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

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.

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.

scholarly journals Two Distinctive POMC Promoters Modify Gene Expression in Cushing’s Disease

2021 ◽  
Author(s):  
Takako Araki ◽  
Yukiko Tone ◽  
Masaaki Yamamoto ◽  
Hiraku Kameda ◽  
Anat Ben-Shlomo ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Methylation Status ◽  
Regulatory Region ◽  
Pituitary Tumors ◽  
Cushing's Disease ◽  
Human Pituitary ◽  
Ectopic Acth ◽  
Pomc Gene ◽  
Acth Secreting

Abstract Context Mechanisms underlying pituitary corticotroph adenoma ACTH production are poorly understood, yet circulating ACTH levels closely correlate with adenoma phenotype and clinical outcomes. Objective We characterized the 5’ ends of proopiomelanocortin (POMC) gene transcripts, which encode the precursor polypeptide for ACTH, in order to investigate additional regulatory mechanisms of POMC gene transcription and ACTH production. Methods We examined 11 normal human pituitary tissues, 32 ACTH-secreting tumors, as well as 6 silent pituitary corticotroph adenomas (SCA) that immunostain for but do not secrete ACTH. Results We identified a novel regulatory region located near the intron2/exon3 junction in the human POMC gene, which functions as a second promoter and an enhancer. In vitro experiments demonstrated that CREB binds the second promoter and regulates its transcriptional activity. The second promoter is highly methylated in SCA, partially demethylated in normal pituitary tissue, and highly demethylated in pituitary and ectopic ACTH-secreting tumors. In contrast, the first promoter is demethylated in all POMC-expressing cells and is highly demethylated only in pituitary ACTH-secreting tumors harboring the USP8 mutation. Demethylation patterns of the second promoter correlate with clinical phenotypes of Cushing’s disease. Conclusion We identified a second POMC promoter regulated by methylation status in ACTH-secreting pituitary tumors. Our findings open new avenues for elucidating subcellular regulation of the hypothalamic-pituitary-adrenal axis and suggest the second POMC promoter may be a target for therapeutic intervention to suppress excess ACTH production.

scholarly journals ХАРАКТЕРИСТИКА НАРУШЕНИЙ РАЗВИТИЯ ПРИ ОБЪЕМНЫХ ЗАБОЛЕВАНИЯХ ГИПОФИЗА У ДЕТЕЙ И ПОДРОСТКОВ

Innova ◽  
2019 ◽  
Vol 15 ◽  
pp. 31-34
Author(s):  
Урманова Ю.М. ◽  
◽  
Мавлонов У.Х. ◽  
Keyword(s):  
Pituitary Gland ◽  
Diabetes Insipidus ◽  
Children And Adolescents ◽  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Developmental Disorders ◽  
Pituitary Tumors ◽  
Cushing's Disease

The aim of the study was to study the nature of developmental disorders in children and adolescents with masses of the Turkish saddle. Material and methods. 44 children and adolescents with large tumors of the Turkish saddle (TS) were under our supervision in the neuroendocrinology department of the RSNPMCE MH RUz. Of 44 sick girls there were 20, boys 24. The average age of girls was 12.1 years, boys - 12.8 years. By the nature of the pathology, the patients were divided into 5 groups: I group. - inactive pituitary adenomas (NAG) - 23 patients (52.3%); II gr. - Itsenko-Cushing's disease - 5 (11.4%); III gr. - craniopharyngioma - 6 (13.6%); IV gr. - prolactinoma - 5 b-x (11.4%); V gr. - germinoma - 5 bx (11.4%). Results. The results obtained indicate that in children and adolescents there are TJ masses of various origins: inactive pituitary adenomas (52%), craniopharyngiomas (13.6%), corticotropinomas (11.4%), prolactinomas (11.4%), and others. The presence of diabetes insipidus (8.6%) indicates the severity of panhypopituitarism that developed as a result of the tumor. Conclusions: 1) disorders of growth and puberty are the most frequent manifestations of pituitary gland masses (34.0%), 2) pituitary tumors in children and adolescents often lead to hypo- and panhypopituitarism (n = 19, or 43.2%).

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

2016 ◽  
Vol 62 (4) ◽  
pp. 11-17
Author(s):  
Patimat M. Khandaeva ◽  
Ija А. Voronkova ◽  
Zhanna E. Belaya ◽  
Ljudmila Ya. 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

Background. Regardless of improvements in MRI, up to 20% of ACTH-secreting pituitary tumors are only identified at surgical exploration. Aim. Тo 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.Material 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.

scholarly journals Effects of chronic administration of PPAR-gamma ligand rosiglitazone in Cushing's disease

2004 ◽  
pp. 173-178 ◽  
Author(s):  
B Ambrosi ◽  
C Dall'Asta ◽  
S Cannavo ◽  
R Libe ◽  
T Vigo ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumors ◽  
Chronic Administration ◽  
Ppar Gamma ◽  
Cushing's Disease ◽  
Controlled Study ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Free Cortisol ◽  
Significant Difference

OBJECTIVE: Rosiglitazone, a thiazolidinedione compound with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-binding affinity, is able to suppress adrenocorticotropic hormone (ACTH) secretion in treated mice and in AtT20 pituitary tumor cells. These observations suggested that thiazolidinediones may be effective as therapy for Cushing's disease (CD). PATIENTS AND METHODS: Rosiglitazone (8 mg/day) was administered to 14 patients with active CD (13 women, one man, 18-68 years). Plasma ACTH, serum cortisol (F) and urinary free cortisol (UFC) levels were measured before and then monthly during rosiglitazone administration. RESULTS: In six patients a reduction of ACTH and F levels and a normalization of UFC were observed 30-60 days after the beginning of rosiglitazone administration: there was a significant difference between basal and post-treatment values for UFC (1238+/-211 vs 154+/-40 nmol/24 h, P<0.03), but not for ACTH (15.9+/-3.7 vs 7.9+/-0.9 pmol/l) and F levels (531+/-73 vs 344+/-58 nmol/l). Two of six cases, followed up for 7 months, showed a mild clinical improvement. Eight patients were nonresponders after 30-60 days of rosiglitazone treatment: their ACTH, F and UFC levels did not differ before and during drug administration. Immunohistochemical analysis of pituitary tumors removed from two responder and two nonresponder patients showed a similar intense immunoreactivity for PPAR-gamma in about 50% of cells. CONCLUSIONS: The administration of rosiglitazone seems able to normalize cortisol secretion in some patients with CD, at least for short periods. Whether the activation of PPAR-gamma by rosiglitazone might be effective as chronic pharmacologic treatment of CD needs a more extensive investigation through a randomized and controlled study.

scholarly journals Selective excision of adenomas originating in or extending into the pituitary stalk with preservation of pituitary function

1997 ◽  
Vol 3 (1) ◽  
pp. E1
Author(s):  
R. Bryan Mason ◽  
Lynnette K. Nieman ◽  
John L. Doppman ◽  
Edward H. Oldfield
Keyword(s):  
Postoperative Period ◽  
Cushing’S Disease ◽  
Pituitary Tumors ◽  
Optic Chiasm ◽  
Anterior Lobe ◽  
Pituitary Function ◽  
Pituitary Stalk ◽  
Cushing's Disease ◽  
Suprasellar Cistern ◽  
Transsphenoidal Resection

When the surgeon identifies an adenoma within the gland and selectively excises it, endocrine-active pituitary tumors are usually cured and pituitary function is preserved. Occasionally ectopic adenomas arise primarily in the pituitary stalk or arise superiorly in the midportion of the anterior lobe and extend upward within the stalk. To determine if these tumors can be selectively excised with preservation of pituitary function, the authors examined the outcome of selective adenomectomy in 10 patients with Cushing's disease with an ectopic adenoma originating in, and confined to, the stalk (four microadenomas) or an adenoma extending superiorly through the diaphragma sella and into the stalk (five microadenomas and one macroadenoma) from an operative series of 516 patients with Cushing's disease. To reach the adenoma transsphenoidally in these patients, the diaphragma sella was incised anteroposteriorly in the midline to the anterior edge of the stalk, the suprasellar cistern was entered, and the adenoma was selectively excised using care to limit injury to the infundibulum. After selective adenomectomy, Cushing's disease remitted in all patients. All patients were hypocortisolemic immediately after surgery and required hydrocortisone for up to 21 months. Apart from the adrenal axis, pituitary function was normal in five patients in the immediate postoperative period, including two patients with tumors confined to the stalk and three patients with preoperative hypothyroidism (one patient) and/or hypogonadism (three patients). Three others with transient postoperative hypothyroidism (one patient) or diabetes insipidus (two patients) had normal pituitary function within 7 months of surgery. One patient with hypothyroidism and one with hypogonadism before surgery had panhypopituitarism postoperatively. A patient with a microadenoma located high in the stalk next to the optic chiasm had bitemporal hemianopsia postoperatively. These results demonstrate the feasibility of achieving curative transsphenoidal resection and preservation of pituitary function in cases of pituitary adenomas that are confined to the pituitary stalk or tumors that extend superiorly within the stalk from an intrasellar origin.

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