bluuebunny/crossref_metadata_2025_split huggingface dataset:
PULSATILE ADMINISTRATION OF GnRH FOR THE TREATMENT OF HYPOGONADOTROPHIC HYPOGONADISM
Authors: MENON V. , BUTT W. R. , CLAYTON R. N. , EDWARDS R. LOGAN , LYNCH S. S. 
Published: March 2008

SUMMARYFourteen patients, aged 22‐35 years, complaining of infertility and failing to ovulate on clomiphene, were treated with GnRH administered in pulses at 90 min intervals. Four patients received a total of eight courses of GnRH given subcutaneously and 13 were given a total of 20 months of treatment with GnRH given intravenously. Serum concentrations of immunoreactive GnRH were measured in six patients before administration of the drug and at regular intervals for 60 min after subcutaneous and intravenous injections of 5, 10 and 20 μg GnRH. Maximum concentrations of GnRH were reached by 5‐10 min after subcutaneous injections and within 2 min after intravenous injections. The peak concentrations were 3.6‐6.3 times and the sums of increments were 2.0‐3.9 times greater following intravenous injections than after subcutaneous injections. Subcutaneous treatments extended for 15‐29 days with doses of 5‐20 μg per pulse. Only one patient ovulated as judged by the luteal phase progesterone and ultrasonic scanning of the follicle. Intravenous treatments were from 12‐22 days with doses of 10 μg per pulse and 16 treatments out of 20 were ovulatory with four pregnancies. HCG (5000 i.u.) was given when ultrasonic scanning indicated adequate follicular growth, but in eight of the cycles, including three of the pregnancies, the follicle had ruptured before HCG was given. Pulsatile administration of GnRH proved to be an effective treatment for infertility in hypogonadotrophic hypogonadism. Possible reasons for the better results by intravenous rather than subcutaneous injections are discussed.
ALTERED PULSATILE SECRETION OF LUTEINIZING HORMONE IN HYPOGONADAL MEN WITH HYPERPROLACTINAEMIA
Authors: WINTERS S. J. , TROEN P. 
Published: March 2008

SUMMARYTo explore the mechanism for the hypogonadism associated with prolactin hypersecretion in men we examined luteinizing hormone (LH) secretory profiles in four hyperprolactinaemic men before and during treatment with bromocriptine. Pretreatment serum prolactin levels were increased 4‐100 fold and serum testosterone levels were low in three men and low‐normal in the fourth subject. Mean LH levels were low‐normal and the frequency of spontaneous LH secretory episodes was less than normal in three of four men. Bromocriptine reduced serum prolactin levels to normal; subsequently, serum testosterone levels increased and libido and potency improved markedly in each man. The rise in serum testosterone levels was associated with an increase in mean LH concentrations and in LH pulse frequency. Mean follicle‐stimulating hormone levels also increased during bromocriptine treatment. Insofar as each LH pulse is believed to reflect a discharge of gonadotrophin releasing hormone from the anterior hypothalamus, our data suggest that a major abnormality in hyperprolactinaemic men with hypogonadism is a disorder of the neuroregulatory mechanism for pulsatile gonadotrophin‐releasing hormone secretion.
ALDOSTERONE DEFICIENCY IN A PATIENT WITH IDIOPATHIC HAEMOCHROMATOSIS
Authors: THOMAS J. P. 
Published: March 2008

SUMMARYPostural hypotension due to low aldosterone secretion was the presenting feature of idiopathic haemochromatosis in a 35‐year‐old man. Repeated venesection is beneficial in this disease but it is suggested that aldosterone deficiency be excluded before treatment to avoid depletion of circulating volume.
SPECIFIC INHIBITION OF ALDOSTERONE RESPONSES TO ENDOGENOUS AND EXOGENOUS ANGIOTENSIN II BY SOMATOSTATIN
Authors: JONES C. R. , MILLAR J. A. , LAWRIE C. , SUMNER D. J. , REID J. L. 
Published: March 2008

SUMMARYAldosterone and renin responses to head‐up tilt (60° for 1 h) and angiotensin II infusions (2, 5 and 10 ng/kg/min) 1 h later were compared in six normal subjects during infusions of somatostatin (3 ±g/kg/min) or saline. The infusions were performed on separate days two weeks apart. The increase in aldosterone due to exogenous angiotensin II and orthostasis were significantly attenuated by somatostatin. Neither the increase in plasma renin activity (PRA) nor the angiotensin II mediated suppression of PRA were affected by somatostatin. These findings are consistent with the recent observation that somatostatin suppresses aldosterone release in response to angiotensin II in rat adrenal cells in culture and they indicate a possible role for somatostatin in the regulation of aldosterone secretion.
EFFECT OF FUSARIC ACID (A DOPAMINE β‐HYDROXYLASE INHIBITOR) ON PHAEOCHROMOCYTOMA
Authors: NAGASAKA A. , HARA I. , IMAI Y. , UCHIKAWA T. , YAMAUCHI K. , SUZUKI S. , TAKATSUKI K. , TOMITA A. , NIINOMI M. , NAKAGAWA H. , ITATSU T. , HIDAKA H. 
Published: March 2008

SUMMARYFusaric acid, an inhibitor of dopamine β‐hydroxylase, which converts dopamine to noradrenaline, lowered the blood pressure and induced a subjective improvement in patients with phaeochromocytoma. These effects may be due either to an impairment of catecholamine biosynthesis or to a direct action on the blood vessels. The use of this drug in the treatment of patients with inoperable malignant phaeochromocytoma or neuroblastoma may improve symptoms and prolong survival.
THE SCREENING OF PATIENTS WITH SUSPECTED THYROTOXICOSIS USING A SENSITIVE TSH RADIOIMMUNOASSAY
Authors: EVANS MARGARET , CROXSON M. S. , WILSON T. M. , IBBERTSON H. K. 
Published: March 2008

SUMMARYA radioimmunoassay was optimized to measure serum TSH with maximum sensitivity (sTSH). With this assay sTSH was < 0·5 mIU/l in 100% of 64 patients with proven thyrotoxicosis and > $5 mIU/l in 92% of 76 normal subjects. sTSH correctly predicted the TSH response to TRH (Δ TSH) in 93% of 125 patients with suspected thyrotoxicosis. In this group thyrotoxicosis was excluded by an sTSH > $5 mIU/l in 52% of patients thus avoiding the need for further testing.
COMPARATIVE EFFECTS OF SODIUM IPODATE AND IODIDE ON SERUM THYROID HORMONE CONCENTRATIONS IN PATIENTS WITH GRAVES' DISEASE
Authors: ROTI E. , ROBUSCHI G. , MANFREDI A. , D'AMATO L. , GARDINI ELIANA , SALVI M. , MONTERMINI MARA , BARLLI ANGELA L. , GNUDI A. , BRAVERMAN L. E. 
Published: March 2008

SUMMARYPatients with thyrotoxic Graves' disease were treated daily for 10 d with 1 g sodium ipodate, an iodine rich X‐ray contrast agent which impairs outer ring (5′‐) deiodination of T4 to T3, or with 12 drops of a saturated solution of potassium iodide (SSKI). T4, T3 and reverse T3 (rT3) concentrations were measured before, during, and 5 and 10 d after the administration of each drug. SSKI therapy induced a decrease in the serum T4 concentration from 14·7 ± 1·3 μg/dl (mean ± SE) to a nadir of 7±9 ± 0·9 on days 9 and 10 of therapy, all values reaching the normal range by day 9; a decrease in the serum T3 concentration from 402 ± 43 ng/dl to a nadir of 143 ±20 on day 10, remaining elevated in all patients until day 5 and decreasing into the normal range in all except one patient on days 9 and 10; and no change in the serum rT3 concentration. Serum T4 and T3 concentrations returned to baseline values 10 d after withdrawal of SSKI. In contrast sodium ipodate therapy induced only a modest decrease in the serum T4 concentration from 15±± 0·7 μg/dl to a nadir on day 9 of 11·3 ± 1·0 and serum T4 remained above the normal range in most patients until day 8; a striking and rapid decrease (within 12 h) in the serum T3 concentration from 340 ± 36 ng/dl to mean values ranging from 79 to 85 during the last 5 d of therapy, with most values below the normal range during the last 3 d; and a marked increase in the serum rT3 concentration from 111 ±15 ng/dl to a peak value of 376 ± 59 on day 5. A significant rebound increase in serum T4 (18·7± 1·7 μg/dl; P < 0·01) and serum T3 (512 ± 72; P < 0·01) concentrations as compared to pretreatment values occurred 10 days after sodium ipodate was discontinued. We conclude that although treatment of hyperthyroidism with
IOPANOIC ACID IS OF MINIMAL BENEFIT IN THE TREATMENT OF SEVERE HYPERTHYROIDISM: CONCLUSIONS FROM A CASE STUDY
Authors: HAMBLIN P. S. , MOHR V. S. , STOCKIGT J. R. , TOPLISS D. J. 
Published: March 2008

SUMMARYIopanoic acid (1 g/d) was used together with propylthiouracil (1200 mg/d) in the treatment of a patient with very severe hyperthyroidism and associated cardiac failure. Although serum total T3 decreased by 75% within 48 h and reached normal after 72 h, free T3 levels did not fall to normal. Total and free T4 remained markedly elevated and features of hyperthyroidism persisted. Estimations of theoretical in vivo occupancy of nuclear thyroid hormone receptors, based on serum free T4 and free T3, suggest that the marked decrease in total T3 would not result in a corresponding decrease in thyroid hormone action. Hence, estimates of potential benefit from oral cholecystographic contrast agents, based only on measurements of total T3, may be unduly optimistic. When temporary agranulocytosis developed in this patient, the prior use of iopanoic acid, by markedly reducing thyroidal iodine uptake, restricted the therapeutic options. Caution should, therefore, be exercised in the use of iodine‐containing contrast media as adjunctive antithyroid agents.
A NEW AND DISTINCTIVE ALBUMIN VARIANT WITH INCREASED AFFINITIES FOR BOTH TRIIODOTHYRONINES AND CAUSING HYPERTHYROXINAEMIA
Authors: LALLOZ M. R. A. , BYFIELD P. G. H. , HIMSWORTH R. L. 
Published: March 2008

SUMMARYA new variant albumin with increased affinities for iodothyronines has been identified. A euthyroid woman had raised total serum concentrations of T4 (155 nmol/l), T3 (3·0 nmol/l) and rT3 (700 pmol/l) but normal levels of all three iodothyronine‐binding proteins. The affinity constant for T3 binding to the albumin was substantially raised (2·2 × 105 l/mole; normal immeasurable), that for rT3 (1·4 × 106 l/mole) was five‐fold greater than normal, and that for T4 (6±× 105 l/mole) was increased three‐fold. This new albumin binds the analogues of T4 and T3 used in Amerlex free‐hormone assays more strongly than does normal albumin, resulting in erroneously elevated estimates of serum free‐T4 and free‐T3 by this method. The new variant albumin was indistinguishable from normal albumin in molecular size and by electrophoretic and immunological techniques. Three distinct variant albumins exhibiting differential binding of iodothyronines have now been defined: Type I causes a raised total serum T4 only; Type II produces increased total T4 and rT3; Type III (the present example) results in elevated total T4, rT3 and T3. All three variants have normal free‐T4 by dialysis but spuriously raised results by the Amerlex free‐T4 method. Type III also causes an artificial increase in Amerlex free‐T3. The pattern of thyroid function test results in Type III can readily be confused with both hyperthyroidism and with partial peripheral resistance to thyroid hormones.
GLUCOSE TOLERANCE AND PLASMA IMMUNOREACTIVE INSULIN LEVELS IN ACROMEGALICS BEFORE AND AFTER SELECTIVE TRANSSPHENOIDAL SURGERY
Authors: ROELFSEMA F. , FRÖLICH MARIJKE 
Published: March 2008

SUMMARYThe glucose and immunoreactive insulin (IRI) responses to a 100 g oral glucose tolerance test (oGTT) administered to 23 acromegalic patients before and after transsphenoidal adenomectomy and to a sex and age‐matched control group were studied. The preoperative growth hormone levels, ranging from 11 to 360 mU/l, had normalized (i.e. ≤ 5 mU/l) after surgery in all cases. Before surgery paradoxical increases in the GH level, either after i.v. TRH injection or during the oGTT were seen in 14 patients. After surgery, the paradoxical reaction to the oGTT had normalized in all cases and the increase measured after the TRH injection normalized in nine out of 12 cases. The disturbed glucose tolerance (either impaired tolerance or frank diabetes) was cured by surgery. The plasma glucose levels determined 1 and 2 years after surgery did not differ from those found for the control group. Preoperative plasma IRI levels were significantly elevated, whereas after surgery the IRI levels had decreased. Fasting levels were normalized in all patients. Two years after surgery, eight patients still showed some abnormalities of the insulin secretion (as revealed by the integrated sum and the maximum increment in IRI levels during the oGTT) despite the presence of normal circulating GH levels and a normalized paradoxical reaction to TRH. The data show that after normalization of GH levels in acromegalics, increased insulin secretion may still occur after glucose ingestion in some patients. It is suggested that this abnormality could be the result of an increased pancreatic islet β‐cell mass, as a persisting abnormality of the acromegalic state, although peripheral insulin resistance cannot be excluded totally.
INTRANASAL THYROTROPHIN RELEASING HORMONE IS A POTENT STIMULUS FOR TSH RELEASE IN MAN (COMPARISON WITH INTRAVENOUS AND ORAL TRH)
Authors: STAUB J. J. , RYFF‐DELÈCHE A. S. , PAUL S. , GIRARD J. , POLC B. , VON DER OHE M. 
Published: March 2008

SUMMARYIntranasally administered TRH was tested and compared to i.v. and oral TRH in respect to its efficacy of TSH stimulation and thereby the stimulation of thyroid reserve. TSH release after nasal application is as prompt as after the i.v. route, reaching a peak at 20 to 30 min. After that, however, compared to the i.v. administration its stimulatory effect is prolonged, lasting over 3 h. At the dose used in this study the peak TSH response after intranasal TRH administration was 14·7 · 1·6 mU/l compared to 8·4 · 1·4 and 23±· 4·4 mU/l after i.v. and oral administration respectively (P < 0·005). Intranasal application of TRH is as potent as i.v. or oral TRH for the stimulation of thyroid reserve. At 3 h a marked increase of T3 and a smaller elevation of FT4 is observed (Δ T3 = 48·4%, Δ FT4 = 31·6%). The nasal peptide was well tolerated locally and systemic side effects were comparable to those of i.v. TRH. This form of application offers a practical advantage by avoiding intravenous injections. Its diagnostic potential in investigation of thyroid disease and its possible therapeutic application have yet to be elucidated.
THE EFFECTS OF CHOLINERGIC BLOCKADE ON THE GROWTH HORMONE AND PROLACTIN RESPONSE TO INSULIN HYPOGLYCAEMIA
Authors: EVANS P. J. , DIEGUEZ C. , FOORD S. , PETERS J. R. , HALL R. , SCANLON M. F. 
Published: March 2008

SUMMARYThe effect of cholinergic blockade on growth hormone (GH) and prolactin (PRL) secretion during insulin‐induced hypoglycaemia was assessed in six normal male volunteers (mean age 23, age range 21–25). Each subject underwent two insulin tolerance tests with and without atropine. GH responses were significantly lower 45 min after insulin administration with atropine (17.5 · 2.5 mU/l (mean · SEM) than with placebo (37.6 · 3.6 mU/l, P < 0.0006). In contrast PRL responses were higher (P < 0.01) at 45 and 90 min after insulin during treatment with atropine. These data demonstrate that cholinergic mechanisms are involved in stimulatory and inhibitory pathways in the medication of the respective GH and PRL responses to insulin induced hypoglycaemia in man.
PREMENARCHEAL ENDOCRINE CHANGES IN RELATION TO AGE AT MENARCHE
Authors: APTER D. , VIHKO R. 
Published: March 2008

SUMMARYPubertal development preceding menarche in normal girls having menarche at a relatively early age (11.3–12.9 years) was compared with the development of girls having menarche later (13.0–14.9 years of age). Eighty‐four premenarcheal girls, 7.3–14.3 years old, were examined and their age at menarche was recorded during this longitudinal study. Girls with early menarche had a larger increase in serum oestradiol at about 10 years of chronological age, and after that age the concentrations remained higher than in girls having later menarche. Serum FSH concentrations tended to be slightly higher at the onset of puberty in the former group, even before differences in serum oestradiol concentrations were observed. Pubertal development was faster in girls having early menarche, as indicated by the significantly shorter time from both breast and pubic hair stage 2 to menarche. This rapid sequence can be related to the higher oestradiol levels. A dissociation between gonadarche and adrenarche was evident. The oestradiol/dehydroepiandrosterone (DHEA) ratio was higher in girls developing early menarche. Around the onset of puberty (9.0–11.5 years of age) there was a complete lack of correlation between serum DHEA concentrations and age at menarche, whereas serum FSH and oestradiol concentrations displayed strong correlations with age at menarche. The present data support the view that girls with early menarche have a more profound decrease in the sensitivity of the hypothalamic‐pituitary unit to the negative feed‐back of circulating steroids.
A NEW FAMILY WITH DEXAMETHASONE‐SUPPRESSIBLE HYPERALDOSTERONISM: ALDOSTERONE UNRESPONSIVENESS TO ANGIOTENSIN II
Authors: FALLO F. , SONINO N. , ARMANINI D. , LUZZI T. , PEDINI F. , PASINI C. , MANTERO F. 
Published: March 2008

SUMMARYA family with nine siblings in which three siblings have been shown to have dexamethasone‐suppressible hyperaldosteronism was studied. All three showed no significant changes of plasma aldosterone during angiotensin II infusion at incremental rates under baseline conditions. After dexamethasone administration (2 mg/d for 4 weeks) plasma renin activity (PRA) rose to normal‐supranormal range, while plasma and urinary aldosterone were maintained at low‐normal levels. No restoration of aldosterone response to angiotensin II was observed on dexamethasone. Two other siblings were found to be hypertensive with normal baseline data; however, both showed plasma aldosterone hyperresponsiveness to ACTH. In the four normotensive siblings aldosterone response to ACTH was normal. The family pedigree was consistent with autosomal dominant transmission of the disorder. HLA typing showed haplotype A3 Bw35 in all five hypertensive sibs and in one normotensive. In conclusion, low aldosterone compared to PRA, and plasma aldosterone unresponsiveness to angiotensin II infusion before and during dexamethasone, show functional impairment, at least temporary, of the zona glomerulosa. These findings support the hypothesis that aldosterone may be derived from the zona fasciculata in this disorder.
ARE THERE GENETIC DETERMINANTS FOR THE GLUCOSE INTOLERANCE OF ACROMEGALY?
Authors: HITMAN G. A. , KATZ J. , LYTRAS N. , JOWETT N. I. , WASS J. A. H. , BESSER G. M. , GALTON D. J. 
Published: March 2008

SUMMARYA genetic marker identifying the two parental insulin genes has been studied in 51 Caucasian acromegalics by Southern blot hybridization techniques using a cloned insulin gene probe. Two main DNA insertion classes were detected corresponding to the class 1 and class 3 alleles and thus the following genotypes were found: 1/1, 1/3 and 3/3. The acromegalics were subdivided depending on whether they had a normal (n= 30) or abnormal (n= 21) response to a 50 gm oral glucose tolerance test before treatment. The phenotype frequencies in the former group were 1/1, 43%; 1/3, 53%; and 3/3, 4%; and in the latter group the corresponding figures were 76%, 24% and 0%. The relative incidence of concordance of the phenotype 1/1 with abnormal glucose tolerance in acromegaly was 4.2. This phenotype is also associated with insulin dependent (Type 1) diabetes mellitus.
PROOPIOMELANOCORTIN‐DERIVED PEPTIDES IN THE IMMUNE SYSTEM
Authors: BLALOCK J. E. 
Published: March 2008

SUMMARYCells of the immune system have recently been recognized as a source of the proopiomelanocortin (POMC)‐derived peptides, ACTH and endorphins, and their receptors. In this review, the nature of the immunoregulatory and hypothalamic signals which elicit the production of these leukocyte‐derived hormones is discussed. Further, comparisons are made between the various proteolytic processing patterns of POMC in leukocytes as compared with those observed in the hypothalamus and anterior or intermediate lobes of the pituitary gland. The possible functioning of leukocyte‐derived ACTH and endorphins as well as their pituitary counterparts in a complete regulatory loop between the neuroendocrine and immune systems is described.
HLA ANTIGENS AND FAMILIAL BENIGN HYPERCALCAEMIA
Authors: PATERSON C. R. , LEHENY W. , O'SULLIVAN A. F. 
Published: March 2008

SUMMARYWe have determined the blood groups and HLA haplotypes in 15 members in four generations of a large kindred with familial benign hypercalcaemia (familial hypocalciuric hypercalcaemia). No linkage was seen between the disorder and ABO or Rh blood groups or the HLA antigens.
THE ROLE OF PLASMA OSMOLALITY, ANGIOTENSIN II AND DOPAMINE IN VASOPRESSIN RELEASE IN MAN
Authors: MORTON J. J. , CONNELL J. M. C. , HUGHES M. J. , INGLIS G. C. , WALLACE E. C. H. 
Published: March 2008

SUMMARYA sensitive and specific radioimmunoassay for arginine vasopressin was used to compare the relative importance of changes in plasma osmolality, angiotensin II and dopamine in the regulation of vasopressin secretion in man. One hour after water loading plasma vasopressin fell from 0·40 to 0·06 pmol/1, while 8 h and 24 h fluid restriction resulted in a rise of vasopressin from 0·29 to 0·54 and 1·37 pmol/1 respectively. In contrast neither dietary sodium deprivation, when plasma angiotensin II increased 5‐fold, nor dopamine infusion, at a rate which increased circulating dopamine levels up to 244‐fold, had any effect on basal plasma vasopressin values. These results confirm that, under physiological conditions, osmoregulation is the major mechanism controlling vasopressin release and suggests that circulating angiotensin II and dopamine have no significant part to play.
THE EFFECT OF SPIRONOLACTONE ON HIRSUTISM AND FEMALE ANDROGEN METABOLISM
Authors: DORRINGTON‐WARD P. , MCCARTNEY A. C. E. , HOLLAND S. , SCULLY J. , CARTER G. , ALAGHBAND‐ZADEH J. , WISE P. 
Published: March 2008

SUMMARYAn objective evaluation of the anti‐androgen effects of spironolactone was performed in a consecutive series of 12 hirsute patients receiving a daily dose of 150 mg; nine completed the study. Using a computer assisted image analyser, hair diameter on two weekly shavings decreased significantly over a 12 month period in three of the patients, although growth rate and mean diameter did not change in the group as a whole. Plasma testosterone fell significantly to a mean of 53% of basal levels. The mean free testosterone (derived) fell significantly to 64% of basal by the sixth month (P= > 0·005) and remained significantly depressed for the remainder of the study. There was subjective benefit in hair growth and greasiness and a significant reduction in the semi‐objective Ferriman‐Gallwey index in nine of 10 subjects assessed for at least 9 months. We conclude that although spironolactone was not consistently successful, it may represent effective therapy for a sub group of patients with hirsutism.
THYROID STIMULATION BY (FAB)2 AND FAB FRAGMENTS OF TSH RECEPTOR ANTIBODY
Authors: CREAGH F. M. , PARKES A. B. , TUNN E. , GINSBERG J. , HASHIM F. , SMITH B. REES 
Published: March 2008

SUMMARYThe TSH receptor binding and thyroid stimulating properties of (Fab)2 and Fab fragments of Graves’ IgG have been investigated. (Fab)2 fragments were prepared by pepsin digestion of IgG and Fab fragments by reduction of (Fab)2 or papain digestion of IgG. (Fab)2 and Fab were effective in inhibiting TSH binding to its receptor with all five patients’ sera studied and both preparations stimulated cyclic AMP release from isolated thyroid cells. However Fab fragments were less active thyroid stimulators than their parent (Fab)2 in all five cases. These studies indicate that antibody divalency is not essential for thyroid stimulation by TSH receptor antibodies.