Identification Of Potential Markers For Cushing’s Disease

Endocr Pract. 2016 Jan 20. [Epub ahead of print]

Abstract

OBJECTIVE:

Cushing’s disease (CD) causes a wide variety of nonspecific symptoms, which may result in delayed diagnosis. It may be possible to uncover unusual combinations of otherwise common symptoms using ICD-9-CM codes. Our aim was to identify and evaluate dyads of clinical symptoms or conditions associated with CD.

METHODS:

We conducted a matched case-control study using a commercial healthcare insurance claims database, designed to compare the relative risk (RR) of individual conditions and dyad combinations of conditions among patients with CD versus matched non-CD controls.

RESULTS:

With expert endocrinologist input, we isolated 10 key conditions (localized adiposity, hirsutism, facial plethora, polycystic ovary syndrome, abnormal weight gain, hypokalemia, deep venous thrombosis, muscle weakness, female balding, osteoporosis) with RR varying from 5.1 for osteoporosis to 27.8 for hirsutism. The RR of dyads of these conditions ranged from 4.1 for psychiatric disorders/serious infections to 128.0 for hirsutism/fatigue in patients with vs. without CD. Construction of uncommon dyads resulted in further increases in RR beyond single condition analyses, such as osteoporosis alone had RR of 5.3, which increased to 8.3 with serious infections and to 52.0 with obesity.

CONCLUSION:

This study demonstrated that RR of any one of 10 key conditions selected by expert opinion was ≥5 times greater in CD compared to non-CD, and nearly all dyads had RR≥5. An uncommon dyad of osteoporosis and obesity had an RR of 52.0. If clinicians consider the diagnosis of CD when the highest-risk conditions are seen, identification of this rare disease may improve.

KEYWORDS:

Cushing’s disease; delay in diagnosis; disease markers; insurance claims; relative risk

PMID:
26789346
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/26789346

Addison’s disease may cause psychosis, say researchers

adrenal-glands

 

Research suggests that chronic adrenal insufficiency, more commonly known as Addison’s disease, may be responsible for psychiatric symptoms in those who suffer with it. Unfortunately, these symptoms are poorly understood and inadequately studied. In one case, a 41-year-old construction worker was admitted to a psychiatric clinic complaining of depression. He had trouble sleeping and concentrating and had lost 6 pounds due to a loss of appetite. He was placed on 20mg of fluoxetine but returned 2 weeks later complaining that the therapy did not work, and even reported hallucinating his ex-wife, who had recently died in a car accident. He returned again later 4 months later and was found to have a weak pulse, major hypotension, and hyponatremia and hyperkalemia. It was at this point that he was diagnosed with Addison’s disease.

The disease was first described by Thomas Addison in the mddle of the 19th century. It involves inadequate secretion from the adrenal glands, leading to lower secretion of glucocorticoids. Its usual symptom pigmentation involves fatigue, weight loss, nausea, vomiting, weakness and abdominal pain. Among its psychiatric symptoms are psychosis and delirium.

Endocrine Society Releases Guidelines on Treatment of Cushing’s Syndrome

To lessen the risk for comorbidity and death, the Endocrine Society’s newly published guidelines on the treatment of Cushing’s syndrome focus on surgical resection of the causal tumor with the goal of normalizing cortisol levels. Furthermore, there is increased emphasis on individualizing treatment options when choosing a second-line treatment.

In July 2015, the Endocrine Society published treatment guidelines to assist endocrinologists in appropriately initiating treatment or referring patients with Cushing’s syndrome to treatment. A task force of experts compiled evidence from systematic reviews and graded the strength of the recommendations.

“We hope that it will lead to improved treatment of comorbidities both before and after definitive treatment of the syndrome, and to increased individualization of patient treatment,” said chair of the task force Lynnette Nieman, MD, who is chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center.

“There are two new drugs that were approved in 2012, and so I think that is what prompted the review. Still, medications are not the first line of treatment, but we have some new therapeutic options, and I think the idea was to help people understand where to use them,” Julie Sharpless, MD, assistant professor and director of the UNC Multidisciplinary Pituitary Adenoma Program, told Endocrinology Advisor.

“The primary treatment is surgical resection of the causal tumor(s). If that cannot be done (because the tumor is occult or metastatic) or is not successful, then the choice of secondary treatment should be individualized to the patient. The comorbidities of Cushing’s syndrome, for example hypertension and diabetes, should be treated separately as well,” Nieman said.

For example, the guidelines recommend surgical removal of the causative lesion, with the exception of cases which are unlikely to cause a drop in glucocorticoids or in patients who are not surgical candidates.

Likewise, in patients with benign unilateral adrenal adenoma, adrenalectomy by an experienced surgeon has a high rate of cure in children and adults. Because of the poor prognosis associated with adrenal carcinoma, the guidelines highlight the need for complete resection and possibly medical treatment to stabilize cortisol levels.

Other first-line treatment options include recommending surgical resection of ectopic ACTH-secreting tumors; referring to an experienced pituitary surgeon for transsphenoidal selective adenomectomy; treatments to block hormone receptors in bilateral micronodular adrenal hyperplasia; and surgical removal in bilateral adrenal disorders.

The elevated mortality rate seen in patients with Cushing’s syndrome is due to infection, venous thrombosis and cardiovascular disease (CVD). Appropriately lowering cortisol levels improves hypertension, insulin resistance, dyslipidemia and obesity in patients with Cushing’s syndrome. Therefore, the guidelines highlight the need for restoring cortisol levels and treating the associated comorbidities.

Nevertheless, the task force specifically recommends against treatment without an established diagnosis or when there are no signs of Cushing’s syndrome and hypothalamic-pituitary-adrenal laboratory studies are borderline.

In patients who are not surgical candidates or in cases of noncurative resection, the decision on whether to consider second-line treatment options such as medical therapy, radiation, bilateral adrenalectomy or repeat transsphenoidal surgery should be based on several factors. For instance, the guidelines recommend taking into consideration location and size of the tumor, patient desires, goals of treatment and level of biochemical control.

The guidelines note medical therapy should be based on cost, efficacy and individualization of treatment. Endocrinologists can approach medical therapy with a goal of establishing normal cortisol levels or reducing cortisol levels to very low levels and replacing to achieve desired levels.

Remission in Cushing’s syndrome is associated with notable improvement; however, long-term follow-up is recommended for osteoporosis, CVD and psychiatric conditions.

After treatment, patients may experience reductions in weight, blood pressure, lipids and glucose levels that may allow reduction or discontinuation of medications. Even so, patients with a history of Cushing’s syndrome tend to have higher rates of hypertension, hyperlipidemia and diabetes. Likewise, rates of myocardial infarction are higher in this population, further emphasizing the need for treatment and management of diabetes and hypertension.

Sharpless highlighted that Cushing’s syndrome is rare.

“There are multiple studies that have shown that patients do better when they are treated in a specialty center where people see a lot of cases of this. So in that sense, treatment is not usually going to fall to the general practitioner,” she said.

She continued that the guidelines are helpful and provide guidance to endocrinologist who “can’t readily refer their patient to a pituitary center.”

Sharpless went on to describe the multidisciplinary care involved in Cushing’s syndrome including endocrinologists, neurosurgeons, radiologists, counselors and radiation oncologist.

“When the care is complicated, you want to ensure all of your providers have reviewed your case together and figured out the best plan.”

The guidelines were co-sponsored by the European Society of Endocrinology. Nieman received salary support for her work on the manuscript from the Intramural Research Program of the Eunice Kennedy Shiver Institute of Child Health and Human Development. Members of the task force reported multiple disclosures.

Reference

  1. Nieman LK et al. J Clin Endocrinol Metab. 2015;100(8):2807-2831.

From http://www.endocrinologyadvisor.com/adrenal/cushings-syndrome-endocrine-society-guidelines/article/434307/

Depressed? Anxious? It Could Be An Early Symptom Of These Illnesses

In the January 2015 edition of Psychotherapy and Psychsomatics, a group of Italian researchers explored whether depression, anxiety, and other psychiatric mood disorders might be early symptoms of medical disorders, as opposed to being “just” psychological symptoms.

Their research showed that depression in particular can be a strong indicator of other forms of illness, finding it “to be the most common affective prodrome [early symptom] of medical disorders and was consistently reported in Cushing’s syndrome, hypothyroidism, hyperparathyroidism, pancreatic and lung cancer, myocardial infarction, Wilson’s disease, and AIDS.”

Read the entire article here: Depressed? Anxious? It Could Be An Early Symptom Of These Illnesses.

Cushing’s syndrome – A structured short- and long-term management plan for patients in remission

European Journal of Endocrinology, 08/30/2013  Review Article

harvey-bookRagnarsson O et al. – One–hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name.

The focus of the long–term specialized care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and to detect possible recurrence of Cushing’s syndrome.


Source

O Ragnarsson, Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

One-hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name. In patients with Cushing’s syndrome body composition, lipid-, carbohydrate- and protein-metabolism is dramatically affected and psychopathology and cognitive dysfunction is frequently observed.

Untreated patients with Cushing’s syndrome have a grave prognosis with an estimated five-year survival of only 50%. Remission can be achieved by surgery, radiotherapy and sometimes with medical therapy.

Recent data indicate that the adverse metabolic consequences of Cushing’s syndrome are present for years after successful treatment. In addition, recent studies have demonstrated that health related quality of life and cognitive function is impaired in patients with Cushing’s syndrome in long-term remission.

The focus of specialized care should therefore not only be on the diagnostic work-up and the early post-operative management, but also the long-term follow-up.

In this paper we review the long-term consequences in patients with Cushing’s syndrome in remission with focus on the neuropsychological effects and discuss the importance of these findings for long-term management. We also discuss three different phases in the postoperative management of surgically treated patients with Cushing’s syndrome, each phase distinguished by specific challenges; the immediate post-operative phase, the glucocorticoid dose tapering phase and the long-term management. The focus of the long-term specialized care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and to detect possible recurrence of Cushing’s syndrome.

PMID:
23985132
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/23985132

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