Late-night Salivary Cortisol a Poor Approach for Detecting Cushing’s in Obese Patients

Posted on March 30, 2018 by MaryO

Assessment of late-night salivary cortisol (LNSC) levels is a poor diagnostic tool for detecting Cushing’s disease in obese patients, a new study from Germany shows.

The test demonstrated a particularly poor sensitivity in obese people, meaning it will often suggest a patient has Cushing’s disease when that is not the case — called a false-positive.

The study, “Specificity of late‑night salivary cortisol measured by automated electrochemiluminescence immunoassay for Cushing’s disease in an obese population,” appeared in the Journal of Endocrinological Investigation.

Although excessive weight gain is a common symptom of Cushing’s disease, existing indications advise clinicians to test for Cushing’s in obese people only if the disease is clinically suspected.

The utility of measuring LNSC for Cushing’s disease screening is well established. However, differences in assays, sample collection methods, and controls have led to a great variability in the proposed reference ranges and cut-off values. Also, according to the Endocrine Society, the influence of gender, age, and co-existing medical conditions on LNSC concentrations is still unclear.

Regarding obesity, data on the specificity of assessing late-night salivary cortisol levels is contradictory, as some studies found no differences while others reported lower specificity compared to healthy individuals.

An additional factor complicating LNSC measures in obese people is the prevalence of type 2 diabetes mellitus (T2DM), which may also lead to elevated cortisol levels.

Research showed a high rate of false-positive LNSC measurements in obese patients with poorly controlled type 2 diabetes. Also, in patients with recently diagnosed diabetes, investigators found that LNSC had very low specificity — the proportion of patients with Cushing’s who test positive — and a poor predictive value.

Recent reports showed a high diagnostic accuracy using automated electrochemiluminescent assays (ECLIA) in patients with Cushing’s disease. These methods use special labels conjugated to antibodies that produce light when they bind to a specific target.

The research team used an ECLIA assay to test the specificity of LNSC in obese patients both with and without diabetes. The investigators also intended to establish a reference range and cut-off value for this diagnostic approach.

Adults who requested weight loss treatment were included in the study, including 34 patients with a confirmed diagnosis of Cushing’s and 83 obese people, defined as having a body mass index (BMI) of at least 35 kg/m2. Forty healthy individuals were also analyzed.

Eight out of the 34 Cushing’s patients had a BMI within the obese range, which correlates with an overlap in patients awaiting bariatric surgery for weight loss, the investigators observed.

All subjects underwent LNSC assessment at 11 p.m. Results revealed significant differences in mean LNSC values — 19.9 nmol/L in Cushing’s disease patients, 10.9 nmol/L in obese subjects, and 4.7 nmol/L in those of normal weight.

Compared to healthy and obese participants, measuring LNSC in Cushing’s disease patients had a maximum sensitivity of 67.6% and a specificity of 85.4%. This was lower than prior data from obese patients with two features of Cushing’s disease.

The cut-off value for detecting Cushing’s was 12.3 nmol/L, which is in line with other studies “and underlines the importance of an evaluation with an obese cohort vs. [Cushing’s disease],” the investigators wrote.

Results did not show an association between BMI, type 2 diabetes, and LNSC for all groups.

“In our obese cohort, we found that LNSC assayed by ECLIA had a low specificity in the diagnosis of [Cushing’s disease],” the researchers wrote. “However, the clear advantage of LNSC over other tests is the simple and stress-free sampling method.”

From https://cushingsdiseasenews.com/2018/03/29/nighttime-salivary-cortisol-poor-approach-detect-cushings-disease-obese-patients/

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USC’s 7 Tesla MRI scanner first to identify Cushing’s disease in US patient

Posted on March 24, 2018 by MaryO

A noninvasive 7 Tesla MRI scanner at University of Southern California is the first 7T scanner to be used on a patient with Cushing’s disease in the U.S., according to a USC news release.

When a brain tumor was found to be “MRI-negative” in a 28-year-old female patient, physicians at the USC’s Pituitary Center were unsatisfied with the results. After deciding to use the Neuroimaging and Informatics Institute’s (INI) new ultrahigh field 7 Tesla MRI scanner to localize the tumor, the patient was officially diagnosed with Cushing’s disease and researchers were finally able to [be] see the tumor that would’ve otherwise appeared hidden in a standard MRI.

Cushing’s disease is caused by a pituitary microadenoma, or very small tumor, which results in chronically elevated cortisol. Symptoms include weight gain, skin bruising and hair loss and if left untreated, the condition can be fatal.  Because of this case, USC researchers believe the 7T scanner will be able to replace the standard, and invasive, method of clinical diagnosis, according to the news release.

“It’s clear that this is the beginning of a new frontier for ultrahigh field MR technologies,” said Arthur Toga, PhD, director of the INI, in a prepared statement. “The enhanced image quality opens many doors for neuroscientists in both research and clinical settings.”

From http://www.healthimaging.com/topics/neuroimaging/uscs-7-tesla-mri-scanner-first-identify-cushings-disease-us-patient

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ACTH/Cortisol Ratio May Be Simple, Reliable Test to Diagnose Cushing’s Disease

Posted on March 16, 2018 by MaryO

The ratio between adrenocorticotropic hormone levels and cortisol levels in the blood is higher among Cushing’s disease patients than in healthy people, a new study has found, suggesting that measurement could be used to help diagnose the disease.

Also, higher values at diagnosis could predict if the disease will recur and indicate larger and more invasive tumors.

The research, “The Utility of Preoperative ACTH/Cortisol Ratio for the Diagnosis and Prognosis of Cushing’s Disease,” was published in the Journal of Neurosciences in Rural Practice.

Cushing’s syndrome (CS) is characterized by excess levels of cortisol. In patients with suspected CS, clinicians recommend testing late-night salivary or plasma (blood) cortisol, 24-hour urine-free cortisol (UC), as well as morning cortisol levels after low-dose suppression with dexamethasone, a corticosteroid.

CS may be ACTH-dependent or ACTH-independent, meaning that the high cortisol levels are caused by excess ACTH production.

Patients with CD have elevated levels of ACTH. A tumor, usually an adenoma, causes the pituitary gland to produce excess levels of ACTH, which stimulate the release of cortisol from the adrenal glands. Cortisol usually inhibits ACTH production. However, in CD patients, this feedback mechanism is absent.

Despite extensive research and clinical data, the variable and usually nonspecific signs and symptoms of CD still represent relevant challenges for diagnosis. Clinical manifestations must be associated with biochemical tests, which often have led to conflicting results.

Studies showed that although ACTH levels correlate with the size of the pituitary adenoma, the levels of cortisol do not increase as much. In fact, lower cortisol/ACTH ratios have been reported in patients with macroadenoma – which is greater than 10 millimeters in size – than in those with microadenoma, which is smaller than 10 millimeters.

Conversely, the research team hypothesized that besides their utility for determining the cause of CS, the inverse ratio – ACTH/cortisol – also may be useful for diagnosis.

The team evaluated the pretreatment plasma ACTH/cortisol levels in CS patients with excess cortisol production due to abnormal pituitary or adrenal function. Data from patients were compared with that of individuals without CS.

The study included 145 CS patients diagnosed from 2007 to 2016, 119 patients with CD, 26 with ACTH-independent CS (AICS), and 114 controls with no CS.

Patients’ clinical, laboratory, imaging, postsurgical and follow-up data were analyzed.

Results showed that patients with CD had a significantly higher basal ACTH/cortisol ratio than controls or those with AICS.

“These results showed ACTH/cortisol ratio might be a simple and useful test for the diagnosis of ACTH-dependent CS,” the researchers wrote.

Importantly, the scientists observed that a ACTH/cortisol ratio above 2.5 indicated identified 82 percent of positive CS cases and 63 percent of controls.

Overall, “an ACTH/cortisol ratio [greater than] 2.5 would be beneficial to diagnose CD together with other diagnostic tests,” they concluded.

Patients with recurrent CD showed higher pretreatment ACTH levels and ACTH/cortisol ratio than those who achieved sustained remission. CD patients also exhibited more invasive, atypical and larger tumors, as well as lower postoperative remission and higher recurrence rates.

“Higher ACTH/cortisol ratio might predict poorer prognosis,” the investigators said.

From https://cushingsdiseasenews.com/2018/03/16/acth-cortisol-ratio-reliable-test-diagnose-cushings-disease/

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Mild Cortisol Increases Affect Cardiovascular Changes Linked to Heart Disease in Cushing’s

Posted on March 14, 2018 by MaryO

Increases in cortisol secretion, even if mild, induce early heart and blood vessel changes that may increase the risk for cardiovascular disease, according to Italian researchers.

The findings continue to support the role of the hormone cortisol in heart disease, and demonstrate the need for carefully monitoring cardiovascular risk in patients with high levels of the hormone, including those with Cushing’s disease.

The study, “Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas,” was published in the European Journal of Endocrinology.

While most patients with adrenal incidentalomas don’t have symptoms, nearly half have excess cortisol production. Adrenal incidentalomas are masses in the adrenal glands discovered only when a patient undergoes imaging tests for another unrelated condition.

These asymptomatic, mild cortisol-producing cases are defined as possible autonomous cortisol secretion (pACS), according to the European Society of Endocrinology Guidelines.

Excess production of the hormone, seen in Cushing’s disease patients, is associated with increased mortality, mainly due to heart diseases. Patients with asymptomatic adrenal adenomas and mild cortisol secretion also have more cardiovascular events and generally die sooner than those with normal cortisol levels.

But little is known about the causes behind cardiac and vessel damage in these patients.

To shed light on this matter, a research team at Sapienza University of Rome evaluated the cardiovascular status of patients with pACS. This allowed them to study the impact of cortisol in the heart and blood vessels without the interference of other hormone and metabolic imbalances seen in Cushing’s disease.

The ERGO trial (NCT02611258) included 71 patients. All had been diagnosed with adrenal incidentalomas, 34 of which were pACS with mildly increased levels of the hormone and 37 were defined as nonfunctioning adenoma (NFA) — adrenal masses with normal hormone levels.

The two groups were very similar, with no significant differences in metabolic and cardiovascular risk factors. Adrenal lesions in the pACS group, however, were significantly bigger, which was linked to cortisol levels.

Looking at the heart morphology, researchers found that pACS patients had a significantly higher left ventricular mass index (LVMI), which is a well-established predictive measure of adverse cardiovascular events.

Further analysis revealed that LVMI scores were associated with levels of the hormone, suggesting it has an “independent effect of cortisol on cardiac function,” the researchers wrote.

Slightly more than half of pACS patients (53%) also had a thicker left ventricle, a feature that was seen only in 13.5% of NFA patients. The performance of the left ventricle during diastole (muscle relaxation) was also affected in 82.3% of pACS patients, compared to 35.1% in those with NFA.

Patients with pACS also had less flexible arteries, which may contribute to the development of vascular diseases.

The results show that “mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling” in patients who appear apparently healthy, the researchers said.

“The morphological and functional cardiovascular changes observed in pACS underline the need for further studies to correctly define the long-term management of this relatively common condition,” they added.

From https://cushingsdiseasenews.com/2018/03/13/cushings-disease-increased-cortisol-affects-cardiovascular-changes-heart-disease/

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Steroid Medication for Nasal Obstruction in Infants May Cause Cushing’s Syndrome

Posted on March 10, 2018 by MaryO

Intranasal steroid drops used to treat nasal obstruction may cause Cushing’s syndrome and adrenal insufficiency in infants, a case study of two patients suggests.

The study, “Iatrogenic Cushing’s syndrome and adrenal insufficiency in infants on intranasal dexamethasone drops for nasal obstruction – Case series and literature review,” was published in the International Journal of Pediatric Otorhinolaryngology.

Children with nasal obstruction may have severe delays in development and can face life-threatening complications later in life such as obstructive sleep apnea and cardiopulmonary problems.

While intranasal steroid drops have become increasingly popular as a substitute for surgery, they can have adverse effects. In addition to suppressing the immune system and changing metabolism, high levels of corticosteroids in the blood may cause Cushing’s syndrome.

Researchers at Weill Cornell Medical College presented two cases of adrenal gland insufficiency and Cushing’s syndrome caused by intranasal dexamethasone drops. Dexamethasone is a type of corticosteroid medication.

First, they described the case of a 3-month-old boy who was taken to the hospital following a life-threatening episode at home after feeding. A physical evaluation revealed nasal congestion with no additional anatomic abnormalities.

Treatment with nasal dexamethasone drops three times a day improved his breathing. While the dosage was later decreased to three drops once daily, a congestion episode led the mother to increase the dose back to the initial recommendation.

After seven weeks of treatment, the boy was noted to have facial puffiness, leading to an endocrine evaluation that revealed low cortisol levels. The dose was eventually reduced, and the boy’s cortisol levels returned to normal after several months.

The second case was a 6-week-old boy with a history of chronic congestion and difficulty feeding. He had severe nasal obstruction and required intubation due to respiratory distress. A nasal exam revealed damaged mucosa with severe nasal cavity narrowing, and he began treatment with three ciprofloxacin-dexamethasone drops three times a day.

After two and a half weeks of treatment, the boy’s cortisol levels were considerably low, and adrenal insufficiency was diagnosed. The treatment dose was reduced in an attempt to improve cortisol levels, but nasal obstruction symptoms continued.

The child then underwent surgery to resolve his nasal obstruction, and the treatment with steroid drops was discontinued. While his cortisol levels subsequently improved, they continued to be low, suggesting that he may have a hormone-related disease.

Despite the benefits of steroid-based nasal drops, small infants are more sensitive to steroid compounds. In addition, nasal drops are more easily absorbed than nasal sprays, suggesting that infants taking these medications should be better controlled for side effects.

“Patients started on this therapy must be closely monitored in a multi-disciplinary fashion to ensure patient safety and optimal symptom resolution,” the researchers suggested.

From https://cushingsdiseasenews.com/2018/03/09/cushing-syndrome-infants-can-be-caused-by-steroid-based-nasal-drops-study-suggests/

Filed under: adrenal, adrenal crisis, Cushing's, symptoms | Tagged: , , , , , , , , | Leave a comment »

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