Growth hormone induced lipolysis during short- and long-term administration in adult Prader–Willi patients

Prader-Willi syndrome (PWS) is a complex genetic disease, clinically characterised by short stature, abnormal body composition, with more body fat than lean body mass, hyperphagia and obesity. Partial growth hormone (GH) deficiency is common, and GH treatment to PWS children and adults has shown beneficial effects on body composition. In this study, we have evaluated indices of GH's lipolytic effect in 6 PWS adults analysing glycerol, lactate and glucose in dialysate from microdialysis in subcutaneous abdominal adipose tissue. The patients were four men and two women, 19-37 years old; all hypogonadal. BMI was 24.2-49.1, mean 35.9 kg/m(2). All had normal serum insulin levels. They received GH therapy (Genotropin Pfizer) during 12 months and doses were individually titrated to normal serum IGF-I for age. Immediately before treatment start and at 12 months, 30-36 h after the last GH injection, sampling of dialysate was carried out at night (11 p.m. to 7 a.m.), as well as after intravenously injection of a standardised GH dose (0.8 mg). At baseline individual mean night time glycerol and lactate were similar to levels in adults without PWS (160.7-278.1 micromol/L and 0.80-3.99 mmol/L, respectively), and did not change with 12 months GH treatment. Glucose levels were normal, except in a patient with diabetes, and did not change during the study. Compared to baseline the immediate effect of GH injection resulted in a significant increase in glycerol levels after 12 months. In conclusion, night time lipolytic response in this small group of PWS adults seemed normal and did not change after 12 months GH treatment. On the other hand short-term GH induced lipolysis increased, indicating normal lipolytic response in PWS.     

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

In early childhood, individuals with Prader‐Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: “PWS” AND “therapy” OR “[drug name]”; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long‐term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off.     

Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion – Preliminary report

BACKGROUND: There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. OBJECTIVE: To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. SUBJECTS: We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. METHODS: Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. RESULTS: Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). CONCLUSION: NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.     

Peutz–Jeghers syndrome: case reports and update on diagnosis and treatment

OBJECTIVE: To analyze the etiology and diagnostic methods of Peutz–Jeghers syndrome (PJS) and thus establish a treatment strategy. METHODS: Clinical data from six patients with PJS were evaluated from the aspect of familial history, carcinogenesis and recurrence of polyps. RESULTS: The fathers of four and the mother of one of the six patients had PJS. The grandfather of three of the six patients had PJS. There was a history of cancer in three of the five families. Case 4 underwent two laparotomies for intussusceptions caused by recurrent polyps of the small intestine. Case 5 also had recurrent small intestinal polyps and required a laparotomy after 1 year of initial treatment. Polyps in cases 1 and 4 showed adenomatous changes and those in case 2 were associated with gastric cancer. CONCLUSIONS: Patients with PJS have a strong family history of cancer and a high incidence of recurrence of small intestinal polyps. Malignant changes of polyps may follow the hamartoma–adenoma–carcinoma sequence. Careful follow‐up is mandatory for gastrointestinal tract symptoms, and other solid organs that are susceptible to malignant change.     

Pubarche and serum dehydroepiandrosterone sulphate levels in children with Prader–Willi syndrome

Context Premature pubarche (PP) is reported in children with Prader–Willi Syndrome (PWS). Pubarche is preceded by adrenarche – an increase in serum levels of adrenal androgens, most specifically dehydroepiandrosterone sulphate (DHEAS). Objectives To assess DHEAS levels, the age at and progression of pubarche and the prevalence of PP in children with PWS. Design/Patients In the Dutch PWS Cohort Study, 120 children (6 months–17 years) are prospectively followed. Their age at onset of pubarche and various pubic hair stages and prevalence of PP were determined. Serum DHEAS levels were assessed in 97 children. Results Median serum DHEAS levels were significantly higher in children with PWS than in healthy age‐matched controls at ages 3–6 years (girls: P = 0·004 and boys: P = 0·010) and 6–10 years (girls: P = 0·045 and boys: P = 0·001). Age and gender significantly influenced DHEAS levels in children with PWS. The median [P10–P90] age at onset of pubarche in children with PWS was significantly younger than in healthy peers, 9·04[6·75–11·84] years in PWS girls (P < 0·0001) and 10·31 [8·65–12·29] years in PWS boys (P = 0·003). The prevalence of PP in children with PWS was 30·0% in girls and 16·1% in boys. Conclusions Compared to healthy children, children with PWS have significantly higher DHEAS levels from 3 to 10 years of age. They are younger at onset of pubarche and have a higher prevalence of premature pubarche. DHEAS levels in PWS are influenced by age and gender. Our findings indicate earlier maturation of the zona reticularis of the adrenal glands in children with PWS.     

Adenocarcinoma and multiple adenomas of the large intestine, associated with Cronkhite–Canada syndrome

The Cronkhite-Canada syndrome is a rare non-hereditary disorder with generalised gastrointestinal polyposis, associated with ectodermal changes. We report here a case of adenocarcinoma and multiple adenomas of the large intestine associated with Cronkhite-Canada syndrome in a 61-year-old Japanese man. Histologically, the rectal tumour was composed of well-differentiated tubular adenocarcinoma, admixed with foci of adenomatous components, and associated with hyperplastic mucosa of Cronkhite-Canada syndrome. Multiple polyps, >20 polyps < or = 2.0 cm in diameter, were found near the carcinoma of the resected rectum. Histologically, superficial parts of the polyps were composed of tubular adenomas, and basal parts of the polyps were hyperplastic dilated glands. It was speculated that, in the present case, the rectal adenocarcinoma arose from mucosal hyperplasia (Cronkhite-Canada polyp)-adenoma-carcinoma pathway. This suggested that Cronkhite-Canada syndrome has definite malignant potential, although the frequency of malignant transformation is thought to be low in Cronkhite-Canada syndrome.     

Bernard–Soulier syndrome in pregnancy

Bernard–Soulier syndrome (BSS) is a rare autosomal recessively inherited bleeding disorder. Pregnancy in patients with BSS is characterized by ante‐, intra‐, or postpartum haemorrhage, which may be delayed and severe. There is no consensus in the management of BSS in pregnancy and so far only 16 pregnancies in nine patients have been described. We report a further three pregnancies in two women with the syndrome. We also outline our management of pregnant patients with BSS.     

Responder criteria for operant and cognitive–behavioral treatment of fibromyalgia syndrome

Objective

To predict the effects of cognitive–behavioral therapy (CBT) and operant–behavioral therapy (OBT) in fibromyalgia syndrome (FMS).

Methods

A total of 125 patients who fulfilled the American College of Rheumatology FMS criteria were randomly assigned to CBT (n = 42), OBT (n = 43), or attention placebo (AP; n = 40). The pretreatment to 12‐month followup reliability change index was used to determine clinically meaningful changes in pain intensity and physical impairment. Multinominal logistic regression analyses were used to determine the predictors of improvement in pain intensity and physical impairment for the entire sample. Analyses of variance were computed to compare the characteristics of responders and nonresponders in each of the 3 interventions.

Results

At the 12‐month followup, 53.5%, 45.2%, and 5% of patients in the OBT, CBT, and AP groups, respectively, reported clinically meaningful improvements in pain intensity. Similarly, 58.1%, 38.1%, and 7.5% of patients treated with OBT, CBT, and AP, respectively, reported clinically significant improvements in physical impairment. Prior to treatment, the OBT physical impairment responders displayed significantly more pain behaviors, physical impairment, physician visits, solicitous spouse behaviors, and level of catastrophizing compared with nonresponders. The CBT physical impairment responders, compared with nonresponders, reported higher levels of affective distress, lower coping, less solicitous spouse behavior, and lower pain behaviors.

Conclusion

The results of this study suggest that pretreatment patient characteristics are important predictors of treatment response and may serve as a basis for matching treatments to patient characteristics. Prospective outcome studies are needed to confirm whether the tailoring of treatment actually leads to better outcomes for patients with FMS.     

Guillain–Barré syndrome associated with resistant cytomegalovirus infection after face transplantation

A 39‐year‐old male, who received a facial allograft (cytomegalovirus [CMV] donor‐seropositive, recipient‐seronegative), developed multidrug‐resistant CMV infection despite valganciclovir prophylaxis (900 mg/day) 6 months post transplantation. Lower extremity weakness with upper and lower extremity paresthesias developed progressively 11 months post transplantation, coinciding with immune control of CMV. An axonal form of Guillain–Barré syndrome was diagnosed, based on electrophysiological evidence of a generalized, non‐length‐dependent, sensorimotor axonal polyneuropathy. Treatment with intravenous immunoglobulin led to complete recovery without recurrence after 6 months.     

Budd–Chiari syndrome: Focus on surgical treatment

Budd–Chiari syndrome (BCS) is caused by an obstruction in the hepatic venous outflow tract at various levels from small hepatic veins to the inferior vena cava (IVC) due to thrombosis or fibrous sequelae. This rare disease mainly affects young adults. Risk factors have been identified and patients often have multiple risk factors. Myeloproliferative diseases of atypical presentation account for nearly 50% of patients in Europe and North America countries. Multistep management is required for such patients. Interventional revascularization and transjugular intrahepatic portosystemic shunt procedure are indicated after initial anticoagulation therapy, whereas IVC plasty using a patch graft is indicated for obstruction of the IVC. Liver transplantation (LT) is usually indicated as a treatment for liver failure despite various treatments. The outcomes of LT are good, with a 5‐year survival after LT of nearly 70%.