bluuebunny/crossref_metadata_2025 huggingface dataset:
CYCLICAL CUSHING'S SYNDROME PRESENTING AS SHORT STATURE IN A BOY WITH RECURRENT ATRIAL MYXOMAS AND FRECKLED SKIN PIGMENTATION
Authors: CARSON D. J. , SLOAN J. M. , CLELAND J. , RUSSELL C. F. J. , ATKINSON A. B. , SHERIDAN B.
Published: March 2008

A young male patient demonstrated unusual features of Cushing's syndrome, atrial myxomas and freckled skin pigmentation. At 4.5 years of age he presented with intermittent swelling of his face and abdomen associated with weight gain and mild hypertension. A left atrial myxoma, suspected from routine physical examination, was surgically removed at 6.1 years of age. The initial mild symptoms clinically thought to be due to Cushing's syndrome, persisted intermittently without any consistent biochemical abnormality. At 10 years of age height velocity decreased and at 12 years early osteoporosis was observed radiologically. Repeated dexamethasone tests revealed a paradoxical increase in cortisol and corticotrophin from normal basal levels. Further investigation showed a cyclical pattern of hypercortisolism. The removal of a pituitary microadenoma failed to correct the features of Cushing's syndrome or prevent intermittent hypercortisolism. At 15.3 years a second left atrial myxoma was removed. This was followed by bilateral adrenalectomy. Histologically the features were consistent with primary pigmented nodular adrenocortical disease. This is the first patient described with cyclical Cushing's syndrome as part of this unusual complex of disorders.
THE HUMAN LEUCOCYTE SODIUM PUMP IN CUSHING'S SYNDROME
Authors: NG L. L. , EVANS D. J. , BURKE C. W.
Published: March 2008

Because corticosteroids have important effects on sodium homeostasis, we studied leucocyte 22Na efflux in patients with Cushing's syndrome. The ouabain‐sensitive 22Na+ efflux rate constant was raised in Cushing's syndrome (mean ± SD 2.84 ± 0.32 vs 2.35 ± 0.53/h, P < 0.001, n= 15). This efflux rate constant correlated with the urinary free cortisol (rs= 0.61, P < 0.02), but less significantly with the 0900 h plasma cortisol (rs=0.46, P <0.08). There was no correlation with the supine plasma aldosterone. Intracellular sodium content was significantly lower in Cushing's syndrome (21.1 ± 4.6 vs 27.8 ± 9.5 mmol/kg dry weight, P < 0.01), with a raised intracellular potassium to sodium content ratio (16.1 ± 3.3 vs 12.9 ± 3.6, P < 0.01). After treatment of the Cushing's syndrome by trans‐sphenoidal adenomectomy or adrenalectomy, these defects in cellular sodium balance were corrected. Thus, the distribution of sodium between intra‐ and extracellular fluid may be affected by adrenal corticosteroids via an action on the sodium pump.
NEUROFIBROMATOSIS ASSOCIATED WITH SOMATOSTATINOMA: A REPORT OF TWO PATIENTS
Authors: SWINBURN B. A. , YEONG MEE LING , LANE M. R. , NICHOLSON G. I. , HOLDAWAY I. M.
Published: March 2008

Two patients with neurofibromatosis and somatostatinoma are described, one patient in addition having a parathyroid adenoma diagnosed post mortem. The other patient had a partial somatostatinoma syndrome with diabetes, abdominal pain and cholelithiasis. The tumour was diagnosed preoperatively and metabolic studies demonstrated mild diabetes mellitus apparently due to supression of insulin secretion by somatostatin, since oral glucose tolerance returned to normal post‐operatively despite hemipancreatectomy. The tumour also secreted gastrin. There are now 18 reported cases of neurofibromatosis and duodenal carcinoid tumours which makes a genuine association between these two conditions very likely. With the present two cases, seven of the carcinoid tumours in this group have been positively identified as somatostatinomas. The histological finding of psammoma bodies is important in the diagnosis of duodenal somatostatinomas.
CHANGES IN SERUM INSULIN CONCENTRATION DURING PUBERTY AND THEIR RELATIONSHIP TO GROWTH HORMONE
Authors: HINDMARSH P. , DI SILVIO L. , PRINGLE P. J. , KURTZ A. B. , BROOK C. G. D.
Published: March 2008

In 40 tall and short children we have demonstrated using oral glucose tolerance tests that there is an increase in serum insulin concentration during puberty with no change in blood glucose concentration. Fasting serum insulin concentration rose from a pre‐pubertal value between 4.0 and 5.7 mU/l to values between 11.0 and 14.6 mU/l during puberty. This rise in both fasting serum insulin concentration and the incremental area under the insulin curve is probably due to changes in circulating GH concentrations. In 16 tall girls a rise in serum GH concentration was observed during pubertal growth and the rise was accompanied by a two‐ to three‐fold increase in fasting serum insulin concentration. In 13 children in whom 24 h growth hormone profiles were recorded higher insulin concentrations were seen in those who secreted the most growth hormone. These data suggest that during pubertal growth in diabetic children the standard dosage of insulin administered (0.9 units/kg per day) should be doubled or possibly tripled to maintain good metabolic control and maximize pubertal growth.
THE EFFECT OF ANTITHYROID DRUGS ON B AND T CELL ACTIVITY IN VITRO
Authors: WILSON R. , McKILLOP J. H. , CHOPRA M. , THOMSON J. A.
Published: March 2008

This study examined the abilities of methimazole, propylthiouracil (PTU) and propranolol to exert an immunosuppressive effect in vitro. Incubation of peripheral blood lymphocytes (PBL) with propranolol showed the drug to have no effect on either B‐ or T‐cell activity. Methimazole or PTU at concentrations of ≥ 10−5M resulted in significantly lower amounts of IgG and IgM being released into the culture medium. Both drugs were also found to have a direct effect on T‐cell function as they caused the percentage of total and suppressor cells to increase towards normal levels. The three drugs were all found to have some free radical scavenging ability. These ranked PTU > methimazole > propranolol. These in‐vitro findings would suggest that both methimazole and PTU have some direct effect on the immune system. It would seem more likely however that these effects are mediated via interleukin 2 rather than by their ability to act as free radical scavengers.
COMPARATIVE STUDY OF NEUROLOGICAL AND MYXOEDEMATOUS CRETINISM ASSOCIATED WITH SEVERE IODINE DEFICIENCY
Authors: CHAOUKI M. L. , MAOUI R. , BENMILOUD M.
Published: March 2008

The clinical and biochemical features of myxoedematous and neurological cretinism were studied in an endemic goitre area in Algeria (goitre prevalence 51.3%; endemic cretinism 1.1 %; mean urinary iodine level 127.6 nmol/l). When comparing the data collected in six different villages of the area, significant negative correlations were found between the decrease in urinary iodide and iodide/thiocyanate ratio (I/SCN) and the increase in prevalences of visible goitres, endemic cretinism and transient neonatal hypothyroidism. The cretins were divided on clinical signs into two groups: myxoedematous (MC) and neurological (NC) cretinism. Differences were noted in the neurological signs and the type of deafness encountered in both types. Although some overlap did exist, proximal spasticity and rigidity were characteristic of NC. The hormonal profiles of the two groups, including TRH tests, were clearly different. The two groups were similar with regard to the percentage of palpable thyroids, the absence of antimicrosomal and anti‐thyroglobulin antibodies, seropositive viral antibodies and thiocyanate concentrations in serum and urine. Thus it is unlikely that these factors have any significant aetiological role in NC. The data collected in the general population in this area and those obtained in the mothers of the myxoedematous and neurological cretins support the hypothesis that the neurological signs are the result of hypothyroxinaemia in the mothers and the fetus at different periods of pregnancy. They could be aggravated by neonatal hypothyroidism, which may be transient in NC and permanent in MC.
THE VALUE OF THYROID VOLUME MEASURED BY ULTRASONOGRAPHY IN THE DIAGNOSIS OF GOITRE
Authors: BERGHOUT A. , WIERSINGA W. M. , SMITS N. J. , TOUBER J. L.
Published: March 2008

Thyroid volume was measured by ultrasonography in 80 euthyroid patients with sporadic nontoxic goitre and in 50 healthy adults, all residing in non‐iodine deficient areas. All patients were referred because of complaints of goitre and had been diagnosed as cases of goitre by inspection and palpation. The thyroid volume in 15 patients with goitre (19%) was within the normal reference range (4.9–19.1 ml). Fourteen of the 15 patients had thyroid nodules larger (mean diameter 2.9 ± 1.1 cm) than those detected in nine of the healthy adults (mean diameter 0.8 ± 0.6 cm; P < 0.001). Thyroid size as estimated by inspection and palpation (grade OA to III according to Stanbury et al, 1974) was poorly related to thyroid volume measured by ultrasonography. In conclusion: (1) a thyroid volume within the normal reference range does not rule out the presence of nodular goitre; and (2) application of thyroid volume measurement by ultrasonography may prevent overestimation of goitre prevalence in epidemiological surveys.
GLUCOCORTICOIDS AND GLUCOSE METABOLISM: HEPATIC GLUCOSE PRODUCTION IN UNTREATED ADDISONIAN PATIENTS AND ON TWO DIFFERENT LEVELS OF GLUCOCORTICOID ADMINISTRATION
Authors: MALERBI D. , LIBERMAN B. , GIURNO‐FILHO A. , GIANNELLANETO D. , WAJCHENBERG B. L.
Published: March 2008

Plasma glucose, insulin levels and hepatic glucose production rates were studied after an overnight fast in six Addisonian patients in three different conditions: off replacement treatment, on substitution therapy and on high‐dose glucocorti‐coid treatment. For comparison eight normal subjects were evaluated in basal conditions. Fasting plasma glucose and hepatic glucose production did not change significantly with either level of glucocorticoid treatment when compared to the untreated state and the normal controls, but there was a significant increase in plasma glucose levels in the high‐dose cortisone‐treated Addisonian patients when compared to the untreated state. Insulin levels were significantly lower in the untreated state and significantly higher in the high dose‐treated patients when compared to the normal controls. It is suggested that in these experimental conditions the peripheral actions of glucocorticoids are predominant over the hepatic effects by virtue of their ability to produce secondary changes in insulin levels, keeping the hepatic glucose production constant.
RECOVERY FROM GLUCOCORTICOID INHIBITION OF THE RESPONSES TO CORTICOTROPHIN‐RELEASING HORMONE
Authors: WATSON A. C. , ROSENFIELD R. L. , FANG V. S.
Published: March 2008

We have characterized the recovery of the hypothalamic‐pituitary‐adrenal (HPA) axis from inhibition by short‐term prednisolone administration. Predni‐solone was given in a dosage averaging 25 mg at 12 h intervals orally for up to 2 weeks to adult volunteers. Human corticotrophin releasing hormone (hCRH) tests were performed at 0901 h using a bolus injection of 1 μg/kg before and 24–48 h after discontinuing the prednisolone. In the initial control study, hCRH stimulated a two‐fold rise in plasma ACTH and a 30% rise in plasma cortisol within 30 min (ACTH rose from 18.5 ± 4.5, SEM, pg/ml to 36.5 ± 12.6 pg/ml and cortisol from 415 ± 58 to 531 ± 69 nmol/l in response to hCRH. One dose of prednisolone had no effect on the ACTH or cortisol response to hCRH administered 24 h later. Twenty‐four hours after discontinuing a 1 week course of prednisolone, baseline plasma ACTH (3.9 ± 0.6 pg/ml) and cortisol (146 ± 17 nmol/l) were markedly suppressed, as was the cortisol response to hCRH (peak 198 ± 22). However, the plasma ACTH response to hCRH was not significantly suppressed. Forty‐eight hours after discontinuing prednisolone, the recovery of ACTH secretion was complete (baseline 10.9 ± 4.2, peak 36.4 ± 14.8 pg/ml), but the cortisol response to hCRH was still depressed (peak 294±66 nmol/l). Recovery from a 2 week course of prednisolone had similar characteristics except plasma cortisol was depressed more profoundly. Plasma dehydroepian‐drosterone (DHA) during hCRH tests and dehydroepiandrosterone sulphate (DHAS) paralleled plasma cortisol. We interpret these data to suggest that the sequence of recovery from 1 to 2 weeks of glucocorticoid inhibition is characterized first by return to normal of ACTH secretion, followed by sequential returns to normal of CRH and adrenal steroid secretion. During recovery from this relatively short course of glucocorticoids, the events reported to be characteristic of withdrawal from chronic glucocorticoid therapy appear to occur in foreshortened sequence.
OUTCOME FOLLOWING STANDARDIZED 185 MBq DOSE 131I THERAPY FOR GRAVES' DISEASE
Authors: WATSON A. B. , BROWNLIE B. E. W. , FRAMPTON C. M. , TURNER J. G. , ROGERS T. G. H.
Published: March 2008

The clinical outcome of 199 patients with Graves' disease treated with standardized 185MBq 131I therapy doses has been analysed. Most patients were controlled with antithyroid drugs prior to the 131I therapy, and also received antithyroid drugs for several months following 131I. The median follow‐up period was 5.5 years. The single 185MBq 131I dose successfully treated 72.4% of patients. The 1,2 and 5 year hypothyroid figures were 15.5%, 19.3% and 27.3%, respectively. Previous thyroidectomy was associated with an increased hypothyroid rate. Retreatment was required by 25.6%, with 3.5% requiring more than two 131I doses. Discriminant analysis of pretreatment variables suggests that patients with large goitres or severe disease (serum T3 > 10nmol/l) should be treated with higher doses of 131I.
EFFECTS OF THYROID HORMONES (T4, T3), BROMOCRIPTINE AND TRIAC ON INAPPROPRIATE TSH HYPERSECRETION
Authors: SALMELA P. I. , WIDE L. , JUUSTILA H. , RUOKONEN A.
Published: March 2008

Inappropriate TSH hypersecretion was diagnosed in a 38‐year‐old woman (case 1) and in a 38‐year‐old man (case 2). Both of them had earlier been treated by ablative therapy for hyperthyroidism. The present diagnosis was based on elevated basal serum TSH levels despite elevated serum free thyroid hormone levels. Both of them had exaggerated TSH responses to TRH (peak value 240 mU/l in case I and 408 mU/l in case 2). Their albumin and prealbumin levels were normal. The serum TBG level was normal in case 1 but was elevated in case 2. Serum levels of alpha‐subunits of TSH, and pituitary CT scans were normal. Despite mild clinical hyperthyroidism, peripheral indices of thyroid hormone action were normal. They had also relatives with apparent resistance to thyroid hormones. In view of the possibility that prolonged pituitary thyrotrophic stimulation is detrimental, various therapeutic approaches to suppress TSH levels were tried. Both T3 and T4 treatments lowered serum TSH levels, but were poorly tolerated. Acute administration of L‐dopa or bromocriptine reduced serum TSH levels, but this was not seen during long‐term therapy. TRIAC treatment lowered serum TSH levels, and the drug was well tolerated. Serum TSH responses to TRH were not blunted during T3, T4 or TRIAC treatments. Somatostatin also reduced serum TSH levels, but did not potentiate the effect of low dose T3 therapy. Our results suggest that the patients had unbalanced pituitary and peripheral thyroid hormone resistance, predominantly at the pituitary level. Of the drugs studied, TRIAC seemed to be the most suitable therapy.
CONTINUOUS SUBCUTANEOUS GROWTH HORMONE RELEASING FACTOR ANALOGUE AUGMENTS GROWTH HORMONE SECRETION IN NORMAL MALE SUBJECTS WITH NO DESENSITIZATION OF THE SOMATOTROPH
Authors: BRAIN C. , HINDMARSH P. C. , BROOK C. G. D. , MATTHEWS D. R.
Published: March 2008

The effects of 8 day continuous subcutaneous (s.c.) infusions of growth hormone releasing hormone analogue (NLE27GRF(1–29)NH2 (GHRH.A)) on growth hormone (GH) secretion were studied in 14 normal adult male volunteers. GHRH.A was administered in doses which ranged from 7.5 to 120 ng/kg/min in doubling steps. Baseline GH profiles obtained during a 24 h infusion of normal saline in each subject were compared with profiles performed on days 1 and 8 of the infusion. Doses above 30 ng/kg/min augmented GH pulse amplitude and frequency. Doses of 60 ng/kg/min and 120 ng/kg/min appeared more satisfactory as these represented doses on the upwards slope of the dose response curve. However, at a dose of 120 ng/kg/min the GH secretion did not return to baseline for 12 of the 24 h. There was no evidence of desensitization or of depletion of the releasable GH pool with any dose. The possibility of treatment of short children with depot preparations of GHRH.A appears promising.
GROWTH HORMONE (GH) RESPONSES TO ARGININE AND L‐DOPA ALONE AND AFTER GHRH PRETREATMENT
Authors: PAGE M. D. , DIEGUEZ C. , VALCAVI R. , EDWARDS C. , HALL R. , SCANLON M. F.
Published: March 2008

In order to investigate the mechanisms by which arginine and L‐dopa cause GH release in humans we measured the GH response to GHRH 1–44 (200 μg i.v.), arginine (30 g i.v. over 30 min) and L‐dopa (500 mg orally) administered alone and 120 minutes following pretreatment with GHRH 1–44 (200 μg i.v.) in normal male subjects. Prior GHRH administration abolished the GH response to subsequent GHRH. Arginine infusion induced a rise in GH levels maximal at 45 min. Following GHRH pretreatment the GH response to arginine was enhanced, with peak values of 19.3 ± 6.4 vs 53.3 ± 16.5 mU/l (mean + SEM) respectively (P < 0.02). L‐dopa alone induced a rise in GH levels maximal at 90 min (17.6 ± 7.4 mU/l, mean ± SEM) but this rise was abolished by pretreatment with GHRH.
THE RELATIONSHIP BETWEEN THE RESPONSE TO GROWTH HORMONE THERAPY AND PRE‐TREATMENT GROWTH HORMONE SECRETORY STATUS
Authors: HINDMARSH P. C. , SMITH P. J. , PRINGLE P. J. , BROOK C. G. D.
Published: March 2008

In 35 children (22 M, 13 F) aged between 5.3 years and 10.3 years who received Somatrem therapy for 1 year there was a curvi‐linear relationship between pre‐treatment GH secretory status (x) and response (y) (change in height velocity standard deviation score (SDS)) to therapy described by the equation y= A + B (e−Cx). A, B and C are constants. Dose of GH administered was found to be an important additional factor in determining respone to therapy. This was confirmed by stepwise multiple regression which resulted in a correlation coefficient of 0.74. These data suggest that in the assessment of response to GH therapy, pretreatment height velocity and/or GH secretory status as well as dose and frequency of GH administration need to be taken into account.
BLOCKAGE OF THE POSITIVE FEEDBACK EFFECT OF OESTRADIOL DURING PROLONGED ADMINISTRATION OF CLOMIPHENE CITRATE TO NORMAL WOMEN
Authors: MESSINIS IOANNIS E. , TEMPLETON ALLAN
Published: March 2008

The effect of clomiphene citrate on the occurrence and timing of the endogenous LH surge in superovulated cycles is unclear. To study further this event, five normally ovulating women were treated with clomiphene citrate 100 mg per day in two different cycles, that is, for 5 days in one cycle (days 2 to 6, CC‐5) and for 15 days in another cycle (days 2 to 16, CC‐15). During the CC‐5 cycle, the normal pattern of LH levels seen in spontaneous cycles was observed with an endogenous LH surge in all women followed by ovulation and normal luteal function. In contrast, during the CC‐15 cycle, a continuous and progressive increase of basal LH levels was seen with no surge, resulting in follicular luteinization but no ovulation. The results suggest that in normal women treated with clomiphene the occurrence of an endogenous LH surge is dependent on a significant decrease in the circulatory concentration of clomiphene at mid‐cycle.
THE EFFECT OF CALCITONIN ON GROWTH HORMONE SECRETION IN MAN
Authors: LOOIJ B. J. , ROELFSEMA F. , VAN DER HEIDE D. , FROLICH M. , SOUVERIJN J. H. M. , KRUSEMAN A. C. NIEUWENHUIJZEN
Published: March 2008

To determine whether human calcitonin inhibits GH secretion in man, as has been described for salmon calcitonin, the effect of an i.v. bolus of human calcitonin or saline on GH release after either insulin‐induced hypoglycaemia or the administration of GH‐releasing hormone (GHRH) or saline was studied. After the injection of calcitonin, no spontaneous GH surges were seen; the GH response to hypoglycaemia was diminished and the response to GHRH almost completely suppressed. Administration of calcitonin also caused a small and transient rise in plasma PRL and TSH but not LH levels, and no change in the integrated PRL or TSH response. Calcium and magnesium levels did not change. It is concluded that human calcitonin suppresses GH secretion in man, but not by suppressing GHRH and probably not by increasing somatostatin release. In addition, calcitonin has limited PRL and TSH‐releasing activity.
HLA CLASS II DNA GENOTYPES IN GRAVES' DISEASE: CLUES TO INHERITANCE OF THE HLA‐LINKED COMPONENT OF SUSCEPTIBILITY
Authors: FLETCHER J. , FRANKLYN J. A. , McLACHLAN S. M. , YOUNG E. , SHEPPARD M. C.
Published: March 2008

Restriction fragment length polymorphism analysis using DQα, DQβ and DRβ cDNA probes was performed in Graves' disease patients and control subjects. The following restriction fragment patterns were increased in frequency in patients compared with control subjects: 10 + 70 + 4.0kb DRβ/Taq1 fragments (66%vs32%; P < 0.01;corrected P< 0.06),7.0+4.0 kbDQβ/BamHI fragments (55%vs 15%; P< 0.001; corrected P<0006), and a DQα/TaqI 4.6kb fragment (75%vs 36%; P< 0.005; corrected P < 0.02). These associations could be accounted for by the known association of the B8‐DR3 haplotype with the disorder. No non‐DR3‐related restriction fragment pattern was associated with the disease using any of the probes with restriction enzymes TaqI and BamHI.

The 10+7‐0 + 4‐0kb DRβ/TaqI restriction pattern was identified in 23 of 35 Graves' disease patients. All 23 subjects were heterozygous for this pattern. This was inconsistent with simple recessive inheritance of the DR3‐associated component of disease susceptibility (P=001).

The implications of these findings are discussed with reference to models for the inheritance of the HLA‐linked component of Graves' disease susceptibility.
NORMAL NEONATAL SURGE OF GONADOTROPHINS AND SEX STEROIDS IN INFANTS OF MEN WITH ISOLATED HYPOGONADOTROPHIC HYPOGONADISM
Authors: ROSE SUSAN R. , CASSORLA FERNANDO , SHERINS RICHARD J.
Published: March 2008

The inheritance of isolated hypogonadotrophic hypogonadism (IHH) is not fully determined. Although men with this diagnosis can be treated to induce fertility, it is not known whether their offspring will inherit the hormonal deficiency. We evaluated the hypothalamic‐pituitary‐gonadal axis in nine children (born to men with IHH) during the first few months of life. This axis normally shows activation in infancy similar to that which occurs at puberty. Luteinizing hormone (LH) releasing hormone stimulated a peak LH response in excess of prepubertal levels (39.0 ± 11 mIU/ml [mean ± SD]). Testosterone in males (6.2 ± 2.8 nmol/1 and oestradiol in two of the females (320 and 100 pmol/1) were also in excess of prepubertal levels. These infants of men with IHH showed no evidence of inheriting hypogonadotrophic hypogonadism. While further studies will be conducted at the usual age of puberty to confirm spontaneous activation of the hypothalamic‐pituitary‐gonadal axis, our studies suggest that it may be possible to assess the integrity of this axis at a much younger age.
SPECTRUM OF THYROID FUNCTION ABNORMALITIES IN GESTATIONAL TROPHOBLASTIC NEOPLASIA
Authors: DESAI R. K. , NORMAN R. J. , JIALAL I. , JOUBERT S. M.
Published: March 2008

The relative influences of the putative thyroid stimulator, pregnancy state and non‐thyroidal illnesses, were assessed in 52 patients with gestational trophoblastic neoplasia (GTN). In this study biochemical thyroid status was assessed with the aid of thyrotrophin (TSH) measurements by a sensitive immunoradiometric assay and measurement of total and free thyroid hormone concentrations. The reference group consisted of 63 patients with normal pregnancy. Thyroid function in the GTN patients was also compared with that in 36 female patients with Graves' disease and 34 female patients with non‐thyroidal illnesses. We found the major influence on thyroid functions in Group I (‘Hyperthyroid’) patients with GTN to be the presence of the thyroid stimulator, while non‐thyroidal illnesses played an important role in Group II (‘High T4 syndrome’) and III (‘euthyroid’) patients with GTN. Thyroid function was also stimulated in Group II patients. The influence of pregnancy was seen in all three groups of patients with GTN, who had higher TBG concentrations than non‐pregnant patients. We conclude that there is a spectrum of thyroid function abnormalities in GTN, and that thyroid function in an individual patient is determined by the relative influence of the thyroid stimulator, non‐thyroidal illnesses and the pregnancy.
FAMILIAL POLYCYSTIC OVARIES: A GENETIC DISEASE?
Authors: HAGUE WILLIAM M. , ADAMS JUDITH , REEDERS STEPHEN T. , PETO TIMOTHY E. A. , JACOBS HOWARD S.
Published: March 2008

High resolution ultrasonography was used to establish the presence of polycystic ovaries (PCO) in 50 women with symptoms of polycystic ovary syndrome and in 17 women with congenital adrenal hyperplasia. One hundred and thirty‐seven post‐menarcheal, premenopausal female members of the families of these patients were scanned to assess the heredity of the condition. Familial PCO was found in 56 of the 61 pedigrees (92%) in which sufficient members were available for study. The frequency of PCO in the relatives of the patients with congenital adrenal hyperplasia was no different from that found in the main group. Twenty‐four out of thirty‐six (67%) mothers of probands and 45 out of 52 (87%) sisters of probands were affected. The segregation ratio (fraction of females affected) for all sibships was 107 out of 133 (80.5%). The volumes of the polycystic ovaries (mean 9.97 ml, 95% confidence limits (CL) ±0.75) were significantly different from those of the normal ovaries (mean 5.38 ml, 95% CL ±0.26) (P<00001), although there was no significant difference between the volumes of the ovaries of the probands and those of their affected relatives. Even after allowing for a high frequency of PCO in the general population (22%), the observed segregation ratios were significantly different from those predicted for autosomal dominant (P < 10−4) and X‐linked dominant (P=0.0002) modes of inheritance. A number of mechanisms which might account for the observed segregation ratio are considered. These include meiotic drive due to a genetic segregation distorter, vertical transmission of an infective agent, and environmental factors, such as the effect of maternal androgen on gonadal develpment.
BIOACTIVE LH IN WOMEN WITH POLYCYSTIC OVARIES AND THE EFFECT OF GONADOTROPHIN SUPPRESSION
Authors: MAVROUDIS K. , EVANS A. , MAMTORA H. , ANDERSON D. C. , ROBERTSON W. R.
Published: March 2008

Discrepancies between levels of bioactive LH (B‐LH) and immunoreactive LH (5‐LH) in polycystic ovarian syndrome (PCO) have been reported previously. Serum levels of I‐LH, B‐LH (by dispersed Leydig cell assay), FSH, oestradiol (E2) and progesterone (Prog) were measured once to three times weekly over 4 weeks in 13 women with classical clinical, ultrasound and endocrine features of PCO. Eleven women attending for infertility but whose profiles when studied three times weekly by combined endocrine and ultrasound assessment were normal and ovulatory served as controls. Seven of the women with PCO were evaluated during and after 3 weeks suppression with ethinyloestradiol (30 μg) plus 150 μg either of desogestrel or levonorgestrel; two were given both treatments. Both I‐LH and B‐LH levels were higher in PCO patients (20 ± SD 5 U/l and 46 ± 9 U/l respectively, P< 0.0001), compared with all phases of the normal cycles except the mid‐cycle peak. The B‐LH to I‐LH (B: I LH) ratio in PCO patients (2.5 ± 0.7) was higher than in all the control cycle phases (P < 0.05). I‐LH, B‐LH, B: I LH ratio, FSH and E2 were all suppressed from the second week of oestrogen‐progestogen treatment (P<001) and returned gradually to pretreatment levels by the third or fourth week after suppression. The LH and FSH levels and B:I LH ratio in PCO patients during suppression were comparable with levels in the early and mid‐follicular phases of control cycles but the LH/FSH ratio remained significantly raised (P < 001) at 2.3 ± 0.7. Significant correlations were found between I‐LH and B‐LH (P<0.02) and between E2 levels and B:I LH ratio (P<005). We conclude that the abnormal B: I LH ratio in PCO is reversed by suppression with sex steroids, suggesting that qualitatively abnormal LH circulating in this condition is a secondary rather than a primary abnormality.
ORCADIAN VARIATION OF GH‐INDEPENDENT IGF‐BINDING PROTEIN IN DIABETES MELLITUS AND ITS RELATIONSHIP TO INSULIN. A NEW ROLE FOR INSULIN?
Authors: HOLLY J. M. P. , BIDDLECOMBE R. A. , DUNGER D. B. , EDGE J. A. , AMIEL S. A. , HOWELL R. , CHARD T. , REES L. H. , WASS J. A. H.
Published: March 2008

Evidence is accumulating that a non‐GH dependent insulin‐like growth factor‐binding protein (IGF‐BP) is not only a carrier protein but also has an active role in the growth process.

We have measured levels of this IGF‐BP, using a specific RIA, over 12 or 24‐h periods in 11 adolescents with diabetes mellitus and five normal adults. In each of the normals the IGF‐BP was undetectable for most of the day but with a broad nocturnal peak observed, with levels up to 50 μU/l. The levels of IGF‐BP were unrelated to the secretory pattern for GH but correlated inversely with the concentration of circulating insulin. In the diabetics a very similar pattern was observed, but with detectable levels throughout the day and much higher peak levels seen at night. Peak levels were up to 120 μg/1 if a long‐acting insulin preparation was administered in the evening but were 400–500 μg/1 if the long‐acting preparation was administered in the morning. The IGF‐BP was strongly correlated with plasma glucose in this latter group.

In a further group of diabetics overnight profiles were obtained on two separate nights, a normal night and a night with euglycaemia maintained with a glucose clamp technique. Euglycaemia failed to affect peak levels of the binding protein, although the shape of the nocturnal peak was altered consistent with the altered pattern of circulating free insulin. In this group a strong inverse correlation was obtained between the IGF‐BP and free insulin levels.
SELLA SIZE AND CONTENTS IN SHEEHAN'S SYNDROME
Authors: SHERIF IBRAHIM H. , VANDERLEY CHRISTINE M. , BESHYAH SALEM , BOSAIRI SOAD
Published: March 2008

High‐resolution computerized tomography was used to assess the size and contents of the pituitary fossa in 57 patients with Sheehan's syndrome and 17 female control subjects. No correlation was found either in the patients or the control group, between sella volume and age, weight, height, parity or time interval from postpartum haemorrhage to scan. The sella volume showed wide variation. The mean sella volume for all patients was 565 mm3 (SD 292) in contrast to a mean volume for the controls of 922 mm3 (SD 155). The difference was statistically significant (P> 0.001) using the Mann‐Whitney test. The stalk was visualized in 46 patients (81 %) (20 of these showed other pituitary tissue in addition). The remaining 11 patients showed no pituitary tissue, and only pure CSF density was observed.
THE CARDIOVASCULAR EFFECTS OF OCTREOTIDE TREATMENT IN ACROMEGALY: AN ECHOCARDIOGRAPHIC STUDY
Authors: THUESEN LEIF , CHRISTENSEN STIG E. , WEEKE JØRGEN , ØRSKOV HANS , HENNINGSEN PER
Published: March 2008

Nine acromegalic patients were treated by the somatostatin analogue SMS 201–995 octreotide (Sandostatin (octreotide), Sandoz, Basle, Switzerland)) 250 μg/ day in 4 divided s.c. injections (50 + 50 + 50 +100 μg) for 1 month, 250 μg/24 h as continuous s.c. infusions for another month and thereafter 200 μg three times daily as s.c. injections. Echocardiography was performed before the treatment, following 1 month of octreotide s.c. infusion/injection and after 6 and after 12 months of octreotide treatment. No differences in serum growth hormone, heart rate, blood pressure, cardiac contractility or left ventricular wall mass or wall thickness were found between the infusion and the injection periods. As compared to the pretreatment levels serum growth hormone decreased by 62 and 66%, respectively following 6 and 12 months octreotide treatment. The heart rate per minute (± SD) decreased from the pretreatment level of 75 ± 12 to 63·13 (P> 0.007) at month 12. The systolic and the diastolic blood pressure decreased from the pretreatment level of 121 ± 8 and 79 ± 5 mmHg respectively to 108 ± 7 (P> 0.0007) and 71 ± 7 mmHg (P> 0.0001) respectively at month 12. The left ventricular wall thickness was reduced from 26 ± 3 mm before treatment to 24 ± 3 mm (P> 0.05) at month 6 and to 24 ± 4 mm (P> 0.04) at month 12. The left ventricular wall mass was 168 ± 48 g/m2 before octreotide treatment, 156 ± 46 g/m2 (NS) after 6 months and 157 ± 52 g/m2 after 12 months (P> 0.08) of octreotide treatment. In age and sex‐matched normal control subjects the left ventricular wall thickness was 20 ± 2 mm, and the left ventricular wall mass was 122 ± 26 g/m2. The wall thickness and the wall mass were increased in the acromegalic patients as compared to the controls before and following the octreotide treatment periods. We suggest that reduction of serum growth hormone levels by octreotide in acromegalic patients is associated with a decrease of the left ventricular wall thickness, but the wall thickness is not reduced to levels of normal control subjects.
MONOAMINE OXIDASE (MAO) ACTIVITY AND ITS FORMS IN NORMAL AND PATHOLOGICAL HUMAN THYROID TISSUES
Authors: CABANILLAS A. M. , MASINI‐REPISO A. M. , COLEONI A. H.
Published: March 2008

Monoamine oxidase (MAO) activity and its forms were measured in normal human thyroid glands (39 samples from necropsy and four from perinodular tissues) and in pathological thyroid glands (13 multinodular goitres, three carcinomas, seven chronic thyroiditis, five Graves’ disease and seven follicular, seven foetal and five embryonal adenomas). MAO activity in carcinomas was lower than in normal perinodular thyroid control tissue; in Graves’ disease, foetal and embryonal adenomas it was significantly higher than in the normal control. The use of clorgyline (a selective MAO A inhibitor) and deprenyl (selective MAO B inhibitor) allowed estimation of the relative proportion of MAO forms. A high proportion of MAO A (more than 90%) was observed, both in normal and in pathological thyroid tissues. Changes in total thyroid MAO activity, but not in its forms, were found in different pathologies of the thyroid gland.
STEROID RESPONSES TO ACTH IN WOMEN WITH POLYCYSTIC OVARIES
Authors: HAGUE W. M. , HONOUR J. W. , ADAMS J. , VECSEI P. , JACOBS H. S.
Published: March 2008

Sixty‐three women with ultrasonically detected polycystic ovaries (PCO) were investigated for a disorder of adrenal steroid biosynthesis. Serum was obtained before, and at 30 and 60 min after, the administration of 250 μg tetracosactrin, and assayed for 17α‐OH‐progesterone, 21‐deoxycortisol, 17α‐OH‐pregnenolone and dehydroepiandrosterone by radioimmunoassay following paper chromatography. Results were compared with those in 11 women with normal ovaries, seven adult females with congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency (21OHD), and 15 women heterozygous for this defect. Although the basal‐peak steroid concentration differences were significantly greater when ACTH tests were conducted between 1400 and 1700 h than between 0900 and 1000 h, absolute peak steroid concentrations were not different at either time of day. Four of 63 (6.4%) women with PCO had responses to ACTH characteristic of non‐classical (late onset) 21OHD CAH, and about half the remainder had responses characteristic of 21OHD heterozygotes. There was no clear cut evidence for a deficiency in 3β‐hydroxysteroid dehydrogenase activity in women with PCO.
REASONS FOR THE VARIABILITY IN GROWTH HORMONE (GH) RESPONSES TO GHRH CHALLENGE: THE ENDOGENOUS HYPOTHALAMIC‐SOMATOTROPH RHYTHM (HSR)
Authors: DEVESA J. , LIMA L. , LOIS N. , FRAGA C. , LECHUGA M. J. , ARCE V. , TRESGUERRES J. A. F.
Published: March 2008

The aims of this study were: (1) to test the possibility that pre‐GHRH plasma GH values could reflect the functional status of the hypothalamic‐somatotroph rhythm (HSR) at testing, and thus explain if it is responsible for the marked variability in GH responsiveness to GHRH challenge and (2) to see if exogenous somatostatin (SS) could disrupt this endogenous HSR and thus make the GH responses homogeneous.

(1) Two to 14 GHRH acute tests (GRF‐29, 1 μg/kg, i.v. bolus) were performed in 12 normal men and 10 normal women at the same time (0830 h) at random intervals (2 to 60 days). Blood samples to measure plasma GH were drawn at 15 min intervals before and after GHRH challenge. Given that the increments in pre‐GHRH plasma GH values (I=value at 0 min minus value at ‐ 15 min) were highly correlated with either GHRH‐elicited peaks of GH (men, r= 0.81; women; r= 0.69; P<0.0001) or the rise in GH after the challenge (r=0.685; P<0.0001, in the total of tests performed), three theoretical HSR phases were proposed: (A) I > 0.4 μg/l Secretory Phase; (B) I < 0, (from GH at −15 min < 1.5 μg/l), Secretion Plateau; (C) I < 0, (from GH at − 15 min < 1.5 μg/l), Refractory Phase. Individually, 91% of the men and 86% of the women showed a constant HSR phase when tested at the same time of day independently of the intervals between tests. GH responses (peaks, mean‐± SEM, g/l) in Phase A (women, 51.5 ± 4.1; men, 31.4 ± 3.2) were significantly higher (P < 0.01) than those in Phase B (women, 22.6 ± 1.8; men, 19.7 ± 1.5), and these than those in Phase C (women, 9.2 ± 1.5; men, 6.2 ± 0.5). The great dispersion observed when GH peaks were analysed as a whole disappeared (except in Phase A in women) when they were evaluated according to the HSR Phase at testing.
CORTICOTROPHIN‐RELEASING FACTOR‐LIKE IMMUNOREACTIVITY IN HUMAN 24 H URINE
Authors: MASER‐GLUTH CHRISTIANE , VECSEI PAUL
Published: March 2008

This report is the first demonstration of the presence of corticotrophin‐releasing factor‐like immunoreactive material (CRF‐LI) in human urine. Our studies, using immunoaffinity chromatography for extraction, followed by reverse phase high performance liquid chromatography for further purification, and radioimmunoassay for final peptide measurement, suggest that CRF‐LI from human urine is similar, if not identical, to human CRF. Urinary CRF‐LI excretion in normal subjects was 1.48 ± 0.69 ng/24 h (mean ± SD; n= 20) with no significant differences between the sexes. During pregnancy, urinary CRF‐LI excretion increased, and a significant correlation between urinary CRF‐LI excretion and the gestational age was seen (r = 0.62; P <0.0001). We suggest that urinary 24‐h CRF‐LI excretion may reflect the secretion of CRF into the circulation. Measurements of CRF‐LI in the urine may have several advantages over determinations of hormone levels in plasma.
FREE RADICALS AND GRAVES' DISEASE: THE EFFECTS OF THERAPY
Authors: WILSON R. , CHOPRA M. , BRADLEY H. , MCKILLOP J. H. , SMITH W. E. , THOMSON J. A.
Published: March 2008

Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH) and superoxide dismutase (SOD) activity were measured in 30 patients with newly diagnosed Graves'disease (GD). Compared to control subjects (C) PSH and SOD were significantly reduced (C vs GD, 507 vs 449 pmol/l, P <0.01; 2. 1 vs 1.6 pmol/l, P<0.01 respectively) and LSH was significantly raised (C vs GD 181 vs 298 pmol/l). Treatment with carbimazole produced a significant rise in LSH and SOD. Propylthiouracil (PTU) treatment raised LSH levels but 131I treatment produced no significant change.

All four parameters are involved in different ways in oxygen metabolism and together provide an indication of oxidative stress across the red‐cell membrane. In addition LSH is a general radical scavenger and SOD a specific O‐2 scavenger. In Graves'disease the increased oxidative stress and increased general radical scavenging may result from raised free‐radical activity. These changes, which have not previously been reported in Graves'patients, were modified by antithyroid drug therapy, but it is not clear whether this is a direct or indirect effect.
THE HALF‐LIFE OF EXOGENOUS GROWTH HORMONE AFTER SUPPRESSION OF ENDOGENOUS GROWTH HORMONE SECRETION WITH SOMATOSTATIN
Authors: HINDMARSH P. C. , MATTHEWS D. R. , BRAIN C. E. , PRINGLE P. J. , DI SILVIO L. , KURTZ A. B. , BROOK C. G. D.
Published: March 2008

We have estimated the half‐life of serum growth hormone (GH) in six subjects on 14 occasions following an intravenous bolus injection of either 50 or 500 mU of biosynthetic human growth hormone (B‐hGH) while endogenous GH secretion was suppressed by a continuous infusion of somatostatin. The disappearance curve of serum GH was mono‐exponential and the mean half‐life was 8.9 min (SD 1.5). This is less than previously reported and has important implications for the performance of GH profiles, which should be performed with 10–15 min sampling intervals, and the calculation of pituitary GH secretion rates.
SHORT‐TERM FASTING INHIBITS THE NOCTURNAL MELATONIN SECRETION IN HEALTHY MAN
Authors: RÖJDMARK S. , WETTERBERG L.
Published: March 2008

To investigate whether short‐term fasting influences hormone release from human pinealocytes, nocturnal melatonin (MT) secretion was studied before and at the end of a 2‐day fast in seven normal subjects (group A). Serum MT was measured every second hour between 1800 and 0800 h, and the nocturnal MT secretion, as reflected by the MT incremental area (MT area appearing above the 1800 h level), was calculated and compared before and during the fast. MT excretion by the urine (between 2200 and 0700 h) was also determined before, during, and after the period of food deprivation. Body weight and blood glucose concentration fell by 2.5 ± 0.2 kg (mean ± SEM, P<0.001) and 1.7 ± 0.2 mmol/l (P<0.001) respectively during the fast. Nocturnal MT secretion declined by 19 ± 3% (P<0.002), in contrast to urinary MT excretion which remained unaffected. In order to prevent blood glucose from falling significantly during the period of food deprivation, six additional normal subjects (group B) were given eight small oral doses of glucose (each dose 0.5 g/kg) at regular intervals during the 2‐day fast. This did not prevent a weight loss (2.1 ± 0.5 kg, P<0.01) of similar magnitude as in group A, but it restored a normal nocturnal MT secretion. The fact that glucose supplementation during fasting returns a decreased MT secretion to normal suggests that human pinealocytes require a certain minimal glucose delivery to function normally.
ABNORMALITIES OF THYROTROPHIN (TSH) EVENING RISE AND PULSATILE RELEASE IN HAEMODIALYSIS PATIENTS: EVIDENCE FOR HYPOTHALAMIC‐PITUITARY CHANGES IN CHRONIC RENAL FAILURE
Authors: WHEATLEY TREVOR , CLARK PENELOPE M. S. , CLARK JOHN D. A. , HOLDER ROGER , RAGGATT PETER R. , EVANS DAVID B.
Published: March 2008

Using a sensitive enzyme amplified immunoassay for TSH, the evening rise and pulsatile release of TSH were studied in 10 men with chronic renal failure treated by haemodialysis. Compared to euthyroid male controls the evening rise of TSH was attenuated (median 0.066 vs 0.195 mU/l/h, P <0.01) and the rate of rise correlated with the TSH response to TRH (r= 0.93, P <0.001). All subjects showed TSH pulsatility in at least one method of data analysis but the less sensitive incremental method showed no significant difference in pulse frequency and amplitude between the two groups. However, with time series analysis, periodicity was shorter (median 45 vs 95 min, P= 0.013) and pulse amplitude smaller (median 0.06 vs 0.175 mU/l, P=0.017) in renal patients. Pulse amplitude, but not periodicity, correlated with the TSH response to TRH (r= 0.68, P <0.05). In addition, serum total thyroxine, free thyroxine and free triiodothyronine concentrations were reduced, while serum prolactin and 17 β‐oestradiol concentrations were raised. These changes in TSH evening surge and pulsatile release may contribute to the reduction in thyroidal hormone concentrations seen in renal failure and emphasize the value of sensitive methods of hormone and pulse data analysis.
ELEVATED SERUM LEVELS OF CALCITONIN GENE‐RELATED PEPTIDE (CGRP) BUT NO EVIDENCE FOR CGRP GENE EXPRESSION IN NON‐SMALL CELL LUNG CARCINOMAS
Authors: SCHIFTER SØREN , JOHANNSEN LIS , AAGAARD MICHAEL T. , GOLTERMANN NILS , PARKES HELEN C. , CRAIG ROGER K.
Published: March 2008

Calcitonin gene‐related peptide (CGRP) is a hormone formed by alternative post‐transcriptional processing of the calcitonin gene. It is a neuropeptide localized to discrete regions of the central nervous system (CNS) and in nerve fibres associated with blood vessels. It is also expressed in medullary carcinomas of the thyroid and lung carcinoma cell lines. The latter finding suggests a possible value for CGRP as tumour marker in lung carcinomas. In this investigation of 22 patients undergoing operation for lung tumours, pre and post‐operative levels of serum CGRP were measured. Preoperative as well as postoperative serum CGRP levels were significantly elevated when compared to age‐matched normals. However, no evidence could be found for CGRP gene expression in tumour tissue from the same patients as judged by immunocyto‐chemistry or in‐situ hybridization using CGRP cRNA probes. CGRP has been localized to nerve fibres in relation to pulmonary blood vessels and has been shown to be a potent vasodilator. These findings, and the absence of evidence for synthesis in tumours, as opposed to cell lines derived from lung carcinomas, suggests that the lack of post‐operative normalization of serum CGRP concentrations may be related to physiological changes in cardiovascular haemodynamics following surgery. Elevated pre‐operative serum CGRP levels may also reflect a consequence of the lung carcinoma leading to increased release of CGRP from sites in the vasculature yet to be determined, but does not indicate synthesis de novo and secretion of CGRP by the tumours.
EVIDENCE FOR A SLOW TISSUE ADAPTATION TO CIRCULATING THYROXINE IN PATIENTS WITH CHRONIC L‐THYROXINE TREATMENT
Authors: NYSTRÖM E. , LUNDBERG P. ‐A. , PETERSEN K. , BENGTSSON C. , LINDSTEDT G.
Published: March 2008

We measured serum procollagen‐III‐peptide in 67 women with long‐term L‐thyroxine treatment and compared the results with age‐matched controls. The strong correlation between serum free thyroxine and procollagen‐III‐peptide concentrations previously found after 6 months of L‐thyroxine treatment was not found after long‐term treatment. There were slightly higher procollagen‐III‐peptide concentration values in those chronically treated patients who had high free thyroxine levels but this increase was less marked than in patients previously studied after short‐term treatment.

An increase in procollagen‐III‐peptide concentration reflects an increased biosynthesis of collagen III, which is present in connective tissues throughout the body, and our findings may be explained by slow tissue adaptation to increased levels of thyroxine. We conclude that the increased thyroxine levels found in L‐thyroxine‐treated patients are of less clinical importance than thought previously. We also conclude that peripheral markers of thyroid hormone peripheral effects such as procollagen‐III‐peptide may be of less use than thought previously due to this slow tissue adaptation to changes in thyroxine concentration.