scholarly journals Clinical, Biological, Radiological Pathological and Immediate Post-Operative Remission of Sparsely and Densely Granulated Corticotroph Pituitary Tumors: A Retrospective Study of a Cohort of 277 Patients With Cushing’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Beata Rak ◽  
Maria Maksymowicz ◽  
Monika Pękul ◽  
Grzegorz Zieliński
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumors ◽  
Signs And Symptoms ◽  
Cortisol Concentration ◽  
Cushing's Disease ◽  
Ki 67 ◽  
Remission Status ◽  
Multiple Data ◽  
The Mean ◽  
Corticotroph Adenomas

PurposeCushing’s disease is the most common cause of endogenous hypercortisolemia due to a corticotroph pituitary tumor. Up-to-date there is no reliable biomarker of invasiveness among corticotroph tumors, while it is well established in the literature that sparsely granulated somatotroph tumors are characterized by poorer prognosis. The aim of the study was to correlate multiple data including clinical, biochemical, radiological, and pathological findings (including granulation pattern) as well as immediate post-operative remission status among patients operated on due to corticotroph tumors.MethodsWe enrolled all patients consecutively operated on for planned transsphenoidal neurosurgery due to corticotroph PitNETs in years 2010–2018. We excluded from analysis silent corticotroph tumors, plurihormonal PitNETs, and the Crooke’s cell adenomas.ResultsWe recorded 348 hormonally active corticotroph PitNETs. The results of the analysis showed the female predominance 79.88% (n = 278), with the mean age of Cushing’s disease occurrence 43.27 years of age. The mean time from the first signs and symptoms to the operation was 2 years. The women were diagnosed earlier (20–40 years of age vs. 50–60 years of age among men). We performed a detailed analysis of 277 cases classified by granularity pattern as DG or SG corticotroph PitNETs. Densely granulated tumors (DG) occurred four times more frequently than sparsely granulated (SG) (n = 225 vs. n = 52), at similar age (mean 42.94; median 40 vs. mean 45.46; median 45.5; p = 0.3896), but were characterized by lower Knosp’s scale grades (p = 0.0147*), smaller preoperative tumors’ volumes measured at MRI, and more commonly exhibited lower Ki-67 labeling index (<3%) (p = 0.0168*). What is more, DG adenomas more frequently achieved an immediate remission status (measured as postoperative cortisol concentration <2 µg/dl; p = 0.0180*), and the mean postoperative cortisol concentration in DG group was lower than in SG group (mean 5.375 µg/dl vs. 10.47 µg/dl; median 2.49 µg/dl vs. 6.52 µg/dl; p = 0.0028**).ConclusionsOur study indicates that DG corticotroph adenomas occurred at younger age, more commonly were microadenomas as compared to SG tumors, less frequently had invasive features in comparison to SG corticotroph adenomas (p = 0.0019**), and more commonly achieved an immediate postsurgical hormonal remission (p = 0.0180*). We highlight the need for an accurate differentiation of DG and SG subtypes in the pathomorphological diagnosis of corticotropic tumors, especially in invasive PitNETs.

scholarly journals Highly Aggressive and Radiation-Resistant, “Atypical” and Silent Pituitary Corticotrophic Carcinoma: A Case Report and Review of the Literature

2019 ◽  
Vol 12 (1) ◽  
pp. 139-146 ◽  
Author(s):  
Laura Flores ◽  
Richard Sleightholm ◽  
Beth Neilsen ◽  
Michael Baine ◽  
Andjela Drincic ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cushing’S Disease ◽  
Treatment Plan ◽  
Treatment Options ◽  
Pituitary Tumors ◽  
Response To Therapy ◽  
Cushing's Disease ◽  
Ki 67 ◽  
Radiation Resistant ◽  
Metastatic Sites

Background: Pituitary tumors typically remain silent unless interaction with nearby structures occurs. Rare subsets of pituitary tumors display aggressive phenotypes: highly mitotic, locally invasive, metastatic, chemotherapy and radiation resistant, etc. Disease progression and response to therapy is ill-defined in these subtypes, and their true prognostic potential is debated. Thus, identifying tumor characteristics with prognostic value and efficacious treatment options remains a challenge in aggressive pituitary tumors. Case Presentation: A 45-year-old female presented with a nonfunctioning corticotropic pituitary macroadenoma with biomarkers suggestive of an “atypical” subtype: Ki-67 of 8–12%, increased mitosis, and locally invasive. Despite resections and radiation, growth continued, eventually affecting her vision. Although histologically ACTH positive, the patient remained clinically asymptomatic. Twelve months later, an episode of Cushing’s disease-induced psychosis prompted a PET-CT scan, identifying sites of metastasis. Temozolomide was added to her medical regimen, and her metastatic liver lesions and boney metastases were treated with radiofrequency ablation and stereotactic body radiation therapy, respectively. Systemic treatment resulted in a drop in her ACTH levels, with her most recent scans/labs at 12 months following RFA suggesting remission. Conclusions: This is a unique presentation of a pituitary tumor, displaying characteristics of both clinically silent corticotropic and “atypical” macroadenoma subtypes. Although initially ACTH positive while clinically silent, the patient’s disease ultimately recurred metastatically with manifestations of Cushing’s disease and psychosis. With the addition of temozolomide to her treatment plan, her primary and metastatic sites have responded favorably to radiation therapy. Thus, the addition of temozolomide may be beneficial in the treatment of aggressive pituitary tumors.

scholarly journals A Prospective Trial With Ketoconazole Induction Therapy and Octreotide Maintenance Treatment of Cushing’s Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A517-A518
Author(s):  
Ticiana Paes ◽  
Rob Van der Pas ◽  
Peter H Bisschop ◽  
Leo J Hofland ◽  
Richard Abraham Feelders
Keyword(s):  
Cushing’S Disease ◽  
Somatostatin Receptor ◽  
Treatment Success ◽  
Prospective Trial ◽  
Cushing's Disease ◽  
Receptor Subtype ◽  
Free Cortisol ◽  
The Mean ◽  
Cortisol Levels ◽  
Corticotroph Adenomas

Abstract Context: The lack of efficacy of octreotide in the medical treatment of Cushing’s disease (CD) may result from suppressive effects of hypercortisolism on somatostatin receptor subtype 2 (SST2) expression by corticotroph adenomas. We previously demonstrated that SST2 mRNA expression levels in corticotroph tumor cells from patients preoperatively treated with cortisol-lowering therapy are significantly higher compared to those from patients with uncontrolled CD at time of surgery. It may be hypothesized that control of cortisol production induced by steroidogenesis inhibitors may reverse SST2 expression and increase efficacy of tumor-directed therapy with octreotide. Objective: To evaluate the efficacy of a sequential strategy of initiation treatment with ketoconazole (KTC) to reduce cortisol levels, followed by octreotide as maintenance therapy in patients with CD. Patients and Design: 14 adult patients with CD were prospectively enrolled. All patients started on KTC (600-800 mg/day), and once cortisol levels were normalized, octreotide 20 mg/4 weeks was initiated which could eventually be increased to 30 mg/4 weeks. After two months of combined therapy, patients were maintained on octreotide monotherapy until the end of the study period (9 months). Treatment success was assessed by the mean of 2 collections of urinary free cortisol (UFC) levels. Results: The mean age of our study population (14 patients) was 48.6 years, 64% (n=8) were female, 85% (n=12) were newly diagnosed and naïve in treatment. Ketoconazole was able to normalize UFC level in 11 (79%) patients. Subsequently, octreotide effectively sustained normal UFC levels in 3 patients (27%) (responders). Four (36%) other patients showed a partial response to octreotide. In 3 patients, normal UFC levels were sustained for one- or two-months following discontinuation of KTC and in the other partial responder, the UFC levels at follow-up decreased by at least 50% of the baseline levels. The remaining 4 (36%) patients developed hypercortisolism as soon as ketoconazole was stopped (non-responders). Responders to octreotide had lower UFC levels at baseline when compared to partial and non-responders (1.40 ± 0.06 vs. 2.05 ± 0.20 ULN, p=0.08). Two of three responders showed improvement in weight, waist circumference, and systolic and diastolic blood pressure during the treatment period. In terms of side effects, one patient discontinued KTC because of gastrointestinal intolerance and 5 patients had a transient increase in liver enzymes. Conclusions: This proof-of-concept study shows that the sequential treatment with ketoconazole to lower cortisol levels followed by octreotide to maintain normal cortisol production seems effective in a subset of patients with mild CD. Ongoing studies aim to evaluate whether this is the result from increased SST2 expression in corticotroph adenomas.

scholarly journals Linear Growth and Final Height after Treatment for Cushing’s Disease in Childhood

2000 ◽  
Vol 85 (9) ◽  
pp. 3262-3265
Author(s):  
Marie-Christine Lebrethon ◽  
Ashley B. Grossman ◽  
Farhad Afshar ◽  
P. Nicholas Plowman ◽  
G. Michael Besser ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Final Height ◽  
Growth Failure ◽  
Height Velocity ◽  
Cushing's Disease ◽  
Childhood And Adolescence ◽  
Target Height ◽  
Gnrh Analog ◽  
The Mean ◽  
The Difference

Abstract Cushing’s disease is associated with growth failure in childhood and adolescence. Growth and final height were analyzed in 10 patients who were cured or in remission after treatment of Cushing’s disease. Seven males and 3 females, aged 6.8–17.6 yr (bone age, 3.3- 15.4 yr), had transsphenoidal surgery, which was combined with pituitary irradiation (4500 cGy in 25 fractions) in 5 patients. At presentation, 5 patients were prepubertal (males), and 5 were pubertal (2 males and 3 females). The mean height sd score was −2.15 ± 1.26 (range, −0.21 to −4.32) compared with mean target height sd score of −0.43 ± 0.58. Height velocity in 6 patients was subnormal (0.9–3.8 cm/yr). After treatment, short-term height velocity, over a mean interval of 0.57 yr, in 8 patients not receiving human GH (hGH) therapy, was variable (range, 0.8–7.6 cm/yr). GH stimulation tests (insulin tolerance test/glucagon) in 9 subjects showed peak GH levels of 0.5–20.9 mU/L. Eight were treated with hGH (14 IU/m2·wk), combined in 2 girls and 1 boy with a GnRH analog. After 1 yr of hGH, the mean height sd score had increased from −2.45 ± 1.0 at initiation of hGH to −2.07± 1.2 (P = 0.01). GH therapy was continued until final height or latest assessment. The mean final height sd score (n = 6) was −1.24 ± 1.38, and at the latest assessment the mean height sd score (n = 4) was− 1.52 ± 1.33. Combining these 2 groups, the mean height sd score was −1.36 ± 1.29. The difference between final or latest height sd score and target height sd score was 0.93 ± 1.13, i.e. less (P = 0.005) than the difference between height and target height sd score of 1.72 ± 1.26 at presentation. In conclusion, catch-up and favorable long-term growth was seen after treatment for Cushing’s disease. Posttreatment GH deficiency was frequent, and early hGH replacement may have contributed to the encouraging outcome.

Gamma Knife surgery for Cushing's disease

2007 ◽  
Vol 106 (6) ◽  
pp. 980-987 ◽  
Author(s):  
Jay Jagannathan ◽  
Jason P. Sheehan ◽  
Nader Pouratian ◽  
Edward R. Laws ◽  
Ladislau Steiner ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Cranial Nerve ◽  
Gamma Knife Surgery ◽  
Cushing's Disease ◽  
Free Cortisol ◽  
Radiation Induced ◽  
The Mean

Object In this study the authors address the efficacy and safety of Gamma Knife surgery (GKS) in patients with adrenocorticotropic hormone–secreting pituitary adenomas. Methods A review of data collected from a prospective GKS database between January 1990 and March 2005 was performed in patients with Cushing's disease. All but one patient underwent resection for a pituitary tumor, without achieving remission. Successful endocrine outcome after GKS was defined as a normal 24-hour urinary free cortisol (UFC) concentration posttreatment after a minimum of 1 year of follow up. Patient records were also evaluated for changes in tumor volume, development of new hormone deficiencies, visual acuity, cranial nerve neuropathies, and radiation-induced imaging changes. Ninety evaluable patients had undergone GKS, with a mean endocrine follow-up duration of 45 months (range 12–132 months). The mean dose to the tumor margin was 23 Gy (median 25 Gy). Normal 24-hour UFC levels were achieved in 49 patients (54%), with an average time of 13 months after treatment (range 2–67 months). In the 49 patients in whom a tumor was visible on the planning magnetic resonance (MR) image, a decrease in tumor size occurred in 39 (80%), in seven patients there was no change in size, and tumor growth occurred in three patients. Ten patients (20%) experienced a relapse of Cushing's disease after initial remission; the mean time to recurrence was 27 months (range 6–60 months). Seven of these patients underwent repeated GKS, with three patients achieving a second remission. New hormone deficiencies developed in 20 patients (22%), with hypothyroidism being the most common endocrinopathy after GKS. Five patients experienced new visual deficits or third, fourth, or sixth cranial nerve deficits; two of these patients had undergone prior conventional fractionated radiation therapy, and four of them had received previous GKS. Radiation-induced changes were observed on MR images in three patients; one had symptoms attributable to these changes. Conclusions Gamma Knife surgery is an effective treatment for persistent Cushing's disease. Adenomas with cavernous sinus invasion that are not amenable to resection are treatable with the Gamma Knife. A second GKS treatment appears to increase the risk of cranial nerve damage. These results demonstrate the value of combining two neurosurgical treatment modalities—microsurgical resection and GKS—in the management of pituitary adenomas.

scholarly journals Treatment effectiveness of pasireotide on health-related quality of life in patients with Cushing's disease

2014 ◽  
Vol 171 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Susan M Webb ◽  
John E Ware ◽  
Anna Forsythe ◽  
Min Yang ◽  
Xavier Badia ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cushing’S Disease ◽  
Treatment Effectiveness ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Cushing's Disease ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related

ObjectiveCushing's disease (CD) can significantly impair patients' health-related quality of life (HRQOL). This study investigated the treatment effectiveness of pasireotide on HRQOL of CD patients, and assessed the relationships between HRQOL and urinary free cortisol (UFC) and CD-related signs and symptoms.DesignIn this phase III, randomized, double-blind study, patients with UFC ≥1.5×upper limit of normal (ULN) received s.c. pasireotide 600 or 900 μg twice daily. The trial primary endpoint was UFC at or below ULN at month 6 without dose titration. Open-label treatment continued through month 12. HRQOL was measured using the Cushing's Quality of Life Questionnaire (CushingQoL) instrument at baseline and follow-up visits until month 12 during which clinical signs and features of CD, and the Beck Depression Inventory II (BDI-II), were also collected.MethodsPearson's/Spearman's correlations between changes in CushingQoL and changes in clinical signs and symptoms were assessed. Changes in CushingQoL and the proportion of patients achieving a clinically meaningful improvement in CushingQoL were also compared among patients stratified by mean UFC (mUFC) control status (controlled, partially controlled, and uncontrolled) at month 6. Analyses were also conducted at month 12, with multivariable adjustment for baseline characteristics and CushingQoL.ResultsChange in CushingQoL was significantly correlated with changes in mUFC (r=−0.40), BMI (r=−0.39), weight (r=−0.41), and BDI-II (r=−0.54) at month 12 but not at month 6. The percentage of CushingQoL responders at month 12 based on month 6 mUFC control status were as follows: 63, 58.8, and 37.9% in the controlled, partially controlled, and uncontrolled groups respectively. Adjusted CushingQoL scores at month 12 were 58.3 for controlled patients (Δ=11.5 vs uncontrolled,P=0.012) and 54.5 for partially controlled patients (Δ=7.7 vs uncontrolled,P=0.170).ConclusionsPasireotide treatment can result in a meaningful HRQOL improvement among those who complete a 12-month treatment period, most often among patients achieving biochemical control.

Immunochistochemical characteristics of blood vessels in non-visualized and visualized on MRI pituitary adenoma in patients with Cushing’s disease

2016 ◽  
Vol 62 (5) ◽  
pp. 65-66
Author(s):  
Patimat M. Khandaeva ◽  
Iya A. Voronkova ◽  
Zhanna E. Belaya ◽  
Lyudmila Y. Rozhinskaya ◽  
Aleksandr V. Vorontsov ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Blood Vessels ◽  
Cushing’S Disease ◽  
Pituitary Tumor ◽  
Pituitary Tumors ◽  
Average Diameter ◽  
Cushing's Disease ◽  
Retrospective Evaluation ◽  
Acth Secreting ◽  
Microvessels Density

Backgraund. Regardless of improvements in MRI, up to 20% of ACTH-secreting pituitary tumors are only identified at surgical exploration.Aim: to estimate whether there is any difference in blood vessels and the subsequent ability to uptake contrast agent in visualized microadenoma as compared to non-visualized on MRI ACTH-secreting pituitary tumors.Materials and methods. retrospective evaluation of ACTH-positive pituitary tumors from patients with Cushing’s disease (n=39) with either non-visualized pituitary tumor on MRI (n=17) or pituitary tumor less then 25 mm (n=22). MRI was performed using Siemens Magnetom Harmony 1.0T with gadolinium. Selected tumors were stained with anty-СD34 antibody (clone QBEnd/10, RTU, Leica) and anty-D2-40 antibody (clone D2-40, RTU, Dako). We evaluated the microvessels density and measured the diameter of larger and smaller vessel.Results. The microvessels density were not different in subject with visualized (123 [77;136]) and non-visualized (112 [110,0;126,5]) pituitary adenomas as well as number of slit-shaped vessels (32 [5;50] in visualized vs 25 [5;50] in non-visualized pituitary adenoma). The diameter of these vessels also did not differ: the diameter of the largest vessels in patients without visualization 53 µm [32,5;63,5] vs 33 µm [30,0;51,5], the average diameter of the blood vessels 15 µm [14,5-26,0] against 13 µm [12;14].Conclusions. The diameter and microvessels density in ACTH-producing pituitary adenoma does not affect the visualization of adenoma on MRI in patients with Cushing 's disease.

Intraoperative ultrasound-directed resection of pituitary tumors

1995 ◽  
Vol 83 (2) ◽  
pp. 225-230 ◽  
Author(s):  
Zvi Ram ◽  
Thomas H. Shawker ◽  
Mary H. Bradford ◽  
John L. Doppman ◽  
Edward H. Oldfield
Keyword(s):  
Mr Imaging ◽  
Cushing’S Disease ◽  
Intraoperative Ultrasound ◽  
Pituitary Tumors ◽  
Thyroid Stimulating Hormone ◽  
Cushing's Disease ◽  
Content Type ◽  
Normal Pituitary Gland ◽  
Intraoperative Localization ◽  
Fine Print

✓ Microadenomas of the pituitary vary in size, particularly those related to Cushing's disease. They are often not visualized on preoperative magnetic resonance (MR) imaging and may be difficult to find during surgical exploration of the pituitary. To enhance intraoperative localization of pituitary adenomas, we assessed the feasibility of using ultrasound to detect and localize pituitary tumors. Intraoperative ultrasound (IS) in the axial and sagittal planes was performed with an Intrascan system using a 12-MHz mechanically oscillating, end-firing transducer. Interpretation of the scans was performed by two individuals, who were usually blinded to the results of preoperative MR imaging or petrosal sinus sampling. Twenty-eight patients were examined. Eighteen of these patients had microadenomas (1.5–7 mm), all with Cushing's disease; nine had macroadenomas (10–20 mm), three of which were adrenocorticotropic hormone—secreting, three growth hormone—secreting, two thyroid-stimulating hormone—secreting, and one nonfunctioning; and one patient had an intrasellar craniopharyngioma. Normal sellar and parasellar structures, such as intrapituitary cysts, the intracavernous carotid arteries, and the diaphragma sella were easily visualized. Twenty-three of the 28 tumors, including 13 of the 18 microadenomas, were detected on IS (82% sensitivity). Tumors were seen as hyperechoic masses in 19 patients, mixed echogenicity in three, and isoechoic in one. In most macroadenomas IS allowed visualization of the interface between the tumor and the normal pituitary gland. These results indicate the potential of IS to aid the intraoperative localization and definition of pituitary tumors.

Cyproheptadine-Induced Remission of Cushing's Disease Due to Pituitary Basophil Adenoma

1982 ◽  
Vol 16 (12) ◽  
pp. 962-965 ◽  
Author(s):  
J. Jimenez-Alonso ◽  
J. Munoz-Avila ◽  
L. Jaimez ◽  
F. Pérez-Jimenez ◽  
C. Bellido ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumors ◽  
Corticotropin Releasing Factor ◽  
Cushing's Disease ◽  
Patient Support ◽  
Acth Secretion ◽  
Hypothalamic Regulation ◽  
Potent Antagonist ◽  
Factor Secretion ◽  
Acth Release

Serotonin is involved in the control of ACTH secretion, possibly by stimulating corticotropin releasing factor secretion from the hypothalamus. Cushing's disease seems to be due to defective hypothalamic regulation of ACTH release from the pituitary gland. Cyproheptadine is a potent antagonist of serotonin and has been used successfully in some patients with Cushing's disease, although, generally, in women without radiological evidence of pituitary tumors. We report the successful use of cyproheptadine in a 54-year-old man with Cushing's disease due to pituitary basophil adenoma. Significant clinical and biochemical improvement was noted 45 days after treatment began. The results in this patient support our findings that cyproheptadine can be effective in patients with Cushing's disease due to pituitary tumors, as well as in preparing very ill patients for surgery or managing such patients until radiotherapy takes effect.

Differences in secretion characteristics in Cushing’s disease with and without radiologically evident pituitary tumors

1980 ◽  
Vol 3 (3) ◽  
pp. 257-262 ◽  
Author(s):  
S. W. J. Lamberts ◽  
J. G. M. Klijn ◽  
F. H. de Jong ◽  
J. C. Birkenhäger
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumors ◽  
Cushing's Disease
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