Adiponectin level may serve as predictor of subclinical Cushing’s syndrome

Unal AD, et al. Int J Endocrinol. 2016;doi:10.1155/2016/8519362.

 

In adults with adrenal incidentaloma, adiponectin levels may help predict the presence of subclinical Cushing’s disease, according to recent findings.

Asli Dogruk Unal, MD, of the department of endocrinology and metabolism at Memorial Atasehir Hospital in Istanbul, and colleagues analyzed data from 40 patients with adrenal incidentaloma (24 women; mean age, 61 years) and 30 metabolically healthy adults without adrenal adenomas or hyperplasia (22 women; mean age, 26 years). All patients with type 2 diabetes were newly diagnosed and not on any antidiabetic therapies; included patients were not using statin therapy for about 12 weeks.

Participants provided blood samples

Among patients with adrenal incidentaloma, eight (20%) were diagnosed with subclinical Cushing’s syndrome; median adenoma diameter in these patients was 3.05 cm. The remaining patients were classified as nonfunctional adrenal incidentaloma. Compared with patients who had nonfunctional adrenal incidentaloma, patients with subclinical Cushing’s syndrome had a higher median midnight cortisol level (9.15 µg/dL vs. 5.1 µg/dL; P = .004) and urinary free cortisol level (249 µg per 24 hours vs. 170 µg per 24 hours; P = .007).

In two group comparisons, researchers found that only adiponectin level was lower in the subclinical Cushing’s syndrome group vs. the nonfunctional adrenal incidentaloma group (P = .007); there were no observed between-group differences for age, BMI, waist circumference, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR) or lipid profiles.

Adiponectin level was negatively associated with insulin level, HOMA-IR, triglyceride level and midnight cortisol level, and was positively associated with body fat percentage, HDL and adrenocorticotropic hormone levels. In linear regression analysis, age was found to be an increasing factor, whereas sex, HOMA-IR, LDL, waist circumference and presence of subclinical Cushing’s syndrome were decreasing factors.

In evaluating the receiver operating characteristic analysis, researchers found that adiponectin level had a predictive value in determining the presence of subclinical Cushing’s syndrome (area under the curve: 0.81; 95% CI, 0.67-0.96). Sensitivity and specificity for an adiponectin value of 13 ng/mL or less in predicting the presence of subclinical Cushing’s syndrome were 87.5% and 77.4%, respectively; positive predictive value and negative predictive value were 50% and 96%, respectively.

“Presence of [subclinical Cushing’s syndrome] should be considered in case of an adiponectin level of 13 ng/mL in [adrenal incidentaloma] patients,” the researchers wrote. “Low adiponectin levels in [subclinical Cushing’s syndrome] patients may be important in treatment decision due to the known relation between adiponectin and cardiovascular events. In order to increase the evidences on this subject, further prospective follow-up studies with larger number of subjects are needed.” – by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B81c38f07-b378-4ca1-806b-d5c17bea064c%7D/adiponectin-level-may-serve-as-predictor-of-subclinical-cushings-syndrome

Recurrent sellar mass after resection of pituitary macroadenoma

A Puerto Rican woman aged 50 years presented to an ophthalmologist with complaints of vision changes, including difficulty seeing images in her peripheral vision in both eyes and difficulty in color perception. Her medical history was significant for menopause at age 43 years, type 2 diabetes and hypertension. She had no prior history of thyroid disease, changes in her weight, dizziness or lightheadedness, headaches, galactorrhea or growth of her hands or feet.

Formal visual fields showed bitemporal superior quadrantopsia, and she was sent to the ED for further evaluation.

Imaging and laboratory tests

A pituitary protocol MRI was performed that showed a large 3 cm x 2 cm x 2.2 cm mass in the pituitary with mild osseous remodeling of the sella turcica and mass effect on the optic chiasm (Figure 1). The mass was isointense with the brain parenchyma on T1-weighted and T2-weighted images and homogeneously enhanced after IV gadolinium contrast administration.

Baseline laboratory samples drawn at 11 p.m. in the ED showed a cortisol of 16.9 µg/dL (nighttime reference range: 3-16 µg/dL), adrenocorticotropic hormone 65 pg/mL (reference range: 6-50 pg/mL), prolactin 19.4 ng/mL (reference range: 5.2-26.5 ng/mL), thyroid-stimulating hormone 1.36 µIU/mL (reference range: 0.35-4.9 µIU/mL), free thyroxine 0.9 ng/dL (reference range: 0.6-1.8 ng/dL), triiodothyronine 85 ng/dL (reference range: 83-160 ng/dL), follicle-stimulating hormone (FSH) 11.1 mIU/mL (postmenopausal reference range: 26.7- 133.4 mIU/mL) and luteinizing hormone (LH) 1.2 mIU/mL (postmenopausal reference range: 5.2-62 mIU/mL).

 

Figure 1. T1-weighted MRI images with and without contrast of the pituitary. Coronal (A) and sagittal (C) images showed a large isodense (with brain parenchyma) 3 cm x 2 cm x 2.2 cm mass (red arrow) in the sella with superior extension to the optic chiasm. After gadolinium contrast, coronal (B) and sagittal (D) images show the mass homogenously enhances consistent with a pituitary adenoma.

Images courtesy of Pavani Srimatkandada, MD.

Given the patient’s high nighttime cortisol and adrenocorticotropic hormone (ACTH) levels, she underwent an overnight dexamethasone suppression test with 1 mg dexamethasone. Her morning cortisol was appropriately suppressed to less than 1 µg/dL, excluding Cushing’s disease.

Pituitary adenoma resection

The patient was diagnosed with a nonsecreting pituitary adenoma with suprasellar extension and optic chiasm compression with visual field deficits. The macroadenoma caused an inappropriately normal LH and FSH in a postmenopausal woman consistent with hypogonadotrophic hypogonadism.

She underwent transnasal transsphenoidal resection of the nonsecreting pituitary adenoma. The dural defect caused by the surgery was patched with an abdominal fat graft with a DuraSeal dura patch. A postoperative MRI showed complete resection of the adenoma with no evaluable tumor in the sella (Figure 2). Her postoperative course was complicated by transient diabetes insipidus requiring intermittent desmopressin; however, this resolved before her discharge from the hospital.

Figure 2. T1-weighted MRI images with contrast. Coronal views before (A) and after (B) transphenoidal tumor resection show complete resolution of the enhancing pituitary mass (A; red arrow) that is replaced with a new hypodense mass in the sella (B; yellow arrow). This mass is filled with cerebrospinal fluid with a residual rim of enhancing tissue. This is consistent with the development of a pseudomeningocele in the sella.

 

Postoperative testing confirmed secondary deficiency of the adrenal, thyroid and ovarian axes requiring hormone therapy. The patient had stable temporal hemianopia in the left eye with improved vision in the right eye.

Recurrent mass detected

One year after surgery, during a routine follow-up appointment, the patient reported no dizziness, lightheadedness, worsening vision changes, rhinorrhea or headache. She had a follow-up MRI of the brain with and without contrast, which showed the interval appearance of a mass in the sella that extended from the sphenoid sinus into the sella and came in contact with the optic nerve (Figure 3).

Figure 3. Axial MRI images of the sella after resection of pituitary adenoma. On T1-weighted images the mass (red arrow) in the sella is hypodense (black) compared with the brain parenchyma. On T2-weighted images, the mass (red arrow) is hyperdense (bright) compared with the brain, consistent with fluid. Cerebrospinal fluid in the sulci on the brain surface and the vitreous fluid within the eye are also hyperintense on T2-weighted images (yellow arrows).

 

On MRI, the mass was isodense with the cerebral spinal fluid (CSF) with a residual rim of enhancing normal pituitary tissue. This appearance is consistent with the postoperative development of a pseudomeningocele and not a solid mass in the sella (Table).

Pseudomeningoceles are abnormal collections of CSF that communicate with the CSF space around the brain; these occur after brain surgery involving duraplasty (incision and repair of the dura). Unlike meningoceles, pseudomeningoceles are not completely encased by a surrounding membrane, and they communicate with the circulating CSF. Similar to CSF, a pseudomeningocele is hypodense (dark) compared with brain on T1-weighted MRI images and hyperdense (bright) on T2-weight images.

 

Pseudomeningocele treatment

Treatment may be conservative or may involve neurosurgical repair if symptomatic. Little published data addresses the development of pseudomeningoceles after transsphenoidal pituitary surgery, but this complication occasionally occurs, especially if the dural incision is large. One study noted that pseudomeningoceles are one of the most common complications after suboccipital decompression for Chiari’s malformation, but the effect of this complication is unclear.

Endocrinologists must recognize that recurrent development of pituitary masses after transsphenoidal pituitary adenoma surgery may not represent regrowth of pituitary tissue, but instead development of a meningocele/pseudomeningocele. Pseudomeningocele can be easily confirmed because this fluid collection has very different MRI characteristics than pituitary adenoma (Table). Given that patients may remain asymptomatic after the development of a pseudomeningocele, periodic MRI imaging, hormonal evaluation and ophthalmologic monitoring of visual fields are required after transsphenoidal pituitary surgery.

References:
  • Hernandez Guilabert PM. Poster No C-1330. Presented at: European Society of Radiology; March 7-11, 2013; Vienna.
  • Parker SL, et al. J Neurosurg. 2013;doi:10.3171/2013.8.JNS122106.
For more information:
  • Stephanie L. Lee, MD, PhD, ECNU, is an associate professor of medicine and associate chief, in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Lee can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118; email: stephanie.lee@bmc.org. Lee reports no relevant financial disclosures.
  • Pavani Srimatkandada, MD, is an endocrinology fellow in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Srimatkandada can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118. She reports no relevant financial disclosures.

From http://www.healio.com/endocrinology/thyroid/news/print/endocrine-today/%7B82430fb6-bbe4-4908-a389-447eee8cd005%7D/recurrent-sellar-mass-after-resection-of-pituitary-macroadenoma

Screening for Cushing’s syndrome: Is it worthwhile?

The data suggests that Cushing is not frequent enough to support the use of routine screening in patients with morbid obesity and type 2 DM. Also only 1 % of hypertensive patients have secondary hypertension due to CS. However, screening should be considered in young patients with resistant DM and/or hypertension. Among patients with osteoporosis and vertebral fractures up to 5 % were diagnosed with subclinical hypercortisolism; most of these had adrenal adenoma. Screening for CS is important in subjects with adrenal incidentaloma, and many studies show a high prevalence (~10 %) of Cushing or subclinical CS in these patients.

Abstract

Introduction

Cushing’s syndrome (CS) is a rare disease characterized by a collection of signs and symptoms, also common in the general population without elevated cortisol secretion. During the last years more patients with CS are identified earlier and with milder disease. Many of these patients are diagnosed during screening efforts performed for certain or isolated complaints like weight gain, diabetes mellitus (DM), hypertension, osteoporosis, elevated white blood cell counts and more.

Methods

In this review article the most popular screening test performed in the studies cited was the 1-mg dexamethasone suppression test.

Conclusions

Cushing is not frequent enough to support the use of routine screening in patients with morbid obesity and type 2 DM. Also only 1 % of hypertensive patients have secondary hypertension due to CS. However, screening should be considered in young patients with resistant DM and/or hypertension. Among patients with osteoporosis and vertebral fractures up to 5 % were diagnosed with subclinical hypercortisolism; most of these had adrenal adenoma. Screening for CS is important in subjects with adrenal incidentaloma, and many studies show a high prevalence (~10 %) of Cushing or subclinical CS in these patients.

Buy this article for $39.00 at http://link.springer.com/article/10.1007%2Fs11102-015-0634-9

Cushing’s Awareness Challenge: Day 9

cushings-women

Another of Robin’s fine awareness graphics.  I had all these symptoms except Type 2 Diabetes.

After my pituitary surgery, I had diabetes mellitus for a while but that went away.

It was the easy bruising that finally got me diagnosed.

In 1986 I started bruising incredibly easily. I could touch my skin and get a bruise.

On New Year’s Day of 1987 I started bleeding under the skin. My husband made circles around the outside perimeter each hour with a marker, like the rings of a tree. When I went to my Internist the next day he was shocked at the size. He now thought I had a blood disorder so he sent me to a Hematologist/Oncologist.

Fortunately, the Hematologist/Oncologist ran a twenty-four hour urine test and really looked at me. Both he and his partner recognized that I had Cushing’s. Of course, he was sure that he did the diagnosis. No matter that I had been pursuing this with other doctors for 3 years.

However, he couldn’t help me any further so the Hematologist referred me to an Endocrinologist and I was finally on the way to my diagnosis.

 

maryo colorful zebra

 

When to think Cushing’s syndrome in type 2 diabetes

ESTES PARK, COLO. – Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing’s syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing’s syndrome. The prevalence of this form of hypercortisolism is even greater – estimated at up to 11% – among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it’s 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado.

“Endogenous Cushing’s syndrome is not rare. I suspect I’ve seen more cases than I’ve diagnosed,” he observed. “I’ve probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic.”

There are three screening tests for endogenous Cushing’s syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test.

“I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion – if a patient really looks like he or she has Cushing’s syndrome – then I would use at least two screening tests to rule out endogenous Cushing’s syndrome,” the endocrinologist continued.

The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row and mailing them to an outside laboratory. The overnight dexamethasone suppression test entails taking 1 mg of dexamethasone at bedtime, then measuring serum cortisol the next morning. A value greater than 1.8 mcg/dL is a positive result.

Pregnant women constitute a special population for whom the screening method recommended in Endocrine Society clinical practice guidelines (J. Clin. Endocrinol. Metab. 2008;93:1526-40) is the 24-hour urine cortisol test. That’s because pregnancy is a state featuring high levels of cortisol-binding globulins, which invalidates the other tests. In patients with renal failure, the recommended screening test is the 1-mg dexamethasone suppression test. In patients on antiepileptic drugs, the 24-hour urine cortisol or bedtime salivary cortisol test is advised, because antiseizure medications enhance the metabolism of dexamethasone.

Dr. McDermott said that “by far” the most discriminatory clinical features of endogenous Cushing’s syndrome are easy bruising, violaceous striae on the trunk, facial plethora, and proximal muscle weakness.

“They’re by no means specific. You’ll see these features in people who don’t have Cushing’s syndrome. But those are the four things that should make you really consider Cushing’s syndrome in your differential diagnosis,” he stressed.

More widely recognized yet actually less discriminatory clinical features include facial fullness and the “buffalo hump,” supraclavicular fullness, central obesity, hirsutism, reduced libido, edema, and thin or poorly healing skin.

Endogenous Cushing’s syndrome can have three causes. An adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma accounts for 80% of cases. A cortisol-secreting adrenal tumor is the cause of 10%. And another 10% are due to an ectopic ACTH-secreting tumor, most commonly a bronchial carcinoid tumor.

Once the primary care physician has a positive screening test in hand, it’s typical to refer the affected patient to an endocrinologist in order to differentiate which of the three causes is present. This is accomplished based upon the results of a large, 8-mg dexamethasone suppression test coupled with measurement of plasma ACTH levels.

Dr. McDermott recommended as a good read on the topic of evaluating a patient with endogenous Cushing’s syndrome a recent review article that included a useful algorithm (N. Engl. J. Med. 2013;368:2126-36).

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

From http://www.clinicalendocrinologynews.com

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