bluuebunny/crossref_metadata_2025 huggingface dataset:
BIOACTIVE AND PERIPHERAL ANDROGENS IN PREPUBERTAL SIMPLE HYPERTRICHOSIS
Authors: BALDUCCI R. , TOSCANO V.
Published: March 2008

Prepubertal simple hypertrichosis is characterized by excessive growth of vellus hair in children without other signs of endocrinopathies. The aetiology is unknown and it is not clear if it is an abnormal entity or an extreme form of the normal range of hair growth. Sixteen girls (aged 7 |Mp 1‐9 years, mean |Mp SD) with prepubertal simple hypertrichosis and, as controls, 12 normal age‐matched girls were studied. All patients were in preadrenarchal age and in all patients an ACTH test was performed to exclude non‐classical forms of congenital adrenal hyperplasia. Testosterone (T), androstenedione (A), dehydroepiandrosterone sulphate (DHA‐S), dihydrotesterone (DHT), 3α‐androstanediol (3Ad) and its glucuronide (3AG), and sex hormone binding globulin (SHBG) were evaluated and free testosterone (FT) and T/SHBG ratio were calculated in all subjects. In all patients we found T, A and DHA‐S plasma levels comparable to controls, excluding an increased glandular androgen secretion. No significant differences, compared to controls, were observed for SHBG, FT and T/SHBG ratio, suggesting a normal T bioavailability. DHT plasma levels were significantly increased with respect to controls (0‐42 |Mp 0‐04 vs 0‐11 |Mp 0.03 nmol/l; P < 0‐002) whereas 3Ad and 3AG were comparable to controls. The very significant increase in DHT plasma levels, without a parallel increase in 3Ad and 3AG found in our cases with prepubertal simple hypertrichosis, is difficult to explain. The clinical and biochemical significance of the high DHT plasma values needs more investigation.
THE GROWTH HORMONE RELEASING HORMONE (GHRH) RESPONSE TO A MIXED MEAL IS BLUNTED IN YOUNG ADULTS WITH INSULIN‐DEPENDENT DIABETES MELLITUS WHEREAS THE SOMATOSTATIN RESPONSE IS NORMAL
Authors: FOOT A. B. M. , DAVIDSON K. , EDGE J. A. , WASS J. A. H. , DUNGER D. B.
Published: March 2008

Following a standard mixed meal, plasma concentrations of growth hormone releasing hormone (GHRH), somatostatin (SMS) and growth hormone (GH) were measured every 30 min for 300 min in six young adults with type I insulin‐dependent diabetes mellitus (IDDM) and five normal controls. Mean blood glucose concentrations were higher and mean free insulin levels lower in the diabetics compared with controls both in fasting specimens and at all times following the mixed meal. Basal concentrations (mean±SEM) of GHRH were similar in diabetic (12.7±1.8 pg/ml) and control subjects (11.8±1.1 pg/ml). Following ingestion of the mixed meal, a rise in GHRH was observed in the control subjects maximal between 30 and 240 min (P < 0.025) but the response was blunted in the diabetics. Mean GHRH concentrations were greater in the controls than in the diabetic subjects at all stages during the test, the maximum difference being noted at 120 mins (P < 0.04). Basal SMS concentrations and those observed after the mixed meal were similar in diabetic and control subjects. These results indicate that glucose and insulin may play a role in the regulation of GHRH release following a mixed meal but circulating levels of GHRH and SMS are unlikely to be relevant to the abnormal regulation of GH in IDDM.
VALUE OF SCREENING THYROID FUNCTION IN ACUTE MEDICAL ADMISSIONS TO HOSPITAL
Authors: SMALL M. , BUCHANAN L. , EVANS R.
Published: March 2008

During a 4‐month period an audit was performed to assess the value of thyroid function test (TFT) screening of all medical admissions, without known thyroid disease, to a single hospital. Abnormal TFTs were found in 125 of the 630 patients admitted (20%). Carbimazole or thyroxine was started in 13 patients (2.1%) discovered to have thyrotoxicosis (n=4) or hypothyroidism (n=9). In only four of these patients was the diagnosis of thyroid disease apparent clinically. The sick euthyroid state was found in 73 patients (11.6%), while the TSH compensated hypothyroid state was detected in 39 patients (6.2%). The low detection rate of new thyroid disease would suggest that unselective screening of all admissions is unjustified. However, the problem of diagnosing thyroid disease and the morbidity of untreated thyroid disease suggests that biochemical screening of TFTs in a selective group of medical patients admitted to hospital may be justified.
HILUS CELL PATHOLOGY AND HIRSUTISM
Authors: MCLELLAN A. R. , MOWAT A. , CORDINER J. , BEASTALL G. H. , WALLACE A. M. , CONNELL J. M. C. , DAVIES D. L.
Published: March 2008

Hilus cell abnormalities are uncommon causes of hirsutism with virilization. Although hilus cell tumours have been well described, hilus cell hyperplasia is rare and is poorly defined clinically. We describe three cases of hilus cell hyperplasia and compare them with a case of hilus cell tumour. Both pathologies were associated with increased testosterone and oestradiol secretion. Suppression of testosterone to the ‘normal range’in response to exogenous oestrogen was seen only in the cases with hyperplasia; only partial responsiveness was seen in the case with hilus cell tumour. Bilateral oophorectomy offers the potential for cure for both hilus cell hyperplasia and tumour.
DIFFERENCES IN CLINICAL AND ENDOCRINE FEATURES BETWEEN OBESE AND NON‐OBESE SUBJECTS WITH POLYCYSTIC OVARY SYNDROME: AN ANALYSIS OF 263 CONSECUTIVE CASES
Authors: KIDDY D. S. , SHARP P. S. , WHITE D. M. , SCANLON M. F. , MASON H. D. , BRAY C. S. , POLSON D. W. , REED M. J. , FRANKS S.
Published: March 2008

Two hundred and sixty‐three women with ultrasound‐diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI > 25 kg/m2‐). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non‐obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5α‐reductase activity, were higher in obese than in non‐obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8‐h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio‐availability of androgens to peripheral tissues and enhanced activity of 5α‐reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.
ANDROSTERONE GLUCURONIDE IS A MARKER OF ADRENAL HYPERANDROGENISM IN HIRSUTE WOMEN
Authors: THOMPSON DAVID L. , HORTON NATALIE , RITTMASTER ROGER S.
Published: March 2008

Androsterone glucuronide (Andros‐G), a dihydrotestosterone metabolite, is present in serum at concentrations at least tenfold greater than those of androstanediol glucuronide. To investigate the significance of serum androsterone glucuronide, we developed a direct radioimmunoassay for this compound and measured its levels in normal women, women with mild or severe idiopathic hirsutism (IH), hirsute women with polycystic ovarian syndrome (PCO), and non‐hirsute obese women. To determine the source of Andros‐G precursors, serum levels were measured before and after selective ovarian suppression with leuprolide, combined ovarian and adrenal suppression with leuprolide and dexamethasone, and adrenal stimulation with ACTH. Androsterone glucuronide levels (nmol/l; mean±SD) were significantly higher (P < 0.025) in women with mild idiopathic hirsutism (IH) (185±91), severe IH (173±97), and hirsute women with polycystic ovarian syndrome (PCO) (178±102) than in normal women (110±26). Levels in non‐hirsute obese women (64±19) were lower than in normal women (P <0.01). Baseline levels (mean±SEM) in hirsute women given 20 μg/kg/day leuprolide for 5‐9 months (171±15) were not significantly changed after leuprolide alone (153±18), and were decreased after adding dexamethasone (19±6; P < 0.001). Andros‐G levels did not increase significantly in normal women 60 min after i.v. ACTH (112±14 to 126±19), but rose in IH (170±24 to 216±26; P<0.001) and in PCO (179±26 to 238±31; P= 0002). We conclude that Andros‐G in women arises primarily from adrenal gland precursors and is elevated in hirsute women as a group. Its levels do not correlate with the severity of hirsutism, or the presence or absence of PCO, but reflect an increased production of adrenal androgens in both IH and PCO.
THE INFLUENCE OF PREGNANCY AND REPRODUCTIVE SPAN ON THE OCCURRENCE OF AUTOIMMUNE THYROIDITIS
Authors: PHILLIPS D. I. W. , LAZARUS J. H. , BUTLAND B. K.
Published: March 2008

A study comparing the reproductive histories of 89 women affected by Hashimoto's thyroiditis (HT) with 89 matched controls has been carried out to determine whether endogenous hormones contribute to the development of the disease. There was no evidence of an association between HT and parity and no trend to an increasing disease risk with increasing parity. However, patients with HT had a longer reproductive span. There was a significant trend to a lower risk with later age at menarche (relative risk (RR) of menarche at 13‐14 years compared with ≤ 12 years =0.71, and ≥ 15 years compared with ≤ 12 years = 0.45), and an increased risk with a later menopause (≥ 51 years compared with ≤ 50 years, RR = 3.00, P < 0.025). An additional finding was an increased hysterectomy rate among the cases. These observations may be explained if the hyperoestrogenic state associated with a longer reproductive span acted to modulate the immune process in autoimmune thyroid disease.
FOLLICULAR FLUID CONCENTRATIONS OF INSULIN‐LIKE GROWTH FACTOR 1, EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR‐ALPHA AND SEX‐STEROIDS IN VOLUME MATCHED NORMAL AND POLYCYSTIC HUMAN FOLLICLES
Authors: EDEN J. A. , JONES J. , CARTER G. D. , ALAGHBAND‐ZADEH J.
Published: March 2008

Thirty‐three samples of follicular fluid (FF) were collected from 14 patients with the polycystic ovary (PCO) syndrome and matched for FF‐volume with small follicles collected from subjects with normal ovaries. The median (range) FF concentration of insulin‐like growth factor I (IGF1) in the group with PCO, 0.42 (0.13‐1.20) U/ml was significantly higher than that of the controls, 0.33 (0.04‐0.59) U/ml. All samples tested had < 1 ng/ml of FF‐epidermal growth factor (EGF) and transforming growth factor‐alpha (TGF‐α). The patients with PCO syndrome (PCOS) had similar FF‐testosterone (T) and FF‐progesterone (P) concentrations to volume matched controls, but significantly higher levels of FF‐androstenedione (AD) and lower FF‐oestradiol (E2). These results suggest that the granulosa cells within the polycystic follicle have a functional defect in their aromatase enzyme complex.
A COMPARISON OF CALCIUM PENTAGASTRIN AND TRH TESTS IN SCREENING FOR MEDULLARY CARCINOMA OF THE THYROID IN MEN IIA
Authors: O'CONNELL J. E. , DOMINICZAK A. F. , ISLES C. G. , McLELLAN A. R. , DAVIDSON G. , GRAY C. E. , CONNELL J. M. C.
Published: March 2008

Intravenous injections of calcium gluconate and pentagastrin (CPG) or TRH were compared as secretagogues for calcitonin (CT) in screening for medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type IIA (MEN IIA). Administration of CPG resulted in a prompt increase in plasma CT in all five patients with MTC studied, one of whom had a normal baseline value (peak 412‐371000 ng/l, 636‐4847% above basal). TRH produced a rise in plasma CT levels only in MTC patients with elevated basal values; the magnitude of increase was less than that observed with CPG (peak 168‐17 200 ng/l, 113‐180% above basal). CT levels did not rise above 300 ng/l with either test in four unaffected first‐degree relatives of MEN IIA patients, three subjects with sporadic unilateral phaeochromocytomas and five controls with essential hypertension. CPG remains the CT secretagogue of choice in screening for MTC in MEN II A.
EFFECT OF DOPAMINE AND A DOPAMINE D‐1 RECEPTOR AGONIST ON PULSATILE THYROTROPHIN SECRETION IN NORMAL WOMEN
Authors: BOESGAARD S. , HAGEN C. , HANGAARD J. , ANDERSEN A. NYBOE , ELDRUP E.
Published: March 2008

The inhibitory effect of a pharmacological dose of dopamine and the specific dopamine D‐1 receptor agonist fenoldopam on basal and pulsatile TSH secretion was investigated in normal women. The TSH response to fenoldopam and subsequent releasing hormone administration was also studied. Six women received placebo or dopamine infusion (4.0 μg/kg min) for 17 h. After 9 h, blood samples were collected every 10 min between 0800 and 1600 h for measurement of TSH. Eight women received 8‐h (0900‐1700 h) infusions of either fenoldopam (0.5 μg/kg min) or placebo. After 7 h of infusion 10 μg TRH, 5 μg GnRH and 25 CRF was given i.v. Blood samples were collected every 10 min. Dopamine infusion as well as fenoldopam infusion significantly reduced both mean basal TSH secretion and TSH pulse frequency compared with corresponding control infusions (P < 0.05). However, while the effect on TSH pulsatility was comparable (P > 0.05), the percentage decrease in basal TSH levels after 16 h of dopamine infusion was 51±16% (mean±SD) and after 7 h of fenoldopam infusion 19±12% (P < 0.05). Neither of the drugs affected TSH pulse amplitude and fenoldopam did not influence TRH‐stimulated TSH release (P> 0.05). The results suggest that dopamine D‐1 receptors are involved in modulation of TSH pulsatility probably at the hypothalamic level. It is argued that dopaminergic inhibition of basal TSH secretion and TSH pulsatility is predominantly regulated through dopamine D‐2 receptors at the pituitary level, and through D‐1 receptors at the hypothalamic level, respectively.
BIOACTIVE AND IMMUNOREACTIVE FSH IN SERUM OF NORMAL AND OLIGOSPERMIC MEN
Authors: FAUSER B. C. J. M. , BOGERS J. W. , HOP W. C. J. , DE JONG F. H.
Published: March 2008

In men suffering from idiopathic oligospermia and azoospermia the hypothesis was tested that decreased spermatozoa production could be due in part to inadequate hormonal stimulation of spermatogenesis. In 53 healthy male subjects with normal spermatozoa production (n = 10), varying degrees of oligospermia (n = 40), and azoospermia (n = 3), serum immunoreactive LH, testosterone (T), and oestradiol (E2), and immunoreactive and bioactive FSH concentrations were determined. FSH bioactivity was estimated using the rat granulosa cell aromatase bioassay. Mean LH, T, and E2 levels were similar in the control group (spermatozoa concentration > 40 × 106/m1) compared with men exhibiting mild (10‐20 × 106/m1), moderate (5‐10 × 106/m1), or severe oligospermia (1‐5 × 106/ml), and in the azoospermia group. An inverse correlation was found between immunoreactive FSH levels and spermatozoa concentration (P < 0‐05), with elevated levels (twofold increase) of FSH in the combined severe oligospermia and azoospermia (P <0.01) groups. Moreover, augmented (P < 0‐01) bioactive FSH levels were also observed in this group of patients. The mean bioactive to immunoreactive FSH ratio was also negatively correlated with sperm counts (P < 0‐005). In addition, T/LH ratios were inversely correlated with immunoreactive (P <0.05) and bioactive (P <0.05) FSH, which may indicate that altered Leydig cell function is involved in the augmented secretion of FSH. The data presented in this study indicate that immunoreactive FSH, as measured in oligospermia and azoospermia, does not exhibit decreased bioactivity.
INSULIN‐LIKE GROWTH FACTOR‐I (IGF‐I) AND IGF‐I BINDING PROTEIN IN THE FOLLICULAR FLUIDS OF GROWTH HORMONE TREATED PATIENTS
Authors: BARRECA A. , MINUTO F. , VOLPE A. , CECCHELLI E. , CELLA F. , MONTE P. DEL , ARTINI P. , GIORDANO G.
Published: March 2008

The presence of GH, insulin‐like growth factor‐I (IGF‐I), epidermal growth factor (EGF), oestradiol (E2) and progesterone (PG) were investigated in the fluids obtained from various ovarian follicles of seven patients in whom the induction of super‐ovulation was achieved only after GH (0.1 U/kg BW/day) was added to the gonadotrophin therapy. The follicular fluids of six patients responsive to treatment with gonadotrophin alone served as a control. In patients treated with combined therapy, the results demonstrated the presence in the follicular fluids of GH (M±SEM: 8.5±0.6 mU/1), E2 (771±38 nmol/l), and PG (16.4±0.7 pmol/l) in significantly higher concentrations compared to that in control follicles (6.2±0.8 mU/l, 681±30 nmol/l, and 14.4±0.6 pmol/l; P= 0.002, 0.012, 0.0001 respectively). Acid‐extractable IGF‐I (143±9 ng/ml) and EGF (3.9±0.3 ng/ml) concentrations were similar to those of control fluids (1 24±10 ng/ml and 2.9±0.7 ng/ml respectively) and were highly correlated with each other (P<0.001), suggesting a stimulatory effect of EGF on the local IGF‐I production. A correlation between GH and IGF‐I (n=51, r=0‐36), as well as between IGF‐I and PG (n=48, r=0.77) and E2 (n=48, r=0.55) was evident only in the follicular fluid of GH‐treated subjects. In patients with gonadotrophin‐resistant anovulation the significant correlation (P < 0.01) between GH and IGF‐I suggests that GH administration influences the IGF‐I local concentration, and therefore, as IGF‐I becomes correlated with PG (PeO.001) and E2 (P < 001), it promotes the growth and maturation of the follicles. In the same patients, no correlation was evident between LH and IGF‐ I, E2 and PG, while a significant correlation was present between FSH and IGF‐ I, as well as with PG (P 0.001). The IGF‐I binding protein (BP) assay also demonstrated the presence of a considerable amount of IGF‐I binding sites in all fluids. The characterization of these IGF‐I binding sites demonstrated an IGF‐I‐BP complex of 35 kDa, similar to that found in the amniotic fluid and to the placental protein 12. These data support a role for GH and IGF‐I in the control of follicular growth and development in humans. This also supports the hypothesis of a proliferative and/or permissive effect of IGF‐I in ovarian tissue.
CORRELATION OF ORBITAL COMPUTED TOMOGRAPHY AND ANTIBODIES IN PATIENTS WITH HYPERTHYROID Graves'DISEASE
Authors: CHANG T. C. , HUANG K. M. , CHANG T. J. , LIN S. L.
Published: March 2008

The purpose of this study was to elucidate the incidence of orbital changes in computed tomography, and the relationships of orbital changes with eye‐muscle antibody (EMAb), thyrotrophin‐binding inhibitor immunoglobulin (TBII), antithyroglobulin antibody (TgAb) and anti‐thyroid microsomal antibody (MsAb), in 55 consecutive patients with hyperthyroid Graves'disease. EMAb was demonstrated by an immunoperoxidase technique. The results showed that the prevalence of orbital fat increase, extraocular muscle enlargement, lacrimal gland enlargement and optic nerve swelling were 54.5, 41.8, 21.8 and 16.5% respectively. There were 32.7% of patients without any orbital changes. The patients with extraocular muscle enlargement, lacrimal gland enlargement and optic nerve swelling had higher titres of EMAb than the patients without these orbital changes. The patients with lacrimal gland enlargement had a lower TBII index than those without. There was no difference in TgAb or MsAb between the patients with extraocular muscle enlargement, lacrimal gland enlargement, optic nerve swelling or orbital fat increase and those patients without these orbital changes. The patients with extraocular muscle enlargement, optic nerve swelling and orbital fat increase had a higher degree of exophthalmos than the patients without these orbital changes. EMAb was negatively correlated with TBII. However, there was no correlation between EMAb and TgAb or MsAb. The degree of exophthalmos was positively correlated with EMAb and negatively correlated with age. There was no correlation between exophthalmos and TBII, TgAb or MsAb. In conclusion, although the pathogenesis of orbital changes and hyperthyroidism is different, a close link between these two entities is suggested by the high incidence of orbital changes in hyperthyroid Graves'disease. Extraocular muscle enlargement is related to EMAb. Although not related to TBII or definitely related to EMAb, increased orbital fat also plays a role in exophthalmos.
A DOUBLE‐BLIND STUDY COMPARING A NEW NON‐ERGOT, LONG‐ACTING DOPAMINE AGONIST, CV 205‐502, WITH BROMOCRIPTINE IN WOMEN WITH HYPERPROLACTINAEMIA
Authors: HOMBURG ROY , WEST CHRISTINE , BROWNELL JUDITH , JACOBS HOWARD S.
Published: March 2008

Twenty‐two hyperprolactinaemic women were randomly allocated to two groups and treated with bromocriptine or the new, non‐ergot, long‐acting dopamine agonist, CV 205‐502. The study was double‐blind for 6 months. Four patients in the bromocriptine group, but none in the CV 205‐502 group, discontinued the study because of adverse reactions. Adverse reactions in those receiving the new drug were milder and more transient than with bromocriptine. With once‐daily doses of 0.075 mg CV 205‐502, eight of 11 women achieved normal PRL concentrations after 8 weeks treatment (median (95% confidence limits), 352 (70‐987) mU/1) compared with two of nine receiving a divided daily dose of 5 mg bromocriptine (1802 (1205‐4438) mU/1) (P < 0.002). With doses of 0.075‐0.15 mg of CV 205‐502, 10 of 11 women achieved normal PRL concentrations at 24 weeks compared with three of the remaining seven women on doses of 5‐10 mg of bromocriptine. Regular menstrual bleeding was restored and galactorrhoea relieved in the majority of patients, with marginally greater efficacy with CV 205‐502. CV 205‐502 is highly effective for the long‐term treatment of hyperprolactinaemia. It is better tolerated than bromocriptine, is effective in a once‐daily dose, appears to be safe, and provides a valuable alternative to the dopamine agonist drugs in use today.
ESTIMATION OF INSTANTANEOUS SECRETORY RATE OF LUTEINIZING HORMONE IN WOMEN DURING THE MENSTRUAL CYCLE AND IN MEN
Authors: GENAZZANI A. D. , RODBARD D. , FORTI G. , PETRAGLIA F. , BARAGHINI G. F. , GENAZZANI A. R.
Published: March 2008

In both men and women the pulsatile secretory pattern of LH has been extensively characterized. In the present study we used the algorithm for computation of instantaneous secretory rate (ISR) incorporated into the DETECT program to evaluate the secretory activity of gonadotrophs in vivo. We studied the pulsatile release of LH in four healthy women during four phases of the same menstrual cycle (early and late follicular and luteal phases) and in five healthy men. Computation of ISR permitted us to estimate the frequency and the duration of the secretory events from the gonadotrophs. Samples were collected every 10 min for 6 h. The apparent LH pulsatile frequency during the menstrual cycle varied from 5.0±0.8 (mean±SD) during the early follicular phase (EFP) to 5.3±1.2 peaks/6h during the late follicular phase (LFP), to 3.3±1.0 during early luteal phase (ELP) and to 5.3±0.4 peaks/6h during the late luteal phase (LLP). The mean pulse duration also changed throughout the phases of the cycle (EFP 47.4±13‐2 min; LFP 55‐4±21.6 min; ELP 100±50.4 min; LLP 48.1±11 min). In healthy men the LH pulse frequency was 3.8±1.6 peaks/6h and the duration was 71‐5±35.7 min. When time series were analysed for ISR determination no significant changes were observed between the LH pulse frequency detected on ISR and that observed on plasma concentrations. Conversely, a significant reduction of the duration of the pulses was found when using ISR instead of plasma concentration. The mean pulse duration in ISR does not show any significant difference between men (22±10.3 min) and women in the four different phases of the cycle investigated (EFP = 25.2±12 min; LFP = 28±12 min; ELP = 21.6±11 min; LLP = 20±13 min). In conclusion these data suggest that the duration of the LH secretion by the gonadotrophs is not different in men and in women and implied that LH mass and the rate, but not the duration, of the secretory bursts are regulated by GnRH and that steroids affect LH pulsatile secretion by influencing the frequency and/or amplitude of the pulses.
NORMALIZATION OF THYROID BLOOD FLOW IN Graves'HYPERTHYROIDISM FOLLOWING RADIOACTIVE IODINE THERAPY
Authors: CHANG D. C. S. , WOODCOCK J. P. , SHEDDEN E. J. , LAZARUS J. H. , WHEELER M. H. , McGREGOR A. M.
Published: March 2008

In a group of 12 patients with Graves'hyperthyroidism, administration of 514±43 (mean±SD) MBq iodine‐131 was associated with a fall of superior thyroid artery (STA) blood flow in two at 6 months and in eight at 11 months. The reduction in time‐averaged velocity at 11 months correlated with the reduction in FT4 (r = 0.72, P < 0.01) and in FT3 (r = 0.64, P < 0.025) at this time. In four patients who had persistent elevated STA blood flow, two were still hyperthyroid. The diameter of the STA was unchanged at 6 months and only half the patients had reduction of their STA size at 11 months after radioiodine (RAI) therapy. These data indicate that normalization of STA blood flow precedes normalization of STA size in patients treated with RAI. Further work is required to determine whether STA blood flow measurements are of predictive value in treatment outcome.
SEXUAL PRECOCITY INDUCED BY OVARIAN FOLLICULAR CYSTS. IS AUTOIMMUNITY INVOLVED?
Authors: STOKVIS‐BRANTSMA W. H. , VAN WEISSENBRUCH M. M. , WIT J. M. , SCHOEMAKER J. , DREXHAGE H. A.
Published: March 2008

A 2‐year‐old girl presented with gonadotrophin‐independent precocious puberty due to ovarian follicles. Central precocious puberty was excluded by several GnRH‐tests and overnight LH sampling. There were no signs of McCune‐Albright syndrome. An ovarian tumour was excluded by laparotomy and biopsies. Abdominal sonography demonstrated follicles occurring mostly in the left, sometimes in the right, ovary. Immunoglobulin G (IgG) purified from the patient's serum was capable of stimulating DNA synthesis in granulosa cells of rat ovarian segments kept in organ culture. Since FSH had a similar in‐vitro action it is hypothesized that this patient's IgG mimics the action of FSH.
LH AND FSH SECRETION AND RESPONSES TO GnRH AND TRH IN PATIENTS WITH CLINICALLY FUNCTIONLESS PITUITARY ADENOMAS
Authors: WHITE M. C. , DANIELS M. , NEWLAND P. , THOMPSON C. J. , COOK D. , DEWAR J. , PERRY R. , JEWITT R. , MATHIAS D. , MURDOCH A. P. , KENDALL‐TAYLOR P.
Published: March 2008

Serum concentrations of LH and FSH and their response to the separate administration of GnRH (100 μg i. v.) and TRH (200 μg i. v.) have been studied preoperatively in 12 patients with a clinically functionless pituitary adenoma, of whom nine (3F:6M) were found to secrete gonadotrophins in vitro. In three patients with a gonadotrophin‐secreting adenoma (GSA) the pulsatile release of LH and FSH was also assessed preoperatively. An elevated serum FSH was recorded in six of nine patients with a GSA, and was subnormal in one, whilst an elevated LH was recorded in only two and was subnormal in six. A doubling of LH occurred in only four of the nine patients after GnRH and in three of six after TRH. None of the three patients with a non‐GSA was shown to have an aberrant response to GnRH or TRH. In patients with a GSA, pulsatile release of LH and FSH was usually asynchronous and neither hormone demonstrated any regular harmonic pattern. These data show that in patients with a GSA the serum FSH level is usually elevated but this is not invariable, and the LH may well be low. Pathological responses of LH are frequently found following the administration of either GnRH or TRH and these stimulation tests should be performed separately in patients presenting with a clinically‘non‐functioning’pituitary tumour to assist in the preoperative diagnosis. The absence of normal LH and FSH pulsing also appears to be a feature of GS adenomas, and suggests that tumorous gonadotrophin secretion is not under physiological control by hypothalamic GnRH.
CYTOFLUOROMETRIC ANALYSIS OF LYMPHOCYTE SUBSETS IN THYROID ASPIRATES FROM PATIENTS WITH AUTONOMOUSLY FUNCTIONING NODULE*
Authors: FARSETTI A. , PONTECORVI A. , ANTONOZZI I. , ANDREOLI M. , GAETANO C.
Published: March 2008

A microscale method, based on two‐colour dye immunolabelling and flow sorting cytofluorometry, was used to characterize lymphocyte subsets in thyroid tissue specimens obtained by fine‐needle aspiration (FNA) in 21 patients with autonomously functioning thyroid nodule (AFTN) and five patients with cold thyroid nodule (CTN). Inversion of the ratio between CD4+ and CD8+ lymphocytes, due to a relative increase of CD8+ cells, was found among intrathyroidal lymphocytes in AFTN patients. The abnormal lymphocyte subset distribution was not observed in the peripheral blood of the same group of patients. In patients with CTN the lymphocyte subset distribution was normal, both in the thyroid and in the peripheral blood. In AFTN patients, a significant correlation was observed between the decrease of intrathyroidal CD4+/CD8+ ratio and the increase of plasma thyroid hormone levels. Whether the immunological abnormalities found in AFTN could play a pathogenetic role in the clinical presentation and outcome of the disease remains to be established. The FNA‐applied micromethod used in this study could be extended as a routine investigation to characterize the immunogenic substrate of thyroid disorders.
PROLACTIN SECRETION IN WOMEN DURING THE OESTRADIOL‐INDUCED LUTEINIZING HORMONE SURGE WITH OR WITHOUT PROGESTERONE
Authors: MESSINIS I. E. , TEMPLETON A. A.
Published: March 2008

To study the role of progesterone (P4) in the control of PRL increase during the midcycle LH surge, eight normally ovulating women were treated with i. m. injections of oeštradiol benzoate (E2B) every 12h during the early follicular phase of two different cycles (from cycle days 2 to 4). In the second cycle P4 injections were also given to the women every 12 h starting at the end of the E2B treatment (from cycle days 4 to 6). Circadian periodicity of serum PRL levels during the E2‐induced LH surge did not differ significantly between the E2B and the E2B + P4 experiments. Evening PRL levels increased significantly in both experiments with a peak during the LH surge and no significant difference between them. We conclude that administration of P4 to normal women does not alter the increase in PRL secretion during the LH surge induced by exogenous oestrogen. It is suggested that P4 is not involved in the mechanism controlling midcycle PRL secretion.
METABOLIC EFFECTS OF AN INSULIN‐LIKE FACTOR CAUSING HYPOGLYCAEMIA IN A PATIENT WITH A HAEMANGIOPERICYTOMA
Authors: BENN J. J. , FIRTH R. G. R. , SÖNKSEN P. H.
Published: March 2008

We have studied a patient with fasting hypoglycaemia and skin lesions (sign of Leser‐Trélat) related to a retroperitoneal haemangiopericytoma in whom removal of the tumour resulted in immediate cure of hypoglycaemia. Before removal of the tumour, severe fasting hypoglycaemia was associated with undetectable insulin and C‐peptide levels. She required 16.9 μmol/kg/min (10.4 g/h) of glucose intravenously to prevent hypoglycaemia and endogenous glucose production (measured using tritiated glucose) was suppressed to 1.3 μmol/kg/min while the whole‐body glucose utilization rate was elevated at 18.2 μmol/kg/min. After removal of the tumour both endogenous glucose production rate and utilization rate returned to normal (11‐5 μmol/kg/min). Resting energy expenditure, measured by indirect calorimetry, was markedly elevated at 2109 kcal/day (161% of predicted) and fell to 1205 (97% of predicted) after the tumour was removed. Glucose oxidation was also enhanced at 8.5 μmol/kg/min and fell to 3‐3 μmol/kg/min after removal of the tumour. Other metabolites and hormones measured, and their response to oral glucose, were all consistent with the presence of a circulating substance with similar properties to insulin. We conclude that her hypoglycaemia resulted primarily from suppression of endogenous glucose production but also from enhanced glucose utilization. These effects were the result of a circulating growth factor sharing many metabolic effects with insulin, but with a much greater effect on resting energy expenditure and glucose oxidation.
COLON CANCER AND POLYPS IN ACROMEGALY: INCREASED RISK ASSOCIATED WITH FAMILY HISTORY OF COLON CANCER
Authors: BRUNNER JOHN E. , JOHNSON CHRISTINE COLE , ZAFAR SAEED , PETERSON EDWARD L. , BRUNNER JOHN F. , MELLINGER RAYMOND C.
Published: March 2008

A cohort of 52 subjects diagnosed with acromegaly in southeastern Michigan and northern Ohio between 1935 and 1985 were followed to determine the incidence of colon cancer and polyps. Medical records were reviewed, subjects or their next‐of‐kin were interviewed, and screening examinations of the colon were offered to the living patients who were located. Data on demographics, personal histories of cancer and colon polyps, family history of colon cancer, and cure from acromegaly were obtained for both living and deceased subjects. The risk for colon cancer compared to the general population was estimated using standardized incidence ratios (SIRs). The expected number of cases was determined utilizing age, sex and race‐specific rates provided by the cancer registry in southeastern Michigan. Among the 52 subjects, one could not be located and nine were deceased, none from colon cancer, with one known to have a history of colon polyps. Of 13 (31 %) who declined the screening physical, one had a history of polyps and none reported a history of colon cancer. Two of 29 screened patients were found to have right‐sided adenocarcinoma of the colon. Of the entire cohort, eight people (including one deceased) had a current or previous diagnosis of polyps, with five known to be histologically adenomatous. The SIR for colon cancer was 4.7 (95% confidence interval 0.6–17.1). Seven subjects, including the two with detected adenocarcinoma and four of the six living subjects with polyps only, reported a family history of colon cancer. The SIR for the subset of subjects with a family history of colon cancer was 29.1 (95% confidence interval of 3.5–104.6). Logistic regression analysis of the subset of the acromegalic cohort that was screened demonstrated that family history of colon cancer and male gender were predictive of the presence of colonic neoplasms at P< 0.001 and P< 0.009, respectively. This study supports the association between acromegaly and colon cancer reported by others and suggests that an increased risk of colon cancer in these patients may be associated with a family history of colon cancer. We recommend that patients with acromegaly routinely undergo colon cancer screening, particularly those with a positive family history for colon malignancies.
TESTOSTERONE REDUCES THE BIOACTIVITY OF LUTEINIZING HORMONE (LH) IN MAN
Authors: TSATSOULIS A. , SHALET S. M. , RICHARDSON P. , ROBERTSON W. R.
Published: March 2008

The effect of testosterone on LH bioactivity was investigated in six adult men (aged 40–56 years) with primary hypogonadism. Two men received a 400 mg testosterone implant, another two 800 mg, and the final two patients received both doses in consecutive courses separated by at least 4 weeks. Plasma samples, obtained before and at 1,2,4,8,16 and 24 weeks after treatment, were analysed for bioactive LH by the mouse Leydig cell bioassay, and immunoreactive LH and testosterone (T) by standard radioimmunoassays. The bioactive to immunoreactive (B: I) LH ratio, an index of LH biopotency, was calculated and the results compared with those from a group (n= 17) of healthy adult men. Before treatment, both bioactive and immunoreactive LH levels in the patients were higher and T levels lower than in the normal men (P< 0.0001). The mean ± SD B: I LH ratio (3.5 ± 0.6) in the patients was greater (P <005) than in the controls (2.7±0.7), indicating that in primary testicular failure, increased amounts of LH with enhanced bioactivity are secreted. Following T administration, a dose‐related increase in circulating T and a reciprocal decrease in LH levels was observed between 1 and 16 weeks of treatment. However, there was a more pronounced decline in bioactive rather than immunoreactive LH levels, so that the B:I LH ratios decreased (P<0.001) from basal values after treatment. There was a negative correlation (r=−0.82, P<0.001) between circulatingT levels and B: I LH ratios; the stronger the feedback signal, the lower the B: I LH ratio. It is concluded that testosterone negative feedback modifies not only the quantity but also the biological quality of secreted LH.
PLASMA CORTICOTROPHIN‐RELEASING FACTOR AND VASOPRESSIN RESPONSES TO HYPOGLYCAEMIA IN NORMAL MAN
Authors: ELLIS M. J. , SCHMIDLI R. S. , DONALD R. A. , LIVESEY J. H. , ESPINER E. A.
Published: March 2008

The plasma Cortisol, ACTH, AVP and corticotrophin‐releasing factor (CRF) responses to insulin‐induced hypoglycaemia were investigated in six normal men using a controlled, randomized, cross‐over design. Hormonal concentrations were determined following insulin or saline injection. The maximum Cortisol response was seen at 90 min while plasma ACTH, AVP and CRF concentrations peaked at 45 min following insulin injection. The responses of the insulin‐treated and control groups were compared by assessing the incremental response from baseline (pre‐injection) to peak hormone levels. A significant increase was observed for each hormone following insulin injection. The mean of the incremental responses between 30 and 120 min in each subject was also statistically greater for each hormone in the insulin‐treated group when compared with the control group. These results are consistent with the hypothesis that AVP and CRF are both physiological mediators of ACTH secretion induced by a hypoglycaemic stress.
Thyroxine replacement in post‐radioiodine hypothyroidism
Authors: Bearcroft C. P. , Toms G. C. , Williams S. J. , Noonan K. , Monson J. P.
Published: March 2008

Thyroxine replacement dose in 70 patients with postradioiodine (for Graves’ thyrotoxicosis) hypothyroidism was compared with that in 34 patients with autoimmune hypothyroidism matched for age and sex and diagnosed during the same period. Median replacement dose In the post‐radlolodine group (100 μg daily) was significantly lower (P = 0·006) than in the autoimmune hypothyroid group (137·5 μg daily). Furthermore there was marked variation in the time elapsing from onset of post–radio‐Iodine hypothyroidism to achievement of a given maintenance dose. These findings may be explained by persistence of non–TSH mediated thyroid function, after radioiodine therapy for Graves’ thyrotoxicosis. The observations indicate the potential risk of overtreatment'with thyroxine In post‐radioiodine hypothyroidism unless the dose is carefully titrated against serum TSH levels. Final thyroxine requirements may not be evident in the initial phase of treatment and patients with apparently low maintenance thyroxine requirements require long‐term follow up
The diagnosis of polycystic ovaries in women with oligo‐amenorrhoea: predictive power of endocrine tests
Authors: Fox Robert , Corrigan Elizabeth , Thomas Paul A. , Hull Michael G. R.
Published: March 2008

The ability of several endocrine tests to distinguish between women with and without polycystic ovaries (PCO) has been studied prospectively in a series of 65 patients with functional oligo‐amenorrhoea using ultrasonography as a reference test. In terms of overall diagnostic accuracy, the free androgen Index (FAI) (94%) and the progestogen challenge (89%) gave similar results (CI =–5 to 15%) but both were significantly better than all the other tests including measurement of serum LH (69%), total testosterone (71%) and androstenedlone (74%) (minimum CI = 6 to 23%). The FAI together with LH measurement was the most accurate of the combinations (97%) but this was not significantly better than the best of the combinations Incorporating the progestogen challenge (92%; CI =–3% to 13%). Given the limited availability of the assay for SHBG, these results show that assessment of oestrogen state is a useful method for categorizing patients with functional oligo‐amenorrhoea
High permanent plasma adrenaline levels: a marker of adrenal medullary disease in medullary thyroid carcinoma
Authors: Visteile R. , Grulet H. , Gibold C. , Chaufour‐Higel B. , Delemer B. , Fay R. , Delisie M. J. , Caron J.
Published: March 2008

Increases in urinary, plasma and tumour adrenaline have been previously observed In MEN II patients with phaeochromocytoma. However, the sensitivity of adrenaline for early detection of adrenal medullary disease has not been accurately evaluated. Twenty‐five patients with medullary thyroid carcinoma (MTC) histologically confirmed but without clinical or biological evidence of phaeochromocytoma have been studied. Medullary adrenal status was evaluated by adrenal CT‐scan. MIBG scintigraphy, determination of urinary VMA, metanephrines and total catecholamine levels, measurement of nyctohemeral plasma adrenaline or noradrenaline concentrations (every 2 h during 24 h) and clonidine suppression test. Four of the 25 patients had evidence of adrenal medullary disease In view of the coexistence of CT‐scan, MIBG scintigraphy and plasma adrenaline abnormalities. Moderate adrenal enlargement (unilateral, n= 3; bilateral, n= 1) was observed on scans together with a high adrenal MIBG uptake (bilateral, n= 4). Among the urinary parameters studied, a minor MN increase was observed In only one of the four patients. Plasma adrenaline levels were significantly (P > 0·01) different from those of the other 21 patients (mean + SD 115 + 110 pmol/I). This plasma adrenaline increase is reproducible and not suppressed by clonidine. Unilateral adrenalectomy performed in one patient confirmed a phaeochromocytoma and induced normalization of plasma adrenaline levels. In contrast, the plasma noradrenaline levels of the four patients were not statistically different from those of the other 21 patients. These data suggest that persistent high plasma adrenaline levels may be selectively increased in MTC patients together with a moderate adrenal CT‐scan enlargement and a high adrenal MIBG uptake, despite a normal urinary excretion of total catecholamines and catecholamines metabolites. These preliminary results allow us to propose that the determination of plasma free adrenaline concentrations be used for the early detection of adrenal medullary disease.
Withdrawal of bromocriptine after long‐term therapy for macroprolactinomas; effect on plasma prolactin and tumour size
Authors: Van't Verlaat Johanna W. , Croughs Ronald J. M.
Published: March 2008

The present study describes the effect on plasma prolactin values and tumour size of bromocrlptine withdrawal in 12 patients who had been treated for macroprolactinomas for a period of 3·5–7 (mean 4·9) years. Pretreatment plasma prolactin values ranged from 12000 to 210000 (mean: 66000) mU/I. Immediately before bromocriptine withdrawal plasma prolactin values were In the normal range (> 350 mU/I for men; > 450 mU/I for women). Bromocriptine treatment was associated with tumour reduction in all cases. The following observations were made upon withdrawal of bromocrlptlne:

(1) In 11 patients hyperprolactinaemia redeveloped although plasma prolactin levels remained below 600 mU/I In two of these patients during a follow‐up period of 1 year. In the other nine patients bromocriptine treatment was reinstituted after 4–12 weeks

(2) Hyperprolactinaemla was associated with tumour re‐expansion In one case and Increased density of the tumour in two cases

(3) In one patient plasma prolactin remained undetectable during a follow‐up period of 1 year and no tumour re‐expansion was found

It Is concluded that tumour regrowth is uncommon and of small extent after cessation of long‐term bromocriptine treatment for macroprolactinomas
Role of peripherally infused angiotensin II on the human hypothalamic–pituitary–adrenal axis
Authors: Calogero Aldo E. , Fornito Marla C. , Aiiffl Antonia , Vicarl Enzo , Moncada Marla L. , Mantero Franco , Polosa Pietro , D'Agata Rosario
Published: March 2008

Although angiotensin II (All), a potent vasoconstrictor agent, has been reported to stimulate the hypothalamicpituitary‐adrenal (HPA) axis of laboratory animals, Its role In the regulation of this axis In humans appears to be controversial. To examine this question, All (Val5‐All amide) was Infused Intravenously Into 19 male normal volunteers at the doses of 0, 1, 3·3 and 10 ng/kg/mln for 30 min. All had no effect on plasma ACTH, cortical, corticotrophin‐releasing hormone, arginine vasopressin, and atrial natriuretic factor concentrations, nor did it increase systolic or diastolic arterial blood pressure. On the other hand, All caused a dose‐dependent Increase of plasma aldosterone concentrations, suggesting that the doses and the mode of All Infusion were effective. Thus, our data show that peripherally Infused All has no detectable effect on the HPA axis function in humans, at doses capable of stimulating plasma aldosterone secretion, Its specific target hormone

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Induction of c‐fos and c‐myc mRNA expression by immunoglobulin G from patients with Graves’ disease in thyrotrophin‐dependent rat thyroid cell line (FRTL5)
Authors: Hatabu H. , Kasagl K. , Lida Y. , Nosaka T. , Misaki T. , Hidaka A. , Tokuda Y. , Endo K. , Mori T. , Lee K. , Tsubol K. , Hatanaka M. , Konishl J.
Published: March 2008

The present study was conducted to evaluate effects of autoantlbodles In patients with Graves’ disease on Induction of c‐fos and c‐myc mRNA expression In rat thyroid cell line (FRTL5). IgG fractions were Isolated from 11 patients with Graves’ disease, and six healthy subjects, with protein A‐Sepharose. FRTL5 cells which had been grown to subconfluency and deprived of TSH for a week were exposed to the IgG for an hour. Expression of c‐fos and c‐myc mRNAs was examined by the Northern blot method using nick‐translated v‐fos and c‐myc probes. C‐fos and c‐myc transcripts were Induced by IgGs from two patients with Graves’ disease, which displayed much higher activities In assays for TSH binding Inhibitor Immuno‐globullns, thyroid stimulating antibodies and thyroid growth‐stimulating Immunoglobullns, assessed by measuring Inhibition of 125I‐TSH binding to the TSH‐receptor, cAMP production and 3H‐thymldine Incorporation In FRTL5 cells, respectively, compared with those In the remaining patients. The Induction of c‐fos and c‐myc mRNAs by IgG from a patient with Graves’ disease was suppressed by prelncubatlon with IgGs from two patients with primary myxoedema who were known to have a blocking type TSH‐receptor antibody. These data suggest that the binding of the antibodies to the TSH–receptor followed by cAMP production Is related to the induction of c‐fos and c‐myc mRNAs and, thus, to the growth of FRTL5 cells. To our knowledge, this Is the first report demonstrating that autoantibodies Induce proto‐oncogene mRNA expression.