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The long-term effects of cranial external beam radiotherapy are emerging as survival rates for cerebral tumours improve. Cerebral cavernoma are a recognized consequence of cranial irradiation. Endocrinologists managing the life-long complications of hypopituitarism associated with irradiation need to be aware and vigilant of the risks of cavernoma formation, in particular in the population with a history of childhood irradiation. We present three cases of young patients who were diagnosed with cerebral cavernoma many years after childhood irradiation treatment and review the current literature on this condition. We discuss implications for endocrine practice as rising numbers of patients survive childhood cancer and irradiation and are now attending adult endocrine services for long-term management of secondary hypopituitarism. [ABSTRACT FROM AUTHOR]

Hypopituitarism is not currently considered as a potential cause of immune disruption in humans. Accumulating data from in vitro and animal models support a role for the pituitary gland in immune regulation. Furthermore, the increased mortality risk noted in patients with adult hypopituitarism remains poorly explained and immune dysfunction could conceivably contribute to this observation. In a recent issue of Clinical & Experimental Immunology, we presented new data relating to immune status in adults with treated, severe hypopituitarism. We observed humoral immune deficiency in a significant proportion, despite stable pituitary replacement, including growth hormone (GH). This was especially evident in those with low pretreatment IGF-I levels and appeared independent of anticonvulsant use or corticosteroid replacement. These observations require substantiation with future studies. In this short review, we summarize existing data relating to the effects of pituitary hormones on immune function and discuss potential clinical implications surrounding the hypothesis of immune dysregulation in severe hypopituitarism. [ABSTRACT FROM AUTHOR]

Quantitatively, GH secretion exists as a continuum in states ranging from good health through to hypopituitarism. Currently, GH replacement is considered only for adults designated as being severely GH deficient (GHD). In clinical practice the gold standard, on which the biochemical diagnosis of severe GHD is based, centres on the presence of two or more additional anterior pituitary hormone deficits. Cohorts of adults with partial GHD (Growth Hormone Insufficiency [GHI]) have been reported with adverse body composition changes, dyslipidaemia, insulin resistance, altered cardiac performance and increased carotid intima-media thickness. The diagnosis of GHI in an individual patient, however, is extremely difficult because such patients rarely exhibit additional anterior pituitary hormone deficits, and the levels of GH-dependent proteins, including IGF-I, are normal in the majority. Currently, GH replacement therapy should only be considered in a patient characterized as GHI by dynamic GH testing in whom there is a plausible cause for hypopituitarism and in whom the IGF-I level is pathologically low. [ABSTRACT FROM AUTHOR]

Objective Craniopharyngioma (CP) is a benign tumour of the suprasellar region that is associated with increased morbidity and mortality in comparison with other causes of hypopituitarism. We aimed to establish the rate and causes of mortality and morbidity in patients with CP who attended our centre. Design We performed a retrospective case note audit of patients with CP who were managed by our service. We established the standardized mortality ratio (SMR) for patients with CP. We compared obesity prevalence with two other hypopituitary groups who are managed by our service. Patients We identified 70 patients with CP, 97% of whom had undergone surgery and 42% radiotherapy. We compared the prevalence of obesity with that of 89 patients with hypopituitarism secondary to surgery for nonfunctioning pituitary adenoma and 29 patients with post-traumatic hypopituitarism (PTHP). Measurements Standardized mortality ratio for patients with CP was 8·75 (95% CI of 5·4-13·3); SMR for women was 10·51 (95% CI 5·04-19·3) and 7·55 (95% CI 3·77-13·52) for men. The rates of growth hormone (GH), gonadotrophin, adrenocorticotrophic hormone (ACTH) and TSH deficiencies were 91%, 93·5%, 92% and 86%, respectively. The rate of diabetes insipidus (DI) was 81%; 7·1% had adipsic DI. Dyslipidaemia was present in 46·9% and diabetes mellitus in 11·5%. Obesity affected 66% of patients with CP, 47% of patients with nonfunctioning adenoma and 31% of those with PTHP ( P < 0·001). Conclusions Patients with CP suffer from high rates of mortality and morbidity. The underlying causes for mortality and for obesity in this population remain poorly understood. [ABSTRACT FROM AUTHOR]

Background The long-term risk of hypothyroidism following postpartum thyroid dysfunction (PPTD) is uncertain. Most previous studies have been small, short-term or have lacked a control group. Objective To ascertain the long-term risk of hypothyroidism in women following PPTD. Design and participants A 12-year longitudinal study of 409 women (including 71 with PPTD) who previously participated in a PPTD prevalence study. Measurements The primary outcome measure was hypothyroidism (defined as TSH greater than 4 mU/l or on thyroxine replacement) at follow-up. Outcomes in women with and without PPTD were compared by logistic regression. Receiver operating characteristic analysis was used to determine the optimal cut-off for baseline TSH as a predictor of hypothyroidism in the cohort. Results At follow-up, hypothyroidism was present in 27 of 71 women who had PPTD at baseline (38%) and 14 of 338 women without PPTD (4%). From multivariate analysis, odds ratios (with 95% confidence intervals) for hypothyroidism were – 4·8 (1·6, 14·1) for PPTD; 8·2 (2·8, 24·6) for positive thyroid peroxidase antibodies (TPOAb); 9·7 (2·6, 37·0) for the hypothyroid phase of PPTD and 51·4 (19·2, 137·5) for hypothyroid PPTD with positive TPOAb. A baseline TSH above 2·6 mU/l was the optimal cut-off for predicting hypothyroidism (sensitivity 76%, specificity 86%). Conclusions PPTD is a strong predictor of hypothyroidism in the long-term. Women who present with postpartum hypothyroidism or have positive TPOAb are at particularly high risk, suggesting that close long-term follow-up is advisable if thyroxine replacement is not instituted at an early stage. [ABSTRACT FROM AUTHOR]

Objective Aneurysmal subarachnoid haemorrhage (SAH) has recently been reported as a common cause of chronic hypopituitarism, and introduction of routine neuroendocrine screening has been advocated. We aimed at estimating the risk of hypopituitarism after SAH using strict criteria including confirmatory testing in case of suggested insufficiency. Design Cross-sectional evaluation with a nested prospective subgroup. Patients and measurements Endocrine evaluation was performed at a median of 14 months (range 11–26) post-SAH in 62 patients with SAH and 30 healthy controls. Twenty-six patients were followed prospectively (median 7 days, and 12 months post-SAH). Endocrine evaluation included baseline evaluation, which was combined with an insulin tolerance test (ITT) or, if contraindicated, GHRH + arginine tests and a standard ACTH test at evaluation 1–2 years post-SAH. Pituitary insufficiencies were confirmed by re-evaluation. Results Early post-SAH hormone alterations mimicking central hypogonadism were present in 58% of the patients and associated with a worse clinical state ( P < 0·05). One to 2 years post-SAH, initial neuroendocrine evaluation identified seven patients (11%) with abnormal results; three had free T4 and TSH suggestive of central hypothyroidism, three men had testosterone below 10 nm, and one had an insufficient GH and cortisol response to the ITT. None of these abnormalities was confirmed upon confirmatory testing. Conclusion In the largest reported cohort of patients with SAH to date, with early and late endocrine evaluation, none of the patients had chronic hypopituitarism. Based on these findings, the introduction of routine neuroendocrine screening is not justified, and the data suggest the importance of using strict diagnostic criteria in patients with a low pretest probability of hypopituitarism. [ABSTRACT FROM AUTHOR]

Background TSH secretion in hypopituitary patients may be decreased due to TSH deficiency but it also remains under feedback inhibition by free thyroxine (fT4). We propose a TSH index (TSHI), as ‘fT4-adjusted TSH’, that corrects for any physiological TSH suppression, to provide a true estimate of pituitary thyrotroph function and any pathological pituitary suppression. Methods A total of 9519 thyroid function tests (TFTs) (Bayer Immuno-1®) in 4064 patients of our institution were examined, including 444 patients investigated for hypopituitarism. Based on the physiological log-linear relationship between fT4 and TSH, we estimated the amount of feedback-induced change in log TSH per change in fT4, which allowed the extrapolation of log TSH to a fixed fT4 of 0, defining the TSHI. TSHIs were compared with other measures of pituitary function. Results Feedback inhibition was estimated to cause a 0·1345 decrease in log TSH (mU/l) for 1 pmol/l increase in fT4 concentration, therefore TSHI = log TSH + 0·1345 × fT4. Patients with lower peak-stimulated GH and cortisol concentrations had a significantly lower TSHI ( P < 0·0001). TSHIs measured before pituitary stimulation tests predicted highly significantly the risk of test failure ( P = 0·0002). Of all potential fT4–TSH combinations within the current reference ranges, 21·9% were identified as abnormal on the basis of the TSHI. Conclusion The TSHI provides an accurate estimate of the severity of pituitary dysfunction in hypopituitary patients based on simple TFTs. It predicts the probability of pituitary stimulation test failure and extends the diagnosis of TSH deficiency into areas of the normal TFT reference ranges. [ABSTRACT FROM AUTHOR]

Objective We evaluated the German Acromegaly Register for clinical variables associated with the initial biochemical activity of patients with acromegaly. Design Retrospective analysis of data in the registry. Patients A total of 1485 patients with acromegaly (males 45·6%, females 54·4%) were treated in 42 German endocrine centres until November 2005. Linear regression models were used to estimate the influence of various parameters on biochemical activity. Results Male patients with acromegaly were significantly younger at the time of diagnosis than female patients (41 vs. 47 years, P < 0·0001) and had significantly higher random GH levels than females (21 vs. 14 ng/ml, P < 0·005) and IGF-1 levels (773 vs. 679 ng/ml, P < 0·0001), respectively. Age at initial presentation turned out to be the most important independent risk factor associated with random GH levels, oral glucose tolerance test-suppressed GH levels, IGF-1 levels, body mass index (BMI), tumour size and prevalence of hypopituitarism. Sex was an independent risk factor for IGF-1 levels, BMI and prevalence of hypopituitarism. Tumour size was an independent risk factor for both GH and IGF-1 levels. Conclusions In summary, initial biochemical activity of acromegaly is influenced by patient’s age and to a lesser degree by patient’s sex. Male patients are on an average 6 years younger than females. [ABSTRACT FROM AUTHOR]

Objective Recent studies have suggested that mutations in genes encoding several hypothalamo–pituitary (H–P) transcription factors result in hypopituitarism [isolated GH deficiency (IGHD) and combined pituitary hormone deficiency (CPHD)], which may in turn be related to the neuroanatomy revealed by magnetic resonance (MR) imaging. Although studies have focused on patients with either optic nerve hypoplasia (ONH) or isolated hypopituitarism with normal optic nerves, few studies have compared the two groups. We aimed to relate the clinical phenotype of a large cohort ( n = 170) of children with congenital hypopituitarism including septo-optic dysplasia (SOD) attending a single centre to the neuroradiological and genetic findings. Design Clinical, biochemical, MR imaging and molecular data were analysed retrospectively in 170 patients with or ‘at-risk’ (with ONH) of hypopituitarism to determine predictors of hypopituitarism. Results The presence of ONH was significantly associated with an absent septum pellucidum [odds ratio (OR) 31·5, 95% confidence intervals (CI) 7·3–136·6, P < 0·001], an abnormal corpus callosum (OR 10·5, 95% CI 3·8–28·6, P < 0·001) and stalk abnormalities (OR 2·3, 95% CI 1·2–4·2, P = 0·009). The risk of hypopituitarism was 27·2 times greater in patients with an undescended posterior pituitary (95% CI 3·6–205·1, P < 0·001). Anterior pituitary hypoplasia (OR 3·1, 95% CI 1·3–7·0, P = 0·006) and an absent pituitary stalk ( P < 0·001) were also significantly associated with hypopituitarism. With respect to the type or severity of hypopituitarism, CPHD was more often associated with an abnormal corpus callosum (OR 6·1, 95% CI 1·4–27·4, P = 0·008) and stalk abnormalities (OR 2·8, 95% CI 1·3–6·1, P = 0·006). Male to female ratio was significantly greater in patients with normal optic nerves (3·3:1) as compared with those with ONH (1·2:1). The prevalence of diabetes insipidus, thyrotrophin and ACTH deficiencies was significantly greater in patients with ONH as compared with ‘idiopathic’ hypopituitarism. Mutations in pituitary transcription factors and genes regulating GH secretion were rare (5/170) in this cohort of patients with sporadic hypopituitarism. Conclusion Our data suggest that individuals presenting with ONH are at high risk for neuroradiologic and endocrine abnormalities. The neuroradiologic features are predictive not only of the presence, but also of the type, of hypopituitarism. The association of midline abnormalities with hypopituitarism in this cohort suggests a common developmental origin for these features, the aetiology of which remains unidentified in the majority of cases. [ABSTRACT FROM AUTHOR]

Background Several studies have reported a high prevalence of hypopituitarism after traumatic brain injury (TBI). Risk stratification is a prerequisite for cost-effective hormonal screening of these patients. However, it is still unclear which risk factors predispose patients to develop anterior hypopituitarism after TBI. Objective To assess clinical and radiological risk factors for post-traumatic hypopituitarism. Patients and methods Seventy-eight consecutive patients (52 men, 26 women; mean age 36·0 years, range 18–65 years) with mild, moderate or severe TBI were studied. Endocrine and clinical parameters were assessed 3 and 12 months after TBI. Results We found diffuse axonal injury, basal skull fracture and older age to be major risk factors of post-traumatic hypopituitarism. Conclusions We have defined specific risk factors for the development of post-traumatic hypopituitarism that are consistent with pathophysiological considerations. These findings might help to identify at-risk patients. [ABSTRACT FROM AUTHOR]

Objective LHX4 and HESX1 are important in early stages of pituitary development and their mutations can be associated with an ectopic posterior lobe (EPL) in the pituitary of patients with hypopituitarism. The EPL can be located at the median eminence or at the path of the pituitary stalk. The aim of this study was to analyse LHX4 and HESX1 and characterize the hormonal deficiency profiles, establishing relationships with magnetic resonance imaging (MRI) findings in these patients. Patients and design Sixty-two patients with hypopituitarism associated with EPL were submitted to evaluation of pituitary function, analysis of MRI with EPL location and molecular analysis of LHX4 and HESX1 using polymerase chain reaction (PCR), digestion with restriction enzyme and automatic sequencing. Results Forty-two patients had a nonvisualized pituitary stalk (NPS), and 20 a visualized pituitary stalk (VPS). Most patients (95%) with NPS had combined pituitary hormone deficiency (CPHD), with ACTH deficiency in 85%. In patients with VPS, CPHD was found in 50% and ACTH deficiency occurred in only 20%. The frequency of the location of EPL was similar in patients with VPS and NPS: 35% at median eminence and 65% at the path of the stalk. No mutations in LHX4 and HESX1 were identified. Three new polymorphisms in LHX4 were found. Conclusions ACTH deficiency is frequent in patients with hypopituitarism and NPS (85%), the location of EPL at the median eminence was not predictive of the hormonal profile [isolated GH deficiency (IGHD) or CPHD], and LHX4 and HESX1 genes mutations remain rare causes of hypopituitarism associated with EPL. [ABSTRACT FROM AUTHOR]

Background and objective Previous studies on hypopituitarism and mortality have concluded that insufficient pituitary function is associated with decreased survival. For several reasons the results are difficult to compare – particularly because definitions and treatment of hypopituitarism have varied and various underlying disorders have been included. The purpose was to assess the relationship between mortality and pituitary function. Patients and design One hundred and sixty consecutive patients (99 men and 61 women) with functionless, suprasellar pituitary adenoma. All were operated on transsphenoidally during the period 1985–1996. Additional radiotherapy was given to 29 patients. Mortality was calculated 12·4 years (median, range 8·1–19·9) after operation. Postoperative hormonal deficits were treated in most, though GH substitution was given only to a minority of patients. Results Postoperatively 30% of the patients had normal pituitary function (normal adrenocortical, thyroid and gonadal function), 26% were panhypopituitary and 36% had partial pituitary insufficiency. Forty-one patients had died (34·7 expected) yielding a standard mortality ratio (SMR) of 1·18 (95% confidence limits (CI) 0·87–1·60). SMR was significantly increased in women (1·97, CI 1·20–3·21) but not in men (0·83, CI 0·55–1·26). SMR in patients with normal pituitary function, panhypopituitarism and partial insufficiency were not different from that in the general population. SMR in hypopituitary women was substantially higher than in men with pituitary insufficiency. Treatment with growth hormone in GH-deficient patients did not influence survival. Conclusion Pituitary surgery for nonfunctioning adenoma and subsequent pituitary insufficiency had no effect on mortality in men, but was associated with significantly increased mortality in women. Suboptimal hormonal substitution in women may play a role. [ABSTRACT FROM AUTHOR]

Background Women with hypopituitarism are known to have a poor outcome once pregnancy has been achieved by ovulation induction. There are no data, however, recording the efficacy of ovulation induction and pregnancy rates in this group of subfertile women. Methods The outcome of fertility treatments in all 19 women with hypopituitarism attending the fertility clinics of University College London Hospitals over the past 20 years was audited. Results Ovulation was achieved in almost all women (95%) but occurred in only 60% of treatment cycles. Pregnancy was achieved in 47% of women or 11% of cycles resulting in a live birth rate of 6·7% per cycle. Seven of the 18 pregnancies (39%) miscarried. Only 42% of women treated achieved a live birth. Conclusion Ovulation induction in women with hypopituitarism yields relatively low pregnancy rates in comparison to other causes of anovulation and a high miscarriage rate. Pituitary hormone deficiency beyond gonadotrophins has a major adverse effect on achieving pregnancy. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) has been associated with hypopituitarism and GH deficiency. However, TBI-mediated hypopituitarism may be more frequent than previously thought. The present work, performed in patients with severe TBI at least 1 year before, had three aims: (i) to evaluate the prevalence of hypopituitarism, (ii) in particular to evaluate the prevalence of GH deficiency, and (iii) to compare three different tests of GH reserve in this cohort.From a nonselected group of 249 patients admitted to our Clinical Centre for severe TBI over the last 5 years, 200 of them answered a custom made questionnaire of symptoms of hypopituitarism enclosed in the invitation letter to participate in the study. A total of 170 (99 men and 14 women), accepted to participate in the study (study cohort); 57 had normal questionnaires and were not further studied, 14 discontinued the study, and 99 attended the hospital for dynamic tests of pituitary hormone deficiencies. From these, 44 subjects with IGF-I in the lower range were tested with GHRH+GHRP-6; ITT; and glucagon tests of GH reserve, on three different occasions.Pituitary hormones plus IGF-I and target gland hormones were analysed.With regard to the initial cohort of 170 subjects (100%), three (1·7%) showed diabetes insipidus; 10 (5·8%) TSH deficiency, 11 (6·4%) ACTH deficiency and 29 (17%) gonadotrophin deficiency. In 10 subjects (5·8%), GH deficiency was diagnosed by strict criteria. Finally, 15 (8·8%) showed combined deficit of several hormones.After severe head trauma, gonadotrophin deficiency was the most common pituitary deficit. GH deficiency showed a prevalence similar to ACTH and TSH deficits, i.e. near 6% of the cohort. Taken together, 24·7% of the subjects studied showed any type of pituitary hormone deficiency. [ABSTRACT FROM AUTHOR]

Little is known of the long-term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency (GHD). In this study, the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD.A prospective, open-label, single-centre study.Twenty-six (12 male and 14 female) consecutive hypopituitary adults with adult onset GHD, mean age 65·0 (range 61–74) years.Upper leg muscle strength was measured using a Kin-Com dynamometer. Right and left handgrip strength were measured using an electronic grip force instrument.The mean insulin-like growth factor-I (IGF-I) SD score increased from−1·10 at baseline to 1·21 at end of the study. Body weight was unchanged during the 5-year study. A sustained increase in lean body mass and a sustained reduction of body fat was observed as measured using dual-energy X-ray absorptiometry (DEXA). The GH replacement therapy induced a sustained increase in isometric (60°) knee flexor strength. After statistical correction for age and sex variables using observed/predicted value ratios, a sustained increase was also observed in concentric knee flexor strength at an angular velocity of 60°/s, concentric knee extensor strength at 60°/s and 180°/s, and peak right handgrip strength. At baseline, knee flexor strength was 90–96% of predicted, knee extensor strength was 85–87% of predicted, and hand-grip strength was 74–80% of predicted values. At study end, knee flexor strength was 98–106% of predicted, knee extensor strength was 90–100% of predicted, and hand-grip strength was 80–87% of predicted values.Elderly patients with adult onset GH deficiency had decreased baseline muscle strength also after correction for age and sex. The 5-year GH replacement therapy normalized knee flexor strength and improved, but did not fully normalize, knee extensor strength and handgrip strength. [ABSTRACT FROM AUTHOR]

Current data suggest a permissive role for the somatotrophic axis in the reproductive process, mainly by affecting the onset of puberty and the maintenance of regular menstrual cyclicity. To assess a possible interface between GH and reproductive axes in determining the uterus size, we retrospectively evaluated 58 pelvic ultrasound scans in adult women with either isolated growth hormone deficiency (GHD;n = 12), hypogonadotrophic hypogonadism (HH;n = 24) or hypopituitarism (HP;n = 22) of prepubertal onset. Pelvic ultrasound was performed before oestrogen replacement in patients with HH or HP, and after completion of GH treatment in the majority of patients with HP. Eight women with HH and seven with HP had a second pelvic ultrasound examination after being established on oestrogen replacement therapy. A group of 19 young healthy women with no previous history of pregnancy or miscarriage were included for comparison of ultrasound data.Uterine measurements, length and uterine cross-sectional area (UXA) were significantly less in the three study groups compared to healthy controls[median UXA: GHD 18·0 cm2 (range 9·9–28·6 cm2), HH 7·0 cm2 (range 1·3–18·5 cm2), HP 11·8 cm2 (range 1·6–21·8 cm2) and controls 23·0 cm2 (range 16·1–31·7 cm2);P < 0·001]. The median age of oestrogen replacement was significantly later in HH[19 years (range 16–26 years)] compared to HP[16·5 years (range 13–20 years)] P = 0·03, while the median age of menarche of GHD patients was 14·5 years (range 11–16 years), which was not statistically different from controls[13·0 years (range 12·5–14·5 years)]. Repeat uterine measurements on oestrogen in the subgroup of 15 patients did not reach the normal values[pretreatment UXA: 4·2 cm2 (range 1·6–16·1 cm2), post-treatment UXA: 12·6 cm2 (range 4–23 cm2)]. Ovarian volume was smaller in the two groups of women with gonadotrophin deficiency (HH and HP), while a polycystic ovarian morphology was notably more prevalent in the two groups who had received GH treatment being found in 75 and 58% of women with GHD and HP, respectively, compared with 12·5% in women with HH (P < 0·004).Our findings suggest that GHD might have an independent effect in determining uterus size and therefore the consequences of GHD plus oestrogen deficiency on uterus growth might be additive. The fact that uterine measurements between HH and HP patients did not differed significantly in this study may be explained by the fact that oestrogen replacement has been substituted earlier in the latter group. Furthermore, it appears that standard oestrogen replacement therapy did not result in normal uterine growth. A polycystic ovarian morphology may be a consequence of GH treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE AND DESIGN: Hypopituitarism, in particular GH deficiency, is prevalent in patients with clinically nonfunctioning pituitary adenomas (NFPAs) both before and after surgery. The factors regulating the growth of pituitary adenomas in general and residual tumour tissue in particular are not fully characterized, and the effect of GH and IGF-l on human pituitary cell proliferation has not previously been reported. In NFPA tissue from 14 patients we evaluated GH receptor (GHR) expression and signal transduction, and the effect of GH and IGF-l exposure on cell proliferation and hormone secretion in vitro. MEASUREMENTS: Tissue samples from 14 NFPAs were investigated. Expression of GHR in tissue samples was assessed by reverse transcription polymerase chain reaction (RT-PCR). Six tumours were immuno-stained with a GHR antibody. In the cell cultures, STATS (signal transducer and activator of transcription 5) phosphorylation was measured by Western blot analysis as an index of GHR signalling; cell proliferation was evaluated by [H³]-thymidine incorporation and glycoprotein hormone production analysed by radio-immunoassay (RIA). RESULTS: All adenomas investigated expressed the GHR, but there was no detection of STATS phosphorylation. Overall, GH and IGF-l administration did not significantly stimulate cell proliferation in vitro, although some individual adenomas exhibited a proliferative response to various extents. GH also did not significantly influence glycoprotein hormone secretion In vitro. CONCLUSION: GH receptors are expressed in human pituitary adenoma cells but their functional role is uncertain. GH and IGF-l do not consistently influence the proliferation of cultured pituitary adenoma cells. [ABSTRACT FROM AUTHOR]

OBJECTIVETo determine the prevalence and incidence of hypopituitarism in the general population. POPULATIONThe study population comprised an average population sample of 146 000 adult inhabitants in South Galicia (northwestern Spain). The Medical Register of the General Hospital of Vigo ensured virtually complete case ascertainment for diagnosed hypopituitarism in this sample population. Only patients residing in the study area were included. The diagnosis of hypopituitarism was based on baseline and hormonal dynamic tests. DESIGNThe study comprised two cross-sectional surveys, the first from January to December 1992 and the second from January to December 1999, together with a longitudinal survey performed between January 1993 and December 1999. MAIN RESULTSIn the first survey the prevalence of hypopituitarism was 29/100 000 (CI, 19·88–37·72), without sex differences. In the second survey, the prevalence observed was higher than in the first, 45·5/100 000 (CI, 34·92–56·08). In the second survey, which included almost all cases registered in the first study, the cause of hypopituitarism was a pituitary tumour in 61%, a non-pituitary tumour in 9% and a non-tumour cause in 30%. Around 50% of patients had 3–5 pituitary hormonal deficiencies, with LH/FSH being the most prevalent. Patients with tumour-induced hypopituitarism showed a tendency to suffer GH deficiency more frequently than those due to non-tumour causes. In the longitudinal study with a population of 1020 764 people-years of observation, the average annual incidence rate of hypopituitarism was 4·21 cases/100 000 (CI, 2·95–5·47), with this incidence being similar for both sexes. The annual incidence of hypopituitarism remained stable during the study period. CONCLUSIONWe present for the first time data on the prevalence and incidence of hypopituitarism in the general adult population. These patients showed a tendency to suffer LH/FSH deficiency as the most prevalent hormone deficit. Furthermore, patients with hypopituitarism due to a tumour or its treatment showed a greater tendency to suffer GH deficiency than those with a non-tumour cause. These data may be useful for producing a rational programme for patients suffering from this condition and also for comparison with future data in our country and elsewhere in the world. [ABSTRACT FROM AUTHOR]

OBJECTIVE The within subject variability of the insulin tolerance test (ITT) for assessment of growth hormone (GH) status and cortisol reserve has rarely been examined, particularly in patients with hypopituitarism. This becomes important when biochemical criteria are used to determine which adults with hypopituitarism should receive GH and/or cortisol replacement. In the present study we assessed the reproducibility of GH and cortisol responses in repeated ITTs. Baseline insulin-like growth factor 1 (IGF-1) levels were also assessed for reproducibility on each occasion. DESIGN and PATIENTS Three consecutive ITTs were performed in seven normal adult men (ages 22–27 years) and two ITTs in 11 men with hypopituitarism and suspected GH deficiency (ages 23–48 years). MEASUREMENTS Serum GH and IGF-1 were measured by immunoradiometric and cortisol by immunofluorimetric assays. RESULTS In normal men group peak GH responses did not differ between the three tests. There was no correlation between individual peak values. The within subject peak GH variability was between 4·6 and 59·3%, and the overall variability in 21 tests was 35%. The lowest peak GH concentration was 70 mU/l (27 µg/l). All hypopituitary men had severe GH deficiency (all peak GH concentrations < 4 mU/l (1·5 µg/l) in both tests). There was a highly significant correlation between individual peak GH values (r = 0·95, P < 0·0001). Basal IGF-1-values in normal and hypopituitary men were highly correlated between tests (r = 0·98, P < 0·0001). The overall within subject variability of IGF-1-values was 11·9% in normal and 22·7% in hypopituitary men. In normal men group peak cortisol responses were not different between the three tests. There was a good correlation between individual peak cortisol responses in the three ITTs. The within subject peak cortisol variability (median 8·3%; range 0·7–21·5%) was significantly less than that of GH (P < 0·03) in two of three test comparisons. In hypopituitary men the within subject peak cortisol variability (median 41·6%; range 3·5–92·7%) was significantly greater (P < 0·001) than in normal men. All patients were correctly classified as cortisol deficient or normal in both ITTs. CONCLUSION The cortisol response to repeated hypoglycaemia is very reproducible in normal men but the GH response is less so. In hypopituitary men the reproducibility of the GH response is good while that of the cortisol response is poor. However, a single ITT did not misclassify hypopituitary patients who are severely GH and/or ACTH deficient and was therefore adequate for clinical decisions regarding GH and/or cortisol replacement. Nevertheless, it remains possible that a single ITT could misclassify some hypopituitary patients with partial GH or ACTH deficiency. [ABSTRACT FROM AUTHOR]

Investigates the use of combined pituitary function test in children. Importance of luteinizing hormone; Detection of hypothalamic-pituitary disease; Delay of growth and puberty due to hypopituitarism.

OBJECTIVE It has previously been shown that patients with postpartum pituitary necrosis (Sheehan's syndrome, SS) have paradoxically increased TSH levels and loss of the nocturnal TSH surge. This study sought to determine the circadian and pulsatile characteristics of TSH secretion underlying those abnormalities. DESIGN AND PATIENTS Chronobiological and cluster analyses of 24-h TSH profiles were performed in nine SS patients (43–61 years, median = 52 years) and nine healthy female controls (33–47 years, median = 42 years). MEASUREMENTS Serum concentrations of T3, T4, free T4 (fT4) and cortisol were measured by radioimmunoassay; TSH, GH, PRL and LH were determined by immunometric assays. RESULTS All patients and controls showed significant circadian TSH rhythms, but the percentage amplitude was decreased (7.5% vs. 21.3%, P < 0.0001) and the acrophase was markedly displaced in SS patients, occurring between 0315 h and 1515 h in seven/nine patients and in two/nine controls (P = 0.057). Patients showed increased total 24-h TSH secretion (6054 ± 2293 vs. 2193 ± 340 mU/l/min, mean ± SE, P = 0.04) due to increased non-pulsatile or tonic 24-h TSH secretion (5631 ± 2105 vs. 1925 ± 301 mU/l/min, P = 0.026), but no difference was detected in pulsatile secretion (424 ± 191 vs. 268 ± 41, P = 0.82). The contribution of non-pulsatile to total TSH secretion was also increased in SS patients (93.8% vs. 87.6%, P = 0.002). No significant changes were found in TSH pulse frequency, amplitude, duration or interpeak interval. When cluster parameters were individually analysed in two distinctive 12-h periods corresponding to acrophase and nadir, patients showed increased non-pulsatile TSH secretion in both periods, but no differences were found in pulsatile TSH secretion, pulse frequency or amplitude. The increment of TSH secretion during the acrophase in SS patients was exclusively due to increased non-pulsatile TSH secretion, as opposed... [ABSTRACT FROM AUTHOR]

OBJECTIVESAdult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age-and sex-matched controls. PATIENTSSeventeen hypopituitary adults with GHD (13 male, 4 female) aged 26–54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age- and sex-matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction. MEASUREMENTSUsing an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium-dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium-independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF-1, and studied the relationship of these parameters to endothelial function. RESULTSFlow mediated endothelium-dependent dilatation (FMD), expressed as a percentage change from resting base-line diameter, was significantly impaired in the GHD group (3.70 ± 2.36% vs. 7.30 ± 2.42%, P < 0.001). In contrast, GTN-mediated dilatation was similar in both groups. There were no differences in total cholesterol, HDL cholesterol, LDL cholesterol or plasma triglyceride between the groups. Both fasting insulin (27.1 ± 18.1 vs. 15.89 ± 6.65 mU/l, P < 0.05) and glycated... [ABSTRACT FROM AUTHOR]

In this article, the author discusses hypopituitarism which is a complexity of subarachnoid hemorrhage (SAH). He comments on a study published within this issue which found a little data of permanent hypopituitarism in a group of long term survivors of SAH. He mentions about another study related to hyponatremia following SAH. He states that more data is required on the patients with very severe SAHs and high mortality.