeneity and intercellular network featured in adamantinomatous craniopharyngioma.

Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.

Outcome after pediatric craniopharyngioma: the role of age at diagnosis and hypothalamic damage.

OBJECTIVE: Craniopharyngiomas (CP) are rare malformational tumors. Clinical presentation and outcome of pediatric patients with CP with specific regard to age at diagnosis is not clear. The aim of this cohort study was to determine clinical presentation and outcome in these patients diagnosed at different ages at diagnosis. DESIGN: Seven hundred and nine patients diagnosed with CP were recruited from 1999 to 2021 in HIT-Endo and KRANIOPHARYNGEOM 2000/2007/Registry 2019 and prospectively observed. METHODS: Age at diagnosis was categorized as infants and toddlers (<2 years), early childhood (2-6 years), middle childhood (6-12 years), and early adolescence (12-18 years). Overall and event-free survival (EFS), functional capacity (FMH), and quality of life (QoL) (PEDQOL) were assessed. RESULTS: Severe obesity (body mass index [BMI] >3 standard deviation score [SDS]) was prevalent in 45.4% at last visit. A lower EFS but better QoL was observed in children with age at diagnosis <6 years compared with ≥6 years. Reduced functional capacity percentiles were associated with increased BMI-SDS at last visit (rho = -0.125, 95% confidence interval [CI; -0.21; -0.04]) and age at diagnosis <2 years. Posterior hypothalamic involvement and hypothalamic lesion (HL) were independent risk factors for reduced EFS (hazard ratio = 1.59, 95% CI [1.12-2.26]) and obesity at last visit (odds ratio = 2.94, 95% CI [1.73-5.08]). Age at diagnosis did not contribute to severe obesity and reduced QoL. CONCLUSIONS: Diagnosis of CP at age <6 years may help patients to adapt early to disabilities but may lead to a higher probability of CP relapse. Not age at diagnosis but posterior HL may be the contributing factor to severe obesity and a reduced QoL. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00258453; NCT01272622; NCT04158284.

Unusual circumstance for craniopharyngioma discovery on meningoencephalitis: a pediatric case report.

BACKGROUND: Craniopharyngioma is a rare condition in children, but it is the most frequent tumor that occurs in the hypothalamic pituitary region. Chemical meningitis has been described as an uncommon postoperative complication, but no chemical meningitis due to a spontaneous rupture leading to craniopharyngioma diagnosis in children has been reported. CASE PRESENTATION: This is a case of a 13-year-old boy presenting with fever, vomiting and headache for two days. The CT scan revealed a suprasellar lesion, and lumbar puncture showed aseptic meningitis. The cerebral MRI suggested a craniopharyngioma and the cerebrospinal fluid cholesterol concentration was abnormally high. A thorough medical history indicated some visual disturbance, which improved at the onset of meningitis, and an inflection of the growth curve. The anatomopathological analysis of the tumor confirmed the diagnosis of craniopharyngioma. CONCLUSIONS: This case is the first to report the discovery of a craniopharyngioma with meningoencephalitis caused by the rupture of a craniopharyngioma cyst in a child. Diagnosis was facilitated by determining the cholesterol level in the cerebrospinal fluid, as well as fine anamnesis to identify visual and growth disturbances.

Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPG.co.

PURPOSE: To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. METHODS: We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. RESULTS: The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7-357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. CONCLUSIONS: Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity.

Retrospective dataset and survey analyses identify gaps in data collection for craniopharyngioma and priorities of patients and families affected by the disease.

INTRODUCTION: Craniopharyngioma is a rare, low-grade tumor located in the suprasellar region of the brain, near critical structures like the pituitary gland. Here, we concurrently investigate the status of clinical and genomic data in a retrospective craniopharyngioma cohort and survey-based data to better understand patient-relevant outcomes associated with existing therapies and provide a foundation to inform new treatment strategies. METHODS: Clinical, genomic, and outcome data for a retrospective cohort of patients with craniopharyngioma were collected and reviewed through the Children's Brain Tumor Network (CBTN) database. An anonymous survey was distributed to patients and families with a diagnosis of craniopharyngioma to understand their experiences throughout diagnosis and treatment. RESULTS: The CBTN repository revealed a large proportion of patients (40 - 70%) with specimens that are available for sequencing but lacked relevant quality of life (QoL) and functional outcomes. Frequencies of reported patient comorbidities ranged from 20-35%, which is significantly lower than historically reported. Survey results from 159 patients/families identified differences in treatment considerations at time of diagnosis versus time of recurrence. In retrospective review, patients and families identified preference for therapy that would improve QoL, rather than decrease risk of recurrence (mean 3.9 vs. 4.4 of 5) and identified endocrine issues as having the greatest impact on patients' lives. CONCLUSIONS: This work highlights the importance of prospective collection of QoL and functional metrics alongside robust clinical and molecular correlates in individuals with craniopharyngioma. Such comprehensive measures will facilitate biologically relevant therapeutic strategies that also prioritize patient needs.

Approach to the Patient With Hypothalamic Obesity.

Hypothalamic obesity (HO) is defined as abnormal weight gain due to physical destruction of the hypothalamus. Suprasellar tumors, most commonly craniopharyngiomas, are a classic cause of HO. HO often goes unnoticed initially as patients, families, and medical teams are focused on oncologic treatments and management of panhypopituitarism. HO is characterized by rapid weight gain in the first year after hypothalamic destruction followed by refractory obesity due to an energy imbalance of decreased energy expenditure without decreased food intake. Currently available pharmacotherapies are less effective in HO than in common obesity. While not a cure, dietary interventions, pharmacotherapy, and bariatric surgery can mitigate the effects of HO. Early recognition of HO is necessary to give an opportunity to intervene before substantial weight gain occurs. Our goal for this article is to review the pathophysiology of HO and to discuss available treatment options and future directions for prevention and treatment.