Cushing’s syndrome in a 17-year-old female teenager secondary to a unilateral right adrenal adenoma: A case report

Andrew E Edo; Osariemen A Osunbor

doi:10.4103/ajem.ajem_2_22

CASE REPORT

Year : 2022 | Volume : 12 | Issue : 1 | Page : 56-59

Cushing’s syndrome in a 17-year-old female teenager secondary to a unilateral right adrenal adenoma: A case report

Andrew E Edo¹, Osariemen A Osunbor²
¹ Department of Internal Medicine, University of Benin/University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
² Department of Internal Medicine, Central Hospital, Benin City, Edo State, Nigeria

Date of Submission	18-Mar-2022
Date of Decision	24-Jul-2022
Date of Acceptance	25-Jul-2022
Date of Web Publication	02-Sep-2022

Correspondence Address:
Dr. Osariemen A Osunbor
Department of Internal Medicine, Central Hospital, Benin City, Edo State
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajem.ajem_2_22

Abstract

Cushing’s syndrome is a rare endocrine disorder in the pediatric population. We report a case of a 17-year-old female Nigerian who presented with a 10 months history of progressive weight gain, amenorrhea, facial hair, and striae. She had not used oral contraceptive or steroids. Physical examination revealed an obese teenager with moon-like facies. Blood pressure was 150/90 mmHg. There were widespread striae over the back, upper arms, and thighs. The clinical diagnosis was Cushing’s syndrome. Urine free cortisol was 274.37 µg/24 h (4.3-56 µg/24 h). Plasma cortisol levels before and after dexamethasone suppression were 609.63 mmol/L and 578.71 mmol/L (normal value: <240.61 mmol/L), respectively. Plasma ACTH was 7.8 pg/mL (2.8-64.6 pg/mL). Abdominal magnetic resonance imaging (MRI) scan revealed a right adrenal mass showing mild enhancement on post-contrast. Brain MRI was normal. A right laparoscopic adrenalectomy was done. By 16 weeks post-surgery, patient’s menstrual cycle had resumed. The moon-like facies and striae were largely resolved.

Keywords: Adrenal adenoma, cortisol, Cushing’s syndrome, laparoscopic adrenalectomy

How to cite this article:
Edo AE, Osunbor OA. Cushing’s syndrome in a 17-year-old female teenager secondary to a unilateral right adrenal adenoma: A case report. Afr J Endocrinol Metab 2022;12:56-9

How to cite this URL:
Edo AE, Osunbor OA. Cushing’s syndrome in a 17-year-old female teenager secondary to a unilateral right adrenal adenoma: A case report. Afr J Endocrinol Metab [serial online] 2022 [cited 2023 Jun 10];12:56-9. Available from: http://www.ajemjournal.org/text.asp?2022/12/1/56/355332

Introduction

Cushing’s syndrome is a rare disease caused by overproduction and secretion of cortisol by the adrenal glands. It may result from tumor of the adrenal glands, lungs, or pituitary glands. Cushing’s syndrome is even rarer in the pediatric population. In a nationwide cohort study of all Danish citizens aged 0–20 years from 1977 to 2012, only a total of 40 pediatric patients with Cushing’s syndrome were reported, yielding an annual incidence of 0.89 cases/10⁶ populations.^[1] Of the nine cases of Cushing’s syndrome treated between 1976 and 1996 at the Royal Children’s Hospital, Melbourne, Australia, only one of them was a case of adrenal adenoma.^[2] Of 12 patients aged 7.6–17.8 years with Cushing’s syndrome who were admitted to St Bartholomew’s Hospital between 1978 and 1993, only one of them had adrenal adenoma.^[3] We report a case of a 17-year-old female Nigerian who was managed for Cushing’s syndrome from an adrenal adenoma.

Case report

A 17-year-old female teenager presented to the Endocrinology Clinic in Benin City with history of progressive weight gain, amenorrhea, facial hair, and striae, all of 10 months duration. There was no abdominal distension. She had not used oral contraceptive or steroids in any form prior to presentation. She initially presented to the gynecologist for amenorrhea and had pregnancy test done which was negative. She was not previously known to have hypertension.

Physical examination revealed a teenager, with moon-like facies, obese (weight 78 kg, height 1.6 m², BMI = 31.2 kg/m²), not pale, and had no pedal edema. Her pulse rate was 90 beats/min, regular with normal volume. Blood pressure was 150/90 mmHg. The first and second heart sounds were heard. The other systems were essentially normal. The clinical diagnosis was Cushing’s syndrome.

Results of investigations

Urinalysis showed clear urine, amber with a pH of 7.2, and a specific gravity of 1.015. It was free of protein, blood, glucose, and nitrite. Full blood count results were essentially within normal limits with a packed cell volume of 36% (normal range of 30–54). Erythrocyte sedimentation rate was 21 mm/h (0–12). Fasting blood glucose was 3.98 mmol/L (3.3–5.5). Electrolytes, urea, and creatinine levels were within normal limits. Parameters of liver function test were within normal limits with a total serum protein of 73.9 g/L (66–88) and serum albumin of 54.3 g/L (34–54). Serum calcium and phosphate levels were normal. Lipid profile was essentially normal, with a marginally elevated serum triglyceride of 2.0 mmol/L (0.52–1.95). Viral screening for human immunodeficiency virus (HIV-1 and -2), hepatitis B surface antigen (HBsAg), and antibody to hepatitis C virus (anti-HCV) were all negative. Serum prolactin was 13.84 (2-23 ng/mL). Other results are summarized in [Table 1].

Table 1: Results of laboratory investigations of the patient

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Chest radiograph was normal. Electrocardiography showed sinus rhythm with a heart rate of 93 beats/min. There were no features of left ventricular hypertrophy or prolonged QT. Abdominopelvic ultrasound scan and thyroid scan were normal. Abdominal CT scan revealed a right supra renal heterogeneous enhancing mass measuring 3.42 cm x 2.74 cm x 4.13 cm (AP x W x H) with Hounsfield unit of 28-34 and well-defined margin. Abdominal MRI scan revealed a fairly well defined, oval shaped T2W hypointense right adrenal mass, showing mild heterogenous enhancement on post contrast with consideration of a right adrenal adenoma. It measured about 3.85 cm x 2.95 cm.

Management

She was initially placed on oral carvedilol 12.5 mg daily while being investigated. Intravenous hydrocortisone was given before the commencement of adrenalectomy to prevent the development of acute adrenal insufficiency.

She had a right laparoscopic adrenalectomy done. The specimen was sent for histology which showed an encapsulated round solid mass weighing 20 g, measuring 50 × 40 × 15 mm. The cut surface had a yellowish appearance. Microscopic sections showed an adrenal gland in which there was a mixed cell cortical adenoma with abundant eosinophilic cytoplasm and round nuclei with small nucleoli. An admixed population of cells with foamy cytoplasm was also present. There was no lymphatic or vascular infiltration. Conclusion was that of a right adrenal cortical adenoma without evidence of malignancy. There was a weak correlation between the size of the adrenal mass removed at surgery and its size on abdominal CT scan which underestimated the size of the adrenal mass.

After operation, she was placed on oral candesartan 12 mg at night, oral spironolactone 25 mg twice daily, oral hydrocortisone 10 mg in the morning and 5 mg at night for 4 weeks.

She was counseled to reduce salt intake and keep her follow-up clinic appointments.

At 16 weeks post-surgery, patient’s menstrual cycle resumed, weight has reduced to 70 kg. The moon-like facies and striae were gradually disappearing. Examination of the cardiovascular system revealed a pulse rate of 90 beats/min and a blood pressure of 110/60 mmHg.

Discussion

Cushing’s syndrome is a rare endocrine disorder which can present to different medical subspecialties. It is a state of chronic hypercortisolism caused by exogenous or endogenous exposure to glucocorticoids.^[4] The most common cause is iatrogenic which may be due to prolonged use of synthetic glucocorticoids such as prednisolone; however, non-iatrogenic causes are rare.^[5] In this index patient, she presented to a gynecologist for amenorrhea, later to a dermatologist, and never had exposure to corticosteroids in any form but had a right adrenal mass.

Although Cushing’s syndrome is commoner in female adults, studies show that prepubertal boys are affected more frequently than girls.^[6] As children approach puberty, the sex distribution of Cushing’s disease equalizes, and the trend is reversed, with female being more commonly affected during adulthood. The explanation for this is unclear but is perhaps due to the estrogenic milieu during puberty in females.^[7]

Hypercortisolism can cause alterations in body composition with an increase in visceral adiposity and decreased bone mass.^[8] The most important clinical feature observed in the index patient was weight gain, purple striae on the chest, back, upper arms, and thighs [Figure 1], and new onset hypertension. However, muscle weakness was not present at the physical examination. In fact, this sign (which has high specificity in adult patients) may be less common in adolescent patients.^[9] Several striking features of Cushing’s syndrome, such as central obesity, moon facies, dorsocervical supraclavicular fat pads, and abdominal striae, can be more discriminatory. These features are seen in about half of the patients with cortisol overproduction,^[10] and they were present in our patient.

Figure 1: Widespread striae on the back of the patient

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The presence of purple striae >1 cm in diameter is substantially pathognomonic for Cushing’s syndrome. These striae are most commonly seen on the abdomen and lower flanks, but they can also occur on the shoulders, upper arms, axillae, breasts, buttocks, and upper thighs, as was seen in our patient. In children, the skin is affected at multiple sites; however, the severity of the manifestations does not correlate with biochemical indices of the disease. With the exception of striae, cutaneous effects of endogenous hypercortisolism completely heal within the first year after surgical intervention for the disease.^[11],[12] Sixteen weeks post-surgery, most of the striae had faded away. Hypertension is one of the most distinguishing features of endogenous Cushing's syndrome, as it is present in about 80% of adult patients and in almost half of children and adolescents patients.^[13] Treatment of Cushing's syndrome usually results in resolution or amelioration of hypertension. However, some patients may not achieve normotension and thus require follow up treatment of hypertension to prevent post-surgery cardiovascular morbidity.^[13] Cushing's syndrome is associated with increased morbidity and mortality. Cardiovascular events (such as myocardial infarction and stroke), sepsis, and thromboembolism are the leading causes of mortality.^{[14],[15],[16]} Cushing's syndrome due to benign adrenal adenomas have relatively good survival outcomes often mirroring that of the general population. Clinical complications associated with Cushing’s syndrome include metabolic syndrome, consisting of systemic arterial hypertension, visceral obesity, impairment of glucose metabolism, and dyslipidaemia; musculoskeletal disorders, such as myopathy, osteoporosis, and skeletal fractures; neuropsychiatric disorders, such as impairment of cognitive function, depression, and mania.^[16] Specific monitoring for and treatment of these associated comorbidities are essential to decrease the risk of mortality. This patient should be screened for other endocrine disorders to rule out variants of multiple endocrine neoplasia type 1 (MEN1). It is important that Cushing’s syndrome is considered when female teenagers developed amenorrhea associated with weight gain, especially when there are extensive striae.

Conclusion

Cushing’s syndrome in a teenager is a rare endocrine disorder which can present to different medical subspecialties. Early detection, evaluation, and treatment are keys to improving its morbidity and quality of life.

Limitations

Serum aldosterone and other adrenal hormones were not measured. These assays are important to help screen for other possible endocrine disorders in this patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Holst JM, Horváth-Puhó E, Jensen RB, Rix M, Kristensen K, Hertel NT, et al. Cushing’s syndrome in children and adolescents: A Danish nationwide population-based cohort study. Eur J Endocrinol 2017;176:567-74.
2.	Robyn JA, Koch CA, Montalto J, Yong A, Warne GL, Batch JA Cushing’s syndrome in childhood and adolescence. J Paediatr Child Health 1997;33:522-7.
3.	Weber A, Trainer PJ, Grossman AB, Afshar F, Medbak S, Perry LA, et al. Investigation, management and therapeutic outcome in 12 cases of childhood and adolescent Cushing’s syndrome. Clin Endocrinol (Oxf) 1995;43:19-28.
4.	Lacroix A, Feelders RA, Stratakis CA, Nieman LK Cushing’s syndrome. Lancet 2015;386:913-27.
5.	Chabre O Syndromes de Cushing: physiopathologie, étiologie et principes thérapeutiques [Cushing syndrome: Physiopathology, etiology and principles of therapy]. Presse Med 2014;43:376-92.
6.	Nieman LK Cushing’s syndrome: Update on signs, symptoms and biochemical screening. Eur J Endocrinol 2015;173:M33-8.
7.	Storr HL, Isidori AM, Monson JP, Besser GM, Grossman AB, Savage MO Prepubertal Cushing’s disease is more common in males, but there is no increase in severity at diagnosis. J Clin Endocrinol Metab 2004;89: 3818-20.
8.	Leong GM, Abad V, Charmandari E, Reynolds JC, Hill S, Chrousos GP, et al. Effects of child- and adolescent-onset endogenous Cushing’s syndrome on bone mass, body composition, and growth: A 7-year prospective study into young adulthood. J Bone Miner Res 2007;22:110-8.
9.	Magiakou MA, Mastorakos G, Oldfield EH, Gomez MT, Doppman JL, Cutler GB Jr, et al. Cushing’s syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med 1994;331:629-36.
10.	Savage MO, Lienhardt A, Lebrethon MC, Johnston LB, Huebner A, Grossman AB, et al. Cushing’s disease in childhood: Presentation, investigation, treatment and long-term outcome. Horm Res 2001;55(Suppl. 1):24-30.
11.	Stratakis CA, Mastorakos G, Mitsiades NS, Mitsiades CS, Chrousos GP Skin manifestations of Cushing’s disease in children and adolescents before and after the resolution of hypercortisolemia. Pediatr Dermatol 1998;15:253-8.
12.	Jabbour SA Cutaneous manifestations of endocrine disorders: A guide for dermatologists. Am J Clin Dermatol 2003;4:315-31.
13.	Magiakou MA, Smyrnaki P, Chrousos GP Hypertension in Cushing's syndrome. Best Pract Res Clin Endocrinol Metab 2006;20:467–82.
14.	Javanmard P, Duan D, Geer EB Mortality in patients with endogenous Cushing's syndrome. Endocrinol Metab Clin North Am 2018;47:313-33.
15.	Schernthaner-Reiter MH, Siess C, Micko A, Zauner C, Wolfsberger S, Scheuba C, et al. Acute and life-threatening complications in Cushing syndrome: Prevalence, predictors, and mortality. J Clin Endocrinol Metab 2021;106:e2035-46.
16.	Pivonello R, Isidori AM, De Martino MC, Newell-Price J, Biller BM, Colao A Complications of Cushing's syndrome: State of the art. Lancet Diabetes Endocrinol 2016;4:611-29.