Low Cortisol Levels Hours After Surgery Predict Long-term Remission in Cushing’s Patients

The level of decline in blood cortisol levels in the immediate period after transsphenoidal surgery for Cushing’s disease may help predict which patients will achieve long-term disease remission.

The study, “Earlier post-operative hypocortisolemia may predict durable remission from Cushing’s Disease” was published in the European Journal of Endocrinology.

Transsphenoidal surgery (TSS) is a minimally invasive procedure for removing pituitary adenomas and is the primary treatment for Cushing’s disease.

But, while 77 to 98 percent of patients achieve remission after TSS, a third of these patients eventually will see their disease returning.

The surgical removal of the pituitary adenoma often leads to a drop in the adrenocorticotropic hormone (ACTH) and cortisol levels (hypocortisolemia).

“In the post-operative setting, failure to achieve hypocortisolemia is thought to reflect the presence of residual tumor cells,” the researchers wrote in the study. “Therefore, serum cortisol has become a well-established biochemical marker of early surgical remission.”

In an attempt to identify patients with a complete tumor resection – and with lower risk of recurrence – researchers examined the rates of serum cortisol decline in the immediate period after surgery.

The study included 257 Cushing’s disease patients who underwent 291 TSS interventions at the National Institutes of Health (NIH), between 2003 and 2016.

After surgery, patients had their cortisol levels measured every six hours until the third day after surgery. Then, patients had their cortisol levels measured every morning until day 10 or were discharged.

Early remission was defined based on nadir serum cortisol levels – the lowest concentration of cortisol, that is usually reached during the night – below 5 μg/dL.

Of 268 unique admissions, 90 percent of patients (241) achieved remission with a post-operative cortisol nadir below 5 μg/dL within 10 postoperative days.

However, recurrence was seen in 9 percent of these patients. For those with a cortisol nadir below 2 μg/dL, the rates of recurrence dropped to 6 percent.

Interestingly, the team found that cortisol levels below 5 μg/dL by 15 hours after surgery or below 2 μg/dL in the first 21 hours may “accurately predict durable remission in the intermediate term.”

“In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission,” the researchers wrote.

“Such a clinical prediction tool may have significant utility in the management of [Cushing’s disease]. Further validation of its accuracy in a multi-centre prospective study with longer-term follow up is warranted,” the study concluded.

From https://cushingsdiseasenews.com/2018/01/18/low-cortisol-levels-after-surgery-may-predict-remission-cushings-disease/

How to avoid pitfalls in interpretation of adrenal imaging

By Philip Ward, AuntMinnieEurope.com staff writer

January 15, 2019 — A clear understanding of the pitfalls in the performance and interpretation of adrenal CT can help prevent incorrect and inappropriate investigations, award-winning researchers from a top London facility have found. It’s essential to keep aware of the full range of pseudolesions and mimics, they said.

“Evaluation of adrenal tumor function is limited on imaging, but may be inferred from imaging findings,” noted Dr. Gurinder Nandra and colleagues from the department of radiology at St. George’s University Hospitals NHS Foundation Trust in an e-poster presentation that received a cum laude award at RSNA 2018 in Chicago.

Other adrenal pathology, including metastases and adrenocortical carcinoma, may be encountered, and this means it’s important to know about the imaging approaches to evaluate the adrenals, the authors pointed out.

Incidental adrenal nodules are identified in around 5% of patients who undergo CT. The prevalence of detecting incidentalomas increases with age, but most incidentally encountered adrenal pathology is benign and of little clinical relevance, they wrote. Adenomas are by far the most common adrenal pathology identified.

Among the technical aspects that deserve special attention are the following:

  • The region of interest (ROI): Changing the size of the ROI can alter the perceived attenuation of the nodule. The ROI should cover at least two-thirds of the circumference of the nodule, and exclude tiny areas of heterogeneity from the ROI (e.g., flecks of calcification) that are not representative of the adrenal pathology. Unenhanced attenuation of less than 10 Hounsfield units (HU) can be used to diagnose lipid-rich adrenal adenoma (sensitivity 71%, specificity of 98%).
  • Attenuation values on unenhanced CT: A homogenously dense lesion on unenhanced CT suggests a lack of microscopic lipid content. If attenuation on unenhanced CT is greater than 20 to 30 HU, evaluate the enhancement kinetics with CT.
  • Effect of kVp on attenuation values in a dual energy study: To use threshold of less than 10 HU to diagnose a lipid-rich adrenal adenoma, the kVp should be 120. Changing kVp can alter the attenuation values of soft tissues and adrenal glands.
  • Timing of post-contrast acquisitions: “Imaging needs to be performed at the correct times to allow sufficient time for enhancement and washout of contrast. Post-contrast images should be obtained at 60 to 75 seconds and 15 minutes,” the authors stated.
  • Assessment of washout on nondedicated studies: Relative washout can be calculated on nondedicated studies if more than one acquisition is made within 15 minutes post-intravenous contrast.
  • Suspicious attenuation: Attenuation of more than 43 HU on noncontrast CT is suspicious for malignancy, regardless of washout characteristics. PET/CT is of more use than CT and MRI in such cases, and adrenal hemorrhage also is a consideration at this attenuation.
  • Evaluation of small nodules: Minor nodularity of less than 1 cm in diameter does not require further radiological investigation. Also, CT evaluation of small adrenal nodules is limited by partial volume artifacts. MRI evaluation of small adrenal nodules is limited by the India ink artifact, or black boundary artifact, on an out-of-phase sequence. This artifact may give the impression of signal loss and lead to an incorrect diagnosis of a lipid-rich adenoma.
  • Evaluation of large adrenal masses: Malignancy risk increases with size (over 4 cm, 70%; over 6 cm, 85%) when excluding myelolipoma. In the absence of known malignancy, an adrenal lesion of less than 4 cm with indeterminate imaging features is likely to be benign.
  • Enhancement characteristics of metastases: Enhancement/washout characteristics of adrenal metastases are variable, and they can be confused with pheochromocytoma.
  • Adrenal calcification: Calcification is seen in benign adrenal pathology, but also can be seen in cases of malignancy, including adrenocortical carcinoma. “Look for ancillary features of malignancy including size, heterogeneity and invasion,” the authors recommended. “Evaluation of a predominantly calcified adrenal lesion will be limited with chemical shift MRI.”
  • Heterogeneous signal loss: Heterogeneous signal loss is not typical for a small lipid-rich adenoma and raises the possibility of malignant pathology. It also can be seen in larger adenomas because of calcification/cystic change/myelolipomatous metaplasia.

In their RSNA 2018 exhibit, Nandra and colleagues also identified the following list of mimics that can crop up:

  • Mimics arising from gastrointestinal tract: Gastric pathology can extend into the left suprarenal space and mimic adrenal pathology. The most common mimics include gastrointestinal stromal tumors and gastric diverticula. Pathology elsewhere in the gastrointestinal tract can mimic adrenal pathology (e.g., a fluid-filled colon).
  • Mimics arising from solid viscera: Pathology from the spleen, pancreas, liver, and kidneys can extend into the suprarenal space and mimic adrenal pathology. This includes splenic lobulation, splenunculi, upper pole renal pathology, pancreatic tail pathology, and exophytic hepatic lesions.
  • Mimics arising from vessels: Dilated, tortuous, or aneurysmal vessels may extend into the suprarenal space and mimic adrenal pathology. The most common mimics include splenic varices and splenic artery pseudoaneurysms.
  • Mimics arising from retroperitoneal tissues: Various retroperitoneal lesions can extend into the suprarenal space and mimic adrenal pathology, and normal anatomy in the retroperitoneum also can mimic adrenal pathology (e.g., a thickened diaphragmatic crus).

From https://www.auntminnieeurope.com/index.aspx?sec=ser&sub=def&pag=dis&ItemID=616803

Topical Ocular Glucocorticoid Leads to Cushing’s Syndrome in 9-Year-Old

In a case report published online January 19 in Pediatrics, iatrogenic Cushing’s syndrome (CS) is described in a 9-year-old girl who received topical ocular glucocorticoid (GC) treatment for bilateral iridocyclitis.

Daisuke Fukuhara, MD, PhD, from the Kyorin University School of Medicine in Mitaka, Japan, and colleagues present the case of a 9-year-old girl suffering from idiopathic uveitis. She arrived at the ophthalmology department with a complaint of painful eyes, and was diagnosed with bilateral iridocyclitis and started on betamethasone sodium phosphate eye drop treatment.

The authors note that the patient was referred to the pediatric department with stunted growth, truncal obesity, purple skin striae, buffalo hump, and moon face six months after initiation of topical ocular GC treatment. She was diagnosed with iatrogenic CS as her serum cortisol and plasma adrenocorticotropic hormone levels were undetectable. The clinical symptoms of CS were improved after the doses of topical ocular GC were reduced. On genetic analysis, the patient was found to have a single heterozygous nucleotide substitution in the 3′ untranslated region of the NR3C1 gene.

“However, additional investigations are required to determine if our findings can be extrapolated to other patients,” the authors write. “In conclusion, clinicians should be aware that even extremely low doses of topical ocular steroid therapy can cause iatrogenic CS.”

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From http://www.empr.com/news/iatrogenic-cushings-syndrome-topical-ocular-glucocorticoid-iridocyclitis/article/632840/

Cushing’s Syndrome Etiology Affects Adrenal Function Recovery

The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing’s disease (CD), adrenal CS and ectopic CS.

Design:

We performed a retrospective analysis based on the case records of 230 CS patients in our tertiary referral center treated from 1983 to 2014. The mean follow-up time was 8 years.

The probability of recovering adrenal function within a 5 years follow-up differed significantly between subtypes (p=0.001). It was 82 % in ectopic CS, 58 % in Cushing’s disease and 38 % in adrenal CS. In the total cohort with restored adrenal function (n=52) the median time to recovery differed between subtypes: 0.6 (IQR 0.03–1.1) years in ectopic CS, 1.4 (IQR 0.9–3.4) years in CD, and 2.5 (IQR 1.6–5.4) years in adrenal CS (p=0.002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio 0.896, 95% CI 0.822–0.976, p=0.012), independently of sex, BMI, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses.

Conclusions:

Time to recovery of adrenal function is dependent on the underlying etiology of CS.