The diagnostic accuracy and prognostic value of OCT for the evaluation of the visual function in children with a brain tumour: A systematic review

PURPOSE: To systematically review the evidence on the diagnostic accuracy and prognostic value of retinal optical coherence tomography (OCT) to detect visual acuity (VA) or visual field (VF) loss in children with a brain tumour. METHODS: PubMed, Embase and Cochrane Library databases were searched from inception to February 2021. We included studies evaluating retinal OCT and standard visual function parameters (VA and or VF) in children with a brain tumour. Two authors independently extracted data from each included study. They also assessed the methodological quality of the studies using the QUADAS-2 or QUIPS tool. The diagnostic accuracy of OCT was evaluated with receiver operating characteristic analysis, sensitivity, specificity, positive predictive value and negative predictive value. The prognostic value of OCT was evaluated with predictive measures (odds ratio). RESULTS: We included five diagnostic studies, with a total of 186 patients, all diagnosed with optic pathway glioma. No prognostic studies were eligible for inclusion. Included studies evaluated either retinal nerve fiber layer (RNFL) thickness or ganglion cell layer-inner plexiform layer (GCL-IPL) thickness. There was considerable heterogeneity between OCT devices, OCT protocols, visual function parameters and threshold values. Sensitivity and specificity for RNFL thickness measurement ranged from 60.0% to 100.0% and 76.6% to 100%, respectively. For GCL-IPL thickness measurement, area under the curve ranged from 0.91 to 0.98 for different diameters. CONCLUSION: The literature regarding the diagnostic accuracy and prognostic value of OCT parameters in children with a brain tumour is scarce. Due to heterogeneity and a considerable risk of bias of included studies, we cannot draw solid conclusions regarding the accuracy of retinal OCT. Future research should investigate the potential of OCT as diagnostic and prognostic tool for the evaluation of the visual function and detection of visual impairment in children with any type of brain tumour

Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term observational studies in three patients

We report on three newly diagnosed patients with extracranial ectopic GHRH-associated acromegaly with long-term follow-up after surgery of the primary tumor. One patient with a pancreatic tumor and two parathyroid adenomas was the index case of a large kindred of MEN-I syndrome. The other two patients had a large bronchial carcinoid. The first patient is still in remission now almost 22 years after surgery. In the two other patients GHRH did not normalize completely after surgery and they are now treated with slow-release octreotide. IGF-I normalized in all patients. During medical treatment basal GH secretion remained (slightly) elevated and secretory regularity was decreased in 24 h blood sampling studies. We did not observe development of tachyphylaxis towards the drug or radiological evidence of (growing) metastases. We propose life-long suppressive therapy with somatostatin analogs in cases with persisting elevated serum GHRH concentrations after removal of the primary tumor. Independent parameters of residual disease are elevated basal (nonpulsatile) GH secretion and decreased GH secretory regularity

Pituitary-hormone secretion by thyrotropinomas

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells

Hormone Secretion by Pituitary Adenomas Is Characterized by Increased Disorderliness and Spikiness but More Regular Pulsing

CONTEXT: Hormone secretion by functioning pituitary tumors is characterized by increased basal (nonpulsatile) secretion, enhanced pulse frequency, amplified pulse mass, and increased disorderliness. OBJECTIVE: The objective of the study was to quantify (subtle) abnormalities of hormone secretion by pituitary adenomas and the influence of selective pituitary surgery and suppressive medications on these parameters. METHODS: Approximate entropy (ApEn) was quantified with a refined algorithm, spikiness by a new method to evaluate sudden short-lived increases in hormone levels, and pulsing regularity, determined with a fully automated deconvolution program. These 3 distinct measures of secretory disruption were compared in untreated and treated patients with acromegaly, prolactinoma, and Cushing's disease together with matching profiles in healthy controls. RESULTS: ApEn and spikiness were markedly increased in all untreated patient groups and normalized after pituitary surgery in acromegaly and hypercortisolism. In contrast, hormone-suppressive medical treatment in acromegaly and prolactinoma did not normalize ApEn. Spikiness normalized in acromegalic patients but not in prolactinoma. GH and cortisol pulsing regularity was elevated in acromegaly and Cushing's disease, respectively, and normalized after surgery. Medical treatment caused normalization of pulsing regularity in acromegaly but not in prolactinoma patients. CONCLUSION: This study extends the understanding of disorganized hormone secretion by hyperfunctioning pituitary adenomas. The new findings are increased spikiness in all 3 tumor groups and increased pulsing regularity in GH- and ACTH-secreting adenomas. The mechanisms behind the marked pattern irregularity and the selective normalization by surgical and medical therapies are not established yet but may include diminished feedback signaling in addition to the anatomical and functional disorganization of intrapituitary cell networks

Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly

Octreotide is a potent somatostatin analog that inhibits growth hormone (GH) release and restricts somatotrope cell growth. The long-acting octreotide formulation Sandostatin LAR is effective clinically in approximately 60% of patients with acromegaly. Tumoral GH secretion in this disorder is characterized by increases in pulse amplitude and frequency, nonpulsatile (basal) release, and irregularity. Whether sustained blockade by octreotide can restore physiological secretion patterns in this setting is unknown. To address this question, we studied seven patients with GH-secreting tumors during chronic receptor agonism. Responses were monitored by sampling blood at 10-min intervals for 24 h, followed by analyses of secretion and regularity by multiparameter deconvolution and approximate entropy (ApEn). The somatostatin agonist suppressed GH secretory-burst mass, nonpulsatile (basal) GH release, and pulsatile secretion, thereby decreasing total GH secretion by 86% (range 70-96%). ApEn decreased from 1.203 +/- 0.129 to 0.804 +/- 0.141 (P = 0.032), denoting greater regularity. None of GH pulse frequency, basal GH secretion rates, or ApEn normalized. In summary, chronic somatostatin agonism is able to repress amplitude-dependent measures of excessive GH secretion in acromegaly. Presumptive tumoral autonomy is inferred by continued elevations of event frequency, overall pattern disruption (irregularity), and nonsuppressible basal GH secretio

Diminished and irregular thyrotropin secretion with preserved diurnal rhythm in patients with active acromegaly

The hypothalamo-pituitary-thyroid axis in acromegaly may be altered. Previous studies report diminished serum TSH concentrations in patients with active acromegaly and decreased response to TRH. On the other hand, most patients have normal thyroid hormone concentrations. Our aim was to analyze serum TSH profiles in relation to GH profiles in patients with untreated acromegaly, in order to delineate aberrations in the hypothalamo-pituitary-thyroid system. Twenty-one patients with active acromegaly and matched controls underwent a 24-h, 10-min blood sampling study. GH and TSH data were analyzed with a newly developed automated deconvolution program, approximate entropy, and cosinor regression. Basal (10.4 +/- 2.0 vs. 13.8 +/- 1.4 mU/liter . 24 h; P = 0.02) and pulsatile (11.4 +/- 1.7 vs. 18.6 +/- 1.6 mU/liter . 24 h; P = 0.002) TSH secretion was decreased in patients. TSH secretory regularity was diminished with loss of pattern synchrony between TSH and GH. Total TSH secretion correlated with TSH increase after TRH (R = 0.75; P = 0.0001), negatively with the log-transformed GH secretion rate (R = -0.52; P = 0.001), but not with adenoma size. The diurnal TSH rhythm was preserved. Total and free T4 concentrations were similar in patients and controls. Basal and pulsatile TSH secretion is decreased in active acromegaly, although T4 levels are unaffected. Diminished TSH secretion is compatible with enhanced restraint by tumoral GH feedback-driven somatostatin outflow, explaining also the reduced regularity of TSH secretion. Unchanged T4 concentrations might reflect decreased sympathetic function in GH excess states, heightening responsiveness of the thyroid gland to TS

Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

The hypothalamus-pituitary-thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH. We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus-pituitary-thyroid system. Patients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression. Pulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P <0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P <0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P <0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P <0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001). Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 contro

Visual functions in children with craniopharyngioma at diagnosis: A systematic review.

Childhood craniopharyngioma is a rare and slow growing brain tumour, often located in the sellar and suprasellar region. It commonly manifests with visual impairment, increased intracranial pressure and hypothalamic and/or pituitary deficiencies. Visual impairment in childhood adversely affects a child's daily functioning and quality of life. We systematically reviewed the literature to provide an extensive overview of the visual function in children with craniopharyngioma at diagnosis in order to estimate the diversity, magnitude and relevance of the problem of visual impairment. Of the 543 potentially relevant articles, 84 studies met our inclusion criteria. Visual impairment at diagnosis was reported in 1041 of 2071 children (50.3%), decreased visual acuity was reported in 546 of 1321 children (41.3%) and visual field defects were reported in 426 of 1111 children (38.3%). Other ophthalmological findings described were fundoscopic (32.5%) and orthoptic abnormalities (12.5%). Variations in ophthalmological testing methods and ophthalmological definitions precluded a meta-analysis. The results of this review confirm the importance of ophthalmological examination in children with craniopharyngioma at diagnosis in order to detect visual impairment and provide adequate support. Future studies should focus on long-term visual follow-up of childhood craniopharyngioma in response to different treatment strategies to provide insight in risks and ways to prevent further loss of vision

Thyrotropin Secretion in Healthy Subjects Is Robust and Independent of Age and Gender, and Only Weakly Dependent on Body Mass Index

Context: Studies of the influence of sex, age, and body weight on TSH secretion are not unanimous. Most reports are based on a single TSH measurement; studies using frequent blood sampling are scarce and include a limited number of selected subjects. Objective: The goal was to investigate TSH dynamics in 117 healthy adults. Methods: TSH was measured by a sensitive immunofluorometric assay. Secretion parameters were quantified by automated deconvolution, approximate entropy [ApEn], spikiness, and diurnal properties. Results: Mean age was 43 years (range, 22-77 y). Mean body mass index (BMI) was 26.8 kg/m(2) (range, 18.3-39.4 kg/m(2)). Daily TSH secretion was 45.4 mU/L (range, 8.0-207 mU/L). There were no sex differences in secretion parameters, including pulse frequency; basal, pulsatile, and total secretion; pulse mode; half life; pulse regularity; ApEn; spikiness; and nycthemeral properties. BMI was positively related to basal secretion. Total secretion correlated negatively with free T-4 (R = 0.225; P = .018). The onset of the nocturnal surge was delayed by increasing BMI and advanced by increasing age. ApEn and spikiness correlated positively with age, especially in men. The 9AM sample correlated strongly with the total 24-hour secretion, explaining two-thirds of the variability. Conclusion: This study shows that the 24-hour TSH secretion in healthy volunteers is stable and robust and not influenced by sex, BMI, and age. ApEn in the elderly, especially men, is increased, pointing to a less tight feedback control. Furthermore, aging is associated with advance shifting of the TSH rhythm, which is a phenomenon also observed in other biological rhythm