Woman’s case highlights ‘challenges’ seen in cyclic Cushing’s syndrome
Patient, 43, found to have both pituitary tumor and thyroid cancer
A pituitary tumor and thyroid cancer were found in a 43-year-old woman with cyclic Cushing’s syndrome, a form of Cushing’s in which cortisol levels rise and fall over time, according to a case report from China.
The researchers noted that such fluctuations in a person’s cortisol levels can throw off test results, and make it difficult for clinicians to accurately identify the condition — and treat it correctly.
“This case underscores the challenges that clinicians face in diagnosing and treating [cyclic Cushing’s syndrome],” the team wrote. “It is crucial for clinicians to carefully screen and, when necessary, repeat tests to ensure an accurate diagnosis.”
Titled “Cyclic Cushing’s syndrome associated with cadherin-23 and multiple endocrine neoplasia type 1 mutations accompanied by bilateral primary papillary thyroid carcinoma,” the resulting study was published in the Polish Archives of Internal Medicine.
Cushing’s syndrome comprises several conditions driven by elevated levels of the hormone cortisol. It is commonly caused by a tumor in the brain’s pituitary gland, which is known as Cushing’s disease. Such tumors release excessive amounts of adrenocorticotropic hormone, or ACTH, which stimulates cortisol production. Less frequently, Cushing’s is ectopic, or caused by ACTH-producing tumors in other parts of the body.
Clinicians cite risk of misdiagnosis in cyclic Cushing’s syndrome
Here, a team led by researchers at The First Affiliated Hospital of Shandong First Medical University described the complex case of a woman who sought treatment at the hospital due to back pain.
Initial MRI scans revealed fractures in three vertebrae, or spine bones, while bone density testing showed she had osteoporosis, a condition that causes bone to become weak and more susceptible to fractures.
Further evaluation of the woman’s medical history indicated she had severe high blood pressure, known as hypertension, and poorly controlled diabetes. She’d also experienced physical changes, including central obesity, abdominal stretch marks, and infrequent menstrual periods. Additionally, the woman had bipolar disorder, a mental health condition that causes extreme mood shifts.
Considering her clinical manifestations, the team of doctors suspected Cushing’s syndrome. Laboratory work showed she had elevated cortisol and ACTH levels. Both low- and high-dose dexamethasone tests failed to decrease her cortisol levels, confirming the diagnosis.
A small-sized tumor was found in the woman’s pituitary gland. However, its size and the fact that the high-dose dexamethasone test did not reduce cortisol levels led researchers to initially suspect ectopic Cushing’s. Further analysis indicated the patient also had cancer in the thyroid gland, which is responsible for producing hormones that regulate several bodily functions.
The woman’s blood pressure, blood sugar, and cortisol levels dropped without treatment. Upon subsequent inquiry on the woman’s medical history, it was found that she had been having episodic symptoms every four to five months, each lasting one week to one month, since 2014. This suggested she had cyclic Cushing’s syndrome, according to the team.
Diagnosing [cyclic Cushing’s] is challenging because of the periodic fluctuations in cortisol levels, and abnormal results from dexamethasone suppression tests can lead to misdiagnosis.
Four months later, when she experienced another episode of facial swelling, hypertension, and increased blood sugar, the researchers performed additional tests. These included petrosal sinus sampling to measure ACTH levels in the veins that carry blood from the pituitary gland, and desmopressin stimulation, both of which can help differentiate Cushing’s disease from ectopic Cushing’s.
The results confirmed that ACTH levels were higher in the blood coming from the pituitary gland than in the rest of the body, confirming the diagnosis of cyclic Cushing’s disease.
“Diagnosing [cyclic Cushing’s] is challenging because of the periodic fluctuations in cortisol levels, and abnormal results from dexamethasone suppression tests can lead to misdiagnosis,” the researchers wrote.
Genetic analysis showed both CDH23 and MEN1 gene mutations
The woman underwent a minimally invasive surgery to remove the pituitary tumor, after which her blood ACTH and cortisol levels returned to normal. Her Cushing’s symptoms gradually eased, and she stopped taking medications for hypertension and diabetes. Four months later, she underwent surgery to remove the thyroid gland.
Genetic analysis revealed she had mutations in the CDH23 and MEN1 genes. Mutations in the CDH23 gene have been associated with tumors in the pituitary gland and identified in people with Cushing’s disease, while people with MEN1 mutations may develop thyroid cancer.
“These concurrent genetic alterations may represent plausible pathogenic [disease] mechanisms underlying the co-manifestation of [cyclic Cushing’s] and synchronous primary [thyroid cancer] in our patient, though the precise molecular interplay warrants further mechanistic investigation,” the researchers wrote.
Given the high recurrence rate of cyclic Cushing’s, and to further understand the CDH23 and MEN1 disease-causing mechanisms, the researchers planned to continue monitoring the woman over the long term.
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