Avascular Necrosis of Femur as a Complication of Cushing’s Syndrome Due to Adrenocortical Carcinoma
The American Surgeon™ 2023, Vol. 89(6) 2701-2704 @ The Author(s) 2022 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/00031348221129510
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Atul Anand, MBBS’ OD, Chandan K. Jha, MCh’, Prashant K. Singh, MS’, Upasana Sinha, MD2, Abhirami Ganesh, MD3, and Punam P. Bhadani, MD3
Abstract
A wide range of clinical presentations for Cushing’s syndrome has been described in the literature. Avascular necrosis of femur is a well-recognized complication of excessive glucocorticoid administration, but its occurrence due to en- dogenous hypercortisolism is rare. We present the case of a 47-year-old male who presented to us with severe low backache, hypertension, uncontrolled diabetes, and other signs and symptoms of Cushing’s syndrome. Hormonal evaluation confirmed hypercortisolism, and a contrast-enhanced computed tomography of the abdomen localized the lesion in the left adrenal gland. Assessment of the severe low back ache-the main symptom for which the patient came to us-by magnetic resonance imaging of the spine and pelvis revealed avascular necrosis of bilateral femoral heads. Resection of the left adrenal gland revealed an adrenocortical carcinoma. To the best of our knowledge, this is only the second case where an adrenocortical cancer leading to hypercortisolism is the cause of avascular necrosis of hip.
Keywords
hypercortisolism, Cushing’s syndrome, avascular necrosis of femur, adrenocortical carcinoma, ischemic hip disease
Introduction
Avascular necrosis (AVN) of the femur, also referred to as the “coronary hip disease,” is a well-recognized com- plication of excessive glucocorticoid administration.1,2 However, its occurrence due to endogenous hyper- cortisolism is uncommon-with less than 20 cases re- ported to date. Among these cases, there is an almost equal preponderance to a disease process either in the pituitary or adrenals. Further, the pathology in the adrenals could be either an adenoma or hyperplasia. However, we could find only one case where the cause of AVN of the femur was an adrenocortical carcinoma (ACC) secreting cortisol-not an adenoma or hyperplasia.3 To our knowledge, this is the second case of AVN of femur due to endogenous hy- percortisolism caused by an ACC.
Case Presentation
We report the case of a 47-year-old male who presented to us with severe backache and pain in the bilateral hip. On evaluation, he had persistently elevated blood pressure, uncontrolled diabetes, recurrent fungal infections of the skin, facial puffiness, prominent supraclavicular pad of fat, and centripetal obesity (Figure 1A and B). The results of the overnight dexamethasone suppression test and
low-dose dexamethasone suppression test were unsup- pressed. Serum adrenocorticotrophic hormone level was low, indicating an adrenal source of cortisol production. Contrast-enhanced computed tomography of the abdomen with adrenal protocol revealed a 7 cm × 7 cm × 5.8 cm lobulated mass with heterogeneous enhancement and decreased absolute and relative washout (Figure 2A and B), without any involvement of adjacent organs or inferior vena cava, c T2 N0 M0 (clinical stage II as per the American Joint Committee on Cancer, AJCC eighth edition staging for adrenocortical carcinomas). Evaluation with MRI pelvis and lumbosacral spine revealed avascular necrosis of bilateral femur heads with sacral insufficiency fracture (Figure 2C). 24-hour urinary-free metanephrine
“Department of General Surgery, All India Institute of Medical Sciences, Patna, India
2Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna, India
3Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Patna, India
Corresponding Author:
Chandan K. Jha, MCh, Department of General Surgery, All India Institute of Medical Sciences, Patna, Phulwarisharif, Patna 801507, India. Email: cjhadmch@gmail.com
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and nor-metanephrine were normal. The patient un- derwent left open transperitoneal adrenalectomy (Figure 2D). Histopathology revealed a lobulated tumor mea- suring 10x6x4 cm weighing 160 g, invading the adrenal capsule focally (pT3N0, pathological stage III, as per AJCC eighth edition). The tumor showed areas of ne- crosis, with cells arranged predominantly in diffuse and nested patterns. Cells showed pleomorphism, prominent nucleoli, and eosinophilic cytoplasm. Less than 25% of cells had a clear cytoplasm (Figure 3A-C), features consistent with a diagnosis of adrenocortical carcinoma
according to the modified Weiss criteria. Occasional mitotic figures were noted, less than 20 per 50 high power field (histologically low grade).
Discussion
To the best of our knowledge, this is only the second case where AVN was caused due to hypersecretion of cortisol from an ACC. How cortisol excess causes, AVN remains unknown. AVN of the femoral head can be a presenting feature of hypercortisolism-both endogenous and
-
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exogenous. It has also been described in past as “ischemic hip disease.”4 This description comes from the recogni- tion that excess cortisol causes fat embolization within the micro vessels supplying the femoral heads and fat ac- cumulation within the medullary cavity, thus increasing the marrow pressure and compromising the blood supply to femoral heads.5,6 Another possible cause is arterio- sclerosis, secondary to steroids that induce hypertension and insulin resistance.7
Although osteonecrosis of the femoral head induced by exogenous long-term glucocorticoid excess is a well- reported entity, the rarity of its association with endog- enous hypercortisolism may be because of the patient presenting with other signs and symptoms of the cushingoid stigmata, treatment of which inhibit the progression of the bony lesion.8 Endogenous hypercortisolism causing AVN may have its origin in the pituitary (Cushing’s disease), adrenals, or an ectopic site. Among adrenal causes, a thor- ough literature review of cases reported to date attribute cortisol hypersecretion mainly to an adenoma or hyperplasia. Contrary to this, in our case, the final histopathology re- ported an adrenocortical carcinoma (ACC). ACC is a rare neoplasm with an annual incidence of approximately .72/ million, mainly affecting individuals in the 40-50-year age group.9,10 Only half of ACCs are functional.11 Functioning tumors tend to be poly-hormonal, with most of them (~30%) secreting cortisol-the source of endogenous hyper- cortisolism.12 ACC carries a poor prognosis with a reported 5-year cancer specific survival of around 38%.13 In an at- tempt to prognosticate the disease, nomograms have been developed predicting the overall survival (OS) and cancer specific survival (CSS), taking into account various factors like age at diagnosis, histologic grade, stage of the disease, and chemotherapy status, with tumor stage showing a strong association across different studies. 14
Conventional radiography tends to miss the early changes of avascular necrosis. Magnetic resonance im- aging (MRI) remains the gold standard for diagnosing AVN at an early stage when therapeutic interventions could be helpful.15
Similar to other cases reported in the literature, the initial presenting symptoms were attributed to another pathology in
our patient as well. In patients presenting with avascular necrosis of the hip with unknown etiology (no risk factors for bone ischemia or history of trauma), rare causes for os- teonecrosis, such as endogenous hypercortisolism, should be suspected and should prompt consideration of a work-up.
Conclusion
Cushing’s syndrome presents itself with a myriad of non- specific signs and symptoms. The clinician must be vigilant to recognize these seemingly unrelated symptoms and not be swayed to an alternate diagnosis without a careful hormonal work-up.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with re- spect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iD
Atul Anand @ https://orcid.org/0000-0002-8765-4140
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