An ominous cause of hirsutism: Adrenocortical carcinoma
Hirsutism is a common clinical condition seen in female patients of all ages. Classically, hirsutism has been considered a marker of increased androgen levels in females from increased production of androgens (i.e., testosterone) either by the adrenals or due to an ovarian disease.[1,2]
The ovarian causes of hyperandrogenism are polycystic ovarian syndrome (PCOS) and ovarian tumors. Adrenal causes include Cushing’s syndrome, androgen-producing tumors, and congenital adrenal hyperplasia (CAH), most commonly due to 21-hydroxylase deficiency. Hirsutism in prepubertal young girls is generally an ominous sign and could be the indicator of an ovarian or adrenal malignancy. One such cause is an adrenocortical carcinoma associated with late presentation and poor prognosis. Here we present vivid pictures of hirsutism in a young girl that led us to this diagnosis.
A 5-year-old girl from a rural part of eastern India was referred to our endocrine clinic for excess weight gain, height acceleration, and excess facial and body hair. Born out of a non-consanguineous marriage, the youngest of five siblings, the girl had an uneventful birth and developmental history, and she was well till about one year back. The parents accompanying her were normal looking, and none of the siblings had similar features. The weight gain and hirsutism had been progressing rapidly for the last one year.
On examination, she was a stocky girl with a moon face, facial plethora, central obesity, no stria, and excess facial and body hair [Figure 1] Her modified Ferriway Gallman score was 24/36. She appeared depressed and listless, and her abdomen was distended. She was 130 cm tall (+ 5.8 Standard deviation score [SDS] above age and sex height) and weighed 30 kgs (+ 6.6 SDS above age and sex weight). Her blood pressure was 170/100 mmHg (stage 2 hypertension for age) at admission, and her blood glucose values were elevated.
The initial blood work revealed a hemoglobin of 10.8 (N: 12-15g/dL), white blood cells of 10 (N: 4-11 x 109/L), with lymphopenia of 0.7 (N: 1.2- 3.5 × 109/L), an elevated alanine aminotransferase of 517 (N: 5-40 U/L), and lactate dehydrogenase of 818 (N: 110-220 U/L). Her serum potassium was 2.9 mmol/L (Ref range 3.5-5.5).
There was a strong suspicion of Cushing’s syndrome based on the above information. Accordingly, the workup and evaluation was planned as per guidelines,[3] and the initial hormonal workup revealed a raised 8 am cortisol at 38.8 mcg/dl (N: 2-25), which remained unsuppressed after an overnight dexamethasone administration (20.5 mcg/dl).
With the above screening tests in favor of Cushing’s syndrome and the clinical features of androgen excess, we decided to proceed with tests to determine the etiology. The plasma Adrenocorticotrophic hormone (ACTH) was not elevated at 10.5 pg/ml (N: 0-46), serum testosterone was >1600 ng/dl (N: 1-81), serum androstenedione >10 ng/ml (N: 0.3-3.5) and serum DHEAS was >1000 mcg/dl (N: 35-430).
These results supported the diagnosis of ACTH-independent Cushing’s syndrome. In addition, the co-secretion of cortisol and androgens were pointing toward an adrenal tumor which is common at this age in conjunction with androgen excess.[4]
A targeted computed tomography (CT) scan focusing on the adrenals was obtained, which showed a large 15 x 13 x 15 cm heterogeneous enhancing solid mass with calcification extending from the splenic hilum up to the renal hilum and infiltrating the left renal hilum [Figure 2]. Multiple deposits in the left supracolic omentum were also seen. The features were suggestive of a left adrenocortical malignant mass.
Adrenocortical carcinoma
While waiting for surgery, her blood pressure was controlled with increasing doses of tablets aldactone, ramipril, and prazosin. Blood glucose was managed with multiple insulin injections. Tab ketoconazole was added orally. Three weeks after the diagnosis, she finally underwent debulking surgery with open left adrenalectomy and extensive omental clearance and abdominal lymph node clearance. The mass was found infiltrating the spleen, and so a splenectomy was also performed simultaneously. The pathology results confirmed high-grade adrenocortical carcinoma of >10 cm with omental deposits (pT4MxNx). Histology showed a neoplasm arising from the adrenal gland, fulfilling both macroscopic (900 g and 15 * 14 * 8 cm) and nine of nine microscopic (Weiss) criteria for adrenocortical adenocarcinoma (high Fuhrman nuclear grade, more than five mitoses per 50 high-power fields, eosinophilic cytoplasm >90% of tumor cells, and necrosis [Figure 3a-c] [hematoxylin and eosin staining]. Extensive areas of necrosis were seen, along with capsular and vascular invasion.
Unfortunately, because of the late presentation and advanced disease, curative surgery was not possible, and the serum cortisol levels continued to be high postoperatively with recalcitrant hypokalemia. After a post-operative intensive care unit (ICU) stay of more than three weeks, she finally succumbed to the malignancy. These tumors are characterized by poor survival, especially in the context of distant metastases, large tumor volume, and high proliferation.[5]
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a
b
c
Conflicts of interest
There are no conflicts of interest.
ORCID iDs Pankaj Singhania: https://orcid.org/0000-0002-9392-3300 Rana Bhattacharjee: https://orcid.org/0000-0002-0362-5036 Subhankar Chowdhury: https://orcid.org/0000-0002-5853-5249
Pankaj Singhania®, Rana Bhattacharjee®, Subhankar Chowdhury®
Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research/SSKM Hospital, Kolkata, West Bengal, India
Correspondence to: Pankaj Singhania, E-mail: drpankaj007@hotmail.com
References
1. Rittmaster RS. Hirsutism. Lancet 1997;349: 191-5.
2. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med 2005;353:2578-88.
3. Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndrome. N Engl J Med 2017;376: 1451-9.
4. Lodish MB, Keil MF, Stratakis CA. Cushing’s syndrome in pediatrics: An update. Endocrinol Metab Clin North Am 2018;47:451-62.
5. Cecchetto G, Ganarin A, Bien E, Vorwerk P, Bisogno G, Godzinski J, et al. Outcome and prognostic factors in high-risk childhood adrenocortical carcinomas: A report from the European cooperative study group on pediatric rare tumors (EXPERT). Pediatr Blood Cancer 2017;64. doi: 10.1002/pbc. 26368.
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How to cite this article: Singhania P, Bhattacharjee R, Chowdhury S. An ominous cause of hirsutism: Adrenocortical carcinoma. Indian J Cancer 2024;61:350-1. Submitted: 17-Jan-2022 Revised: 01-Mar-2022
Accepted: 05-Apr-2022 Published: 13-Jul-2024
@ 2024 Indian Journal of Cancer | Published by Wolters Kluwer -Medknow