The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing’s syndrome

Posted on July 9, 2015 by MaryO

J Clin Endocrinol Metab. 2004 Mar;89(3):1222-6.

Findling JW1, Raff H, Aron DC.

Abstract

Low-dose dexamethasone suppression testing has been recommended for biochemical screening when Cushing’s syndrome is suspected. The criterion for normal suppression of cortisol after dexamethasone is controversial.

To assess diagnostic utility (sensitivity), we report the results of low-dose dexamethasone suppression testing in 103 patients with spontaneous Cushing’s syndrome. There were 80 patients with Cushing’s disease (78%), 13 with the ectopic ACTH syndrome (13%), and 10 with cortisol-producing adrenocortical adenomas (10%). Fourteen (18%) of 80 patients with Cushing’s disease suppressed serum cortisol to less than 5 micro g/dl (<135 nmol/liter) after the overnight 1-mg test, whereas six patients (8%) actually showed suppression of serum cortisol to less than 2 micro g/dl (<54 nmol/liter). In addition, the 2-d, low-dose dexamethasone suppression test yielded false-negative results in 38% of patients when urine cortisol was used and 28% when urinary 17-hydroxycorticosteroids were used. Serum cortisol after the 1-mg test correlated with baseline urinary free cortisol (r = 0.705, P < 0.001), plasma ACTH level (r = 0.322, P = 0.001), and urinary free cortisol after the 2-d test (r = 0.709, P = 0.001).

This study provides evidence that low-dose dexamethasone may suppress either plasma cortisol or urinary steroids to levels previously thought to exclude Cushing’s syndrome and that these tests should not be used as the sole criterion to exclude the diagnosis of endogenous hypercortisolism.

PMID:
15001614
[PubMed – indexed for MEDLINE]

From http://www.ncbi.nlm.nih.gov/pubmed/15001614

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Crooke’s changes common in patients with Cushing’s syndrome, high cortisol production

Posted on July 9, 2015 by MaryO
Oldfield EH, et al. J Clin Endocrinol Metab. 2015;doi:10.1210/JC.2015-2493.
July 8, 2015

 

Evidence of Crooke hyaline changes in the pituitary gland points to a higher likelihood of Cushing’s syndrome in adults, with the changes in basophil cells occurring in 75% to 80% of patients with the hormonal disorder, according to research in The Journal of Clinical Endocrinology & Metabolism.

In a retrospective review of hospital patient records from adults with Cushing’s syndrome who underwent pituitary surgery, researchers also found that a higher degree of cortisol production, as well as exposure to excess glucocorticoids, are often associated with Crooke’s changes in adults.

“The presence of Crooke’s changes is a clear indication of the presence of Cushing’s syndrome, although the absence of Crooke’s changes does not exclude it,” the researchers wrote.

Edward H. Oldfield, MD, FACS, of the department of neurological surgery at University of Virginia Health System, and colleagues analyzed electronic hospital data from 213 consecutive patients with Cushing’s syndrome who received pituitary surgery between 2008 and March 2014. Researchers reviewed analysis of the normal pituitary tissue included with the specimens obtained at surgery, as well as cortisol production measured by 24-hour urine.

Within the cohort, Crooke’s changes occurred in 74% of patients; Crooke’s changes occurred in 81% of patients with an adrenocorticotropic hormone tumor.

Researchers also found that 91% of patients with an adrenocorticotropic hormone-producing tumor and a urinary free cortisol test at least fourfold the upper limit of normal had evidence of Crooke’s changes vs. 74% of patients with a urine cortisol amount that was less than fourfold the upper limit of normal (P = .008).

“Our results clearly demonstrate a correlation between the degree of cortisol production and the presence of Crooke’s changes,” the researchers wrote. “Patients with cortisol production exceeding fourfold upper limit almost all had Crooke’s changes.”

Researchers said study results indicate that the presence of Crooke’s changes may be used to indicate that a patient has Cushing’s syndrome following a pituitary surgery in which no tumor is found.

“However, the absence of Crooke’s changes does not reliably indicate the absence of Cushing’s syndrome, as 19% of patients with a proven [adrenocorticotropic hormone-producing tumor] did not have Crooke’s changes,” the researchers wrote. – by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B838a3557-f284-4fda-b93d-73dbb4823667%7D/crookes-changes-common-in-patients-with-cushings-syndrome-high-cortisol-production

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Moderately impaired renal function increases morning cortisol and cortisol levels at dexamethasone suppression test in patients with incidentally detected adrenal adenomas

Posted on June 26, 2015 by MaryO
Clin Endocrinol (Oxf). 2015 May 23. doi: 10.1111/cen.12823. [Epub ahead of print]
Olsen H1, Mjöman M2.

Author information

Abstract

OBJECTIVE:

Patients with incidentally detected adrenal adenomas may have subclinical hypercortisolism. We hypothesized that impaired renal function could lead to increased cortisol levels in these patients.

DESIGN:

Descriptive retrospective study of consecutive patients.

PATIENTS:

A total of 166 patients with incidentally detected unilateral adrenal adenomas were examined during 2008-2013.

MEASUREMENTS:

Levels of cortisol, ACTH and cortisol at 1 mg overnight dexamethasone suppression test (DST) were measured. The estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation.

RESULTS:

Renal function was normal, mildly impaired, moderately impaired or severely impaired (eGFR >90, 60-90, 30-60 and 15-30 ml/min/1·73 m2 ) in 34, 54, 10 and 1% of the patients, respectively. Patients with normal and mildly impaired renal function had similar cortisol levels. Patients with moderately impaired renal function, compared to all the patients with eGFR >60 ml/min/1·73 m2 , exhibited increased cortisol (541 vs 456 nmol/l, P = 0·02), increased cortisol at DST (62 vs 37 nmol/l, P = 0·001), but similar ACTH levels (4·1 vs 2·9 pmol/l, P = 0·21). Patients with moderately impaired renal function thus exhibited cortisol at DST ≥50 nmol/l, more often than patients with eGFR >60 ml/min/1·73 m2 (76% vs 30%, P = 0·000), while the prevalence of ACTH below 2 pmol/l was similar (24% vs 31%, P = 0·51).

CONCLUSIONS:

Moderately impaired renal function increases cortisol and cortisol at DST in patients with adrenal adenomas, while mildly impaired renal function has no such effect. Cortisol level at DST ≥50 nmol/l therefore seems to have low specificity in diagnosing subclinical adrenal hypercortisolism, and an additional criterion, for example low ACTH, is required.

© 2015 John Wiley & Sons Ltd.

PMID:
26010731
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/26010731

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Recurrent sellar mass after resection of pituitary macroadenoma

Posted on June 17, 2015 by MaryO

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

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Adrenal insufficiency – how to spot this rare disease and how to treat it

Posted on June 6, 2015 by MaryO

adrenal-glandsAddison’s disease, or adrenal insufficiency, is a rare hormonal disorder of the adrenal glands that affects around 8,400 people in the UK.

The adrenal glands are about the size of a pea and perched on top of the kidneys, and affect the body’s production of the hormones cortisol and sometimes aldosterone.

When someone suffers from adrenal insufficiency, those glands aren’t producing a sufficient amount of these hormones. This can have a detrimental effect on someone’s health and well-being. But because the symptoms are similar to a host of other conditions, Addison’s disease can prove tough to isolate.

What to look out for

According to advice provided by the NHS, the symptoms in the early stages of Addison’s disease, which affects both men and women, are gradual and easy to misread as they’re similar to many other conditions.

People can experience severe fatigue, muscle weakness, low moods, loss of appetite, unintentional weight loss, low blood pressure, nausea, vomiting and salt craving.

“Symptoms are often misread or ignored until a relatively minor infection leads to an abnormally long convalescence, which prompts an investigation,” says Professor Wiebke Arlt from the Centre for Endocrinology, Diabetes & Metabolism at the University of Birmingham.

Life-threatening condition

If Addison’s disease is left untreated, the level of hormones produced by the adrenal gland will gradually decrease in the body. This will cause symptoms to get progressively worse and eventually lead to a potentially life-threatening situation called an adrenal, or Addisonian, crisis. Signs include severe dehydration; pale, cold, clammy skin; rapid, shallow breathing; extreme sleepiness; severe vomiting and diarrhoea. If left untreated, it can prove fatal, so the patient should be admitted to hospital as an emergency.

Back to basics

To understand the disorder, it’s important to get to grips with the basics and that means understanding what the adrenal glands are – and so to the science.

“Adrenal glands have an inner core (known as the medulla) surrounded by an outer shell (known as the cortex) ,” explains Arlt.
The inner medulla produces adrenaline, the ‘fight or flight’ stress hormone. While the absence of this does not cause the disease, the cortex is more critical.

“It produces the steroid hormones that are essential for life: cortisol and aldosterone,” he adds.

“Cortisol mobilises nutrients, enables the body to fight inflammation, stimulates the liver to produce blood sugar and also helps control the amount of water in the body. Aldosterone, meanwhile, regulates the salt and water levels, which can affect blood volume and pressure.”

Why does it happen?

The disorder occurs if the adrenal glands are destroyed, absent or unable to function and failure of the glands themselves is known as primary adrenal insufficiency.

“It’s most often caused by autoimmune disease where the body’s immune system mounts an attack against its own adrenal glands,” explains Arlt.

“However it can also be caused by infection, most importantly by tuberculosis and sometimes by both adrenal glands being surgically removed.”

The pituitary effect

Another important cause is any disease affecting the pituitary gland, which is located behind the nose at the bottom of the brain.
“The pituitary is the master gland that tells the other glands in the body what to do,” continues Arlt.

“The pituitary gland produces a hormone called ACTH (adrenocorticotropic hormone to give it its full name), which travels in the blood stream to the adrenal glands.

“Here it acts as a signal, causing the adrenal glands to produce more cortisol. If the pituitary gland stops making ACTH, [then] cortisol production by the adrenals is no longer controlled properly and a condition called secondary adrenal insufficiency arises.”

But in most cases, aldosterone is still produced, which means that people suffering from secondary adrenal insufficiency have fewer problems than those with primary adrenal insufficiency.

Determining a diagnosis

Due to the ambiguous nature of the symptoms, a Short Synacthen Test (SST) needs to be performed in order to diagnose adrenal insufficiency.

“This measures the ability of the adrenal glands to produce cortisol in response to (the pituitary hormone) ACTH,” says Arlt. “When carrying out this test, a baseline blood sample is drawn before injecting a dose of ACTH, followed by drawing a second blood sample 30 to 60 minutes later. Failing adrenal glands will not be able to produce a certain level of cortisol.”

Getting treatment

If someone has been conclusively diagnosed with adrenal insufficiency, they should receive adrenal hormone replacement therapy as advised by an endocrinologist, a doctor specialising in hormone-related diseases.

“A normal adrenal gland does not need supplements to function properly and there is no recognised medical condition called ‘adrenal fatigue’,” warns Arlt.

“Either the adrenal gland is fine and needs no treatment or there is adrenal insufficiency due to adrenal or pituitary failure.”

So if in doubt, don’t self-diagnose but book an appointment with your GP.

For more information, visit Addison’s Disease Self-Help Group (www.addisons.org.uk) or Pituitary Foundation.

From https://home.bt.com/lifestyle/wellbeing/adrenal-insufficiency-how-to-spot-this-rare-disease-and-how-to-treat-it-11363985141306

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