bluuebunny/crossref_metadata_2025 huggingface dataset:
NEUROPEPTIDE Y IN MULTIPLE ENDOCRINE NEOPLASIA: RELEASE DURING SURGERY FOR PHAEOCHROMOCYTOMA
Authors: CONNELL J. M. C. , CORDER R. , ASBURY J. , MACPHERSON S. , INGLIS G. C. , LOWRY P. , BURT A. D. , SEMPLE P. F.
Published: March 2008

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal <3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak =1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50‐fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.
THE EFFECT OF SUBTOTAL THYROIDECTOMY WITH PROPRANOLOL PREPARATION ON ANTIBODY ACTIVITY IN GRAVES' DISEASE
Authors: STEEL N. R. , TAYLOR J. J. , YOUNG E. T. , FARNDON J. R. , HOLCOMBE M. , KENDALL‐TAYLOR P.
Published: March 2008

The effect of subtotal thyroidectomy on thyroid stimulating antibodies (TSAb), thyrotrophin binding inhibitory immunoglobulins (TBII) and antimicrosomal antibodies (MsAb) was studied in 26 patients with Graves' hyperthyroidism treated pre‐operatively with propranolol, but without antithyroid drugs. Following surgery, two patients relapsed in the first year and eight patients became hypothyroid. Eighteen patients (69%) had detectable TSAb at entry and no significant change in titre was seen during propranolol therapy. Following surgery TSAb levels fell within 24 h in eight patients, and at 6 weeks only seven patients had detectable TSAb. TSAb were still detectable in seven patients at 6 months. TSAb activity did not predict the late relapses. TBII were present in 13 patients (50%) before surgery and titres remained unchanged in all but two patients during the immediate postoperative period. At 6 weeks TBII had disappeared from the serum of only three patients. During the early postoperative period TBII became transiently detectable in five of the 13 patients initially TBII negative. The two patients who subsequently relapsed remained TBII positive throughout. Microsomal antibodies were present in the sera of 22 patients (85%). Surgery was followed by a decline in titre, which was substantial in only six of 13 patients studied in detail. Thus, in 92% patients hyperthyroidism was successfully eradicated. Propranolol treatment had no effect on antibody activity. TSAb and TBII disappeared from the circulation in 61 % and 46% patients, respectively. These data are compatible with the concept that lymphocytes within the thyroid are the major site of TSAb production but other important sites for synthesis of thyroidal autoantibodies probably exist. Although outcome from surgery could not be accurately predicted from TSAb or TBII status either pre‐ or post‐operatively, the two patients who relapsed had the most severe disturbances of thyroid autoimmunity; all patients in whom initially detectable TSAb or TBII disappeared remained in remission.
INAPPROPRIATE ACTH CONCENTRATIONS IN TWO PATIENTS WITH FUNCTIONING ADRENOCORTICAL CARCINOMA
Authors: LAW A. , HAGUE W. M. , DALY J. G. , HONOUR J. W. , TAYLOR N. , JEFFCOATE S. L. , HIMSWORTH R. L. , JOPLIN G. F.
Published: March 2008

Two female patients with functioning adrenocortical carcinomas had plasma ACTH detectable by RIA at presentation. In both patients there was evidence for biological activity of ACTH. There was no evidence for an ectopic source of ACTH, nor for a pituitary tumour. Urinary steroid analysis showed patterns of multiple hormone secretion characteristic of adrenocortical carcinomas. The finding of detectable ACTH concentrations in a patient with Cushing's syndrome does not exclude the presence of an adrenocortical tumour.
A DOUBLE‐BLIND CROSS‐OVER 12‐MONTH STUDY OF l‐THYROXINE TREATMENT OF WOMEN WITH ‘SUBCLINICAL’ HYPOTHYROIDISM
Authors: NYSTRÖM E. , CAIDAHL K. , FAGER G. , WIKKELSÖ C. , LUNDBERG P.‐A. , LINDSTEDT G.
Published: March 2008

Twenty women, who had been randomly selected from women with subclinical hypothyroidism identified in a population study were treated with l‐thyroxine and placebo in a double‐blind cross‐over design during 2·6 months. Three women did not complete the study, one because she moved to another part of the country, and two because of nervousness and sense of tachycardia. None of these ‘drop‐outs’ had any objective signs of overtreatment; they had normal pulse rate and a serum T3 concentration within the reference interval. During l‐thyroxine treatment serum procollagen‐III‐peptide concentration increased in 13 women out of the 17 women completing the study and at the end of treatment the mean concentration was significantly raised (P>0·001). Serum concentrations of procollagen‐III‐peptide then correlated with those of free thyroxine (P>0·01), total thyroxine (P>0·05), and reverse triiodothyronine (P>0·05). The same comparison revealed little or no effect on the concentrations of serum creatine kinase activity, transcortin or sex‐hormone binding globulin. Heart rate‐corrected preejection period and symptom score decreased (P>0·05). Four women starting with l‐thyroxine showed a marked and prolonged (4–6 months) rise in thyrotrophin concentration during the subsequent placebo period, but remained clinically euthyroid. Four women (of 17) improved during therapy as judged by psychometric testing and their own rating. We could not by pretreatment observations identify these four women apart from serum free and total 3,5,3′‐triiodothyronine concentrations in the lower part of the health‐associated reference interval. Subclinical hypothyroidism is common among middle‐aged and old women, and our findings indicate that approximately one woman in four with this ‘subclinical’ condition will benefit from L‐thyroxine treatment.
GROWTH AND GROWTH HORMONE RESPONSES TO OXANDROLONE IN BOYS WITH CONSTITUTIONAL DELAY OF GROWTH AND PUBERTY (CDGP)
Authors: CLAYTON P. E. , SHALET S. M. , PRICE D. A. , ADDISON G. M.
Published: March 2008

Thirteen boys with constitutional delay in growth and/or development aged 7.6 to 16 years received 2.5mg/day of oxandrolone for 3 months. Their growth response on treatment and in the subsequent 3 months was compared to that of 14 age‐matched untreated controls. Growth rates were analysed in groups arbitrarily defined by testicular volume at entry (>4ml prepubertal, >4ml pubertal). Growth velocities increased on oxandrolone (prepubertal, mean 4.4 to 7.5cm/year, P = 0.05: pubertal, mean 4.7 to 8cm/year, p>0.05). Over the next 3 months, the pubertal boys grew at 9.3cm/year, while the prepubertal group decelerated to 6.2cm/year. Both control groups showed no significant change in velocity over 6 months. GH responses to arginine and GRF, and to sleep in prepubertal boys, were unchanged throughout the study. However, in pubertal boys the mean GH levels (‘area under the curve’) during sleep at 3 and 6 months, had increased over baseline values, associated with a significant increase at 6 months in basal somatomedin‐C (140 to 214ng/ml, p>0.05). Oxandrolone does not alter the GH status of prepubertal boys, and thus probably promotes growth by a direct action at the growth plate. In contrast, the persistent growth acceleration of pubertal boys may be associated with increased GH and somatomedin‐C levels: in this group, oxandrolone has proved a useful stimulus to growth.
ANOMALIES IN THE ASSAY OF PARATHYROID HORMONE IN NORMOCALCAEMIC PATIENTS WITH RENAL STONE DISEASE
Authors: ASHBY J. P. , LOVERIDGE N. , BROWN R. C. , ZANELLI J. M. , RINSLER M. G. , WATTS R. W. E.
Published: March 2008

A group of 22 normocalcaemic patients with renal stone disease were retrospectively studied using seven different immunoassays for parathyroid hormone (PTH). N‐terminal immunoradiometric assays and an intact hormone immunochemiluminometric assay sometimes gave results which fell above the normal range. These results were at variance with values obtained in three region‐specific radioimmunoassays and an immunoradiometric assay for the intact hormone. Since these atypical samples contained normal levels of biologically active PTH the elevated immunoassay results were not thought to relate to the normal circulating hormone but rather to interference in the immunometric assays. The interfering substance was thought to be a large molecule which could not be removed by charcoal and did not dilute out in parallel to the PTH standard curve.
CRF IN THE DIFFERENTIAL DIAGNOSIS OF CUSHING'S SYNDROME: A COMPARISON WITH THE DEXAMETHASONE SUPPRESSION TEST
Authors: GROSSMAN A. B. , HOWLETT T. A. , PERRY L. , COY D. H. , SAVAGE M. O. , LAVENDER P. , REES L. H. , BESSER G. M.
Published: March 2008

Accurate differential diagnosis of the precise cause of Cushing's syndrome can be difficult, and conventional tests such as those based on the use of dexamethasone may be misleading. We have therefore studied the cortisol and ACTH responses to ovine corticotrophin‐releasing factor (CRF‐41) in 28 consecutive patients with Cushing's syndrome, and compared the diagnostic value of this test with that of the high‐dose dexamethasone suppression test (8 mg/day for 48 h).

Of 20 patients with confirmed Cushing's disease (pituitary‐dependent Cushing's syndrome), only 16 (80%) showed the expected 50% or more suppression of serum cortisol following high‐dose dexamethasone administration. Four patients each with adrenal adenomas and three patients with the ectopic ACTH syndrome failed to suppress, while a child with probable Cushing's disease showed a variable response depending on the dose used. Following CRF stimulation, 15 out of the 20 patients (75%) with Cushing's disease showed an excessive rise in serum cortisol, outside the normal range, while in five the response to CRF‐41 was normal on at least one occasion. None of the patients with adrenal adenomas or the ectopic ACTH syndrome showed a cortisol response to CRF. Thus, either test on its own may be misleading in differentiating Cushing's disease from other causes of the syndrome. Every patient with Cushing's disease, however, showed either suppression in response to high‐dose dexamethasone or an excessive cortisol response to CRF testing. It appears, therefore, that the combination of the high‐dose dexamethasone and the CRF test, with measurement of serum cortisol, is superior to either test alone in the differential diagnosis of Cushing's syndrome.
LACK OF EFFECT OF ALDOSTERONE ON INTRACELLULAR SODIUM AND POTASSIUM IN MONONUCLEAR LEUCOCYTES FROM PATIENTS WITH PSEUDOHYPOALDOSTERONISM
Authors: WEHLING M. , KUHNLE U. , WITZGALL H. , WEBER P. C. , ARMANINI D.
Published: March 2008

In three patients with pseudohypoaldosteronism the effects of aldosterone on intracellular sodium and potassium were studied and compared with normal controls in whom aldosterone prevents the loss of sodium and potassium in vitro. Mononuclear leukocytes were incubated with or without aldosterone (1.4 n M) in RPMI‐1640 for 1 h at 37°C. After two washes in isotonic MgCl2 the wet cell pellets were weighted and intracellular sodium and potassium determined by flame photometry, results are expressed as mmol/kg wet cells. In the patients intracellular sodium fell from 18,23 and 29 mmol/kg to 14,18 and 11 mmol/kg, respectively, in the absence of aldosterone. With aldosterone added to the incubation medium sodium was not different from values obtained without aldosterone (15,20 and 13 mmol/kg). Corresponding values for potassium were 89, 48 and 75 mmol/kg before and 68, 32 and 51 mmol/kg after incubation without and 69, 36 and 54 mmol/kg after incubation with aldosterone. Thus, incubation with aldosterone did not show an effect on intracellular sodium and potassium as seen in normals. Baseline values of sodium and potassium before the incubation were within the normal range. From these results it is concluded that in patients with pseudohypoaldosteronism the absent or decreased number of mineralocorticoid receptors in mononuclear leucocytes are accompanied by a lack of response of intracellular sodium and potassium to aldosterone in vitro. However, normal baseline intracellular electrolyte concentrations in these patients may indicate that mineralocorticoids are not involved in the maintenance of normal levels of intracellular sodium and potassium.
EPISODIC PULSATILE SECRETION OF FSH, LH, PROLACTIN, OESTRADIOL, OESTRONE, AND LH CIRCADIAN VARIATIONS IN POLYCYSTIC OVARY SYNDROME
Authors: VENTUROLI S. , PORCU E. , FABBRI R. , MAGRINI O. , GAMMI L. , PARADISI R. , FORCACCI M. , BOLZANI R. , FLAMIGNI C.
Published: March 2008

Pulsatile secretion of LH, FSH, PRL, oestradiol and oestrone was studied in a group of 16 patients with micropolycystic ovary syndrome (PCOS) and compared with that of normal ovulatory women in the fifth to sixth day of the cycle. Hormone concentrations were measured at 10 min intervals for 8 h starting at 0930 h. In seven subjects, the study was prolonged for 24 h, with 20 min interval samples, in an attempt to evaluate the circadian rhythm of LH by cosinor analysis. Significant fluctuations occurred in the concentration of each hormone. Values shown are mean ± SD. PCOS subjects had high LH mean values (27.9 ± 5.9 IU/1) (P< 0.005). LH pulse amplitude was higher than controls (11 6 ± 3.7 IU/1 versus 5.2 ± 1.8 IU/1; P<0.005) while no consistent changes in frequency or interpulse interval (62.0±10.7 min versus 65.8 ± 19.2 min; P= NS) were found. A mean of 4.8 ± 1.2 pulses of FSH occurred in 8 h and the mean pulse amplitude was 2.68 ± 1.11 with no differences from controls. All patients were normoprolactinaemic. A mean of 5.5 ± 1.9 pulses occurred in 8 h, the interpulse interval was 76.1 ± 14.4 min and the amplitude was 2.87 ± 0.76 ng/ml and there were no significant differences from controls; 75% of PRL pulses showed a temporal relationship with LH pulses. Oestrone mean basal values were higher in PCOS (47.2 ± 12.5 pg/ml) than controls (32.0 ± 9.9 pg/ml; P<002), while no differences were observed as regards oestradiol. Oestradiol pulse amplitude was nearly the same as oestrone (43.6 ± 18.8 pg/ml and 37.7 ± 16‐1 pg/ml, respectively); 6‐0 ± 2.2 pulses and 6.0 ± 1.6 pulses occurred in 8 h with an interpulse interval of 81.1 ± 27.1 min and 71.8 ± 11.1 min, respectively. Sixty‐five per cent of LH pulses were followed by an oestradiol and oestrone peak. The mean time of the appearance was 17 ± 15 min and 25 ± 23 min, respectively. In the PCOS group a consistent 24 h rhythm in mean plasma
LUTEINIZING HORMONE RESPONSE TO DOMPERIDONE IN HYPERPROLACTINAEMIC WOMEN WITH PITUITARY MICROADENOMAS
Authors: SEKI K. , KATO K.
Published: March 2008

Administration of a dopamine (DA) antagonist, domperidone, increased circulating levels of LH in hyprolactinaemic‐amenorrhoeic women with pituitary microadenomas but not in normal women in the early follicular phase of the menstrual cycle. This drug does not readily cross the blood‐brain barrier and therefore the site of action of domperidone could be the pituitary gland or the median eminence. As the simultaneous administration of GnRH and domperidone did not increase the GnRH‐induced LH release in hyperprolacti‐naemic women, the site of action of domperidone is likely to be the median eminence.
SELECTIVE BILATERAL AND SIMULTANEOUS CATHETERIZATION OF THE INFERIOR PETROSAL SINUS: CRF STIMULATES PROLACTIN SECRETION FROM ACTH‐PRODUCING MICROADENOMAS IN CUSHING'S DISEASE
Authors: SCHULTE H. M. , ALLOLIO B. , GUNTHER R. W. , BENKER G. , WINKELMANN W. , OHNHAUS E. E. , REINWEIN D.
Published: March 2008

Bilateral, selective and simultaneous catheterization of the inferior petrosal sinus with measurements of ACTH after stimulation with ovine corticotrophin‐releasing factor (CRF) is now frequently used to establish the differential diagnosis in patients with Cushing's disease and to determine the side of the microadenoma in the pituitary. To investigate whether CRF has any effect on other pituitary hormones, we also determined prolactin (PRL) concentrations in the samples obtained during this procedure. Fourteen patients under evaluation for Cushing's syndrome and one patient with a hormonally inactive pituitary tumour were catheterized. Baseline PRL levels in the peripheral veins were within the normal range before and after CRF in all patients (3 ‐7‐16‐0 ng/ml). In 10 patients ACTH‐ and PRL concentrations lateralized to one side of the pituitary and could both be stimulated by CRF. The gradient of PRL between inferior petrosal sinus and periphery ranged from 7 to 147 ng/ml after CRF. There was no correlation between ACTH and prolactin increase in response to CRF. In three patients with no ACTH‐gradient but a positive response to CRF, no tumours could be found during transsphenoidal surgery; they had no PRL‐gradient and showed no PRL response to CRF. One patient with the ectopic ACTH syndrome had no ACTH‐ and no PRL response to CRF. The patient with the inactive pituitary tumour showed a normal ACTH‐, but no PRL response to CRF. These data demonstrate for the first time that in normo‐prolactinaemic patients with Cushing's disease, in contrast to patients bearing no microadenoma, PRL is secreted in response to CRF. This constant feature in all patients with pituitary Cushing's disease suggests that in the source of prolactin is the microadenoma and might prove useful clinically in interpreting equivocal ACTH‐gradients during this procedure.
TSH DEPENDENT ELEVATION OF SERUM THYROGLOBULIN IN REVERSIBLE PRIMARY HYPOTHYROIDISM
Authors: SATO K. , OKAMURA K. , IKENOUE H. , SHIROOZU A. , YOSHINARI M. , FUJISHIMA M.
Published: March 2008

Serum levels of thyroglobulin (Tg) were measured using immunoradiometric assay in 18 patients with primary hypothyroidism, whose serum levels of thyroid stimulating hormone (TSH) were higher than 40 mU/1 and anti‐Tg antibodies were negative. In 12 patients, serum Tg levels were extremely elevated above the upper limit of normal (30 ng/ml) and the levels were more than 800 ng/ml in 10 of them. In all of these 12 patients, thyroid function recovered spontaneously with only iodide restriction and the serum Tg levels declined concomitantly with the decrease in serum TSH concentrations, events suggesting the TSH dependency of this Tg elevation. In the other 6 patients without elevated Tg levels, thyroid function did not recover and replacement therapy with l‐thyroxine had to be given. Data from our study show that the TSH dependent Tg secretion is observed in reversible type primary hypothyroidism and that it may proceed vigorously even though thyroid hormone production is subnormal. Measurement of serum Tg may be valuable for predicting the prognosis of primary hypothyroidism.
LONG‐TERM TREATMENT WITH A NEW NON‐ERGOT LONG‐ACTING DOPAMINE AGONIST, CV 205‐502, IN WOMEN WITH HYPERPROLACTINAEMIA
Authors: RASMUSSEN CARSTEN , BERGH TORBJÖRN , WIDE LEIF , BROWNELL JUDITH
Published: March 2008

Twenty‐four hyperprolactinaemic women were treated for 6 months with the new, non‐ergot, long‐acting dopamine agonist, CV 205‐502. The treatment resulted in normalization of PRL secretion in 17 of the 24 women at once‐daily doses of 005 to 0‐15 mg of the drug. Sixteen of these women as well as 4 of those who remained hyperprolactinaemic had regular menstrual bleeding. Five of the patients had previously discontinued bromocriptine therapy because of adverse effects but had no problems tolerating CV 205‐502. Of three bromocriptine‐resistant women, two responded partially while one also remained unresponsive to CV 205‐502 treatment. Mild to moderate galactorrhoea was recorded at baseline in 19 of the 24 women. After 6 months’treatment mild galactorrhoea was still present in six patients, four of whom had attained normal PRL levels. Side‐effects were mild and transient. CV 205‐502 seems to be a valuable compound in the management of patients with hyperprolactinaemia.
CHOLINERGIC MUSCARINIC BLOCKADE PRODUCES SHORT‐TERM SUPPRESSION OF GROWTH HORMONE SECRETION IN CHILDREN WITH TALL STATURE
Authors: HINDMARSH P. C. , PRINGLE P. J. , BROOK C. G. D.
Published: March 2008

We have studied the effects of oral pirenzepine (50 mg twice daily) on growth and growth hormone (GH) secretion in 10 children with tall stature (9F, 1M). Suppression of GH secretion was observed in all children for 2‐3 h after drug administration but was followed by rebound secretion of GH after 4‐6 h. Consequently there was little overall change in GH secretion. In the dose regimen used the disruption of normal pulsatile GH secretion was not sufficiently significant to change final or predicted heights.
ALPHA‐2‐ADRENERGIC PATHWAYS RELEASE GROWTH HORMONE VIA A NON‐GRF‐DEPENDENT MECHANISM IN NORMAL HUMAN SUBJECTS
Authors: VALCAVI R. , DIEGUEZ C. , PAGE M. D. , ZINI M. , CASOLI P. , PORTIOLI I. , SCANLON M. F.
Published: March 2008

Administration of a supramaximal dose of GRF 1‐44 (200 μg, i.v.) to normal human volunteers increased GH levels while a further bolus of GRF (200 μg i.v.) given 2 hours later failed to increase plasma GH levels. In contrast, alphaadrenergic receptor agonism with either propranolol‐adrenaline infusion or clonidine increased plasma GH levels at a time when GH responses to this supramaximal dose of GRF were absent. This indicates that alpha‐adrenergic pathways stimulate GH secretion through a non‐GRF‐dependent mechanism in normal human subjects.
EVIDENCE FOR A HYPOTHALAMIC ALTERATION OF CATECHOLAMINE METABOLISM IN POLYCYSTIC OVARY SYNDROME
Authors: PARADISI ROBERTO , GROSSI GABRIELE , VENTUROLI STEFANO , CAPELLI MAURIZIO , PORCU ELEONORA , FABBRI RAFFAELLA , PASQUALI RENATO , FLAMIGNI CARLO
Published: March 2008

The role of brain catecholamine (CA) activity in the neuroendocrine regulation of the GnRH‐LH system in polycystic ovary syndrome (PCO) was investigated by high‐performance liquid chromatography (HPLC) with electrochemical detector. We measured urinary dopamine (DA), noradrenaline (NA), adrenaline (A), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4‐dihydr‐oxyphenylacetic acid (DOPAC) and total 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) levels in a group of 12 women with PCO before and during peripheral dopa‐decarboxylase blockade, by carbidopa. HVA and DOPAC concentrations were significantly lower (P<0001 and P<0‐005, respectively) in PCO patients compared with twelve control subjects in early follicular phase, whereas total MHPG concentrations and MHPG/VMA ratio were significantly higher (P< 0‐005) in PCO patients. Moreover, HVA and DOPAC concentrations in PCO patients were similar to those of the control subjects in preovulatory phase, while MHPG concentrations remained higher in PCO patients (P<0‐01). DA, NA, A and VMA concentrations were similar to those of control subjects in both phases of the cycle. During carbidopa administration the concentrations of all urinary CAs and metabolites were unchanged, except those of DA which dropped markedly (P<0‐001). These data suggest that (1) an altered central catecholamine metabolism consisting of DA deficiency and NA excess is present in PCO, and (2) the site of DA deficiency may be located in the hypothalamus.
A COMPARISON OF FOLLICULAR FLUID LEVELS OF INSULIN‐LIKE GROWTH FACTOR‐1 IN NORMAL DOMINANT AND COHORT FOLLICLES, POLYCYSTIC AND MULTICYSTIC OVARIES
Authors: EDEN J. A. , JONES J. , CARTER G. D. , ALAGHBAND‐ZADEH J.
Published: March 2008

Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least two samples of clear follicular fluid (FF) collected in the late follicular phase. The cohort concentrations of Insulin‐like Growth Factor‐1 (IGF1) were significantly correlated with serum IGF1 and dominant follicles contained significantly higher concentrations of IGF1 and oestradiol (E2) than their cohorts. After the LH surge, a further significant increase in dominant FF‐IGF1 occurred. FF‐(log)E2 was significantly correlated with both FF‐IGF1 and FF volume. Nine women with the polycystic ovary syndrome (PCOS) and one patient with multicystic ovaries (MCO) associated with weight‐loss related amenorrhoea also had follicular aspiration performed. The mean (SD) FF‐IGF1 in the PCOS group, 0.42 (0.15) U/ml, was not significantly different from that of the cohorts in the control group, 0.39 (0.13) U/ml. The patient with MCO had both serum and FF‐IGF1 concentrations < 10th centile. These results support the hypothesis that IGF1 has a paracrine (and possibly endocrine) role in the regulation of ovarian function in the human female.
STUDIES ON THYROTROPHIN RECEPTOR ANTIBODIES IN PATIENTS WITH EUTHYROID GRAVES' DISEASE
Authors: KASAGI K. , HATABU H. , TOKUDA Y. , IIDA Y. , ENDO K. , KONISHI J.
Published: March 2008

Thyroid stimulating antibodies (TSAb) and TSH‐binding inhibitor immunoglobulins (TBII) were assessed in 30 patients with euthyroid Graves' disease. TSAb were detected in 24 cases (80.0%), the incidence being not significantly different from that in hyperthyroid Graves' disease (29/30,97.6%). On the other hand, the incidence of TBII in patients with euthyroid Graves' disease (12/30, 40.0%) was significantly lower than that in patients with hyperthyroid Graves' disease (30/30, 100.0%). The mean TSAb and TBII activities in the euthyroid patients were significantly lower than in the hyperthyroid patients (P < 0.f005 and P < 0.001, respectively). Both TBII and, more closely, TSAb activities correlated with T3‐nonsuppressibility and inhibition of serum TSH response to TRH stimulation. The findings supported the stimulation in vivo of the thyroid by these antibodies.

Both antithyroglobulin and antimicrosomal antibody titres in euthyroid Graves' disease were significantly lower than in hyperthyroid Graves' disease (P < 0.05, P < 0.01, respectively). Goitre size was significantly smaller (P < 0.001), and 99mTc thyroid uptake was significantly lower (P < 0.001) in the euthyroid than in the hyperthyroid group. Thus, the reduced mass of thyroid tissues responding to the stimulators was considered to be one of the factors responsible for the euthyroidism despite the presence of TSAb.

The high incidence of TSAb and relatively low incidence of TBII in euthyroid Graves' disease indicate that the presence of TSAb does not necessarily lead to hyperthyroidism and that the development of overt thyrotoxicosis may require augmentation of both TSAb and TBII.
TREATMENT OF POLYCYSTIC OVARIAN DISEASE BY INDUCING OVULATION WITH PULSATILE SUBCUTANEOUS ADMINISTRATION OF HUMAN MENOPAUSAL GONADOTROPHIN ASSOCIATED WITH LUTEINIZING HORMONE‐RELEASING HORMONE ANALOGUE
Authors: NAKAMURA YUKIO , YOSHIMURA YASUNORI , TAMAOKA YUUKOKU , UBUKATA YOSHINOBU , YOSHIDA KEIKO , YAMADA HARUHIKO , IIZUKA RIHACHI , SUZUKI MASAHIKO
Published: March 2008

Treatment with a combination of luteinizing hormone‐releasing analogue (GnRHa, Buserelin) and pulsatile administration of hMG (Group I) were used to induce ovulation in nine patients with polycystic ovary syndrome (PCO). The same patients were also treated with pulsatile hMG administration alone (Group II). Ovulation was observed in all twelve treatment cycles in Group I, and there were two pregnancies. In Group II, ovulation occurred in 22 of 26 treatment cycles. Ovarian hyperstimulation occurred in one cycle of Group I and in 5 of 26 cycles of Group II. The total dose per cycle of hMG to induce ovulation in Group I was significantly lower than that needed when only pulsatile hMG administration was used. In response to Buserelin administration, the concentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) increased transiently and then declined to the normal range observed in the early follicular phase. The concentrations of FSH increased in response to hMG administration, resulting in a normal LH/FSH ratio. The present data demonstrated that pulsatile subcutaneous administration of hMG in addition to Buserelin was effective in inducing follicular maturation and ovulation in patients with PCO with a lower incidence of serious side‐effects.
THERAPY OF ACROMEGALY WITH SANDOSTATIN: THE PREDICTIVE VALUE OF AN ACUTE TEST, THE VALUE OF SERUM SOMATOMEDIN‐C MEASUREMENTS IN DOSE ADJUSTMENT AND THE DEFINITION OF A BIOCHEMICAL ‘CURE’
Authors: LAMBERTS S. W. J. , UITTERLINDEN P. , SCHUIJFF P. C. , KLIJN J. G. M.
Published: March 2008

Fifteen acromegalic patient were treated for a mean of 96 weeks with 200–300 μg Sandostatin per day. The mean 24 h GH concentration decreased by 86% from 34.3 ± 6.6 to 4.8 ± 0.7 μ/l (1 μg/l = 46 pmol/1). There was a close correlation between the mean GH levels from 2 to 6 h after the acute administration of 50 μg Sandostatin and the mean 24 h GH levels after chronic therapy (P < 001). Serum Sm‐C levels decreased from 6.9 ± 0.7 to 2.7 ± 0.5 U/ml (−61%) and normalized in eight of these 15 patients. There was a close correlation between the Sm‐C and mean 24 h GH levels after therapy (P < 0001). It is suggested that adjustment of the dose and the number of Sandostatin injections can be made in acromegaly on the basis of the measurement of Sm‐C levels during the follow‐up. This precludes the need of multiple GH determinations throughout the day and/or night. Biochemical ‘cure’(as denned by normalized Sm‐C levels) was reached in eight patients in whom mean 24 h GH levels were suppressed to 3–3 μg/l or less. The normalization of Sm‐C levels was even observed in the presence of two or three GH secretory peaks (never exceeding 7.5–10 μg/l) during the 24 h period occurring towards the next Sandostatin injection.
GONADOTROPHIN, GROWTH HORMONE AND PROLACTIN SECRETION IN CHILDREN WITH PRIMARY HYPOTHYROIDISM
Authors: BUCHANAN C. R. , STANHOPE R. , ADLARD P. , JONES J. , GRANT D. B. , PREECE M. A.
Published: March 2008

We have studied eight children with primary hypothyroidism (6F, 2M) aged 6–7 to 14–2 years. The girls were prepubertal and the boys had early normal pubertal development. Overnight secretion of LH, FSH, TSH, PRL and GH, and ovarian ultrasound morphology were assessed before and up to 9 months after commencing thyroxine treatment. Serum FSH concentrations in all the girls were increased above LH levels and severe hypothyroidism was associated with reduced GH secretion. These abnormalities reversed with thyroxine treatment. The boys had less severe hypothyroidism and did not demonstrate abnormal gonadotrophin or GH secretion. We conclude that primary hypothyroidism in childhood is associated with widespread disturbance of pituitary function, including increased FSH secretion often without signs of early sexual maturation.
SODIUM FLUORIDE STIMULATES OSTEOCALCIN IN NORMAL SUBJECTS
Authors: DANDONA P. , COUMAR A. , GILL D. S. , BELL J. , THOMAS M.
Published: March 2008

To test whether the administration of sodium fluoride in vivo results in an increase in osteocalcin concentration, we administered sodium fluoride to seven healthy male subjects for a period of 3 weeks. Fasting calcium, phosphate, alkaline phosphatase, 25‐hydroxyvitamin D, parathyroid hormone and osteocalcin were measured prior to, during and 6 weeks after fluoride administration. Plasma calcium, phosphate and alkaline phosphatase and serum 25‐hydroxyvitamin D and parathyroid hormone concentrations did not alter. Serum osteocalcin concentrations increased following fluoride administration, and the mean osteocalcin concentration at 3 weeks was significantly higher than the pretreatment mean. Plasma urea and creatinine concentrations did not alter. Six weeks after the cessation of fluoride treatment, the mean serum osteocalcin concentration had returned to the pretreatment baseline. We conclude that fluoride administration in normal subjects over a short period increases serum osteocalcin concentration and probably stimulates osteoblastic activity.
LUNG CARCINOID WITH CUSHING'S SYNDROME: CONTROL OF SERUM ACTH AND CORTISOL LEVELS USING SMS 201–995 (SANDOSTATIN)
Authors: HEARN P. R. , REYNOLDS C. L. , JOHANSEN K. , WOODHOUSE N. J. Y.
Published: March 2008

Two patients with Cushing's syndrome due to lung carcinoid tumours were given the long‐acting somatostatin analogue SMS 201–995 (Sandostatin). One received a single 50 μg dose which produced a 50% reduction in circulating ACTH levels within 4 h. The other has been maintained in clinical and biochemical remission for 10 weeks on 100 μg tid. This is the first report of the successful use of SMS 201–995 in carcinoid‐induced Cushing's syndrome, and suggests that this hormone analogue could be valuable in the long term medical management of such patients.
DYSGERMINOMA IN 45,X TURNER SYNDROME: REPORT OF A CASE
Authors: SINISI A. A. , PERRONE L. , QUARTO C. , BARONE M. , BELLASTELLA A. , FAGGIANO M.
Published: March 2008

Here we report the fourth case of dysgerminoma in a patient with the syndrome of gonadal dysgenesis and 45,X karyotype. Typical Turner's syndrome features were unusually associated with breast development, menarche and secondary amenorrhoea. Exaggerated basal and GnRH stimulated gonadotrophin and low oestradiol levels were typical of post‐pubertal Turner's syndrome. Detailed (standard) chromosome and banding analysis excluded the presence of Y chromosome material. This case suggests that the presence of a Y chromosome is not necessary for abnormal differentiation of germ cells and the occurrence of a gonadoblastoma.
LONG‐TERM TREATMENT OF NELSON'S SYNDROME WITH SODIUM VALPROATE
Authors: KELLY W. , ADAMS J. E. , LAING I. , LONGSON D. , DAVIES D.
Published: March 2008

Eleven patients with Nelson's syndrome were given sodium valproate (Epilim, Sanofi). Plasma ACTH and cortisol levels were measured under carefully controlled conditions which were designed to eliminate spontaneous fluctuations in ACTH. At 6 weeks all 11 patients were reassessed while taking sodium valproate 600 mg/day; there was then a small but significant (P<0.05) reduction in plasma ACTH concentration. Six patients continued to take sodium valproate, and were reassessed at 1 year when five were taking 1200 mg/day and one patient was taking 600 mg/day. At 1 year for these six patients there had been an increase in mean plasma ACTH which was then not significantly different from basal values. The five patients who discontinued sodium valproate were also reassessed at 1 year, when there were no significant differences compared to basal or 6‐week values. During therapy with sodium valproate, there were no significant changes in the half‐life of plasma cortisol, plasma sodium and potassium concentrations, or serum liver enzymes. Weight gain on sodium valproate was the main reason for patients asking to discontinue therapy. Sodium valproate is not an effective long‐term therapy for reducing plasma ACTH for patients with Nelson's syndrome.
DEPRESSED NATURAL KILLER ACTIVITY IN GRAVES' DISEASE AND DURING ANTITHYROID MEDICATION
Authors: WANG PEI‐WEN , LUO SHUE‐FEN , HUANG BIE‐YU , LIN JEN‐DER , HUANG MIAU‐JU
Published: March 2008

To investigate the natural killer (NK) cell mediated immunity in Graves' disease (GD) and the effect of antithyroid drugs upon NK cell activity, 51Cr release assay for NK cytotoxicity against K562 cells was examined in patients with GD before and during antithyroid medication and after drug withdrawal. Fifty‐eight patients were divided into three groups: the untreated thyrotoxic patients (n= 33), the euthyroid patients under antithyroid treatment (n= 19) and the euthyroid patients after drug withdrawal (n= 6). The results of the three groups were compared to 23,15 and 5 sex‐ and age‐matched controls, respectively. The data revealed a significant NK dysfunction in the untreated hyperthyroid patients, although the number of the NK cells was not decreased. NK function was normal when patients were no longer taking antithyroid medication and in euthyroid state. However, euthyroid patients under antithyroid medication had markedly depressed NK activity, suggesting an immunosuppressive effect of the antithyroid drugs. This study demonstrated that both the hyperthyroid state and the antithyroid drugs exerted immunosuppressive effects upon the NK cells. Since such an immunosuppressive effect on NK cells might be associated with a decreased immune surveillance against tumour growth, this study implies that a long‐term follow up of GD patients treated with antithyrdid drugs may be indicated to guard against a possible increased incidence of malignancy.
A BROMOCRIPTINE‐RESPONSIVE CORTICOTROPH ADENOMA SECRETING α‐MSH IN A PATIENT WITH CUSHING'S DISEASE
Authors: HALE A. C. , COATES P. J. , DONIACH I. , HOWLETT T. A. , GROSSMAN A. , REES L. H. , BESSER G. M.
Published: March 2008

Clinical and in‐vitro investigations have been performed on a corticotroph adenoma removed from a patient suffering from Cushing's disease. Prior to surgery, the patient's Cushing's disease had been successfully controlled, clinically and biochemically, by long term administration of bromocriptine. After selective adenomectomy, tumour tissue was investigated by a perfused isolated cell column technique. It was shown that the tumour cells secreted immunoreactive‐ (IR‐) ACTH and IR‐α‐MSH and that the release of both peptides was promptly suppressed by dopamine. Chromatographic analysis of the secreted IR‐α‐MSH revealed a high proportion of acetylated α‐MSH; smaller amounts of desacetyl α‐MSH and diacetyl α‐MSH were present. The relevance of these findings to the proposal that certain corticotroph adenomas are derived from the intermediate lobe of the pituitary is discussed. It is concluded that there is little direct evidence for involvement of the residual zona intermedia of the adult human pituitary in the development of Cushing's disease.
ADRENOCORTICOTROPHIN (ACTH) DEFICIENCY UNDETECTED BY STANDARD DYNAMIC TESTS OF THE HYPOTHALAMIC‐PITUITARY‐ADRENAL AXIS
Authors: TSATSOULIS A. , SHALET S. M. , HARRISON J. , RATCLIFFE W. A. , BEARDWELL C. G. , ROBINSON E. L.
Published: March 2008

Six patients (four females, two males; aged 18–65 years), previously treated by external pituitary irradiation (2000–4000 cGY in 8–15 fractions over 10–20 days) for pituitary tumours, presented with the symptoms of excessive and inappropriate tiredness suggestive of ACTH deficiency, despite a normal peak cortisol response to an insulin tolerance test (four cases) or to a glucagon stimulation test (two cases). These six patients were found to have significantly lower mean 24 h urinary free cortisol levels (100 ± 40 nmol; mean ± SD) compared with the mean value of 31 normal controls (210 ± 70.8 nmol; P<0.01). In addition serum cortisol profiles based on a series of four timed samples between 0900–2300 h were subnormal (mean 130 nmol/l) in comparison with profiles obtained from 12 normal controls (mean 270 nmol/l) (P <0.001). Glucocorticoid replacement therapy promptly abolished their symptoms. These results suggest that a discordance between ACTH secretion under basal circumstances and ACTH response to pharmacological tests may exist in patients with ACTH deficiency. We speculate that defective endogenous corticotrophin‐releasing hormone (CRF) secretion, due to radiation‐induced damage at hypothalamic level, is one cause of this phenomenon.
CHANGES IN SERUM PROLACTIN LEVELS DURING THE FOLLICULAR PHASE AND THE ENDOGENOUS LUTEINIZING HORMONE SURGE OF CYCLES HYPERSTIMULATED WITH FOLLICLE STIMULATING HORMONE
Authors: MESSINIS I. E. , TEMPLETON A.
Published: March 2008

The pattern of serum PRL levels during superovulation induction with pulsatile ‘pure’ FSH was investigated in 10 normally ovulating women. They were studied in two consecutive cycles, i.e. an untreated spontaneous and an FSH stimulated cycle. An endogenous LH surge occurred in all 10 spontaneous cycles and in five of the FSH cycles. Midcycle PRL levels were significantly higher in the FSH stimulated than in the spontaneous cycles (P < 0.01). In both groups of cycles, circadian periodicity of serum PRL levels during the LH surge was different from that during the late follicular phase with higher levels at midnight, although in the FSH cycles PRL secretion showed a sustained increase over 24 h. A nadir of PRL levels was found between 0900 h and 1200 h. In contrast, progesterone secretion during the LH surge showed a nocturnal increase with the highest value between 0600 h and 1200 h and the lowest at midnight. In the FSH cycles without an LH surge, PRL levels increased as long as FSH administration was continued and showed a significant positive correlation with the increasing serum oestradiol levels (r= 0.77). We conclude that ovarian hyperstimulation is a potent stimulus of PRL secretion in women. It is suggested that the midcycle endogenous LH surge facilitates the evening PRL secretion, while induction of multiple folliculogenesis amplifies the 24 h pattern of PRL secretion.
HYPERTHYROIDISM AND THYROID CANCER
Authors: EDMONDS C. J. , TELLEZ M.
Published: March 2008

Ten of 502 patients presenting with thyroid cancer were hyperthyroid due to Graves' disease (4 patients), multinodular goitre (3), an autonomous functioning nodule (1) and a large functioning tumour (2). In addition eight patients had a past history of Graves' disease and four of hyperthyroidism associated with multinodular goitre. Mortality in patients with Graves' disease and with multinodular goitre appeared similar to that of other patients of comparable age. Both patients with large functioning tumours died from progressive disease. Concentration 131I by tumour metastases was present in one patient with active Graves' disease who had a high serum concentration of TSH‐receptor binding antibodies, indicating that these antibodies may chronically stimulate tumour function. The potential for 131I concentration by tumour when TSH secretion is suppressed should therefore be determined in patients with Graves' disease and if demonstrable tumour function is present, reflecting stimulation by Graves' immunoglobulins, then elimination of tumour remnants is particularly important.
DEVELOPMENT OF HYPERTHYROIDISM FOLLOWING PRIMARY HYPOTHYROIDISM: A CASE REPORT WITH CHANGES IN THYROID‐RELATED ANTIBODIES
Authors: TAKEDA K. , TAKAMATSU J. , KASAGI K. , SAKANE S. , IKEGAMI Y. , ISOTANI H. , MAJIMA T. , MAJIMA M. , KITAOKA H. , IIDA Y. , IKEKUBO K. , KONISHI J. , MOZAI T.
Published: March 2008

We report a 48‐year‐old woman who developed hyperthyroidism following primary hypothyroidism. The serum T4 level was initially low and serum TSH level was high with clinical signs of hypothyroidism. The thyroid gland was not enlarged. Therapy with L‐T4 was started. Three years later she developed hyperthyroidism; serum free T4 increased to 29–1 pmol/l after cessation of L‐T4 therapy. The 123I thyroid uptake was increased with no suppression by exogenous T3. When she was hypothyroid, the activity of thyroid stimulating antibodies (TSAb) in serum measured by cyclic AMP production in cultured porcine thyroid cells were negative at 93.4% (normal < 140%), while thyroid stimulation‐blocking antibodies (TSBAb) determined by inhibition of TSH‐induced cyclic AMP increase were positive at 96.1% (normal < 40%). When hyperthyroidism subsequently occurred, TSBAb became negative (30.%), while TSAb became positive (163.3%). The findings indicate that hypothyroidism due to the potent TSBAb activity is not always persistent, but can be changed when various types of thyroid‐relating antibodies change in the course of the disease.
GROWTH HORMONE DEFICIENCY AND THE MEASUREMENT OF SOMATOMEDIN C/IGF‐I: THE INFLUENCE OF SEXUAL MATURATION
Authors: RAYNER P. H. W. , RUDD B. T. , THOMAS P. H. , WILLIAMS J. W.
Published: March 2008

Fifty‐nine short children 2–19 years, 25 females and 34 males, were studied for clinical and biochemical evidence of growth hormone deficiency (GHD). Group 1 (n= 32), mean height SDS — 3.26 ± 1.5, mean retardation of bone age 2 years, had a mean peak GH of 6.1 ± 3.7 mIU/l during tests of GH release, and were classified as GHD. Group 2 (n= 27), had a mean height SDS of ‐ 2.65 ± 1, mean bone age retardation of 1.7 years and had a mean peak GH during provocation tests of 24.3 ± 11.1 mIU/l and were classified as non‐GHD. Basal IGF‐I concentrations were correlated with height and bone age, for both groups and for GHD children, with pubertal score. Neither peak GH values nor integrated GH concentrations in a provocative test were correlated with IGF‐I values. The minimum IGF‐I concentrations occurred at a bone age of 8 years, the reference point that was taken as the average expected time of maturational change. IGF‐I concentrations rose in five GHD children when their bone age exceeded 8 years and when their free testosterone was greater than 10 pmol/l. Eighty‐nine per cent of the GHD children with a bone age at or below 8 years were identified as GHD from their basal IGF‐I values, but for, all bone ages this fell to 62.5%. Basal IGF‐I values appear to be less discriminatory for identification of GHD as sexual maturity and bone age advance.
THE REGULATION AND INTEGRATION OF THYROID FOLLICULAR DIFFERENTIATION AND FUNCTION
Authors: BIDEY S. P. , TOMLINSON S.
Published: March 2008

As in a number of other endocrine tissues in which expression of differentiated function is dependent upon a stable cellular architecture, the control of differentiation of the thyroid follicle requires a coordination between the ultrastructural and morphological responses to a number of endocrine growth factors, which may ultimately involve autocrine or paracrine‐mediated effects within the immediate follicular microenvironment. Through analogy with other cell types, expression of appropriate differentiation characteristics within the thyroid follicle may involve the activation of specific c‐oncogenes within each of the component cells. With the recent development and application of oncogene transfection technology, application of such procedures to the thyroid follicular cell should prove to be a particularly fruitful area for future research within the thyroid gland, leading to elucidation of the mechanisms whereby the cellular responses to growth and tissue‐differentiating factors are mediated. Clearly however, further consideration must also be made of the roles played in maintaining follicular stability by both physical and chemical interactions between the component cells and the immediate extracellular environment. The contributory roles played by basement membrane and cell‐surface components in cellular recognition, together with the physical effects imposed upon the apical surfaces of the follicle by luminal thyroglobulin have already been identified as fundamental factors in this respect. It is also reasily apparent that morphological differentiation of the follicle bears critically upon the chemical characteristics of the microenvironment through the ability of the latter to promote expression of specific apical/basal recognition characteristics of the component cells, and thus maintain the unidirectional polarity upon which the functional capacity of the thyroid follicle is so critically‐dependent.
REVERSIBLE REPRODUCTIVE DYSFUNCTION IN MEN WITH OBSTRUCTIVE SLEEP APNOEA
Authors: SANTAMARIA J. D. , PRIOR J. C. , FLEETHAM J. A.
Published: March 2008

A central, reversible decrease in male sexual function appears related to some aspect of obstructive sleep apnoea (OSA). Lower serum testosterone (T) levels were documented in 15 men with OSA versus nine snorers (no OSA), (9.18 ± 0.92 vs 11.55 ± 0.90 nmol/l, mean ± SEM), P < 0.05 in a consecutive case series of 24 men referred for diagnostic overnight sleep studies. Gonadotrophins did not differ between the two groups. Although the men with OSA did not differ in body mass index (BMI) or weight from the snorers, they were older (51 ± 3.9 vs 44 ± 3.1 years), P < 0.02. Serum T did not correlate with age, but was correlated with minimum nocturnal arterial oxygen saturation (Min SaO2) (r=0.589), P < 0.02. A prospective controlled trial of uvulopalatopharyngo‐plasty therapy (UPP) for OSA in 12 subsequent subjects showed reproductive improvement which was parallel with improved apnoea at 3 months post‐surgery. T increased (13.31 ± 1.07 to 16.59 ± 0.72 nmol/l), P<0.02, without significant changes in BMI, serum PRL, LH or FSH. All seven of the men who reported decreased sexual interest prior to surgery felt their libido and sexual functioning had returned to normal 3 months following UPP. Some aspect of OSA in men appears to produce a reversible hypothalamic‐pituitary reproductive dysfunction.