The Challenge of Obesity in Diagnosing Cushing’s Syndrome and Strategies to Improve Methods

Posted on October 29, 2017 by MaryO

The effects of obesity on the diagnosis of Cushing’s syndrome and strategies to alter the traditional approaches have been addressed in a new review study.

The study, “Diagnosis and Differential Diagnosis of Cushing’s Syndrome,” appeared in The New England Journal of Medicine. The author was Dr. Lynn D. Loriaux, MD and PhD, and a professor of medicine at the Division of Endocrinology, Diabetes and Clinical Nutrition at the School of Medicine, Oregon Health & Science University (OHSU), in Portland, Oregon.

Traditionally, exams of patients with glucocorticoid excess focused on the presence of changes in anabolism (the chemical synthesis of molecules). Given the increase in obesity in the general population, changes in anabolism can no longer distinguish Cushing’s syndrome from metabolic syndrome.

However, analyses of anti-anabolic changes of cortisol – including osteopenia (lower bone density), thin skin, and ecchymoses (injury that causes subcutaneous bleeding) – are an effective way to make this distinction.

The worldwide prevalence of metabolic syndrome in obese people is estimated at about 10%. Conversely, the incidence of undiagnosed Cushing’s syndrome is about 75 cases per 1 million people.

Cushing’s and metabolic syndrome share significant clinical similarities, including obesity, hypertension, and type 2 diabetes. Therefore, “making the diagnosis is the least certain aspect in the care of patients with [Cushing’s],” Loriaux wrote.

Regarding a physical examination, patients with osteoporosis, reduced skin thickness in the middle finger, and three or more ecchymoses larger than 1 cm in diameter and not associated with trauma are more likely to have Cushing’s. Researchers estimate the probability of people with all three of these symptoms having Cushing’s syndrome is 95%.

Measuring 24-hour urinary-free cortisol levels allows the assessment of excess glucocorticoid effects, typical of Cushing’s syndrome. The test, which should be done with the most stringent techniques available, averages the augmented secretion of cortisol in the morning and the diminished secretion in the afternoon and at night.

Dexamethasone suppression is one of the currently used screening tests for Cushing’s syndrome. Patients with obesity and depression should not show decreased plasma cortisol levels when dexamethasone is suppressed. However, given its low estimated predictive value (the proportion of positive results that are “true positives”), “this test should not influence what the physician does next and should no longer be used” to screen for Cushing’s, the author wrote.

Some patients may show evidence of Cushing’s syndrome at a physical examination, but low urinary free cortisol excretion. This may be due to glucocorticoids being administered to the patient. In this case, the glucocorticoid must be identified and discontinued. Periodic Cushing’s assessments that measure urinary free cortisol should be performed.

The opposite can also occur: no clinical symptoms of Cushing’s, but elevated urinary free cortisol excretion and detectable plasma levels of the hormone corticotropin. In these patients, the source of corticotropin secretion, which can be a tumor or the syndrome of generalized glucocorticoid resistance, must be determined.

The disease process can be corticotropin-dependent or independent, depending on whether the hormone is detectable. Corticotropin in Cushing’s syndrome can come from the pituitary gland (eutopic) or elsewhere in the body (ectopic).

Loriaux recommends that the source of corticotropin secretion be determined before considering surgery. Up to 40% of patients with pituitary adenomas have nonfunctioning tumors (the tumor does not produce any hormones) and the corticotropin source is elsewhere. If misdiagnosed, patients will likely undergo an unnecessary surgery, with a mortality rate of 1%.

Patients with an ectopic source of corticotropin should undergo imaging studies in the chest, followed by abdominal and pelvic organs. If these tests fail to detect the source, patients should undergo either the blockade of cortisol synthesis or an adrenalectomy (removal of adrenal glands).

However, corticotropin-independent Cushing’s is usually caused by a benign adrenal tumor that uniquely secretes cortisol.

“Such tumors can be treated successfully with laparoscopic adrenalectomy,” Loriaux wrote. If the tumor secretes more than one hormone, it is likely malignant. Surgical to remove the tumor and any detectable metastases should be conducted.

Overall, “the treatment for all causes of [Cushing’s syndrome], other than exogenous glucocorticoids, is surgical, and neurosurgeons, endocrine surgeons, and cancer surgeons are needed,” Loriaux wrote in the study.

“This level of multidisciplinary medical expertise is usually found only at academic medical centers. Thus, most, if not all, patients with [Cushing’s syndrome] should be referred to such a center for treatment.”

From https://cushingsdiseasenews.com/2017/10/24/diagnosing-cushings-syndrome-amid-challenge-of-obesity-and-strategies-to-improve-methods/

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Cushing’s Syndrome Epidemiology

Posted on August 3, 2016 by MaryO

By Yolanda Smith, BPharm

Cushing’s syndrome is considered to be a rare disorder that results from prolonged exposure to glucocorticoids. However, there are few epidemiological studies to provide adequate data to describe the incidence and prevalence of the condition accurately. Most cases are diagnosed between the ages of 20 and 50, although any individual may be affected at any age.

The presentation of the symptoms of Cushing’s syndrome can vary greatly. In addition, many of the symptoms overlap with those caused by other health conditions, such as metabolic syndrome and polycystic ovary syndrome. This can make the diagnosis of the condition difficult. It is also difficult to establish epidemiological trends in Cushing’s syndrome, because not all cases of the disease are diagnosed. However, it is important that diagnosis is made as soon as possible, because early diagnosis and treatment of the condition are associated with improved morbidity and mortality rates.

Population-based Studies

There are several population-based studies that have reported the incidence and mortality rates of Cushing’s syndrome in certain populations over a discrete period of time.

A study in Denmark followed 166 patients with Cushing’s syndrome for 11 years, finding an incidence of 2 cases per million population per year. Of the 166 patients, 139 had benign disease. There was a mortality rate of 16.5% in the follow-up period of 8 years, with most deaths occurring in the year after the initial diagnosis, often before the initiation of treatment. The causes of death of patients with Cushing’s syndrome in the study included severe infections, cardiac rupture, stroke and suicide.

A study in Spain found 49 cases of Cushing’s syndrome over a period of 18 years, with an incidence of 2.4 cases per million inhabitants per year and a prevalence of 39.1 cases per million. The standard mortality ratio in this study was 3.8, in addition to an increase in morbidity rates.

Incidence

A low incidence of endogenous Cushing’s syndrome was established by the population-based studies outlined above, corresponding to approximately 2 cases per million. Some studies have an estimated incidence as low as 0.7 people per million.

However, the incidence of subclinical Cushing’s syndrome may be underestimated in certain population groups, such as those with osteoporosis, uncontrolled diabetes mellitus or hypertension. For example, of 90 obese patients with uncontrolled diabetes mellitus in one study, three had Cushing’s syndrome. This yielded a prevalence of 3.3%, which is considerably higher than the incidence reported in the population-based studies. However, these findings should be supported by larger studies.

Females are more likely to be affected by Cushing’s syndrome than males, with a risk ratio of approximately 3:1. There does not appear to be a genetic link that involves an ethnic susceptibility to the condition.

Treatment Outcomes

Surgery is the first-line treatment option for most cases of overt disease and remission is achieved in the majority of patients, approximately 65-85%. However, for up to 1 in 5 patients the condition recurs, and the risk does not appear to level off, even after 20 years of follow-up.

The risk of mortality for individuals with Cushing’s syndrome is estimated to be 2-3 times higher than that of the general population, based on epidemiological studies.

Reviewed by Dr Liji Thomas, MD.

From http://www.news-medical.net/health/Cushings-Syndrome-Epidemiology.aspx

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Hospital Staff Didn’t Give Emergency Cortisol to Teenager with Complex Special Needs

Posted on October 14, 2015 by MaryO

solu-cortef

 

A TEENAGER with complex special needs who died in hospital suffered a failure in basic medical communication, an inquest heard today.

Robin Brett, 18, of Blackmore Close, died in June 2014 in the Great Western Hospital after being admitted with chronic constipation and vomiting.

After a blood test indicated a raised white blood cell count, Robin went into cardiac arrest and died.

He had congenital adrenal hyperplasia (CAH) a metabolic disease and genetic defect of the adrenal gland and learning difficulties. He required daily care and medications.

Robin’s parents listed a string of errors they believe contributed to his death including failure to give him his regular medications, infrequent observations and the lack of regular and vital cortisol injections.

His heartbroken mother, Teresa, told the inquest in Salisbury that she had told hospital staff to give Robin an emergency dose of cortisol, which was not topped up after the recommended four hours.

She said: “I asked them to give him cortisol after I noticed he was becoming clammy and had a headache which is a sign of adrenal distress, I was just about to with the syringe in my hand when it was done and he instantly perked up.

 “But this wasn’t done again after four hours and I don’t know why.”

GWH staff nurse Hannah Porte who cared for Robin on his admission said she had concerns about his “alarmingly” high pulse rate when she did observations.

“I spoke with a doctor who assured me that because he had a pre-existing condition it wasn’t of great concern. That is our protocol and I felt comforted and reassured when they said that,” she said.

Robin was described as “rocking backwards and forwards and retching “ shortly before his cardiac arrest.

Mum Teresa broke down as she recalled her “sociable and friendly” son’s decline.

“He asked me to turn his DVD player off which was out of character in itself and he was clammy. All of a sudden he wasn’t breathing,” she said,

Registrar Fahreyer Alam, who examined Robin upon admission, said he could not provide an explanation as to why steroidal drugs were prescribed but not administered to Robin.

“They was nothing about his condition on examination which would link to adrenal crisis,” he said,

“The drugs were written on the drug chart and I cannot say why they were not given to him.”

Dr Alam said he had set an observation schedule of every two hours which he had articulated to nurses, and was not observed.

“All I can is there is an element of trust in the nurses and in a busy department we do have to relay things verbally and that is what you do,” he said.

When questioned by assistant coroner Dr Claire Balysz, Dr Alam said the effect of the seven week constipation may have put pressure on Robin’s vital organs.

“His heart and lungs were smaller than average and slightly underdeveloped. The faecal impaction made his colon stretch, it may have impacted his lungs and his heart and that is something the post mortem found,” he said.

Dr Alam and nurse Porte agreed that more was being done within the trust to improve the accuracy and accessibility of patient records, including a new observation system and the use of electronic prescribing and administration (EPMA) system.

Adapted from http://www.thisiswiltshire.co.uk/news/13843924.Robin_Brett__18__died_in_GWH_after_medics_failed_to_communicate__inquest_hears/

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Cushing’s syndrome vs simple obesity. How can a needle be found in the haystack?

Posted on April 2, 2015 by MaryO

Endocrinology Today 02/2015; 4(1):30-35.

Clinical recognition of Cushing’s syndrome should generally follow from the observation of a constellation of compatible clinical features that progress over time. Screening for Cushing’s syndrome in patients with individual features of the metabolic syndrome, such as obesity, hypertension and hyperglycaemia, is not recommended.

Early diagnosis reduces unnecessary suffering and the ultimate lifetime sequelae of Cushing’s syndrome. Confirmation involves the demonstration of biochemical hypercortisolism, and the extent of diagnostic testing needs to be based on the degree of clinical suspicion.
Read the whole article here, in PDF format

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Is Diabetes in Cushing’s Syndrome a Consequence of Hypercortisolism?

Posted on November 25, 2013 by MaryO
Eur J Endocrinol. 2013 Nov 19. [Epub ahead of print]

Is Diabetes in Cushing syndrome only a consequence of hypercortisolism?

Source

C Giordano, Dipartimento di Medicina Interna e Specialistica (Di.Bi.Mi.S) Sezione di Endocrinologia e Malattie del Metabolismo, University of Palermo, Palermo, Italy.

Abstract

OBJECTIVE:

Diabetes mellitus (DM) is one of the most frequent complications of Cushing syndrome (CS). Aim of the study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients.

DESIGN:

Cross-sectional study on 140 patients with CS.

METHODS:

113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 yr) and 27 men (19 with pituitary disease and 8 with adrenal disease, aged 38.1±20.01 yr) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes) and diabetes (CS/DM).

RESULTS:

71 patients belonged to CS/NGT (49.3%), 26 (18.5%) to CS/prediabetes and 43 (30.8%) to CS/DM. Significant increasing trends in the prevalence of family history of diabetes (p<0.001), metabolic syndrome (p<0.001), age (p<0.001) and waist circumference (p=0.043) and decreasing trends in HOMAβ (p<0.001)and Oral Dispositional Index (DIo) (p<0.002) were observed among the groups. No significant trend in fasting insulin, AUC INS, ISI-Matsuda and VAI was detected.

CONCLUSIONS:

Impairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in the natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of patients at high risk for metabolic complications.

PMID:
24255133
[PubMed – as supplied by publisher]

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