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Urology Case Reports
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Alan Partin, MD, PHD Alan J. Wein, MD, PhD (hon) Editora-in-Chief
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Isolated DHEAS production by an adrenal neoplasm: Clinical, biochemical and pathologic characteristics
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Srinath-Reddi Pingle ª, Fatima Jalil b, Danielle Millar b, Carl D. Malchoff}, Benjamin T. Ristau ”, **
a University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT, 06030-2202, USA
b Division of Endocrinology and Metabolism, 263 Farmington Avenue, University of Connecticut School of Medicine, Farmington, CT, 06030-2202, USA
” Division of Urology, UConn Health, 263 Farmington Avenue, Farmington, CT, 06030-8073, USA
ARTICLE INFO
ABSTRACT
Androgen-secreting adrenal neoplasms have a low incidence, usually secrete multiple hormones, and may pre- sent with hirsutism, acne, and alopecia. We report an exceedingly rare case of a purely dehydroepiandrosterone- sulfate (DHEA-S) secreting adrenal neoplasm found incidentally on cross sectional imaging. The clinical, biochemical, and pathologic findings of this neoplasm are described.
Introduction
Adrenal neoplasms are often found incidentally during imaging studies performed for other reasons. The prevalence of these so-called “incidentalomas” ranges from 1.4% to 15% and increases with age. The vast majority (>90%) of adrenal neoplasms are benign, nonfunc- tional adenomas. Of the remaining functional adrenal tumors, most secrete aldosterone, cortisol, or catecholamines. Androgen or estrogen secreting incidentalomas are much less common and raise suspicion for adrenocortical carcinoma.1,2
Purely androgen secreting adrenal adenomas are rare, but have a higher incidence in women. Clinically, these tumors may present with hirsutism of the face, chest, and back, as well as acne. Clitoral enlarge- ment, irregular menses, and hypertension are less frequent. Serum concentrations of testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and androstenedione can be elevated in these tumors that usually overproduce more than a single androgen.1,2 To our knowledge, isolated DHEA-S production by an ad- renal neoplasm has not been reported. We describe the clinical, biochemical and pathologic features of an adrenal neoplasm with iso- lated DHEA-S production and otherwise normal serum concentrations of other androgens, cortisol and aldosterone.
Case presentation
A 57 year old G4P4 post-menopausal Indian female being evaluated for chronic ileitis was incidentally found to have a 4 cm right adrenal mass on CT scan. Her past medical history was notable for type 2 dia- betes mellitus, Crohn’s colitis, and hypertension. She had no history of amenorrhea prior to menopause. She denied any dietary supplements containing DHEA or DHEA-S. She reported generalized hair thinning on the scalp. She denied deepening of voice, acne and excessive hair growth on the face, back, or chest. Physical examination confirmed mild hair thinning to the crown and frontal scalp. There was no clitoromegaly.
Biochemical evaluation included a serum DHEA-S concentration on two separate occasions of 671 and 741 mcg/dL (nl. 26-200). Other serum androgen concentrations were normal including a free testos- terone of 2.3 pg/mL (nl. 0.6-3.8); DHEA of 2.41 ng/ml (nl. 0.60-5.73); and androstenedione of 0.529 ng/ml (nl. 0.130-0.820). Circulating concentrations of cortisol, aldosterone, estrone, estradiol, and meta- nephrines were within normal limits. Plasma ACTH concentration was not suppressed; serum FSH and LH concentrations were appropriately elevated for the post-menopausal state.
CT imaging revealed a heterogeneous 4 cm right adrenal mass that contained several areas measuring less than 8.7 Hounsfield units on non- contrast imaging. An MRI demonstrated a 4.1 x 3.3 cm heterogeneously enhancing adrenal mass abutting the right hepatic lobe (Fig. 1A). Arterial phase imaging showed delineation between the adrenal tumor
Abbreviations: DHEA, Dehydroepiandrosterone; DHEA-S, Dehydroepiandrosterone-sulfate; ACC, Adrenocortical Carcinoma; ACTH, Adrenocorticotropic Hormone; FSH, Follicle Stimulating Hormone; LH, Luteinizing Hormone.
* Corresponding author.
E-mail address: benristaumd@gmail.com (B.T. Ristau).
https://doi.org/10.1016/j.eucr.2020.101148
Received 12 February 2020; Accepted 22 February 2020
2214-4420/ 2020 The
INCHES
CM
-
2
-
A
N
01
4cm right adrenal mass
9
A
B
A
0
A
B
706
DHEA-S (MCG/DL)
274
132
91
Normal 26-200 MCG/DL
2 8
PRE-OP
19 HOURS POST-OP
1 MONTH POST-OP
5 MONTH POST-OP
11 MONTH POST-OP
and the liver capsule.
The size of the lesion and the biochemical abnormality were considered risk factors for malignancy, and robotic assisted laparoscopic right adrenalectomy was performed. There was no evidence of adjacent organ involvement intraoperatively. The post-operative course was un- complicated, and the patient was discharged on the second post- operative day.
Grossly, the right adrenal gland weighed 46 g and measured 5.8 x 4.5 × 3.7 cm (Fig. 1B). Histologically, it appeared as a partially encap- sulated nodule (Fig. 2A) with dilated vasculature composed of cords and islands of cells with mild focal pleomorphism separated by a reticulin framework with uniform thickness and size (Fig. 2B). There was no evidence of vascular invasion or anaplasia, and the tumor cells showed a
low mitotic rate consistent with an adrenal adenoma.
Post-operatively the serum DHEA-S concentration fell to 274 mcg/dl at 19 hours post-adrenalectomy with the mean pre-operative concen- tration having been 706 mcg/dL. At 1 month post-adrenalectomy DHEA- S had fallen to 91 mcg/dL and remained normal at 11 months of follow- up (Fig. 3). Clinically, there was thickening of her scalp hair following resection of the adrenal adenoma.
Discussion
Androgen secreting adrenal neoplasms are rare. To our knowledge, we report the first description of isolated DHEA-S production by an adrenal neoplasm.
The serum concentration of DHEA-S was more than 3 times the upper normal limit suggesting that the 4 cm adrenal mass was the source of the DHEA-S. The serum half-life of DHEA-S is between 7 and 22 hours. The isolated DHEA-S production by the adrenal neoplasm was confirmed by the rapid decrease in the DHEA-S serum concentration by 60% within 19 hours of resection and subsequent normalization. Adrenal vein sampling was not performed pre-operatively, since the relatively long DHEA-S half-life would likely have precluded finding a central to peripheral gradient.
The pre-operative normal concentrations of androstenedione, DHEA, and testosterone demonstrate that this neoplasm was producing only DHEA-S and no other androgens. Although rare, most androgen secreting adrenal neoplasms produce multiple androgens.1,2 The path- ologic findings suggest that this was a benign adenoma.
Most adrenal tumors are found incidentally on cross-sectional im- aging. The diagnosis and management of such incidental findings is dependent on tumor size, imaging features, and hormone production. All adrenal incidentalomas should undergo functional workup at initial diagnosis since up to 10% may exhibit excess hormone secretion.3,4
Radiologic evaluation can provide insight into the threat posed by
incidentally detected adrenal masses. Tumor size is important since only 2% of adrenal masses less than 4cm in size are malignant while up to 25% of tumors greater than 6cm represent adrenocortical carcinoma (ACC).5 In this case, we used MRI as an adjunct to help identify the soft tissue plane between the adjacent liver and the right adrenal gland, so that we were confident that the adrenal mass could be removed lapa- roscopically. Management decision-making for this lesion included the size greater than 4 cm and androgen production that increased the risk of adrenal cortical carcinoma necessitating resection for definitive diagnosis.
Conclusion
We describe the clinical, biochemical, and pathologic findings of an exceedingly rare adrenal adenoma with isolated DHEA-S production.
Consent
N/A.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
None.
References
1. Cordera F, Grant C, Van Heerden J, et al. Androgen-secreting adrenal tumors. In: Surgery. 2003. https://doi.org/10.1016/S0039-6060(03)00410-0.
2. Moreno S, Montoya G, Armstrong J, et al. Profile and outcome of pure androgen- secreting adrenal tumors in women: experience of 21 cases. Surgery. 2004. https:// doi.org/10.1016/j.surg.2004.06.046.
3. Zeiger MA, Thompson GB, Duh QY, et al. American Association of clinical endocrinologists and American Association of endocrine surgeons medical guidelines for the management of adrenal incidentalomas: executive summary of recommendations. Endocr Pract. 2009;15(5):450-453. https://doi.org/10.4158/ EP.15.5.450.
4. Grumbach MM, Biller BMK, Braunstein GD, et al. Management of the clinically inapparent adrenal mass (“incidentaloma”). In: Annals of Internal Medicine. 2003. https://doi.org/10.7326/0003-4819-138-5-200303040-00013.
5. Sturgeon C, Shen WT, Clark OH, Duh QY, Kebebew E. Risk assessment in 457 adrenal cortical carcinomas: how much does tumor size predict the likelihood of malignancy? J Am Coll Surg. 2006. https://doi.org/10.1016/j.jamcollsurg.2005.11.005.