High levels of neutrophils may point to subclinical Cushing’s: Case study

Rare diagnosis in woman with neutrophilia, fatigue but no other overt symptoms

Joana Vindeirinho, PhD avatar

by Joana Vindeirinho, PhD |

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A drawing of white and red blood cells.

High levels of white blood cells, particularly neutrophils, without an infectious or blood-related cause may be a sign of subclinical Cushing’s disease, according to a case study.

The report describes the case of a woman who had palpitations and fatigue, but no other overt symptoms. She was found to have high neutrophil counts — neutrophilia — and increased levels of adrenocorticotropic hormone (ACTH) and cortisol, leading doctors to discover benign pituitary gland tumors called silent corticotroph adenomas (SCAs).

“Patients with subclinical Cushing’s disease due to pathological confirmed SCAs presented with elevated neutrophils are rare. This case indicated that leukocytosis [high white blood cell count] might occur in subclinical Cushing’s disease,” researchers wrote.

The study, “Neutrophilia with subclinical Cushing’s disease: A case report and literature review,” was published in the journal Open Life Sciences.

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Subclinical Cushing’s marked by mild hypercortisolism without symptoms

Cushing’s disease is caused by benign tumors in the pituitary gland, a small structure at the base of the brain. These tumors trigger the excessive production of ACTH, a hormone that stimulates the adrenal glands sitting atop the kidneys, to produce the steroid hormone cortisol. Excessive levels of cortisol cause the various symptoms that are characteristic of Cushing’s disease.

Unlike ACTH-producing pituitary tumors, SCAs do not produce excessive levels of ACTH and are not usually associated with Cushing’s disease, although some do progress and eventually cause the condition.

More recently, a subset of the disease, called subclinical Cushing’s disease, has been studied. This condition is characterized by a mild increase in cortisol levels due to ACTH, but without the typical clinical symptoms of Cushing’s disease.

Researchers at the Tianjin Medical University General Hospital, in China, described the case of a 37-year-old woman who went to the hospital with complaints of palpitations and fatigue that had started a week earlier and were getting worse. She also mentioned that occasionally, she had an increase in the frequency and urgency to urinate.

She had previously gone to another hospital where she underwent a routine blood analysis. This revealed she had elevated white blood cell counts, particularly neutrophils, which is usually a sign of an infection. She was given antibiotics, but her condition did not improve.

On the visit to the second hospital, her white blood cell counts were still high and she still had neutrophilia. Because of this, “urinary tract infection, which is also one of the causes of palpitations and fatigue, could not be ruled out,” the researchers wrote.

She was given another type of antibiotic, but her white blood cell counts increased, and her palpitations and fatigue remained, prompting doctors to admit her for further treatment.

Her clinical examination did not reveal any new symptoms. New blood tests were done and, apart from neutrophilia and increased white blood cell counts, she had normal levels of several other inflammatory markers.

“We concluded that the increase in the neutrophil count was not related to infection,” the researchers wrote.

Doctors proceeded to examine the woman’s bone marrow for any signs of a blood disease that might explain her increased neutrophil levels. Findings showed normal function of the bone marrow, ruling out blood diseases.

In blood tests, doctors noted that ACTH and cortisol levels were high. This led them to check the adrenal glands with an ultrasound scan and the pituitary gland with an MRI scan.

Ultrasound scans found no abnormalities in the adrenal glands, but the MRI scan revealed masses in the small chamber where the pituitary gland is, called sella turcica, and in the area above it, the suprasellar region. These scans suggested the presence of pituitary tumor lesions.

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Eye exam revealed vision loss in left side of patient’s field of vision

The optic nerve, which transmits information from the eyes to the brain, passes very close to the pituitary gland and the area where the tumors were. In a likely consequence, an ophthalmological examination revealed the woman had loss of vision in the left side of her field of vision in both eyes.

She underwent surgery to remove the lesions, and the following analysis confirmed the diagnosis of pituitary SCAs and subclinical Cushing’s disease.

After surgery, her blood levels of neutrophils, white blood cells, and cortisol were back to normal, further confirming that the elevated number of neutrophils and white blood cells was connected to the increased levels of cortisol.

Although high white blood cell counts are often found in people with Cushing’s disease, the researchers noted that neutrophilia as an initial symptom in patients with subclinical Cushing’s disease is rare.

“The increase in the level of neutrophils following subclinical Cushing’s disease is an uncommon clinical phenomenon that is characterized by insignificant biochemical or clinical evidence of [high cortisol levels],” the researchers wrote.