A novel “total pituitary hormone index” as an indicator of postoperative pituitary function in patients undergoing resection of pituitary adenomas

Abstract Surgery is the treatment of choice for many pituitary tumors; pituitary function may suffer after operation, but relief of pressure on the normal pituitary may also favor postoperative recovery of hypo-pituitarism. The aim of this study was to investigate the frequency of new appearance and recovery of hypopituitarism after neurosurgery and try to identify features associated with it. Pre- and postoperative anterior pituitary functions were investigated in 234 patients with pituitary adenomas (56 nonfunctioning, 71 PRL-secreting, 66 GH-secreting, 39 ACTH-secreting, 1 LH/FSH-secreting, and 1 TSH-secreting tumors). Eighty-eight new postoperative pituitary hypofunctions appeared in 52 patients (12 NF, 14 PRL-secreting, 15 GH-secreting, 10 ACTH-secreting, and 1 LH/FSH-secreting adenomas). They corresponded to 27% ACTH deficiencies (in 29 of the 107 patients with normal preoperative ACTH in whom postoperative evaluation was complete), 14.5% (15 of 103) new GH deficiencies, 10.5% (15 of 143; P < 0.0005, significantly less than ACTH deficiency) new TSH deficiencies, 16.5% (20 of 121) new gonadotropin deficiencies, and 13% (9 of 71) new PRL deficiencies. Preoperatively, 93 were deficient in at least 1 pituitary hormone; after surgery, 45 (48%) recovered between 1 and 3 hormones. The 2 patients with LH/FSH- and TSH-secreting macroadenomas did not recover pituitary function. Factors associated with a higher probability of postoperative pituitary function recovery were: no tumor rests on postoperative pituitary imaging (P = 0.001) and no neurosurgical (P = 0.001) or pathological evidence (P = 0.049) of an invasive nature. Tumor size did not differ significantly between those who did and those who did not recover pituitary function after surgery. Even if clear hypofunction is observed at initial work-up, patients should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.

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Pituitary Morphology and Function in 43 Children with Central Diabetes Insipidus

International Journal of Endocrinology ◽

10.1155/2016/6365830 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Wendong Liu ◽

Limin Wang ◽

Minghua Liu ◽

Guimei Li

Keyword(s):

Diabetes Insipidus ◽

Central Diabetes Insipidus ◽

Pituitary Function ◽

Pituitary Stalk ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Initial Manifestation ◽

Stalk Diameter ◽

And Function

Objective. In pediatric central diabetes insipidus (CDI), etiology diagnosis and pituitary function monitoring are usually delayed. This study aimed to illustrate the importance of regular follow-up and pituitary function monitoring in pediatric CDI.Methods. The clinical, hormonal, and neuroradiological characteristics of children with CDI at diagnosis and during 1.5–2-year follow-up were collected and analyzed.Results. The study included 43 CDI patients. The mean interval between initial manifestation and diagnosis was 22.29 ± 3.67 months (range: 2–108 months). The most common complaint was polyuria/polydipsia. Causes included Langerhans cell histiocytosis, germinoma, and craniopharyngioma in 2, 5, and 4 patients; the remaining were idiopathic. No significant changes were found during the 1.5–2 years after CDI diagnosis. Twenty-three of the 43 cases (53.5%) had ≥1 anterior pituitary hormone deficiency. Isolated growth hormone deficiency was the most frequent abnormality (37.5%) and was not associated with pituitary stalk diameter. Multiple pituitary hormone deficiencies were found in 8 cases with pituitary stalk diameter > 4.5 mm.Conclusion. Diagnosis of CDI is usually delayed. CDI with a pituitary stalk diameter > 4.5 mm carries a higher risk of multiple pituitary hormone deficiencies. Long-term MRI and pituitary function follow-ups are necessary for children with idiopathic CDI.

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Heterozygous Orthodenticle Homeobox 2 Mutations Are Associated with Variable Pituitary Phenotype

Endocrine Reviews ◽

10.1210/edrv.31.1.9987 ◽

2010 ◽

Vol 31 (1) ◽

pp. 133-133

Author(s):

Sumito Dateki ◽

Kitaro Kosaka ◽

Kosei Hasegawa ◽

Hiroyuki Tanaka ◽

Noriyuki Azuma ◽

...

Keyword(s):

Target Genes ◽

Japanese Patients ◽

Dominant Negative ◽

Pituitary Function ◽

Hormone Deficiency ◽

Dominant Negative Effect ◽

Pituitary Hormone ◽

Positive Role ◽

Negative Effect ◽

And Function

ABSTRACT Context Although recent studies have suggested a positive role of OTX2 in pituitary as well as ocular development and function, detailed pituitary phenotypes in OTX2 mutations and OTX2 target genes for pituitary function other than HESX1 and POU1F1 remain to be determined. Objective We aimed to examine such unresolved issues. Subjects We studied 94 Japanese patients with various ocular or pituitary abnormalities. Results We identified heterozygous p.K74fsX103 in case 1, p.A72fsX86 in case 2, p.G188X in two unrelated cases (3 and 4), and a 2,860,561-bp microdeletion involving OTX2 in case 5. Clinical studies revealed isolated GH deficiency in cases 1 and 5; combined pituitary hormone deficiency in case 3; abnormal pituitary structures in cases 1, 3, and 5; and apparently normal pituitary function in cases 2 and 4, together with ocular anomalies in cases 1-5. The wild-type Orthodenticle homeobox 2 (OTX2) protein transactivated the GNRH1 promoter as well as the HESX1, POU1F1, and IRBP (interstitial retinoid-binding protein) promoters, whereas the p.K74fsX103-OTX2 and p.A72fsX86-OTX2 proteins had no transactivation functions and the p.G188X-OTX2 protein had reduced (∼50%) transactivation functions for the four promoters, with no dominant-negative effect. cDNA screening identified positive OTX2 expression in the hypothalamus. Conclusions The results imply that OTX2 mutations are associated with variable pituitary phenotype, with no genotype-phenotype correlations, and that OTX2 can transactivate GNRH1 as well as HESX1 and POU1F1.

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SOX 2 Expression in Human Pituitary Adenomas–Correlations With Pituitary Function

In Vivo ◽

10.21873/invivo.11442 ◽

2018 ◽

Vol 33 (1) ◽

pp. 79-83 ◽

Cited By ~ 2

Author(s):

CRISTINA CAPATINA ◽

ANCA MARIA CIMPEAN ◽

MARIUS RAICA ◽

MIHAIL COCULESCU ◽

CATALINA POIANA

Keyword(s):

Pituitary Adenomas ◽

Pituitary Function ◽

Human Pituitary ◽

Human Pituitary Adenomas

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Peel-off resection of the pituitary gland for functional pituitary adenomas: pathological significance and impact on pituitary function

Pituitary ◽

10.1007/s11102-019-00980-w ◽

2019 ◽

Vol 22 (5) ◽

pp. 507-513

Author(s):

Yuichi Nagata ◽

Kazuhito Takeuchi ◽

Taiki Yamamoto ◽

Takayuki Ishikawa ◽

Teppei Kawabata ◽

...

Keyword(s):

Pituitary Gland ◽

Pituitary Adenomas ◽

Pituitary Function

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Radiation Tolerance of Functioning Pituitary Tissue in Gamma Knife Surgery for Pituitary Adenomas

Neurosurgery ◽

10.1227/01.neu.0000043709.53906.31 ◽

2003 ◽

Vol 52 (2) ◽

pp. 309-317 ◽

Cited By ~ 71

Author(s):

Vilibald Vladyka ◽

Roman Liščák ◽

Josef Novotný ◽

Josef Marek ◽

Jana Ježková

Keyword(s):

Gamma Knife ◽

Pituitary Adenomas ◽

Growth Control ◽

Gamma Knife Surgery ◽

Pituitary Function ◽

Radiation Tolerance ◽

Early Results ◽

Treatment Dose ◽

Treatment Plans

Abstract OBJECTIVE This study is intended to contribute to a determination of the sensitivity of preserved hypophyseal function to focal radiation in pituitary adenomas. METHODS We compared two subgroups of patients followed up for a median of 5 years after gamma knife surgery (GKS). Subgroup 1 (n = 30) showed postirradiation hypopituitarism. Subgroup 2 (n = 33) was continually eupituitary. These subgroups were taken from a previously published study relating to a larger group of 163 patients with pituitary adenomas treated by GKS and evaluated after a median follow-up period of 2 years. A relatively high treatment dose was used in this larger group (median, 20 Gy to the tumor margin for growth control in nonfunctioning adenomas; median, 35 Gy for hypersecreting adenomas). Early results approached those of microsurgery, and there were only a few side effects. In the present study, we compared 16 different variables in the same two subgroups to discover the relationships that caused a delayed appearance of postirradiation hypopituitarism. The main pretreatment and treatment parameters were measured on reconstructed treatment plans. This database was used for statistical evaluation. RESULTS The relationship between the mean dose and the volume of functioning hypophysis was stronger in terms of worsening of pituitary function than that of the spot dose to different intrasellar structures. We found that for our group of patients, the safe mean dose of radiation to the hypophysis was 15 Gy for gonadotropic and thyrotropic functions and 18 Gy for adrenocorticotropic function. The worsening of pituitary function was also significantly dependent on the dose to different anatomic levels of the infundibulum, but we did not succeed in fully characterizing this relationship. In addition, we discovered significant levels of dependency of postirradiation pituitary damage to different pretreatment and treatment variables. CONCLUSION Knowledge of the radiation tolerance of functioning pituitary structures subjected to GKS can ensure better preservation of pituitary function after irradiation. This is valid for the group of patients we studied. Our study's findings can be used as a guideline for GKS treatment of new patients with pituitary adenomas, and it can serve for comparison with the experience of other gamma knife centers.

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Endocrine function and gland volume after endoscopic transsphenoidal surgery for nonfunctional pituitary macroadenomas

Journal of Neurosurgery ◽

10.3171/2018.5.jns181054 ◽

2019 ◽

Vol 131 (4) ◽

pp. 1142-1151 ◽

Cited By ~ 1

Author(s):

Maya Harary ◽

Aislyn C. DiRisio ◽

Hassan Y. Dawood ◽

John Kim ◽

Nayan Lamba ◽

...

Keyword(s):

Pituitary Gland ◽

Tumor Size ◽

Transsphenoidal Surgery ◽

Endocrine Function ◽

Pituitary Function ◽

Pituitary Hormone ◽

Tumor Diameter ◽

Endoscopic Transsphenoidal Surgery ◽

Gland Volume ◽

The Relationship

OBJECTIVELoss of pituitary function due to nonfunctional pituitary adenoma (NFPA) may be due to compression of the pituitary gland. It has been proposed that the size of the gland and relative perioperative gland expansion may relate to recovery of pituitary function, but the extent of this is unclear. This study aims to assess temporal changes in hormonal function after transsphenoidal resection of NFPA and the relationship between gland reexpansion and endocrine recovery.METHODSPatients who underwent endoscopic transsphenoidal surgery by a single surgeon for resection of a nonfunctional macroadenoma were selected for inclusion. Patients with prior pituitary surgery or radiosurgery were excluded. Patient characteristics and endocrine function were extracted by chart review. Volumetric segmentation of the pre- and postoperative (≥ 6 months) pituitary gland was performed using preoperative and long-term postoperative MR images. The relationship between endocrine function over time and clinical attributes, including gland volume, were examined.RESULTSOne hundred sixty eligible patients were identified, of whom 47.5% were female; 56.9% of patients had anterior pituitary hormone deficits preoperatively. The median tumor diameter and gland volume preoperatively were 22.5 mm (interquartile range [IQR] 18.0–28.8 mm) and 0.18 cm3 (IQR 0.13–0.28 cm3), respectively. In 55% of patients, endocrine function normalized or improved in their affected axes by median last clinical follow-up of 24.4 months (IQR 3.2–51.2 months). Older age, male sex, and larger tumor size were associated with likelihood of endocrine recovery. Median time to recovery of any axis was 12.2 months (IQR 2.5–23.9 months); hypothyroidism was the slowest axis to recover. Although the gland significantly reexpanded from preoperatively (0.18 cm3, IQR 0.13–0.28 cm3) to postoperatively (0.33 cm3, IQR 0.23–0.48 cm3; p < 0.001), there was no consistent association with improved endocrine function.CONCLUSIONSRecovery of endocrine function can occur several months and even years after surgery, with more than 50% of patients showing improved or normalized function. Tumor size, and not gland volume, was associated with preserved or recovered endocrine function.

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Heterozygous Orthodenticle Homeobox 2 Mutations Are Associated with Variable Pituitary Phenotype

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1334 ◽

2010 ◽

Vol 95 (2) ◽

pp. 756-764 ◽

Cited By ~ 66

Author(s):

Sumito Dateki ◽

Kitaro Kosaka ◽

Kosei Hasegawa ◽

Hiroyuki Tanaka ◽

Noriyuki Azuma ◽

...

Keyword(s):

Target Genes ◽

Japanese Patients ◽

Dominant Negative ◽

Pituitary Function ◽

Hormone Deficiency ◽

Dominant Negative Effect ◽

Pituitary Hormone ◽

Positive Role ◽

Negative Effect ◽

And Function

Abstract Context: Although recent studies have suggested a positive role of OTX2 in pituitary as well as ocular development and function, detailed pituitary phenotypes in OTX2 mutations and OTX2 target genes for pituitary function other than HESX1 and POU1F1 remain to be determined. Objective: We aimed to examine such unresolved issues. Subjects: We studied 94 Japanese patients with various ocular or pituitary abnormalities. Results: We identified heterozygous p.K74fsX103 in case 1, p.A72fsX86 in case 2, p.G188X in two unrelated cases (3 and 4), and a 2,860,561-bp microdeletion involving OTX2 in case 5. Clinical studies revealed isolated GH deficiency in cases 1 and 5; combined pituitary hormone deficiency in case 3; abnormal pituitary structures in cases 1, 3, and 5; and apparently normal pituitary function in cases 2 and 4, together with ocular anomalies in cases 1–5. The wild-type Orthodenticle homeobox 2 (OTX2) protein transactivated the GNRH1 promoter as well as the HESX1, POU1F1, and IRBP (interstitial retinoid-binding protein) promoters, whereas the p.K74fsX103-OTX2 and p.A72fsX86-OTX2 proteins had no transactivation functions and the p.G188X-OTX2 protein had reduced (∼50%) transactivation functions for the four promoters, with no dominant-negative effect. cDNA screening identified positive OTX2 expression in the hypothalamus. Conclusions: The results imply that OTX2 mutations are associated with variable pituitary phenotype, with no genotype-phenotype correlations, and that OTX2 can transactivate GNRH1 as well as HESX1 and POU1F1.

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