Amal Shibli-Rahhal

Cushing's syndrome

Cushings syndrome results from prolonged exposure to excess glucocorticoids. Patients with Cushings syndrome may develop multiple metabolic problems including obesity, hyperglycemia, hypertension, depression, low bone mass, muscle atrophy, and hypogonadism. Cutaneous manifestations of hypercortisolism include skin atrophy, excessive bruising, purple striations, poor wound healing, facial plethora, vellous hypertrichosis and hirsutism. Diagnostic tests used to screen for Cushings syndrome include 24-hour urine cortisol, the 1 mg dexamethasone suppresion test, and late night salivary cortisol. A normal screening test excludes the diagnosis of Cushings. Patients with an abnormal screening test should be referred to an endocrinologist for complete evaluation of the pituitary-adrenal axis.

The effects of hyperprolactinemia on bone and fat

Many patients with prolactin secreting pituitary tumors have decreased bone mineral. The bone loss is associated with an increase in bone resorption and is secondary to prolactin-induced hypogonadism. In both sexes trabecular bone in the spine and hip is more affected than cortical bone in the distal radius. Normalization of prolactin and restoration of gonadal function increases bone density but is not associated with normalization of bone mass. It is not known whether the bone loss in hyperprolactinemic subjects represents a failure to achieve peak bone mass or is due to accelerated bone loss. Despite low bone density hyperprolactinemic subjects do not demonstrate increased fractures. The association between prolactin, weight gain and obesity suggests that prolactin may also be a modulator of body composition and body weight. It is not known whether hyperprolactinemia associated weight gain is due to stimulation of lipogenesis or due to disruption of central nervous system dopaminergic tone. Hyperprolactinemia is also associated with insulin resistance and endothelial dysfunction which may improve after normalization of prolactin. The clinical significance of these findings and the precise role of prolactin in regulation of weight and metabolism remain to be elucidated.

Effects of TZD Use and Discontinuation on Fracture Rates in ACCORD Bone Study

CONTEXT In trials, thiazolidinediones (TZDs) increase fracture risk in women, but the effects of discontinuation are unknown. OBJECTIVE The objective was to investigate the effects of TZD use and discontinuation on fractures in women and men. DESIGN This was a longitudinal observational cohort study using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone ancillary study. Duration of TZD use and discontinuation during ACCORD, assessed every 2-4 months at clinic visits, were modeled as time-varying covariates in proportional hazards models for occurrence of first non-spine fracture. PARTICIPANTS We studied a total of 6865 participants in ACCORD BONE. MAIN OUTCOME MEASURES Main outcome measures were centrally adjudicated non-spine fracture. RESULTS Average age was 62.4 (SD, 6.6) years; average duration of diabetes was 11.1 (SD, 7.8) years. Rosiglitazone was used by 74% and pioglitazone by 13% of participants. During a mean follow-up of 4.8 (SD, 1.5) years, 262 men and 287 women experienced at least one non-spine fracture. The fracture rate was higher in women with 1-2 years of TZD use (hazard ratio [HR] = 2.32; 95% confidence interval [CI], 1.49, 3.62) or >2 years of TZD use (HR = 2.01; 95% CI, 1.35, 2.98), compared with no use. The fracture rate was reduced in women who had discontinued TZD use for 1-2 years (HR = 0.57; 95% CI, 0.35, 0.92) or > 2 years (HR = 0.42; 95% CI, 0.24, 0.74) compared with current users. TZD use and discontinuation were not associated with non-spine fractures in men. CONCLUSIONS TZD use was associated with increased non-spine fractures in women, but not men, with type 2 diabetes. When women discontinued TZD use, the fracture effects were attenuated.

Bone density and alendronate effects in Duchenne Muscular Dystrophy patients

Introduction: Patients with DMD have low bone mineral density (BMD) and are at high risk for fractures. We examined changes in BMD and the effects of alendronate in DMD patients treated at our institution in the last decade. Methods: Retrospective cohort study of 39 DMD patients. Results: Patients had screening dual energy x‐ray absorptiometry (DXA) at an average age of 12 years. The vast majority had low Z‐scores at the total hip and lumbar spine. Patients treated with glucocorticoids had a significantly lower Z‐score at the spine than those not treated with glucocorticoids. Z‐scores at the hip trended down without alendronate (P = 0.07) and trended up with alendronate (P = 0.4). Conclusions: By age 12 years, most patients with DMD had low Z‐scores. They may have benefitted from earlier screening. Z‐score at the hip trended downward without alendronate and trended upward (stabilized) with alendronate, but these trends were not statistically significant. Muscle Nerve 49:506–511, 2014

Hyperprolactinemia and infertility.

Prolactin-secreting pituitary tumors are a common cause of amenorrhea and infertility in premenopausal women. The goals of therapy are to normalize prolactin, restore gonadal function and fertility, and reduce tumor size, and dopamine agonists are the preferred therapy. Clinically significant tumor enlargement during pregnancy is uncommon and dependent on tumor size and prepregnancy treatment.

Possible mechanisms for the skeletal effects of antipsychotics in children and adolescents

The increasing use of antipsychotics (APs) to treat pediatric psychiatric conditions has led to concerns over the long-term tolerability of these drugs. While the risk of cardiometabolic abnormalities has received most of the attention, preclinical and clinical studies provide preliminary evidence that APs can adversely impact bone metabolism. This would be most concerning in children and adolescents as suboptimal bone accrual during development may lead to increased fracture risk later in life. However, the potential mechanisms of action through which APs may impact bone turnover and, consequently, bone mineral content are not clear. Emerging data suggest that the skeletal effects of APs are complex, with APs directly and indirectly impacting bone cells through modulation of multiple signaling pathways, including those involving dopamine D2, serotonin, adrenergic, and prolactin receptors, as well as by affecting gonadotropins. Determining the action of APs on skeletal development is further complicated by polypharmacy. In children and adolescents, APs are frequently coprescribed with psychostimulants and selective serotonin reuptake inhibitors, which have also been linked to changes in bone metabolism. This review discusses the mechanisms by which APs may influence bone metabolism. Also covered are preclinical and pediatric findings concerning the impact of APs on bone turnover. However, the dearth of clinical information despite the potential public health significance of this issue underscores the need for further studies. The review ends with a call for clinicians to be vigilant about promoting optimal overall health in chronically ill youth with psychopathology, particularly when pharmacotherapy is unavoidable.

Effect of dehydroepiandrosterone (DHEA) on vascular function in postmenopausal women with diabetes: a randomized controlled trial

Abstract Background: DHEA stimulates endothelial nitric oxide (NO) production in vitro and its prolonged use in humans improves vascular function. It is believed that this effect is mediated by metabolism of DHEA to

Prolactinomas: Diagnosis and~Management

Prolactin-secreting adenomas account for 40% of all pituitary tumors and are classified as microadenomas ( 10mm). Microprolactinomas are more common in women and most women present with menstrual dysfunction, infertility or galactorrhea. Men commonly present with large tumors and although prolactinomas in men lead to hypogonadism, most men seek medical attention because of headaches or neurologic deficits.