bluuebunny/crossref_metadata_2025_split huggingface dataset:
The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic–pituitary–adrenal axis following pituitary surgery
Authors: Courtney  , McAllister  , McCance  , Hadden  , Leslie  , Sheridan  , Atkinson  
Published: March 2003

OBJECTIVETo compare the insulin hypoglycaemia test with the short overnight metyrapone test in the assessment of the hypothalamic–pituitary–adrenal (HPA) axis posthypophysectomy.DESIGNProspective comparative study of the insulin hypoglycaemia test and the overnight metyrapone test in 32 patients 4–6 weeks after pituitary surgery.SUBJECTSThirty‐two patients with known pituitary disease. None with present or previous Cushing's syndrome.OUTCOME MEASUREMENTSMaximum serum cortisol achieved during insulin induced hypoglycaemia compared with 0900 hours serum 11‐deoxycortisol level following a weight related oral dose of metyrapone at 0000 h.RESULTSOne of the 32 patients required further surgery and was studied twice after each operation. Thirty‐three results are therefore compared. Twenty‐six of these had a normal cortisol response of 550 nmol/l or above leading to the cessation of replacement hydrocortisone. Six of these 26 patients however, failed the metyrapone test (11‐deoxycortisol level less than 200 nmol/l). After 3–40 months (median 20 months) of follow‐up off steroid therapy, no patient to date has displayed any clinical evidence of steroid deficiency. Of the seven patients who failed the insulin hypoglycaemia test, six also failed the metyrapone test.CONCLUSIONSThe overnight metyrapone test identified more patients with possible ACTH deficiency than the insulin hypoglycaemia test. Further follow‐up of these patients is required before a final judgement can be made as to whether more subtle but clinically relevant ACTH deficiency can be detected by the metyrapone test. Our clinical follow‐up to date would not support this.
Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre‐and postmenopausal women
Authors: O'leary Peter , Feddema Peter , Chan Katherine , Taranto Mario , Smith Margaret , Evans Sharon 
Published: March 2003

OBJECTIVEThe use of topically applied micronised (‘natural’) progesterone as a substitute for synthetic oestrogens and progestogen preparations is controversial. The aim of this study was to examine the changes in blood and salivary concentrations of progesterone following a single topical application of a progesterone cream.PATIENTS AND MEASUREMENTSWe investigated six premenopausal women in the luteal phase and six postmenopausal women to determine the short‐term changes in serum, urinary and salivary progesterone concentrations following a single 64 mg topical application of micronised progesterone.RESULTSSerum progesterone concentrations did not increase during the first 3 hours after application of progesterone cream, however, salivary values rose significantly in both premenopausal and postmenopausal women, consistent with the view that progesterone is absorbed and transported through the body. Salivary progesterone concentrations were significantly elevated above basal levels by 30–60 minutes and reached peak levels at 1–4 h, with mean levels approximately fivefold higher in premenopausal, than in menopausal women.CONCLUSIONSSalivary progesterone measurements confirm that topically applied progesterone is absorbed, despite the lack of change in serum progesterone concentrations. However, at the dose administered, serum progesterone levels do not reach those observed after oral or vaginally delivered progesterone preparations. Higher doses may be required to induce biological responses within the endometrium.
Relationship between blood pressure and glucose tolerance in acromegaly
Authors: Jaffrain‐Rea M.‐L. , Moroni C. , Baldelli R. , Battista C. , Maffei P. , Terzolo M. , Correra M. , Ghiggi M. R. , Ferretti E. , Angeli A. , Sicolo N. , Trischitta V. , Liuzzi A. , Cassone R. , Tamburrano G. 
Published: March 2003

BACKGROUNDHypertension represents a well‐known risk factor for cardiovascular diseases. The pathogenesis of hypertension in acromegaly is commonly viewed as multifactorial, but the possible influence of metabolic disorders on blood pressure (BP) in affected patients is largely unknown.OBJECTIVEThe aim of the present study was to evaluate the impact of glucose metabolism abnormalities on BP values in a series of patients with active acromegaly.DESIGNAn open multicentre prospective study.PATIENTSSixty‐eight patients with active disease, aged 47·5 ± 11·7 years, have been studied. Thirty‐nine had normal glucose tolerance (NGT), 16 impaired glucose tolerance (IGT) and 13 suffered from diabetes mellitus (DM).MEASUREMENTSMean clinical BP values were calculated as the mean of BP values obtained by sphygmomanometric measurement in three separate occasions and mean 24‐h, diurnal and nocturnal systolic (SBP) and diastolic (DBP) values were obtained by 24‐h ambulatory blood pressure monitoring (ABPM).RESULTSPatient's age and the degree of glucose tolerance abnormalities were found to significantly and independently influence BP values. All clinical and ABPM SBP and DBP values significantly increased with age by linear regression (P < 0·02 for all BP values, 0·30 ≤ R ≤ 0·43), and the independent influence of this parameter on BP values was confirmed by mutivariate analysis. Similarly, the independent influence of glucose tolerance abnormalities on BP values was confirmed when introducing age as a covariable in a multivariate analysis, and patients with DM presented significantly higher clinical SBP and 24‐h, diurnal and nocturnal SBP and DBP than patients with NGT (P < 0·02 for clinical SBP, P < 0·015 for all ABPM values, respectively). In addition, patients with DM showed significantly higher 24‐h, diurnal and nocturnal DBP than those with IGT (P < 0·05 in all cases). In contrast, no significant difference was found between NGT and IGT patients. No significant influence of disease duration, BMI, GH, IGF‐I, or fasting and 2‐h post glucose load insulinaemia on BP values was observed.CONCLUSIONSAbnormalities of glucose metabolism significantly contribute to increase systolic blood pressure and especially diastolic blood pressure in acromegalic patients. Careful control of blood pressure and of risk factors for developing systemic hypertension, with special reference to glucose tolerance, is mandatory to decrease cardiovascular morbidity and mortality in such patients.
Screening for an AIRE‐1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome
Authors: Meyer G. , Donner H. , Herwig J. , Böhles H. , Usadel K. H. , Badenhoop K. 
Published: March 2003

Autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) is a rare systemic autoimmune disorder of monogenic and autosomal‐recessive inheritance. To date, 29 APECED causing mutations have been identified in the responsible gene AIRE‐1, coding for a regulator of transcription. The aim of this study was to examine whether mutations in AIRE‐1, in their heterozygous form, predispose to the more common isolated autoimmune endocrinopathies Addison's disease, type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis.Patients with isolated autoimmune endocrine disorders as well as healthy controls were analysed for two of the most common AIRE‐1 mutations, mutation R257X in exon 6 and a 13‐bp deletion in exon 8. Mutations were detected by polymerase chain reaction based techniques.In total, 726 individuals were investigated for mutation R257X. Subjects comprised patients with Addison's disease, IDDM, Graves' disease and Hashimoto's thyroiditis. With regard to the 13 bp deletion we could screen 91 patients with Addison's disease. In addition, six patients with the APECED syndrome including one family were analysed for both mutations.Out of the 12 alleles in APECED patients six contained either mutation R257X or the 13 bp deletion, confirming that these mutations prevail in Europe. R257X was found in one subject with Hashimoto's thyroiditis in its heterozygous form. The 13 bp deletion was not detected in any subject with Addison's disease.The two studied AIRE‐1 mutations are so rare in the general population that they can not contribute to susceptibility for the more common isolated autoimmune disorders.
Prevalence of diabetes and impaired glucose tolerance in adult hypopituitarism on low dose oral hydrocortisone replacement therapy
Authors: McConnell E. M. , Bell P. M. , Hadden D. R. , McCance D. R. , Sheridan B. , Atkinson A. B. 
Published: March 2003

OBJECTIVE The conventional dosage of hydrocortisone, used for many years in the management of hypopituitarism (30 mg per day), has now been shown to be more than is physiologically necessary. On this conventional corticosteroid therapy studies have demonstrated an increased prevalence of diabetes and impaired glucose tolerance, which may contribute to the increased vascular morbidity and mortality reported in the condition. In these studies no information is available on oral glucose tolerance test (OGTT) timing in relation to administration of oral steroid and variable hydrocortisone doses were employed.PATIENTS In order to assess glucose tolerance in patients treated with lower, more physiological doses, we performed a 75‐g OGTT at least 1 month after hydrocortisone therapy was adjusted to 15 mg at 0800 h and 5 mg at 1700 h in 45 adult onset hypopituitary patients (30 M, 15 F). Mean (± SD) duration of hypopituitarism was 12 ± 10 years, mean age 52 ± 14 years and BMI 29·3 ± 5·1 kg/m2. All were on hydrocortisone, 43 on thyroxine, 31 on sex steroids, 9 on desmopressin and 33 had documented growth hormone deficiency. Hydrocortisone 15 mg was taken at 0800 and the OGTT commenced at 0900.RESULTS Using standard WHO criteria 36 patients (80%) had normal glucose tolerance, 1 (2%) had newly diagnosed diabetes and 8 (18%) had impaired glucose tolerance. Using the recently announced American Diabetes Association criteria for diagnosis 96% had normal glucose tolerance, 2% had diabetes and 2% impaired fasting glucose.CONCLUSION The markedly reduced prevalence of diabetes and impaired glucose tolerance on lower hydrocortisone replacement doses in our series of patients with hypopituitarism, not previously known to be diabetic, is of great interest. This lower prevalence may eventually result in reduced vascular complication rates.
Histocompatibility leucocyte antigens and closely linked immunomodulatory genes in autoimmune thyroid disease
Authors: Hunt P. J. , Marshall S. E. , Weetman A. P. , Bunce M. , Bell J. I. , Wass J. A. H. , Welsh K. I. 
Published: March 2003

OBJECTIVES Associations between autoimmune thyroid disease and antigens of the major histocompatibility complex (MHC) have long been recognized. Graves' disease (GD) is associated with the histocompatibility leucocyte antigen (HLA) haplotype A*01‐B*0801‐DRB1*0301‐DQA1*0501‐DQB1*0201 (or B8/DR3) whereas autoimmune hypothyroidism (AIH) has been weakly associated with HLA DRB1*03, *04 and *11/*12 alleles (or DR3, DR4 and DR5). However, the presence of important immunoregulatory genes within the HLA Class II and III regions raises the possibility that these genes harbour the primary susceptibility locus. This study examines genetic variation across the MHC in UK Caucasoid subjects with autoimmune thyroid disease.PATIENTS AND METHODS DNA extracted from venous blood samples from 215 patients with autoimmune thyroid disease (GD 135, AIH 77) and 267 control subjects was analysed. Genotyping was performed using polymerase chain reaction and sequence specific primers for HLA Class I and II alleles and polymorphisms within the TAP1, TAP2, tumour necrosis factor (TNF), lymphotoxin α (LTα), heat shock protein (HSP)70‐1, HSP70‐2 and HSP70‐Hom genes.RESULTS For GD, the strongest association was with DRB1*03 [56% patients positive vs. 24% controls, P = 2 × 10−10, odds ratio (OR) 4·0]. Positive associations were also seen for DRB1*03 linked alleles, B*0801, DRB3*01/02, DQA1*05, DQB1*02 and DPB1*0101 (OR 2·3–3·4). Specific TNF and LTα alleles were strongly associated with GD (Pc = 3 × 10−5 and 0·001) and weak associations were seen for HSP70‐1 + 190C and HSP70‐2 + 1267G polymorphisms (Pc = 0·05 and 0·01). These associations were not significant when DRB1*03 status was considered. Patients with AIH showed only a weak association with DQB1*03 (P = 0·02).CONCLUSIONS These results show that, of the polymorphisms tested within the MHC, GD is most strongly associated with DRB1*03, and associations with other immunoregulatory genes previously described in Caucasian subjects most likely reflect linkage disequilibrium. AIH differs from GD, being less influenced by the MHC region.
Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour?
Authors: Erfurth Eva Marie , Bülow Birgitta , Mikoczy Zoli , Svahn‐Tapper Gudrun , Hagmar Lars 
Published: March 2003

OBJECTIVE To assess the incidence of second brain tumours in patients operated and irradiated for pituitary tumours.DESIGN AND PATIENTS The study base consisted of a consecutive series of 325 patients operated and irradiated for pituitary tumours, excluding patients with acromegaly and Cushing's disease. Comparison was made with the general population from the same catchment area as the patients. The follow‐up period started in 1958 and on an individual basis patients were followed from the onset of postoperative irradiation until December 1995, or until date of death, emigration or a second brain tumour diagnosis, whichever occurred first.RESULTS Three brain tumours (two astrocytomas and one meningioma) were observed, compared with 1·13 expected (standardized incidence ratios (SIR) 2·7; 95% confidence interval (CI) 0·6–7·8).CONCLUSION The present study gives no firm support for an increased incidence of a second brain tumour in patients operated and irradiated for pituitary tumours. A crude meta‐analysis of the present and previously published cohort studies of patients with irradiated pituitary tumours gives an SIR of 6·1 (95% CI 3·16–10·69). Thus, the results of the meta‐analysis are in favour of an increased risk for second brain tumours. A genetic trait that predisposes to both pituitary tumours and brain tumours is an alternative causal factor. There is no definite proof that cranial irradiation per se is the causal factor. This question cannot be fully answered until sufficient cohort studies of nonirradiated pituitary tumour patients have been carried out.
Increased prevalence of heterozygous 21‐OH germline mutations in patients with adrenal incidentalomas
Authors: Baumgartner‐Parzer S. M. , Pauschenwein S. , Waldhäusl W. , Pölzler K. , Nowotny P. , Vierhapper H. 
Published: March 2003

Summaryobjective As a result of the widespread use and the enhanced quality of high‐resolution radiological techniques [computed tomography (CT), magnetic resonance imaging (MRI)] a high frequency (4–10%) of adrenal incidentalomas has been detected in the general population. It is still debated whether undiagnosed 21‐hydroxylase (21‐OH) deficiency, accounting for more than 90% of congenital adrenal hyperplasia (CAH) cases, predisposes for adrenal tumours. We therefore performed an analysis of the prevalence of 21‐OH germline mutations in patients with non‐functional adrenal incidentalomas.subjects and methods Fifty Austrian patients with non‐functional adrenal adenomas detected by CT for unrelated reasons were screened by PCR‐based sequencing for the most common point mutations and by Southern blot analysis for large gene deletion/conversion events of the 21‐OH gene.results Heterozygosity for large gene conversions was shown in 5 (10%), for Q318 point mutations in 2 (4%) and for the Intron2splice mutation in 1 (2%) of the 50 patients with adrenal adenomas. One (2%) patient (70 years of age), identified to have a chimeric CYP21AB gene with a junction site before Intron 2 on one and a large (30 kb) deletion on the other allele, was diagnosed to be affected by CAH.conclusion 21‐OH mutation screening indicates a higher frequency of classic CAH carriers (16%) and of manifest CAH (2%) due to 21‐OH‐deficiency among patients with adrenal adenomas than in the general population (1–2% carrier frequency for classic CAH).
The low‐dose ACTH test does not provide a useful assessment of the hypothalamic–pituitary–adrenal axis in secondary adrenal insufficiency
Authors: Suliman Abdulwahab M. , Smith Thomas P. , Labib Mourad , Fiad Tarek M. , McKenna T. Joseph 
Published: March 2003

SummaryOBJECTIVE The 1 µg ACTH stimulation test has been introduced to improve the sensitivity of ACTH as a test of the integrity of hypothalamic–pituitary–adrenal axis (HPAA). This study aims to compare the sensitivity, specificity and diagnostic accuracy of the ‘low‐dose’ 1 µg ACTH (LDACTH) test and the ‘standard dose’ 250 µg ACTH (SDACTH) test, with the overnight metyrapone test (OMT) which assesses the entire HPAA.DESIGN A prospective evaluation of the performance of SDACTH and LDACTH screening tests in a diverse cohort of patients with possible adrenal insufficiency as routinely encountered in clinical practice using the OMT as the reference method.PATIENTS A total of 51 patients (26 with asthma on inhaled glucocorticoid, nine with hypopitutarism, three with hypothyroidism, one with hyponatraemia, one with Crohn’s disease, one with encephalitis and 10 with non‐specific symptoms) each underwent SDACTH, LDACTH and OMT tests in random sequence at least 1 week apart.MEASUREMENTS Blood was sampled for plasma cortisol levels at 0 and 30 min after intravenous administration of 1 µg and 250 µg of ACTH. Metyrapone 30 mg/kg body weight was taken orally at midnight, and plasma samples were taken for measurement of 11‐deoxycortisol and cortisol next morning between 08·00 and 09·00 h. The OMT was deemed to be abnormal when both 11‐deoxycortisol and cortisol levels were less than 200 nmol/l.RESULTS The sensitivity and specificity at an empirical ‘normal’ plasma cortisol threshold value of 500 nmol/l were 67% and 100% for the SDACTH test, and 73% and 81% for the LDACTH test, respectively. As the plasma cortisol cut‐off value was increased to 550 nmol/l and 600 nmol/l, the sensitivity of the SDACTH test was 67% and 80% and specificity was 97% and 92%, respectively. The sensitivity of the LDACTH test increased from 93% at plasma cortisol cut‐off value of 550 nmol/l to 100% at plasma cortisol cut‐off value of 600 nmol/l. However, the specificity of the LDACTH test fell from 72% to 56% as the plasma cortisol cut‐off value was increased from 550 nmol/l to 600 nmol/l. A receiver operating characteristic curve demonstrated that the specificity of the SDACTH test was higher than the specificity of the LDACTH test at any given level of sensitivity.CONCLUSIONS Both the LDACTH and SDACTH tests fail to achieve acceptable levels of sensitivity and specificity to be useful as screening tests for secondary adrenal insufficiency. In this context the OMT can be safely used to assess the integrity of the entire HPAA.
The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant
Authors: Van Wassenaer Aleid G. , Stulp Maykel R. , Valianpour Fredoen , Tamminga Pieter , Ris Stalpers Carrie , De Randamie Janine S. E. , Van Beusekom Christien , De Vijlder Jan J. M. 
Published: March 2003

Summarybackground Thyroid hormone is crucial for brain development during foetal and neonatal life. In very preterm infants, transient low levels of plasma T4 and T3 are commonly found, a phenomenon referred to as transient hypothyroxinaemia of prematurity. We investigated whether breast milk is a substantial resource of thyroid hormone for very preterm neonates and can alleviate transient hypothyroxinaemia. Both the influence of breast feeding on plasma thyroid hormone levels and the thyroid hormone concentration in preterm human milk were studied.methods Two groups were formed from the placebo group of a randomized thyroxine supplementation trial in infants born at < 30 weeks’ gestational age on the basis of the mean breast milk intake during the third, fourth and fifth weeks of life. One group received more than 50% breast milk (mean breast milk intake 84%, n = 32) and the other group less than 25% breast milk (mean breast milk intake 3·3%, n = 25). Plasma thyroid hormone concentrations were compared between the two groups. Breast milk was collected from mothers of infants participating in the same trial and the thyroxine concentration in breast milk was measured with RIA after extraction.results No significant differences were found between both groups in plasma concentrations of T4, free T4, T3, TSH, rT3 and thyroxine‐binding globulin (TBG), which were measured once a week. Thyroxine concentration in breast milk ranged between 0·17 µg/l and 1·83 µg/l (mean 0·83, SD 0·3 µg/l) resulting in a maximum T4 supply of 0·3 µg/kg via ingested breast milk. In formula milk, the T4 concentration was equally low. Protease treatment did not influence the measured T4 concentrations.conclusions No differences in plasma thyroid hormone between breast milk‐fed and formula‐fed infants were found. The amount of T4 present in human milk and formula milk is too low to alter the hypothyroxinaemic state of preterm infants.
Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours
Authors: Tannahill L. A. , Visser T. J. , McCabe C. J. , Kachilele S. , Boelaert K. , Sheppard M. C. , Franklyn J. A. , Gittoes N. J. L. 
Published: March 2003

Summaryobjective Thyroid hormones (THs) perform essential roles in pituitary function. They regulate anterior pituitary hormone secretion and are also key determinants of pituitary cell proliferation and differentiation. The critical role of deiodinase enzymes, which serve as prereceptor regulators of TH action, remains largely unexplored. Three deiodinase enzymes metabolize active and inactive THs and thereby determine tissue concentrations of the biologically active ligand, tri‐iodothyronine (T3). We hypothesized that aberrant expression of deiodinase enzymes and/or altered enzyme activity in pituitary tumours may change tissue concentrations of THs and influence their growth and secretory characteristics.study design and patients We studied 105 pituitary tumours and 10 normal pituitaries for expression of deiodinase enzyme mRNAs encoding types 1 (D1), 2 (D2) and 3 (D3) using real‐time RT‐PCR. Enzyme activity data from 20 pituitary samples were also obtained.results Pituitary tumours expressed significantly increased D3 mRNA (6·5‐fold, P < 0·0005) compared with normal pituitaries. D2 mRNA was also increased 2·6‐fold (P = 0·005) in pituitary tumours compared with normals. The rare TSH‐secreting pituitary tumour subtype expressed a 13·1‐fold excess of D3 mRNA and reduced D2 mRNA (0·1‐fold of normal pituitaries). D2 mRNA expression in ACTH‐secreting tumours was similarly reduced to 0·1‐fold that in normal pituitaries.conclusions Pituitary adenomas express abnormal levels of deiodinase enzymes compared to normal pituitaries. These abnormalities may have functional consequences on pituitary tumour growth. In the case of TSH‐secreting pituitary adenomas, the observed pattern of deiodinase mRNA expression may explain the ‘resistance’ of this tumour type to TH feedback.