Delays complicate Cushing’s disease diagnosis, treatment for woman, 33
Case highlights condition's potential ‘variable clinical presentations’
The diagnosis of a 33-year-old woman with Cushing’s disease was delayed due to the presence of mild, nonspecific symptoms, a tumor in the adrenal glands, and normal blood levels of the adrenocorticotropic hormone (ACTH), according to a new case study.
The woman’s move from Canada to the U.K. also complicated her diagnosis and treatment, the researchers noted.
But, the team stressed in their report, hypercortisolism, or too much of the hormone cortisol in the body — the underlying cause of Cushing’s — “can have variable clinical presentations,” making it important for physicians to take all factors into account when making a diagnosis.
“This case highlights the approach to obtaining the correct diagnosis and the impact of treatment on weight and metabolic health in patients with hypercortisolism,” the researchers wrote.
Their report, “Cushing disease presenting with hypertension in association with nonfunctioning unilateral adrenal adenoma,” was published in the Canadian Medical Association Journal.
Woman’s Cushing’s disease diagnosis delayed by move, other factors
Cushing’s syndrome is marked by excessive levels of the stress hormone cortisol, which is produced by the adrenal glands located atop the kidneys. This can cause a wide range of symptoms, with patients typically experiencing weight gain, a moon face, unusual stretch marks, easy bruising, muscle wasting, and high blood pressure, or hypertension.
Cushing’s disease, one of the most common forms of the syndrome, is caused by a tumor in the brain’s pituitary gland that produces excessive amounts of ACTH, a hormone that triggers cortisol production.
Less frequently, tumors in the adrenal glands themselves can boost cortisol production and cause Cushing’s syndrome independently of ACTH. As such, measuring ACTH levels in people with suspected Cushing’s syndrome may help discriminate between Cushing’s disease and adrenal forms, the researchers noted.
However, “interpretation of ACTH levels can be nuanced,” the team wrote, adding that “patients with Cushing disease do not always exhibit levels above the reference range” — as was the case for this patient.
In their report, the team of U.K. researchers detailed the case of a woman with Cushing’s disease whose diagnosis was first delayed due to her mild symptoms and a relocation across continents, and later complicated by the detection of an adrenal tumor and normal ACTH levels.
The woman sought care once in England for worsening, treatment-resistant high blood pressure, or hypertension, that had first developed seven years before, when she was living in Canada.
She also was obese and had a history of easy bruising, but no other classic symptoms of Cushing’s, such as moon face, muscle weakness, or stretch marks.
When she had first sought treatment in Canada for hypertension, examinations detected hypercortisolism and a tumor in her left adrenal gland. However, the researchers noted, “further investigations and management were not undertaken because she relocated to England.”
The earlier findings made the U.K. researchers suspicious of Cushing’s syndrome associated with an adrenal tumor.
Surgery led to remission for patient, as well as weight loss
Blood tests done in England confirmed the woman’s hypercortisolism, and no response to a low-dose dexamethasone suppression test. In normal conditions, administration of a low dose of the corticosteroid dexamethasone results in a reduction in blood cortisol levels, but in Cushing’s syndrome patients, this has no effect on cortisol levels.
While this supported a diagnosis of adrenal Cushing’s syndrome, the woman had normal levels of ACTH and the adrenal-produced dehydroepiandrosterone sulfate, or DHEAS, whose production would normally be suppressed in a case of adrenal Cushing’s.
As such, the researchers hypothesized that the woman’s condition could be due to a pituitary tumor, which was detected in a subsequent brain scan. This, along with an analysis of blood coming out of the pituitary gland that showed excessive ACTH production, confirmed a diagnosis of Cushing’s disease.
“Identifying the underlying cause of Cushing syndrome can be challenging, yet important, as there is a distinct therapeutic approach to each,” the researchers wrote.
The team noted that “levels of ACTH can vary, and while they are often high-normal [in Cushing’s disease], midrange readings can cause diagnostic uncertainty.” They added that, “in our patient, ACTH levels did not clearly differentiate between a pituitary and adrenal cause of hypercortisolism.”
Identifying the underlying cause of [Cushing’s] can be challenging, yet important, as there is a distinct therapeutic approach to each.
The woman underwent surgery to remove the pituitary tumor, and her cortisol levels returned to normal. Her ACTH levels, meanwhile, showed a reduction, but were still within the normal range.
Following surgery, the woman’s blood pressure normalized, and she was maintained in remission for more than 1.5 years, even after discontinuation of antihypertensive treatment. She also lost 20 kg, or 44 pounds, and was no longer classified as obese or overweight.
“Delayed diagnosis of early or mild Cushing syndrome is not uncommon,” the researchers wrote, adding that “recognition becomes clinically less difficult when hypercortisolism is severe.”
The team noted that, while the woman’s adrenal tumor suggested a form of Cushing’s syndrome in which excessive cortisol production was not driven by ACTH, that form would result in lower than normal ACTH levels.
The detection of normal ACTH levels also further complicated this case, but the subsequent brain scan showing the pituitary tumor confirmed the diagnosis of Cushing’s disease and prompted the appropriate treatment that effectively controlled the woman’s condition.
