Din aceeași categorie

Obstetrica şi Ginecologia

Masterclass european de endometrioză

Obstetrica şi Ginecologia

IN MEMORIAM DR. EMIL GHEORGHIŢĂ

Obstetrica şi Ginecologia

Opinii şi recomandări curente pentru utilizarea meşei în chirurgia ginecologică – review al literaturii

1. Introduction

The most common cause of congenital adrenal hyperplasia (CAH) is 21-hydroxylase (CYP21A2) deficiency, accounting for 90-95% of CAH cases^(1,2). The salt-wasting form is generally diagnosed at birth, either through screening programs based on 17-hydroxiprogesterone levels, where available, or following a salt-wasting crisis. Although genetic testing is needed to confirm the underlying cause of CAH, in some cases it is not available, and this seems the norm in many medical centers all over the world^(3-5).

Moreover, a certain index of suspicion with respect to CAH diagnosis should be kept in mind in young females admitted with menstrual cycle anomalies that may be mistakenly considered as having polycystic ovary syndrome (PCOS) since many of the clinical features and even some laboratory traits are common^(6-8).

Our purpose is to introduce a mostly unique case of CAH that associated an adrenal tumor apparently in relationship with the presence of enzymatic defect.

2. Materials and method

This is a case report. The patient agreed for retrospectively using her medical records. The gynecological profile, in terms of menstrual cycle profile, is provided in addition to the specific hormonal panel and the imagery assessment of the adrenal glands. The outcome following medical and surgical intervention is also provided.

3. Results – case description

A 27-year-old female was admitted for gynecological and endocrine evaluation six months following right adrenalectomy for a large tumor. The patient was diagnosed with salt-wasting congenital adrenal hyperplasia as a neonate, and she was under glucocorticoid substitution treatment ever since. However, she had poor adherence to follow-up appointments, with a consequent lack of glucocorticoid dose adjustment. Specific medical records and family history were irrelevant as far as the patient provided them.

At the age of 22 years old, the female complained of diffuse abdominal pain and discomfort. An abdominal ultrasound was performed and uncovered a large right adrenal mass and bilateral adrenal hyperplasia, further confirmed by computed tomography (right adrenal mass of 41 by 47 by 55 mm and a left adrenal mass of 18 by 15 mm). She was only then referred for a secondary endocrine evaluation. On admission, the patient was stable (blood pressure 120/80 mmHg). The clinical examination revealed that she did not reach her target height (patient’s height was 160 cm, mid-parental target height was 171 cm). Moreover, the young lady was suffering from secondary amenorrhea ever since experiencing menarche at 15 years old.

Hormonal evaluation revealed poor glucocorticoid substitution under 10 mg of prednisone daily. Serum electrolytes were normal, such as sodium 141 mmol/L (normal: 136-145 mmol/L) and potassium 4.05 mmol/L (normal: 3.5-5.1 mmol/L) – Table 1.
 

The patient was switched to 15 mg hydrocortisone and 0.5 mg dexamethasone daily. At the eight-month follow-up, she had regular menstrual cycles, but she seemed mildly overtreated with glucocorticoids (Table 2).
 

Computed tomography reconfirmed a 46 by 44 by 35 mm right adrenal tumor and a subsequent 15 by 11 by 10 mm left adrenal tumor. During the evaluation, the patient also underwent a pituitary computed tomography, which revealed a pituitary microadenoma of 8.8 by 6 mm. Adrenal surgery and genetic testing were recommended, but the patient was lost to follow-up for three years amid the COVID-19 pandemic. She then presented at the age of 26 years old, with amenorrhea and insufficient glucocorticoid substitution (Table 3).
 

Her serum electrolytes were normal: sodium 139 mmol/L (normal: 136-145 mmol/L) and potassium 4.2 mmol/L (normal: 3.5-5.1 mmol/L) under treatment with 0.1 mg of fludrocortisone weekly. Considering the growth of the adrenal tumor as shown by computed tomography, reaching 57.3 by 45.6 by 45.9 mm in size, and the need for differential diagnosis, surgery was recommended once more (Figure 1).
 

The patient also underwent computed tomography monitoring of the pituitary which revealed once again a microadenoma of 4.4 by 3.3 mm that was considered a pituitary incidentaloma (with nonfunctioning profile that was accidentally detected amid these mentioned investigations) – Figure 2.
 

The patient underwent uneventful right adrenalectomy and the pathology revealed an adrenocortical oncocytic neoplasm, without criteria for malignancy, associated with a predominant myeloma component. Six months postoperatively, the patient had spontaneous menstruation.

Following biochemical monitoring and evaluation of plasma cortisol concentrations at two hours post-dose, the patient continued the treatment with 15 mg hydrocortisone and 0.5 mg dexamethasone daily and 0.1 mg of fludrocortisone daily (Tables 4 and 5).
 

Pituitary computed tomography revealed that the microadenoma did not enlarge (5 by 3 mm). Hormonal evaluation showed a normal prolactin level (Table 6).
 

Long-term surveillance is mandatory, as well as genetic testing (which the patient currently declined). An adjustment of the glucocorticoid replacement is needed in case of future pregnancy, as well as preconception genetic counseling.

4. Discussion

This challenging case introduces a long history of secondary amenorrhea that was early identified since menarche and it was partially corrected under poor glucocorticoids replacements; apparently, the removal of the adrenal tumor improved the menstrual cycle profile (while the subject remained under specific medical therapy for CAH-related chronic adrenal failure). Here are four distinct points amid this sample case.

4.1. The issue of genetic testing in CAH

Even though genetic testing was repeatedly recommended to our patient, she refused the genetic testing. Therefore, she was diagnosed with CYP21A2 deficiency, based on the clinical picture with salt-wasting at birth, on biochemical studies and considering it is the most frequent cause of CAH. Genetic background is very useful in daily practice; however, a patient’s choice and her family options should be taken into consideration. Also, some countries with increased prevalence of some type of enzymatic defects provide screening protocols for general population at birth^(9-11).

4.2. Long-term requirement of oral glucocorticoids

The patient had poor compliance to treatment and was lost to follow-up all throughout adolescence, with consequent clinical disturbances, including amenorrhea and consequent laboratory anomalies as indicated by the hormonal panel showing high values of ACTH, 17-hydroxiprogesterone and androgens. Even though ACTH is not recommended for monitoring the response to treatment in patients with CAH, this is very useful in the everyday exploration of such patients^(1,12,13). Moreover, there are data indicating that high levels of ACTH are involved in adrenal tumor development in these patients^(14,15). However, no clear guideline recommendation has been established so far in this specific matter. On the other hand, the patient’s compliance to periodic checkup under oral steroids was poor, and especially the COVID-19 pandemic period should be mentioned, since a large number of endocrine and gynecologic conditions reshaped their clinical presentation due to restrictions, overall stress, limited access to non-emergency controls etc.^(16,17)

4.3. Adrenal tumors in females diagnosed with classical CAH forms 

The prevalence of adrenal tumors in CAH patients reaches 30%, with the most frequent tumors being represented by myelolipomas^(1,18,19). Although rare, adrenal carcinoma cases have previously been described in CAH^(20,21). When faced with an adrenal tumor in a patient with CAH, both differential diagnoses with carcinoma and tumor size are to be considered. Even though myelolipomas are benign, they may sometimes reach impres­sive sizes and compress the nearby structures, causing abdominal or urinary symptoms^(22-24). Considering the size of the tumor and the need for differential diagnosis, our patient underwent surgery, and the pathology revealed an oncocytic neoplasm, with a myeloma component (oncocytic adrenocortical adenoma mixed with a myelolipoma). To our knowledge, only a few similar cases have been reported⁽²⁵⁾.

Adrenocortical oncocytic neoplasms are nonfunctional tumors and, despite being considered benign, some data suggest that they may have malignant potential. Immunohistochemistry and the Lin-Weiss-Bisceglia criteria come to aid in differentiating the malignant potential and choosing the proper surveillance of these patients⁽²⁵⁾.

4.4. CAH among endocrine causes of amenorrhea

This young lady had the salt wasting form of CAH as cause of secondary amenorrhea. This mentioned type of adrenal function anomaly due an enzymatic defect is among the rarest endocrine causes when compared to PCOS or even usual thyroid anomalies such as chronic autoimmune thyroiditis and associated disturbances of hormones or comorbidities as non-thyroid autoimmune conditions (for instance, those located at adrenal glands or ovary)^(26,27). Similar rare causes of secondary amenorrhea involve endocrine tumors and hormonally active ovarian tumors^(28,29). In this case, the adrenal tumor might be the tip of an iceberg, showing an uncontrolled disease⁽³⁰⁾. Also, the patient had a pituitary incidentaloma that did not seem related to the underlying adrenal disease, noting that one out of ten individuals from the general population had this diagnosis⁽³¹⁾. Poor glucocorticoids substitution is most likely related to the adrenal, not pituitary mass. Also, overtreatment with oral steroids might bring unwanted effects at bone and cardiometabolic levels, as well as menstrual cycle profile as seen in exogenous Cushing’s syndrome, thus becoming an additional issue in this particular case^(32-34).

5. Conclusions

The management of patients with adrenal tumors and CAH is challenging and complex, due to the link with CAH control and compliance to treatment, the need for differential diagnosis, and finding the proper timing for surgery. To our aware, the presence of adrenocortical tumor mixed with a myelolipoma is one of the rarest scenarios of HAC evolution.  

Corresponding author: Ana-Maria Gheorghe, e-mail: anamaria.gheorghe96@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.