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

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/

Video: Adrenalectomy for Cushing’s Syndrome Surgical Management

Adrenalectomy for Cushing Syndrome Surgical Management by Dr Anup Gulati

History of Patient
A 35 yrs old female with complaint of…
Weight Gain over last 2 years (weighing 115 kg at present)
Pulse 70, BP 124/76. No history of episodes of hypertension.
CECT whole abdomen suggestive of left adrenal 5×5 cm cystic mass
Dexamethasone suppression test positive for Cushing’s disease.
Rest all hormone profile normal.

Adrenal glands are attached with kidneys sometimes release excess hormones which cause cushing’s disease. Urologists do Adrenalectomy procedure which can cure Cushing’s disease.

 

Resolution of the physical features of Cushing’s syndrome in a patient with a cortisol secreting adrenocortical adenoma after unilateral adrenalectomy

A 37-year-old woman developed clinical manifestations of Cushing’s syndrome over a span of 2 years. Physical examination revealed features that best describe Cushing’s syndrome, such as wide purple striae (>1 cm) over the abdomen, facial plethora and easy bruisability.1  Other features observed were hypertension, moon facies, acne, a dorsocervical fat pad, central obesity and dyslipidaemia.

The diagnosis of hypercortisolism was confirmed using a 1 mg overnight dexamethasone suppression test (19.7 ng/dL, N: <1.8) and 24 h urine free cortisol (185.9 μg/24 h, N: 3.5–45). A suppressed adrenocorticotropic hormone (ACTH) level (4 pg/mL, N: 5–20) and a lack of hyperpigmentation suggested ACTH-independent Cushing’s syndrome. Further work up using CT with contrast of the adrenals showed a 2.4×2.3×2.4 cm right adrenal mass. The patient then underwent laparoscopic adrenalectomy of the right adrenal gland. Steroids was started postoperatively and tapered over time. Histopathology results were consistent with an adrenocortical adenoma (2.5 cm widest dimension). Six months after surgery, there was resolution of the physical features, weight loss and improvement in blood pressure.

Figure 1 is a serial photograph of the physical features seen in Cushing’s syndrome, such as moon facies, a dorsocervical fat pad and wide purple striae, taken preoperatively, and at 3 and 6 months after surgery. With treatment, physical and biochemical changes of Cushing’s syndrome both resolve through time.2 The time course of the resolution of these changes, however, is varied.2 ,3 We observed that the physical features were ameliorated at 3 months and resolved at 6 months.

Learning points

  • Physicians as well as patients should be aware that improvement of the features of Cushing’s syndrome after treatment does not occur immediately.

  • Dramatic resolution of the physical features of Cushing’s syndrome, however, can be observed as early as 6 months after surgery.

Figure 1

Physical features of Cushing’s syndrome (top to bottom: moon facies, a dorsocervical fat pad and wide purple striae (>1 cm) over the abdomen) documented before surgery, and at 3 and 6 months after surgery.

Footnotes

  • Twitter Follow John Paul Quisumbing at @jpquisumbingmd

  • Contributors JPMQ worked up the case and wrote the case report. MASS reviewed the case report and critically appraised it. JPMQ incorporated his suggestions.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

References

From http://casereports.bmj.com/content/2016/bcr-2016-215693.short?rss=1

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