Bone turnover in patients with endogenous Cushing’s syndrome before and after successful treatment

Summary  

We investigated bone turnover and its restoration in a large number of patients in the active phase and after cure of endogenous Cushing’s syndrome. Furthermore, the usefulness of serum osteocalcin and collagen breakdown products as potential markers of active Cushing’s syndrome was also evaluated.     

Quantitative Ultrasound of Bone and Markers of Bone Turnover in Cushing’s Syndrome

Quantitative ultrasound (QUS) of bone is a valuable tool in the assessment of postmenopausal osteoporosis. QUS and new markers of bone turnover have been poorly assessed in Cushing’s syndrome, however. Twenty-five patients with Cushing’s syndrome (20 women, 3 men; mean age ± SEM: 38 ± 2 years) were studied and compared with 35 age- and sex-matched control patients (mean age ± SEM: 38 ± 2 years). The following variables were measured in both groups: QUS parameters at the heel (BUA; SOS; Stiffness Index, SI); bone mineral density (BMD) at both the lumbar spine (LS) and femoral neck (FN) by dual-energy X-ray absorptiometry; and serum markers of bone turnover (osteocalcin, procollagen type I N- and C-terminal propeptides (PINP and PICP), bone alkaline phosphatase (BAP), procollagen type I C-terminal telopeptide (ICTP) and urinary type I collagen C-telopepetide breakdown products (CTX)). Both BUA and SI were decreased in patients with Cushing’s syndrome (p<0.01) but not SOS (p=0.08). BMD was also strongly decreased in Cushing’s syndrome, at both the LS and FN (p<0.005). The two markers of bone turnover statistically significantly different between the two groups were osteocalcin (mean ± SEM: 3.5 ± 0.7 ng/ml (Cushing’s syndrome) vs 6.4 ± 0.5 ng/ml (controls, p<0.01)) and CTX (mean ± SEM: 148.7 ± 17.1 μg/mmol Cr (Cushing’s syndrome) vs 220.8 ± 22.9 μg/mmol Cr (controls), p<0.05). The areas under the receiver operating characteristic curve (AUC) were 0.72 (BUA), 0.73 (SI), 0.90 (BMD_LS), 0.81 (BMD_FN), 0.83 (osteocalcin) and 0.64 (CTX) respectively. AUC was significantly higher for BMD_LS than for both BUA and SI (p<0.05). Conversely AUC was not statistically significantly different for BMD_FN as compared with either BUA or SI. AUC was also higher for osteocalcin than for other markers of bone turnover. In conclusion, QUS of bone seems to be a relevant tool for assessing bone involvement in Cushing’s syndrome. QUS does have a lower sensitivity compared with DXA, however, and the relevance of QUS cannot be ascertained until some longitudinal data are forthcoming. Except for CTX, the other new markers of bone turnover assessed in this study (PINP, PICP, BAP and ICTP) do not seem of interest in Cushing’s syndrome. Received: February 2000 / Accepted: 24 August 2000     

Endoscopic bilateral adrenalectomy in patients with ectopic Cushing’s syndrome

Background  

Bilateral adrenalectomy (BLA) is a treatment option to alleviate symptoms in patients with ectopic Cushing’s syndrome (ECS) for whom surgical treatment of the responsible nonpituitary tumor is not possible. ECS patients have an increased risk for complications, because of high cortisol levels, poor clinical condition, and metabolic disturbances. This study aims to evaluate the safety and long-term efficacy of endoscopic BLA for ECS.     

Bone complications in patients with Cushing’s syndrome: looking for clinical,biochemical, and genetic determinants

Summary

This is the first study examining the impact of both clinical, biochemical, and genetic determinants in the occurrence of bone complications in patients with overt Cushing’s syndrome (CS). It demonstrates that the degree and duration of hypercortisolism seem to play a major role in bone loss and fractures development in these patients.

Introduction

Bone loss and fractures are a common complication of CS. We investigate the role of gender, disease etiology, duration, and degree of hypercortisolism as well as the impact of glucocorticoid receptor (GR) polymorphisms on the development of bone complications in CS.

Methods

Fifty-two patients with active CS (38 Cushing’s disease and 14 with cortisol-secreting adrenal adenoma) were genotyped for GR polymorphisms (BclI, N363S, ER22/23EK, and A3669G). In all patients, clinical, hormonal, and biochemical markers of bone turnover, densitometric parameters [lumbar spine and left femur bone mineral density (BMD), T-score, Z-score] as well as the prevalence of bone demineralization and both vertebral and peripheral fractures were assessed.

Results

No differences were found in bone complications according to gender, disease etiology, and genetic variants distribution. Fractured patients compared to non-fractured ones showed increased levels of urinary free cortisol (UFC) and a more compromised densitometric profile. UFC levels correlated with the occurrence of vertebral fractures (r?=?0.43, p = 0.009) while midnight serum cortisol correlated with L1–L4 BMD values (r?=??0.35, p = 0.04). Disease duration correlated with the presence of peripheral fractures (r?=?0.36, p = 0.04).

Conclusions

While GR gene variants as well as gender and disease etiology seem not to play a role, the degree and duration of hypercortisolism seem to be the major determinants of bone loss and fractures in this group of patients. More investigations are needed to understand the real impact of these determinants on the development of bone complications in patients with hypercortisolism.     

Bone Quality in Paget’s Disease of Bone

Paget’s disease of bone is produced by a localized increase in osteoclastic and osteoblastic activity which can progress slowly to involve an entire bone if untreated. A common feature is enlarged bones which are deformed, particularly in weight-bearing regions of the skeleton such as the lower extremity. Pathologic fractures may be a consequence, and nonunion of femoral fractures is not uncommon. Analyses of bone biopsies from patients with Paget’s disease indicate that there is a lower, heterogeneous degree of bone mineralization and a younger tissue age than that found in control bone. Pagetic bone also has less resistance to plastic deformation and a straighter crack path than control bone.     

Ectopic Cushing’s syndrome due to a mesenteric neuroendocrine tumour

INTRODUCTION

Neuroendocrine tumours (NETs) are tumours that commonly involve the gastrointestinal system. Common primary sites in the gastrointestinal system include the small intestine, appendix, rectum and pancreas. Mesenteric NETs are extremely rare entities and are sparsely reported in the literature.

CASE HISTORY

We report the case of a 62-year-old woman with ectopic Cushing’s syndrome due to excessive adrenocorticotropic hormone secretion by a primary mesenteric tumour in the small intestine and its liver metastases.

CONCLUSIONS

Although rare, the mesentery can be a primary site for NETs. It can cause similar symptoms and require similar treatment options. Tumour resection and debulking are acceptable ways to improve both the survival and symptoms.     

Anaesthesia in Turner’s syndrome

A patient with Turner’s syndrome anaesthetized on several occasions for laparoscopy, vaginoplasty and change of dressings is presented. Intubation was difficult due to webbing of the neck and a shortened tracheal length. Other problems in palients with this syndrome include difficulty in venipuncture, delayed excretion of drugs, associated cardiovascular anomalies and contraindication to regional blockade, in view of spinal deformities.     

Tourette’s syndrome in children

Opinion statement This paper will provide a review of the Tourette’s syndrome (TS) in children, focusing on treatment options, including a drug-by-drug evaluation of available pharmacologic agents and other treatments. Despite increasing knowledge of the neurophysiologic basis of the tics of TS, ideal and universally effective treatments do not yet exist. Affected children may present a wide variety of phenotypes, which are best managed in a case-by-case manner, with the well-informed patient and family weighing the risks and benefits of interventions together with a knowledgeable and committed clinician. The clinician treating TS will encounter a wide range of tic severity, comorbidity, adherence to treatment, and treatment response. The clinician’s most important task is to identify the main sources of distress and impairment, and set priorities for their management. Common treatment may involve education and reassurance, psychosocial and school interventions, and choices from an array of pharmacologic agents. Decisions regarding treatment ought to be made collaboratively with the clinician and family, after a careful discussion of symptom extent and severity, psychosocial impact, desired outcome, and realistic treatment expectations and side effects. Given the waxing and waning course of tics in TS, clinicians often monitor each patient for several weeks before starting a somatic treatment, based on a judgement that even when tics are at their best, they are severe enough to warrant pharmacotherapy. With children for whom the decision has been taken to target tics with medication, the authors recommend beginning with guanfacine or clonidine, especially when there are any hyperactivity symptoms. The next choice would be a low-dose neuroleptic. Patience and close ongoing monitoring of efficacy and side effects is necessary, whenever a clinical trial of medications is undertaken, to achieve an acceptable balance between tic control and side effects. Treatments should be targeted at specific symptoms and comorbidities, such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. Clinicians tend to treat comorbid conditions first because they may be the greatest sources of difficulty. On occasion, the successful treatment of a comorbid condition will lead to an amelioration of tics.     

Surgical outcomes of laparoscopic adrenalectomy for patients with Cushing’s and subclinical Cushing’s syndrome: a single center experience

Objective  

We retrospectively examined the outcome of patients who underwent laparoscopic adrenalectomy for Cushing’s/subclinical Cushing’s syndrome in our single institute.     

Colonic Crohn’s disease – decision is more important than incision: A surgical dilemma

The most common localization for intestinal Crohn’s disease (CD) is the terminal ileum and ileocecal area. It is estimated that patients with CD have one in four chance of undergoing surgery during their life. As surgery in ulcerative colitis ultimately cures the disease, in CD, regardless of the extent of bowel removed, the risk of disease recurrence is as high as 40%. In elective surgery, management of isolated Crohn’s colitis continues to evolve. Depending on the type of surgery performed, colonic CD patients often require further medical or surgical therapy to prevent or treat recurrence. The elective surgical treatment of colonic CD is strictly dependent on the localization of disease, and the choice of the procedure is dependent of the extent of colonic involvement and previous resection. The most common surgical options in colonic CD are total proctocolectomy (TPC) with permanent ileostomy, segmental bowel resection, subtotal colectomy. TPC completely removes all colonic and rectal disease and avoids the use of a potentially diseased anus. We will review current options for the elective surgical treatment of colonic CD, based on the current literature and our own personal experience.     

Surgical Considerations in Subclinical Cushing’s Syndrome. When is it Time to Operate?

Subclinical Cushing’s syndrome (SCS) is a disorder characterized by autonomous cortisol secretion and the presence of an adrenal incidentaloma, in the absence of clinical features of Cushing’s syndrome. SCS is of special interest because it has been associated with several disorders, such as atherosclerosis and arterial hypertension. Despite decades of research, SCS continues to generate controversy regarding its diagnosis and subsequent management. Several issues remain to be resolved. A universal agreement on the hormonal diagnosis of the syndrome remains elusive. Autonomous cortisol secretion has been ill defined and several definitions have been offered. The heterogeneity in diagnostic criteria creates heterogeneity in studies evaluating optimal management. Minimally invasive adrenalectomy has been documented to ameliorate SCS associated disorders in certain patients. Identifying these patients should be the focus of future research on the subject. In this review we summarize current concepts regarding SCS and indications for its surgical management.     

Meniere’s syndrome

Opinion statement The primary goals of treatment in Meniere’s syndrome are to control attacks of vertigo and, if possible, to arrest the progression of hearing loss. Initial treatment consists of rigid dietary sodium restriction, possibly with the addition of a thiazide diuretic. If disabling attacks of vertigo persist despite sodium restriction, surgical intervention should be considered. Endolymphatic shunting is an option for patients who desire a less invasive surgical remedy, but recurrence of vertigo occurs in about 40% of cases. Vestibular nerve ablative surgery is the definitive surgical treatment for patients with intractable attacks of vertigo who still have useful hearing on the affected side. Labyrinthectomy is a surgical option when there is no serviceable hearing in the damaged ear. Intra-aural gentamicin instillation is an option in carefully selected cases