Postoperative hormonal modulation in a patient with granulosa cell tumor and myasthenia gravis: a gyneco-oncologic perspective.

A 38-year-old woman (gravida 0, para 0), married for 8 years, presented to our gynecology outpatient clinic with a 2-week history of dull lower abdominal pain, intensifying during menstruation. Her menstrual cycles were regular. She had a known diagnosis of MG for 2 years, managed with pyridostigmine 60 mg three times daily, and hypothyroidism for 3 years, controlled with levothyroxine. The patient had regular menstrual cycles with no history of abnormal uterine bleeding. She was nulliparous and had no prior gynecologic disorders. There was no history of endometriosis, ovarian cysts, pelvic inflammatory disease, or prior abdominal surgeries. She had no family history of breast, ovarian, or endocrine tumors. Routine laboratory parameters, including thyroid function tests and preoperative hormonal profile, were within normal limits (estradiol not measured). Tumor markers such as inhibin B were not done due to cost, and CA-125 was 50. Preoperative/MRI revealed an 8 × 8 cm adnexal mass with Complex cystic mass with hemorrhagic/proteinaceous content, Well-defined, non-invasive appearance, Mass effect without infiltration, No fat or classic endometriotic stigmata, Location consistent with ovarian origin, well-defined, complex cystic pelvic mass with T1 hyperintensity and T2 shading, located posterior to the bladder and likely arising from the posterior uterus or adnexa. Pelvic ultrasound revealed a left adnexal complex cyst. MRI pelvis demonstrated a 7 × 7 cm well-defined cystic lesion in the left ovary with peripheral blooming artifact, asymmetrical wall thickening, and a hyper-enhancing solid component. Endometrial thickening consistent with hyperplasia was noted. Tumor markers (CA-125, inhibin B, LDH, AFP) were within normal limits. Given the imaging features suggestive of malignant transformation of an endometrioma, a decision was made for comprehensive staging surgery. The patient underwent preoperative cardiopulmonary and neurological clearance with detailed anesthetic planning to mitigate risks related to MG. Under carefully titrated general anesthesia avoiding long-acting neuromuscular blockers, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and peritoneal cytology. Intraoperative findings included: Intraoperatively, a 9 × 8 cm encapsulated left ovarian mass was identified with a smooth surface and no external excrescences (Fig. 1 ). There were minimal adhesions to the adjacent bowel, no ascites, and no peritoneal deposits. The uterus and right adnexa appeared grossly unremarkable (Fig. 2 ). Figure 1. Intraoperative view showing a 9 × 8 cm encapsulated left ovarian mass with a smooth surface, no external excrescences, and minimal adhesions to the adjacent bowel. Figure 2. Resected uterus and adnexa showing grossly unremarkable uterus and right ovary; the left ovary corresponds to the encapsulated mass shown in Fig. 1 . Intraoperatively, a 9 × 8 cm encapsulated left ovarian mass was identified with a smooth surface and no external excrescences (Fig. 1 ). There were minimal adhesions to the adjacent bowel, no ascites, and no peritoneal deposits. The uterus and right adnexa appeared grossly unremarkable (Fig. 2 ). Intraoperative view showing a 9 × 8 cm encapsulated left ovarian mass with a smooth surface, no external excrescences, and minimal adhesions to the adjacent bowel. Resected uterus and adnexa showing grossly unremarkable uterus and right ovary; the left ovary corresponds to the encapsulated mass shown in Fig. 1 . Peritoneal washings were obtained, infracolic omentectomy was performed, and no suspicious lymph nodes were noted. Final histopathology confirmed an adult-type GCT, with a mitotic index of 3/10 HPF and positive inhibin immunostaining. Peritoneal washings were obtained, infracolic omentectomy was performed, and no suspicious lymph nodes were noted. Final histopathology confirmed an adult-type GCT, with a mitotic index of 3/10 HPF and positive inhibin immunostaining. Frozen section of the ovarian mass revealed features consistent with a sex cord-stromal tumor. Postoperative recovery was uneventful for the first 48 hours. On postoperative day 3, the patient developed palpitations, chest discomfort, progressive fatigue, and drowsiness. Oxygen saturation declined on room air, and serum potassium was found to be mildly low (corrected promptly). Electrocardiogram showed new-onset first-degree atrioventricular block. Echocardiography revealed mild tricuspid regurgitation without hemodynamic compromise. Despite correction of metabolic parameters and continuation of pyridostigmine, the patient remained symptomatic. Neurological and cardiac teams advised supportive management without escalation. In the absence of infection, hemodynamic instability, or structural cardiac disease, the possibility of hormonal withdrawal following bilateral oophorectomy was considered. Given the estrogenic nature of GCTs, and abrupt cessation of endogenous estrogen, the patient was initiated on oral estradiol valerate 1 mg daily. Within 48 hours, there was marked improvement in energy levels, cardiopulmonary status, and sensorium. She was transitioned to the high-dependency unit and subsequently discharged home in a stable condition on postoperative day 9. Final histopathology confirmed an adult GCT of the left ovary with no capsular invasion, surface involvement, or lymphovascular emboli. Endometrium showed simple hyperplasia without atypia. Cytology and omental biopsy were negative for malignancy. FIGO staging was IA. Given the early stage and favorable histology, no adjuvant therapy was indicated. At 6-month follow-up, the patient remains asymptomatic on maintenance estrogen and pyridostigmine, with no evidence of disease recurrence or neurologic exacerbation. The patient was discharged in good general condition and continued follow-up uneventfully.

Adult-type granulosa cell tumors (AGCTs) are rare, estrogen-secreting ovarian neoplasms of the ovary accounting for approximately 3–5% of all ovarian malignancies [ 1 ] . Typically presenting with abnormal uterine bleeding or pelvic masses, they may be associated with endometrial hyperplasia or carcinoma due to chronic unopposed estrogen exposure. Surgical staging remains the cornerstone of management in early-stage disease. Perioperative management becomes significantly more complex in patients with neuromuscular conditions such as myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating skeletal muscle weakness. MG can be exacerbated by stress, infection, electrolyte imbalance, or anesthetic agents. Herein, we describe a case of surgically managed stage I GCT in a woman with MG and hypothyroidism, who experienced postoperative instability that was unexpectedly ameliorated with estrogen therapy. This case report has been reported in line with the SCARE criteria [ 2 ] . Perioperative management of granulosa cell tumors (GCTs) becomes significantly more complex in patients with neuromuscular conditions such as myasthenia gravis (MG). Comprehensive surgical staging remains the standard of care for apparent early-stage AGCT. The possibility of cardiac arrythmia should be considered after oophorectomy in patients with MG and GCTs. Abrupt cessation of estrogen after removal of estrogen secreting tumors can lead to various complications. Perioperative management of granulosa cell tumors (GCTs) becomes significantly more complex in patients with neuromuscular conditions such as myasthenia gravis (MG). Comprehensive surgical staging remains the standard of care for apparent early-stage AGCT. The possibility of cardiac arrythmia should be considered after oophorectomy in patients with MG and GCTs. Abrupt cessation of estrogen after removal of estrogen secreting tumors can lead to various complications.

AGCTs should be considered in the differential diagnosis of hormonally active adnexal masses in reproductive-aged women. Comprehensive surgical staging is essential even in radiologically early disease due to the tumor’s recurrence potential. Perioperative planning in MG requires avoidance of triggering agents, multidisciplinary input, and close monitoring. Estrogen withdrawal post-oophorectomy may exacerbate systemic symptoms in MG, and estrogen replacement therapy (ERT) may play a stabilizing role. The safety and potential benefit of ERT in early-stage AGCT patients with surgical menopause should be individualized based on comorbidities, age, and disease status. AGCTs should be considered in the differential diagnosis of hormonally active adnexal masses in reproductive-aged women. Comprehensive surgical staging is essential even in radiologically early disease due to the tumor’s recurrence potential. Perioperative planning in MG requires avoidance of triggering agents, multidisciplinary input, and close monitoring. Estrogen withdrawal post-oophorectomy may exacerbate systemic symptoms in MG, and estrogen replacement therapy (ERT) may play a stabilizing role. The safety and potential benefit of ERT in early-stage AGCT patients with surgical menopause should be individualized based on comorbidities, age, and disease status.

The majority of AGCT present during perimenopausal or early postmenopausal age groups, although younger patients can also be affected. Most patients present with either abdominal/pelvic pain or manifestations of hyperestrogenism such as abnormal uterine bleeding, endometrial hyperplasia, or even endometrial carcinoma [ 3 , 4 ] . Reproductive considerations are also important in AGCT patients, particularly for women in the reproductive age group, where fertility preservation and postoperative endocrine management may influence treatment decisions [ 5 ] . In our case, the patient presented with dull lower abdominal pain that was exacerbated during menstruation – an unusual but noteworthy symptom in AGCTs. MRI findings suggested malignant transformation of an endometriotic cyst, highlighting the diagnostic complexity, especially when imaging features mimic epithelial malignancies. The diagnosis of AGCT was confirmed postoperatively based on histopathologic examination, which remains the gold standard. Inhibin B, anti-Müllerian hormone, and FOXL2 (C134W) mutation testing may support the diagnosis, although these were not elevated in our case – likely due to early-stage disease [ 6 ] . From a gynecologic oncologic perspective, comprehensive surgical staging remains the standard of care for apparent early-stage AGCT. This includes total hysterectomy, bilateral salpingo-oophorectomy, omental biopsy, and peritoneal washings, with selective lymphadenectomy considered in cases with suspicious nodes [ 7 ] . The patient’s co-morbid MG added significant complexity to the perioperative planning. MG is an autoimmune disorder characterized by antibodies against the nicotinic acetylcholine receptor at the neuromuscular junction, leading to fatigable muscle weakness. Female predominance is evident in MG, with peak incidence in the third to fourth decades – coinciding with the age group affected by AGCTs [ 8 ] . Anesthetic management in MG patients undergoing laparotomy requires meticulous planning. Postoperative respiratory failure remains a major concern, especially in those with bulbar involvement or poor preoperative control [ 9 ] . Although our patient remained stable intraoperatively and during early recovery, she developed delayed cardiopulmonary symptoms including bradyarrhythmia, palpitations, and drowsiness on postoperative Day 3. While initially attributed to hypokalemia, her symptoms persisted despite correction. Cardiac manifestations in MG are under-recognized but can include arrhythmias, conduction disturbances, and even myocarditis. First-degree atrioventricular block, as seen in our case, has been reported in MG patients and may signal autonomic instability or unmasking of subclinical cardiac involvement [ 10 ] . Interestingly, our patient demonstrated rapid symptomatic improvement following initiation of oral estradiol valerate, raising important considerations regarding hormone withdrawal and its impact on systemic function, particularly in MG. Bilateral oophorectomy results in an abrupt drop in circulating estrogen levels. Estrogens have known neuroprotective and immunomodulatory properties. In vitro and animal models suggest that estradiol can modulate acetylcholine receptor sensitivity and expression at the neuromuscular junction, which may have therapeutic relevance in MG [ 11 , 12 ] . Moreover, estradiol attenuates pro-inflammatory cytokines such as IL-6 and TNF-α, both implicated in autoimmune exacerbation [ 13 ] . Serum estradiol levels were not measured postoperatively in our case; however, the clinical picture strongly supported abrupt estrogen withdrawal as the precipitating factor. A retrospective analysis by Kaminski et al noted that female MG patients frequently report worsening symptoms during periods of hormonal transition – such as postpartum, menopause, or post-oophorectomy [ 14 ] . Although hormone replacement therapy (HRT) is not routinely prescribed for MG, there is growing evidence to suggest that estrogen deprivation may worsen neuromuscular symptoms, particularly in estrogen-sensitive individuals. In the context of GCTs, which are hormone sensitive, abrupt estrogen withdrawal may not only impact general homeostasis but also affect residual tumor cell behavior and patient-reported outcomes. While the primary role of HRT in oncology is controversial due to concerns of stimulating microscopic disease, in early-stage, completely resected AGCTs, estrogen therapy has not been associated with increased recurrence risk and may be beneficial in managing surgical menopause, particularly in young women [ 15 ] . Our patient, who had no immediate cardiopulmonary or infective cause for her deterioration, responded within 48 hours of initiating low-dose estradiol. This clinical response—though anecdotal—highlights the possible benefit of early hormonal repletion in selected cases, especially when oophorectomy is performed in premenopausal women with comorbid neuromuscular disorders. This case highlights that abrupt estrogen withdrawal after oophorectomy can precipitate postoperative cardiorespiratory instability in MG patients, and timely estrogen replacement therapy can be rapidly therapeutic.

This case reinforces the need for tailored surgical and postoperative strategies in women with complex comorbidities undergoing gynecologic oncology procedures. At the same time, it underscores the importance of recognizing hormonal withdrawal as a reversible cause of postoperative instability in MG patients undergoing gynecologic surgery, and highlights the potential role of timely estrogen replacement therapy.