bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension in disguise—a trap for the unwary
Authors:   Rajasoorya, Chee Thomas Swee-Guan , Boon-Keng Ng
Published: December 2008

Rajasoorya, Chee TS-G, Ng B-K. Hypertension in disguise—a trap for the unwary. Eur J Endocrinol 1995;133:93–6. ISSN 0804–4643

A 36-year-old asymptomatic Chinese male with polycystic kidney disease (PKD) developed hypertension 1 year after the diagnosis of PKD. The patient was treated initially as for hypertension associated with PKD. However, over a 6-year period his hypertension became progressively difficult to control and he developed severe symptomatic hypokalaemia. Subsequent investigations confirmed the presence of primary hyperaldosteronism. The initial computed tomographic scans of the adrenals did not reveal any definite adenomas. The patient subsequently underwent bilateral adrenal venous sampling, which suggested a left-sided source of aldosterone excess. A repeat computed tomography of the adrenals with fine cuts revealed a 6-mm diameter adenoma of the left adrenal gland. He underwent an uncomplicated left adrenalectomy. All antihypertensive and potassium supplements were stopped on the 5th postoperative day. Two and half years after the adrenalectomy he remains normotensive and normokalaemic without any medication. The case illustrates the importance of measuring serum potassium before initiation of any therapy and the need to consider secondary causes even if a primary association is known. It also reinforces the fact that when hypertension becomes difficult to control, a secondary cause has to be searched actively. The association between primary aldosteronism and renal cysts has been highlighted only recently. The association of polycystic kidneys and primary aldosteronism has been reported in the literature only once previously.

Rajasoorya, Department of Medicine, Alexandra Hospital, Alexandra Rd, Singapore 0314
Transient pseudohypoparathyroidism of the neonate
Authors: Minagawa Masanori , Yasuda Toshiyuki , Kobayashi Yasuyuki , Niimi Hiroo
Published: December 2008

Minagawa M, Yasuda T, Kobayashi Y, Niimi H. Transient pseudohypoparathyroidism of the neonate. Eur J Endocrinol 1995:133:151–5. ISSN 0804–4643

We report three neonates with transient hypoparathyroidism with elevated parathyroid hormone (PTH) levels to clarify further the pathogenesis of late neonatal hypocalcemia and calcium homeostasis. Clinical signs were seizures starting at the age of 10 and 11 days. The biochemical features were characterized by transient hypocalcemia and hyperphosphatemia due to a high transport maximum of the phosphate/glomerular filtration rate, despite high PTH levels. All had normal magnesium and calcidiol levels (at least 5 μg/l) for their age, and this precludes hypoparathyroidism due to low magnesium levels and hyperparathyroidism due to overt vitamin D deficiency. To diagnose pseudohypoparathyroidism type I, intravenous human PTH (1–34) infusions were performed; however, they showed brisk responses of plasma and/or urine cyclic AMP in response to the PTH infusion, but the phosphaturic response to the PTH was sluggish compared to the controls. All three showed an increase in serum alkaline phosphatase activity, suggesting PTH stimulation of osteoblasts. They were treated initially with calcium lactate or (1α)-hydroxycalciol/calcitriol. Their hypoparathyroid condition, however, was transient: they maintained normal serum calcium and PTH levels without medication before the age of 6 months. The etiology, possibly intracellular signal transduction distal to cyclic AMP and/or distinct from adenylate cyclase in the kidney, is developmental and the condition was resolved completely within 6 months of age. We have termed this condition "transient pseudohypoparathyroidism of the neonate".

M Minagawa, Department of Pediatrics, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan
Octreotide, but not bromocriptine, increases circulating insulin-like growth factor binding protein 1 levels in acromegaly
Authors: de Herder Wouter W , Uitterlinden Piet , van der Lely Aart-Jan , Hofland Leo J , Lamberts Steven WJ
Published: December 2008

de Herder WW, Uitterlinden P, van der Lely A-J, Hofland LJ. Lamberts SWJ. Octreotide, but not bromocriptine, increases circulating insulin-like growth factor binding protein 1 levels in acromegaly. Eur J Endocrinol 1995;133:195–9. ISSN 0804–4643

Twenty-three patients with active acromegaly underwent serum sampling for growth hormone (GH), insulin and insulin-like growth factor binding protein 1 (IGFBP-1) after placebo or single doses of octreotide or bromocriptine. Integrated 24-h serum GH levels decreased by 90% after octreotide and 49% after bromocriptine. A statistically significant correlation between the course of GH levels after octreotide and bromocriptine was observed (p < 0.001). Octreotide, but not bromocriptine, induced a significant increase in integrated 24-h serum IGFBP-1 levels to 37.4 times the baseline values. Bromocriptine caused a non-significant increase in integrated 24-h serum IGFBP-1 levels, which argues against a direct regulatory effect of GH on IGFBP-1 production in acromegaly. In conclusion, octreotide induces in acromegaly the production of IGFBP-1, which occurs independently of the number of somatostatin receptors on the GH-secreting pituitary adenoma. The supposed inhibitory effect of IGFBP-1 on the biological effect of IGF-I might result in an additional clinical benefit in acromegalic patients as compared to treatment directed at the pituitary level.

WW de Herder, Department of Internal Medicine III and Clinical Endocrinology, University Hospital Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Prevalence of thyroid dysfunction in different geriatric subpopulations from a moderately iodine-deficient Hungarian region. Comparative clinical and hormonal screening
Authors: Szabolcs István , Kovács Zsuzsa , Gönczi Judit , Kákosy Tibor , Góth Miklós , Dohán Orsolya , Kovács László , Szilágyi Géza
Published: December 2008

Szabolcs I, Kovács Z, Gönczi J, Kákosy T, Góth M, Dohán O, Kovács L, Szilágyi G. Prevalence of thyroid dysfunction in different geriatric subpopulations from a moderately iodine-deficient Hungarian region. Comparative clinical and hormonal screening. Eur J Endocrinol 1995;133:294–9. ISSN 0804–4643

The aim of this study was to investigate the prevalence of thyroid dysfunction in different geriatric subpopulations from a moderately iodine-deficient Hungarian region and to compare the efficacy of clinical versus hormonal screening. A screening study was done on 279 chronically ill geriatric patients (Group I) and 256 consecutive hospital admissions over 60 years of age (Group II). The method of clinical screening was different from those used so far: the object was not to search for symptoms of hypo- or hyperthyroidism but to find any sign justifying a further thyrotrophin-based biochemical evaluation, i.e. history of thyroid disease or goitre or any clinical sign of hormonal dysfunction. The rates of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism and subclinical hyperthyroidism discovered by the hormonal screening were 2.9, 1.1, 3.6 and 5.7% in Group I and 3.5, 2.3, 3.9 and 2.0% in Group II. The sensitivities of the clinical screening to suspect overt or overt + subclinical dysfunctions were, respectively, 0.82 and 0.64 in Group I and 1.0 and 0.7 in Group II (or 0.67 and 0.4 if the clinical investigation was done not by an endocrinologist but by the medical attendants). A primarily clinical investigation-based screening would have spared 171/279 thyrotrophin estimation in Group I and 161/256 in Group II, but would have missed 2/11 overt and 11/26 subclinical dysfunctions in Group I. In Group II, no overt but 9/15 subclinical dysfunctions would have been lost in this way. Our approach of a clinical investigation-based screening was rather efficient in suspicion of overt thyroid dysfunction but failed to detect many cases with subclinical dysfunction. As there is increasing evidence from the literature on the clinical importance of subclinical thyroid dysfunction states, the primary screening method should be biochemical, at least in the elderly sick. The prevalence of overt and subclinical dysfunctions would justify the screening of chronically ill hospitalized geriatric patients.

I Szabolcs, HIETE I. Bel, Budapest, PO Box 112, H-1389, Hungary
Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test
Authors: Hoeck Hans C , Vestergaard Peter , Jakobsen Poul E , Laurberg Peter
Published: December 2008

Hoeck HC, Vestergaard P, Jakobsen PE, Laurberg P, Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endocrinol 1995;133:305–12. ISSN 0804–4643

The insulin tolerance test (ITT) is regarded as the most reliable provocative test in the diagnosis of growth hormone (GH) deficiency in adults. In the present study the test was evaluated by investigating the range of GH responses in normal adult males and females and the intra-individual reproducibility of the test. Sixteen healthy non-obese adults, eight males (median age 31.5 years) and eight females (median age 31.8 years) were tested twice with the ITT, with a minimum of 72 h between each test. The females were tested between day 3 and day 10 of their menstrual cycles. Adequate hypoglycemia was achieved in all cases with a median nadir blood glucose of 1.3 mmol/l (range 0.8–2.0). Growth hormone in serum was measured by immunoradiometric assay and low values were confirmed by a different assay. Median peak GH concentration responses to the ITT were: in males 27.9 μg/l, range 5.0–71.1 (test 1) and 30.5 μg/l, range 7.9–69.5 (test 2); and in females 9.0 μg/l, range 4.1–17.9 (test 1) and 8.4 μg/l, range 0.09–42.4 (test 2). The rise in GH concentration during the ITT was higher in males than in females. In the males, all stimulated GH values were ≥5.0 μg/l. In the females, four out of 16 tests gave values below 5.0 μg/l and in one test the GH value was around the detection limit of the assays. There was poor reproducibility during repeated testing, with no correlation between the results of the two tests. The results did not correlate to the magnitude of the hypoglycemia. The results of this study illustrate the complexity of the regulation of GH secretion and indicate that the ITT is less useful for diagnosing GH deficiency in adults than previously anticipated. The diagnosis of GH deficiency in adults and especially in adult females should not be based on the results of a single ITT alone.

Hans C Hoeck, Department of Endocrinology, Aalborg Regional Hospital, Reberbansgade, DK-9000 Aalborg, Denmark
High prevalence of abnormal adrenal response in girls with central precocious puberty at early pubertal stages
Authors: Lazar Liora , Kauli Rivka , Bruchis Celia , Nordenberg Jardena , Galatzer Avinoam , Pertzelan Athalia
Published: December 2008

Lazar L, Kauli R, Bruchis C, Nordenberg J. Galatzer A, Pertzelan A. High prevalence of abnormal adrenal response in girls with central precocious puberty at early pubertal stages. Eur J Endocrinol 1995;133:407–11. ISSN 0804–4643

Abnormal adrenal response is often observed in girls with precocious adrenarche (1). We studied the adrenal response in 112 girls with idiopathic true central precocious puberty (CPP) at early stages of puberty compared to that in 21 girls with normal puberty (controls). The aims of this study were to determine the prevalence of abnormal adrenal response at early stages of puberty, the possible correlation of abnormal adrenal response with pubertal signs at onset of puberty and with plasma androgen levels, and a possible association with the activity of the hypothalamic-pituitary-gonadal (HPG) axis. All participants underwent a combined iv adrenocorticotropic hormone (ACTH)gonadrotropin-releasing hormone (GnRH) test at Tanner stage 2-3: 62 of the CPP girls before and 50 during treatment with GnRH analog. The stimulated levels of 17-hydroxypregnenolone (17OHPreg) and the stimulated 17OHPreg/17-hydroxyprogesterone ratio were analyzed and compared to previously reported norms. The result revealed three patterns of adrenal response: normal (17OHPreg ⩽24 nmol/l and 17OHPreg/17OHP ratio ⩽7) in 50/112 (44.6%) CPP patients and 17/21 (80.9%) controls; exaggerated (17OHPreg> 24 nmol/l, 17OHPreg/17OHP ratio ⩽ 7) in 50/112 (44.6%) CPP patients and 3/21 (14.3%) controls; and non-classical 3β-hydroxysteroid dehydrogenase deficiency (17OHPreg> 24 nmol/l and 17OHPreg/17OHP ratio > 7) in 12/112 (10.8%) CPP patients and 1/21 (4.8%) controls. The clinical features at onset of puberty were comparable in all girls with the CPP in spite of the different adrenal response patterns. The levels of androstenedione and testosterone were within normal range in all cases. Dehydroepiandrosterone sulfate was significantly elevated only in 3β-hydroxysteroid dehydrogenase deficiency, 4.8 ± 2.7 (p < 0.03) as expected. The adrenal response was not affected by GnRH analog therapy. In conclusion, an abnormal adrenal response was found in 55.4% of girls with CPP in early puberty. This response did not cause clinical signs and laboratory findings of a hyperandrogenic state at early stages of puberty and was not affected by the activity of the HPG axis. Its role in evoking precocious puberty remains to be explored further.

A Pertzelan, Institute of Adolescent Endocrinology, Children's Medical Center of Israel, Beilinson Medical Campus, Petah Tiqva 49202, Israel
Changes in prostaglandin synthesis and metabolism associated with labour, and the influence of dexamethasone, RU 486 and progesterone
Authors: Brennand Janet E , Leask Rosemary , Kelly Rodney W , Greer Ian A , Calder Andrew A
Published: December 2008

Brennand JE, Leask R, Kelly RW, Greer IA, Calder AA. Changes in prostaglandin synthesis and metabolism associated with labour, and the influence of dexamethasone, RU486 and progesterone. Eur J Endocrinol 1995;133:527–33. ISSN 0804–4643

The objective was to compare the changes in prostaglandin synthesis and metabolism occurring within the fetal membranes that are associated with the onset of parturition and to study the effect of steroid hormones on prostaglandin metabolism. A tissue explant study was made of discs of amnion and chorion obtained from 24 pregnant women at 37–42 weeks' gestation following spontaneous labour and delivery (12 women) and elective caesarean section (12 women). Significantly more prostaglandin E2 (PGE2) and PGE2α were synthesized by amnion obtained following spontaneous labour than elective caesarean section. Arachidonic acid stimulated both PGE2 and PGE2α synthesis by amnion in both groups. Phorbol myristoyl acetate stimulated PGE2 synthesis in both groups. There was no difference between the groups in the capacity of the chorion to metabolize prostaglandins. Mifepristone (RU 486) reduced the metabolism of added PGE2 following spontaneous labour, while dexamethasone and progesterone had no effect on prostaglandin metabolism. In conclusion, the increase in concentration of PGE2 and PGE2α associated with the onset of spontaneous labour is the result of an increase in synthesis rather than a reduction in metabolism. There was no decrease in metabolism to account for the increase in prostaglandin concentrations and, with the exception of mifepristone, metabolism was not altered by the addition of steroid hormones.

Janet Brennand, Department of Obstetrics and Gynaecology, Glasgow Royal Maternity Hospital, Rottenrow, Glasgow G4 ONA, UK
Review of Turkish patients with growth hormone insensitivity (Laron type)
Authors: Yordam Nurşen , Kandemir Nurgün , Erkul Ibrahim , Kurdoğlu Selim , Hatun Şükrü
Published: December 2008

Yordam N, Kandemir N, Erkul I, Kurdoğlu S, Hatun S. Review of Turkish patients with growth hormone insensitivity (Laron type). Eur J Endocrinol 1995;133:539–42. ISSN 0804–4643

Clinical spectrum and endocrine details of thirteen Turkish children (age 0.3–14.2 years; eight females and five males; ten prepubertal, three pubertal) with growth hormone insensitivity are presented. All patients display phenotypical features of severe growth hormone deficiency, The diagnosis based on height standard deviation score (SDS), basal growth hormone (GH), basal insulin-like growth factor I (IGF-I, IGF-I response in an IGF generation test and growth hormone binding protein (GHBP) measurements. The median height SDS was −7.4 (range −3.2 to −10), weight for height index was 100 (range 81–152) and bone age/height age ratio was 2 (range 1.6–3.3). Endocrine investigations showed a median basal GH concentration of 61.4 mU/l (range 23.5–120 mU/l), Basal IGF-I level was below 10 ng/ml in all patients except one. None of the patients showed a significant IGF-I response to injections of GH (0.1 U/kg body weight for 4 days). The median IGFBP-3 level was 0.23 mg/l (range 0.1–0.56 mg/l). The GHBP level was undetectable in all of 10 patients. The high number of patients in our center may be due to the high rate of consanguinity among the Turkish population and the referral facility of our center in the area. These patients may benefit from the new therapy with recombinant human IGF-I.

Nurgün Kandemir, Hacettepe University, Department of Pediatrics, Division of Endocrinology, 06100 Ankara, Turkey
Identification and characterization of a corticotrophin-releasing hormone receptor in human placenta
Authors: Clifton Vicki L , Owens Phillip C , Robinson Phillip J , Smith Roger
Published: December 2008

Clifton VL, Owens PC, Robinson PJ, Smith R. Identification and characterization of a corticotrophinreleasing hormone receptor in human placenta. Eur J Endocrinol 1995;133:591–7. ISSN 0804–4643

Corticotrophin-releasing hormone (CRH) causes vasodilatation in the human fetal–placental circulation and has paracrine actions in placental tissue, suggesting that CRH receptors may be present in the human placenta. We have now identified and characterized placental CRH binding sites and compared them to those described previously in human myometrium and rat pituitary. Radiolabelled ovine CRH binding to placental membranes was pH-, time-, temperature- and divalent cation-dependent and was reversible in the presence of 1 μmol/l unlabelled ovine CRH. Scatchard analysis of placentae delivered vaginally or by elective caesarean section revealed dissociation constants (Kd) of 214.5 ± 84 pmol/l (N = 8) and 45.4 ± 23.9 pmol/l (N = 9), respectively. The Kd for caesarean placental binding sites was similar to that of human myometrium (59.6 pmol/l, N = 3) and rat pituitary (82.5 pmol/l, N = 3) receptors. However, in vaginally delivered placentae the CRH binding sites had a much lower affinity (p < 0.05). The receptor densities (Bmax) of vaginally delivered and caesarean-delivered placentae were 28.6 ± 9.6 and 6.1 ± 2.8 fmol/mg, respectively (p < 0.05). Chemical cross-linking studies using disuccinimidyl suberate indicated that the molecular weight of the CRH receptor in the placenta and rat pituitary is 75 kD. We conclude that there is a high-affinity population of CRH binding sites in the human placenta that are physicochemically similar to pituitary and myometrial CRH receptors. The CRH receptor properties in the placenta change in response to labour, when CRH levels in maternal blood are highest, suggesting that placental CRH may regulate its receptor.

R Smith, Endocrinology Unit, John Hunter Hospital, Locked Bag 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia
Quantity of Na/K-ATPase and glucose transporters in the plasma membrane of rat adipocytes is reduced by in vivo triiodothyronine
Authors: Voldstedlund Marianne , Tranum-Jensen Jørgen , Handberg Aase , Vinten Jørgen
Published: December 2008

Voldstedlund M. Tranum-Jensen J, Handberg A, Vinten J. Quantity of Na/K-ATPase and glucose transporters in the plasma membrane of rat adipocytes is reduced by in vivo triiodothyronine. Eur J Endocrinol 1995:133:626–34. ISSN 0804–4643

The expression of sodium-potassium pumps and glucose transporters in pure adipocyte plasma membranes from a hyperthyroid animal model was studied. Hyperthyroidism was induced by enteral administration of five doses of 90 μg of triiodothyronine every second day to 8-week-old rats. Following isolation of epididymal adipocytes, 3-O-methylglucose transport was measured and the number of Na/K-ATPase-(α1- and α2-isoforms) and glucose transporter (GLUT1 and GLUT4) molecules in sheets of adipocyte plasma membrane were determined by quantitative immunoelectron microscopy, using gold labelling. Maximal in vitro insulin stimulation of adipocytes increased the glucose transport rate and the amount of GLUT4 in the plasma membrane 15-fold, whereas the amount of α2 was unaffected, In adipocytes from hyperthyroid rats, mean adipocyte volume was decreased by 18% and the quantities of GLUT4 per unit area of plasma membrane (maximal insulin stimulation) and of α2 were decreased by 19% and 15% respectively. Thus, hypotrophia of fat tissue in the hyperthyroid state is associated with a decreased expression in the plasma membrane of the glucose transporter GLUT4 and the α2 -isoform of Na/K-ATPase.

Marianne Voldstedlund, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark
Regulation of luteal function by luteinizing hormone and prolactin at different times of the luteal phase
Authors: Hinney Bernd , Henze Christina , Wuttke Wolfgang
Published: December 2008

Hinney B, Henze C, Wuttke W. Regulation of luteal function by luteinizing hormone and prolactin at different times of the luteal phase. Eur J Endocrinol 1995;133:701–17. ISSN 0804–4643

In 54 healthy women luteal function was assessed by sequential withdrawals of blood samples at 10-min intervals for 8–10 h. Subgroups of the women were studied during the early and late ovulatory period and during the early, mid- and late luteal phase. Bio- and immunoreactive luteinizing hormone (LH), prolactin, testosterone, estradiol and progesterone levels were determined in each sample. While the bio- and immunoreactivity of LH pulses correlated fairly well, a number of bio- or immunoreactive LH pulses were observed that were not detected by the respective other method. Responsivity of the corpus luteum to LH episodes developed during the second half of the luteal phase and was most marked in cases where LH episodes were accompanied by prolactin episodes. In the absence of prolactin episodes, LH episodes did not stimulate progesterone or estradiol secretion. The highest incidence of coincident LH and prolactin pulses was observed during the mid- and late luteal phase. Serum testosterone levels showed also some fluctuations but these were independent of immuno- or bioactive LH episodes and therefore most likely not of luteal origin. Prior to menstruation LH episodes were not any more stimulatory to progesterone secretion, indicating that it is not the withdrawal of LH but, rather, another possibly intraovarian mechanism that results in luteolysis. In a number of women, increased estradiol and progesterone secretion was strictly related to the prior occurrence of LH and prolactin pulses. In other subjects, both gonadal steroids fluctuated largely with no discernible correlation to LH fluctuations. This may indicate that in these subjects the corpora lutea have some degree of autonomous regulation.

W Wuttke, Abteilung für Klinische und Experimentelle Endokrinologie, Universitäts-Frauenklinik, Robert-Koch-Strasse 40, D-37075 Gottingen, Germany
A clinically useful diabetes electronic medical record: Lessons from the past; pointers toward the future
Authors: Gorman Colum , Looker James , Fisk Tom , Oelke William , Erickson David , Smith Steven , Zimmerman Bruce
Published: December 2008

Gorman C, Looker J, Fisk T, Oelke W, Erickson D, Smith S, Zimmerman B. A clinically useful diabetes electronic medical record. Lessons from the past; pointers toward the future. Eur J Endocrinol 1996;134:31–42. ISSN 0804–4643

We have analysed the deficiencies of paper medical records in facilitating the care of patients with diabetes and have developed an electronic medical record that corrects some of them. The diabetes electronic medical record (DEMR) is designed to facilitate the work of a busy diabetes clinic. Design principles include heavy reliance on graphic displays of laboratory and clinical data, consistent color coding and aggregation of data needed to facilitate the different types of clinical encounter (initial consultation, continuing care visit, insulin adjustment visit, dietitian encounter, nurse educator encounter, obstetric patient, transplant patient, visits for problems unrelated to diabetes). Data input is by autoflow from the institutional laboratories, by desk attendants or on-line by all users. Careful attention has been paid to making data entry a point and click process wherever possible. Opportunity for free text comment is provided on every screen. On completion of the encounter a narrative text summary of the visit is generated by the computer and is annotated by the care giver. Currently there are about 7800 patients in the system. Remaining challenges include the adaptation of the system to accommodate the occasional user, development of portable laptop derivatives that remain compatible with the parent system and improvements in the screen structure and graphic display formats.

Colum Gorman, Division of Endocrinology and Metabolism, Mayo Clinic, Rochester. MN. USA
Study of serum 3,5,3′-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness
Authors: Santini Ferruccio , Chiovato Luca , Bartalena Luigi , Lapi Paola , Palla Roberto , Panichi Vincenzo , Velluzzi Fernanda , Grasso Lucia , Chopra Inder J , Martino Enio , Pinchera Aldo
Published: December 2008

Santini F, Chiovato L, Bartalena L, Lapi P, Palla R. Panichi V, Velluzzi F, Grasso L, Chopra IJ, Martino E. Pinchera A. Study of serum 3,5,3′-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness. Eur J Endocrinol 1996;134:45–9. ISSN 0804–4643

Sulfation is an important pathway of triiodothyronine (T3) metabolism. Increased serum T3 sulfate (T3S) values have been observed during fetal life and in pathological conditions such as hyperthyroidism and selenium deficiency. Similar variations have also been reported in a small number of patients with systemic non-thyroidal illness, but the underlying mechanisms have not been elucidated. In this study, serum T3S concentrations have been measured by a specific radioimmunoassay in 28 patients with end-stage neoplastic disease (ESND) and in 44 patients with chronic renal failure (CRF); 41 normal subjects served as controls. Both ESND and CRF patients had lower serum total T4 (TT4) and total T3 (TT3) than normal controls, while serum reverse T3 (rT3) was increased significantly in ESND (0.7 ±0.5 nmol/l; p < 0.001 vs. controls) but not in CRF (0.3 ± 0.1 nmol/l). The TT3/rT3 ratio, an index of type I iodothyronine monodeiodinase (type I MD) activity, was reduced significantly in both groups of patients. Serum T4-binding globulin (TBG) was decreased in CRF but not in ESND patients. Serum T3S was significantly higher both in ESND (71 ± 32 pmol/l) and CRF 100 ± 24 pmol/l) than in controls (50 ± 16 pmol/l, p < 0.001). Serum T3S values showed a positive correlation with rT3 values and a negative correlation with both TT3 and FT3 values in ESND, but not in CRF. In the latter group a positive correlation was observed between T3S and TBG values. The T3S/FT3 ratio was higher both in CRF (18 ± 5) and in ESND (23 ± 18) as compared to controls (10 ± 4). Serum inorganic sulfate was increased and correlated positively with T3S values in CRF patients. In conclusion, the results of this study in a large series of patients confirm that patients with systemic non-thyroidal illness have increased serum T3S levels. The mechanisms responsible for these changes appear to be different in ESND and CRF patients. In ESND the increase in serum T3S levels is mainly related to reduced degradation of the hormone by type I MD, whereas in CRF it might be driven by the enhanced sulfate ion concentration, and could be partially dependent on the impaired renal excretion of T3S Because T3S can be reconverted to T3. it is possible that increased T3S concentrations contribute to maintenance of the euthyroid state in systemic non-thyroidal disease.

Ferruccio Santini, Institute of Endocrinology, University of Pisa. Viale del Tirreno 64. 56018 Tirrenia, Pisa, Italy
Plasma GH responses to human GHRH-antagonist in normal subjects
Authors: Hanew Kunihiko , Tanaka Aki , Utsumi Atsushi , Sugawara Akira , Abe Keishi
Published: December 2008

Hanew K, Tanaka A, Utsumi A, Sugawara A, Abe K, Plasma GH responses to human GHRH-antagonist in normal subjects. Eur J Endocrinol 1996;134:67–72. ISSN 0804–4643

The effect of GHRH-antagonist {N-Ac-Tyr1, d-Arg2) GRF-(1–29)-NH2} on plasma GH morning and evening secretion was evaluated in 14 normal subjects (10 males, 4 females, aged 19–25 years). Plasma GH was determined using a high sensitivity IRMA kit (detection limit, 0.006 μg/l). After intravenous infusion of GHRH-antagonist (100 μg/100 ml saline over 75 min) in the morning, plasma GH remained constant during the 150 min post-infusion (N = 6). In contrast, when GHRH-antagonist was administered in the evening, plasma GH showed a clear and gradual decrease through the initial 90 min and returned to baseline levels at 150 min. Plasma GH values were also significantly lower from 75 min to 135 min when compared to physiological fluctuations in plasma GH (P < 0.05). Other anterior pituitary hormones remained unaffected by GHRH-antagonist. In conclusion, our data suggest that evening basal GH secretion, but not morning GH secretion, is maintained by endogenous GHRH.

K Hanew, The Second Department of Internal Medicine, Tohoku University School of Medicine. 1-1 Seiryocho, Sendai 980, Japan
Overnight dexamethasone suppression test: comparison of plasma and salivary cortisol measurement for the screening of Cushing's syndrome
Authors: Barrou Zina , Guiban Dominique , Maroufi Amel , Fournier Claudine , Dugué Marie-Annick , Luton Jean-Pierre , Thomopoulos Pierre
Published: December 2008

Barrou Z, Guiban D, Maroufi A, Fournier C, Dugué M-A, Luton J-P. Thomopoulos P. Overnight dexamethasone suppression test: comparison of plasma and salivary cortisol measurement for the screening of Cushing's syndrome. Eur J Endocrinol 1996:134:93–6. ISSN 0804–4643

The overnight 1-mg dexamethasone suppression test is a very good screening test for subjects suspected of having Cushing's syndrome. To simplify the procedure, we evaluated the 1-mg dexamethasone suppression test with measurement of salivary cortisol. We performed this test with plasma and salivary cortisol measurements in 27 patients with Cushing's syndrome and 64 normal controls. The sensitivity and specificity of plasma cortisol measurements were 100% and 87%, respectively, for a cut-off point of 100 nmol/l, in accordance with previous studies. The results of salivary cortisol showed the absence of overlap between the two groups, with a sensitivity and specificity of 100% for a cut-off point of 2.8 nmol/l, On a larger series, however, one might occasionally miss the diagnosis of a patient with Cushing's syndrome. Therefore, we favor a cut-off point of 1.9 nmol/l, the sensitivity remaining at 100% and the specificity being 94%. In conclusion we recommend the overnight dexamethasone suppression test with measurement of salivary cortisol as a screening test for Cushing's syndrome.

Pierre Thomopoulos. Clinique des maladies endocriniennes et métaboliques. Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
Increased number of myocardial voltage-gated Ca2+ channels and unchanged total β-receptor number in long-term streptozotocin-diabetic rats
Authors: Gøtzsche Liv Bjørn-Hansen , Rosenqvist Ninna , Grønbæk Henning , Flyvbjerg Allan , Gøtzsche Ole
Published: December 2008

Gøtzsche LB-H, Rosenqvist N. Grønbœk H, Flyvbjerg A, Gøtzsche O. Increased number of myocardial voltage-gated Ca2+ channels and unchanged total β-receptor number in long-term streptozotocin-diabetic rats. Eur J Endocrinol 1996;134:107–13. ISSN 0804–4643.

In order to elucidate further the abnormal myocardial Ca+ metabolism in diabetes mellitus, voltage-gated Ca2+ channels and β-receptors were quantified in myocardial membranes of short- and long-term diabetic rats. Diabetes was induced by an injection of streptozotocin (STZ). Animals were killed 2, 4, 7, 90 and 200 days after STZ. A group of diabetic animals were treated with insulin for 20 days following 180 days of untreated diabetes. Diabetic animals developed low triiodothyronine syndrome. During short-term diabetes, the maximum binding capacity (MBC) for Ca+ channels was reduced by 25% at day 4 p<0.05) and the β-receptor MBC was reduced by 48% p<0.05). A normalizing tendency was observed at day 7 for both receptor types; insulin-treated rats did not differ from controls at that time. After 90 and 200 days of untreated diabetes the Ca+ channel MBC had increased by 36% and 27%, respectively (p < 0.05). Twenty days of strictly regulated blood glucose following 180 days of untreated diabetes totally normalized the Ca+ channel MBC. This is in contrast to a previous report where insulin treatment did not normalize the Ca+ channel MBC. Total β-receptor MBCs did not differ from control values 90 and 200 days after STZ. In conclusion, an increase in rat myocardial Ca2+ channel MBC during long-term diabetes was fully normalized by short-term insulin treatment. The increase in sarcolemmal Ca2+ channels could serve to compensate for a defect coupling of the β-receptor to adenylate cyclase. An elevated Ca+ channel number may, at least theoretically, lead to increased Ca2+ flow across the cardiac sarcolemma and in this way contribute to the diabetic cardiomyopathy by increasing the intracellular Ca2+ concentration.

Liv Bjørn-Hansen Gøtzsche, Dept. of Internal Medicine M, (Diabetes and Endocrinology), Aarhus Kommunehospital, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark.
Effect of growth hormone on follicular fluid androgen levels in patients treated with gonadotropins before in vitro fertilization
Authors: Bergh Christina , Carlström Kjell , Selleskog Ulrika , Hillensjö Torbjörn
Published: December 2008

Bergh C, Carlström K, Selleskog U, Hillensjö T. Effect of growth hormone on follicular fluid androgen levels in patients treated with gonadotropins before in vitro fertilization. Eur J Endocrinol 1996;134:190–6. ISSN 0804–4643

Forty normally ovulating women aged 25–38 years from one private and two university in vitro fertilization (IVF) centres were used in this randomized, double-blind, parallel, placebo-controlled study to explore the effect of recombinant human growth hormone (GH) on follicular fluid (FF) levels of steroid hormones, particularly androgens. All the women had tubal factor infertility and were classified as poor responders with at least two previously performed and failed IVF treatments in which less than five oocytes had been retrieved following ovarian hyperstimulation. Growth hormone (GH 0.1 IU/kg body wt per day) or placebo was given as pretreatment during down-regulation with gonadotropin-releasing hormone agonist and during stimulation with human menopausal gonadotropin (hMG) according to the randomized protocol. Follicular fluid concentrations of steroids were measured and changes related to the levels of insulin-like growth factor I (IGF-I) and IGF binding proteins 1 and 3 and to the mode of GH administration. Pretreatment with GH, i.e. administration of GH before hMG stimulation only, caused significantly elevated follicular fluid concentrations of estrone, testosterone and dehydroepiandrosterone (DHEA) and higher values for markers of aromatase activity (ratios between estrone and androstenedione and between estradiol-17β and androstenedione) than in the placebo group, as well as in the two groups receiving GH during hMG stimulation. The highest values for markers of steroid sulfatase activity (ratios between DHA and DHEA sulfate and between unconjugated and conjugated estrone) were found in the patients pretreated with GH. Positive correlations were found between follicular fluid IGF-I and IGF binding protein 3 on the one hand and androgens on the other. This study showed that the administration of adjuvant GH to women who were poor responders to gonadotropins alters the endocrine/paracrine ovarian response to gonadotropins.

Torbjörn Hillensjö, Department of Obstetrics and Gynecology, Huddinge University Hospital, S-141 86 Huddinge, Sweden
Relationship between serum dehydroepiandrosterone sulfate, androstenedione, and sex hormones in men and women
Authors: Phillips Gerald B
Published: December 2008

Phillips GB. Relationship between serum dehydroepiandrosterone sulfate, androstenedione, and sex hormones in men and women. Eur J Endocrinol 1996;134:201–6. ISSN 0804–4643

Previous reports of a correlation between serum dehydroepiandrosterone sulfate (DHEAS) and testosterone in both men and women have led to the suggestion that adrenal and gonadal secretion are related. In the present study, the correlation of DHEAS with testosterone and free testosterone (FT) in both normal men and women was tested. Androstenedione, estradiol, sex hormone binding globulin (SHBG), and insulin were also measured and their correlations determined. All correlations were controlled for age and body mass index. In the men in the study, DHEAS did not correlate with testosterone or FT but correlated strongly with androstenedione. In the women, DHEAS correlated strongly with testosterone, FT. and androstenedione; androstenedione in turn correlated strongly with testosterone and FT. DHEAS showed no correlations with estradiol, SHBG, or insulin in the men or women. The lack of a correlation between DHEAS and testosterone in normal men is consistent with the independent secretion of these hormones by the adrenal and testis, respectively. The finding of a strong DHEAS-testosterone correlation in normal women may be explained by parallel adrenal secretion in response to trophic stimuli, i.e., without invoking an adrenal-gonadal interaction.

GB Phillips, Roosevelt Hospital, 428 West 59th Street, New York, NY 10019, USA
Effect of modified brain histamine contents on prolactin and thyrotropin secretion in male rats
Authors: Tuominen Raimo K , Tuomisto Leena , Männistö Pekka T
Published: December 2008

Tuominen RK, Tuomisto L, Männistö PT. Effect of modified brain histamine contents on prolactin and thyrotropin secretion in male rats. Eur J Endocrinol 1996;134:209–14. ISSN 0804–4643

Effects of modified brain histamine contents on thyrotropin and prolactin secretion were studied in male rats. Under basal conditions the histamine content in the hypothalamus was approximately 8–10-fold higher than that in the striatum and the rest of the brain. l-Histidine (1000 mg/kg, ip), a histamine precursor, and metoprine (20 mg/kg, ip), an inhibitor of histamine methyltransferase, elevated histamine content in the brain by 65% and 167%, respectively. When the treatments were given together an additive effect (119–250% increase) on brain histamine was observed. Metoprine significantly decreased serum prolactin levels, while l-histidine had no effect. This effect of metoprine was not modified by treatment with l-histidine. Thus, metoprine has an inhibitory effect on prolactin secretion that is not related to elevated brain histamine contents. The increased brain histamine content after l-histidine treatment had no effect on prolactin secretion. Basal levels of serum thyrotropin were decreased by both l-histidine and metoprine, l-histidine being more potent. In rats treated with α-fluoromethylhistidine, an inhibitor of l-histidine decarboxylase, the cold-induced (rats kept for 60 min at +4°C) thyrotropin secretion was increased while the stress-induced prolactin secretion was decreased. In these rats, metoprine did not affect thyrotropin release but blunted the prolactin response. In conclusion, endogenous histamine inhibits thyrotropin secretion but does not affect prolactin release. Owing to its other effects, metoprine is not suitable as a tool to elevate endogenous histamine contents in the brain, at least when the regulation of anterior pituitary hormone release is being studied.

Raimo K Tuominen, Institute of Biomedicine, Department of Pharmacology and Toxicology, PO Box 8, FIN-00014 University of Helsinki, Finland
Hypothyroid patients showing shortened responsiveness to oral iodized oil have paradoxically low serum thyroglobulin and low thyroid reserve. Thyroglobulin/thyrotropin ratio as a measure of thyroid damage
Authors: Contempre B , Duale GL , Gervy C , Alexandre J , Vanovervelt N , Dumont JE
Published: December 2008

Contempre B, Duale GL, Gervy C, Alexandre J, Vanovervelt N, Dumont JE. Hypothyroid patients showing shortened responsiveness to oral iodized oil have paradoxically low serum thyroglobulin and low thyroid reserve. Thyroglobulin/thyrotropin ratio as a measure of thyroid damage. Eur J Endocrinol 1996:134:342–51. ISSN 0804–4643

In Central Africa, all of northern Zaire is very severely deficient in iodine. A peculiar feature of this endemia is that iodine deficiency and the ensuing thyroid gland stimulation not only leads to goitre formation but also to progressive thyroid involution and to myxoedematous cretinism. An iodine supplementation trial based on oral administration of small doses of iodine was made in 81 schoolchildren. All of them received a small dose of iodine (0.1 ml containing 48 mg) per os and the thyroid status was followed during 4 months. Blood and urine samples were collected at the start of the study, then 2 weeks, 2 months and 4 months after iodine administration. Before iodine supplementation, the mean urinary iodine level was 0.18 ± 0.02 μmol/l, and 10% of the subjects had a urinary iodine level below 0.08 μmol/l, Fifty-two percent of the subjects had a serum thyrotropin (TSH) level above 10 mU/l. All the subjects responded to the administration of iodine, and all of them recovered a euthyroid status. Most of them were still euthyroid at the end of the study. However, within 4 or even 2 months, some subjects (15% of the total) reverted to hypothyroidism. At the entry of the study these subjects were all hypothyroid and had elevated TSH and paradoxically low serum thyroglobulin (TG) values. In myxoedematous cretins living in the same area, even lower serum TG levels were found. Together with the absence of goitre, a paradoxically low serum TG suggests a low thyroid reserve, and in the present case a reduced amount of functional thyroid tissue. We show that the serum TG/TSH ratio may be used as a predictive index of thyroid reserve and of positive response to iodine administration. These data further suggest that thyroid damage is not confined to myxoedematous cretins, but is widely distributed in the phenotypically normal population. Widely distributed thyroid damage may render iodine prophylaxis based on oral administration unpredictable.

B Contempre, IRIBHN, CP 602, Free University of Brussels, Medicine Faculty, 808 route de Lennik, B-1070 Brussels, Belgium
New approach to the diagnosis of growth hormone deficiency in adults
Authors: Ghigo Ezio , Aimaretti Gianluca , Gianotti Laura , Bellone Jaele , Arvat Emanuela , Camanni Franco
Published: December 2008

Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 1996;134:352–6. ISSN 0804–4643

Pyridostigmine (PD), a muscarinic cholinergic agonist, and arginine (ARG) clearly increase the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) in man. The current study was undertaken to investigate the value and safety of PD + GHRH and ARG + GHRH tests as well as the measurement of serum insulin-like growth factor I (IGF-I) in diagnosing GH deficiency in adults. Fifty-four patients considered GH deficient from extensive organic or idiopathic pituitary disease and 326 healthy adults were studied. The IGF-I concentrations were lower than the 3rd percentile of normal values in only 31 of the 54 (57.4%) patients with hypopituitarism. However, the IGF-I levels in hypopituitary patients and in normal subjects overlapped more frequently between 41 and 60 years (50%) and between 61 and 80 years (92.3%) as opposed to between 20 and 40 years (8.6%). In contrast to the IGF-I measurement, the ranges of peak GH responses to PD + GHRH and ARG + GHRH tests were clearly differentiated between the hypopituitary (0.2–6.8 and 0.1–9.5 μg/l, respectively) and normal subjects 17.7–114 and 16.1–119 μg/l, respectively). However, the PD + GHRH test was reliable only in subjects of 20–40 years of age. In conclusion, IGF-I measurement had no value in the diagnosis of GH deficiency in adults aged over 40 years, but is reliable enough when young adults of 20–40 years of age are considered. Both PD + GHRH and ARG + GHRH testing should be considered more reliable biochemical measurements of GH deficiency. In contrast to the PD + GHRH test, the ARG + GHRH test is reliable throughout the adult lifespan and appears to be the most appropriate for patient compliance and safety.

F Camanni, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy
Gonadotropins and gonadotropin receptors during the perimenopause
Authors: Vihko Kimmo K , Kujansuu Erkki , Mörsky Pertti , Huhtaniemi Ilpo , Punnonen Reijo
Published: December 2008

Vihko KK, Kujansuu E, Mörsky P, Huhtaniemi I, Punnonen R. Gonadotropins and gonadotropin receptors during the perimenopause. Eur J Endocrinol 1996;134:357–61. ISSN 0804–4643

Twenty-two perimenopausal patients (aged 47–56 years) admitted for elective abdominal hysterectomy and salpingo-oophorectomy were selected to understand better the clinical significance of increasing gonadotropin levels as an indicator of target organ responsiveness. Prior to anesthesia, blood was drawn from the patients for subsequent analyses of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and 17β-estradiol (E2) levels. Ovarian tissue was obtained during surgery and frozen at −70°C for subsequent analyses for FSH and LH receptor content. The phase of the menstrual cycle of the patients or postmenopause was determined by serum gonadotropin and E2 levels and histological evaluation of the endometrium. Patients with no detectable FSH receptors showed significantly higher serum FSH and LH levels (4.7- and 4.3-fold, respectively) when compared to patients with detectable FSH receptors; FSH receptors were present in 27% of the patients, LH receptors were present in 68% of the patients and a negative correlation was found between serum LH levels and ovarian LH receptors. In postmenopausal patients, neither FSH receptors nor LH receptors were detectable. High serum gonadotropin levels in perimenopausal patients thus suggest the existence of low or undetectable ovarian gonadotropin receptor levels.

Kimmo Vihko, Department of Obstetrics and Gynecology, Tampere University Hospital, PO Box 2000, FIN-33521 Tampere, Finland