Purpose To assess the reliability and safety of a postsurgical evaluation strategy of adrenal function using CRH stimulation and basal cortisol concentrations after transsphenoidal pituitary... Show morePurpose To assess the reliability and safety of a postsurgical evaluation strategy of adrenal function using CRH stimulation and basal cortisol concentrations after transsphenoidal pituitary surgery.Methods Retrospective cohort study of all patients undergoing endoscopic transsphenoidal surgery from 2010 to 2017, in whom early postoperative basal cortisol and/or CRH-stimulated cortisol secretion were available, including confirmation of adrenal function during follow-up. Patients with Cushing's disease were excluded. Optimal test performances were assessed using ROC analysis.Results A total of 156 patients were included. Sensitivity and specificity of the CRH test were 78% and 90%, respectively, and 86% and 92% for basal cortisol, respectively, using an optimal cutoff of 220 nmol/L. Eight patients had false-negative test results with the CRH test (normal test but adrenal insufficient at follow-up), and six patients with basal cortisol, the majority of which had multiple pituitary hormone deficiencies and fluid imbalances. No clinical adverse events occurred in patients with false-negative test results. The diagnostic performance of a single basal cortisol measurement was superior to the CRH test.Conclusions The early postoperative basal cortisol is a safe and simple measurement to guide (dis)continuation of hydrocortisone replacement. However, disturbing factors, e.g., sodium balance disorders, contraceptives, untreated hypopituitarism, and illness impact the interpretation and in those cases this measure is unreliable. We propose an algorithm in which hydrocortisone replacement at discharge is based on basal cortisol <220 nmol/L on postoperative day 2 or 3 in a stable condition. Show less
Maintenance and repair is of key importance for the proper functioning of cells, tissues, and integrated physiology. We hypothesize that the balance between investments in growth, development, and... Show moreMaintenance and repair is of key importance for the proper functioning of cells, tissues, and integrated physiology. We hypothesize that the balance between investments in growth, development, and reproduction versus maintenance and repair is regulated by the brain. Specifically (the interplay of) hormones of the different hypothalamic-pituitary-target gland axes seem to be key regulators in constantly adjusting this balance to its optimal state. This thesis describes the associations between familial longevity and hormones of different hypothalamic-pituitary-target gland axes. In Chapter 2, the question is addressed whether circulating insulin-like growth factor 1 (IGF‐1) axis parameters associate with old age survival and functional status in nonagenarians from the LLS. In Chapter 3, we use growth hormone (GH) concentrations measured every 10 min over 24 h to derive and compare GH secretion parameters between offspring of long-lived families and their partners. In Chapter 4, we investigate the association between hypothalamic-pituitary-gonadal axis parameters and familial longevity. In Chapter 5, we use 24-h time series data of pituitary hormones to investigate how changes in the different hormonal axes are correlated with each other over time. In Chapter 6, we determine the circadian rhythm of bone turnover markers in healthy older subjects. Show less
Lobatto, D.J.; Vries, F. de; Najafabadi, A.H.Z.; Pereira, A.M.; Peul, W.C.; Vlieland, T.P.M.V.; ... ; Furth, W.R. van 2018
Patients with pituitary disease in a stable medical condition demonstrate persistent morbidity. This thesis describes their health outcomes by using a biopsychosocial approach covering a... Show morePatients with pituitary disease in a stable medical condition demonstrate persistent morbidity. This thesis describes their health outcomes by using a biopsychosocial approach covering a continuum ranging from biological and physiological measures, to measures of general health perceptions, as described by the Wilson-Cleary model. Show less
In this thesis, we explored pituitary functioning and extra-pituitary implications of two pituitary disorders in humans. In part A, we focused on the long-term consequences of the diagnosis and... Show moreIn this thesis, we explored pituitary functioning and extra-pituitary implications of two pituitary disorders in humans. In part A, we focused on the long-term consequences of the diagnosis and treatment of nonfunctioning pituitary macroadenoma (NFMA) on hypothalamic regulation of circadian rhythmicity. These patients are at theoretical risk for damage of especially the hypothalamic suprachiasmatic nucleus (SCN), harboring the seat of the body’s central clock, and its projections. The studies aimed to explore symptoms of SCN dysfunctioning and their implications for patients, in order to formulate strategies to prevent or manage these long-term disabilities. In part B, we focused on the clinical characteristics and pathophysiology of the X-linked IGSF1 deficiency syndrome, in order to aid physicians in providing the necessary diagnostic procedures and long-term care for these patients, and to learn about IGSF1’s role in endocrine physiology. Show less
Background: Loss-of-function mutations in immunoglobulin superfamily member 1 (IGSF1) cause an X-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise,... Show moreBackground: Loss-of-function mutations in immunoglobulin superfamily member 1 (IGSF1) cause an X-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise, variable prolactin deficiency and variable partial GH deficiency in childhood. The clinical features and gene expression pattern suggest a pivotal role for IGSF1 in the pituitary, but detailed knowledge on pituitary hormone secretion in this syndrome is lacking. We therefore aimed to study the 24-hour pituitary hormone secretion in male patients with IGSF1 deficiency. Methods: We collected blood samples every 10 min for 24 h in eight adult male IGSF1-deficient patients and measured circulating TSH, prolactin and gonadotropins. Deconvolution, modified cosinor and approximate entropy analyses were applied to quantify secretion rates, diurnal rhythmicity and regularity of hormone release. Results were compared to healthy controls matched for age and body mass index. Results: Compared to healthy controls, IGSF1-deficient patients showed decreased pulsatile secretion of TSH with decreased disorderliness and reduced diurnal variation. Basal and pulsatile secretion of FSH was increased by over 200%, while LH secretion did not differ from healthy controls. We observed a bimodal distribution of prolactin secretion, i.e. severe deficiency in three and increased basal and total secretion in the other five patients. Conclusion: The altered TSH secretion pattern is consistent with the previously hypothesized defect in thyrotropin-releasing hormone signaling in IGSF1 deficiency. However, the phenotype is more extensive and includes increased FSH secretion without altered LH secretion as well as either undetectable or increased prolactin secretion. (C) 2015 S. Karger AG, Basel Show less
This thesis covers the consequences of cranial irradiation of non-pituitary tumors, eg nasopharyngeal carcinoma, on pituitary function. In chapter 2 we have performed a meta-analysis of available... Show moreThis thesis covers the consequences of cranial irradiation of non-pituitary tumors, eg nasopharyngeal carcinoma, on pituitary function. In chapter 2 we have performed a meta-analysis of available data reported in literature on pituitary function after cranial radiotherapy for head and neck and non-pituitary tumours. In this study, we found a 0,66 (CI 0,55-0,76) prevalence of hypopituitarism of any kind in a group of studies with a high level of heterogeneity. In chapter 3 the results of a cohort study are presented, we found that 62% of these had developed hypopituitarism during a variable period after cranial irradiation. Pituitary insufficiency of any form was present in 55% of cases within 5 years after radiotherapy, and amounted to 75% and 90% of patients after 10 and 15 years, respectively. Chapter 4-8 adress the consequences of long-term rGH replacement. rGH replacement can be safely initiated in adult patients with severe GHD and has to be monitored throughout the years, enabling to make individual adaptations based upon alteration in e.g. MS and bone mass for each patient every year. It has to be noted that the long-term effects on quality of life should be more carefully addressed in future research. Show less
This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and... Show moreThis thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described. Show less
