Aggressive Invasive Pituitary Macroadenoma Involving Pituitary Infundibulum.

Pituitary adenomas displaying radiographic invasiveness and an exceptionally high tumor growth rate are referred to as aggressive pituitary tumors (APTs). A pituitary adenoma involving the infundibulum is a rare occurrence. We report the case of a 41-year-old female presenting with headaches for one year, which were progressive in nature, along with blurring of vision. On radiological and histopathological examination, the cause was diagnosed as pituitary adenoma and APT involving the infundibulum.

Endoscopic Resection of Pituitary Macroadenomas Extending Into the Nasal Cavity: A Case Report and Literature Analysis.

Pituitary macroadenomas are benign tumors that typically present with symptoms of hormonal imbalance or visual disturbances due to their location and size. However, in rare instances, these tumors can extend beyond the sellar region into the nasal cavity, leading to unusual clinical presentations. This case report describes a 63-year-old woman who presented with progressive nasal obstruction, episodes of dizziness, and occasional headaches. Physical examination revealed a large, firm mass in the nasopharynx. Nasal endoscopy and computed tomography (CT) imaging confirmed the presence of a pituitary macroadenoma measuring 7.3 x 4 x 4.9 cm, extending from the pituitary gland through the sphenoid sinus into the nasal cavity. The tumor did not affect the optic chiasm despite its significant size, as evidenced by normal visual field tests. The patient underwent successful endoscopic transnasal resection of the tumor, a minimally invasive procedure that allowed for complete removal with minimal morbidity. Postoperative recovery was uneventful, and follow-up imaging showed no residual tumor. The patient reported a significant improvement in symptoms, particularly the resolution of nasal obstruction and headaches. Histopathological examination confirmed the diagnosis of a pituitary macroadenoma. This case highlights the rare presentation of pituitary macroadenomas as nasal masses and emphasizes the importance of considering this diagnosis in patients with atypical nasal symptoms. The successful outcome following endoscopic transnasal surgery demonstrates the effectiveness of this approach in managing complex pituitary adenomas with extensive extracranial extension.

Successful management of refractory Cushing's disease with severe hypercortisolemia using etomidate and temozolomide in post-surgical failure.

Corticotropinomas account for 20% of all aggressive pituitary tumors and pituitary carcinomas and are associated with high mortality. These tumors not only cause neurovascular compromise but can also be fatal due to severe hypercortisolemia itself. Although surgery is considered the primary treatment modality, it is often partially successful or unsuccessful. Moreover, these tumors frequently recur and may be resistant to conventional treatments, including surgery and radiotherapy. Therefore, early multimodal treatment and regular follow-up are necessary. We present a case of aggressive Cushing's disease managed with combined temozolomide therapy and radiotherapy following an unsuccessful transsphenoidal surgery, resulting in significant long-term radiological and biochemical remission. In addition, etomidate infusion was administered to achieve rapid cortisol reduction, highlighting its role as a bridging therapy to other modalities in treating life-threatening and severe hypercortisolemia outside an intensive care setting.

Endoscopic endonasal transpterygoid trans lacero-cavernous resection of Knosp 4 functioning pituitary macroadenoma.

In this video, we demonstrate the technique of endoscopic transpterygoid trans lacerum trans cavernous approach for the excision of Knosp 4 functioning pituitary macroadenomas. We highlight the anatomy and key steps of the approach using cadaveric dissection and present two clinical cases. A 42-year-old female with a growth hormone-secreting tumor and Knosp 4 macroadenoma underwent an extended endoscopic endonasal approach and near-total excision of the tumor. Postoperatively she was neurologically intact. Postoperative MR showed a small residue in the lateral compartment of the cavernous sinus and along the right optic tract superiorly. Due to the proximity of the residual tumor near the optic apparatus, she was offered a pterional approach, and the tumor around the optic apparatus was excised. She was given stereotactic radiosurgery for the small residual tumor in the cavernous sinus and is currently doing well, under remission. The second case was a 23-year young male with acromegaly and bilateral Knosp 4 macroadenoma. He underwent endoscopic transpterygoid trans lacerum trans cavernous approach and gross total excision of the tumor was done. He had transient bilateral ophthalmoplegia in the immediate postoperative period which recovered fully within 6 weeks. He is currently in remission without any need for radiotherapy. To conclude, an in-depth knowledge of the anatomy helps in improving surgical outcomes in extended endoscopic endonasal surgeries.

Postural Change Assists Surgical Maneuverability During Endoscopic Transsphenoidal Surgery for Pituitary Macroadenoma.

BACKGROUND: In endoscopic transsphenoidal surgery for pituitary adenoma with suprasellar extension, the prolapse of the stretched floppy diaphragma sellae can obstruct the surgical corridor, posing challenges during pituitary surgery. We introduce a simple postural change technique to mitigate this issue and share our clinical experience. METHODS: Pituitary surgery is performed on an operating table where the patient's position can be adjusted. During transsphenoidal pituitary surgery, raising the patient's head to a Fowler position causes the diaphragma sellae to move upward, whereas lowering the head to a supine position causes it to descend. This simple adjustment minimizes hindrance from the floppy diaphragma sellae during surgery. RESULTS: We illustrate this technique in pituitary surgery, where diaphragm sellae relocation is necessary. CONCLUSIONS: A simple postural change technique effectively manages prolapsed floppy diaphragma sellae, enhancing visualization and surgical accessibility during endoscopic transsphenoidal pituitary surgery.

A Complex Case of Pituitary Apoplexy Mimicking a Stroke: A Case Report With a Review of the Literature.

Pituitary adenomas, benign tumors originating in the pituitary gland, are classified based on size and hormone activity. Pituitary apoplexy, defined by hemorrhage or infarction of these adenomas, poses a challenge in estimation due to its subtle presentation. It often manifests as sudden, severe headaches, visual disturbances, nausea, and hormone deficiencies. Diagnosis typically involves MRI or, if unavailable, CT scans, alongside hormonal and other laboratory assessments. Here, we present the case of a 71-year-old female patient who was transferred to the hospital for endovascular treatment of a hemorrhagic stroke after presenting with sudden-onset symptoms suggestive of a stroke. Neurological examination revealed right-sided ptosis, diplopia, and bitemporal hemianopsia. The initially performed CT imaging suggested hemorrhagic stroke. Subsequent MRI reviewed pituitary macroadenoma with apoplexy. Immediate surgical management via endoscopic, endonasal, transsphenoidal adenomectomy resulted in gradual symptom improvement. The patient was discharged three days after the procedure with complete symptom improvement and showed no signs of recurrence during regular follow-ups at one and three months post-surgery. This case emphasizes the critical role of accurate imaging in diagnosing and managing patients with pituitary macroadenomas complicated by apoplexy, which can mimic stroke. While CT scans may lack detail, MRI offers precise information. Prompt recognition and evaluation are vital for effective treatment, highlighting the importance of distinguishing between these conditions for optimal patient care.

Visual morbidity in macroprolactinoma: A retrospective cohort study.

OBJECTIVE: The management of visual field damage in patients with macroprolactinomas is a major therapeutic challenge. We aimed to study the visual morbidity associated with macroprolactinoma and its outcomes following medical and surgical treatment. We aimed to identify predictors of visual recovery. METHODS: We retrospectively reviewed patient's data including clinical presentation, serial pituitary magnetic resonance imaging, laboratory tests, visual symptoms and neuro-ophthalmologic examination, visual field tests and optical coherence tomography tests. The main outcome was complete visual field recovery. Descriptive analyses were conducted. Predictors of visual recovery were investigated. PATIENTS: The study cohort included 150 patients with macroprolactinoma [median follow-up, 6.0 years (interquartile range (IQR) 2.9-10.6)]. RESULTS: At diagnosis, visual field defects were evident in 40 patients (26.7%). At the end of follow-up, 24 out of 39 available visual field tests (61.5%) exhibited complete recovery. Patients that achieved complete visual recovery had smaller macroadenomas at diagnosis [30.5 mm (15.0-80.0) vs. 42.0 mm (30.0-85.0), p < .01], lower baseline serum prolactin levels [1414 mcg/L (489-3586) vs. 4119 mcg/L (2715-6315), p < .01], lower rates of central hypogonadism (78.3% vs. 93.3%, p = .05) and central hypothyroidism (20.8% vs. 53.3%, p = .04), lower rates of compressive optic neuropathy (35.3% vs. 87.5%, p = .02) and a better visual acuity (better than 6/8 in both eyes, 93.7% vs. 28.6%, p < .01). CONCLUSIONS: In our cohort of 150 patients with macroprolactinoma, 40 patients (26.7%) presented with visual field defects, of which 61.5% achieved complete visual recovery with treatment. Patients that achieved complete visual recovery presented with smaller macroadenomas, lower serum prolactin levels, lower rates of central hypogonadism and central hypothyroidism, lower rates of compressive optic neuropathy and better visual acuity.

Adrenocorticotropic Hormone Producing Pituitary Carcinoma in the Falx Cerebri, Retroclival Region, Ethmoidal Cells, and Other Locations.

Pituitary carcinoma is a condition defined by metastasis of a pituitary tumor to a distant location, and it is a very rare type of adenohypophyseal tumor. We present a case of a 29-year-old female who was followed up in our Endocrinology Department. Past medical history included the diagnosis of Cushing disease and transsphenoidal tumor resection at 12 years of age, followed by transcranial resection two years later because of persistently elevated adrenocorticotropic hormone (ACTH). Despite the surgical management, the patient persisted with increased ACTH and hypercortisolism, and, thus, bilateral adrenalectomy was performed a year later. Two years after the procedure, the patient presented with a newly diagnosed pituitary macroadenoma, and the diagnosis of Nelson syndrome was made. Linear accelerator radiotherapy was given, which reduced the size of the tumor. Later, several imaging studies showed multiple lesions on the falx cerebri, posterior clinoid process, retroclival region, cerebellopontine angle, pterygopalatine fossa, infratentorial region, and posterior ethmoidal cells. Biopsy and immunohistochemistry of the falx cerebri lesions described ACTH-producing pituitary adenocarcinoma. Treatment was given with intramuscular octreotide, dabrafenib, and trametinib. Despite persistently elevated ACTH levels, the patient has since remained clinically stable, without new development or worsening of symptoms. There are three unique aspects of our case. First, we reported an unusual presentation of this disease, since the patient in our case was a female with an early age of onset. Second, this is the first reported case demonstrating pituitary carcinoma in the falx cerebri. Third, the prognosis of pituitary carcinoma is usually very poor, and mortality is extremely high; however, the patient in our case has been followed up for seven years since the diagnosis of the metastatic lesions and has remained clinically stable.

Retrospective analysis of the outcomes of endoscopic transsphenoidal surgery for Cushing's disease.

Background: The first-line surgical management of an adrenocorticotropic hormone (ACTH)--secreting pituitary adenoma causing Cushing's disease (CD) is endoscopic transsphenoidal resection of the tumor. This study was performed to assess postoperative (postop) complications and remission in endoscopic surgically resected cases of CD. Methods: Data of patients who underwent endoscopic transsphenoidal surgery (ETSS) for CD were collected from the neurosurgery department at a tertiary care center in a retrospective manner from January 2015 to February 2022 and analyzed. Postoperative remission was categorized as - early morning serum cortisol <138 nmol/L within 7 days of the surgery, as per the Endocrine Society Guidelines, with significant clinical improvement in features of hypercortisolism in the operated patient and strict cutoff rate of <50 nmol/L at postop day 3 was also utilized, to look for the early identification of remission. Results: A total of 41 patients were identified who underwent 44 ETSS during the same timeframe. Preoperative magnetic resonance imaging localized an adenoma in all 41 patients, out of which 32 were microadenoma, and nine were macroadenoma (2 with cavernous sinus invasion). Intrapetrosal sinus sampling was performed in 35 (85%) patients. The rate of remission for the initial surgery was 85.4% using the standard criteria and 68.3% using strict criteria. Three patients underwent early repeat surgery for the persistent disease as the day 3 cortisol was high (306-555 nmol/L). Once the outcome of this surgery was also included, the overall rate of remission was 90.2% (37/41). None of the patients had meningitis, cerebrospinal fluid leakage, visual deterioration, or vascular injury. Permanent and transient diabetes insipidus (DI) occurred in 9.75% and 26.8% following the first ETSS, respectively. We also noted a single case of CD recurrence in 9 months during the total follow-up period of 84 months. Conclusion: ETSS has satisfactory rates of remission for the primary treatment of CD, with rates being higher for microadenomas. A long follow-up period is needed to assess the rates of recurrence. Patients must be counseled regarding the risk of postop DI, whether transient or permanent, as a possible complication.

Severe Hyponatremia Secondary to Pituitary Macroadenoma With Internal Hemorrhage in the Postpartum Period: A Case Report.

Pituitary macroadenomas, especially those complicated by internal hemorrhage (pituitary apoplexy), can lead to severe endocrine dysfunction and visual disturbances. This is particularly challenging to diagnose in the postpartum period due to physiological changes associated with childbirth and breastfeeding. This case report aims to highlight the diagnostic and therapeutic complexities of managing severe hyponatremia and visual changes in a woman with a pituitary macroadenoma in the postpartum period.A 34-year-old female, five months postpartum, presented with a one-month history of intermittent nausea, headaches, and blurry vision, which worsened over the past week. Initial laboratory results revealed severe hyponatremia with a sodium level of 112 mEq/L. Imaging studies, including MRI, confirmed a 1.9 x 1.8 x 1.7 cm pituitary macroadenoma with internal hemorrhage exerting mass effect on the optic chiasm. The patient was managed with hypertonic saline for hyponatremia and empiric glucocorticoid supplementation for suspected adrenal insufficiency. A multidisciplinary approach involving endocrinology, neurosurgery, and ophthalmology was employed to address her complex medical needs. This case underscores the importance of considering pituitary pathology in women presenting with severe hyponatremia and visual changes postpartum. A multidisciplinary approach is essential for optimal management and prevention of long-term complications. Early recognition and appropriate intervention are crucial in ensuring a favorable outcome.

Pituitary Adenoma Masquerading as Diabetic Third Nerve Palsy.

A 46-year-old uncontrolled diabetic female visited the ophthalmology outpatient department with a sudden onset of drooping of the upper lid and restriction of movements in adduction, depression, and elevation in the right eye, suggestive of third nerve palsy. Initially, it was thought to be due to a vasculogenic cause due to uncontrolled diabetes, but visual fields revealed bitemporal hemianopia, characteristic of a pituitary adenoma. The diagnosis was confirmed by a CT scan. The patient then underwent a trans-nasal endoscopic removal of the pituitary macroadenoma, followed by a partial recovery of vision.

Complete and Immediate Resolution of See-Saw Nystagmus Following Pituitary Macroadenoma Resection: Case Report and Review of the Literature.

See-saw nystagmus (SSN) is a rare form of nystagmus characterised by alternating elevation with incyclotorsion of one eye and concomitant depression with excyclotorsion of the other eye, often due to abnormalities involving the midbrain and parasellar region. Herein, we highlight a rare case of pendular SSN, which demonstrated complete resolution following resection of a pituitary macroadenoma. A patient in their 40s was identified to have SSN and was diagnosed with a pituitary macroadenoma. They underwent an endoscopic endonasal transsellar approach for resection of the pituitary adenoma. Their nystagmus resolved immediately after surgery. From a review of the literature, resolution and/or significant improvement in SSN occurred in 74% of cases following treatment, with 100%, 86% and 50% following treatment for medication-induced, neurological infarcts, and mass-effect aetiologies of SSN, respectively. SSN is a rare entity with a wide array of aetiologies. Identification of the causative aetiology and appropriate treatment can lead to significant improvement or resolution of the nystagmus in most cases.

An invasive nasopharyngeal carcinoma with extension to the pituitary gland mimicking an invasive pituitary macroadenoma: A case report.

Herein, we report a rare case of invasive nasopharyngeal carcinoma with extension to the pituitary gland misdiagnosed as a pituitary macroadenoma. A 50-year-old woman was referred to our department with a diagnosis of pituitary macroadenoma. She presented with headache, visual disturbances, weakness, nausea, vomiting, and hypoglycemia. Polyuria was not reported. On pituitary magnetic resonance imaging, a large mass was observed to extend from the sella turcica to the sphenoid sinus, optic chiasm, and nasopharynx, leading to the initial diagnosis of an invasive pituitary macroadenoma. Biochemical investigations revealed corticotropin deficiency, secondary hypothyroidism, hypogonadotropic hypogonadism, and moderate hyperprolactinemia. Hormone replacement therapy was initiated. After hydrocortisone initiation, diabetes insipidus was revealed. Subsequent magnetic resonance imaging showed an infiltration of the nasopharynx with an extension to the pituitary gland. An endoscopic biopsy confirmed the diagnosis of undifferentiated nasopharyngeal carcinoma. The patient was referred to the oncology department for chemo and radiotherapy. Invasive nasopharyngeal carcinoma presenting with pituitary extension is very rare. It should be considered in the differential diagnosis of pituitary macroadenoma with hypopituitarism. Proper management of such cases requires a multidisciplinary approach.

Giant Clinically Non-Functioning Pituitary Adenoma Presenting as New Onset Generalized Tonic‒Clonic Seizures: A Case Report.

Background: Giant Clinically Non-Functioning Pituitary Adenomas (GCNFPA) are pituitary neuroendocrine tumours spanning beyond 4 cm in diameter without clinically apparent secretory function. They elicit insidious growth pertaining to its asymptomatic nature and present at large sizes from mass effect. Certain clinical features such as headache and visual disturbances are common presentations of GCNFPAs owing to their size, while others such as seizures are extremely rare. Case Report: A 63-year-old woman presented with back-to-back generalized tonic clonic seizures to the A&E and was treated with Levetiracetam. Following initial normal blood investigations, a visual field analysis revealed a bitemporal upper quadrantanopia and further evaluation using MRI found a giant pituitary lesion with suprasellar extension through the third ventricle into the lateral ventricles with significant mass effect. She underwent neuro-navigation guided endonasal transsphenoidal subtotal resection 2 weeks later. The histological diagnosis of null cell adenoma with a Ki67 of 3% was made. At 3 months of follow-up, she is symptom free and monitored with serial MRIs. Conclusion: Seizures are an uncommon presentation of GCNFPAs limited to a few case reports. This illustrates the importance of careful evaluation of patient presentations to correctly diagnose pituitary neoplasms and prioritizing symptom relief in choosing surgical approaches.

Pituitary Macroadenoma: A Comprehensive Case Study of Surgical Intervention and Postoperative Management.

This case report presents a comprehensive analysis of a 48-year-old woman diagnosed with pituitary macroadenoma, detailing the clinical presentation, surgical intervention, and postoperative management. The patient exhibited a complex array of symptoms, including persistent headaches, insomnia, and anemia, with a history of trauma and blood transfusion. Magnetic Resonance Imaging (MRI) confirmed the presence of a large, lobulated pituitary macroadenoma, prompting a trans-nasal trans-sphenoidal endoscopic excision. The surgical procedure was successful, but postoperative complications, revealed by a CT scan, included hyperdense lesions and mixed-density collections. Incorporating antibiotics, analgesics, antacids, and anti-emetics, vigilant postoperative care addressed these complications. This case underscores the challenges and successes in managing pituitary macroadenomas, highlighting the importance of individualized care, multidisciplinary collaboration, and ongoing research for optimizing patient outcomes. The insights gained from this case contribute to the evolving understanding and refinement of strategies for addressing these complex tumors.

Successful medical management of a pituitary macroadenoma with features of resistant acromegaly and hyperprolactinemia using pasireotide.

BACKGROUND: The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment. CASE PRESENTATION: A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m2). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications. CONCLUSIONS: The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.

Moyamoya Disease with Non-Functional Pituitary Macroadenoma: A Case Report of a Rare Presentation.

Moyamoya disease (MMD) is a rare neurological condition characterized by brain blood vessel narrowing, leading to collateral vessel formation. Diagnosis typically involves cerebral angiography and magnetic resonance angiography (MRA), with surgical revascularization often providing superior outcomes. Here, we present the case of a 55-year-old woman with hypertension, diabetes, and a history of ischemic stroke. She recently experienced a hemorrhagic stroke due to MMD, compounded by a non-functional pituitary macroadenoma. Recognizing signs of a hemorrhagic stroke is crucial to prevent future occurrences and ensure optimal outcomes. However, our understanding of the connection between MMD and pituitary macroadenoma remains incomplete. Further research is essential to refine diagnostic techniques and treatment strategies. Through continued research and awareness, we can strive for improved outcomes and an enhanced quality of life for individuals affected by MMD and its complications.

Predicting the Consistency of Pituitary Macroadenomas: The Utility of Diffusion-Weighted Imaging and Apparent Diffusion Coefficient Measurements for Surgical Planning.

Understanding the consistency of pituitary macroadenomas is crucial for neurosurgeons planning surgery. This retrospective study aimed to evaluate the utility of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) as non-invasive imaging modalities for predicting the consistency of pituitary macroadenomas. This could contribute to appropriate surgical planning and therefore reduce the likelihood of incomplete resections. The study included 45 patients with pathologically confirmed pituitary macroadenomas. Conventional MRI sequences, DWIs, ADC maps, and pre- and post-contrast MRIs were performed. Two neuroradiologists assessed all of the images. Neurosurgeons assessed the consistency of the tumor macroscopically, and histopathologists examined it microscopically. The MRI findings were compared with postoperative data. According to the operative data, macroadenomas were divided into the two following categories based on their consistency: aspirable (n = 27) and non-aspirable tumors (n = 18). A statistically significant difference in DWI findings was found when comparing macroadenomas of different consistencies (p < 0.001). Most aspirable macroadenomas (66.7%) were hyperintense according to DWI and hypointense on ADC maps, whereas most non-aspirable macroadenomas (83.3%) were hypointense for DWI and hyperintense on ADC maps. At a cut-off value of 0.63 × 10-3 mm2/s, the ADC showed a sensitivity of 85.7% and a specificity of 75% for the detection of non-aspirable macroadenomas (AUC, 0.946). The study concluded that DWI should be routinely performed in conjunction with ADC measurements in the preoperative evaluation of pituitary macroadenomas. This approach may aid in surgical planning, ensure that appropriate techniques are utilized, and reduce the risk of incomplete resection.

Pituitary Apoplexy Presenting with Isolated Third Nerve Palsy: A Rare Case Report.

A 46-year-old female came to neurosurgery outpatient department with sudden onset of drooping of RE upper eyelid and restriction of movements in adduction, depression and elevation in right eye. Patient was a known case of diabetes mellitus whose blood sugar levels were deranged. On examination, patient was diagnosed pituitary macroadenoma. Patient was treated for her uncontrolled diabetes mellitus following which she had underwent transsphenoidal pituitary macroadenoma removal. On treatment, patient's ptosis had subsided and restriction of movement has resolved.

Case report: Complete restoration of the HPA axis function in Cushing's disease with drug treatment.

This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.5 mg weekly) normalized prolactin concentrations and induced a major shrinkage of the adenoma. Not only was urinary free cortisol normalized for more than 14 years, but also the treatment induced normal hypothalamo-pituitary-adrenal (HPA) axis function as illustrated by the reappearance of a normal cortisol/ACTH circadian rhythm, cortisol suppression to dexamethasone, and disappearance of the excessive and aberrant responses to CRH and desmopressin, respectively. This case is the first description of complete restoration of the physiological characteristics of the HPA axis by a medication during the treatment of Cushing's disease. Although exceptional, it illustrates that drugs targeting the pituitary adenoma can bring true complete remission of Cushing's disease.