bluuebunny/crossref_metadata_2025 huggingface dataset:
THE REPRODUCTIVE ENDOCRINE SYSTEM IN CYSTIC FIBROSIS: 2. CHANGES IN GONADOTROPHINS AND SEX STEROIDS FOLLOWING LHRH
Authors: REITER E. O. , STERN R. C. , ROOT A. W.
Published: March 2008

Hypothalamic–pituitary–gonadal function was assessed in forty‐seven patients with cystic fibrosis (CF) by the 3‐h infusion of 100 μg of synthetic gonadotrophin‐releasing factor, LHRH and the results compared with a group of children being evaluated for short stature and delayed puberty (‘controls’). Levels of gonadotrophins and sex steroids were measured prior to and during the infusion. In prepubertal boys, LH and FSH release evoked by LHRH was significantly greater (P < 0·001) in ‘control’subjects than in CF patients. In pubertal boys, LH and FSH release was also greater in ‘controls’than in CF, though to a lesser degree (P < 0·05). In pubertal girls, responses to LHRH were comparable for LH and slightly greater (P < 0·05) in ‘controls’for FSH. In the earliest pubertal groups of both sexes (male‐Tanner genitalia stage 2; females‐Tanner breast stage 2), LH secretion was similar in patients with CF and ‘control’subjects. Significant increments of testosterone and oestradiol in pubertal CF patients do not occur until 6 h after the LHRH infusion begins, in contrast to a rise at 3 h in ‘control’subjects. These data suggest that prepubertal boys with CF, who are the most impaired in height, weight and skeletal maturation, also have measurable abnormalities of LHRH‐releasable gonadotrophin secretion. Despite continued impaired weight growth, pubertal patients do attain essentially normal gonadotrophin secretory responses to LHRH administration and are similar to subjects with constitutional delayed adolescent development in reproductive endocrine physiology.
CLOMIPHENE CITRATE DOES NOT MODIFY THE EXAGGERATED THYROTROPHIN RESPONSE TO THYROTROPHIN‐RELEASING HORMONE OCCURRING IN PRIMARY TESTICULAR FAILURE
Authors: SPITZ I. M. , KEREM E. , ZYLBER‐HARAN E. , SHILO S. , LAUFER N. , LIVSHIN Y. , SCHENKER J. G.
Published: March 2008

Patients with primary testicular failure have increased basal TSH levels and an exaggerated TSH response to TRH in the presence of normal circulating levels of thyroid hormones. In order to evaluate if this TSH profile is an oestrogenrelated phenomenon, sixteen patients with primary testicular failure were challenged with 200 μg TRH prior to and after the administration of clomiphene citrate. The latter was given in a dose of 100 mg/day for 4 weeks to ten patients; 200 mg/day for 4 weeks to three patients and 100 mg/day for 2 months to the final three patients.

The patients demonstrated increased mean basal TSH levels with an exaggerated TSH response to TRH. Following the administration of clomiphene citrate, there were no changes in T4, T3 sephadex or total T3 levels and in basal or stimulated TSH levels. Clomiphene did produce an increase in oestradiol, testosterone, basal gonadotrophins and LH response to LHRH. Since the oestrogen antagonist, clomiphene citrate, had no effect on TSH secretion, it is unlikely that the exaggerated TSH response to TRH is mediated by oestrogens.
PREDICTION OF THERAPEUTIC RESPONSE TO RADIOACTIVE IODINE IN GRAVES’DISEASE USING TSH‐RECEPTOR ANTIBODIES AND HLA‐STATUS
Authors: DAVIES T. F. , PLATZER M. , FARID N. R.
Published: March 2008

We have examined the combined usefulness of TSH‐receptor antibody detection and HLA status on the therapeutic response to standard doses of radioactive iodine (RAI) in forty‐three hyperthryoid Graves’patients. Twenty‐three patients had detectable TSH‐receptor antibodies as measured by 125I‐TSH binding‐inhibition (TBI) prior to administration of 7 mCi RAI. Eighteen (78%) of these patients were rendered euthyroid within 3 months. In contrast, twenty patients were TBI negative prior to RAI and sixteen (80%) of these individuals remained hyperthyroid at 3 months and required two, or more, doses of RAI to control their thyroid function. DR3 status alone was not strongly associated with resistance to RAI. However, of sixteen patients without detectable TBI activity and who required two or more doses of RAI, ten patients were DR3 positive (62%) compared with 25% in a control population. Only one patient who was both TBI and DR3 negative required more than one dose of RAI.

These data indicate that TBI may be an accurate predictor of the therapeutic response to RAI in patients with hyperthyroid Graves’disease. Investigation of HLA status alone was of limited value, although it appeared that the combination of TBI and DR3 may be of additional help in developing an overall strategy for the treatment of hyperthyroid Graves’disease.
TRH INJECTION DURING LABOUR: EFFECT ON MATERNAL AND FETAL PROLACTIN SECRETION
Authors: MESSINIS I. E. , LOLIS D. E. , KANELLOPOULOS N. , DALKALITSIS N. , KANARIS C.
Published: March 2008

The effect of TRH injection on PRL levels in maternal serum and in serum of umbilical vein (UV) and artery (UA) was investigated in forty‐six women. Twenty‐two of them, with normal singleton term pregnancy, were given i.v. either saline solution (nine women, control group 1) or 200 μg of synthetic TRH (thirteen women, group 2) 30–45 min before normal delivery. Group 1 PRL values (mean ± SE) (ng/ml) in UV (428 ± 41) and UA serum (434 ± 45) were significantly higher than in maternal serum either before (285 ± 39) or after saline injection (331 ± 14) (P < 0·05). In group 2, TRH induced a marked increase in maternal serum PRL (544 ± 33 v. 285 ± 39, P < 0·001) (difference from corresponding maternal serum PRL of group 1 significant, P < 0·001) but not in UV (409 ± 41) and UA (406 ± 48) PRL values (difference from the corresponding PRL values in UV and UA serum of group 1 non‐significant, P > 0·1). Group 2 maternal serum PRL values after TRH were significantly higher than in UV and UA serum (P < 0·05). A significant positive correlation was found between UV and UA serum PRL values in both group 1 (r=0·858, P < 0·01) and group 2 (r=0·870, P < 0·001). Twelve of the remaining twentyfour women were given TRH either 10–20 min (four women), 60–75 min (four women), or 90–110 min (four women) before delivery. UA serum PRL values did not differ significantly from corresponding controls (twelve women). It is suggested, from these findings in women, that TRH injected into the mother in a single dose of 200 μg stimulates maternal but not fetal pituitary in late pregnancy during labour. This is possibly due to inability of TRH to cross the human placenta.
METABOLIC CLEARANCE AND PRODUCTION RATES OF 3,3′‐DIIODOTHYRONINE, 3′,5′‐DIIODOTHYRONINE AND 3′‐MONOIODOTHYRONINE IN HYPER‐ AND HYPOTHYROIDISM
Authors: FABER J. , LUMHOLTZ I. B. , KIRKEGAARD C. , SIERSBæK‐NIELSEN K. , FRIIS T.
Published: March 2008

Complete turnover studies of thyroxine (T4), 3,5,3′‐triiodothyronine (T3), 3,3′,5′‐triiodothyronine (rT3), 3,3′‐diiodothyronine (3,3′‐T2), 3′,5′‐diiodothyronine (3′,5′‐T2) and 3′‐monoiodothyronine (3′‐T1) were performed in each of eight healthy subjects, eight hyperthyroid and eight hypothyroid patients, using the single injection, non‐compartmental approach. The median metabolic clearance rate (litre per day per 70 kg) in controls was, T4 1·19; T3 19·7. rT3 147; 3,3′‐T2 1073; 3′,5′‐T2 256 and 3′‐T1 518. Hyperthyroid patients had increased and hypothyroid patients reduced values. The median production rate (PR) (nmol per day per 70 kg) in controls was, T4 117, T3 39, rT3 52, 3,3′‐T2 35, 3′,5′‐T2 14 and 3′‐T1 27. The PR of all iodothyronines studied was increased in hyperthyroidism, the increase in PR of T3 being the most pronounced. Hypothyroid patients had reduced PRs, a reduction which was relatively less pronounced for T3. Assuming thyroidal secretion contributes little rT3 and 3′,5′‐T2, the conversion rates (CRs) of T4 to rT3 and further to 3′,5′‐T2 were calculated. CR of T4 to rT3 in controls was in median 34%. By comparison the CR in hyperthyroid patients was increased to 56% (P < 0·05). In contrast the CR of rT3 to 3′,5′‐T2 was similar in controls and hyperthyroid patients, 26% v. 31%.

Our data demonstrate, that quantitatively important amounts of 3,3′‐T2, 3′,5′‐T2 and 3′‐T1 are produced in man, and that deiodination of T4, the T3s and the T2s is a major metabolic pathway both in eu‐, hyper‐ and hypothyroidism. The daily production of all six iodothyronines studied is influenced by hyper‐ and by hypothyroidism. The activity of the 5‐deiodination of T4 seems to be enhanced during hyperthyroidism, possibly tending to counteract the hypermetabolic state. In contrast the 5‐deiodination of rT3 is unaltered in hyperthyroidism, thus suggesting the existence of more than one 5‐deiodinase in man.
RELATIONSHIP OF ALTERED THYROID HORMONE INDICES TO SURVIVAL IN NONTHYROIDAL ILLNESSES
Authors: KAPTEIN ELAINE M. , WEINER JOHN M. , ROBINSON WILLIAM J. , WHEELER WILLIAM S. , NICOLOFF JOHN T.
Published: March 2008

Although alterations of serum thyroid hormone indices are frequent in nonthyroidal illnesses, their relationship to survival is poorly defined. Consequently, the prevalence and prognostic relevance of alterations in thyroidal indices were evaluated prospectively in 195 patients requiring intensive medical therapy and in 75 critically ill patients with serum total T4 (TT4) levels below 3 μg/dl. In the 195 patients, serum total T3 (TT3) and TT4 levels were reduced in 69% and 43% respectively. Decreased TT4 levels had the highest correlation with mortality (P < 0·001) and correctly predicted outcome in 70% of patients. Other thyroidal indices, which were significantly different between survivors and nonsurvivors, correlated with TT4 and did not contribute independently to prediction accuracy when assessed by discriminant function analysis.

In seventy‐five patients with TT4 levels below 3 μg/dl, the nadir TT4 level appeared a median of 9 days (range 1–28) after hospital admission. The nonsurvivors lived a median of 6 days (range 0–42) and the survivors were discharged a median of 20 days (range 4–55) after the TT4 nadir. Only an increased free fraction of T4 (FFT4) was found to correlate significantly with mortality and contribute to prediction accuracy.

An inhibition of serum T4 binding to carrier proteins could account for both the decreased serum TT4 and the increased FFT4 values. Serum TT4 and/or FFT4 levels may be useful in assessing the severity and predicting the clinical outcome of acute critical nonthyroidal illnesses.
MENSTRUAL FUNCTION AND SERUM PROLACTIN LEVELS AFTER LONG‐TERM BROMOCRIPTINE TREATMENT OF HYPERPROLACTINAEMIC AMENORRHOEA
Authors: BERGH TORBJÖRN , NILLIUS SVEN JOHAN , WIDE LEIF
Published: March 2008

Long‐term bromocriptine treatment was discontinued in thirty‐seven women with hyperprolactinaemic amenorrhoea. After cessation of therapy thirty of the thirty‐seven women became hyperprolactinaemic again with amenorrhoea or anovulatory bleeding. Seven of the women continued to have regular ovulatory menstruation but only three were normoprolactinaemic 3 months after stopping treatment. Two of the seven women had evidence of pituitary tumour regression. After the discontinuation they had nearly normal prolactin levels but during 2 years of follow up the serum prolactin levels slowly increased. In the twenty‐seven women with pre treatment prolactin levels below 100 μg/l there was no difference between the prolactin levels before starting and 1 month after stopping treatment, while the women with pretreatment prolactin levels above 100 μ/l had lower levels after therapy. Bromocriptine treatment seldom results in permanent cure of hyperprolactinaemic amenorrhoea.
SALIVARY TESTOSTERONE: RELATIONSHIP TO UNBOUND PLASMA TESTOSTERONE IN NORMAL AND HYPERANDROGENIC WOMEN
Authors: BAXENDALE P. M. , JACOBS H. S. , JAMES V. H. T.
Published: March 2008

A sensitive radioimmunoassay (RIA) was used to measure salivary testosterone levels in normal women, in patients with polycystic ovaries (PCO), and in women with hirsutism. There was a highly significant correlation (r= 0·79, P<0·001) between the concentration of testosterone in saliva [12·3 ± 7·8 (SD) pg/ml] and the concentration of unbound testosterone in plasma (5·2 ± 3·1 pg/ml) in matched samples collected from 56 women including normals, patients with clinical signs of hyperandrogenism, and women treated with a combination of cyproterone acetate (CA) and ethinyl oestradiol (EE). The unbound plasma testosterone was measured in the dialysate directly using a sensitive RIA. Salivary and plasma testosterone levels in patients with PCO (20·6 ± 8·5 and 626 ± 187 pg/ml respectively, n= 14) and in those with hirsutism (13·9 ± 5·6 and 421 ± 170 pg/ml, n= 30) were significantly higher (P<0·001) than levels in normal women (7·7 ± 2·6 and 196 ± 68 pg/ml, n= 36). Treatment for 3 months with CA and EE resulted in a decrease (mean 68%) in salivary testosterone levels in all patients studied (n= 15), but the suppression of plasma testosterone (mean 34%) was not observed in all cases. It is concluded that measurement of salivary testosterone gives a useful indication of levels of biologically available androgen in hyperandrogenic women, before and during CA/EE therapy.
FAILURE OF FSH TO INFLUENCE AROMATIZATION IN HUMAN ADIPOSE TISSUE
Authors: FOLKERD E. J. , JACOBS H. S. , VAN DER SPUY Z. , JAMES V. H. T.
Published: March 2008

Since gonadotrophins are known to influence aromatase activity in gonadal tissue, an attempt was made to correlate serum gonadotrophin concentrations with the activity of aromatase enzyme in adipose tissue. No relationship between in‐vitro measurements of adipose tissue aromatase activity and FSH or LH levels in serum was found. Four of five women studied with premature ovarian failure had low levels of aromatase activity despite having post‐menopausal levels of serum gonadotrophins. In addition, FSH receptors could not be demonstrated on whole adipose tissue, isolated fat cells or stromal‐vascular tissue.
PRIMARY HYPOTHYROIDISM WITH GROSSLY ELEVATED PLASMA TOTAL THYROXINE AND TRIIODOTHYRONINE LEVELS
Authors: BECKETT G. J. , TODD J. A. , HUGHES G. J. , CAMPBELL I. W.
Published: March 2008

In an elderly patient with clinical primary hypothyroidism and a raised basal TSH, the serum free thyroxine (fT4), total thyroxine (TT4) and triiodothyronine (TT3) were consistently and paradoxically grossly elevated when measured by radioimmunoassay. In part these hormone levels were due to a high titre of endogenous IgG immunoglobulins which bound T4, T3 and reverse T3 (rT3) and thus caused gross interference in the radioimmunoassays. However, when this methodological interference was removed by using a methanolic extract of the patient's serum, the concentrations of TT4 and TT3 were still grossly elevated. It was only when basal TSH and the concentration of fT4 and fT3 were measured by equilibrium dialysis that these hormone levels were found to be consistent with primary hypothyroidism.
MICROHETEROGENEITY OF LUTEINIZING HORMONE IN PITUITARY GLANDS FROM WOMEN OF PRE‐ AND POSTMENOPAUSAL AGE
Authors: READER S. C. J. , ROBERTSON W. R. , DICZFALUSY E.
Published: March 2008

Luteinizing hormone from the pituitaries of women of premenopausal (Pre‐M) and postmenopausal (Post‐M) age has been studied to further understand the variations in the quality of plasma LH in women of different ages. The median and range for bioactive LH was 101: 85–155 IU/mg protein and 83: 52–201 IU/mg protein for the Pre‐ and Post‐M groups respectively. The ratios of LH bioactivity/immunoreactivity (B:I) were 1·04 ± 0·13 (Pre‐M) and 0·97 ± 0·02 (Post‐M). Broad range isoelectrophoretic profiles of the pituitary extracts revealed a heterogeneous population of coincident bioactive and immunoreactive LH peaks. Recoveries from the columns were similar in both groups and B:I values of the LH material throughout the columns were between 0·5 and 2·0 in over 90% of the fractions. Between 31·8 and 36·6% of the LH from both groups appeared between pH 7 and pH 8. The most striking difference between the two groups was that > 34% of the bioactive LH from the Post‐M pituitaries, but <6% of the LH from the other group had migrated as a major discrete peak to an acidic region of pH < 6. We conclude that although there is no difference in total LH activity in the pituitaries from the two groups, substantially more ‘acidic’ LH material is stored in the postmenopausal pituitaries. These observations are consistent with the recent finding of greater circulating levels of acidic LH in plasma from post‐menopausal women.
THE CLINICAL PRESENTATION OF HYPOTHYROID MYOPATHY AND ITS RELATIONSHIP TO ABNORMALITIES IN STRUCTURE AND FUNCTION OF SKELETAL MUSCLE
Authors: KHALEELI A. A. , GRIFFITH D. G. , EDWARDS R. H. T.
Published: March 2008

Clinical assessment for the presence of myopathy was performed in fifteen untreated hypothyroid patients. In many of these patients plasma creatine kinase (CK) activities, tests of skeletal muscle function and vastus lateralis needle biopsies were performed. Muscle symptoms were extremely common, occurring in thirteen patients. Proximal muscle weakness, preferentially affecting the legs, muscle pains or cramps and delayed tendon jerk relaxation represented the commonest features of hypothyroid myopathy. Detailed descriptions are given of patients with muscle hypertrophy, muscle atrophy and developmental failure to illustrate the wide clinical spectrum.

If examination revealed signs of myopathy, in particular if there was delayed relaxation of tendon jerks, biochemically severe hypothyroidism (serum thyroxine < 20 nmol/1) was likely (P < 0·01). The latter was a frequent finding in six patients with serous effusions (P <0·01). This subgroup also had a mean plasma CK activity of 1339 IU/1 compared to 679 IU/1 (normal 10–120 IU/1) for the whole hypothyroid group, and all five patients in this subgroup in whom vastus lateralis needle biopsies were performed showed abnormalities.

Quadriceps force measurements and ankle jerk relaxation times were more sensitive than clinical examination in detecting muscle weakness and delayed relaxation. A reduced maximum relation rate (MRR) of the quadriceps, vastus lateralis needle biopsy abnormalities, and myopathic features on electromyography were characteristic.
DOPAMINE BLOCKADE INHIBITS STARVATION KETOSIS IN MAN
Authors: JOHNSTON D. G. , BLESA‐MALPICA G. , BURRIN J. M. , WAUGH C. , COOK D. , ØRSKOV H. , ALBERTI K. G. M. M.
Published: March 2008

The effects of dopamine blockade on the endocrine and metabolic response to starvation have been investigated by administration of metoclopramide, 30 mg daily, or placebo to five normal subjects fasted for sixty hours on two occasions. Blood glucose and alanine concentrations fell with starvation and metoclopramide had no further effect. Concentrations of the other gluconeogenic precursors, lactate and pyruvate, were also unaffected by metoclopramide. The rise in circulating ketone body concentrations with fasting was impaired by metoclopramide, significantly from 44 h onwards (blood total ketone body concentration at 60 h, 3·42·0±94 mmol/1 with placebo; 2·08 ± 0·67 mmol/1 with metoclopramide, P < 0·05). Blood glycerol and plasma non‐esterified fatty acids (NEFA) levels rose with starvation, and metoclopramide had no further effect. Serum insulin concentrations remained low with fasting, while circulating glucagon and growth hormone levels rose. Similar changes were noted with both metoclopramide and placebo. Serum prolactin concentrations during starvation were elevated two to four fold by metoclopramide.

The inhibitory effect of dopamine blockade on ketosis thus occurred despite hyperprolactinaemia, and did not result from measurable alterations in insulin, glucagon or growth hormone secretion. The data suggest a stimulatory role for endogenous dopamine on starvation ketonaemia in man.
STUDIES OF INSULIN‐LIKE GROWTH FACTOR ‐I AND ‐II BY SPECIFIC RADIOLIGAND ASSAYS IN UMBILICAL CORD BLOOD
Authors: GLUCKMAN P. D. , JOHNSON‐BARRETT J. J. , BUTLER J. H. , EDGAR B. W. , GUNN T. R.
Published: March 2008

Somatomedin concentrations in human umbilical sera (n= 206) were measured using a specific radioimmunoassay for insulin‐like growth factor (IGF)‐I and a specific radioreceptor assay for IGF‐II following acid‐ethanol extraction of the sera to remove the somatomedin binding proteins. IGF‐I concentrations were lower (P< 0·001) than adult values and correlated with gestational age (P< 0·001) and birth weight (P< 0·0001). Multiple regression analysis demonstrated that both birth weight expressed independently of gestational age as the standard deviate score (P< 0·0001) and gestational age (P< 0·002) had effects on umbilical cord IGF‐I concentrations. IGF‐II concentrations were similar to adult values and did not correlate with gestational age, birth size or IGF‐I values. IGF‐II concentrations were higher (P< 0·005) in male than female fetuses. These data support a role for IGF‐I in influencing fetal growth and suggest the independent regulation of the secretion of IGF‐I and II in the perinatal period. These was no evidence to suggest a distinct perinatal form of somatomedin.
NATURAL HISTORY OF THYROID FUNCTION IN DIABETICS WITH IMPAIRED THYROID RESERVE: A FOUR YEAR CONTROLLED STUDY
Authors: GRAY R. S. , BORSEY D. Q. , IRVINE W. J. , SETH J. , CLARKE B. F.
Published: March 2008

An attempt was made to compare the natural history of thyroid function in 80 diabetics having raised serum TSH concentrations (median 8·9 mU/l, range 5·8–46·3 mU/l) but serum T4 concentrations within the normal range (Group 1), and in 59 diabetics having normal serum TSH (median 1·9 mU/l, range 0·8–4·7 mU/l) and T4 concentrations (Group 2). Thyroid microsomal antibodies were present initially in 65% of patients in Group 1 and 15% of patients in Group 2. By 1981, 59 patients (74%) in Group 1 and 47 patients (80%) in Group 2 had been followed for a mean ± SD duration of 4·2 ± 1·8 and 4·2 ± 1·5 years, respectively.

Hypothyroidism developed in 9 patients in Group 1, but none from Group 2. Of patients in Group 1, hypothyroidism developed at a rate of 5% per annum in those with thyroid microsomal antibodies, but only 1% per annum in those without antibodies. Therefore, the risk of development of hypothyroidism is greatest in diabetics having both elevated serum TSH concentrations and thyroid microsomal antibodies and such patients should have regular review of thyroid function. Either risk factor alone appears to be a poor predictor of development of hypothyroidism.
CORRECTION BY BROMOCRIPTINE OF HYPOTHALAMIC DYSFUNCTION AND POST‐PRANDIAL HYPOGLYCAEMIC SYMPTOMS IN A 31‐YEAR‐OLD WOMAN
Authors: CORCOS A. P. , WEIDENFELD J. , LEVY J. , BARASH V. , SIEGEL R. A. , GUTMAN A. , CHOWERS I.
Published: March 2008

A 31‐year old female presented with recurrent episodes of post‐prandial hypoglycaemic symptoms. Basal serum levels of ACTH, cortisol, GH, insulin and glucagon were normal. An adrenaline test demonstrated a normal peripheral response. An exercise test failed to produce ACTH, cortisol or FFA responses. Insulin (0·1 u/kg)‐induced‐hypoglycaemia failed to elevate serum ACTH, cortisol or GH. Metyrapone and ACTH tests were normal, demonstrating adequate hypophyseal and adrenal function. These findings suggested that the patient suffered from hypothalamic dysfunction. Brornocriptine (Parlodel, 7·5 mg/d for 5 weeks) resulted in an improved general condition, accompanied by a decrease in sugar consumption. Following treatment, FFA, ACTH and cortisol responses to exercise test were normal, as were ACTH, cortisol and GH responses to insulin‐induced hypoglycaemia. It is concluded that bromocriptine may be useful in the treatment of post‐prandial hypoglycaemic symptoms associated with hypothalamic dysfunction.
EFFECT OF TREATMENT OF CUSHING'S SYNDROME ON SKELETAL MUSCLE STRUCTURE AND FUNCTION
Authors: KHALEELI A. A. , BETTERIDGE D. J. , EDWARDS R. H. T. , ROUND J. M. , ROSS E. J.
Published: March 2008

The time course of recovery in the myopathy of Cushing's syndrome was studied before and after removal of a pituitary adenoma at hypophysectomy in three patients and an adrenal adenoma in another. Serial measurements were performed of quadriceps force, total muscle mass/body weight, individual fibre size on needle biopsies of the lateral muscle mass of the thigh and skeletal muscle cross‐sectional area (CSA) and force/unit CSA on computed (CT) scans of thighs and calves. All patients were weak, and recovery was slow but substantial except in one patient who had persistent Cushing's syndrome. An accompanying increase in overall and type II mean fibre area (MFA) occurred after surgery in the patients with a pituitary adenoma, as did an increase in skeletal muscle CSA and force/unit CSA in both patients having CT scans. The only patient with pronounced muscle wasting showed severe type II fibre atrophy with a reduced total muscle mass/body weight, but muscle morphology and total muscle mass were normal in the other patients. Only in this patient was a significant increase in total muscle mass/body weight noted after surgery. These findings suggest that the increase in muscle mass which may follow hypophysectomy in Cushing's syndrome is due to an increase in individual cell size.
SHOULD ONE MEASURE SERUM THYROGLOBULIN IN THE PRESENCE OF ANTI‐THYROGLOBULIN ANTIBODIES?
Authors: BLACK E. G. , HOFFENBERG R.
Published: March 2008

Thyroglobulin auto‐antibodies (anti‐Tg) may affect measurement of serum thyroglobulin (Tg). We have assayed sera for Tg by RIA regardless of presence or absence of anti‐Tg, and this study was designed to assess the influence of anti‐Tg on the results. Binding of human anti‐Tg by the second antibody in our RIA (sheep anti‐rabbit immunoglobulin) is very low and sera containing anti‐Tg of varying titres do not systematically affect assay of Tg regardless of concentration. In our follow‐up study of patients with thyroid cancer, correlation between clinical state and Tg concentration is greater than 97% whether anti‐Tg is present or absent. These results indicate that in our assay anti‐Tg positive sera do not need to be excluded.
SUSTAINED GONADAL SUPPRESSION IN FERTILE WOMEN WITH THE LHRH AGONIST BUSERELIN
Authors: HARDT W. , SCHMIDT‐GOLLWITZER M.
Published: March 2008

Nine fertile women were treated with the luteinizing‐ hormone‐releasing hormone agonist buserelin (seven women received 800 ųg, two women 1200 ųg intranasally for up to 24 weeks). Both doses produced sustained suppression of ovarian function, accompanied by hot flushes. In five women chemical castration was established within 1 to 5 weeks, whereas in the other four volunteers transient peaks of serum oestradiol occurred between the 6th and 19th weeks. Thereafter low postmenopausal oestradiol levels persisted. Chemical castration was confirmed by hormonal parameters and endometrial biopsies (inactive endometrium). After cessation of treatment normal cyclical function occurred immediately. This reversible chemical castration may be useful for new therapeutical approaches in sexual hormone dependent diseases (endometriosis, precocious puberty, metastatic breast cancer).
FENCLOFENAC‐SECONDARY EFFECTS UPON THE PITUITARY THYROID AXIS
Authors: TAYLOR R. , HUTTON C. , WEEKE J. , CLARK F.
Published: March 2008

To elucidate the mechanism of suppression of TSH responsiveness to TRH induced by the initiation of fenclofenac therapy, the early period of drug administration was examined in detail and the effect of the drug during a thyrotrophin releasing hormone infusion was assessed. In addition, the effect of fenclofenac upon the response of ACTH, cortisol, growth hormone and prolactin to insulin‐induced hypoglycaemia was examined. The effect of fenclofenac upon an equilibrium dialysis method for estimating free thyroid hormones was evaluated and was found to be insignificant within the therapeutic concentration range of the drug. A sharp, short‐lived rise in free thyroxine (21·7 ± 2·0 to 26·8 ± 1·9 pmol/1; P <0·03) was observed 60 min after the first dose of fenclofenac. Repeated peaks of free thyroxine during chronic fenclofenac treatment, superimposed upon the previously described steady decline of free and total serum thyroxine, are postulated to cause the observed suppression of TSH release which is present only until free and total serum thyroxine levels reach their nadir. The time course of the changes seen during thyrotrophin releasing hormone infusion suggested that the pituitary suppression was secondary to a rise in free thyroxine. The responses to hypoglycaemia of those pituitary hormones examined were not affected by fenclofenac.
EFFECT OF FENFLURAMINE ON PROLACTIN SECRETION IN OBESE PATIENTS: EVIDENCE FOR SEROTONINERGIC REGULATION OF PROLACTIN IN MAN
Authors: BARBIERI C. , MAGNONI V. , RAUHE W. G. , ZANASI SILVIA , CALDARA R. , FERRARI C.
Published: March 2008

The present investigation was carried out to study the effect of serotoninergic stimulation on prolactin (PRL) secretion in man. Fenfluramine (60 mg, orally), an anorexiant drug which under acute circumstances stimulates the serotoninergic system, was administered to eight obese patients. Compared with placebo, drug administration increased PRL significantly (P < 0.05 at 180 and 300 min, P < 0.01 at 240 min). No significant changes were observed after fenfluramine in blood pressure, plasma aldosterone (PA), plasma cortisol, plasma renin activity, serum electrolytes or growth hormone. Since it has been reported that dopaminergic blockade raises PA concentration, the lack of change in PA in obese patients treated with fenfluramine suggests that the observed increase in PRL induced by fenfluramine is likely to be mediated by serotoninergic stimulation.
LONGTERM PERGOLIDE TREATMENT OF ACROMEGALY
Authors: KENDALL‐TAYLOR PAT , UPSTILL‐GODDARD GILL , COOK D.
Published: March 2008

The effect of pergolide mesylate, a new potent longacting dopamine agonist, was investigated in eight patients with active acromegaly, none of whom had received pituitary irradiation. Patients were assessed at different dose levels for clinical response and biochemical response by measuring mean fasting growth hormone (GH), mean ambulant GH and glucose‐induced GH response. Six patients had definite clinical improvement. No major side effects were noted. All patients showed a statistically significant reduction in GH, although in two reduction was not below 75% of pretreatment levels. On 500 μg pergolide daily the overall response for the group of eight patients was a reduction of fasting serum GH, mean ambulant GH and of GH response to glucose to 55% of pretreatment values. When the daily dose was increased to 1000 μg there was a further significant reduction in GH in some patients; on this dose the response for the group was a decrease in fasting serum GH and mean ambulant GH to 40% of pretreatment values. In three patients GH concentrations of 5 mU/1 or less were achieved. In two patients the daily dose was increased to 1500 μg but no extra benefit was obtained. We conclude that pergolide given once daily has a beneficial effect in acromegaly, with significant reduction in serum GH; it promises to be a useful therapeutic agent.
INFLUENCE OF OBESITY ON BASAL GLUCAGON LEVELS IN NON‐DIABETIC AND DIABETIC NAURUANS
Authors: ALFORD F. P. , ZIMMET P. , CHISHOLM D. J. , WHITEHOUSE S.
Published: March 2008

Basal plasma glucagon (IRG), insulin (IRI) and glucose levels were measured in normal weight (Body Mass Index (BMI) < 30) and obese (BMI < 30) non‐diabetic and diabetic Micronesians (n= 30) on Nauru Island. This population has a high prevalence of diabetes mellitus. IRG levels were significantly higher (P < 0.02) in the non‐diabetic obese, compared to the non‐diabetic lean subjects (109 ± 19 vs 44 ± 12 SEM pg/ml, respectively) and there was a significant positive correlation between basal IRG and BMI (r= 0.79, P < 0·001). IRG levels were similar in diabetic obese and diabetic lean subjects. The pathophysiological significance of the hyperglucagonaemia in these obese subjects is not known, although it may be related to the frequent development of diabetes in this unique population.
PSEUDOHYPOPARATHYROIDISM: INHERITANCE AND EXPRESSION OF DEFICIENT RECEPTOR‐CYCLASE COUPLING PROTEIN ACTIVITY
Authors: FISCHER J. A. , BOURNE H. R. , DAMBACHER M. A. , TSCHOPP F. , DE MEYER R. , DEVOGELAER J.‐P. , WERDER E. A. , DE DEUXCHAISNES C. NAGANT
Published: March 2008

Pseudohypoparathyroidism, Type I (PSP‐I) is a familial disorder characterized by secondary hyperparathyroidism, resistance of urinary cyclic adenosine‐3′,5′‐monophosphate (cAMP) excretion to exogenous parathyroid hormone (PTH), and by effects upon other hormones, including thyrotrophin (TSH) hyperresponsiveness to thyroliberin (TRH). In the present study, 12 PSP‐I patients in five families exhibited partial deficiency of receptor‐cyclase coupling protein (N protein) in blood cells, in association with the skeletal findings of Albright's hereditary osteodystrophy. In one father and six mothers of PSP‐I patients, deficient N protein activity was associated with normal urinary cAMP responses to PTH. In this group of seven parents, five had Albright's osteodystrophy, two exhibited secondary hyperparathyroidism, and two had TSH hyperresponsiveness to TRH. In a sixth family with none of the features of Albright's osteodystrophy, N protein deficiency did not correlate with urinary cAMP responsiveness to PTH. In this kindred, one mother with N protein deficiency, but normal urinary cAMP responsiveness to PTH had raised serum levels of immunoreactive PTH. We conclude that in the majority of families with PSP‐I the urinary cAMP response to PTH is an inadequate indicator of the genetic defect. In such families, deficiency of N activity more consistently points to metabolic defects, including secondary hyperparathyroidism and TSH hyperresponsiveness, even when urinary cAMP responses are normal.
CHANGES IN CYCLIC AMP AND ELECTROLYTES AFTER PARATHYROIDECTOMY IN PRIMARY HYPERPARATHYROIDISM
Authors: KOHRI KENJIRO , KATAOKA KIYONORI , YACHIKU SUNAO , KURITA TAK‐ ASHI , SONODA TAKAO
Published: March 2008

Changes in the excretion of urinary cyclic AMP, calcium and phosphate, and serum calcium, ionized calcium, and magnesium were studied after parathyroidectomy for primary hyperparathyroidism. Urinary cyclic AMP decreased rapidly and 8 of 11 patients had a significant reduction 1 h postoperatively, but changes in serum calcium and ionized calcium were delayed. Serum calcium concentrations closely parallelled those of serum ionized calcium and phosphate excretion returned to normal almost 7 h later than that of cyclic AMP. Excretion of urinary calcium rose rapidly at 4 h after surgery because calcium clearance improved after the reduction in circulating parathyroid hormone. The fall in urinary calcium at about 24 h was due to the subsequent reduction in serum calcium.
MEASUREMENT OF SEX HORMONE BINDING GLOBULIN IN HUMAN AMNIOTIC FLUID: ITS RELATIONSHIP TO PROTEIN AND TESTOSTERONE CONCENTRATIONS, AND FETAL SEX
Authors: HAMMOND G. L. , LEINONEN P. , BOLTON N. J. , VIHKO R.
Published: March 2008

Sex hormone binding globulin (SHBG) has been identified and quantified in human amniotic fluid. Identification was based on its electrophoretic mobility on polyacrylamide gels and its steroid binding characteristics, which were identical to those attributed to SHBG in pregnancy serum. Amniotic fluid SHBG binding capacity was measured by competitive saturation analysis using [3H]‐5α‐dihydrotestosterone as the labelled ligand, after removal of endogenous steroids with dextran‐coated charcoal. Similar amniotic fluid SHBG binding capacities were found in samples taken during early (13–20 weeks, 8.5 ± 5.1 (SD) nmol/l, n= 10) and late (36–37 weeks, 8.7 ± 3.0 nmol/l, n= 28) pregnancy. In comparison with pregnancy serum SHBG levels (390 ± 140 nmol/l, n= 5), amniotic fluid SHBG was not enriched in relation to the relative concentrations of total proteins, albumin or transferrin. Amniotic fluid is therefore not a better source for the purification of SHBG than pregnancy serum. There were no differences in amniotic fluid SHBG levels with respect to fetal sex, but positive correlations were observed between SHBG binding capacities and testosterone concentrations in amniotic fluid from both male (r= 0.68, P < 0.001) and female (r= 0.53, P < 0.05) fetuses. It is suggested that SHBG may sequester free testosterone in amniotic fluid, and that measurements of SHBG in amniotic fluid may help to more accurately identify fetal sex in cases where borderline amniotic fluid testosterone concentrations are found.
HYPOGONADOTROPHIC HYPOGONADISM RESISTANT TO hCG AND RESPONSIVE TO LHRH: REPORT OF A CASE
Authors: DONALD R. A. , WHEELER M. , SÖNKSEN P. H. , LOWY C.
Published: March 2008

The treatment of hypogonadotrophic hypogonadism with gonadotrophin releasing hormone (LHRH) has proved difficult in the past because of a progressive decline in the pituitary gonadotrophin response. These early studies generally used large relatively infrequent doses of natural LHRH (Davies et al., 1977) or analogues with a prolonged action (Smith et al., 1979).

Recently, several reports have indicated that the lack of gonadotrophin response to LHRH can be overcome by frequent administration of low doses of natural LHRH in a pulsatile fashion (Belchetz et al., 1978; Crowley et al., 1980; Jacobson et al., 1979; Schoemaker et al., 1981; Valk et al., 1980). However, it is not known whether those patients with hypogonadotrophic hypogonadism who fail to respond to human chorionic gonadotrophin (hCG) (Bardin et al., 1969) are capable of responding to LHRH. In this case report of a patient with hypogonadotrophic hypogonadism who was resistant to prolonged hCG therapy, normal pituitary gonadotrophin and testosterone responses were obtained following pulsatile LHRH administration. The sperm count rose to 11 ± 106/ml. His wife became pregnant and was delivered of a normal healthy female infant after an uneventful pregnancy.
OPIATE PEPTIDES CONTROL GROWTH HORMONE THROUGH A CHOLINERGIC MECHANISM IN MAN
Authors: DELITALA G. , GROSSMAN A. , BESSER G. M.
Published: March 2008

Opiate peptides are known to elevate circulating GH in man, and data in other animals suggest that acetylcholine may be involved. We have administered the long‐acting met‐enkephalin analogue DAMME to 6 normal males, and have shown that the resulting elevation in GH is blocked by the specific cholinergic antagonist, pirenzipine. It seems likely that a cholinergic mechanism may interact with opiate‐induced changes in GH in man.
DETECTION OF THYROID TUMOURS USING RADIO‐LABELLED ANTI‐THYROGLOBULIN
Authors: FAIRWEATHER D. S. , BRADWELL A. R. , WATSON‐JAMES S. F. , DYKES P. W. , CHANDLER S. , HOFFENBERG R.
Published: March 2008

IgG antibody to human thyroglobulin was labelled with 131Iodine (131I) and used to locate deposits of thyroid follicular and papillary tumours with a gamma camera. Of twelve patients studied a total of 40 tumour‘areas’were detected by a variety of clinical and radiological techniques. Sixteen of these were detected using conventional 131I uptake scans whereas 34 were positive on the antibody scans. The difficulty of assessing diffuse pulmonary lesions (3 areas) and the possibility that free 131I from labelled antibody may have contributed to the antibody scan results in six areas left 31 definite areas for scan comparison. Twenty seven (87%) areas were positive on the antibody scan, nine (29%) were positive on conventional 131I scans whilst 24 (77%) areas were detected by a combination of clinical and other radiological criteria. Five areas were positive on the antibody scan alone but there was evidence, albeit indefinite, that these areas contained tumour. Four of the 31 areas were not detected by the antibody scans.

The results indicate that anti‐thyroglobulin scanning is more sensitive than conventional 131I‐iodide scans and may contribute to the staging and management of thyroid cancer.
CLINICAL APPLICATIONS OF LHRH AND ITS ANALOGUES
Authors: SANDOW J.
Published: March 2008

The physiological requirement for activation of pituitary gonadotrophin secretion by pulsatile LHRH stimulation is discussed, and compared with the effect of pituitary stimulation by LHRH agonists. Initial stimulation is followed by a phase of progressive pituitary and gonadal inhibition. This inhibition is fully reversible at the end of agonist treatment. Clinical applications of high dose suppression are the treatment of precocious puberty and hormone‐dependent tumours (mammary and prostatic carcinoma). In women, agonist administration by nasal spray is a reversible method of inhibiting ovulation, and may also be useful in the treatment of endometriosis. Clinical advantages of agonist therapy are favourable biological tolerance, lack of side effects and rapid reversibility.
SERUM THYROGLOBULIN AFTER MANTLE IRRADIATION FOR HODGKIN'S DISEASE
Authors: HOLT G. , GALLIGAN J. , WINSHIP J. , ROESER P. , MORTIMER R.
Published: March 2008

Thyroid function and serum thyroglobulin levels were studied in 66 subjects whose Hodgkin's disease had been previously treated by cervical, mediastinal and axillary lymph node (mantle) irradiation. Three patients were already undergoing treatment for thyroid disorders (one for primary hypothyroidism, two for Graves’disease) and a fourth was found to have euthyroid Graves’disease. 36 (Group I) of the remaining 62 patients had normal free thyroxine indices, normal basal thyrotrophin (TSH) levels and normal TSH response to thyrotrophin releasing factor (TRH). In 20 patients (Group II) free thyroxine indices were normal but either basal TSH levels were raised or normal basal TSH levels were associated with an exaggerated response to TRH. In 6 patients (Group III) free thyroxine indices were subnormal. Although results of thyroid function tests in group I lay within the normal range, the mean free thyroxine index was significantly lower and mean basal and peak TSH levels were significantly higher than those of a group of 35 normal subjects, indicating mild thyroid hypofunction. Elevated thyroglobulin levels were demonstrated in 11 irradiated subjects (18%). Mean thyroglobulin levels were significantly raised in each of the three groups of irradiated subjects. Significant positive correlations were found between log serum thyroglobulin and log basal TSH (r = 0.453, P<0.001) and log peak TSH (r = 0.515, P<0.001) levels. Mild thyroid hypofunction is common after mantle irradiation for Hodgkin's disease and raised serum thyroglobulin levels are a sensitive indicator of TSH stimulation of the damaged thyroid gland.
INCREASED SECRETION OF INSULIN BUT UNCHANGED SECRETION OF GROWTH HORMONE IN HYPERGLYCAEMIC TYPE II DIABETICS TREATED WITH ACETYL‐SALICYLIC ACID
Authors: VIERHAPPER H. , BRATUSCH‐MARRAIN P. , WALDHÄUSL W. , NOWOTNY P. , PANZER S.
Published: March 2008

The effect of acetyl‐salicylic acid (ASA, 3 g/d for three days) on basal and arginine‐stimulated concentrations of insulin and growth hormone was studied in seven type II diabetics. From 120 min before until 120 min after the infusion of arginine‐hydrochloride (30 g/30 min) blood glucose concentrations were clamped at hyperglycaemic levels both during treatment with ASA (blood glucose: 12.7 ± 1.2 mmol/l) and during a control experiment without ASA (blood glucose: 12.9 ± 1.3 mmol/l). Concentrations of serum insulin in the hyperglycaemic state prior to arginine infusion were increased during treatment with ASA, whereas increments of serum insulin induced by i.v. arginine were unaffected. No difference was seen in either basal or stimulated concentrations of growth hormone. Thus, ASA enhances glucose‐induced secretion of insulin in type II diabetics but fails to potentiate the glucose‐dependent suppression of arginine‐stimulated growth hormone release. In contrast to the pancreatic β‐cell the glucose‐sensitive regulatory mechanism of growth hormone release appears to be unaffected by the inhibition of endogenous prostaglandin synthesis.
DYDROGESTERONE INCREASES SERUM LACTALBUMIN CONCENTRATION IN THE PUERPERIUM
Authors: MARTIN R. H. , EL SHEIKH M. A. A. , CHAPMAN C.
Published: March 2008

Eight women taking oral dydrogesterone 10 mg twice daily for the first 10 d of the puerperium, had significantly (P < 0.01) greater levels of serum lactalbumin than controls (n= 9), from day 4. No difference was observed in prolactin concentrations between groups.
THE ASSAY OF GRAVES’IMMUNOGLOBULINS: A COMPARISON OF DIFFERENT METHODS
Authors: HARDISTY C. A. , KENDALL‐TAYLOR PAT , ATKINSON S. , HUMPHRIES HAZEL , MUNRO D. S.
Published: March 2008

A multiplicity of techniques has arisen for the measurement of the immunoglobulins specifically associated with Graves’hyperthyroidism, which has led to difficulty in assessing the clinical significance of these immunoglobulins. In this study of untreated toxic Graves’disease we have taken two assays (LATS protector and thyrotrophin binding inhibiting immunoglobulin, TBII) which depend upon the measurement of binding to thyroid cell membranes, and correlated them with a bioassay which measures as the index of activity the biologically relevant end point of T3 secretion from thyroid tissue.

The frequency of positive responses obtained with each method was similar to that of previous studies; combining the results a positive response was found in 100%. No significant correlation was found between any of these three assays. We have also correlated the results of each assay with the serum T4 and serum T3 to assess which method relates most closely to circulating thyroid hormone levels in vivo. A highly significant correlation was obtained for TSAb measured by T3 secretion with both total serum T3 and total serum T4 levels. A positive correlation was also found for LATS protector, but not for TBII.

We conclude that although these assays are specific for Graves’immunoglobulins, they are measuring closely related but not identical immunoglobulin activities.
IMMUNOCYTOCHEMICAL GROWTH HORMONE AND PROLACTIN IN PITUITARY ADENOMAS CAUSING ACROMEGALY AND THEIR RELATIONSHIP TO BASAL SERUM HORMONE LEVELS AND THE GROWTH RESPONSE TO THYROTROPHIN RELEASING HORMONE
Authors: KRUSEMAN A. C. NIEUWENHUIJZEN , BOTS G. Th. A. M. , ROELFSEMA F. , FRÖLICH M. , VAN DULKEN H.
Published: March 2008

Basal prolactin levels and the dynamics of growth hormone secretion in response to intravenous TRH in 34 untreated acromegalic patients were compared with immunocytochemical localization of growth hormone and prolactin in the adenoma cells.

The serum prolactin level was elevated in 13 patients. All adenomas contained growth hormone detectable by immunocytochemistry. Twelve adenomas contained prolactin as well; of these only six were associated with hyperprolactinaemia. In six patients with a mixed adenoma the serum prolactin levels were in the normal range. In 17 patients the growth hormone value more than doubled after TRH. Eight of these patients had hyperprolactinaemia, and in only six did the adenomas contain immunoreactive prolactin; eight were associated neither with hyperprolactinaemia nor with positive immunostaining for prolactin. Eight adenomas had suprasellar extension, six of these were associated with hyperprolactinaemia. Of the seven adenomas with hyperprolactinaemia but no adenomatous prolactin immunoreactivity, four had supprasellar extension. In three patients hyperprolactinaemia was associated neither with prolactin immunoreactivity in the adenoma cells nor with suprasellar extension of the tumour.

It is concluded that in acromegalics (1) there is no relation between hyperprolactinaemia, and the presence of prolactin in the adenoma cells; (2) the hyperprolactinaemia may be due either to adenomatous prolactin secretion or possibly suprasellar mass interference of hypothalamic control of normal prolactin cells; and (3) the presence of hyperprolactinaemia or immunocytochemically defined adenomatous prolactin does not correlate with the reactivity of the adenomatous growth hormone cells to TRH.