bluuebunny/crossref_metadata_2025 huggingface dataset:
CIRCULATING SEX HORMONE‐BINDING GLOBULIN AND TESTOSTERONE IN NEWBORNS AND INFANTS
Authors: BOLTON N. J. , TAPANAINEN J. , KOIVISTO M. , VIHKO R.
Published: March 2008

The concentrations of sex hormone‐binding globulin (SHBG) and testosterone (T) were measured in the cord blood of full‐term newborns (14 boys, 15 girls) and pre‐term newborns (10 boys, 5 girls), and in the venous circulation of 100 full‐term infants aged 1‐204 days. The ratio of T to SHBG (the‘free androgen index’, FAI) was calculated to reflect the level of unbound T (the free, biologically active fraction). In boys’umbilical cord sera, T concentrations were significantly greater in arterial than in venous sera, while there was no such difference in the concentration of SHBG. Levels of SHBG in cord sera were considerably lower than those seen in the maternal circulation at term, but they were significantly greater in boys’than in girls’cord sera. Levels of T, and the FAI, were significantly greater in boys’arterial cord sera than in girls'. In early infancy, SHBG concentrations rose in both sexes, the highest values being seen in girls. In infant girls, levels of T and the FAI were constantly low. In infant boys, the expected peak in serum T concentrations was observed at 1‐3 months the values approaching those seen in men. In contrast, values of the FAI at this age were relatively low, similar to those seen in women. This suggests that the elevation of male serum T during the first months of life lacks biological significance. However, it is important to realise that the FAI in male infants is about one order of magnitude larger than that in female infants at this time.
THE BIOACTIVITY OF IMMUNOREACTIVE ADRENOCORTICOTROPHIN IN HUMAN BLOOD IS DEPENDENT ON THE SECRETORY STATE OF THE PITUITARY GLAND
Authors: GOVERDE HENNY J. M. , PESMAN GERARD J. , SMALS ANTHONY G. H.
Published: March 2008

A highly sensitive bioassay, using preincubated purified isolated rat adrenal cells, has been developed for measuring plasma ACTH. This bioassay enables detection of ACTH in plasma of about 0.9 pmol/1. Bioactive ACTH (B‐ACTH) plasma levels were determined during insulin‐induced hypoglycaemia in 12 female subjects and the values were compared with immunoreactive ACTH (I‐ACTH) levels. The mean (|Mp SD) basal B‐ACTH level amounted to 1·7 ± 0·8 pmol/1, the mean I‐ACTH to 2·9 ± 1·4 pmol/1. The highest mean B‐ACTH plasma value was found 30 min after insulin injection: 14·7 ± 15·7 pmol/1 (I‐ACTH: 12·8 ± 9·9 pmol/1). By 90 min the B‐ACTH level had returned to baseline (1·6 ± 0·8 pmol/1), whereas the I‐ACTH level was still significantly higher (5·4 ± 2·7 pmol/1) than at time zero. Remarkably, the B‐ACTH to I‐ACTH ratio (B/I ratio) showed a biphasic profile during the insulin tolerance test, the ratio increasing from 0·60 ± 0·77 at time zero to 1·08 ± 0·35 at the ACTH peak, and decreasing after that to a lower value of 0·33 ± 0·11 at 90 min.

From these results it is concluded: (1) in the morning hours a considerable amount of circulating I‐ACTH has no steroidogenic activity; (2) the B/I ratio temporarily increases immediately after insulin injection but gradually decreases afterwards to values half the baseline level at 90 min. Whereas this decrease at 90 min can be explained by differences in disappearance rates, the increase of B‐ACTH relative to I‐ACTH at 30 min indicates that estimations of immunoreactive ACTH reflect the biological activity of newly released ACTH with greater precision than at steady state level. Thus, the B/I‐ACTH ratio can be used as a tool for measuring the state of the pituitary releasing activity.
BASAL AND SALINE‐STIMULATED LEVELS OF PLASMA ATRIAL NATRIURETIC FACTOR IN ACROMEGALY
Authors: McKNIGHT JOHN A. , McCANCE DAVID R. , HADDEN DAVID R. , KENNEDY LAURENCE , ROBERTS GERALDINE , SHERIDAN BRIAN , ATKINSON A. BREW
Published: March 2008

We have studied plasma ANF before and after a 4‐h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex‐matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 |Mp 1.5 pmol/1 (mean |Mp SEM) in acromegalic subjects and 5.3 ± 0.7 pmol/1 in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2‐h value, 5.9 ± 0.9; 4‐h value, 5.1 ± 0.9 pmo1/1) but did rise significantly in the control group (2‐h value, 8.9 ± 1.9; 4‐h value 9.5 ± 1.3 pmo1/1, both values P < 0.05 vs basal level). The 4‐h ANF value was significantly higher in the control group than in the acromegalic group (P < 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.
HORMONAL RESPONSE TO BLOOD VOLUME EXPANSION IN DIABETIC SUBJECTS WITH AND WITHOUT AUTONOMIC NEUROPATHY
Authors: O'HARE J. P. , ANDERSON J. V. , MILLAR N. D. , DALTON N. , TYMMS D. J. , BLOOM S. R. , CORRALL R. J. M.
Published: March 2008

The hormonal and renal response to volume expansion, produced by water immersion for 4 h, was studied in 14 insulin‐dependent diabetic subjects (seven without complications, seven with autonomic neuropathy) and in 14 age‐and‐sex‐matched normal control subjects. The diabetic subjects showed an impaired natriuretic response to volume expansion (total amount of sodium excreted 21 mmol compared to 39 mmol in normals, P > 0.01) but the response did not differ in those with and without autonomic neuropathy. There was no significant difference in the suppression of plasma renin or aldosterone during immersion in either group. Plasma catecholamines suppressed on immersion in all groups. Basal values were lowest in the group with autonomic involvement. Atrial natriuretic peptide levels showed a twofold rise (from 4.8 to 9.6 pmol/l, P > 0.01) on immersion. There was no significant difference in the levels of this hormone between diabetic patients and normal subjects or between those diabetics with and those without autonomic neuropathy. The present study confirms that diabetic subjects retain sodium avidly during volume expansion. This enhancement cannot be ascribed to any measurable difference in the levels of circulating hormones known to be involved in natriuresis and is not influenced by the presence of autonomic neuropathy.
REGULATION OF CALCIUM‐PARATHYROID HORMONE FEEDBACK IN PRIMARY HYPERPARATHYROIDISM: EFFECTS OF BISPHOSPHONATE TREATMENT
Authors: ADAMI S. , MIAN M. , BERTOLDO F. , ROSSINI M. , JAYAWERRA P. , O'RIORDAN J. L. H. , LO CASCIO V.
Published: March 2008

Dichloromethylene bisphosphonate (C12MBP), a powerful inhibitor of bone resorption, was administered to 27 patients with primary hyperparathyroidism. It was given by either intravenous infusion (six patients, 500‐1000 mg day), or by intramuscular injection (six patients, 100‐200 mg/day) or by mouth (15 patients, 1600‐2400 mg/day) for 20–180 days. Sustained suppression of bone resorption was observed in all patients, as judged by a fall in the urinary hydroxyproline excretion. In contrast, the hypocalcaemic effect was inconsistent and short‐lived, particularly in the patients without overt bone disease. The fall in serum calcium seemed largely to be due to a transient dissociation between bone resorption and bone formation and was associated with increases in circulating parathyroid hormone (PTH). In ten patients given the bisphosphonate orally for 6 months, serum calcium was unchanged but serum PTH was significantly raised. These results suggest that Cl2MBP may be of use for short‐term correction of severe hypercalcaemia due to hyperparathyroidism, particularly in the patients with overt bone disease. However, its long‐term use should not be recommended because of increased PTH secretion.
Graves'DISEASE IN PREGNANCY: TSH RECEPTOR BINDING INHIBITING IMMUNOGLOBULINS AND MATERNAL AND NEONATAL THYROID FUNCTION
Authors: MORTIMER ROBIN H. , TYACK SHIRLEY A. , GALLIGAN JOHN P. , PERRY‐KEENE DONALD A. , TAN YONG M.
Published: March 2008

We studied interrelationships between maternal and neonatal thyroid function, TSH receptor binding inhibiting immunoglobulins (TBII), and dose of thionamide antithyroid drugs in 44 women with active Graves'disease presenting during 46 pregnancies, and their 48 infants. The women were treated with propylthiouracil (PTU) or carbimazole (CBZ). In 30 pregnancies (30 infants) treatment was withdrawn from 3 to 18 weeks before delivery (Group A). Drug treatment (PTU, n = 10, dose 50‐400 mg/day or CBZ, n = 6, dose 5‐45 mg/day) was continued throughout pregnancy and delivery in 16 pregnancies producing 18 infants (Group B). The maternal TBII at delivery was well correlated with maternal free thyroxine index (FTI) averaged over the third trimester (r = 0.603, P < 0.001) and umbilical venous serum TBII (r = 0940, P < 0.001). Neonatal FTI was independently related to umbilical vein TBII (t = 2.29, P = 0.03) and maternal dose of antithyroid drug (t =−2.21, P = 003). Neonatal thyrotoxicosis was seen in all four infants (8% of births) of women whose TBII levels at delivery exceeded 70%. No child was born with a subnormal FTI but 7/18 infants in group B had raised TSH at birth. This was more likely to occur (P = 0.05) if maternal TBII was <30% (6/10) than if maternal TBII was > 30% (1/8). Four Group B women with FTI in the lower half of the reference range delivered infants with raised TSH compared with 3/14 (21%) women whose FTI was in the upper half of the reference range or above (P = 0.05). In pregnant women with active Graves'disease TBII levels reflect stimulatory TSH receptor antibody activity. TBII measurements are of use in the prediction of neonatal thyrotoxicosis and impaired neonatal thyroid function in infants of women treated with antithyroid drugs.
SUCCESSFUL TREATMENT BY CHEMOTHERAPY FOR ACROMEGALY ASSOCIATED WITH ECTOPIC GROWTH HORMONE RELEASING HORMONE SECRETION FROM A CARCINOID TUMOUR
Authors: HARRIS P. E. , BOULOUX P. M. G. , WASS J. A. H. , BESSER G. M.
Published: March 2008

Acromegaly secondary to the secretion of ectopic growth hormone releasing hormone (GHRH) is rare. We have documented the presentation and unusual clinical course of a patient with a disseminated GHRH‐secreting bronchial carcinoid tumour associated with acromegaly over a 17‐year period. Recurrent widespread metastatic lesions have been treated over a 10‐year period by repeated cycles of the nitrosourea CCNU and 5‐fluorouracil with evidence of tumour regression and reduction of circulating growth hormone (GH) and urinary 5HIAA excretion. This cytotoxic regimen, which has been well tolerated, may prove valuable in the management of disseminated carcinoid tumours.
SUPPRESSION OF PLASMA ANDROGENS BY THE ANTIANDROGEN FLUTAMIDE IN PROSTATIC CANCER PATIENTS TREATED WITH ZOLADEX, A GnRH ANALOGUE
Authors: AYUB M. , LEVELL M. J.
Published: March 2008

Chronic treatment with the GnRH (gonadotrophin hormone releasing hormone) agonist Zoladex causes suppression of testicular androgens. Use of antiandrogens has been advocated to block the effects of the initial surge of androgens, and to block any presumed effects of adrenal androgens. We have measured plasma concentrations of androgens and possible precursors before and during treatment in the following prostate cancer patients: 10 who received Zoladex alone (Z), nine who received Zoladex ± the anti‐androgen flutamide (Z + F) and five who were orchidectomized (O). Testosterone fell in the Z + F group to 0.84±0.21 nmol/l(mean±SD) significantly lower (Wilcoxon P < 0.05) than after Z (1.58±1.84 nmol/1) alone. Progesterone and 17α‐hydroxyprogesterone did not change significantly in any group. Androstenedione and dehydroepiandrosterone sulphate (DHAS) showed significant falls in Z + F (from 3.44±0.34 to 1.92±0.18 μmol/1 and from 3.88±0.64 to 1.92 μ 0.36 μmnol/ 1 respectively) but not in other groups. These results are consistent with our demonstration of an inhibitory effect of flutamide, hydroxyflutamide and other antiandrogens on human adrenal microsomal 17α‐hydroxylase and 17, 20‐lyase activitiesin vitro.
A PRELIMINARY REPORT ON THE ROLE OF SOMATOSTATIN ANALOGUE (SMS 201‐995) IN THE MANAGEMENT OF CHILDREN WITH TALL STATURE
Authors: HINDMARSH P. C. , PRINGLE P. J. , DI SILVIO L. , BROOK C. G. D.
Published: March 2008

We have studied the effect of somatostatin analogue (SMS 201‐995) given as a subcutaneous injection on the growth and growth hormone secretion in seven tall children (two male; five female). SMS 201‐995 was given in doses of 37.5 or 50 μg on a once or twice‐daily regimen. Growth velocity decreased from a pretreatment median of 8.3 cm/year (range 5.5–12.2) to 30 cm/year (range 0.2–4.5) after 6 months treatment (Wilcoxon, P=0.02). In three of the children therapy was discontinued for the next 6 months with restoration of growth rate to pretreatment values in two of the three. Growth hormone secretion decreased as a result of SMS 201‐995 therapy although one child needed a twice‐daily regimen to achieve long‐term suppression. Final height measurements were reduced in four of five patients with an overall reduction between 1.1 and 6.3 cm and no change in the other. No effects of treatment on fasting glucose and insulin, glycosylated haemoglobin or serum thyroxine concentrations were observed. These preliminary studies suggest that SMS 201‐995 may have a role in the management of the growth of tall children but the optimum mode of administration remains to be established.
Endocrine function in patients with Cushing's disease before and after treatment
Authors: Lindholm Jörgen
Published: March 2008

objective To estimate the value of some commonly used tests In diagnosing Cushing's disease and to assess the outcome after treatment

design Follow‐up of a consecutive group of patients for 4·1 to 109·6 months, median 34·4

patients Forty‐six patients assumed to have ACTH dependent hypercorticism (of 50 patients with Cushing's syndrome) were included. Forty‐five underwent trans‐sphenoidal neurosurgery. Ten were treated preoperatively with radiotherapy

measurements Pituitary, adrenal, thyroid and gonadal function, radiology and pituitary histology were evaluated

results One main finding was a significant correlation between the urinary excretion of cortisol before and during administration of dexamethasone. Thus patients with modestly elevated urinary cortisol excretion had an apparently normal suppression. The urinary cortisol values during the dexamethasone test were significantly related to the peak plasma cortisol concentrations at the 30‐minute ACTH tests. Computed tomography failed to Identify an adenoma In 10 of the 19 patients who were histologlcally proved to harbour a corticotroph adenoma. At 6 months after radiotherapy, clinical and biochemical improvement was noted in none. Cure was achieved In 36 after neurosurgery. Eventually, adrenalectomy was needed In eight patients. Sixteen patients developed persisting adrenal Insufficiency after neurosurgery so that the total number of patients on permanent steroid substitution was 24. Post‐operative thyroid and gonadal Insufficiency (In men and women of fertile age) was found In 36 and 49%, respectively

conclusions The diagnostic value of measuring the cortisol excretion during dexamethasone administration appears doubtful. The outcome after neurosurglcal treatment for Cushing's disease Is not entirely satisfactory. Further studies are needed to decide whether adrenalectomy as the first line of therapy should be considered relevant in some patients with Cushing's disease
Morbidity in patients on l‐thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH
Authors: Leese G. P. , Jung R. T. , Guthrie C. , Waugh N. , Browning M. C. K.
Published: March 2008

OBJECTIVE Patients on l‐thyroxine with a ‘suppressed’ TSH (< 0 05 mU/l) were compared to those in whom TSH was detectable but not elevated (0 05– 4 0 mU/l), with regard to morbidity data.

DESIGN Biochemical data from Tayside Thyroid Register was matched to hospital admissions data obtained from Health Board Statistics.

PATIENTS The patients were identified from those registered on the computerized Tayside Register.

MEASUREMENTS Serum T4 and TSH assays, clinical assessment scores, and admission records with regard to ischaemic heart disease, overall fractures, fractured neck of femur and breast carcinoma.

RESULTS Over one year, 1180 patients on thyroxine replacement had clinical and biochemical assessment; 59% had a suppressed TSH and 38%‘normal’ TSH. Patients with a suppressed TSH exhibited higher median serum thyroxine levels (146 nmol/l, range 77– 252 vs 119 nmol/l, 58– 224; P<0001). Patients under the age of 65 years on l‐thyroxine had an increased risk of ischaemic heart disease compared to the general population (female 2 7 vs 0 7%, P<0 001; male 6 4 vs 17%, P<0 01), but the risk was no different between those with suppressed and normal TSH. There was no increase in risk for overall fracture, fractured neck of femur or breast carcinoma in those on thyroxine with suppressed or normal TSH.

CONCLUSION Patients under the age of 65 years on l‐thyroxine had an increased risk of ischaemic heart disease. There was no excess of fractures in patients on l‐thyroxine even if the TSH is suppressed.
Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population
Authors: Contempré B. , Duale N. L. , Dumont J. E. , Ngo B. , Diplock A. T. , Vanderpas J.
Published: March 2008

OBJECTIVE Severe selenlum deficiency has been documented In northern Zaïre, already known as one of the most Iodine deficient regions In the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted In this area to evaluate the effects of a selenium supplementation on thyroid diseases.

DESIGN Placebo or selenium 50 ųg as selenomethionine was administered once dally for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS Fifty‐two healthy schoolchildren from northern Zaire.

MEASUREMENT Selenium status, thyroid function and urinary Iodide were determined.

RESULTS After 2 months of selenium supplementation, mean±SD serum T4 decreased from 73.1 ± 45.4 to 48.3 ± 23.7 nmol/l (P <0.001), serum FT4 from 11.8.6.7 to 8.4.41 pmol/l (P, 0.01), and serum rT3 from 124.115 to 90.72 pmol/l (P < 0.05), without significant change In serum T3 and serum TSH.

CONCLUSION Delodinase type I which has been shown to be a seleno‐enzyme could account for the changes in thyroid hormones In our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism In humans. Selenium could be an Important cofactor in the clinical picture of Iodine deficiency In Central Africa could be Involved In the aetiology of both forms of cretinism.
Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome
Authors: Conway Gerard S. , Agrawal R. , Betteridge D. J. , Jacobs H. S.
Published: March 2008

OBJECTIVE The evidence that some women with the polycystic ovary syndrome (PCOS) are hyperinsulinaemic has brought into question their risk of developing early coronary artery disease. We have focused on three cardiac risk factors which have been associated with hyperinsullnaemia by measuring glucose tolerance, fasting serum lipid concentrations and blood pressure in women with PCOS.

DESIGN Comparison of clinical and biochemical measurements in lean and obese women with PCOS and in women with normal ovaries. Determinants of the risk factors for coronary artery disease were assessed by multiple regression analysis.

PATIENTS One hundred and two women with ultrasound diagnosed PCOS and 19 lean women with normal ovaries were studied. Patients were recruited from a reproductive endocrine clinic.

MEASUREMENTS Fasting total cholesterol, triglycerides, high density lipoproteins (HDL), HDL2, glucose tolerance, fasting and stimulated insulin, gonadotrophins, testosterone and androstenedione were measured during a 2‐hour oral glucose tolerance test. Recumbent blood pressure was measured automatically.

RESULTS Lean women with PCOS were found to be hyperinsulinaemic and have reduced serum HDL and HDL2 concentrations compared to women with normal ovaries; serum insulin concentrations correlated positively with plasma glucose and blood pressure measurements in multiple regression analysis. Obese women with PCOS were in addition found to have higher systolic blood pressure, serum triglyceride and plasma glucose concentration than lean women with PCOS and controls.

CONCLUSIONS These results support the evidence that hyperinsulinaemic women with PCOS have an increased risk of developing cardiovascular disease and therefore form a population in whom metabolic screening is advisable.
Prolonged treatment with finasteride (a 5α‐reductase inhibitor) does not affect bone density and metabolism
Authors: Matzkin Halm , Chen Juza , Weisman Yosef , Goldray David , Pappas Fran , Jaccard Niva , Braf Zvl
Published: March 2008

OBJECTIVE Since it is not clear whether testosterone or dihydrotestosterone is the active hormone in bone metabolism, we wished to assess the effect of finasteride, a 5α‐reductase inhibitor, on vertebral bone mineral density and parameters of bone and mineral metabolism.

DESIGN Patients were treated in a randomized, double‐blind controlled study with either placebo, 1 or 5 mg/day finasteride.

PATIENTS Twenty‐three men with benign prostatic hyper‐plasla (BPH) were included in this study; eight received placebo, seven were allocated to treatment with 1 mg/day, and eight to 5 mg/day finasteride for 12 months.

MEASUREMENTS Vertebral bone mineral density was measured at the lumbar spine by dual energy X‐ray bone densltometry. Serum calcium, phosphorus, parathyroid hormone, osteocalcln and vitamin D metabolites were measured regularly. Urinary calcium and creatinlne excretion were monitored as well.

RESULTS Finasteride caused a significant decrease in serum dlhydrotestosterone after 6 and 12 months, but no effect on serum testosterone. Vertebral bone mineral density remained unaltered. None of the other parameters monitored were affected except for a small unexplained increase in 1,25‐dihydroxyvitamin D in the group receiving 5 mg finasteride/day.

CONCLUSIONS Testosterone is probably the active hormone in bone metabolism. However, oestradiol, the product of testosterone aromatization (which remains unaltered under finasteride) may yet be another possible responsible steroid in the maintenance of bone density. We can also not rule out that the small amount of dihydrotestosterone remaining under finasteride administration is sufficient for maintaining normal bone metabolism.
Cushing's syndrome associated with ectopic production of corticotrophin‐releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma
Authors: O'Brien Timothy , Young William F. , Davlla David G. , Schelthauer Bernd W. , Kovacs Kalman , Horvath Eva , Vale Wylle , van Heerden Jon A.
Published: March 2008

We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin‐releasing hormone (CRH) and corticotrophin (ACTH). A 49‐year‐old white woman presented with a 1‐month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facles, lanugo‐type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high‐dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4‐cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24‐hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohis‐tochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaeochromocytomas, transcribed a lone pituitary‐sized (1200 nucleotide) pro‐oplomelanocortin mRNA. This is the second reported case of a CRH‐secreting phaeochromocytoma.
Impaired thermoregulation in adults with growth hormone deficiency during heat exposure and exercise
Authors: Juul Anders , Behrenscheer Anne , Tims Trine , Nielsen Bodil , Halkjær‐Kristensen Jens , Skakkebæk Niels E.
Published: March 2008

OBJECTIVE It has recently been shown that patients with growth hormone deficiency have a reduced sweating capacity. We hypothesize that reduced sweating might affect thermoregulation in growth hormone deficiency patients. In the present study we have examined thermoregulation in growth hormone deficiency patients.

DESIGN AND PATIENTS Six adult growth hormone deficiency patients and six matched controls were exposed to a 90‐minute heat period (40°C). On a second day the subjects exercised for 30 minutes under standardized conditions.

MEASUREMENTS On both occasions changes in GH secretion, sweating and temperature were registered. Heat storage and evaporation were calculated from these data.

RESULTS We found that during the moderate heat exposure, evaporation was less (56.7 vs 115.6 W, P= 0.0037) and heat storage greater (60.7 v s 37.0 W, P= 0.025) in growth hormone deficiency patients compared to their matched controls. Two of the six patients reacted with severe clinical symptoms of heat exhaustion, whereas the controls were unaffected. After exercise the patients reached significantly higher core temperatures than their matched controls (38.1 vs 37.8°C, P= 0.0097).

CONCLUSIONS Thus, our findings are indicative of a reduced thermoregulatory function in some patients with G H deficiency.
Screening for thyroid diseases in an iodine sufficient area with sensitive thyrotrophin assays, and serum thyroid autoantibody and urinary iodide determinations
Authors: Konno N. , Yuri K. , Taguchi H. , Miura K. , Taguchi S. , Hagiwara K. , Murakami S.
Published: March 2008

OBJECTIVE The present study was designed to investigate the prevalence of thyroid dysfunction and Its relation to thyroid autoantibodies and urine iodide concentration in apparently healthy people residing in Sapporo, a city of northern Japan, where the iodine intake is high.

DESIGN AND SUBJECTS Serum TSH and thyroid autoantibodies, and urine iodide were measured in 4110 people (2931 men and 1179 women) (age 456 ± 103 years (mean ± SD)) who were recruited at the hospital for medical examinations.

RESULTS The thyroid autoantibodies were positive in 6.4% of males and 13.8% of females with an age‐related increase. Of the people with positive antibodies, 87.2% had normal TSH values (0.15–5.0 mU/l) as measured by a sensitive assay. The prevalence of unsuspected hyperthyroidism as defined by suppressed TSH values was 0.61%, of which 64% was diagnosed as Graves' disease based on positive thyrotrophin receptor antibody results. The prevalence of unsuspected hypothyroidism, as evidenced by supranormal TSH, was 0.68% for males and 3.13% for females with an age‐related increase. Of those with hypothyroidism, 45.5% were autoantibody positive. The overall prevalence of Hashimoto's thyroiditis was 13.11% for females and 6.15% for males. The urine iodide levels of hypothyroidism with a positive autoantibody of 38.5 (17.7–83.9)μmol/l and a negative autoantibody of 34.9 (17.9–67.9) μmol/l were both significantly higher than that of normal subjects (26.9 (14.6–49.6) μmol/l) (P <0.01). When iodine intake was restricted for 6–8 weeks for hypothyroid subjects, the elevated TSH and thyroglobulin and low free T4 levels were reversed in the autoantibody negative but not in the positive group.

CONCLUSIONS This study provides further information on the prevalence of thyroid dysfunction and autoimmune thyroid diseases in an iodine sufficient area. In addition, it suggests that more than half of the patients with unsuspected hypothyroidism were negative for autoantibodies and that the excessive iodine intake may be involved in causing latent hypothyroidism.
The relation between clinical manifestations of polycystic ovary syndrome and β‐cell function
Authors: Weber R. F. A. , Pache T. D. , Jacobs M. L. , Doctor R. , Loriaux D. Lynn , Fauser B. C. J. M. , Birkenhäger J. C.
Published: March 2008

OBJECTIVE Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome.

PATIENTS Nine obese (BMI < 25 kg/m2) and nine non‐obese (BMI 19–25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non‐obese) were studied. Oligo or ameno‐rrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria.

MEASUREMENTS Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at –5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C‐peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C‐peptide, glucose, testosterone, sex hormone‐binding globulin (SHBG), free fatty acids and IGF‐I measurements. The free androgen index was calculated according to the formula FAI = testosterone ± 100/SHBG.

RESULTS There were no significant differences in maximal increment and area under the response curve for glucose, C‐peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients.

CONCLUSIONS The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.
Serum FSH bioactivity and response to acute gonadotrophin releasing hormone (GnRH) agonist stimulation in patients with polycystic ovary syndrome (PCOS) as compared to control groups
Authors: Méchain Catherine , Cédrin Isabelle , Pandian Chelvi , Lemay André
Published: March 2008

OBJECTIVE We evaluated the biological activity of FSH in the serum of women with polycystic ovary syndrome before and after acute administration of a GnRH agonist as compared to control groups.

DESIGN FSH, oestradiol and androstenedione response to buserelin (100 μg s.c.) comparing seven polycystic ovary patients, six idiopathic hirsute women, 11 normal women in the follicular phase and nine normal men.

MEASUREMENTS Rat granulosa cell aromatase bioassay in the presence or absence of polyethyleneglycol (PEG) pretreated 2% serum. Serum biological FSH (B‐FSH), immunological FSH (I‐FSH) and B/I ratio at times 0,1, 2, 3, 4, 8, 12 and 24 hours. Serum androstenedione and oestradiol at times 0 and 24 hours.

RESULTS Human gonadotrophin‐free (oral contraceptive user and after FSH immunoabsorption) and PEG‐pre‐treated serum increases the aromatase activity in response to increasing doses of purified FSH. The maximum enzymatic activity is however higher with 2% serum than with 4% serum. The amplitude of the B‐FSH response to the GnRH agonist is markedly decreased in the polycystic group as compared to the group of normal women. There is also a small decrease in the l‐FSH response in the polycystic women. When compared to that of normal women, the area under the curve in the polycystic ovary patients is reduced by 71% for B‐FSH (P<001) and by 23% for l‐FSH (P<0.05). The B‐FSH and I‐FSH responses in men are very small. After an initial decrease the B/I ratio returns to baseline level in normal women but remains low in the other groups. At time 24 hours, there is no significant change in the serum concentration of androstenedione but serum oestradiol, the baseline of which is significantly higher in the polycystic patients than in normal women, is also significantly higher at 24 hours (P< 0.05) in response to the pharmacological release of FSH.

CONCLUSION The gonadotrophin‐free and PEG‐pre‐treated human serum has an inherent stimulatory effect on the rat granulosa aromatase bioassay with a higher activity at 2% serum. Acute GnRH agonist stimulation reveals a deficiency in the FSH response in polycystic ovary patients. The greater deficit in B‐FSH than in l‐FSH would indicate a possible modification in the FSH isoforms in this syndrome. The meaning of this observation for the understanding of the physiopathology of the polycystic ovary syndrome remains to be evaluated.
The short and long‐term effects of octreotide on calcium homeostasis in patients with acromegaly
Authors: Fredstorp Lennart , Pernow Ylva , Werner Sigbritt
Published: March 2008

OBJECTIVE The somatostatin analogue octreotide (Sandostatin, Sandoz) is effective in reducing growth hormone levels in patients with acromegaly. Early and transient gastrointestinal side‐effects are frequent. The aim was to evaluate whether gastrointestinal side‐effects during the initial phase of octreotide treatment affect calcium homeostasis, and whether effects on calcium homeostasis are seen during long‐term treatment with octreotide in patients with optimal effect on GH and subjectively normal gastrointestinal function.

DESIGN We first studied short‐term treatment with octreotide during 14 days. From day 15 of the study medication was withdrawn, and on day 20 follow‐up measurements were made. We then observed the effects of long‐term treatment with octreotide. Mean duration of treatment until the day of blood sampling was 32 months (range 9–48 months).

PATIENTS Sixteen patients with acromegaly were studied, ten in the short‐term study and ten in the long‐term study; four were included in both.

MEASUREMENTS Serum levels of calcium, phosphate, PTH, alkaline phosphatase, 1,25(OH)2 Vit D, vitamin D‐binding protein and sex hormone‐binding globulin (SHBG) were measured before treatment (day 0) and on days 4, 6, 8,14 and 20 during the short‐term study and, except SHBG, before treatment and during therapy in the long‐term study.

RESULTS During the short‐term treatment mean (± SEM) serum calcium decreased significantly (on days 6 and 8, 2.21 ±0.08 and 2.15 ± 0.09 mmol/l, respectively vs basal level, 2.38 ± 0.08 mmol/l), whereas significant increments were seen in mean serum PTH (on day 14, 36 ± 4 vs basal, 24 ± 3 ng/l; ng/l ± 9.425 = pmol/l), mean serum 1,25(OH)2 Vit D (on day 8, 112 ± 7 vs basal 96 ± 8 pmol/l), and ‘free 1,25(OH)2 Vit D‐index', i.e. molar ratio of 1,25(OH)2 Vit D and vitamin D‐binding protein (on days 8 and 14, 1.72 ± 0.09 ± 105 and 1 66 ± 0.11 ± 10–5, respectively vs basal, 1.33 ± 0.09 ± 10–5). The changes were within the normal range. No changes were seen in serum phosphate, alkaline phosphatase, or vitamin D‐binding protein.

During the long‐term study mean serum calcium and phosphate decreased significantly, 2.32 ± 0.04 vs basal 2.42 ± 0.04 mmol/l and 1.24 ± 0.07 vs basal 1.40 ± 0.09 mmol/l, respectively, whereas mean serum PTH increased significantly, 40 ± 8 vs basal 21 ± 5 ng/l. The changes were within the normal range. No changes were seen in serum alkaline phosphatase, 1,25(OH)2 Vit D, free 1,25(OH)2 Vit D‐index, or vitamin D‐binding protein.

CONCLUSION Altered calcium homeostasis during octreotide treatment in acromegaly is not only initial and temporary, but can also be seen after several years of treatment. The clinical relevance of these long‐standing effects needs to be further investigated.
Bone mineral density in patients with endogenous subclinical hyperthyroidism: Is this thyroid status a risk factor for osteoporosis?
Authors: Földes J. , Tarján G. , Szathmari M. , Varga F. , Krasznai I. , Horvath Cs.
Published: March 2008

OBJECTIVE The aim of the present study was to elucidate whether endogenous subclinical hyperthyroidism due to a solitary autonomously functioning thyroid nodule affects bone metabolism and is a risk factor for osteoporosis. DESIGN In a cross‐sectional study measurements of bone mineral density were performed in premenopausal and post‐menopausal women. Patients were categorized into non‐toxic nodular goitre (n= 32), subclinical hyperthyroid (n= 37) and toxic solitary autonomous thyroid nodule (n= 22) subgroups and the results were compared with those of sex and age‐matched control reference population (n= 68).

MEASUREMENTS Lumbar spine and femoral neck bone mineral densities were measured by dual energy X‐ray absorptiometry. Single‐photon absorptiometry was applied to the measurement of bone mineral content in the midshaft of the radius.

RESULTS In the non‐toxic nodular goitre group, bone densities for all the scanned sites did not differ from the sex and age‐matched reference population. At the L2–4 scanning site a significant decrease in the bone mineral density could be observed only in the toxic nodular goitre group and this decrease was more marked in the postmenopausal (P<0 001) than in the premenopausal females (P < 0 05). At the femoral neck and midshaft radius the mean densitometric values were slightly, but significantly, lower only in the post‐menopausal subclinical hyperthyroid group compared with the reference population (P < 0 01). The bone mineral density of the femoral neck, as well as the bone mineral content of the midshaft radius, was significantly decreased in both the premenopausal and post‐menopausal patients with a toxic solitary nodule.

CONCLUSION This study indicates that the bone mineral density of the lumbar spine, femoral neck and the midshaft of the radius are not significantly decreased in premenopausal patients with endogenous subclinical hyperthyroidism resulting from a solitary autonomously functioning thyroid nodule. Conversely, findings hint at the possibility that long‐lasting endogenous subclinical hyperthyroidism may be a contributing factor to the development of osteoporosis in some post‐menopausal women, mostly at sites where cortical bone preponderates.
Does acromegaly really predispose to an increased prevalence of gastrointestinal tumours?
Authors: Ladas S. D. , Thaiassinos N. C. , Loannides G. , Raptis S. A.
Published: March 2008

OBJECTIVE The few published prospective studies suggest a strong association of colonic tumours with acromegaly, but include small numbers of patients. In addition, the upper gastrointestinal tract of these patients has never been prospectively studied. The aim of the present study was to investigate the incidence of gastric and colonic tumours in a large cohort of acromegalic patients.

DESIGN Acromegalic patients consecutively admitted to an Endocrinology Department for diagnosls and follow‐up, were submitted to gastroscopy and colonoscopy, to identify those harbouring gastrointestinal tumours.

PATIENTS Over a 5‐year period, 54 out of 61 patients (78% with active disease) received colonoscopy and 42 out of 61 gastroscopy. No patient had a past history of gastrointestinal malignancy.

MEASUREMENTS All polypoid lesion8 found at colonoscopy and gastroscopy were separately recorded and biopsled.

RESULTS No case of gastrointestinal cancer or gastric polyp was discovered. Nineteen patients (35%) had 1‐8 colonic polyps, including 5 (9·3%) with adenomas. When compared to patients with a normal colon, those with polyps were significantly older (44·±14· vs 52· f 10·9 years, P= 0·47), but the duration of acromegaly (10·±8· vs 10·±7· years, P= 0·9) and the number of patients with active disease were similar in both groups.

CONCLUSIONS Acromegalic patients do not have an increased incidence of gastric tumours. The observed significant variation in the prevalence of colonic adenomas (9‐35%, P= 0·03) and cancer (0‐15%, P= 0·017), between our patients and those of the published prospective studies with similar demographic characteristics, suggest that environmental and hereditary factors may be more important than the presence of acromegaly.
Hyperinsulinaemia and Na+, K+ ‐ATPase activity in thyrotoxic periodic paralysis
Authors: Chan A. , Shinde R. , Chow C. C. , Cockram C. S. , Swaminathan R.
Published: March 2008

OBJECTIVE Thyrotoxic periodic paralysis (TPP) usually follows a heavy carbohydrate meal and this may be explained by hyperinsulinaemia stimulating Na+, K+ ‐ATPase activity. To clarify this the effect of glucose load on serum insulin concentration and platelet Na+, K+ ‐ATPase activity In thyrotoxic periodic paralysis (TPP) was examined.

DESIGN In all subjects a standard 75‐g glucose tolerance test was done and blood samples were taken at 0, 1 and 2 hours.

SUBJECTS Twenty‐five healthy controls (8 M and 17 F), 17 uncomplicated thyrotoxic patients (7M and 10 F), 15 TPP patients who presented with paralysis and 4 TPP patients after treatment with antithyrold drugs.

MEASUREMENTS Plasma glucose was measured by the glucose oxidase method, serum insulin by radioimmunoassay and platelet Na+, K+ ‐ATPase by the release of phosphate from ATP.

RESULTS TPP patients showed glucose intolerance (area under the curve (AUC) 16·5 ± 4·4 (mean ± SD) In TPP compared to 12·9 ± 4·5 In controls (P < 0·01) and hyperinsulinaemia (AUC 189·6 ±100·6 vs 98·5 ±53·4, P < 0·001). In uncomplicated thyrotoxicosis the results were similar to that in healthy controls. Platelet Na+, K+ ‐ATPase were significantly higher in thyrotoxic patients compared to controls and In TPP patients were even higher. Ingestion of glucose increased platelet Na+, K+ ‐ATPase in all groups. AUC for platelet Na+, K+ ‐ATPase in TPP patients were significantly higher than in uncomplicated thyrotoxicosis (601 ±99·3 vs 482 ± 109·4, P < 0·01) or healthy controls (320 ± 107·3). In the 4 TPP patients studied after antithyroid treatment the results were similar to healthy controls.

CONCLUSION Patients with thyrotoxic periodic paralysis have hyperinsulinaemia and this is accompanied by higher Na+, K+‐ATPase activity.
Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity
Authors: Gelding S. V. , Robinson S. , Lowe S. , Niththyananthan R. , Johnston D. G.
Published: March 2008

OBJECTIVES The assessment of insulin sensitivity requires an accurate and reproducible technique. The short insulin tolerance test is a simple and rapid method for screening large numbers of subjects when the fasting glucose level is normal. Conventionally, an insulin dose of 0·1 units/kg is used, but this may result in symptomatic hypoglycaemia in healthy thin subjects who are insulin sensitive. In order to overcome this problem we have employed a lower dose of insulin and have studied the reproducibility of this modified technique comparing it with the euglycaemic hyperinsulinaemic clamp.

DESIGN Subjects were studied on two separate occasions, once by a short insulin tolerance test and on a second occasion by either a euglycaemic hyperinsulinaemic clamp (insulin infusion of 40 mU/m2/min) or a repeat short insulin tolerance test.

PATIENTS Eleven healthy subjects were studied twice with a short insulin tolerance test. A further 10 healthy subjects received a short insulin tolerance test on one day and a euglycaemic hyperinsulinaemic clamp study on another occasion.

MEASUREMENTS Insulin sensitivity was measured in the short insulin tolerance test using the slope of arterialized blood glucose concentration from 3 to 15 minutes after an intravenous bolus of short‐acting insulin, 0·05 units/kg body weight. In the clamp study, insulin sensitivity was derived from the average amount of glucose infused at steady state (M) and the mean plasma insulin level (l).

RESULTS In the short insulin tolerance test no subject developed symptomatic or biochemical hypoglycaemia, defined as a blood glucose < 2·2 mmol/l. The (mean ± SEM) insulin sensitivities for the 11 subjects studied twice were 174±10 and 179±11 μmol/l/min with a coefficient of variation of 6·9±2·6%. There was a close correlation between insulin sensitivity derived from the short insulin tolerance test and that obtained from the euglycaemic clamp studies (so‐called M/l ratio) in the same subjects (r= 0·81; P < 0·005).

CONCLUSION The short insulin tolerance test employing 0·05 units/kg insulin is a safe, valid and reproducible method for the assessment of insulin sensitivity.
Primary adrenal and thyroid insufficiencies associated with hypopituitarism: a diagnostic challenge
Authors: Pholsena Maryse , Young Jacques , Couzinet Beatrice , Schaison Gilbert
Published: March 2008

Polyglandular syndromes have been described for many years but only one case of panhypopituitarism with adrenal and thyroid insufficiencies has been documented. We present a 69‐year‐old woman with the initial diagnosis of idiopathic primary hypopituitarism. An associated primary adrenal disease was suspected on low plasma aldosterone and increased plasma renin values during unjustified withdrawal of treatment. The complete absence of cortisol response to long‐term ACTH administration confirmed the diagnosis. In addition, primary hypothyroidism was demonstrated by the absence of radioiodine uptake by the thyroid gland and the inability to increase T4 secretion after repeated TSH injections. The pattern of hypopituitarism and the coexistence of both adrenal and thyroid deficiencies provide strong evidence for the diagnosis of autoimmune polyglandular syndrome with hypophysitis.
Reduced serum levels of dehydroepiandrosterone sulphate in adrenal incidentalomas: a marker of adrenocortical tumour
Authors: Flecchla D. , Mazza E. , Carllni M. , Blatto A. , Ollvlerl F. , Serra: G. , Camannl F. , Messlna M.
Published: March 2008

BACKGROUND AND OBJECTIVE Reduced serum levels of dehydroeplandrosterone sulphate (DHEAS) have been shown In patients with Cushing's syndrome resulting from adrenocortical adenoma, In contrast with normal DHEAS levels In patients with Cushing's disease. The elm of this study was to verify whether patients with incidentally discovered adrenocortical adenomas also have reduced levels of DHEAS.

DESIGN Evaluation of serum DHEAS, serum and urinary cortisol, plasma ACTH and low dose dexamethasone suppression test In patients with adrenal Incidentaloma and Cushing's syndrome.

PATIENTS Thirty‐two patients with adrenal Incidentaloma and, as controls, 17 patients with overt Cushing's syndrome, were studied.

RESULTS Serum DHEAS levels lower than normal were found In 21/24 (81.5 %) patients with adrenocortical Incidentaloma, but In only 1/8 patients with a mass of non‐adrenocortical origin. This patient had massive bilateral metastatic infiltration of both adrenal glands and primary adrenal failure. The prevalence of low DHEAS levels in the two groups was significantly different (P= 00001). In patients with adrenocortical Incidentaloma, the prevalence of low DHEAS levels was significantly higher (P= 00001) than that found for some hormonal alterations Indicating pre‐clinical hypercortlsoilsm (high urinary cortisol, unsuppressed serum cortisol after low dose dexamethasone administration and low plasma ACTH). Low DHEAS levels were found in all patients with Cushing's syndrome due to adrenocortical adenoma but in none of those with Cushing's disease. CONCLUSIONS Our results Indicate that the finding of low DHEAS levels can be considered a marker of the adrenocortical origin of an adrenal Incidentaloma, provided adrenal failure has been excluded.