bluuebunny/crossref_metadata_2025 huggingface dataset:
INSULIN RESISTANCE IN CIRRHOSIS: EVIDENCE FOR A POST‐RECEPTOR DEFECT
Authors: PROIETTO J. , NANKERVIS ALISON , AITKEN PATRICIA , DUDLEY F. J. , CARUSO GLORIA , ALFORD F. P.
Published: March 2008

Receptor and post‐receptor abnormalities of insulin action and their possible role in the insulin resistance of cirrhosis were examined in eight biopsy‐proven cirrhotic subjects and eight age‐weight matched healthy volunteers. To this end, oral glucose tolerance tests (OGTT), insulin dose response curves and insulin binding to circulating monocytes were determined for each subject. The dose‐response curves for the cirrhotic subjects were significantly shifted to the right compared to the control subjects, indicating the presence of insulin insensitivity (ED50 223 ± 30 versus 64 ± 8 mU/l respectively; P<0.001). The magnitude of the right shift of the insulin‐dose response curves correlated significantly (P< 0.001) with the OGTT 2 h insulin levels (r = 0.74) and the insulin areas under the OGTT curves (r = 0.86). In contrast, insulin responsiveness was marginally elevated in the cirrhotic group (maximal glucose disposal 680 ± 47 versus 574 ± 21 ml/m2/min; P<0.05). Insulin binding to circulating monocytes was normal in the cirrhotic subjects. It is concluded that the insulin resistance of cirrhosis is due to a post‐receptor defect in insulin action which reduces insulin sensitivity but not insulin responsiveness.
THE EFFECTS OF CYPROTERONE ACETATE AND ETHINYL OESTRADIOL ON CARBOHYDRATE METABOLISM
Authors: SEED M. , GODSLAND I. F. , WYNN V. , JACOBS H. S.
Published: March 2008

Carbohydrate metabolism was studied in a group of 66 women, taking cyproterone acetate (CA) and ethinyloestradiol (EO) as anti‐androgen therapy for the treatment of hirsutism and/or acne. A reverse sequential treatment cycle was used and women were studied in two groups: the first when taking the combination of CA and EO during the first 12 days of the treatment cycle, and the second taking EO alone during days 13 to 22. The combination reduced fasting plasma glucose and raised fasting plasma insulin concentrations. There was deterioration of glucose tolerance with increased plasma insulin concentrations and these effects were progressive with time. The plasma insulin response to intravenous tolbutamide was increased by 50% but there was no accompanying change in the glucose nadir as compared with controls. These results show that the combination of CA and EO causes insulin resistance. Plasma C‐peptide concentrations following oral glucose were unchanged compared with controls. This shows that the observed hyperinsulinaemia was due to a reduction of hepatic uptake of insulin rather than its increased secretion. We propose that these effects are due to a CA‐induced elevation of fasting plasma insulin resulting in downregulation of hepatic insulin receptors with subsequent induction of insulin resistance and impairment of hepatic insulin uptake. C‐peptide concentrations following i.v. tolbutamide were significantly higher on treatment with CA and EO than in controls indicating increased pancreatic secretion of insulin. Tests carried out while patients were taking EO alone showed impairment of glucose tolerance only with no change in insulin levels. There was an increase in plasma insulin in response to tolbutamide but this was not significant. We conclude that these results are explained by a reduced but persisting effect of CA.
EFFECTS OF GRF(1–40) AND DOMPERIDONE ON GH SECRETION IN NORMAL MAN
Authors: GIUSTI M. , MAZZOCCHI G. , SESSAREGO P. , MIGNONE D. , LOMEO A. , MONACHESI M. , GIORDANO G.
Published: March 2008

In eight normal adult men pituitary secretion following GRF(1–40) was studied. GRF administration (50 μg i.v.) was followed by an increase in GH release with a peak value between the 15 and 60 min. No effects were noticed on LH, FSH, PRL, TSH and ACTH secretion. GH and PRL release was also studied after domperidone (DOM) (5 mg i.v./h), and GRF plus DOM. PRL increased significantly after DOM and GRF plus DOM. During GRF plus DOM a more marked GH release was observed in comparison with the hormone response to GRF alone at 15–45 and 120 min (P < 005). This phenomenon was found in six out of eight subjects studied. Mean peak and secretory area was greater (P < 005) after GRF plus DOM than after GRF alone. These data suggest that GRF(1–40) at the dose used is a useful tool in the study of GH secretion. The GH pattern during GRF plus DOM seems to indicate that dopaminergic tone may play a direct inhibitory role on GH secretion in man.
SERUM THYROGLOBULIN IN PATIENTS WITH AUTONOMOUS THYROID NODULES
Authors: MADEDDU G. , CASU A. R. , MARROSU A. , MARRAS G. , LANGER M.
Published: March 2008

To investigate further the relationship between thyroid hormones and thyroglobulin (TG) secretion, total and free thyroid hormone levels, TSH and its response to TRH and serum TG concentrations were determined in 61 patients with solitary autonomous thyroid nodules. Thyroid function varied widely from euthyroidism to clearcut thyrotoxicosis. Serum TG levels were significantly higher in patients than in normal controls. Individually they were above the normal range (> 50 ng/ml) in 95% of the patients, as well as in those with normal total and/or free thyroid hormone levels. Patients with high total and/or free thyroid hormone levels had higher TG concentrations than euthyroid patients. TG concentrations were significantly correlated with FT3 values. They were higher in patients in whom TSH was unresponsive to TRH than in the responsive groups. TG was also slightly higher in patients with hot nodules than in those with warm nodules. These data seem to indicate that TG is secreted along with thyroid hormones in the absence of any stimulatory action. It also is a sensitive index of thyroid hyperfunction. Twenty patients were controlled 6 months after nodulec‐tomy. TG levels, though significantly lower than in the preoperative state, were still higher than in normal subjects. This increase was attributed to persistent hyperthyroidism in two patients only. The observation that the increase in TSH after TRH stimulation in post‐operative patients was greater than that found in normal controls led us to believe that in most cases the high TG levels after surgery are due to stimulation of the normal thyroid tissue by rebound TSH secretion.
THE EFFECT OF ENDOGENOUS PROGESTERONE ON SERUM LEVELS OF 5α‐REDUCED ANDROGENS IN HIRSUTE WOMEN
Authors: DEWIS P. , NEWMAN M. , ANDERSON D. C.
Published: March 2008

This study was to examine indirectly the effect of endogenous progesterone, a known competitor for 5α‐reductase, on androgen metabolism in target organs in hirsute women. Serum levels of progesterone, testosterone (T), androstene‐dione (A), dihydrotestosterone (DHT) and 5α‐androstane 3α17β‐diol (3α‐diol) and sex hormone binding globulin (SHBG) were assessed serially over a four week period in normal women, six hirsute women with regular menstrual cycles, eight hirsute women with oligomenorrhoea (and presumptive polycystic ovaries) and seven non‐hirsute women with oligomenorrhoea. Serum T and A levels were significantly higher than normal in both hirsute and non‐hirsute women with oligomenorrhoea, while serum SHBG was significantly lower than normal in the two groups of hirsute women. The calculated free T level was higher than normal in all three groups of patients. DHT levels were not significantly different from normal in any of the three groups of patients. The 3α‐diol level showed considerable overlap with normal in all groups of patients and was only significantly higher than normal in hirsute women with oligomenorrhoea (P& lt;005). There was a small fall in DHT in the late luteal phase of the cycle of those women with a sustained rise in serum progesterone in the second half of the cycle, but no change in serum 3α‐diol. These studies suggest that serum 3α‐diol may not be as good an indicator of peripheral androgen metabolism in hirsute women as previously reported and that a rise in serum progesterone has only a minimal effect on circulating levels of the active 5α‐reduced androgen metabolites. Although in vitro 3α‐diol has been shown to be a potent inhibitor of 5α‐reductase this casts doubt on its role in this regard in vivo.
ENHANCED GLUCONEOGENIC CAPACITY FROM GLYCEROL IN HYPERTHYROID MAN: EVIDENCE IN FAVOUR OF A BETA‐ADRENERGIC MECHANISM
Authors: McCULLOCH A J. , STEELE N. R. , KENDALL‐TAYLOR P. , BAYLIS P.H , ALBERTI K.G.M.M.
Published: March 2008

We have previously shown that gluconeogenesis, assessed by glycerol clearance, is increased in hyperthyroid man. The mechanism underlying this change is uncertain but many of the metabolic changes found in hyperthyroidism are thought to be due to increased catecholamine sensitivity of peripheral tissues. To test the hypothesis that enhanced gluconeogenic capacity from glycerol in hyperthyroidism might be mediated via a β‐adrenergic mechanism we have estimated glycerol clearance in thyrotoxic subjects before and during treatment with a non‐selective β‐adrenergic blocking drug propranolol (Inderal LA). Control subjects of similar age and weight were also tested. In hyperthyroid subjects, blood glucose and blood glycerol concentrations were increased but blood lactate, pyruvate and alanine concentrations were normal. Glycerol clearance was increased and followed a double exponential decay with a shortened second component half‐time. Endogenous glycerol production was increased three fold. Following β‐blockade blood glucose and blood glycerol concentrations fell although blood glucose concentrations remained above normal values. Glycerol clearance and endogenous glycerol production were also decreased but remained significantly higher than in control subjects. Serum thyroxine and serum triiodothyronine concentrations showed no significant change although mean values fell by 10% and 17% respectively. We conclude that the increase in gluconeogenic capacity from glycerol in hyperthyroid subjects is mediated in part by a β‐adrenergic mechanism.
PLASMA RENIN ACTIVITY IN INSULIN‐DEPENDENT DIABETICS WITH RAISED GLOMERULAR FILTRATION RATE
Authors: WISEMAN M. J. , DRURY P. L. , KEEN H. , VIBERTI G. C.
Published: March 2008

Basal and ambulant plasma renin activity (PRA) were measured in 12 insulin‐dependent diabetics (IDDS) with elevated glomerular filtration rate (GFR), 12 IDDs with normal GFR matched for age, sex and duration of diabetes and 12 age and sex matched non‐diabetic control subjects. The two diabetic groups did not differ with respect to extracellular fluid volume, urinary sodium excretion, arterial blood pressure, mean plasma glucose concentration or urinary glucose excretion. Basal PRA did not differ significantly between the three groups. Ambulant PRA was significantly higher (P < 002) in the group of IDDs with elevated GFR than in the control group. Our data suggest that, in IDDs with high GFR, haemodynamic alterations may stimulate a rise in PRA and thus angiotensin, a potent vasoconstrictor. Whether this represents an attempt of the renin‐angiotensin system to normalise GFR or is the result of insensitivity of the renal vasculature to circulating angiotensin remains to be established.
FETAL GROWTH CONTROL: THE ROLE OF INSULIN AND RELATED PEPTIDES
Authors: MILNER R. D. G. , HILL D. J.
Published: March 2008

Both insulin and the related peptides, the insulin‐like growth factors/somatomedins, may function as anabolic factors in the regulation of fetal body size. Infants born to women suffering from diabetes mellitus may show increased deposition of subcutaneous fat and enhanced lean body mass, findings reproduced in experimental animal fetuses with induced hyperinsulinaemia. Fetal adiposity may be associated with a life‐time tendency to obesity and its associated diseases. Insulin‐like growth factors I (IGFI) and II are present in the circulation of the newborn infant and animal fetus and correlate positively with birth size. The fetal tissues are biologically responsive to IGFs in vitro and are rich in specific cell membrane receptors, those predominantly recognizing IGFI being structurally and functionally similar to the insulin receptor. Insulin could theoretically influence fetal tissues by an interaction with either the insulin or IGF receptor. IGF release is a property of multiple fetal tissues in vitro, but, in contrast to postnatal life, is not dependent on growth hormone. Fetal IGF production may be influenced by placental lactogen, especially IGFII which rapidly declines in the circulation following parturition in the rat and sheep. A positive association also exists between circulating levels of insulin and IGFs when the former is experimentally manipulated in the animal fetus. Similarly the infant born with transient diabetes mellitus has low cord blood levels of insulin and IGFI. Insulin has a dual role in prenatal life. In the last trimester insulin functions as a glucoregulatory hormone, but from much earlier in gestation creates an anabolic environment in the fetus supplied with optimal nutrients. This latter mechanism of action is unclear and probably heterogenous, but in overview is permissive rather than obligatory. In contrast the growth‐promoting role of the IGFs is direct but their interaction with fetal tissues, and thus the overall emphasis of fetal growth, may be paracrine.
HYPOMAGNESAEMIA: STUDIES OF PARATHYROID HORMONE SECRETION AND FUNCTION
Authors: ALLGROVE J. , ADAMI S. , FRAHER L. , REUBEN A. , H.O'RIORDAN J. L.
Published: March 2008

Nine patients with hypomagnesaemia have been studied. Six had magnesium deficiency secondary to malabsorption or diarrhoea and three had excessive urinary losses of magnesium. Hypocalcaemia was also present in eight. Parathyroid hormone (PTH) was measured using amino‐terminal and carboxyterminal specific immunoradiometric assays and also, in one patient, using a cytochemical bioassay. Amino‐terminal PTH (N‐PTH) varied directly with the concentration of magnesium; carboxy‐terminal PTH (C‐PTH) was raised in all patients. When magnesium was injected, both N‐PTH and C‐PTH rose regardless of the initial concentration, indicating that hypomagnesaemia was limiting PTH secretion. The clearance of endogenous PTH was measured in one patient, after injection of magnesium. Seven minutes after reaching its peak, C‐PTH had fallen to 69% and N‐PTH fell to 22% of its maximum values; the initial half life of N‐PTH was less than 2 min. In the same study biologically active PTH (bio‐PTH) disappeared rapidly with a half‐time of disappearance of 1–2 min. Responsiveness to PTH was measured by the rise in plasma cyclic 3′5′‐adenosine monophosphate (cAMP) following PTH injection. The rise in plasma cAMP was inversely related to the concentrations of magnesium and PTH at the time. It is suggested that the concentration of PTH rather than the degree of hypomagnesaemia is the most important factor determining the responsiveness of target tissues to PTH in magnesium deficiency,
STUDIES IN CONSTITUTIONALLY TALL ADOLESCENTS: SOMATOSTATIN DECREASE ASSOCIATED WITH GROWTH HORMONE INCREASE AFTER TRH INJECTION
Authors: BLANCO MATILDE GARCIA , BRION DANIELE EVAIN
Published: March 2008

The paradoxical GH response to TRH observed in certain adolescents with constitutional tall stature is associated with a 60% fall in plasma levels of somatostatin. Conversely, those tall subjects who do not show a GH increase after TRH, or during a saline control infusion maintain steady levels of somatostatin in plasma. It is thus hypothesized that the GH release after TRH is due to a decreased inhibitory effect of somatostatin at the pituitary level and that this reduced effect may play an aetiological role in certain children with ‘constitutional’ tall stature.
ADRENALINE CAUSES HYPOKALAEMIA IN MAN BY β2 ADRENOCEPTOR STIMULATON
Authors: And A. D. STRUTHERS , REID J. L.
Published: March 2008

Increased circulating adrenaline produces systemic hypokalaemia by the stimulation of a membrane bound Na/K ATPase. In man, this enzyme appears to be linked to an adrenoceptor of the β‐subtype. We have further studied the subtype of β‐adrenoceptor involved by infusing adrenaline intravenously in normal volunteers after pretreatment with either a selective β2 antagonist (ICI 118551) or placebo. During the adrenaline infusion the serum potassium fell from 4.08 ± 0.21 to 3.32 ± 0.25 mmol/1 (P <0.002). This adrenaline induced hypokalaemia was completely blocked by ICI 118551 (3.82 ± 0.13 to 4.03 ± 0.22 mmol/1, NS). Adrenaline also caused electrocardiographic changes of T wave flattening (–1.8 ± 1.5 mm, P <005) whereas the T wave height increased after ICI 118551 (51.0 ± 0.9 mm, P <005). This suggests that adrenaline acts via β2 adrenoceptors in man to cause potassium influx and systemic hypokalaemia.
THE EFFECT OF PLASMA GLUCOSE ON THE GROWTH HORMONE RESPONSE TO HUMAN PANCREATIC GROWTH HORMONE RELEASING FACTOR IN NORMAL SUBJECTS
Authors: SHARP P. S. , FOLEY K. , CHAHAL P. , KOHNER E. M.
Published: March 2008

Pituitary responsiveness to 44 amino acid human pancreatic growth hormone releasing factor was tested under conditions of euglycaemia and hyperglycaemia in six normal subjects. A 100 μg dose of growth hormone releasing factor was given at a fasting blood glucose of 5.1 ± 0.4 mmols/1 (mean ± S.D.), and at a blood glucose level of 10.9 ± 1.5. Under conditions of hyperglycaemia, the GH response to releasing factor was significantly depressed when compared to results obtained at fasting blood glucose (n= 6, t = 3.902, P= 0.0114). This is in keeping with the hypothesis that hyperglycaemia, mediated by the hypothalamus, causes decreased pituitary sensitivity to natural growth hormone releasing hormone.
THE PROLACTIN RESPONSE TO SUCKLING
Authors: GLASIER ANNA , MCNEILLY A. S. , HOWIE P. W.
Published: March 2008

Changes in prolactin concentration during single suckling episodes in twenty breast‐feeding women from four to 40 weeks post partum have been investigated. Basal prolactin concentration and the increase in prolactin secretion in response to single suckling episodes and amount of milk taken by the infant were both independent of time post partum until the introduction of supplementary feeds, when a significant decrease with time was apparent. Basal concentrations of prolactin were dependent upon the interval between suckling episodes, and the magnitude of the prolactin response varied with the time of day when suckling took place. The relationship between acute suckling episodes and the long term pattern of prolactin secretion over time post partum is discussed.
MEASUREMENT OF IMMUNOREACTIVE γ‐MSH IN HUMAN PLASMA
Authors: HALE ANN C. , RATTER SALLY J. , TOMLIN SUSAN J. , LYTRAS N. , BESSER G. M. , REES LESLEY H.
Published: March 2008

A radioimmunoassay for immunoreactive γ‐MSH (IR‐γ‐MSH) in human plasma has been developed. The assay is capable of detecting normal basal circulating levels which range from < 20‐100 ng/1 at 0900 h. Plasma levels are raised concomitantly with ACTH during insulin induced hypoglycaemia and CRF stimulation and suppressed with dexamethasone. Chromatographic characterisation of IR‐γ‐MSH in plasma demonstrates a major peak of IR‐γ‐MSH, corresponding to purified glycosylated N‐terminal pro‐opiome‐lanocortin 1‐76, when IR‐γ‐MSH is secreted from the pituitary. In contrast IR‐γ‐MSH produced ectopically appears to be heterogeneous.
SERUM THYROGLOBULIN LEVELS IN PRETERM NEONATES
Authors: NAYER PH. DE , CORNETTE C. , VANDERSCHUEREN M. , EGGERMONT E. , DEVLIEGER H. , JAEKEN J. , BECKERS C.
Published: March 2008

Serum thyroglobulin (Tg) levels were determined in preterm neonates. Very high values were found at birth. A significant negative correlation was observed between Tg levels and gestational age. A longitudinal study indicates that a very sharp decrease in Tg levels occurred after birth. Three weeks after birth, the values were close to the values of full‐term neonates. These high hTg values could result either from an increased turnover of hTg or from a lower clearance rate of this iodoprotein.
A SIMPLE DHEAS LOADING TEST IN THE ANTEPARTUM DIAGNOSIS OF PLACENTAL SULPHATASE DEFICIENCY
Authors: SELBY C. , JEFFCOATE W.J. , ROSE F.A. , TAYLOR N.F.
Published: March 2008

The accurate antenatal diagnosis of placental sulphatase deficiency (PSD) is essential if this condition is to be distinguished from others in which levels of oestrogen are low. In this study we have evaluated a simple protocol determining the serum oestradiol response to 50 mg of dehydroepiandrosterone sulphate (DHEAS) given intravenously to twelve women with low serum or urinary oestrogens. Seven of the women had PSD confirmed by other means, the remaining five had other reasons for the low oestrogen levels. In affected pregnancies the rise in oestradiol was lower, the peak occurred earlier and the level fell towards baseline at 60 min. In the unaffected women, timing of the peak value was not consistent and there was no trend towards basal values at 60 min. There was clear discrimination between the two groups at all times after the injection. but the separation was greater at 60 min.
THE TREATMENT OF HYPOGONADOTROPHIC HYPOGONADISM IN MEN BY THE PULSATILE INFUSION OF LUTEINISING HORMONE‐RELEASING HORMONE
Authors: MORRIS D. V. , ADENIYI‐JONES R. , WHEELER M. , SONKSEN P. , JACOBS H. S.
Published: March 2008

The effects of chronic subcutaneous infusion of luteinising hormone‐releasing hormone (LHRH) have been studied in a group of 17 male patients with hypogonadotrophic hypogonadism (HH). Ten of the patients had primary and seven secondary failure of gonadotrophin release, and all but four had previously been treated with gonadotrophin injections. Treatment was continued for between one and 18 months and was well tolerated by all except one patient who became allergic to LHRH. An increase in the basal gonadotrophin concentrations occurred in all except four patients within one week of the initiation of therapy, and this was associated with a rise in the serum testosterone level in eight patients. Increased spermatogenesis was demonstrated in seven cases and three pregnancies have resulted thus far. Pituitary desensitisation to the effects of LHRH was found in five subjects with primary HH who failed to produce any increase in testosterone secretion despite an initial stimulation of gonadotrophin release. We conclude that chronic pulsatile infusion of LHRH is an effective technique for the treatment of some cases of hypogonadotrophic hypogonadism.
RESPONSE OF CIRCULATING SOMATOSTATIN, INSULIN, GASTRIN AND GIP, TO INTRADUODENAL INFUSION OF NUTRIENTS IN NORMAL MAN
Authors: LUCEY M. R. , FAIRCLOUGH P. D. , WASS J. A. H. , KWASOWSKI P. , MEDBAK S. , WEBB J. , REES L. H.
Published: March 2008

We have studied the effect of direct infusion of nutrients into the duodenum of normal subjects on circulating plasma somatostatin, insulin, gastrin and gastric inhibitory polypeptide (GIP) levels. Six normal subjects were given on four separate occasions 150 ml of isotonic solutions containing 100 calories of carbohydrate, protein, or fat, and a control solution of saline, by infusion into the second part of the duodenum. Plasma somatostatin rose slightly after carbohydrate, mean basal 30 ± 3 pg/ml, peak 46±16 pg/ml at 15 min; and more markedly after protein, peak 57 ± 9 pg/ml at 30 min. However, fat was the most potent intraduodenal stimulus to plasma somatostatin release into circulation, peak 101 ± 11 pg/ml at 30 min. The plasma insulin rise was greatest after carbohydrate, peak 68 ± 10 i.u., but there was a significant rise after protein also, peak 34 ±6 i.u. Plasma gastrin rose significantly after protein only, peak 70 ± 22 pg/ml. Plasma GIP rose markedly after carbohydrate, basal 506 ± 50 pg/ml, peak 1480 ± 120 pg/ml. Protein was also a potent stimulus of circulating plasma GIP release, peak 1200 ± 190 pg/ml, while fat was the least potent, peak 730±190 pg/ml. Thus, calorie for calorie, fat is the most potent intraduodenal nutrient stimulus of circulating somatostatin. We postulate therefore that somatostatin may be an enterogastrone–a circulating hormone released by intraduodenal fat which inhibits gastric acid secretion. Fat is the least potent intraduodenal nutrient stimulus of circulating GIP release. This is evidence against the hypothesis that circulating GIP acts as an enterogastrone.
MAMMARY GIGANTISM AND D‐PENICILLAMINE
Authors: FINER N. , EMERY P. , HICKS B. H.
Published: March 2008

Mammary gigantism is a rare complication of D‐penicillamine treatment. We report a further case with pathological and endocrine details together with a review of the seven cases previously reported and possible mechanisms.
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

Fourteen 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

To 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

Postural 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

Aldosterone 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

Fusaric 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

A 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

Patients 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

Iopanoic 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

A 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

The 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

Intranasally 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

The 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

Pubertal 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

A 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

A 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

Cells 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.
THE INTERACTION OF TRH AND DOPAMINERGIC MECHANISMS IN THE REGULATION OF STIMULATED PROLACTIN RELEASE IN MAN
Authors: HO K. Y. , SMYTHE G. A. , LAZARUS L.
Published: March 2008

The manner by which dopaminergic and TRH mechanisms interact to control PRL release is not known. Whilst dopamine receptor antagonists and TRH both release PRL, it is not known if the PRL released by these two mechanisms reflects similar aspects of physiological control, or if PRL responses to these mechanisms of release can be dissociated. We addressed this question by studying the PRL responses to maximal stimulatory dose of TRH and domperidone (a DA receptor antagonist), which were administered sequentially, simultaneously or separately on different occasions. Six normal volunteers undertook three sets of studies: (1) standard PRL stimulation tests to 400 μg TRH, 5 mg domperidone or simultaneous TRH/domperidone administration, (2) domperidone bolus‐infusion study in which either 5 mg domperidone or 400 μg TRH was administered i. v. at 120 min during a 240 min infusion of domperidone (50 μg/min) which was preceded by a 5 mg i. v. bolus of the drug, and (3) TRH bolus‐infusion study in which domperidone or TRH was administered i. v. at 120 min during a 240 min infusion of TRH (0.4 μg/min) which was preceded by a 400 μg i. v. bolus of the drug. In Study 1, simultaneous TRH/domperidone administration induced an incremental rise in PRL (5195 · 940 mIU/1) which was significantly greater (P < 0.0005) than with either domperidone (3730 · 825 mIU/1) or TRH (1335 · 300 mIU/1) alone. In study 2, TRH administration at 120 min resulted in a significant rise (P < 0.01) in PRL (ΔPRL 960 · 232 mIU/1) whilst the second dose of domperidone did not, thus suggesting that the initial bolus and subsequent infusion had resulted in complete DA receptor blockade. In Study 3, domperidone administered at 120 min induced a marked rise in PRL (ΔPRL 3609 · 963 mIU/1). In contrast, the corresponding TRH stimulus resulted in a small rise (ΔPRL 142 · 42 mIU/1) suggesting that the PRL release induced by the initial bolus and subsequent infusion had been near maximal. Thus, TRH is able to induce significant PRL release in the presence of maximal DA receptor blockade, and domperidone, in
HYPERPROLACTINAEMIA, AMENORRHOEA AND GALACTORRHOEA DUE TO A PITUITARY THYROTROPH ADENOMA
Authors: SCANLON M. F. , HOWELLS S. , PETERS J. R. , WILLIAMS E. D. , RICHARDS S. , HALL R. , THOMAS J. PICTON
Published: March 2008

A case of hyperprolactinaemia/amenorrhoea‐galactorrhoea syndrome is described. A prolactinoma was diagnosed, but histology of the excised tumour revealed it to be a thyrotoph adenoma, α‐subunit and β‐TSH levels were lowered after the operation. The significance of this tumour is discussed.
PROLACTIN RESPONSES TO THYROTROPHIN RELEASING HORMONE DO NOT DISTINGUISH PATIENTS WITH ISOLATED GONADOTROPHIN DEFICIENCY FROM NORMALS
Authors: HAWTHORNE G. , SHERIDAN B. , TRAUB A. I. , ATKINSON A. B.
Published: March 2008

Prolactin secretion in response to TRH has been assessed in six patients with isolated gonadotrophin deficiency (IGD) and in eight normal controls. In all six subjects with IGD, serum oestradiol was below the detection limit of the method. There was no statistical difference between either the basal or maximum increment of serum prolactin between the two groups. Recent claims that prolactin responses to TRH distinguish constitutional delay of puberty from IGD have therefore not been supported.