Knee pain tied to obesity was 1st sign of woman’s Cushing’s disease

Pituitary surgery proved successful in reducing cortisol levels, per case study

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by Andrea Lobo |

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A 66-year-old woman in South America was diagnosed with Cushing’s disease after being referred for a consultation with a specialist for obesity associated with pain and reduced mobility in the right knee, according to a new case study.

Titled “From Knee Pain Consultation to Pituitary Surgery: The Challenge of Cushing Disease Diagnosis,” the study was published in the journal JCEM Case Reports.

After she sought treatment, further testing of this patient indicated that she had low bone density consistent with osteoporosis, central obesity, diabetes, and high blood pressure.

According to the researchers, recognizing the combination of these symptoms as valuable clinical signs is key in identifying Cushing’s, a rare disease that’s caused by excess production of the hormone cortisol.

“Understanding the evolving nature of [Cushing’s disease] signs highlights the importance of vigilance during medical examinations, prioritizing the diagnostic focus, and enabling prompt initiation of treatment,” the team wrote.

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Cushing’s disease is a specific type of Cushing’s syndrome, a broader umbrella term that includes any condition caused by high levels of cortisol (hypercortisolism). Cushing’s disease generally is caused by a tumor in the brain’s pituitary gland called a pituitary adenoma. These tumors release high amounts of adrenocorticotropic hormone (ACTH), a molecule that signals the adrenal glands, located atop the kidneys, to produce cortisol.

If left untreated, Cushing’s disease is associated with a poor prognosis, with an estimated five-year survival rate of 50%.

“However, surgical removal of a pituitary adenoma can result in complete remission, with mortality rates similar to those of the general population,” the researchers wrote.

In this report, the researchers described the case of a woman in Colombia who was diagnosed with Cushing’s disease after being referred to endocrinology for obesity associated with right knee arthropathy — a type of joint disease that can cause swelling, pain, and a reduction in the range of movements.

An initial physical examination also revealed she had high blood pressure, or hypertension, and a proportion of glycated hemoglobin (HbA1c) of 6.9%, consistent with her previous history of type 2 diabetes mellitus. HbA1c reflects the proportion of hemoglobin — the protein that transports oxygen in red blood cells — that is bound to blood sugar; a proportion of HbA1c equal to or greater than 6.5% indicates the presence of diabetes.

The woman also complained of muscle weakness in the limbs.

Given her age, she was evaluated for osteoporosis, which was confirmed by tests showing she had reduced bone density. Osteoporosis causes bones to become weak and brittle, and occurs more frequently in older women after menopause.

Considering all her symptoms, the patient was suspected of having hypercortisolism. Laboratory tests revealed her late-night salivary cortisol levels were high. Her blood cortisol levels also remained high after a low-dose dexamethasone suppression test, confirming the Cushing’s diagnosis.

The patient’s cortisol levels did drop after a high-dose dexamethasone suppression test, indicating she had an ACTH-dependent form of hypercortisolism, consistent with the possibility of Cushing’s disease.

The diagnosis was confirmed by an MRI scan revealing the presence of a 4 mm adenoma in her pituitary gland, prompting the decision to remove the tumor by transsphenoidal surgery — a minimally invasive surgery commonly used to remove pituitary tumors through the nose.

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One month after surgery, the woman’s cortisol levels were below the normal limit. After one year, her recovery was deemed satisfactory.

However, her blood pressure remained high, and she developed diabetes insipidus. This condition is marked by an imbalance of fluids in the body that can cause excessive thirst and a high production of urine. She also developed hypothyroidism, which occurs when there is insufficient production of thyroid hormones.

At the latest follow-up, her HbA1c levels were within the non-diabetes range, below 5.7%. During follow-up, her medications included prednisolone, a corticosteroid used to help normalize cortisol levels, as well as medications to treat high blood pressure, diabetes, and hypothyroidism.

The researchers noted that “moving forward, it is important to emphasize certain clinical signs and symptoms for diagnosing [Cushing’s disease].” In particular, the team noted the combination of osteoporosis, obesity, diabetes, and hypertension.