Hypothalamic Disorders Research Articles

Missed Diagnoses and Health Problems in Adults With Prader-Willi Syndrome: Recommendations for Screening and Treatment.

ContextPrader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. Annual mortality of patients with PWS is high (3%). In half of the patients, the cause of death is obesity related and/or of cardiopulmonary origin. Health problems leading to this increased mortality often remain undetected due to the complexity and rareness of the syndrome.ObjectiveTo assess the prevalence of health problems in adults with PWS retrospectively.Patients, Design, and SettingWe systematically screened 115 PWS adults for undiagnosed health problems. All patients visited the multidisciplinary outpatient clinic for rare endocrine syndromes at the Erasmus University Medical Center, Rotterdam, Netherlands. We collected the results of medical questionnaires, interviews, physical examinations, biochemical measurements, polygraphy, polysomnography, and radiology.Main outcome measuresPresence or absence of endocrine and nonendocrine comorbidities in relation to living situation, body mass index, genotype, and demographic factors.ResultsSeventy patients (61%) had undiagnosed health problems, while 1 in every 4 patients had multiple undiagnosed health problems simultaneously. All males and 93% of females had hypogonadism, 74% had scoliosis, 18% had hypertension, 19% had hypercholesterolemia, 17% had type 2 diabetes mellitus, and 17% had hypothyroidism. Unfavorable lifestyles were common: 22% exercised too little (according to PWS criteria) and 37% did not see a dietitian.ConclusionsSystematic screening revealed many undiagnosed health problems in PWS adults. Based on patient characteristics, we provide an algorithm for diagnostics and treatment, with the aim to prevent early complications and reduce mortality in this vulnerable patient group.

Conventional autoantibodies against brain antigens are not routinely detectable in serum and CSF of narcolepsy type 1 and 2 patients

Narcolepsy with cataplexy (NT1) is a chronic hypothalamic disorder with a presumed immune-mediated etiology leading to a loss of hypocretin neurons. Previous studies reported conflicting results in terms of presence of auto-antibodies involved in narcolepsy pathophysiology. A total of 86 patients with primary/idiopathic narcolepsy (74 NT1, 12 NT2) and 23 control patients with excessive daytime sleepiness due to other causes were tested for the presence of a wide range of anti-neuronal antibodies in both serum and cerebrospinal fluid (CSF). Anti-neuronal antibodies were rarely found in patients with narcolepsy (n = 2) and in controls (n = 1). Our results are in line with previous reports. We can therefore support the current evidence, that conventional anti-neuronal antibodies are not routinely detected during the workup of NT1 and other CDH patients.

A CASE STUDY OF MADHUTAILIKA BASTI AND UDVARTANA IN MEDOROGA WITH SPECIAL REFERENCE TO OBESITY

The disease Sthaulya has been mentioned by Acharya Charaka in Ashtaunindita purushadhyaya. symptomps like heaviness and bulkiness of the body due to extreme growth especially in Udaradi (Abdomen) region is termed as “Sthula” and the state (Bhava) of Sthula is called as “Sthaulya”. Charaka has mentioned the Beejadosha Swabhavata as one ofthe important etiological factors besides other for the disease. nowadays maximum percentages of carbohydrates & high-tech machineries which makes a person less active & prone to Sthaulya. organs, Kshudra shwasa, Anga gauravata and other various signs andsymptoms. In modern medical science Sthaulya is compared with Obesity and it is defined asexcess of body fat that poses a health risk. It is caused by excess calorieintake, but endocrine disorders like hypothalamic disorders, Hypothyroidism, Cushing‟s syndrome etc. can also be the cause of Obesity.
 Here in the case study a female patient of age 44 years presenting with clinical features of Sthaulya and was treated with madhutailik basti and Udvartana got relief within 15 days.

Testosterone Supplementation Rescues Spermatogenesis and In Vitro Fertilizing Ability of Sperm in Kiss1 Knockout Mice.

Restoration of spermatogenesis and fertility is a major issue to be solved in male mammals with hypogonadotropic hypogonadism. Kiss1 knockout (KO) male mice are postulated to be a suitable animal model to investigate if hormonal replacement rescues spermatogenesis in mammals with this severe reproductive hormone deficiency, because KO mice replicate the hypothalamic disorder causing hypogonadism. The present study investigated whether testosterone supplementation was able to restore spermatogenesis and in vitro fertilization ability in Kiss1 KO mice. To this end, spermatogenesis, in vitro fertilization ability of Kiss1 KO sperm, and preimplantation development of wild-type embryos inseminated with Kiss1 KO sperm, were examined. The newly generated Kiss1 KO male mice showed infertility with cryptorchidism. Subcutaneous testosterone supplementation for 6 weeks restored plasma and intratesticular testosterone levels, elicited testicular descent, and induced complete spermatogenesis from spermatocytes to elongated spermatids in the testis, resulting in an increase in epididymal sperm number in testosterone-supplemented Kiss1 KO male mice. Epididymal sperm derived from the testosterone-supplemented Kiss1 KO mice showed normal in vitro fertilization ability, and the fertilized eggs showed normal preimplantation development, while the males failed to impregnate females. These results suggest that the failure of spermatogenesis in Kiss1 KO mice is mainly due to a lack of testosterone production, and that Kiss1 KO sperm are capable of fertilizing eggs if the animals receive the appropriate testosterone supplementation without local kisspeptin signaling in the testis and epididymis. Thus, testosterone supplementation would restore spermatogenesis of male mammals showing hypogonadotropic hypogonadism with genetic inactivation of the KISS1/Kiss1 gene.

MON-238 A Diagnostic “Headache” in a Pregnant Woman with Diabetes Insipidus: Blame the Placenta or the Pituitary?

BackgroundDiabetes insipidus (DI) occurs in 1/30,000 pregnancies and can be difficult to recognize due to normal peripartum physiology. The most common etiology is excess production of placental vasopressinase, which degrades maternal anti-diuretic hormone. Although rare, hypothalamic and pituitary disorders must also be considered in pregnant patients presenting with DI. We present the case of a pregnant woman presenting with diabetes insipidus and pituitary apoplexy.Clinical caseWe were called to see a 33 year old female with polyuria and polydipsia on post-partum day #2. She had presented to the ED at 29.4 weeks of her 5th pregnancy (G5P4) with an unrelenting headache, nausea, and vomiting for 12 hours. She was tachycardic, hypertensive, and had no focal neurologic deficits. Fetal evaluation was reassuring. Admission labs included serum sodium of 147 mEq/L (n 136-145), serum potassium 2.8 mEq/L (n 3.4-4.4), and urine specific gravity of 1.003 (n 1.005-1.030). Glycemic parameters, renal function, and hepatic function were normal. She remained tachycardic despite vigorous IV fluid administration. Overnight into hospital day #3 she began to have uterine contractions with fetal decelerations, and betamethasone was given. It was noted that she had produced 8L of urine over the preceding 24 hours. Serum sodium was 159 mEq/L with urine osmolality of 78 mOsmol/kg (n 300-900). A presumptive diagnosis of gestational DI was made and 2 mcg of subcutaneous DDAVP was given. Shortly thereafter she delivered a healthy infant. Maternal blood loss was minimal. Over the next 12 hours her urine became concentrated and her serum sodium decreased, but by the next morning she re-developed dilute polyuria.At the time of our evaluation, her headache had resolved and she had no focal neurologic deficits. She had no apparent signs of glucocorticoid or thyroxine deficiency but had not begun to lactate. Biochemical evaluation included early morning cortisol of 4.6 ug/dL (n 3.5-18.3), TSH 0.46 uIU/mL (n 0.35-4.94), free T4 0.76 ng/dL (n 0.70-1.48), and prolactin 26.6 ng/mL (n 5.2-26.5). Pituitary MRI showed a mildly enlarged gland with central T1 hyperintensity, consistent with apoplexy. A regimen of hydrocortisone and DDAVP was initiated.ConclusionPituitary apoplexy is uncommon during pregnancy but is potentially life-threatening for the mother and fetus if it goes unrecognized. The significant physiologic growth of the pituitary during pregnancy may increase the risk of apoplexy. A severe headache is the most common symptom and may be accompanied by signs of pituitary dysfunction. Although diabetes insipidus is more often caused by placental physiology, pituitary apoplexy must also be considered in a pregnant woman who has concurrent neurologic symptoms.

MON-284 Systematic Screening Reveals Large Number of Undiagnosed and Untreated Cardiovascular Risk Factors in Adults with Prader-Willi Syndrome

Introduction: Prader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hypotonia, intellectual disability (ID), pituitary hormone deficiencies and hyperphagia. In PWS, up to 3% of patients die every year. In half of the patients, the cause of death is obesity related and / or of cardiovascular (CV) origin.Obesity is caused by hyperphagia combined with a low energy expenditure. Untreated hormone deficiencies like hypogonadism and hypothyroidism can cause low muscle mass and low basal rest metabolism (BRM) leading to this low energy expenditure. Patients with PWS should exercise one hour daily to compensate for their low BRM. However, hormone deficiencies usually cause fatigue, leading to exercise intolerance. Musculoskeletal and / or behavioral problems can also cause reduced physical activity. The subsequent sedentary lifestyle can induce CV risk factors like hypertension, hypercholesterolemia and diabetes mellitus (DM).Another risk factor often present in PWS is sleep apnea, which can be central (CSA), obstructive (OSA) or both. Both CSA and OSA can lead to pulmonary hypertension and a further increase in obesity.The above mentioned health problems often remain unnoticed and untreated, which is partly due to the behavioral phenotype of PWS (patients seldomly report pain and hardly ever complain about physical problems). However, if left untreated, these risk factors can cause CV complications leading to hospital admission or even death. To reveal yet undiagnosed health problems, we performed a systematic health screening among adults with PWS. Methods: We systematically screened 115 adults with PWS (mean age 31.4 ± 12.1 y, mean BMI 31.8 ± 9,5 kg/m2) for the presence of undiagnosed health problems and cardiovascular risk factors. Based on a medical questionnaire, medical file search, extensive interview, thorough physical examination and biochemical measurements we made an overview of the undiagnosed health problems in adults with PWS. If possible, we performed polygraphy to test for sleep apnea. Results: Undiagnosed health problems (hypertension, DM, hypercholesterolemia, sleep apnea, hypothyroidism and hypogonadism) were present in 50% of the patients. 10% had multiple undiagnosed health problems simultaneously. All males and 94% of females had hypogonadism and 15% had hypothyroidism. Hypertension and / or hypercholesterolemia were present in 20% and DM was present in 16%. One third of patients was not on a diet and 22% exercised less than 30 minutes a day. Sleep apnea was present in 17 of 26 patients tested. Conclusion: We detected a striking number of undiagnosed health problems among adults with PWS which, if left untreated, can pose a serious health threat. Systematic screening is needed to detect these problems in an early phase. This will prevent burdensome and expensive complications and might even reduce mortality in this vulnerable patient population.

Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment.

Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known ashypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep-wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses onour current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep-wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the 'narcoleptic borderland', including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed.

Pattern of Paediatric Endocrine Disorders According to ICD-10 Classification in a Tertiary Centre in Southern Nigeria

Aim: To describe the spectrum of various endocrine disorders seen in children and adolescents in Port Harcourt over the period 2013-2017 using modified European Society of Paediatric endocrinology ICD -10 classification.
 Study Design: Descriptive, Cross sectional study.
 Place and Duration: Paediatric endocrinology Unit, Department of Paediatrics, University of Port Harcourt Teaching Hospital. Study was done with data from January 2013 to August 2017.
 Methods: A retrospective review of 178 patients with various endocrine diseases was reported. Data on biodata, clinical presentations and investigations with diagnosis were retrieved from the clinic and ward records and endocrine unit registers.
 Results: A total of 178 patients were seen with various endocrine disorders over the study period accounting for 4.5% of Paediatric specialist clinic consultations. There were 89(50.0%) females and 80(44.9%) males. Nine (5.1%) had genital ambiguity. The ages of patients ranged from 12days to 17years with a mean age of 6.9 ± 5.1years. The commonest endocrine disorders were pubertal disorders, diabetes mellitus, thyroid disorders and calcium phosphate metabolism and bone disorders in 34(17%), 27(14%) 23(12%), 22(11%) and 22(11%) respectively. Twenty two (11%) of the patients had obesity and 10(5%) had syndromes with endocrine features. Other disorders seen were sex development and gender disorders, testicular/male reproductive tract disorders, growth disorders (short stature) ovarian/female reproductive tract disorders, pituitary/ hypothalamic disorders and adrenal disorders in 17(9%), 17(9%) 10(5%),7(4%), 5(2.5%) and 3(1.5%) respectively. Type 1 DM remained the commonest type of DM. Most of the patients were of the middle social class (social class III). Challenges to management included high cost of investigations and drugs, high rate of loss to follow up.
 Conclusion: Pubertal disorders, type 1 Diabetes mellitus, thyroid disorders, calcium and phosphate metabolism and bone disorders and obesity were the commonest cases in our review. Most investigations were available in private laboratories with high cost of investigation leading to loss to follow up and continuation of care.

The effect of copy number variations in chromosome 16p on body weight in patients with intellectual disability.

Syndromic monogenic obesity is a rare and severe early-onset form of obesity. It is characterized by intellectual disability, congenital malformations, and/or dysmorphic facies. The diagnosis of patients is challenging due to the genetic heterogenicity of this condition. However, the use of microarray technology in combination with public databases has been successful on genotype-phenotype correlations, especially for body mass index (BMI) alteration. In this study, the relationship between copy number variations (CNVs) detected by microarray mapping on 16p region and BMI alterations in syndromic patients were assessed. In order to achieve this goal, 680 unrelated Spanish children with intellectual disability were included. 16p region was characterized by using microarray platforms. All detected variants were classified as: (I) one previously non-described 10-Mb duplication in 16p13.2p12.3 region considered causal of intellectual disability and severe overweight, and (II) eleven 16p11.2 CNVs of low prevalence but with recurrence in syndromic patients with severe BMI alteration (nine proximal and two distal). Proximal 16p11.2 CNVs have a dose-dependent effect: underweight in carriers of duplication and obesity in carriers of deletion. KCTD13 was identified as a possible candidate gene for BMI alteration on proximal syndromes, whereas SH2B1 gene was identified as candidate for distal syndromes. The results shown in this paper suggest that syndromic patients could constitute a reliable model to evaluate hypothalamic satiety and obesity disorders as well as generate a wide expectation for primary prevention of comorbidities. Furthermore, 16p13.2p12.3 showed to be an important region on the regulation of body fatness.

The effect of hormone therapy on bone mineral density and cardiovascular factors among Iranian female athletes with amenorrhea/oligomenorrhea: A randomized clinical trial.

Background: Functional hypothalamic menstrual disorder (FHMD) has a destructive effect on the athlete’s bone mineral density and cardiovascular system. Utilizing hormone replacement therapy to treat FHMD in athletes is controversial. This study was conducted to examine the effect of hormone therapy on bone density and the cardiovascular system of professional female athletes with FHMD. Methods: In this study, 18 female athletes with at least a 2- year history of FHMD were recruited in a 9-month single blind randomized clinical intervention (RCT) and randomly classified into 2 groups: the oral contraceptive pills (OCP) group, who received a lowdose combined oral contraceptive (OC) containing 30 µg ethinyl estradiol and 150 µg levonorgestrel (n= 10), and the control group (n= 8). Bone mineral densitometry (BMD) and certain cardiovascular risk factors were measured before and after the 9-month trial. The Chi square test was used to compare the quantitative and qualitative results. Results: Bone mineral density did not change significantly in either group. Very low density lipoprotein (VLDL) (p= 0.035) and Apolipoprotein B (Apo B) (p= 0.04) reduced significantly in the OCP group. An increase was observed in the serum levels of Apolipoprotein A (Apo A) (p= 0.01) in the control group. Changes in the Apo B to Apo A ratio was significant in both groups (OCP group: p= 0.018, control group: p= 0.040). No significant changes were observed in the other measured factors. Conclusion: Although the administration of estrogen did not significantly increase bone mineral density, it had positive effects on the cardiovascular system and lipid profile.

Hypothalamic Obesity: 4 Years of the International Registry of Hypothalamic Obesity Disorders.

Hypothalamic obesity (HyOb) is a rare cause of rapid weight gain and early metabolic comorbidities. Effective treatment strategies are limited. The registry collected participant data and compared treatment approaches. The International Registry of Hypothalamic Obesity Disorders (IRHOD) was created as a registry portal to provide education. Data collected from the initial 4 years were evaluated. Eighty-seven participants were included for analysis (median age: 27 years, range: 3-71 years). A total of 96.5% had obesity, and 3.5% had overweight at maximal weight. Seventy-five had brain tumors (86%)-the majority were craniopharyngiomas (72% of those with tumors). Nontumor etiologies included congenital brain malformation (4.6%), traumatic brain injury (3.4%), and genetic anomaly (2.3%). Ninety percent received obesity treatments including nutritional counseling (82%), pharmacotherapy (59%), bariatric surgery (8%), and vagal nerve stimulation (1%). Forty-six percent reported follow-up BMI results after obesity treatment. Surgery was most effective (median BMI decrease: -8.2 kg/m2 , median interval: 2.6 years), with lifestyle intervention (BMI: -3.4 kg/m2 , interval: 1.2 years) and pharmacological therapy (BMI: -2.3 kg/m2 , interval: 0.8 years) being less effective. Eighty percent of participants reporting follow-up weight remained in the obesity range. IRHOD identified a large cohort with self-reported HyOb. Surgical therapy was most effective at weight reduction. Nutritional counseling and pharmacotherapy modestly improved BMI. Stepwise treatment strategy for HyOb (including nutritional, pharmacological, and surgical therapies in an experienced center) may be most valuable.

Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus.

The mitogen-activated kinase phosphatase-3 (MKP-3) has gained great importance in the scientific community by acting as a regulator of the cell cycle through dephosphorylation of FoxO1, an important transcription factor involved in the insulin intracellular signaling cascade. When dephosphorylated and translocated to the nuclei, FoxO1 can promote the transcription of orexigenic neuropeptides (NPY/AgRP) in the hypothalamus, whereas insulin signaling is responsible for the disruption of this process. However, it is not understood if the hypothalamic activation of MKP-3 affects FoxO1 phosphorylation, and we hypothesized that MKP-3 overexpression reduces the capacity of the insulin signal to phosphorylate FoxO1. In the present study, we overexpressed the DUSP6 gene through an injection of adenovirus directly into the hypothalamic third ventricle of Swiss mice. The colocalization of the adenovirus was confirmed by the immunofluorescence assay. Then, MKP-3 overexpression resulted in a significant reduction of hypothalamic FoxO1 phosphorylation after insulin stimulation. This effect was independent of changes in Akt phosphorylation. Thus, the role of MKP-3 in the hypothalamus is closely associated with FoxO1 dephosphorylation and may provide a potential therapeutic target against hypothalamic disorders related to obesity and unbalanced food intake control.

Adipsic diabetes insipidus in adult patients.

Adipsic diabetes insipidus (ADI) is a very rare disorder, characterized by hypotonic polyuria due to arginine vasopressin (AVP) deficiency and failure to generate the sensation of thirst in response to hypernatraemia. As the sensation of thirst is the key homeostatic mechanism that prevents hypernatraemic dehydration in patients with untreated diabetes insipidus (DI), adipsia leads to failure to respond to aquaresis with appropriate fluid intake. This predisposes to the development of significant hypernatraemia, which is the typical biochemical manifestation of adipsic DI. A literature search was performed to review the background, etiology, management and associated complications of this rare condition. ADI has been reported to occur in association with clipping of an anterior communicating artery aneurysm following subarachnoid haemorrhage, major hypothalamic surgery, traumatic brain injury and toluene exposure among other conditions. Management is very difficult and patients are prone to marked changes in plasma sodium concentration, in particular to the development of severe hypernatraemia. Associated hypothalamic disorders, such as severe obesity, sleep apnoea and thermoregulatory disorders are often observed in patients with ADI. The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.

Adrenal Insufficiency

Adrenal insufficiency means hypo-function of the adrenal cortex, usually glucocorticoid, may be associated with mineralocorticoid and rarely adrenal androgen. It can be categorized into two types: Primary adrenal insufficiency, or Addison’s disease (cortisol low and ACTH high) or secondary/ tertiary adrenal insufficiency due to pituitary or hypothalamic disorders (both cortisol and ACTH are low). Identification of etiology is very important for plan of treatment. The reported incidence of adrenal insufficiency varies greatly depending on the population studied, the test and cut off levels used, and the cause. Many patients may present with adrenal crisis, some of them have subtle symptoms, hyperpigmentation, hypotension, electrolyte imbalance, shock etc. Many of them have iatrogenic adrenal insufficiency with features of Cushing’s syndrome. So, the manifestations of adrenal insufficiency are numerous and nonspecific, and clinicians should have a high index of suspicion and be alert to see important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension (that are refractory to fluids and vasopressors), diarrhea, weight loss, vomiting, fever etc. without any clear causation. Treatment of adrenal insufficiency is usually life-long, of course based on etiology. Short acting glucocorticoid is better, like hydrocortisone. Patients may be treated with prednisolone. Patients should be provided a “steroid card”. Sometimes it is essential to take patients under “withdrawal protocol”.Birdem Med J 2015; 5(1) Supplement: 43-48

Metabolic syndrome and obesity in childhood and adolescence

This book is the 19th volume in the series ‘Pediatric and Adolescent Medicine’. It presents an exhaustive review of various aspects of obesity and the closely related metabolic syndrome, which are undoubtedly amongst the most rapidly emerging and challenging clinical problems affecting all age groups in the current time. It is well established that childhood and adolescent obesity tracks into adulthood. Since the obesogenic behaviours and lifestyle patterns are established during childhood, it is important to focus on this period, both to enhance our understanding of genesis of obesity, and aid in devising means of preventing it. Also, the seeds for major cardiovascular and metabolic sequelae that are a major cause of morbidity and mortality during adulthood are sowed during this period. The content of the book is categorized under five sections namely, Definitions and Clinical Aspects, Causes, Consequences, Societal Aspects and Prevention, and Obesity Management. The chapter on definition brings out the complexities involved in defining metabolic syndrome in children and gives reference values for individual components. The next chapter on hypothalamic obesity describes the defects in hypothalamic energy regulating pathways in various acquired hypothalamic disorders as well as single gene mutations and genetic syndromes associated with obesity. The first chapter in the section, ‘Causes’ deals with the genetics of obesity and current state of information related to both individual genes as well as genome wide linkage scans. Subsequent chapters in this section are dedicated to the role of nutrition and sedentary lifestyle in the genesis of obesity. The last chapter on the socio-economic aspects brings out elegantly how socio-economic differences in lifestyle, weight and health result from unequal distribution of resources and opportunities within a society. The section, ‘Consequences’ presents updated information about the impact of obesity on its consequences like carbohydrate metabolism, pubertal development and orthopedic complications. In addition, a chapter is devoted to the less frequently recognized and discussed urogenital complications including renal disease, urolithiasis, enuresis and stress urinary incontinence. The next section, ‘Societal Aspects and Prevention’ deals with the less frequently discussed aspects of obesity - environmental conditions promoting obesity and dietary characteristics associated with metabolic syndrome. The chapter on the economic perspective provides an insight into cost of obesity and the cost-effectiveness of interventions to prevent/manage it. The chapter on obesity prevention, discusses the barriers in the management of obesity. It brings out a novel approach to obesity management- shifting the focus of responsibility away from target individuals, to modification of the environment, by development of community-wide health-promoting infrastructure that would promote sustainable implementation of a healthy lifestyle for all community members. The last section, ‘Obesity Management’ has a chapter dedicated to the role and efficacy of comprehensive treatment programmes focussing on diet, exercise and behaviour therapy. Another chapter presents the current information and experience with bariatric surgery during adolescence. Obesity is a global problem affecting both the developed and the developing countries. Thus, including the developing world's perspective would have enriched this book further. Also, there is no mention of the role of drugs (or lack of it) in the management of childhood obesity. It would have been good to include a chapter on the efficacy and safety of various drugs tried for management of adolescent obesity and metabolic syndrome and the current status of their clinical use. Overall this book presents a holistic view of the complex problems of obesity and metabolic syndrome, not just the medical issues. Authors with expertise and personal experience in a wide variety of domains including endocrinology, paediatrics, nutrition, orthopaedics, social sciences, and environmental health have contributed. The content is well organised and presented in a logical sequence, in a lucid and crisp manner. Apart from clinicians and nutritionists dealing with obese children and adolescents, the book would be of interest to, social scientists and economists interested in understanding the phenomenal rise in global prevalence of obesity. It would also help researchers in the above fields in identifying current gaps in our knowledge and developing appropriate research protocols to fill them.

Central Diabetes Insipidus in Infancy With or Without Hypothalamic Adipsic Hypernatremia Syndrome: Early Identification and Outcome.

Neonatal central diabetes insipidus (CDI) with or without adipsia is a very rare complication of various complex hypothalamic disorders. It is associated with greater morbidity and a high risk of developing both hypernatremia and hyponatremia, due to the condition itself or secondary to treatment with vasopressin analogs or fluid administration. Its outcomes have yet to be evaluated. To investigate the clinical outcomes of patients with neonatal-onset CDI or adipsic CDI with hypernatremia. All patients diagnosed with neonatal CDI in a university hospital-based observational study and followed between 2005 and 2015 were included and analyzed retrospectively. The various causes of CDI were grouped. Clinical outcome and comorbidities were analyzed. Ten of the 12 patients had an underlying condition with brain malformations: optic nerve hypoplasia (n = 3), septo-optic dysplasia (n = 2), semilobar holoprosencephaly (n = 1), ectopic neurohypophysis (n = 3), and unilateral absence of the internal carotid artery (n = 1). The other two were idiopathic cases. During the median follow-up period of 7.8 (4.9-16.8) years, all but one patient displayed anterior pituitary deficiency. Transient CDI was found in three (25%) patients for whom a posterior pituitary hyperintense signal was observed with (n = 2) and without (n = 1) structural hypothalamic pituitary abnormalities, and with no other underlying cerebral malformations. Patients with permanent CDI with persistent adipsia (n = 4) and without adipsia (n = 5) required adequate fluid intake and various doses of desamino-D-arginine-8-vasopressin. Those with adipsia were more likely to develop hypernatremia (45 vs 33%), hyponatremia (16 vs 4%) (P < .0001), and severe neurodevelopmental delay (P < .05) than those without adipsia. Comorbidities were common. The underlying cause remains unknown at the age of 23 years for one patient with CDI and normal thirst. Neonatal CDI may be transient or permanent. These vulnerable patients have high rates of comorbidity and require careful monitoring.

Association between Primary Amenorrhea and Early Maternal Age: A Population Study

Primary Amenorrhea (PA) is one of the most common reproductive disorders found in women can be characterized by the absence of menstruation cycle during puberty as well as throughout life that lead to infertility. The major cause of PA includes hypothalamic disorder and ovarian disorder. In this study a promising association between early maternal age and PA is found. This present study was carried out to perceive the effect of early maternal age (age of conception) in the etiology of PA. A population based study of approximately 993 PA cases and 1027 controls have been investigated in our laboratory (from 2004 and 2013). PA cases born to mothers of age less than 20 years are 71.70% and the mean age of mother is 16.15 years. A highly significant association of primary amenorrhea patient with the younger mother (≤ 20 years age) (OR = 5.51; 95% CI = 4.47- 6.79; p < 0.0001) has been found. On the other hand, association with older women is not significant (≥ 30 years) (OR = 1.17; 95% CI = 0.86-1.61; p < 0.315). Unpaired t-test analysis has shown statistical significant impact of younger maternal age on PA occurrence. The partial correlation of coefficient between maternal age and PA occurrence while keeping paternal age constant is 0.593. Statistical assessment shows a significant association between younger mother and daughter facing primary amenorrhea at puberty. There are different causes of PA which have been revealedbut the allianceof early maternal age with PA may be highlighted as the etiology of PA.

Adrenal Insufficiency In Critically Ill Patients

Adrenal insufficiency means hypo function of the adrenal cortex, usually resulting in low glucocorticoid level and it may be associated with low mineralocorticoid, rarely low adrenal androgen level. It can be categorized into two types: primary and secondary. Primary adrenal insufficiency or Addison's disease is associated with low cortisol and high ACTH level. Secondary/tertiary adrenal insufficiency is due to pituitary or hypothalamic disorders and is associated with both low cortisol and ACTH level. Among critically ill patients (CIP) adrenal insufficiency is not uncommon. The reported incidence of adrenal insufficiency varies greatly depending on the population of critically ill patients studied, the type of test, cut off levels used, and the severity of illness. Several studies have shown increased mortality in patients with very low or very high baseline cortisol levels. Manifestations of adrenal insufficiency in the critically ill patient are numerous and nonspecific, so clinicians are urged to have a high index of suspicion while taking history and doing physical examination and be alert to important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension, that are refractory to fluids and vasopressor without any clear causation. In current literature there is no consensus level of cortisol (basal/random/stimulated) in critically ill subjects. But it is shown that both high and low cortisol level is associated with increased mortality. In one study Basal Serum Cortisol &lt;414 nmol/L and &gt; 696 nmol/L is shown as indicative of higher risk among critically ill patients. Even with Septicemia or ARDS all subjects don’t suffer from adrenal insufficiency often termed relative adrenal insufficiency or critical illness associated adrenal insufficiency. It has been observed that short term low dose IV hydrocortisone may be beneficial in selective group of patients in intensive care unit (ICU) with critical illness. Diagnosis of adrenal insufficiency associated with critical illness is still challenging for physicians working in ICU. Treatment should be started without delay in emergency situation with Injection Hydrocortisone intravenously or even intramuscularly. Since the condition appears to be common in patients with septic shock, clinicians should have a high index of suspicion for its occurrence in critically ill patients with persistent hypotension despite adequate fluid resuscitation and/or poor hemodynamic response to vasopressor. Adrenal insufficiency associated with other illnesses in ICU are attributed to previous primary or secondary adrenal insufficiency. Treatment with physiologic doses of corticosteroids should be started as soon as possible since short-term treatment carries very few risks and has been shown to decrease both morbidity and mortality. Only suspected cases should be evaluated and could be treated with 100-200 mg Hydrocortisone in divided doses for 5-7 days. Glucocorticoid cannot be recommended as a routine adjuvant therapy in all cases of septic shock or ARDS. But glucocorticoid earned its position among other rescue strategies in subgroups of ICU patients with the highest mortality risk. Steroid use is an art and needs to be used by experienced physician. Otherwise it may do more harm than benefit.Bangladesh Crit Care J March 2015; 3 (1): 27-30

Functional hypothalamic amenorrhoea — diagnostic challenges, monitoring, and treatment.

Functional hypothalamic amenorrhoea (FHA) is associated with functional inhibition of the hypothalamic-pituitary-ovarian axis. Causes of FHA can be classified into the three groups: 1) stress-related factors, 2) consequences of weight loss and/or underweight, and 3) consequences of physical exercise or practicing sports. Diagnosis of FHA should be based on a history of menstrual disorders. During physical examination, patients with FHA present with secondary and tertiary sex characteristics specific for the pubertal stage preceding development of the condition and with the signs of hypoestrogenism. Laboratory results determine further management of patients with amenorrhea, and thus their correct interpretation is vital for making appropriate therapeutic decisions. Treatment of chronic anovulation, menstrual disorders, and secondary amenorrhea resulting from hypothalamic disorders should be aimed at the elimination of the primary cause, i.e. a decrease in psycho-emotional strain, avoidance of chronic stressors, reduction of physical exercise level, or optimisation of BMI in patients who lose weight. If menses do not resume after a period of six months or primary causative treatment is not possible, neutralisation of hypoestrogenism consequences, especially unfavourable effects on bone metabolism, become the main issue. Previous studies have shown that oestroprogestagen therapy is useful in both the treatment of menstrual disorders and normalisation of bone mineral density. Hormonal preparations should be introduced into therapeutic protocol on an individualised basis.

Early and Long-term Undernutrition in Female Rats Exacerbates the Metabolic Risk Associated with Nutritional Rehabilitation

Human studies have suggested that early undernutrition increases the risk of obesity, thereby explaining the increase in overweight among individuals from developing countries who have been undernourished as children. However, this conclusion is controversial, given that other studies do not concur. This study sought to determine whether rehabilitation after undernutrition increases the risk of obesity and metabolic disorders. We employed a published experimental food-restriction model. Wistar female rats subjected to severe food restriction since fetal stage and controls were transferred to a moderately high-fat diet (cafeteria) provided at 70 days of life to 6.5 months. Another group of undernourished rats were rehabilitated with chow. The energy intake of undernourished animals transferred to cafeteria formula exceeded that of the controls under this regime and was probably driven by hypothalamic disorders in insulin and leptin signal transduction. The cafeteria diet resulted in greater relative increases in both fat and lean body mass in the undernourished rats when compared with controls, enabling the former group to completely catch up in length and body mass index. White adipose tissues of undernourished rats transferred to the high-lipid regime developed a browning which, probably, contributed to avoid the obesigenic effect observed in controls. Nevertheless, the restricted group rehabilitated with cafeteria formula had greater accretion of visceral than subcutaneous fat, showed increased signs of macrophage infiltration and inflammation in visceral pad, dyslipidemia, and ectopic fat accumulation. The data indicate that early long-term undernutrition is associated with increased susceptibility to the harmful effects of nutritional rehabilitation, without causing obesity.