Hypothalamic-pituitary Function Research Articles

Sexual Function in Chronic Kidney Disease

Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.

Evaluation of IGF-I levels during long-term somatostatin analogs treatment in patients with gastroenteropancreatic endocrine tumors

Previous experiments reported desensitization to SS action in rat anterior pituitary cells and cell lines. The aim of the study was to verify whether the lack of desensitization to SS analogs (SSa) observed in acromegalic patients was also present in subjects with normal hypothalamic-pituitary function. The effect of chronic treatment with octreotide long-acting release (o-LAR, 10-30 mg/28 days) on IGF-I levels was then evaluated in 23 patients with gastroenteropancreatic (GEP) endocrine tumors (8 gastrinomas, 6 carcinoids, and 9 functioning pancreatic tumors). Serum IGF-I, clinical symptoms, plasma chromogranin-A (CgA) and markers of hepatic synthesis were evaluated before and after a short-term period in all the patients (median 4.5 months), after a medium-term period in 12 (median 18 months) and after a long-term follow-up period in 9 of them (median 48 months). Mean IGF-I levels decreased from 17.3+/-7.0 to 12.8+/-6.2 nmol/l in the short-term (p<0.005) being reduced from baseline concentrations in 87% and under the normal range for age in 35% of patients. Afterwards, they always remained stable both in the medium- and long-term periods, still being low in 3/12 and 2/9 patients, respectively. No alterations in biochemical markers of liver function were found either before or during therapy. No correlation between IGF-I levels, CgA concentrations and/or clinical definitive outcome was observed. In conclusion, the study demonstrated that: a) similarly to that observed in acromegalic patients, chronic o-LAR treatment did not induce desensitization of pituitary SS receptors (SSR) in humans with intact hypothalamic-pituitary axis, and b) in patients with GEP endocrine tumors, GH/IGF-I inhibition did not contribute to SSa efficacy.

Effects of Alcohol on Intraovarian Nitric Oxide Synthase and Steroidogenic Acute Regulatory Protein in the Prepubertal Female Rhesus Monkey*

In addition to affecting hypothalamic-pituitary function, alcohol is a gonadal toxin capable of inhibiting ovarian function and suppressing circulating levels of estradiol (E2) in female rats, rhesus monkeys, and adolescent girls. Both nitric oxide (NO) and steroidogenic acute regulatory protein (StAR) are intraovarian substances that influence steroidogenesis in opposite directions. This study was undertaken to determine whether alcohol exposure affects prepubertal ovarian steroidogenesis in female rhesus monkeys by altering nitric oxide synthase (NOS), StAR, or both. At 20 months of age, monkeys received a single intragastric dose of alcohol (2.4 g/kg) or an equal volume of a saline/sucrose solution daily until they were 36 months old. Blood and ovaries were then collected for assessment of serum hormone levels and tissue gene and protein expression. Alcohol caused depressed levels of serum E2 (p < .05) and luteinizing hormone (p < .05) but not follicle-stimulating hormone. Real-time polymerase chain reaction (RT-PCR) assessment of ovarian mRNA encoding the three isoforms (i.e., neuronal [n] NOS, endothelial [e] NOS, and inducible [i] NOS) of NOS revealed that alcohol exposure did not alter gene expression of nNOS but caused increased basal levels of eNOS (p < .05) and iNOS (p < .01) mRNA expression compared with control ovaries. Alcohol also increased expression of eNOS (p < .01) and iNOS (p < .05) proteins. In contrast, ovaries from monkeys exposed to alcohol showed decreased (p < .05) StAR gene expression compared with controls. We showed previously that alcohol exposure during adolescence suppressed E2 and delayed development of regular monthly menstruation patterns in rhesus monkeys. The present results suggest that the combined action of alcohol to elevate ovarian NOS and suppress StAR synthesis contributes to these abnormalities.

Bone mineral density in survivors of childhood brain tumours

Osteopenia has been reported in children surviving acute lymphoblastic leukaemia, apparently as consequence of therapy. Few studies have been published on bone mineral density (BMD) evaluation in children surviving from brain tumours. The endocrine system in these patients is frequently affected as consequence of therapeutic interventions such as cranial irradiation and anti-neoplastic agents: growth hormone deficiency is the most common adverse sequel. The pathogenesis of osteopenia in brain cancer survivors is multi-factorial but still uncertain. The aim of this study is to examine bone mass in 12 brain cancer survivors and its relationship with their hormonal status. We observed that most of the patients had a BMD that was lower than normal in both the lumbar column and in the femoral neck. Bone mass loss was higher in the lumbar region rather than in the femoral neck, due to spinal radiation therapy and to the effect of hormonal deficiencies. Particularly hypogonadism, but also multiple hormonal deficiencies, are associated with lower BMD values. Experience in clinical care of these patients suggests the importance of periodic evaluations of BMD, especially in those with secondary hormone deficiencies. Moreover, the periodic assessment of the hypothalamus-pituitary function is essential for an early diagnosis of hormonal insufficiency, primarily hypogonadism, to precociously detect bone mineral loss and to prevent pathological fractures, thus improving the quality of life.

Hypothalamic Pituitary Adrenal Function during Critical Illness: Limitations of Current Assessment Methods

Activation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of several important responses to stressful events and critical illnesses. Despite a large volume of published data, several controversies continue to be debated, such as the definition of normal adrenal response, the concept of relative adrenal insufficiency, and the use of glucocorticoids in the setting of critical illness. The primary objective was to review some of the modulating factors and limitations of currently used methods of assessing HPA function during critical illness and provide alternative approaches in that setting. This was a critical review of relevant data from the literature with inclusion of previously published as well as unpublished observations by the author. Data on HPA function during three different forms of critical illnesses were reviewed: experimental endotoxemia in healthy volunteers, the response to major surgical procedures in patients with normal HPA, and the spontaneous acute to subacute critical illnesses observed in patients treated in intensive care units. The study was conducted at an academic medical center. Participants were critically ill subjects. There was no intervention. The main measure was to provide data on the superiority of measuring serum free cortisol during critical illness as contrasted to those of total cortisol measurements. Serum free cortisol measurement is the most reliable method to assess adrenal function in critically ill, hypoproteinemic patients. A random serum free cortisol is expected to be 1.8 microg/dl or more in most critically ill patients, irrespective of their serum binding proteins. Because the free cortisol assay is not currently available for routine clinical use, alternative approaches to estimate serum free cortisol can be used. These include calculated free cortisol (Coolens' method) and determining the free cortisol index (ratio of serum cortisol to transcortin concentrations). Preliminary data suggest that salivary cortisol measurements might be another alternative approach to estimating the free cortisol in the circulation. When serum binding proteins (albumin, transcortin) are near normal, measurements of total serum cortisol continue to provide reliable assessment of adrenal function in critically ill patients, in whom a random serum total cortisol would be expected to be 15 microg/dl or more in most patients. In hypoproteinemic critically ill subjects, a random serum total cortisol level is expected to be 9.5 microg/dl or more in most patients. Data on Cosyntropin-stimulated serum total and free cortisol levels should be interpreted with the understanding that the responses in critically ill subjects are higher than those of healthy ambulatory volunteers. The Cosyntropin-induced increment in serum total cortisol should not be used as a criterion for defining adrenal function, especially in critically ill patients. The routine use of glucocorticoids during critical illness is not justified except in patients in whom adrenal insufficiency was properly diagnosed or others who are hypotensive, septic, and unresponsive to standard therapy. When glucocorticoids are used, hydrocortisone should be the drug of choice and should be given at the lowest dose and for the shortest duration possible. The hydrocortisone dose (50 mg every 6 h) that is mistakenly labeled as low-dose hydrocortisone leads to excessive elevation in serum cortisol to values severalfold greater than those achieved in patients with documented normal adrenal function. The latter data should call into question the current practice of using such doses of hydrocortisone even in the adrenally insufficient subjects.

Presentation and evolution of organic central precocious puberty according to the type of CNS lesion

To evaluate the influence of the type and treatment of CNS lesion causing central precocious puberty (CPP) on the presentation, hypothalamic-pituitary function and final height. One hundred patients with CPP caused by central nervous system (CNS) lesion. The CPP was the presenting symptom of the lesion in 25 (10 boys) and occurred in 75 patients (23 boys) previously treated for lesions. These were optic glioma or astrocytoma (n = 45), hydrocephalus (n = 22), hypothalamic hamartoma (n = 15), suprasellar arachnoid cyst (n = 10) and others (n = 8). The percentages of patients with increased height, bone age advance, testicular volume, LH/FSH peaks ratio after gonadotrophin-releasing hormone (GnRH) test and plasma testosterone concentration in boys and oestradiol in girls varied from one aetiology to another. The boys with hamartoma were significantly taller and had greater bone age advance, LH peak and testosterone than boys with optic glioma. The girls with hamartoma and suprasellar arachnoid cyst were significantly younger and had greater LH peak than girls in the other groups. All patients treated for optic glioma had hypothalamic-pituitary deficiencies, including GH (100%), thyrotrophin (71.4%), corticotrophin (12.5%) and pubertal (34.3%) deficiencies. Sixty percent of those with suprasellar cysts lacked GH. Final height was below -2 SD in 15/59 (25%) patients, including 5/11 not treated with GnRH analogue, 3/5 not treated with GH despite GH deficiency, and 2 with hydrocephalus as a result of meningomyelocele. The type of CNS lesion influences the presentation of CPP. This is probably caused by differences in the mechanisms inducing puberty and to the hypothalamic-pituitary deficiencies associated with the CPP as a result of a lesion and/or its treatment.

Commentary

The frequency of decreased or absent libido/potency was studied in 65 males with tumors in the region of the sella turcica. The presence or absence of sexual dysfunction was correlated to the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and prolactin; to the LH response to LH-releasing hormone (LH-RH); and to certain tumor characteristics. Seventy-six per cent of the patients had decreased or absent libido/potency. The corresponding figures for those with an intrasellar tumor and those with a large tumor with extention into the suprasellar region were 54% and 88%, respectively. Only 1 of 20 patients whose first symptom of a tumor was a decrease in libido or potency consulted a doctor because of this symptom. The serum levels of FSH and LH in the group of patients with decreased or absent libido/potency were within the normal range in 47% and 34%, respectively, but almost all of these patients had low serum levels of testosterone. The LH response to LH-RH was better related to the presence or absence of sexual dysfunction than was the basal LH level. There was no significant relationship between decreased or absent libido/potency and increased serum prolactin levels. A low serum testosterone level indicates an endocrine etiology of the sexual dysfunction. When combined with a normal or decreased level of gonadotropins, a primary disturbance of hypothalamic-pituitary function is probable.

Hypoglycemia, an Old Tool for New Findings in the Adrenomedullary Hormonal System in Patients with Rheumatic Diseases

Over the past decades, research in patients with rheumatic disorders showed enormous progress in detecting various perturbations of the neuroendocrine system including those affecting autonomic nervous function. There is, however, a substantial lack of data on adrenomedullary hormonal system (AMHS) function in those patients. Insulin-induced hypoglycemia (IIH) represents a metabolic stressor, which elicits a counterregulatory stress response not only of the hypothalamic-pituitary axis but also of the AMHS. Therefore, in addition to traditional testing of hypothalamic-pituitary function, IIH can be used as a well-controlled functional test of the AMHS. Our recent studies showed, for the first time, attenuated epinephrine and norepinephrine responses to IIH in premenopausal females with rheumatoid arthritis (RA) and systemic sclerosis (SSc). These findings are suggestive of downregulation, or possibly defects, of the AMHS in those patients. This article reviews mechanism of the AMHS activation during IIH and demonstrates applications of the test in neuroendocrine-immune research.

Abnormalities of the Hippocampus are Similar in Deoxycorticosterone Acetate‐Salt Hypertensive Rats and Spontaneously Hypertensive Rats

Hippocampal neuropathology is a recognised feature of the brain in spontaneously hypertensive rats (SHR), but similar studies are lacking in another model of hypertension, the mineralocorticoid-salt-treated rat. The present study aimed to compare changes in hippocampal parameters in 16-week-old male SHR (blood pressure approximately 190 mmHg) and their normotensive Wistar-Kyoto controls, with those of male Sprague-Dawley rats receiving (i) 10 mg deoxycorticosterone acetate (DOCA) every other day during 3 weeks and drinking 1% NaCl solution (blood pressure approximately 160 mmHg) and normotensive controls treated with (ii) DOCA and drinking water, (iii) drinking water only or (iv) 1% NaCl only. In these experimental groups, we determined: (i) cell proliferation in the dentate gyrus (DG) using the 5-bromo-2'-deoxyuridine-labelling technique; (ii) the number of glial fibrillary acidic protein (GFAP) positive astrocytes under the CA1, CA3 and DG; (iii) the number of apolipoprotein E (ApoE) positive astrocytes as a marker of potential neuronal damage; and (iv) the number of neurones in the hilus of the DG, taken as representative of neuronal density in other hippocampal subfields. Changes were remarkably similar in both models, indicating a decreased cell proliferation in DG, an increased number of astrocytes immunopositive for GFAP and ApoE and a reduced number of hilar neurones. Although hypertension may be a leading factor for these abnormalities, endocrine mechanisms may be involved, because hypothalamic-pituitary function, mineralocorticoid receptors and sensitivity to mineralocorticoid treatment are stimulated in SHR, whereas high exogenous mineralocorticoid levels circulate in DOCA-treated rats. Thus, in addition to the deleterious effects of hypertension, endocrine factors may contribute to the abnormalities of hippocampus in SHR and DOCA-treated rats.

Hormonal Regulation of Postnatal Growth in Children Born Small for Gestational Age

Children born small for gestational age (SGA) are at high risk of permanent short stature, with approximately 10% continuing to have stature below the third centile throughout childhood and adolescence and into adulthood. The mechanisms involved in catch-up growth, and those that prevent catch-up growth, are still unknown. To date, no reliable anthropometric or endocrine parameter predictive of postnatal catch-up growth has been identified. However, subtle abnormalities in the growth hormone-insulin-like growth factor axis, the hypothalamic-pituitary-adrenal axis and thyroid function have been described, and a mechanism involving intrauterine programming of hypothalamic-pituitary function has been proposed.

Effects of Opium Dependency on Hypothalamic Pituitary Gonadal Axis

The aim of this study was to determine the effect of opium on hypothalamic pituitary gonad function. Fifty-six opium dependent (28 men and 28 women; mean age, 25±5 year) were enrolled for hypothalamic pituitary gonadal axis. The control group considered of 56 non-opium dependent subject (28 men and 28 women; mean age 25±5 year). Decreased libido or impotency was present in 26 of 28 opium dependent men. The serum testosterone level was below 9 nmol L-1 in 24 of 28 men and was significantly lower than that in the control group (p<0.001). The free androgen index was below normal in 16 of 28 men and was significantly lower than that in the control group (p<0.001). The serum LH level was less than 2 U L-1 in 17 of 28 men significantly lower than that in the control group (p<0.001). Serum FSH was normal in both groups. Decreased libido was present in 16 of 28 women opium dependent. Serum LH, estradiol and progesterone levels were lower in opium group. In conclusion, of all opium addicts the large majority of men and all of women developed hypogonadotropic hypogonadism. The results reveal that opium can extract deleterious actions upon male and female hypothalamic pituitary gonadal axis and these findings suggested that further investigations are required to determine the need for endocrine work-up in opium dependent and the important substitutive therapy.

Expression and Intracellular Signaling of Estrogen α- and β-Receptor Subtypes in Native and Immortalized GnRH Neurons

Pulsatile GnRH release is an intrinsic property of the GnRH neuron and is modulated by neurotransmitters, pituitary hormones, and gonadal steroids. Despite the prominent role of estrogen in the regulation of hypothalamic-pituitary function, its ability to exert receptor-mediated actions directly on the GnRH neuron has only recently been demonstrated. We and others have demonstrated that estrogen receptors are expressed in both hypothalamic GnRH neurons and their immortalized counterparts, GT1-7 cells. This report describes the roles of estrogen receptor subtypes in GnRH neuronal signaling and secretion. Cell culture; cellular perifusion studies; cAMP and GnRH radioimmunoassay (RIA); patch-clamp recording of action potentials. GT1-7 cells were cultured in DMEM/F-12 medium with 10% heat-inactivated fetal bovine serum, and then in serum- and steroid-free medium prior to stimulation with estradiol or selective ERα and ERβ ligands. The roles of ERα and ERβ in cAMP production and pulsatile GnRH release were determined in perifused GT1-7 cells. cAMP formation and GnRH levels were measured by RIA after treatment with ERα and ERβagonist and antagonist analogs. Action potential firing was recorded by patch-clamping in hypothalamic cell cultures obtained from enzymatically dispersed E18 fetal Sprague-Dawley rat hypothalami. Identified GnRH neurons were subjected to recording in the absence and presence of estradiol, and ERα and ERβ agonist and antagonist analogs. Our previous research showed that physiological estrogen concentrations caused rapid inhibition of spontaneous cAMP production that was prevented by the ER antagonist ICI 182,780. The estrogen receptor that mediates this effect on cAMP could be immunoprecipitated with an antibody to the α-receptor. In the present study, pulsatile GnRH release in cultured hypothalamic cells, cAMP production, and the rate of firing of spontaneous action potentials by identified hypothalamic GnRH neurons, were inhibited during activation of the Gi-coupled ERα receptor. In contrast, selective activation of the Gs-coupled ERβ receptor increased GnRH release, stimulated cAMP production, and increased the rate of firing of action potentials. The ability of estrogen to activate ERα and/or ERβ receptors in a time- and dose-dependent manner regulates the adenylyl cyclase/cAMP signaling pathway, and thereby modulates the frequency and amplitude of pulsatile GnRH release. This process, in conjunction with the modulation of spontaneous electrical activity of the GnRH neuron, is a major factor in the control of the pulsatile mode of neuropeptide secretion that is characteristic of GnRH neuronal function.

Glucagon‐like peptide‐1 reduces the pulsatile component of testosterone secretion in healthy males

Glucagon-like-peptide-1 (7-36) amide (GLP-1), a potent regulator of glucose homeostasis, has been implicated in the control of hypothalamic-pituitary function. In vivo it is a relevant neuroendocrine modulator of gonadotropin-releasing hormone release, suggesting its possible role as a metabolic signal to the reproductive system. The present study was undertaken to establish its effect on luteinizing hormone (LH) and testosterone secretion in nine healthy male volunteers. Each subject underwent an oral glucose tolerance test to establish LH, testosterone, and GLP-1 responses to glucose. Euglycaemic clamp experiments (6 h) were performed on two occasions with saline or with a constant infusion of GLP-1 (0.4 pmol kg(-1) min (-1)). Blood samples were drawn at 10-min intervals to measure the pulsatile pattern of LH and testosterone secretion. Ingestion of oral glucose resulted in a reduction in plasma testosterone levels at 30 min compared with baseline (P < 0.004) despite unaltered LH levels (P = 0.5). Constant GLP-1 infusion resulted in no change in LH (P = 0.83), testosterone (P = 0.96), follicle stimulating hormone (FSH) (P = 0.86) and leptin levels (P = 0.3). Pulse analysis revealed no significant difference in the number (P = 0.1) or median absolute amplitude (P = 0.3) of the LH pulses. However, there was a significant decrease in the number (3.0 +/- 0.6 vs. 1.3 +/- 0.4; P < 0.05) and a tendency for increased duration of testosterone pulses (97.4 +/- 16.7 vs. 170 +/- 27.1 min; P = 0.06). Oral glucose ingestion and intravenous GLP-1 infusion reduce the pulsatile component of testosterone secretion by a mechanism independent of LH release.

Delayed adrenal insufficiency long after unilateral adrenalectomy: Prolonged glucocorticoid therapy reduced reserved secretory capacity of cortisol

A 51-year-old woman with Cushing's syndrome underwent unilateral adrenalectomy for left adrenal adenoma. After 7 years of prednisolone treatment (with some interruptions), followed by 4 years of total withdrawal from prednisolone treatment, she presented with hypotension, weight loss, general fatigue, nausea, hyponatremia and hypoglycemia. These clinical features together with a low response in the rapid adrenocorticotropic hormone test led to the diagnosis of acute adrenal insufficiency. Relatively low serum adrenocorticotropic hormone levels in the face of increased demand for cortisol during adrenal crisis suggested a disordered hypothalamic-pituitary function, indicating secondary adrenal insufficiency. This patient demonstrated the etiology of acute adrenal insufficiency long after unilateral adrenalectomy in association with subsequent glucocorticoid therapy. A reduction in the reserved secretory capacity of cortisol after prolonged prednisolone treatment was considered to have induced secondary adrenal insufficiency, even after 4 years of total withdrawal from prednisolone.

The pattern of growth hormone secretion during the menstrual cycle in normal and depressed women

Major depression is associated to altered hypothalamic-pituitary function. Stress is linked to elevated cortisol as well as menstrual cycle disturbance; however, there is no known relationship between depression and menstrual cycle disruption. The aim of this study was to investigate changes of growth hormone (GH) secretion during the menstrual cycle in normal and depressed women. Case-control study. Nineteen women affected with depression and 24 normal controls were included. The two groups had comparable body mass index (BMI), and age (29.4 +/- 9.8 vs. 28.6 +/- 9.7 years). Nine depressed and 10 controls were studied in the follicular phase, while 10 depressed and 14 controls were studied in the luteal phase of the cycle. GH was sampled every 10 min for 24 h, and the data were analysed by the cluster pulse detection method. There was no difference in 24-h mean GH concentrations between depressed and control subjects (P = 0.93), even after accounting for menstrual cycle phase (P = 0.38). GH pulse frequency was higher during the follicular phase of the cycle (P = 0.032), and nocturnal GH was higher in the follicular phase of the cycle (P = 0.05, and after adjusting for 24-h GH, P = 0.0138) regardless of whether the subjects were depressed or healthy. In studies of GH secretion in women with or without depression, it is necessary to control for the phase of menstrual cycle.

Age-related differences in serum gonadotropin (FSH and LH), salivary testosterone, and 17-? estradiol levels among Ache Amerindian males of Paraguay

Age-related differences in serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), salivary testosterone, and 17-beta estradiol levels are reported for Ache Amerindian males (n = 17; mean age, 37.1 +/- 14.2 SD) of Paraguay in order to explore population variation in patterns of male reproductive senescence in a foraging/agricultural community. Hormone associations were examined to test various hypotheses for age-related differences in hypothalamic-pituitary function. Significant increases in FSH (r = 0.75, P < 0.0005) and LH (r = 0.65, P < 0.01) were noted in association with aging. No significant correlation was observed between morning or evening testosterone and age. Morning and evening estradiol levels were associated with morning and evening testosterone, respectively (morning, r = 0.53, P = 0.05; evening, r = 0.63, P = 0.02). Evening estradiol was also positively associated with LH (r = 0.66, P = 0.02), suggesting testicular production to be an important source of circulating estradiol. Morning estradiol tended to rise with age, but was not significant (r = 0.39, P = 0.15). Anthropometric measurements of height, weight, body mass index, and fat percent did not change significantly with age. In contrast to testosterone, age-related differences in gonadotropin levels may be independent of energetic status, less variant, and more universal among male populations. Implications for gonadotropin function and aging on human male reproductive senescence and life histories are discussed.

The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours

Survival rates are improving following cancer therapy for childhood brain tumours. There is therefore a growing cohort of survivors at risk of late effects of cancer therapy. Endocrine problems are very common in these patients. The recognition and prompt management of these are essential to prevent further morbidity and impairment of quality of life. Cranial radiation can damage hypothalamic-pituitary function, most frequently affecting GH status; however, higher radiation doses may cause more widespread hypothalamic-pituitary damage. Early puberty secondary to cranial irradiation is now being managed with gonadotrophin-releasing hormone analogues to improve final height. Prompt diagnosis and management of GH deficiency may improve final height outcome; continued GH therapy beyond final height aids the achievement of adult body composition (lean body mass and bone mass) and GH therapy in adulthood improves quality of life. Both cranial irradiation alone and with spinal irradiation can result in radiation damage to the thyroid resulting in hypothyroidism and thyroid nodules, a high proportion of which are malignant. Gonadal damage secondary to spinal irradiation and adjuvant chemotherapy may have long-term consequences including infertility.

Endocrine abnormalities in patients with Jacobsen (11q-) syndrome.

Jacobsen syndrome (JS), a rare disorder with multiple dysmorphic features, is caused by the terminal deletion of chromosome 11q. Short stature has been reported in this syndrome, however very few of these patients have undergone endocrine evaluation. Serum insulin-like growth factor-1 (IGF-1) levels are an indirect indicator of growth hormone activity and are a useful initial screening tool in the assessment of an individual's growth hormone axis. We studied nine children with JS, eight of whom had short stature. Four out of eight children with short stature (50%) had low IGF-1 values, with three low for age and one low for Tanner stage. Four out of six males (67%) had cryptorchidism, a potential sign of hypogonadism. We conclude that low IGF-1 is common in patients with JS and short stature, and that growth hormone status and possibly hypothalamic-pituitary function should be evaluated in this patient population.

Intrasellar pressure in pituitary tumors . Relation study: intrasellar pressure vs hypothalamic-pituitary function

Intrasellar pressure in pituitary tumors . Relation study: intrasellar pressure vs hypothalamic-pituitary function

Transition from paediatric to adult endocrinology: hypopituitarism.

For patients at the transition stage between childhood and adulthood, cooperation between paediatric and adult endocrinologists is essential for optimum care. Evaluations of patients in transition consist of retrospective assessments of what happened in childhood combined with prospective planning for treatment and follow up into adult life. Successful transfer of patients in transition from paediatric to adult care should follow a general sequence tailored to local circumstances. First, all patients with GH deficiency and their families should be informed by their paediatric endocrinologist about the long term consequences of GH deficiency in adulthood and the potential need for life-time GH replacement therapy. Second, retesting will be needed for evaluating hypothalamic pituitary function, re-evaluation of the need for replacement therapy for other pituitary hormone deficits, measurement of fasting lipid concentration and assessment of skeletal integrity. Third, the patient and physicians should consider the option of attending an out-patient clinic having both a paediatric and an adult endocrinologist. Regardless, the wishes of the patient should be respected as much as possible. It is essential that those patients who had childhood-onset GH deficiency and who were treated with GH be followed throughout adult life.