Osteoporosis associated with Cushing’s Syndrome

Journal of Medical Case Reports

Case Presentation

A 20-year-old Brazilian man presented to the hospital with lower back pain for the past 8 months, however, he hadn’t suffered any injuries. The doctors performed an X-ray of his spine. The X-ray showed several abnormalities, so doctors referred him to the Orthopedics Service of the Hospital of the Federal University of Juiz de Fora.

The X-ray spine revealed a significant weakening of the bone structures, a curved spine leaning towards the left, and a decrease in the height of the lumbar vertebrae. There were also partial collapses of the vertebrae at the levels of T12, L1, L2, L3, and L5. The same abnormalities were visible in a posterior magnetic resonance imaging (MRI) scan. They also conducted bone scintigraphy, which did not show any abnormal blood flow or hyperemia in the thoracolumbar spine. However, later images of the scan revealed higher tracer uptake in the lumbar spine (vertebrae T10-T12, L2-L4), which had a nonspecific appearance. This caused doctors to suspect the presence of bone and joint disorders, or ankylosing spondylitis. Thus, they prescribed the patient orthopaedic braces and recommended physical therapy.

Further Testing

Doctors at the Orthopedics Service of the Hospital of Federal University of Juiz de Fora; further referred him to the Osteometabolic Diseases outpatient clinic of the Endocrinology and Rheumatology Services of the same hospital.

Physical Examination

During the physical examination, doctors found no areas of pigmented skin or moles, however, they observed broad purplish streaks on the upper limbs and abdomen. The patient also had increased fat on his face in the temporal region. There were bruises on the limbs, along with decreased muscle mass in the arms and thighs, central obesity, and a curved spine. His blood pressure was 150/90 mmHg, his body mass index (BMI) was 26.09 kg/m2, and his waist circumference was 99 cm. Although his height was 1.55 meters.


Doctors conducted further tests at this clinic, including dual-energy X-ray absorptiometry (DEXA). The results revealed low bone mineral density (BMD) in the lumbar spine, femoral neck, and total femur when compared to the Z Score values. Based on these findings, the doctors diagnosed the patient with osteoporosis. They initiated treatment, which included a weekly dose of 7000 IU of vitamin D due to insufficient levels of vitamin D3, along with a weekly dose of the bisphosphonate alendronate (70 mg). The patient had a previous history of syphilis and surgical removal of perianal condyloma. He also told the doctors that his maternal uncle had died from systemic sclerosis. The patient denied consuming alcohol and denied current or past smoking.

Furthermore, doctors performed a computed tomography (CT) scan of the abdomen with an adrenal protocol. This showed the presence of nodules in the left and right adrenal glands, measuring 1.5 cm and 0.6 cm, respectively. The nodules had a density of about 30 Hounsfield units (HU) and showed enhancement after contrast injection. Doctors administered adrenal vein catheterization, however, it was unsuccessful in enhancing the lesions due to high serum cortisol levels. The catheter placement, as confirmed by the selectivity index, indicated good positioning.

A magnetic resonance imaging (MRI) scan of the upper abdomen conducted by the doctors, revealed thickened nodules in the left adrenal gland, suggesting the presence of an adenoma. The scan also showed a small nodular thickening in the right adrenal gland.

Management: Cushing’s Syndrome

The doctor prescribed medication to the patient. This included Ketoconazole, vitamin D, and ramipril to manage Cushing’s syndrome and secondary hypertension. Additionally, they added zoledronic acid as a replacement for alendronate due to the severity of osteoporosis.

Considering the patient’s age, clinical presentation, and imaging findings; doctors suspected primary pigmented nodular adrenocortical disease (PPNAD) or cancer. After discussions with the patient and family, doctors decided to perform surgical resection of the left adrenal gland to investigate the possibility of malignancy and prevent bilateral adrenalectomy, which could lead to permanent adrenal insufficiency. This allowed for the analysis of the removed gland.

The macroscopic analysis of the surgically removed adrenal gland revealed a multinodular gland surrounded by adipose tissue, weighing 20 grams and measuring 9.3 cm x 5.5 cm x 2.0 cm. The gland showed expansion of the zona fasciculate, with the formation of multiple nonencapsulated nodules composed of polygonal cells. These cells had abundant cytoplasm and a reduced lipid content. There were no signs of necrosis or active cell division. Based on these findings, doctors suggested the diagnosis of cortical-pigmented micronodular hyperplasia of the adrenal gland.

Thus, doctors decided to conduct genetic testing for mutations in the PRKAR1A, PDE11A, PDE8B, and PRKACA genes. This was done to determine the need for contralateral adrenalectomy or long-term corticosteroid therapy. However, this genetic analysis was not available.

Cushing’s Syndrome

Cushing’s syndrome can be caused by factors outside the body (exogenous) or within the body (endogenous). In this case, the syndrome was endogenous and characterized by independent ACTH hypercortisolism. The patient experienced typical changes, such as severe osteoporosis, and high blood pressure. Osteoporosis in Cushing’s syndrome occurs due to decreased bone formation, loss of bone cells, and increased reabsorption caused by excess cortisol binding to bone cells. Excess cortisol also affects vitamin D metabolism, parathyroid hormone secretion, calcium absorption, growth hormone release, and body mass.

Research has shown that a large number of individuals with Cushing’s syndrome experience bone loss, osteopenia, and osteoporosis. Fragility fractures are also common and can have an adverse impact on quality of life. Diagnosing Cushing’s syndrome is challenging due to various factors, including physiological states of hypercortisolism, corticosteroid use, and the increasing incidence of diabetes and obesity in the general population. Several tests are used to confirm this disorder, such as measuring cortisol levels over 24 hours, salivary cortisol at night, and cortisol levels after suppression with dexamethasone.

Further tests are performed to determine the cause of the disorder, including measuring ACTH levels and performing adrenal CT scans. In this case, the patient’s ACTH levels were suppressed, indicating independent ACTH action. The CT scan revealed bilateral adrenal nodules.

Differential Diagnosis

The main differential diagnoses for bilateral adrenal hyperplasia include primary bilateral macronodular adrenal hyperplasia, McCune-Albright syndrome (MAS), bilateral primary pigmented nodular hyperplasia (PPNAD), and adrenal hyperplasia secondary to long-term adrenal stimulation in patients with Cushing’s disease or ectopic ACTH production. Primary macronodular adrenal hyperplasia typically occurs in women aged 50–60 years and may be sporadic or familial. It can be treated with beta-blockers or GnRH agonists. A bilateral adrenalectomy may be needed.

McCune-Albright syndrome (MAS) is caused by activating mutations in the GNAS1 gene and is characterized by hyperfunction in multiple tissues. In some cases, it can lead to adrenal adenomas and Cushing’s syndrome.

PPNAD is characterized by small bilateral pigmented nodules and may be associated with the Carney complex. Cortisol levels can help differentiate PPNAD from other adrenal conditions. Carney complex is a multiple neoplastic syndromes that involves various tumours, including PPNAD.

Adenomas are usually small and unilateral, while carcinomas are larger and may be bilateral. Carcinomas are more common in children and adolescents and can cause both hypercortisolism and hyperandrogenism.

Conclusion: Cushing’s Syndrome

In conclusion, diagnosing Cushing’s syndrome can be challenging due to the overlapping symptoms. Various tests are used to confirm hypercortisolism and determine its cause. Treatment depends on the diagnosis and can range from medications to surgery.


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