Consecutive Resections of Double Pituitary Adenoma for Resolution of Cushing Disease

Posted on December 20, 2025 by MaryO

BACKGROUND

Double pituitary adenomas are rare presentations of two distinct adenohypophyseal lesions seen in <1% of surgical cases. Increased rates of recurrence or persistence are reported in the resection of Cushing microadenomas and are attributed to the small tumor size and localization difficulties. The authors report a case of surgical treatment failure of Cushing disease because of the presence of a secondary pituitary adenoma.

OBSERVATIONS

A 32-year-old woman with a history of prolactin excess and pituitary lesion presented with oligomenorrhea, weight gain, facial fullness, and hirsutism. Urinary and nighttime salivary cortisol elevation were elevated. Magnetic resonance imaging confirmed a 4-mm3 pituitary lesion. Inferior petrosal sinus sampling was diagnostic for Cushing disease. Primary endoscopic endonasal transsphenoidal resection was performed to remove what was determined to be a lactotroph-secreting tumor on immunohistochemistry with persistent hypercortisolism. Repeat resection yielded a corticotroph-secreting tumor and postoperative hypoadrenalism followed by long-term normalization of the hypothalamic-pituitary-adrenal axis.

LESSONS

This case demonstrates the importance of multidisciplinary management and postoperative hormonal follow-up in patients with Cushing disease. Improved strategies for localization of the active tumor in double pituitary adenomas are essential for primary surgical success and resolution of endocrinopathies.

ABBREVIATIONS

ACTH = adrenocorticotrophic hormone;  BMI = body mass index;  DHEA-S = dehydroepiandrosterone sulfate;  FSH = follicle-stimulating hormone;  GH = growth hormone;  IHC = immunohistochemical;  IPSS = inferior petrosal sinus sampling;  LH = luteinizing hormone;  MRI = magnetic resonance imaging;  POD = postoperative day;  T4 = thyroxine;  TF = transcription factor;  TSH = thyroid-stimulating hormone;  UFC = urinary free cortisol

Pituitary adenomas are adenohypophyseal tumors that can cause endocrinopathies, such as pituitary hormone hypersecretion or anterior hypopituitarism. Cell lineages are used to classify these tumors on the basis of immunohistochemical (IHC) staining of transcription factors, hormones, and other biomarkers.1 Pituitary adenomas differentiate from pluripotent stem cells along one of three lineage pathways, depending on the following active transcription factors (TFs): pituitary transcription factor 1 (PIT-1), T-box transcription factor (TPIT), or steroidogenic factor-1 (SF-1). Rarely, two or more discrete pituitary adenomas from different lineages are identified in patients; however, the etiology remains unclear.2 The incidence of multiple pituitary adenomas has been reported to be 1%–2% of all resected pituitary adenomas but is likely underestimated based on data from large autopsy series.1–4 Pluri-hormonal adenomas are also rare entities in which a single tumor contains multiple TF lineages with one or more hormonal excesses.1–3 Preoperative recognition of multiple or pluri-hormonal pituitary adenomas is rare, and most tumors are discovered incidentally upon autopsy, intraoperatively, or on histological analysis.2,3,5

In cases of multiple synchronous pituitary adenomas, only one hormone excess syndrome is most frequently evident on clinical presentation and endocrine workup. Silent pituitary tumors positive for prolactin on immunohistochemistry are the most prevalent additional, incidentally found tumor in cases of multiple pituitary adenomas.5 This is particularly true in Cushing disease.6,7 It is important to recognize the presence of multiple pituitary adenomas especially in the setting of hormonally active pituitary adenomas to provide optimal management for this subset of patients. Complete resection is curative for Cushing disease with the standard of care achieved through a transsphenoidal approach. Localization of the tumor presents a challenge because of suboptimal sensitivity of magnetic resonance imaging (MRI) in demonstrating microadenomas, the inconsistency of lateralization with inferior petrosal sinus sampling (IPSS), and delays in pathological analysis.1,8,9 Additionally, the presence of an additional pituitary adenoma can obscure the microtumor through its large size and mass effect and can act as a “decoy lesion” during MRI, IPSS, and resection.6

Consideration of multiple pituitary tumors is necessary for successful resection. In a patient with a biochemical picture of Cushing disease, the demonstration of an adenoma with negative adrenocorticotrophic hormone (ACTH) immunostaining and the absence of postoperative hypoadrenalism may indicate the existence of a double adenoma. Few cases have described a lack of remission of an endocrinopathy after transsphenoidal resection due to the presence of an additional adenoma,2,6,10 and even less so in the instance of the persistence of Cushing disease.6 We present a rare case of double pituitary adenomas in a patient presenting with Cushing disease who underwent two endoscopic endonasal transsphenoidal resections and immunostaining for prolactin and ACTH, respectively, with long-term normalization of her hypothalamic-pituitary-adrenal (HPA) axis.

Illustrative Case

History and Presentation

A 32-year-old female, gravida 0 para 0, with a history of a pituitary lesion and hyperprolactinemia presented to our institution for the evaluation for Cushing disease. Ten years earlier, the patient had presented to a gynecologist with hirsutism, galactorrhea, and oligomenorrhea. Her endocrine workup was remarkable for an elevated prolactin at 33.8 ng/mL (2.3–23.3 ng/mL), while follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) levels were normal. No ACTH or cortisol levels were available. MRI demonstrated a 5 × 6 × 5–mm T1-weighted isointense pituitary lesion protruding into the suprasellar cistern due to a small sella size. She was treated with bromocriptine 2.5 mg daily for 5 years, with normalization of her prolactin level. Subsequent MRI demonstrated a stable lesion size and T1 and T2 hyperintensity in the region of the known pituitary lesion, considered to be posttreatment cystic change with proteinaceous contents and blood. After the normalization of her prolactin levels, she continued to have oligomenorrhea and abnormal hair growth. Polycystic ovaries were not visualized on ultrasound. She was started on oral contraceptives and then switched to the etonorgestrel implant.

A decade after initial presentation, she presented to endocrinology at our institution with 3 years of weight gain, hirsutism, and potential oligomenorrhea. Vital signs were stable (blood pressure: 122/86; heart rate: 72 beats/min), and facial fullness and striae on her bilateral breasts were appreciated on physical examination. She was taking isoniazid and pyridoxine for a recent diagnosis of latent tuberculosis and had discontinued bromocriptine 5 years earlier. Her weight was 66.3 kg and body mass index (BMI) was 23.9 kg/m2. She reported that her maternal uncle had a pituitary tumor. Laboratory analysis was positive for elevated urinary free cortisol (UFC) of 109 µg per 24 hours (2.5–45 µg/24 h; Table 1) and nighttime salivary cortisol of 142 ng/mL (<100 ng/dL) with high-normal prolactin of 22.8 ng/mL (2.3–23.3 ng/dL) and normal FSH, LH, TSH, and thyroxine (T4). Dehydroepiandrosterone sulfate (DHEA-S) was 128 µg/dL (98.8–340.0 µg/dL). Imaging demonstrated a 4 × 4 × 4–mm pituitary lesion with decreased T1-weighted and increased central T2-weighted signal intensity in the left lateral pituitary (Fig. 1A–C). Desmopressin (Ferring Pharmaceuticals DDAVP) stimulation increased a basal ACTH of 49.9 pg/mL to ACTH of 91.2 pg/mL, and cortisol increased from 13.7 µg/dL to 21.2 µg/dL, consistent with neoplastic hypercortisolism. IPSS was performed, which showed a right-sided, central-to-peripheral ACTH gradient (Table 2). The patient elected to undergo endoscopic endonasal resection with the initial target as the left-lateral pituitary mass to achieve a cure for Cushing disease.

TABLE 1Urinary free cortisol at baseline and 3, 5, and 7 months after the primary resection

Variable Baseline 3 Mos 5 Mos 7 Mos on Osilodrostat
Urinary free cortisol (4–50 µg/24 hrs) 109 134.2 125.4 40.3
Urinary creatinine (0.5–2.5 g/24 hrs) 0.995 1.17 1.42 1.11
Urinary vol (mL) 1950 2300 2100 2125
FIG. 1
FIG. 1

Preoperative coronal precontrast (A) and postcontrast (B) T1-weighted magnetic resonance imaging (MRI) and T2-weighted MRI (C) demonstrated a 4-mm3 lesion (arrows) with decreased T1 and increased central T2 signal intensity in the left lateral pituitary. Two days after surgery, coronal precontrast (D) and postcontrast T1-weighted (E) and T2-weighted (F) MRI demonstrated the unchanged adenoma.

TABLE 2Preoperative inferior petrosal sinus sampling with corticorelin ovine triflutate 68 µg

Time (mins) ACTH (pg/mL) Prolactin (ng/mL)
Peripheral Petrosal Sinus ACTH Ratio Peripheral Petrosal Sinus Prolactin Ratio
Rt Lt Rt Lt Rt Lt Rt Lt
−5 50.6 225 1586 4.45 31.34 21 124 295 5.90 14.05
0 48.8 389 1376 7.97 28.20 22.2 185 198 8.33 8.92
3 69.8 4680 1333 67.05 19.1 22.1 396 32.5 17.92 1.47
5 80.9 4590 1623 56.74 20.06 22.1 436 32.2 19.73 1.46
10 112 4160 1660 37.14 14.82 20.2 367 42 17.90 2.05

ACTH or prolactin ratio = inferior petrosal sinus ACTH or prolactin/peripheral blood ACTH or prolactin.

Primary Resection and Outcomes

During the primary resection, abnormal tissue was immediately visible after a linear incision along the bottom of the dura, with an excellent plane of dissection. The inferomedial adenoma was distinct from the known left lateral lesion, and the resection was considered complete by the primary neurosurgeon. Subsequently, the left-sided adenoma was not pursued because of the historical prolactinoma diagnosis and an assumption that the newly discovered adenoma was the cause of ACTH hypersecretion. However, pathology of the inferomedial tumor was strongly and diffusely positive for prolactin (Fig. 2B), synaptophysin, and cytokeratin, with an Mindbomb Homolog-1 (MIB-1) proliferative index of 2.4%. ACTH, growth hormone (GH), FSH, LH, and TSH immunostaining were negative. TF immunohistochemistry was not available. On postoperative day (POD) 1, pituitary MRI was performed and demonstrated the unchanged 4-mm3 T1-weighted hypointense lesion with small central T2-weighted hyperintensity in the left lateral gland (Fig. 1D–F). Cortisol levels ranged from 9.7 to 76.2 µg/dL (4.8–19.5 µg/dL), and ACTH was 19.5 pg/mL (7.2–63.3 pg/mL) on POD 1.

FIG. 2
FIG. 2

Histological examination of surgical specimens from the inferomedial (A–C) and left lateral (D–F) lesions. The initial resection (hematoxylin and eosin [H&E], A) was strongly and diffusely positive for prolactin (B) with normal reticulin levels (C) indicating a lactotrophic pituitary adenoma. The second operation (H&E, D) was diagnostic for a corticotropic pituitary adenoma with diffusely positive adrenocorticotrophic hormone (ACTH) (E) and decreased reticulin (F). Original magnification ×100.

Early reoperation was discussed with the patient based on the pathology and persistent hypercortisolism; however, she elected to pursue conservative management with close follow-up. Postoperative cortisol nadir was 4.8 µg/dL (4.8–19.5 µg/dL) on POD 2 during her 4-day hospital stay. DHEA-S was significantly decreased from baseline at 22.3 µg/dL (98.8–340.0 µg/dL) and a prolactin level of 3.4 ng/mL (2.3–23.3 ng/dL) was low-normal. No glucocorticoids were administered during her hospital course. There was no clinical evidence of vasopressin deficiency while she was an inpatient.

Three months postoperatively, the patient reported insomnia, poor hair quality, fatigue, nocturnal sweating, and continued increasing weight gain with fat accumulation in the supraclavicular and dorsal cervical area. She had one spontaneous menstrual period despite the use of etonogestrel implant. UFC was increased at 134.2 µg/24 hours (4–50 µg/24 h; Table 1). The 8:00 am serum cortisol was 10.2 µg/dL (5.0–25.0 µg/dL). She was started on osilodrostat 2 mg twice daily for her persistent hypercortisolism, and she reported some clinical improvement; however, she had continued elevation in her late-night salivary cortisol levels up to 7.0 nmol/L. Other endocrine lab work was normal, with a prolactin of 13.5 ng/mL (2.8–23.3 ng/mL) and TSH of 3.67 µIU/mL (0.4–4.0 µIU/mL). Her weight had increased by 4.9 kg to 71.2 kg with a BMI of 25.3 kg/m2. Approximately 6 months postoperatively, she was amenable to a secondary resection targeting the remaining left lateral pituitary adenoma.

Secondary Resection and Outcomes

After obtaining adequate exposure for the secondary resection, the lesion in the left lateral aspect of the pituitary was targeted. The tumor was clearly identified and completely resected without intraoperative complication. IHC staining was diffusely positive for ACTH (Fig. 2E), synaptophysin, and cytokeratin with decreased reticulin and an MIB-1 index of 3.3%. Prolactin, GH, TSH, LH, and FSH immunostaining were negative. Postoperative cortisol monitoring demonstrated decreased levels, with a nadir of 2.0 µg/dL on POD 0. Levels of ACTH and DHEA-S were decreased at 4.4 pg/mL (7.2–63.3 pg/mL) and 13.3 µg/dL (98.8–340 µg/dL), respectively, on POD 1. Prolactin remained within the normal range at 8.2 ng/mL (2.8–23.3 ng/mL). The patient was started on intravenous hydrocortisone 50 mg every 8 hours for adrenal insufficiency. Postoperative symptoms of nausea, headache, and muscle weakness resolved with hydrocortisone administration. She was discharged on hydrocortisone 60 mg daily in divided doses for adrenal insufficiency and had no signs of vasopressin deficiency during her 2-day hospital course.

By 3 months, the patient reported decreased fatigue, myalgia, and insomnia and improved overall well-being and physical appearance. She was weaned down to a total daily dose of 20 mg of hydrocortisone and had lost 5.2 kg. Her menstruation returned while having an etonogestrel implant. Rapid ACTH stimulation was abnormal, with decreased cortisol at 30 minutes of 4.1 µg/dL (7.2–63.3 pg/mL) demonstrating continued adrenal insufficiency. Follow-up MRI demonstrated miniscule remaining left pituitary adenoma (Fig. 3). Seven months after her second surgery, she was started on 50 µg levothyroxine for primary hypothyroidism in the setting of slightly elevated TSH of 4.1 µIU/mL (0.4–4.0 µIU/mL) and a low-normal T4 of 0.8 ng/dL (0.7–1.5 ng/dL).

FIG. 3
FIG. 3

Postoperative imaging 3 months after the second operation demonstrates near gross-total resection (yellow arrows: surgical cavity) of the left lateral pituitary adenoma on coronal precontrast (A) and postcontrast T1-weighted (B) and T2-weighted (C) MRI.

Two years after the second resection, the patient lost 10.1 kg (weight, 61.1 kg; BMI, 21.76 kg/m2). Her ACTH stimulation test became normal, and hydrocortisone therapy was discontinued. At the 2-year time point, the patient and her husband successfully conceived a child.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Double or multiple pituitary adenomas are discovered in 0.37%–2.6% of resected pituitary lesions.3,4,6,11,12 A majority of multiple pituitary adenomas are not suspected before surgery with an inconclusive clinical presentation or endocrine laboratory workup.6 The presentation of multiple synchronous neoplasms is thought to be more common than having a single neoplasm with multiple lineages.1 Studies have shown that additional pituitary adenomas are seen at a rate of 1.6%–3.3% in Cushing disease in studies including both contiguous and noncontiguous double pituitary adenomas.6 Additional pituitary adenomas that are hormonally active make up 40% of resected double pituitary adenomas, with most staining for gonadotroph adenoma.13 Overall, the most common incidental pituitary adenoma is prolactinoma,6 which occurs most frequently with GH or ACTH adenomas.5 In very rare instances, Cushing cases can present with hyperprolactinemia and Cushing synchronously.6 Hormonal secretion and clinical presentation are variable, with the pathology most often attributed to only one component of double pituitary adenoma.3,14 The multiple-hit theory is the most common hypothesis for double pituitary adenoma etiology with coincidental monoclonal expansion of two or more lineages, which present with separate pseudo-capsules for each lesion.15

Observations

On presenting with Cushing disease, the differential diagnosis before the initial operation considered that the known left lateral pituitary adenoma could be a mixed tumor with both prolactin and ACTH lineages. Therefore, it was the initial target of the resection until discovering the second adenoma intraoperatively. With two distinct adenomas, the inferomedial adenoma was presumed to be the source of the ACTH hypersecretion and was subsequently resected. The left lesion was thought to be a prolactinoma and hormonally inactive after historical dopaminergic therapy and thus was not pursued during the initial surgery. However, pathology confirmed that the opposite was true. Few cases have also involved incidental pituitary tumors that look like the hormonally active adenoma and encourage resection of it, leaving the primary pituitary adenoma behind.6,7 It has been reported that these “decoy lesions” can cause surgical failure and require secondary operations.6,7,10,16 Intraoperative localization and confirmation of the adenoma classification may have also been helpful during the case, including tissue-based ACTH antibody assay,9 plasma ACTH measurements with a immunochemiluminometric method,17 or intraoperative ultrasound.5,6

The inferomedial second tumor was not appreciated or reported throughout her serial MRI studies from 2010 to 2020. Interestingly, imaging did demonstrate the left pituitary adenoma that was medically treated as a prolactinoma, although it was later diagnosed as an ACTH-secreting lesion on IHC staining. Preoperative visualization of a pituitary adenoma in Cushing disease is reported to be limited, with a reported 50% incidence with negative MRI with standard 1.5 T.1,18,19 MRI technical refinements in magnet strength, slice thickness, or enhanced spin sequences have increased sensitivity, but one-third of patients with Cushing disease still have negative scans.20 Small prolactinomas, especially those near the cavernous sinus, are also notoriously difficult to visualize on MRI, although recent advances using co-registration of 11C-methionine positron emission tomography–computed tomography with MRI (Met-PET/MRICR) may prove useful.21 Difficulty with preoperative visualization complicates a diagnosis of multiple adenomas, with or without multiple endocrinopathies, and negatively affects surgical planning. In a single-institution retrospective review of MRI in all cases of double pituitary tumors, only one of eight patients (12.5%) over 16 years of age had a positive MRI for double pituitary tumors and was diagnosed preoperatively.2

The patient’s preoperative IPSS demonstrated a right central-to-peripheral gradient. This was incongruent with the MRI demonstrating the single left-sided tumor. While IPSS is useful in confirming Cushing disease, its sensitivity for lateralization has been reported at only 59%–71%.9 With this in mind and a known left-sided adenoma on MRI, exploration of the right side of the pituitary was not originally planned. Ultimately, the left-sided adenoma was the source of ACTH hypersecretion, which remains incongruent with preoperative IPSS. It has been suggested that multiple pituitary adenomas in Cushing disease could further decrease its accuracy.1,6

The patient’s initial historical prolactin levels (33.8 ng/dL) were lower than reported levels of 100–250 ng/dL for microadenoma and >250 ng/dL in cases of macroadenoma. Normally, in active single prolactinoma, prolactin secretion is correlated to size. We do not suspect that the presence of more than one pituitary adenoma would affect the level of prolactin hypersecretion.6 Slight elevations in prolactin can be attributed to causes such as pituitary stalk effect, medications, and physiological stimulation. During the 5 years of bromocriptine therapy, the effect on the inferomedial prolactinoma was unknown, as it was not appreciated on MRI. There are reports of prolactinomas being less responsive to dopaminergic agonist therapy in cases of double adenomas.14,22 Upon resection of the inferomedial prolactinoma during the initial operation, there was no further change in the patient’s prolactin levels, which could most likely be attributed to prior dopaminergic therapy. Unfortunately, the initial endocrine laboratory workup did not include levels of ACTH or cortisol. In addition to hyperprolactinemia, Cushing disease can also present with changes in menstruation. After the secondary resection and removal of the ACTH-secreting pituitary adenoma, the patient’s oligomenorrhea resolved and she achieved pregnancy. Retrospectively, it remains unclear if the prolactinoma was once truly active hormonally.

Lessons

The rare presence of two pituitary adenomas can complicate the diagnosis, medical and surgical management, and long-term outcomes for patients. A complete endocrine workup is essential when a pituitary adenoma is suspected and can help screen for pluri-hormonal and multiple pituitary adenomas. In our patient, it is unknown when the onset of hypercortisolism was with the limited initial hormonal workup.

Currently, localizing and resecting the hormonally active adenoma in double or multiple pituitary adenomas remain a challenge, with limitations in preoperative imaging and intraoperative measures. After encountering the additional inferomedial lesion during surgery, resection of both adenomas during the initial surgery may have been prudent to ensure the resolution of Cushing disease. Although exploration for additional pituitary adenomas is not usually recommended, it could be considered in cases of multiple pituitary adenomas and uncertainty of the culprit of Cushing disease.

The current characterization of pituitary tumors by the World Health Organization includes immunohistochemistry for both transcription factors and pituitary hormones, with clinical usefulness to be determined by future studies. Multiple lineages can occur mixed in a single pituitary adenoma or across different noncontiguous adenomas and can only be determined by TF immunostaining. The left ACTH-staining lesion in our patient had some shrinkage and MRI changes, which may have been a response to dopaminergic therapy. Full characterization of the tumor cell lineages in this case remains undetermined without staining for TFs.

In conclusion, we report a rare case of Cushing disease concurrent with a prolactinoma leading to the need for repeat resection. This is one of the few reported cases of a double pituitary adenoma leading to a lack of biochemical remission of hypercortisolism after the initial surgery. Strategies for localization of the active tumor in double pituitary adenomas are essential for primary surgical success and the resolution of endocrinopathies.

Author Contributions

Conception and design: Zwagerman, Tavakoli, Shah, Findling. Acquisition of data: Zwagerman, Armstrong, Tavakoli, Shah, Ioachimescu, Findling. Analysis and interpretation of data: Zwagerman, Armstrong, Tavakoli, Shah, Coss, Ioachimescu, Findling. Drafting of the article: Zwagerman, Armstrong, Shah. Critically revising the article: Zwagerman, Armstrong, Tavakoli, Shah, Ioachimescu, Findling. Reviewed submitted version of the manuscript: Zwagerman, Armstrong, Tavakoli, Shah, Laing, Ioachimescu, Findling. Approved the final version of the manuscript on behalf of all authors: Zwagerman. Statistical analysis: Armstrong, Shah. Administrative/technical/material support: Zwagerman, Armstrong, Shah. Study supervision: Zwagerman, Tavakoli, Shah, Laing.

References

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Risk Comparison and Assessment Model of Deep Vein Thrombosis in Patients with Pituitary Adenomas After Surgery

Posted on October 22, 2025 by MaryO

Abstract

Background

Deep vein thrombosis (DVT), a major component of venous thromboembolism (VTE), is a common postoperative complication. Its occurrence after pituitary adenoma surgery is influenced by multiple factors.

Methods

This retrospective study analyzed 1440 pituitary adenoma cases treated at Beijing Tiantan Hospital (2018–2023). The incidence of postoperative DVT was recorded, and logistic regression was used to identify associated risk factors. Differences across pituitary adenoma subtypes were compared. Additionally, Regression and machine learning models were developed to predict DVT.

Results

Among 397 patients who underwent postoperative lower limb ultrasound, 104 (7.2 %) developed DVT. Significant risk factors included advanced age, higher body mass index (BMI), intravenous cannulation, prolonged hospital stay, shorter preoperative activated partial thromboplastin time (APTT), longer thrombin time (TT), elevated platelet count, and higher postoperative D-dimer levels. Patients with Cushing’s disease exhibited a significantly higher DVT incidence, potentially related to decreased pre- and postoperative APTT and PT/INR values. Conversely, patients with prolactin-secreting adenomas had a lower DVT incidence, possibly due to younger age and higher postoperative PT values. A support vector machine (SVM) model showed strong predictive performance (AUC: 0.82; accuracy: 86.08 %; specificity: 96.72 %).

Conclusion

DVT incidence varies by pituitary adenoma subtype. Machine learning enhances predictive models for postoperative DVT in pituitary adenoma patients.

Introduction

Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism, is a common cardiovascular disorder. It typically presents with clinical symptoms such as lower limb swelling, chest pain, tachypnea, and, in severe cases, may result in fatal outcomes [1]. The development of VTE is influenced by three factors known as the Virchow triad: altered venous blood flow, endothelial or vessel wall damage, and hypercoagulability [2]. Surgical procedures can increase the risk of VTE, particularly DVT in the lower extremities, due to intraoperative injuries and postoperative hemodynamic changes [[3], [4], [5]]. In the absence of anticoagulant prophylaxis, the incidence of VTE following brain tumor surgery ranges from 3 % to 30 % [[6], [7], [8]]. Although pituitary adenomas are commonly considered benign cranial tumors, emerging evidence suggests that patients undergoing resection of pituitary adenomas may have a higher risk of postoperative VTE compared to those with other sellar or parasellar tumors such as craniopharyngiomas, meningiomas, or chordomas [9].
This disparity may be attributed to the unique hormone secretion functions of pituitary adenomas, as well as dysregulation of water and electrolyte balance—following surgery. Despite this, the risk factors contributing to the development of postoperative VTE in pituitary adenomas have not been extensively explored. Limited studies have identified a particularly elevated VTE risk in patients with Cushing’s disease, a hormone-secreting subtype of pituitary adenoma [10]. Given the relatively high incidence of postoperative DVT in this population, the present study aims to systematically investigate risk factors associated with lower extremity DVT after pituitary adenoma surgery. Furthermore, we seek to compare thrombotic risk across different clinical subtypes of pituitary adenomas and to construct a tailored risk prediction model to guide perioperative thromboprophylaxis in affected patients.

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Changing face of Cushing’s Disease Over Three Decades in Pituitary Center

Posted on October 1, 2025 by MaryO

Abstract

Objective

Cushing Disease (CD) presents with typical clinical findings, even though, there is a wide spectrum of manifestations. Over the years, the sings and symptoms of Cushing’s syndrome (CS) have become more subtle and atypical forms of CS have emerged. In this study, we aimed to investigate the changes in the clinical presentation of CD in recent years.

Materials and methods

In this study, CD patients followed by our center were examined. A total of 258 patients with CD were included in the study. The clinical findings at the time of presentation, laboratory and imaging findings, treatment modalities and remission status in the first year after treatment were evaluated.

Results

The mean age of the patients included in the study was 41.3 ±13.28 years. CD patients diagnosed between 2013 and 2023 were older than those diagnosed between 1990 and 2012 (p < 0.001). There was no difference between the groups in terms of gender. Moon face, purple striae, hirsutism, and menstrual irregularities were statistically significantly less frequent in the last 10 years than in previous years (p < 0.001; p = 0.004; p < 0.001; p < 0.001, respectively). In addition, patients who applied after 2013 had lower baseline cortisol and adrenocorticotropic hormone (ACTH) levels, and a smaller median size of the pituitary adenoma. Limitations of the study include its retrospective design and the subjectivity of clinical data.

Conclusion

As the clinical presentation of Cushing’s disease changes over time, waiting for the typical Cushing’s clinic can delay diagnosis. It is important that clinicians take this into account when they suspect CD.

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Pregnancy Case: Cushing’s Syndrome with Diabetes Insipidus

Posted on September 3, 2025 by MaryO

Cushing’s Syndrome, a rare but complex endocrine disorder characterized by excessive cortisol production, presents unique challenges and risks during pregnancy. Recent advancements in medical understanding have led to greater awareness of the implications of this syndrome when coupled with conditions like diabetes insipidus, particularly in pregnant patients. The coexistence of these disorders emphasizes the need for a multidisciplinary approach to manage these high-risk pregnancies effectively.

In a groundbreaking case report published in BMC Endocrine Disorders, researchers Hata et al. provide an illuminating examination of a pregnant patient diagnosed with Cushing’s Syndrome along with diabetes insipidus. This syndromic constellation is particularly alarming considering the metabolical and physiological adaptations that occur during pregnancy. The researchers delve deeply into the complexities presented by this rare overlap, offering insight into potential therapeutic pathways and management strategies.

Cushing’s syndrome is often the result of pituitary adenomas or adrenal tumors that result in a hypercortisolemic state. When analyzing its manifestation during pregnancy, clinicians are faced with the delicate balance of managing both maternal and fetal health. In this compelling case, the authors explore the detrimental effects of high cortisol levels and the complications that arise from diabetes insipidus on maternal health.

Diabetes insipidus in pregnancy can further complicate the management of Cushing’s syndrome. It is primarily characterized by an inability of the kidneys to concentrate urine due to a deficiency in the antidiuretic hormone (ADH). This disorder can lead to severe dehydration, electrolyte imbalances, and complications such as preterm labor or uterine atony. By detailing the clinical features of the patient, the report underscores the need for vigilant monitoring and timely interventions to prevent adverse outcomes.

Central to the case is the interplay between the hormonal milieu of pregnancy and the pathological processes of Cushing’s syndrome. The physiological increase in cortisol can mask or exacerbate the symptoms of diabetes insipidus. Thus, clinicians must be astute in recognizing the overlays of these conditions to adjust management plans accordingly. This is especially critical in the prenatal period, where traditional approaches might clash with the unique requirements of pregnancy.

Therapeutic management for such patients is multifaceted. Close collaboration among obstetricians, endocrinologists, and neonatologists is essential to ensure that both maternal and fetal welfare are prioritized. This case illustrates the complexity involved in choosing appropriate pharmacotherapy while minimizing risks to the developing fetus. Importantly, the authors suggest that non-invasive monitoring techniques may help in realizing a safer management regime.

The psychological impact on mothers grappling with these intertwined conditions cannot be overstated. The report sheds light on the emotional strain that awaits patients who must anticipate the uncertainties surrounding their pregnancies. Understanding these layers can aid healthcare providers in offering holistic support not just medically, but psychologically as well.

An often-overlooked aspect of such complex cases is the significance of postnatal follow-up. After delivery, the management of Cushing’s Syndrome may need reevaluation as hormonal levels return to baseline. In this case, the potential resolution of diabetes insipidus after childbirth rejuvenates discussions regarding long-term monitoring and treatment adherence, ensuring that mothers receive the care they need as they transition into motherhood.

Women with Cushing’s Syndrome and diabetes insipidus can experience heightened fatigue, which complicates the already demanding experience of pregnancy. The authors advocate for the integration of lifestyle modifications and supportive measures to help manage energy levels, further illustrating the multifaceted management required in such cases. These alterations can significantly contribute to improving the quality of life for these women in an already challenging scenario.

The ethical considerations surrounding the treatment of pregnant patients with rare syndromes add another layer of complexity. The authors emphasize the importance of informed consent, particularly as clinical decisions might involve experimental therapies or interventions that are not standard for pregnant patients. Open dialogues between patients and providers about risks and benefits can lead to better decision-making processes tailored to individual patient needs.

In conclusion, Hata et al.’s illuminating case report on Cushing’s Syndrome with diabetes insipidus in pregnancy serves as a pivotal reference for clinicians navigating the complexities of these coexisting conditions. As medical science continues to evolve, the insights offered in this report will undoubtedly inform best practices for managing intricate cases, further enhancing maternal-fetal medicine. The need for ongoing research and clinical trials remains crucial as we strive to optimize pregnancy outcomes in patients suffering from this rare combination of disorders.

As we look toward the future, the challenges presented by these conditions urge the medical community to prioritize collaborative care models, innovative therapeutic strategies, and comprehensive support systems for affected patients. While this case report sheds light on the clinical intricacies involved, it also heralds a call to action for further exploration into Cushing’s Syndrome and its implications in pregnancy, ensuring that mothers receive the best possible care during one of life’s most critical journeys.

Subject of Research: Cushing’s Syndrome with diabetes insipidus in pregnancy

Article Title: Cushing’s Syndrome with diabetes insipidus in pregnancy: a case report

Article References:

Hata, S., Shinokawa, N., Harada, Y. et al. Cushing’s Syndrome with diabetes insipidus in pregnancy: a case report.
BMC Endocr Disord 25, 197 (2025). https://doi.org/10.1186/s12902-025-01946-9

Image Credits: AI Generated

DOI: 10.1186/s12902-025-01946-9

Keywords: Cushing’s Syndrome, diabetes insipidus, pregnancy, maternal-fetal medicine, endocrine disorders, case report, hypercortisolism, antidiuretic hormone, multidisciplinary approach, healthcare management.

From https://bioengineer.org/pregnancy-case-cushings-syndrome-with-diabetes-insipidus/

Filed under: adrenal, Cushing's, pituitary, Rare Diseases | Tagged: , , , , | Leave a comment »

Severe Psychosis Due to Cushing Syndrome

Posted on August 28, 2025 by MaryO

Cushing syndrome (CS) is a rare clinical condition resulting in excess cortisol production. Neuropsychiatric disturbances are prevalent, in addition to the well-known metabolic effects. Depression and anxiety are the most common manifestations, while mania and psychosis are rare.1,2 We report the case of a patient who presented with severe psychosis due to adrenocorticotropic hormone (ACTH)–dependent CS due to a pituitary adenoma (PA).

Case Report

A 47-year-old woman was brought to the hospital after she was found wandering on someone’s property 2 days after her parents had filed a missing person report. She was disoriented, had difficulty recalling events, and reported intrusive thoughts. She had a history of hypertension, hyperlipidemia, prediabetes, and schizoaffective disorder diagnosed 10 years ago when she had an episode of acute psychosis. She was noncompliant with her medications.

On presentation, her blood pressure was 160/111 mm Hg, pulse rate was 111 bpm, and body mass index was 24.14 kg/m2. The psychiatric examination revealed disorientation, thought disorganization, subdued mood, blunted affect, and impaired memory and attention. She had central adiposity and coarse terminal hair growth on her chin; the rest of the physical examination was unremarkable. She was started on olanzapine but developed catatonia after 10 days. Olanzapine was discontinued after 4 weeks as her catatonia worsened. Due to the worsening of hypertension, her random cortisol level was checked and found to be elevated at 51.8 μg/dL (2.9–19.4 μg/dL). Further workup was deferred due to testing difficulty in the setting of acute psychosis. A trial of aripiprazole was initiated but was discontinued after 10 days due to the persistence of catatonia. She then received electroconvulsive therapy on alternate days for 11 sessions, with improvement in her symptoms.

The workup of CS was initiated due to the difficulty in managing her symptoms, weight gain, worsening of hypertension, and pedal edema. Laboratory investigations showed potassium of 2.7 mEq/dL (3.5–5.5 mEq/dL), elevated serum cortisol of 39.3 μg/dL (2.9–19.4 μg/dL), and ACTH of 100.2 pg/dL (7.2–63.3 pg/dL). Her 24-hour urinary free cortisol level was 2,340 and 1,180 (≤45 μg/dL) on 2 separate occasions, thyroid-stimulating hormone was 0.02 (0.4–4.0 mIU/L), and free thyroxine was 0.6 (0.7–1.9 ng/dL). The dexamethasone suppression test was also abnormal. Given that her ACTH level was elevated, there was a high concern for a PA. A magnetic resonance imaging scan revealed a 9.3 x9.6–mm nonenhancing focus on the posterior aspect of the pituitary, which confirmed the diagnosis of ACTH-dependent CS. Central hypothyroidism was attributed to the mass effect of the PA. Transsphenoidal PA resection was performed with subsequent improvement in her symptoms.

Discussion

Acute psychosis may be the initial manifestation of CS. This can easily be overlooked, especially in patients with preexisting psychiatric conditions. CS can be indolent, with clinical and neuropsychiatric features often beginning years before diagnosis. In this case, the initial presentation a decade ago could also be attributed to CS. Many antipsychotic drugs can result in metabolic syndrome, which can be hard to differentiate from manifestations of CS.3 Individuals with neuropsychiatric disorders can have elevation in their cortisol levels due to activation of the hypothalamic-pituitary axis, especially in the evening, without the presence of any pituitary or adrenal adenomas (these result in pathological hypercortisolism).4 This is known as pseudo-CS or physiological hypercortisolism.5 Based on clinical features alone, physiological and pathological hypercortisolism can be hard to distinguish. A high index of clinical suspicion is needed, with repeat testing often required, as there are no specific cutoffs to distinguish between these conditions.6,7

In patients with severe neuropsychiatric illness and features of metabolic syndrome, a diagnosis of CS should be strongly considered, especially in those not responding to conventional treatment strategies. Early recognition and treatment can lead to improved outcomes, though complete recovery of psychiatric symptoms may not be seen in some patients.8,9

AnchorArticle Information

Published Online: August 21, 2025. https://doi.org/10.4088/PCC.25cr03957
© 2025 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2025;27(4):25cr03957
Submitted: March 6, 2025; accepted April 30, 2025.
To Cite: Dhaliwal G, MD; Kaur JK, Batra J, et al. Severe psychosis due to Cushing syndrome. Prim Care Companion CNS Disord 2025;27(4):25cr03957.
Author Affiliations: Department of Endocrinology, Diabetes and Metabolism, HealthPartners Institute, Minneapolis, Minnesota (Dhaliwal, JK Kaur, J Kaur); Department of Endocrinology, University of Nebraska, Omaha, Nebraska (Batra).
Corresponding Author: Jasleen Kaur, MD, Department of Endocrinology, Diabetes and Metabolism, HealthPartners Institute, 401 Phalen Blvd, St Paul, MN 55130 (jasleen.x.kaur@healthpartners.com).
Relevant Financial Relationships: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect patient anonymity.
ORCID: Jasleen Kaur: https://orcid.org/0000-0002-0584-4638

From https://www.psychiatrist.com/pcc/severe-psychosis-due-cushing-syndrome/

Filed under: Cushing's, pituitary, symptoms | Tagged: , , , , , | Leave a comment »

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