Could setmelanotide be the game-changer for acquired hypothalamic obesity?

Children with acquired hypothalamic obesity, e.g. following treatment for pediatric craniopharyngioma are at great risk for metabolic syndrome, cardiovascular health problems and premature mortality. Treatment for acquired hypothalamic obesity has thus far been disappointing. Several interventions were reported to be partially successful, including dextro-amphetamine and GLP-1R agonists, although results in acquired hypothalamic obesity are conflicting. Disruption of signaling through the melanocortin-4 receptor (MC4R) pathway results in hyperphagia and severe early-onset hypothalamic obesity. Recently, the MC4R agonist setmelanotide has shown promising results in children with genetic forms of hypothalamic obesity; POMC, PCSK1 and LEPR. Patient quotes such as "we have our family life back" illustrate the magnitude of the effect. Targeted hormone replacement therapy with a MC4R agonist for acquired hypothalamic obesity could be a game-changer. Preliminary results of setmelanotide treatment in 14, mostly pediatric, patients with acquired hypothalamic obesity are promising. The FDA has recommended that a prospective, randomized, blinded trial be conducted over a 12 months treatment period, comparable to pivotal trials for other obesity drugs. It may be discussed whether setmelanotide should be regarded as an obesity drug or whether it may be envisioned as an agent for hypothalamic substitution therapy. In this commentary we discuss the trial that is currently recruiting patients with acquired hypothalamic obesity

Hormone replacement in survivors of childhood cancer and brain tumors: safety and controversies

Childhood cancer survivors are at risk for developing endocrine disorders, including deficits in growth hormone, thyroid hormone and sex hormones. Th e influence these hormones have on cell growth and metabolism has raised concerns regarding the safety of their use as treatments in survivors of childhood cancer and brain tumors. This article offers a summary of current knowledge, controversies and areas f or future research pertaining to this area

Аналіз ефективності використання потенціалу матеріальних ресурсів підприємства

Метою даного дослідження виступає пошук аналітичних можливостей комплексної оцінки та аналізу використання потенціалу матеріальних ресурсів та визначення шляхів підвищення ефективності використання матеріальних ресурсів підприємства

A 14-year-old girl with premature ovarian insufficiency but with a positive pregnancy test

Objectives: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test. Case presentation: A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17 bèta-estradiol: hCG levels normalized. Conclusions: The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.</p

A 14-year-old girl with premature ovarian insufficiency but with a positive pregnancy test

Objectives: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test. Case presentation: A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17 bèta-estradiol: hCG levels normalized. Conclusions: The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.</p

Children with multiple endocrine neoplasia type 2B: Not tall and marfanoid, but short with normal body proportions

Objective: Multiple endocrine neoplasia 2B (MEN2B) is characterised by early-onset medullary thyroid carcinoma (MTC), pheochromocytoma and several nonendocrine manifestations. Unfortunately, MEN2B is often diagnosed late, after the development of clinically significant MTC. Marfanoid habitus is considered an important related feature, which may lead to the assumption that patients with MEN2B have tall stature. Here, we describe the longitudinal growth and body proportions of eight MEN2B patients during childhood. Design: It is a retrospective case series. Methods: Patients were under the care of a Dutch MEN expertise centre. Growth patterns were assessed and interpreted in relation to body mass index (BMI), age at diagnosis and at thyroidectomy, extensiveness of disease manifestations and parental height. Results: Seven patients were short during childhood, of whom four showed growth below target height range (THR) and three at the lowest margin of THR. Only one patient grew well within THR. All patients who attained final height (n = 4) ended within THR, despite short stature during childhood. Arm span/height ratio was not increased and upper segment/lower segment ratio was not reduced in any patient. Short stature in childhood in this study did not seem to be associated with age at diagnosis, age at thyroidectomy, extensiveness of MTC, endocrine deficiencies or BMI. Conclusions: This study shows that children with MEN2B may well present with short rather than tall stature. Thereafter, final height within THR was attained in those who already reached adulthood, but none had tall stature. Finally, body proportions were normal in all children and adults in this case series, not underlining a ‘marfanoid’ body habitus

Presentation and outcome of subsequent thyroid cancer among childhood cancer survivors compared to sporadic thyroid cancer:a matched national study

Objective: Childhood cancer survivors (CCS) are at increased risk to develop differentiated thyroid cancer predominantly after radiotherapy (subsequent DTC). It is insufficiently known whether subsequent DTC in CCS has a different presentation or outcome than sporadic DTC. Methods: Patients with subsequent DTC (n = 31) were matched to patients with sporadic DTC (n = 93) on gender, age and year of diagnosis to compare presentation and DTC outcomes. Clinical data were collected retrospectively. Results: Among the CCS with subsequent DTC, all but one had received chemotherapy for their childhood cancer, 19 (61.3%) had received radiotherapy including the thyroid region, 3 (9.7%) 131I-MIBG and 8 (25.8%) had received treatment with chemotherapy only. Subsequent DTC was detected by surveillance through neck palpation (46.2%), as a self-identified mass (34.6%), or by chance. Among sporadic DTC patients, self detection predominated (68.8%). CCS with subsequent DTC tended to have on average smaller tumors (1.9 vs 2.4 cm, respectively, (P = 0.051), and more often bilateral (5/25 (60.0%) vs 28/92 (30.4%), P = 0.024). There were no significant differences in the occurrence of surgical complications, recurrence rate or disease-related death. Conclusion: When compared to patients with sporadic DTC, CCS with subsequent DTC seem to present with smaller tumors and more frequent bilateral tumors. Treatment outcome seems to be similar. The finding that one-third of subsequent DTC cases had been treated with chemotherapy only needs further investigation. These results are important for the development of surveillance programs for CCS at risk for DTC and for treatment guidelines of subsequent DTC

Diagnostic criteria for the hypothalamic syndrome in childhood

OBJECTIVE: Hypothalamic syndrome (HS) in childhood is a rare condition. Its epidemiology is not well known because incidence and prevalence are related to very rare underlying diseases. In addition, different criteria for the syndrome are used across studies. Recognizing the HS may be difficult, due to its rareness and variety of symptoms. Having diagnostic criteria for signs and symptoms of hypothalamic dysfunction may aid in early recognition and diagnosis, in the reporting and understanding of its etiology, in predicting its course and its management. We aimed to define diagnostic criteria for hypothalamic dysfunction and a score for the presence of HS in childhood. METHODS: Diagnostic criteria for hypothalamic dysfunction were developed and subdivided into hyperphagia, hypophagia, body mass index, behavioral problems, sleep disorders, temperature regulation disorders, pituitary dysfunction, radiological hypothalamic assessment, and presence/suspicion of a hypothalamic genetic syndrome. Subsequently, the scoring system was tested in a retrospective cohort of 120 patients at risk for hypothalamic dysfunction. RESULTS: A score for presence of HS was developed. Using this new hypothalamic score, in total 52.5% were scored as having HS. Of these patients, 76.7% were diagnosed with pituitary dysfunction, 32.5% with hyperphagia, 40% with sleep disorders, and 14.2% with temperature dysregulation. For several criteria, clinical data was missing in more than 50% of cases. CONCLUSIONS: The here proposed diagnostic criteria for hypothalamic dysfunction and score for presence of HS may be used for care purposes and to aid in early recognition. Also it will be useful for research or registration purposes

Endocrine Health in Childhood Cancer Survivors

Endocrine late effects, including reproductive disorders and secondary thyroid cancer, have been reported in up to 50 %childhood cancer survivors (CCS) more than 5 years after treatment. Most endocrine disorders are amenable to treatment; awareness of symptoms is therefore of great importance. Recognition of these symptoms may be delayed however because many are nonspecific. Timely treatment of endocrine disorders improves quality of life in CCS and prevents possible consequences, such as short stature, bone and cardiovascular disorders, and depression. At-risk CCS must therefore be regularly and systematically monitored. This article provides a summary of the most commonly reported endocrine late effects in CCS

Thyroid function after diagnostic I-123-metaiodobenzylguanidine in children with neuroblastic tumors

BACKGROUND: Metaiodobenzylguanidine (MIBG) labeled with radioisotopes can be used for diagnostics 123I-) and treatment (131I-) in patients with neuroblastic tumors. Thyroid dysfunction has been reported in 52% of neuroblastoma (NBL) survivors after 131I-MIBG, despite thyroid protection. Diagnostic 123I-MIBG is not considered to be hazardous for thyroid function; however, this has never been investigated. Therefore, the aim of this study was to evaluate the prevalence of thyroid dysfunction in survivors of a neuroblastic tumor who received diagnostic 123I-MIBG only. METHODS: Thyroid function and uptake of 123I- in the thyroid gland after 123I-MIBG administrations were evaluated in 48 neuroblastic tumor survivors who had not been treated with 131I-MIBG. All patients had received thyroid prophylaxis consisting of potassium iodide or a combination of potassium iodide, thiamazole and thyroxine during exposure to 123I-MIBG. RESULTS: After a median follow-up of 6.6 years, thyroid function was normal in 46 of 48 survivors (95.8%). Two survivors [prevalence 4.2% (95% CI 1.2-14.0)] had mild thyroid dysfunction. In 29.2% of the patients and 11.1% of images 123I- uptake was visible in the thyroid. In 1 patient with thyroid dysfunction, weak uptake of 123I- was seen on 1 of 10 images. CONCLUSIONS: The prevalence of thyroid dysfunction does not seem to be increased in patients with neuroblastic tumors who received 123I-MIBG combined with thyroid protection. Randomized controlled trials are required to investigate whether administration of 123I-MIBG without thyroid protection is harmful to the thyroid gland