Neuroendocrine Syndromes
1. Dr. Aidarbek Aidanek
2. Nashreen Mohamed
Mohammad Adil
Bhushan Modak
Lingdale Muktai
(1. Lecturer, Dept. of OB-GYN, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. Students, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Background: Gynecologic practice frequently encounters conditions where endocrine pathology produces reproductive, menstrual or genital abnormalities. This review synthesizes current evidence on four conditions that bridge gynecology and neuroendocrinology: intrauterine adhesions (Asherman syndrome), hyperprolactinemia presenting as galactorrhea–amenorrhea, postpartum hypopituitarism (Sheehan’s syndrome), and adrenogenital syndromes (congenital adrenal hyperplasia and related androgen excess).
Objectives: To summarize epidemiology, pathophysiology, clinical presentation, diagnosis, management, reproductive implications and outcomes; identify research gaps; and provide practical recommendations for gynecologists.
Methods: Narrative evidence synthesis of recent reviews, clinical guidelines and primary literature (2018–2025).
Key results: Hysteroscopic diagnosis and adhesiolysis remain central to Asherman management with adjuvant strategies to restore endometrium and fertility. Hyperprolactinemia is an important, reversible cause of amenorrhea and infertility; dopamine agonists are first-line therapy. Sheehan’s syndrome, though rarer with modern obstetric care, causes lifelong hypopituitarism requiring hormone replacement and has important delays in diagnosis. Adrenogenital syndromes (most commonly 21-hydroxylase deficiency CAH) require lifelong endocrine management and have complex gynecologic and reproductive consequences.
Conclusions: Early recognition and multidisciplinary management (endocrinology + gynecology + reproductive medicine) optimize outcomes. Greater awareness, prompt endocrine testing in menstrual/infertility workups, and standardized follow-up improve patient care.
Introduction
Neuroendocrine syndromes in gynecology encompass a spectrum of conditions where neuroendocrine processes intersect with reproductive function, producing a range of presentations from amenorrhea and galactorrhea to structural sequelae in the endometrium. The curated articles, presented in chronological order, map a trajectory from conceptualization of gynecologic neuroendocrine tumors and related endocrine disturbances to diagnostic challenges, imaging considerations, and therapeutic outcomes in syndromic contexts such as Asherman syndrome and Sheehan-like presentations.
(Lopes Dias et al., 2015) provide an imaging-grounded entry point, detailing neuroendocrine tumors of the female genital tract within gynecology. The article foregrounds classification schemes and clinical behavior, underscoring diagnostic challenges and the implications for imaging and pathology correlation in gynecologic neuroendocrine neoplasms. This work sets the stage for recognizing how neuroendocrine differentiation can influence symptomatology and management in the gynecologic domain, even before overt functional disturbances become clinically apparent.
Chronicling a developmental and diagnostic lens, SUN-069 by (Chakravarthy & Ejaz, 2020) centers on primary amenorrhea, exemplified by Swyer syndrome. While not exclusively a neuroendocrine tumor, the case highlights how disorders of sexual development intersect with gonadal endocrinology and risk for gonadal malignancies. The discussion informs the broader context in which neuroendocrine disruptions may be implicated in adolescent presentations of sexual development failure, emphasizing vigilance for underlying gonadal and endocrine pathology in amenorrheic patients.
Extending into pituitary-related neuroendocrine activity, (Ntalli & Capatina, 2022) address functioning gonadotroph tumors as a subset of pituitary adenomas. Although often hormonally silent, these tumors can manifest with gonadotropin-related syndromes, including menstrual disturbances and ovarian hyperstimulation in premenopausal individuals, as well as precocious puberty in children. This review highlights that functioning gonadotroph adenomas, while rare, can produce clinically significant reproductive sequelae, reinforcing the need to consider pituitary neuroendocrine etiologies in syndromic gynecologic presentations.
Siddiqui et al. (2022) contribute a practical, case-series perspective on Sheehan's syndrome in non-obstetric critical care. The work documents presentations with postpartum hemorrhage histories and secondary amenorrhea, with hormonal profiles revealing low prolactin and thyroid axis dysfunction, and imaging often showing empty or partially empty sella. The authors emphasize the variable severity and multi-system involvement, illustrating how pituitary neuroendocrine disruption can translate into gynecologic and systemic manifestations requiring multidisciplinary management ((Sarwar Siddiqui et al., 2022)).
Finally, (Siferih et al., 2024) provide an integrative, resource-limited perspective on Asherman syndrome within a broader discussion of neuroendocrine syndromes in gynecology. Although primarily focused on hysteroscopic treatment outcomes for Asherman's syndrome, the article situates endometrial scarring within the neuroendocrine framework by addressing etiologies, symptomatology (including hypomenorrhea and infertility), and management implications in settings with constrained resources. This study reinforces the practical relevance of recognizing neuroendocrine contributors to gynecologic pathology and the importance of context-sensitive therapeutic approaches
Collectively, these articles illuminate a continuum from neuroendocrine tumor biology and diagnostic imaging to syndromic gynecologic conditions-such as amenorrhea, galactorrhea-amenorrhea spectra, and endometrial pathology-that demand integrated endocrine and gynecologic assessment. The literature highlights diagnostic challenges, the need for cross-disciplinary collaboration (endocrinology, radiology, gynecology), and the expanding recognition of neuroendocrine processes as pivotal in shaping clinical presentations and treatment pathways in gynecology.
Objectives
Provide a concise but comprehensive clinical and reproductive review of:
·Asherman syndrome (intrauterine adhesions)
·Galactorrhea–amenorrhea due to hyperprolactinemia
·Sheehan’s syndrome (postpartum pituitary necrosis and hypopituitarism)
·Adrenogenital syndromes (congenital adrenal hyperplasia and androgen excess)
Describe pathophysiology linking neuroendocrine dysfunction to gynecologic presentations.
1. Summarize best-practice diagnostic approaches and modern management options relevant to gynecologists and reproductive specialists.
2. Synthesize implications for fertility, obstetric risk, and long-term endocrine care.
3. Identify gaps and propose practical recommendations for clinical practice and future research.
Methods
Design: Narrative review and synthesis.
Data sources: PubMed / MEDLINE, NCBI/StatPearls, recent specialty society guidelines (Endocrine Society), and high-quality reviews (2018–2025). Priority given to systematic reviews, clinical practice guidelines and large cohort studies.
Search terms: “Asherman syndrome”, “intrauterine adhesions”, “hyperprolactinemia”, “galactorrhea amenorrhea”, “Sheehan’s syndrome”, “postpartum hypopituitarism”, “congenital adrenal hyperplasia”, “adrenogenital syndrome”, plus “diagnosis”, “management”, “fertility”, “hysteroscopy”, “dopamine agonist”, “hormone replacement”.
Inclusion: English-language reviews, guidelines and clinical studies addressing the gynecologic and reproductive aspects of each condition.
Synthesis: Extracted epidemiology, pathogenesis, clinical features, diagnostic algorithms, treatment options, fertility outcomes, and knowledge gaps.
Results — literature synthesis (condition-by-condition)
Asherman syndrome (Intrauterine adhesions)
Overview & epidemiology
Asherman syndrome = intrauterine adhesions (IUA) with partial or complete obliteration of the uterine cavity leading to menstrual disturbances (hypomenorrhea/amenorrhea), infertility and obstetric complications. Risk factors: postpartum curettage, retained products of conception, pelvic surgery (e.g., myomectomy), infections and instrumentation. Recent reviews emphasize that incidence is underestimated and varies with the population and index procedure.
Pathophysiology
Endometrial trauma causes fibrotic repair and scarring: loss of basalis layer and replacement with fibrous tissue leading to adhesion formation that blocks endometrial regeneration and normal menstruation. Molecular studies indicate altered stromal–epithelial signaling and fibrotic gene expression.
Clinical presentation
Amenorrhea or hypomenorrhea, cyclic pelvic pain (if partial cavity), infertility, recurrent pregnancy loss, and abnormal placentation in future pregnancies.
Diagnosis
Hysteroscopy is gold standard for both diagnosis and treatment; sonohysterography and 3D ultrasound are useful non-invasive screens. Classification systems (mild–severe) guide prognosis.
Management
Hysteroscopic adhesiolysis is mainstay. Adjuvant measures include intrauterine devices or balloons to prevent re-adhesion, post-operative estrogen therapy to stimulate endometrial regeneration, and second-look hysteroscopy. Multidisciplinary fertility support and assisted reproduction may be needed for conception. Surgical outcomes depend on extent (mild vs severe) and residual endometrium.
Reproductive outcomes & complications
Pregnancy can be achieved post-treatment, especially in mild–moderate disease, but risk of placenta accreta spectrum and obstetric hemorrhage is increased; close obstetric follow-up recommended.
Galactorrhea–amenorrhea (Hyperprolactinemia)
Overview & epidemiology
Hyperprolactinemia is one of the common endocrine causes of amenorrhea and infertility. Causes include prolactin-secreting pituitary adenomas (prolactinomas), medications (dopamine antagonists such as antipsychotics), hypothyroidism, chest wall stimulation/trauma and renal failure; macroprolactin and physiologic states (pregnancy, lactation) should be considered.
Pathophysiology
Elevated prolactin suppresses GnRH pulsatility → decreased LH/FSH → anovulation, oligomenorrhea or amenorrhea. Direct stimulation of lactogenesis causes galactorrhea. Pituitary masses may cause mass effects.
Clinical presentation
Galactorrhea (typically bilateral, non-bloody), menstrual irregularities up to amenorrhea, decreased libido, infertility. In men: erectile dysfunction, decreased libido, gynecomastia. Evaluate for headaches, visual field defects.
Diagnosis
Serum prolactin (timed, avoid nipple stimulation prior), exclude pregnancy and hypothyroidism, consider macroprolactin assays, MRI pituitary if prolactin levels are significantly elevated or mass suspected. Evaluate medications.
Management
Dopamine agonists (cabergoline, bromocriptine) are first-line for prolactinomas and symptomatic hyperprolactinemia — effective at normalizing prolactin, restoring menses and fertility, and shrinking microadenomas. For medication-induced hyperprolactinemia, consider stopping or switching offending drug when feasible. Surgery or radiotherapy reserved for resistant tumors or intolerance to medical therapy.
Reproductive considerations
Women desiring pregnancy: medical therapy can restore ovulation; for prolactinomas, obstetric planning and endocrine follow-up required. Infertility treatment may require coordinated care between endocrinology and reproductive medicine.
Sheehan’s syndrome (Postpartum hypopituitarism)
Overview & epidemiology
Sheehan’s syndrome results from ischemic necrosis of the anterior pituitary following severe postpartum hemorrhage and hypotension. Incidence has declined in high-resource settings but remains a concern where obstetric hemorrhage care is limited. Clinical presentation ranges from subtle to severe, often leading to delayed diagnosis.
Pathophysiology
The pituitary, already enlarged in pregnancy, is vulnerable to hypoperfusion. Ischemia leads to selective loss of pituitary hormones (commonly GH and prolactin, then gonadotropins, ACTH, and TSH variably), resulting in lactation failure, amenorrhea and secondary adrenal insufficiency.
Clinical presentation
Failure of lactation in the immediate postpartum period, secondary amenorrhea, fatigue, loss of secondary sexual characteristics, hypotension, hyponatremia, and sometimes adrenal crisis. Onset may be immediate or delayed years later.
Diagnosis
High clinical suspicion in women with history of severe PPH plus lactation failure or later amenorrhea; hormonal assays demonstrating hypopituitarism; MRI may show an empty sella or pituitary atrophy.
Management
Lifelong hormone replacement tailored to deficiencies (glucocorticoids for ACTH deficiency before starting thyroid replacement if present; levothyroxine for central hypothyroidism; sex steroid replacement if indicated). Education on adrenal crisis prevention and obstetric planning for future pregnancies is essential. Regular follow-up with endocrinology and attention to fertility options (ovarian stimulation may be required) are important.
Adrenogenital syndromes (Congenital adrenal hyperplasia—CAH and related androgen excess states)
Overview & epidemiology
The most common form is 21-hydroxylase deficiency CAH. CAH manifests a spectrum from classic salt-wasting to simple virilising to nonclassical (late-onset) forms. Adult gynecologic manifestations include virilization, menstrual irregularities, infertility, and psychosocial issues. Guidelines for adult management emphasize lifelong endocrine care and genetic counselling.
Pathophysiology
Enzyme deficiency → impaired cortisol synthesis → ACTH-driven adrenal androgen excess → virilization and disturbed gonadal function. Androgen excess can produce clitoromegaly, hirsutism, oligomenorrhea/amenorrhea, and infertility.
Clinical presentation (gynecologic)
Ambiguous genitalia at birth in classic forms, menstrual irregularity, hirsutism, severe acne, infertility in adult women; psychosexual issues and obstetric management challenges require multidisciplinary care.
Diagnosis
Serum 17-hydroxyprogesterone screening (basal and ACTH-stimulated), adrenal steroid profiling, and genetic testing for CYP21A2 in suspected cases. New-born screening programs exist for classic CAH.
Management
Lifelong glucocorticoid replacement to suppress excess ACTH and androgens; mineralocorticoid replacement for salt-wasting forms; surgical reconstruction in some with significant genital ambiguity (timing individualized); fertility treatments, psychological support and genetic counseling are integral. Transition-of-care from pediatric to adult endocrine/gynecology services is crucial.
Discussion
Neuroendocrine–gynecologic interface: All four conditions demonstrate how endocrine disorders produce primary gynecologic presentations (amenorrhea, infertility, abnormal genital development, menstrual changes) and how gynecologists are often the first to detect endocrine disease. Early endocrine screening (prolactin, TSH, morning cortisol when indicated, and targeted steroid panels) should be a routine part of amenorrhea/infertility workups.
Timeliness and multidisciplinary care: Rapid recognition (e.g., lactation failure after PPH suggesting Sheehan’s) prevents morbidity. Collaboration between gynecology, endocrinology, reproductive medicine, and sometimes pediatric surgery (for CAH) improves outcomes.
Fertility and pregnancy planning:
Asherman: Hysteroscopic management improves fertility in many cases; however follow-up and obstetric vigilance for abnormal placentation is needed.
Hyperprolactinemia: Dopamine agonists restore ovulation in most women desiring pregnancy — coordinate withdrawal or continuation of therapy per tumor size and obstetric plan.
Sheehan’s: Hormone replacement (especially glucocorticoids) is essential during pregnancy and delivery; fertility may be assisted with gonadotropin therapy.
CAH: Preconception counseling, genotype-informed risk assessment, and optimized glucocorticoid regimen are fundamental.
Diagnostic pearls for clinicians:
- Avoid interpretative errors — e.g., transient mild PRL elevation after nipple stimulation, stress or some medications; always repeat abnormal tests appropriately. Use MRI imaging when prolactin is markedly elevated or mass suspected.
- In suspected Asherman, prioritize hysteroscopy for definitive diagnosis and treatment.
Research gaps: comparative effectiveness of different anti-adhesion strategies after hysteroscopy; long-term reproductive outcomes after severe Asherman; optimized protocols for transition care in CAH and late-diagnosed Sheehan’s; real-world data on medication-induced hyperprolactinemia in reproductive-aged women.
Practical recommendations (for gynecologists)
Include prolactin in initial endocrine panels for amenorrhea/infertility and interpret in clinical context.
For failed lactation or history of severe PPH, evaluate endocrine function for Sheehan’s (check morning cortisol, TSH, free T4, LH/FSH, prolactin) and refer to endocrinology urgently.
For suspected IUA/Asherman, arrange diagnostic hysteroscopy (or sonohysterography if not immediately available) and counsel about fertility prognosis and the possibility of repeat procedures.
For virilization or ambiguous genitalia, measure serum 17-hydroxyprogesterone and refer for definitive endocrine/genetic testing and multidisciplinary counseling
References
1.Lopes Dias, J., Margarida Cunha, T., Veloso Gomes, F., Callé, C., & Félix, A., 2015. Neuroendocrine tumours of the female genital tract: a case-based imaging review with pathological correlation. Ncbi.nlm.nih.gov
2.Chakravarthy, V. & Ejaz, S., 2020. SUN-069 A 14 Year Old Female with Primary Amenorrhea. Ncbi.nlm.nih.gov
3.Ntali, G. & Capatina, C., 2022. Updating the Landscape for Functioning Gonadotroph Tumors. Ncbi.nlm.nih.gov
4.Sarwar Siddiqui, S., Dominic, N., Kumar, S., Usman, K., Saran, S., Agrawal, A, Gurjar, M., & Nabeel Muzaffar, S., 2022. A Challenging Diagnosis of Sheehan’s Syndrome in Non-obstetric Critical Care and Emergency Settings: A Case Series of Five Patients with Varied Presentations.ncbi.nlm.nih.gov
5.Siferih, M., Gebre, T., Hunduma, F., Abebe, A., Gebremichael, A., Sewunet, H., & Shibabaw, T., 2024. Review of Asherman syndrome and its hysteroscopic treatment outcomes: experience in a low-resource setting.ncbi.nlm.nih.gov