Obesity is a growing public health problem that is already reaching epidemic proportions and is increasingly encompassing young children and adolescents. Despite the increasing prevalence and the health risks associated with obesity, the pharmacotherapeutic options for treating obesity are limited. The endogenous cannabinoid or endocan-nabinoid system (ECS) was discovered in the early 1990s in relation to work on the action of components of marijuana. Central activation of the ECS promotes food ingestion. The endogenous cannabinoids exert their pharmacologic action through interaction with the specific receptors, CB(1) and CB(2). CB(1) receptors are located predominantly in the brain and peripherally in adipose tissue, liver, skeletal muscle and the gastrointestinal tract. In July 2006, European regulatory authorities approved the use of rimonabant, SR141716, a selective CB1 receptor antagonist, in obese patients (BMI > or =30kg/m(2), or >27kg/m(2) with complications). However, in June 2007, despite extensive clinical trial data, the FDA's Endocrine and Metabolic Drugs Advisory Committee (EMDAC) concluded that the safety of rimonabant had not been adequately demonstrated by the manufacturer Sanofi-Aventis; the full application was subsequently withdrawn. This review article provides evidence and outlines some patents for the use of rimonabant and potential safety concerns which still prevent its use in the single largest market for drugs of its kind.

Weight gain, during and after the menopause is common. Contributing factors include ethnicity, reduced physical activity, reduced lean mass, reduced resting metabolic rate and treatment with certain drugs, e.g. steroids, insulin, glitazones. Excess body weight increases the risk of medical conditions including type 2 diabetes, hypertension, osteoarthritis, certain cancers and is associated with increased mortality. This review examines pharmacological approaches to promote weight loss. Pharmacological therapy should be considered as an adjunct to diet and lifestyle changes. The licensed drugs orlistat, sibutramine and rimonabant are discussed. Obesity increases the risk of type 2 diabetes. Thus, the effects of metformin and exenatide are examined.

The differential diagnosis of abdominal pain with associated hyponatraemia should include acute intermittent porphyria. Development of hyperthyroidism in a patient with latent porphyria may precipitate an acute attack and increase disease severity. Treatment of hyperthyroidism may prevent recurrent episodes.

Introduction: Cushing’s syndrome is very rare in pregnancy with around 200 cases reported in literature. It remains a diagnostic dilemma as pregnancy itself is a hypercortisolemic state. Several clinical characteristics of Cushing’s syndrome such as insulin resistance and hirsutism may overlap with normal variants of pregnancy and therefore leading to a missed diagnosis. We hereby present a case of a young pregnant woman with severe insulin resistance, with workup consistent with Cushing’s syndrome. Clinical Case: This was a 27-year-old pregnant woman with DM type 2 diagnosed about 7 years ago. During her pregnancy she was started on insulin and was later admitted to the hospital at 32 weeks for inpatient management of pre-eclampsia and uncontrolled hyperglycemia. Endocrine was consulted for severe insulin resistance and persistent hyperglycemia. On exam patient was noted to be obese with facial plethora, frontal balding and significant facial hirsutism. During the pregnancy she had noted significant weight gain with substantial worsening of frontal balding and hirsutism. Her current pregnancy was spontaneous but was after many years of trying to conceive. Prior pregnancy 8 years ago was uncomplicated with no history for GDM at that time. Review of recent pre-pregnancy imaging revealed left adrenal mass measuring 3.5 cm with 40 HU which measured around 2 cm 8 years ago. Biochemical work up revealed elevated 8 am cortisol at 35.4 ug/dL (ref range 6.2 - 19.4) with suppressed ACTH <5 pg/mL (6 – 50). Testosterone was high at 299 ng/dL (8 – 48) and DHEAS was low normal at 37 mcg/dL (18 – 391). Plasma and 24 hour urine metanephrine collection results were normal. 24-hour urine free cortisol was measured and was elevated at 628.5 mcg/24(4.0–50.0). Midnight salivary cortisol was 0.87 mcg/dL (<OR=0.09). Patient was managed conservatively with plan for surgical intervention post-delivery. Pregnancy was complicated by PPROM at 35 weeks with subsequent cesarean section. Baby was of average weight but developed mild hyperbilirubinemia which required short NICU stay. On reevaluation at 4-week postpartum period, repeat biochemical workup revealed elevated cortisol of 22.5 mcg/dL, ACTH <5 pg/ml, elevated 24-hour urine cortisol 163.9 mcg/24h with appropriate urinary creatinine. Testosterone level was improved postpartum to 9 ng/dL. DHEAS was 39 mcg/dL. Repeat imaging with CT with adrenal protocol revealed left adrenal mass measuring 2.3 cm with 20 HU with absolute washout of 79%. She was started on ketoconazole is now awaiting surgical intervention. Conclusion: We suspect that this patient may have had pregestational subclinical Cushing’s syndrome which eventually progressed to Cushing’s syndrome during pregnancy. Although this is a rare finding during pregnancy, workup for Cushing’s should be considered in pregnant women with severe insulin resistance, hirsutism, hypertension and pre-eclampsia.

Controlling blood pressure in diabetes is essential. Professor Steve Bain and Dr Ashish Samat describe how this can be done