bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of big, big prolactin in patients with hyperprolactinaemia
Authors: Lelte Valerlano , Cosby Helle , Sobrinho Luis G. , Fresnoza Agnes , Santos M. Amparo , Frlesen Henry G.
Published: March 2008

OBJECTIVE The present study was designed to characterize the clinical findings of patients with macroprolactin‐aemia (sustained hyperprolactinaemia where the predominant form of prolactin is of large molecular size) and to further assess the bioactivity and structure of big, big prolactin (BB‐PRL).

DESIGN The patients with macroprolactinaemia were identified by the domperidone test and by gel filtration of their serum samples. The bioactivity of sera and fractions containing BB‐PRL was evaluated and the fractions analysed by affinity chromatography and electrophoresis.

PATIENTS Eleven patients with hyperprolactinaemia in whom BB‐PRL was the predominant form (group 1) were studied. Sera were also examined from eight patients with prolactinomas (group 2). Thirty‐one first‐degree relatives from patients in group 1 were screened for macroprolactinaemia.

MEASUREMENTS Prolactin in the sera and fractions was measured by radiolmmunoassay (RIA), immunoradiometric assay (IRMA) and Nb2 cell bioassay (Nb2 BA). The distribution of BB‐PRL was also investigated after protein A Sepharose chromatography, Immunoprecipitation, SDS‐PAGE and Western blotting.

RESULTS (1) Seven out of 11 patients in group 1 had galactorrhoes, menstrual disturbances or both; (2) the ratio Nb2 BA/RIA in whole serum was similar to the ratio found in group 2 patients; (3) the ratios Nb2 BA/RIA and Nb2 BA/IRMA in the BB‐PRL fractions obtained after gel filtration were significantly lower than in whole serum (P < 0.003); (4) in group 1 patients, RIA estimates of PRL did not correlate either with Nb2 BA or with IRMA, while Nb2 BA and IRMA were correlated. In group 2 patients, RIA and Nb2 BA were correlated (r= 0.881; P= 0.02); (5) 24–86% of BB‐PRL reacted as immunoglobulin‐bound PRL as demonstrated by protein A Sepharose and by SDS‐PAGE; (6) a high percentage of BB‐PRL (54, 49 and 43%), was found in three of the serum samples obtained from 31 first‐degree relatives of patients in group 1.

CONCLUSIONS Macroprolactinaemia must be suspected not only in patients with asymptomatic hyperprolactinaemia but also in women with galactorrhoea and/or menstrual disturbances who have normal responses to PRL stimulating tests. Our results also suggest that the absence of symptoms in these women is not explained by a lower bioactivity of BB‐PRL. Instead, we postulate that due to the high molecular weight, BB‐PRL does not easily cross the capillary walls. During gel chromatography either a change in the structure of BB‐PRL and/or a removal of substances which potentiate the bioactivity of PRL occurs, explaining the lower bioactivity of fractions containing BB‐PRL in comparison with the serum. In this study we demonstrated that at least half (range 24–86%) of BB‐PRL behaves as an immunoglobulin‐bound PRL. Finally, we found that macroprolactinaemia was not genetically transmitted to first‐degree relatives in the majority of the cases studied.
Oncogenous osteomalacia and malignancy
Authors: Harvey J. N. , Gray C. , Belchetz P. E.
Published: March 2008

An example of oncogenous osteomalacia is described in association with the rare mesenchymal chondroblastoma. The tumour was characterized with a variety of immunohistochemical antibodies which confirmed its mesenchymal origin. Despite several surgical excisions of local recurrence, plasma 1,25‐dihydroxyvitamin D3 concentrations (off treatment) indicate continued tumour activity and the continuing need for vitamin D therapy. This case and two others briefly discussed illustrate some of the difficulties in diagnosis and in achieving a cure in cases of oncogenous osteomalacia.

Oncogenous osteomalacia in association with any malignant tumour is rare, there being eight previously recorded cases. Details of these cases are briefly reviewed for comparison. Despite undoubted malignancy our patient has survived 30 years from presentation indicating the benefits of aggressive surgical management.
Parathyroid hormone‐related protein: a possible endocrine function in lactation
Authors: Grill Vivian , Hillary Janet , Ho Patricia M. W. , Law Frieda M. K. , Macisaac Richard J. , Maclsaac Ian A. , Moseley Jane M. , Martin T. John
Published: March 2008

OBJECTIVE Parathyroid hormone‐related protein (PTHrP), initially discovered as the factor responsible for the syndrome of humoral hypercalcaemia of malignancy, has also been found to be expressed in placenta, in pregnant uterus, in the fetus at many locations, and in the lactating mammary gland. This study sought to establish whether PTHrP reaches the maternal circulation when it is expressed in mammary tissue during lactation or in the maternal reproductive tract during gestation.

DESIGN Blood samples were collected from 53 subjects: 18 pregnant women in all stages of gestation, 19 lactating mothers and 16 non‐lactating post‐partum controls.

MEASUREMENTS PTHrP was measured using a specific and validated radioimmunoassay. Parathyroid hormone was measured by two‐site immunoradiometric assay. Total calcium was measured by atomic absorption spectre‐photometry.

RESULTS Circulating levels of PTHrP were readily detectable in 12 of 19 nursing mothers (range 2.7–7.8 pmol/1) but in none of the mothers who were bottle feeding. PTHrP was also detected in one of 18 pregnant subjects. Parathyroid hormone concentrations were lower in lactating mothers (2.3 ± 1.0 pmol/1), than in non‐lactating mothers (3.5 ± 1.2 pmol/1) (P <0.01).

CONCLUSION PTHrP reaches the maternal circulation during lactation in amounts which could produce a systemic effect.
Circulating lipids and minor abnormalities of thyroid function
Authors: Parle J. V. , Franklyn J. A. , Cross K. W. , Jones S. R. , Sheppard M. C.
Published: March 2008

OBJECTIVE We determined the effect of subclinical hyperthyroidism (defined as low circulating TSH with normal serum free T4) and subclinical hypothyroidism (raised serum TSH with normal free T4) on fasting levels of blood lipids.

DESIGN Prospective study of lipid concentrations in patients identified as having abnormal TSH.

PATIENTS Patients were identified in a population screening study of those over 60 years, with persistently low TSH with normal free T4 (n= 27) or high TSH but normal free T4 (n= 57). Patients were matched to controls with normal serum TSH by age, sex and body mass index.

MEASUREMENTS Serum TSH, free T4, free T3, total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol.

RESULTS Serum free T4 measurements were significantly higher in those with subclinical hyperthyroidism than in their controls (P <0.001) and lower in those with subclinical hypothyroidism than in matched controls (P <0.001). Measurement of fasting lipids in patients and controls revealed a marked (12.2%) reduction in serum total cholesterol in subclinical hyperthyroidism (P <0.01); no significant difference in fasting lipids between patients with subclinical hypothyroidism and controls was observed.

CONCLUSIONS Differences in free T4 between those with low or high TSH and controls with normal TSH suggest that abnormalities of TSH directly reflect thyroid hormone excess and deficiency. A reduction in cholesterol in those with subclinical hyperthyroidism suggests a direct influence of thyroid hormone excess on lipid metabolism in these patients.
Failure to find an association of blood group P1 with thyroid‐associated ophthalmopathy
Authors: Weetman A. P. , Poole Joyce
Published: March 2008

OBJECTIVE Genetic factors have been proposed to account for the development of ophthalmopathy in a proportion of patients with Graves' disease. The aim of this study was to confirm the previously reported association between blood group P1 and thyroid‐associated ophthalmopathy.

DESIGN A prospective study of sequential Caucasian patients.

PATIENTS We studied 169 patients with Graves' disease, 84 of whom had grade 3,4 or 6 ophthalmopathy and 85 had no eye signs.

MEASUREMENTS Blood group P1 was measured by a standard serologlcal technique.

RESULTS The frequency of the P1 blood group was 74.1% in the patients without eye signs and 77.4% in those with ophthalmopathy (X2= 025, P>0.1). By Woolf's method there was no significant difference in the test for heterogeneity of estimates between the present and the previously reported series of Graves' patients. Combining the results (n= 279), the pooled relative risk for ophthalmopathy with blood group P1 did not differ significantly from 10(X2= 233, P>0.1).

CONCLUSIONS The presence of blood group P1 In patients with Graves' disease does not appear to be associated with an increased risk of developing thyroid‐associated ophthalmopathy.
Correlation between ovarian steroids and lipid fractions in relation to age in premenopausal women
Authors: Brideau Natalie‐Anne , Forest Jean‐Claude , Lemay André , Dodin Sylvie
Published: March 2008

OBJECTIVE We evaluated the effect of sex steroids on the lipid fractions (cholesterol, triglycerldes, LDL‐C, HDL‐C and subtractions HDL2‐C and HDL3‐C) and on the apollpo‐proteins (A‐I and B) in relation to age in women.

DESIGN Twenty‐eight normally cycling women belonging to three age groups (20–29, n= 11; 30–39, n= 10; 40–49, n= 7) had blood samples taken dally during one cycle.

MEASUREMENTS Serum lipld fractions, apollpoprotelns (Apo) and ovarian steroids were measured daily during the menstrual cycle. Diet and exercise were also evaluated.

RESULTS Each age group had comparable profiles for dally serum concentrations of oestradiol, progesterone and testosterone. There were no significant variations of the lipid fractions or of the ApoA‐I and ApoB during the menstrual cycle in each group. Using regression analysis, modifications of cholesterol, triglycerides, LDL‐C and ApoB were partially but significantly correlated with age. These changes occurred in spite of similar serum concentrations of oestradiol, progesterone and testosterone in the three groups. Lipld fractions were also affected by the increase of body mass index with age, especially HDL‐C and HDL2C. However, there were no differences in lipld and energy intake or in energy expenditure during physical leisure activities.

CONCLUSIONS These results indicate that physiological fluctuations of ovarian steroids have no effects on llplds and Apo in normally cycling women of increasing age. In this study, the age related changes in the lipld fractions were partially correlated with body mass index but not with energy intake or exercise.
Low recurrence rate after partial hypophysectomyfor prolactinoma: the predictive value ofdynamic prolactin function tests
Authors: Webster Jonathan , Page Michael D. , Bevan John S. , Richards Stephen H. , Douglas‐Jones Anthony G. , Scanlon Maurice F.
Published: March 2008

objective To determine the factors influencing the outcome of transethmoidal partial hypophysectomy for suspected prolactinoma and the predictive value of pre and post‐operative dynamic PRL function tests.

design A retrospective study of patients undergoing surgery for a suspected prolactinoma in Cardiff between 1979 and 1989.

patients Eighty‐two hyperprolactlnaemlc patients (75 women, seven men) diagnosed as having a prolactinoma on the basis of dynamic PRL function tests, radiological investigation and exclusion of other causes.

measurements TSH and PRL responses to domperidone (10 mg i.v.) and TRH (200 μg i.v.) measured preoperatively, 2 months post‐operatively, and annually thereafter. CT scan performed preoperatively in 58 patients. Operative findings, including adenoma size, documented in each case.

results Forty‐two patients (51%) had microadenomas (< 10 mm), 37 (46%) had macroadenomas and in three no tumour was found at operation. Preoperatively, normal responses of both TSH (incremental rise < 2·0 mU/l) and PRL (> 100% rise) to domperidone were observed in two patients only: both had an abnormal vascular supply to the pituitary rather than an adenoma. Serum PRL was normalized in the early post‐operative period (< 72 h; ‘early cure’) in 65 patients (79%). The highest early cure rate (96%, n= 26) was in patients with adenomas of 5–9 mm, lower rates being achieved for lesions of 10–19 mm (80%, n= 30), < 5 mm (63%, n= 19) or ± 20 mm (57%, n= 7). The early cure rate was strongly correlated with preoperative PRL, ranging from 100% in patients with PRL < 1000 mU/l (n= 13) to zero in those with PRL > 10 000 mU/l. Dopamine agonist therapy of between 5 weeks and 4 years duration prior to surgery was associated with a significantly reduced early cure rate (60 vs 94%, P < 0·02) in macroadenoma but not microadenoma patients.

Recurrent hyperprolactlnaernia during mean follow‐up of 51·7 months occurred in eight patients (12%), in five cases within 2 months of surgery and in the others at 26, 48 and 50 months. Recurrence could not be predicted from any preoperative parameter, but a serum PRL > 150 mU/l 1·3 days following microadenomectomy was associated with early recurrence and probably indicates failed surgery. An abnormal response of TSH to domperidone was documented 2 months post‐operatively in 11/60 patients with normal basal PRL, and preceded all three late recurrences. Of four patients with abnormal responses of both PRL and TSH at this time, two have relapsed to date.

conclusions In carefully selected patients, partial hypophysectomy is an acceptable alternative to medical treatment for prolactinoma. Preoperatively, dynamic tests accurately identified those patients whose hyperprotactinaemia was non‐adenomatous in origin and, post‐operatively, identified a subgroup of patients at increased risk of late recurrence.
Insulin secretion and insulin‐like growth factor‐I levels in active and controlled acromegaly
Authors: Hopkins K. D. , Holdaway I. M.
Published: March 2008

objective We examined the contributions of growth hormone (GH) and Insulin‐like growth factor‐I (IGF‐I) to Insulin sensitivity and beta‐cell function in acromegaly.

design A cross‐sectional study was used with continuous Infusion of glucose with model assessment todetermine Insulin sensitivity and beta‐cell function.

patients Ten patients with active acromegaly, seven with controlled disease and 22 normal Individuals werestudied.

measurements Glucose and insulin levels were measured fasting and at the end of the one‐hour glucose Infusion to calculate insulin sensitivity and beta‐cell function. Random GH and IGF‐I were recorded. Most patients had values of GH taken after a 100‐g oral glucose tolerance test and K values from Intravenous glucosetolerance tests.

results Patients with active acromegaly had significantly decreased Insulin sensitivity compared to thenormal population (P < 0·001), while those with controlled disease did not. There was a significant negative correlation between IGF‐I and insulin sensitivity In those with active disease (P < 0·05). Beta‐cell function in both active and controlled patient groups was elevated compared tothe normal population (P < 0·05, P < 0·01 respectively) and this was significantly related to IGF‐I in the active group (P < 0·05). GH levels did not correlate with fasting Insulin, glucose, Insulin sensitivity or beta‐cell function In either group.

conclusions Patients with active acromegaly have decreased insulin sensitivity and Increased beta‐cell function that are significantly related to IGF‐I but not GH levels. When the disease is controlled, beta‐cell function remains elevated but Insulin sensitivity Improves.
The role of thyroid stimulating antibody (TSAb) in the thyroid function of patients with post‐partum hypothyroidism
Authors: Hara Takeshi , Tamai Hajime , Mukuta Toshio , Fukatat Shujl , Kuma Kanji
Published: March 2008

objective We investigated the association between thyroid function and the biological activities of thyroid stimulating antibodies (TSAb) and thyroid stimulation blocking antibodies (TSBAb) in patients with post‐partum hypothyroidism.

design A prospective study.

patients We studied 25 patients with post‐partum hypothyroidism who visited our thyroid clinic during the period from 1985 to 1990.

measurements We measured TSH binding Inhibitory immunoglobulin (TBII) and TSAb activity at the initial presentation of each of the 25 patients. Women found to have elevated TSAb activity were followed up. Upon finding negative TSAb activity along with positive TBII activity In the serum at the initial presentation, we measured TSBAb activity. Women found to have elevated levels of TSBAb at the Initial presentation were also followed up.

results Elevated TBII activity was found in six of the 25 patients, as was high TSAb activity (205–2651 %, normal 55·0–145·0%) in five of these six and in one other patient at the initial presentation. Markedly elevated TSBAb activity (89%) was found in one TBII positive patient. We were able to follow up serially five TSAb positive patients and the TSBAb positive patient over periods ranging from 11·5 to 26·5 months post‐partum. The maximal value of TSAb activity was observed at the initial presentation in all TSAb positive patients, following which the activities gradually decreased.

One of these patients developed Graves' hyperthyroidism associated with high TSAb activity (1223%) at 10·5 months post‐partum. One of the other patients was restored to euthyrold with elevated TSAb activity (279%), but thereafter developed hypothyroidism in conjunction with the disappearance of TSAb activity at 26·5 months post‐partum. In the other two patients, normalization of thyroid function was observed with elevated TSAb activity. Thereafter, thyroid function remained within the normal range even with the disappearance of TSAb activity. In the other patient, normalization of thyroid function was observed at 11·5 months post‐partum, 3 months after the disappearance of TSAb activity. In the TSBAb positive patient, TSBAb activity decreased to 21 % by 17·5 months post‐partum associated with normalization of thyroid function.

conclusion The present study demonstrates the presence of elevated levels of TSAb activity in some patients with post‐partum hypothyroidism. In these patients, Graves' hyperthyroldism may be induced by TSAb activity, and hypothyroidism may reoccur with the disappearance of the TSAb activity. Furthermore, post‐partum hypothyroidism may be due to increased TSBAb activity in some patients.
Nicotinamide and 3‐aminobenzamide inhibit recombinant human interferon‐γ‐induced HLA‐DR antigen expression, but not HLA‐A, B, C antigen expression, on cultured human thyroid cells
Authors: Hiromatsu Yuji , Sato Masayuki , Yamada Kentaro , Nonaka Kyohei
Published: March 2008

objective We wished to investigate the effects of nicotinamide and 3‐aminobenzamlde, well known as inhibitors of poly(ADP ribose) synthetase, on interferon‐γ‐induced HLA‐DR antigen expression using cultured human thyroid cells from patients with Graves' disease.

design and measurements Cultured thyroid cells were Incubated for 3 days with 10–400 U/ml of interferon γ in the presence of nicotinamlde, 3‐amlnobenzamlde, superoxide dismutase or catalase. The surface expression of HLA‐DR and HLA‐A, B, C antigen was measured by flow cytometry.

results Nicotinamide and 3‐aminobenzamide dose‐dependently inhibited the induction of HLA‐DR antigen expression by interferon γ, but not HLA‐A, B, C antigen expression on cultured thyroid cells. Neither catalase nor superoxide dismutase, which are free‐radical scavengers, Inhibited the expression of HLA antigens on thyroid cells.

conclusions Our data suggest that inhibitors of poly(ADP ribose) synthetase may have differential effects on interferon‐γ‐induced HLA‐DR and HLA‐A, B, C antigen expression, and suppress the autoimmune reactions associated with autoimmune thyroid disorders via the reduction of HLA‐DR antigen expression on thyroid cells. The mechanism of the suppression of HLA‐DR antigen expression is unlikely to be due to the free radical scavenging.
Long‐acting gonadotrophin releasing hormone agonist implant causes variable duration of suppression of ovarian steroid and inhibin secretion
Authors: Fraser H. M. , Hainlng R. , Cowen G. M. , Sandow J. , Smith K. B. , Smith S. K.
Published: March 2008

objective The duration of action of a gonadotrophin releasing hormone (GnRH) agonist implant designed to be effective for 3 months was investigated in women by monitoring drug release and ovarian hormone secretlon. Serum inhibin secretion was measured to determine whether the secondary rise in serum FSH concentrations observed during long‐term GnRH agonist treatment was attributable to changes in inhibin secretion.

design and patients The implants Of Slowly bio‐degradable polylactide/glycolide (molar ratio 75:25) containing 3·3 mg buserelin, d‐Ser (BUt)8‐GnRH (1–9)‐nonapeptide‐ethylamide, in a rod 1 cm long and 0·13 cm diameter were injected s.c. in patients with endometriosis (3·3 mg busereiin in four patients, 6·6 mg busereiin in six patients).

measurements Urinary secretion of oestrone, pregnanediol, LH and buserelin were determined in daily samples collected for 2 cycles before treatment, during treatment, and for 2 recovery cycles. Oestradiol, progesterone, inhibin, LH and FSH were measured in serum collected once per week.

results in all patients ovarian hormone secretion was suppressed successfully but considerable varlability occurred in the length of time taken for ovarian function to recommence, time to return to ovulation being 100–194 days (median 118 days) (3·3 mg group) and 79–290 (median 178 days) (6·6 mg group). After implant injection, there was a rapid rise in the urinary buserelin excretion followed by an early fast phase of buserelin release, half life (t1/2) = 9 days for 3·3 mg implant and 11 days for 6·6 mg implant. This was followed by a second phase representing a plateau of release, t1/2= 50 days (3·3 mg implant) and 90 days (6·6 mg implant). During this second phase, an excretion rate of > 0·2 nmol buserelin/mol Cr was associated with oestrone excretion at or below early follicular phase values. Once buserelin excretion fell below 0·1 nmol/mol Cr, ovarian function returned in all patients. The period for which buserelin secretion was maintained between 0·1 and 0·2 nmol/mol Cr corresponded to the time taken to recovery of ovulatory cycles in 8/10 of the women. In 9/10 patients serum immunoreactive inhibin concentrations declined at 2 weeks, along with the suppression of oestradiol, and remained suppressed throughout the period of anovulation. Recovery of FSH secretion began after 4–5 weeks.

conclusions While this implant should have important clinical application where chronic treatment is indicated, further work is needed on design of long‐term implants so that such preparations can be used when precise return to ovarian activity is required. A fall in inhibin secretion may contribute to the secondary rise in FSH by withdrawal of negative feedback but these events are not closely correlated.
Osteoporosis and Klinefelter's syndrome
Authors: Horowitz M. , Wishart J. M. , O'Loughlin P. D. , Morris H. A. , Needt A. G. , Nordin B. E. C.
Published: March 2008

objective We wanted to measure forearm mineral density and bone‐related biochemical variables in patients with Klinefelter's syndrome.

design Measurements made in patients with Klinefelter's syndrome were compared to those obtained in age‐matched normal male volunteers.

patients We studied 22 patients with Klinefelter's syndrome (12 of whom had received sex hormone therapy) and 22 control subjects.

measurements We measured forearm mineral density, forearm fat content, fat‐corrected forearm mineral density, plasma calcium and ionized calcium, serum osteocalcin, testosterone and dehydroepiandrosterone sulphate, and urinary hydroxyproline/creatinine ratio.

results Forearm mineral density was lower in the Klinefelter's group than in the control sublets (P < 0·05) and below the control range in 5 patients. The fat content of the forearm was greater in the Klinefelter's group (P < 0·002). Serum osteocalcin and testosterone were lower, while ionized calcium and the urinary hydroxyproline/creatinine ratio were higher in the Klinefelter's group (P < 0·002). Serum dehydroeplandrosterone sulphate and testosterone were significantly related in the Klinefelter's group (r= 0·64, P < 0·001), but not in the controls (r= 0·22, NS). Forearm mineral density and fat‐corrected forearm mineral density were significantly related to serum testosterone in the Klinefelter's group (r < 0·63; P < 0·01), but not in the control subjects (r < 0·03, NS).

conclusions Decreased bone density occurs in about 25% of patients with Klinefelter's syndrome and probably reflects both decreased bone formation and increased bone resorption.
Thyroxine replacement therapy and circulating lipid concentrations
Authors: Franklyn J. A. , Daykin J. , Betteridge J. , Hughes E. A. , Holder R. , Jones S. R. , Sheppard M. C.
Published: March 2008

OBJECTIVE Hypothyroidism is a common disorder and while the association of overt hypothyroidism with hyper‐cholesterolaemia is clear, the effect upon lipids of the minor abnormalities of thyroid function often found in those receiving T4 replacement therapy is unclear. The aim of the present studies was to define in those with hypothyroidism the effect upon circulating lipids of subtle changes in thyroid status, indicated by serum TSH values below or above the normal range.

DESIGN (i) Prospective study of short‐term T4 treatment of those with subclinical hypothyroidism, (ii) Cross‐sectional study of long‐term T4 treatment, comparing non‐T4 treated controls and T4 treated patients with serum TSH values either below or within the normal range. PATIENTS Short‐term T4 therapy was examined in 11 post‐menopausal females with subclinical hypothyroidism (high TSH, normal free T4) studied before therapy and 6 weeks after T4 at incremental doses (50, 100, 150 μg/ day). Long‐term T4 treatment for hypothyroidism was investigated in 105 females on therapy for at least 1 year compared with 105 controls matched for age and menopausal status.

MEASUREMENTS Fasting levels of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and HDL subtractions were determined in patients and controls.

RESULTS (i) T4 treatment of subjects with subclinical hypothyroidism resulted in reductions in total and LDL cholesterol with increasing T4 dose (P <0 001). Comparison of lipid results pretreatment with those when TSH was restored to normal revealed no significant difference in lipids; in contrast, comparison of lipids in those with normal TSH compared with the same subjects when TSH was suppressed revealed reductions in total and LDL cholesterol, (ii) Long‐term T4 treatment was associated with a reduction in total and LDL cholesterol measurements in those over 55 years receiving suppressive doses of T4 but no significant difference in lipids in those with normal serum TSH compared with non‐T4 treated controls.

CONCLUSION Effects of T4 upon lipid measurements suggest that patients with subclinical hypothyroidism should receive replacement therapy. Doses of T4 which suppress TSH to below normal may have a more significant influence upon lipids than doses of T4 which restore TSH to the normal range.
Induction of testicular growth and spermatogenesis by pulsatile, intravenous administration of gonadotrophin‐releasing hormone in patients with hypogonadotrophic hypogonadism*
Authors: Van de Waal Henrietta A. Delemarre
Published: March 2008

OBJECTIVE To induce testicular growth including spermatogenesis, 38 patients with hypogonadotrophic hypogonadism were treated with long‐term pulsatile GnRH administration.

PATIENTS The group of patients comprised 17 individuals with idiopathic hypogonadotrophic hypogonadism, 11 with Kallmann's syndrome, four with multiple pituitary hormone deficiencies and six with a secondary hypogonadotrophic hypogonadism due to surgical removal of a brain tumour. Thirteen patients (seven with idiopathic hypogonadotrophic hypogonadism and six with Kalmann's syndrome) had undescended testes, of whom six had undergone surgery on both testes and four on one testis. Sixteen of the 17 had previously received androgen therapy and six others had received gonadotrophin treatment, of whom three had long‐term treatment to induce testicular development, without success.

TREATMENT GnRH was administered intravenously in a dose of 2‐20 μg per pulse every 90 minutes. After GnRH discontinuation, hCG treatment was instituted, 1500–3000 III (i.m.) twice weekly.

RESULTS During treatment plasma levels of LH, FSH and testosterone increased. In 35 out of the 38 patients plasma testosterone levels increased into the normal adult range. In all patients testicular volume increased. Mean pretreatment testicular volume per patient group ranged from 2 4 to 4.8 ml and increased to 11.5–18.1 ml by the end of treatment. There was a significant difference in the achieved testicular volumes between the patients with Kallmann's syndrome and the brain tumour patients.

GnRH treatment mean lasted between 46 and 75 weeks In the different groups. On hCG therapy, testicular development was either maintained or improved. Semen analysis revealed the presence of spermatogenesis in 31 out of the 38 patients (26 patients already on GnRH, and in another five patients on hCG therapy). All three patients pretreated with gonadotrophins as well as three patients with bilateral testicular surgery developed a detectable sperm count. In 19 adolescent patients with growth potential, an adequate height velocity was observed during GnRH treatment.

CONCLUSIONS GnRH is a feasible way to induce testicular growth as well as spermatogenesis In hypogonadotrophic male patients, even in patients in whom gonadotrophin treatment has failed. After GnRH treatment, hCG alone can maintain or even improve testicular development, including spermatogenesis. GnRH treatment may also induce a physiological growth spurt In hypogonadotrophic adolescents.
Presence of anti‐pituitary hormone antibodies in patients with empty sella syndrome and pituitary tumours*
Authors: Mau Marjorie , Phillips Terry M. , Ratner Robert E.
Published: March 2008

OBJECTIVE We evaluated the presence of anti‐pituitary hormone autoantibodies (APHA) in patients with primary empty sella syndrome and pituitary tumours and examined the correlation of positive antibodies with the hormonal deficiencies.

DESIGN Case‐control, retrospective study.

PATIENTS Eleven patients were identified with primary empty sella syndrome or a pituitary tumour by magnetic resonance imaging or computed tomography scanning. Six healthy, normal subjects without evidence of a pituitary problem served as the control group.

MEASUREMENTS Anti‐pituitary hormone autoantibodies against purified pituitary hormones were measured in ail subjects utilizing an immunoblotting technique. All patients with pituitary disease had their medical records reviewed for any hormonal evaluation.

RESULTS All of the normal subjects were negative for antipituitary hormone antibodies. Forty‐five per cent of patients with pituitary disease (pituitary tumours or primary empty sella syndrome) had positive antipituitary hormone antibodies. Of the five patients with positive antipituitary hormone antibodies, anti‐ACTH antibodies were the most common (5/5) followed by anti‐TSH and anti‐GH antibodies (2/5 for each). The hormonal deficiencies failed to correspond with the antipituitary hormone antibodies. Anti‐ACTH antibody had a sensitivity of 50% with a specificity of 56%. The anti‐TSH antibody yielded a sensitivity of 67% with a specificity of 100%. The anti‐FSH/ LH antibody reported a 0% sensitivity.

CONCLUSIONS Detection of antipituitary hormone antibody was unable to discriminate between empty sella syndrome and pituitary tumours. The presence of these antipituitary hormone antibodies were neither specific for, nor predictive of, the endocrine deficiencies.
Influence of hyperthyroidism on growth hormone secretion
Authors: Valcavi Roberto , Dieguer Carlos , Zini Michele , Muruais Covadonga , Casanueva Felipe , Portioli Italo
Published: March 2008

OBJECTIVE Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue.

DESIGN Study 1: GHRH (1 μg/kg b.w.) was injected i.v. in 38 hyperthyroid patients and in 30 normal subjects; in 11 of the patients the GHRH test was repeated following methimazole‐induced remission of hyperthyroidism. Study 2: hGH (2 U i.v.) or saline were administered 3 hours prior to GHRH; six hyperthyroid patients and six normal subjects were studied. Study 3: ten normal subjects and ten hyperthyroid patients were given 75 g oral glucose or water 30 minutes before GHRH. Study 4: 11 normal subjects and eight hyperthyroid patients were studied. TRH or vehicle were dissolved in 250 ml of saline solution and infused at a rate of 400 μg/h for 150 minutes. Thirty minutes after the beginning of the infusions, l‐arginine (30 g infused over 45 min i.v.) was administered.

PATIENTS Hyperthyroid patients were compared to normal subjects.

MEASUREMENTS Growth hormone was measured by RIA at 15‐minute intervals.

RESULTS GH responses to GHRH were subnormal in hyperthyroid patients. Following antithyroid drug treatment with methimazole, GH responses to GHRH increased in these patients in comparison to pretreatment values. Serum IGF‐I levels, which were elevated before treatment, decreased after methimazole administration. Exogenous GH administration induced a clear decrease of GH responses to GHRH in both control and hyperthyroid subjects. On the other hand, oral glucose load decreased the GH responses to GHRH in normal but not in hyperthyroid subjects. TRH administration did not modify the GH responses to arginine in either normal subjects or hyper‐thyroid patients.

CONCLUSIONS Hyperthyroidism is associated with increased serum IGF‐I levels and marked alterations in the neuroregulation of GH secretion. These changes involve decreased GH responsiveness to GHRH at the pituitary level and, at the hypothalamic level, a lack of suppressive effect of an oral glucose load. The normal inhibitory effect of exogenous GH administration but not of an oral glucose load in hyperthyroid patients suggests that these two feedback signals act through different mechanisms. The lack of effect of a TRH infusion on GH responses to l‐arginine in normal and hyperthyroid patients makes an inhibitory role for TRH in GH secretion unlikely, at least in Caucasian subjects.
Ultrasonically guided chemical parathyroidectomy in patients with primary hyperparathyroidism: a follow‐up study
Authors: Karstrup Steen , Hegedüs Laszlo , Holm Hans Henrik
Published: March 2008

OBJECTIVE We evaluated the long‐term results in two different groups of patients with primary hyperparathyroidism treated with ultrasonically guided percutaneous ethanol (96%) injection into parathyroid tumours.

DESIGN A prospective long‐term follow‐up (more than 6 months). Ethanol (96%) was injected under ultrasonic guidance into biopsy verified solitary parathyroid tumours. Basic treatment included a maximum of three treatments with an interval of about 1 month (group 1) or 1 week (group 2). Dose of ethanol was half the volume of the parathyroid tumour.

PATIENTS Two different groups of patients with only one ultrasonically detected and biopsy verified parathyroid tumour were treated. Group 1 (n= 18) were treated regardless of the severity of the hyperparathyroid disease. Group 2 (n= 14) were selected for treatment either due to severe hypercalcaemic symptoms (n= 3), a high surgical risk (n= 5), or refusal of surgery (n= 6).

MEASUREMENTS The volume of the parathyroid tumours was measured as half the product of maximum length, width, and depth. Blood tests included measurements of ionized calcium, total calcium and PTH.

RESULTS In group 1, 12 of 18 patients (66%) could be followed more than 6 months. Follow‐up ranged from 12 to 58 months (median 45 months). A significant decrease (P < 0 001) in serum concentrations of ionized calcium and total calcium was observed. Eight patients (44%) later underwent surgical parathyroidectomy. Injection therapy was regarded as successful in 10 of 18 patients (56%). In group 2,11 of 14 patients (79%) were followed more than 6 months. Follow‐up ranged from 18 to 50 months (median 39 months). A significant decrease (P <0 001) in serum concentrations of ionized calcium, total calcium and intact PTH (1–84) was observed. Treatment was successful in 11 of 14 patients (79%). Two patients required parathyroid surgery. Re‐examination with ultrasound showed a significant reduction in the volume of the treated parathyroid tumours. Fibrosis surrounding the parathyroid tumours was detected in eight of 10 patients who subsequently had operations. One patient from each group had a complication of a unilateral permanent vocal cord paralysis following injection therapy.

CONCLUSION Partial or complete long‐term remission of primary hyperparathyroidism can be achieved using ultrasound‐guided chemical parathyroidectomy. However, the intervals between treatments should be short and the treatment should be reserved only for patients not fit for surgery.
Intracranial dissemination of a macroprolactinoma
Authors: Assies J. , Verhoeff N. P. L. G. , Bosch D. A. , Hofland L. J.
Published: March 2008

A patient with a macroprolactinoma and extrasellar extension was treated by incomplete transfrontal surgery, external irradiation and additional bromocriptine (Br) treatment. After 4 years, partial bromocriptine resistance developed (a rare occurrence) together with the appearance of intracranial metastases. 123l‐lodobenzamide was helpful In evaluating the dopamine D2 receptor status of the metastatic tumour both in vivo using single‐photon emission computed tomography (SPECT) and in vitro. Prolactin release by the cultured metastatic tumour cells was more potently inhibited by CV 205–502 than by bromocriptine. The patient, treated by surgery, irradiation and CV 205–502, developed a ptosis of the left eye and a transient psychiatric delusional state, the latter probably an effect of the dopamine agonist. As the right frontal metastasis was markedly positive on SPECT with 111ln‐SMS, somatostatin treatment was added to the CV 205–502.
Thyroxine treatment increases circulating levels of insulin‐like growth factor binding protein‐1: a placebo‐controlled study
Authors: Angervo M. , Tiihonent M. , Leinonen P. , Välimaki M. , Seppälä M.
Published: March 2008

OBJECTIVE Thyroid hormones affect carbohydrate metabolism in the liver, and hepatic insulin‐like growth factor binding protein‐1 (IGFBP‐1) participates in glucose counter‐regulation, so we studied the effects of oral thyroxine on serum IGFBP‐1.

DESIGN The study was performed on a placebo‐controlled cross‐over basis covering 3 months’ thyroxine and 3 months’ placebo administration.

PATIENTS Eight patients taking anticonvulsant medication and four patients with hypothalamic hypothyroidism were given thyroxine, 150–200 μg daily for 3 months, or placebo.

MEASUREMENTS Serum IGFBP‐1, sex hormone binding globulin, free T3 and free T4, TSH and IGF‐I levels were measured after an overnight fast before treatment, and at the end of each 3‐month period.

RESULTS Anticonvulsant medication had no significant effect on serum IGFBP‐1. After 3 months’ thyroxine treatment the serum IGFBP‐1 levels (69; 58‐167 μ g/l; median and interquartile range, respectively) were significantly higher than those after placebo treatment (44; 23‐58 μ g/l; P= 0 002), or the pretreatment levels (54; 19‐81 μ g/l, P= 0 005). The IGFBP‐1 levels rose in all 12 patients after thyroxine treatment, the median rise being 2.1‐fold compared to placebo levels. No change was found in serum IGF‐I concentrations.

CONCLUSIONS Oral thyroxine produces a rise in serum IGFBP‐1 level without a change in serum IGF‐I concentration.
Gestational thyrotoxicosis and hyperemesis gravidarum: possible role of hCG with higher stimulating activity
Authors: Kimura Motoko , Amino Nobuyuki , Tamaki Haruo , Ito Eriko , Mitsuda Nobuaki , Miyai Kiyoshi , Tanizawa Osamu
Published: March 2008

OBJECTIVE The thyroid gland is physiologically stimulated in normal early pregnancy. However, clinical thyrotoxicosis in normal pregnancy has not been well described. In order to clarify this we examined thyroid function and thyrotoxic symptoms in relation to emesis in normal pregnancy. We also investigated the possible mechanism of gestational thyrotoxicosis.

DESIGN Thyroid function was evaluated in view of the clinical thyrotoxic symptoms and the severity of gestational emesis in early pregnancy of 51 normal women. Two pregnant women who showed clinical thyrotoxicosis were followed serially during and after pregnancy.

MEASUREMENTS Serum free T4, free T3 and TSH were measured by radioimmunoassay and hCG by fluoroimmunoassay. Thyroid‐stimulating activity of pregnancy sera was measured by cAMP increase in cultured FRTL‐5 cells. RESULTS Fifty‐one pregnant women were divided into three groups: those without emesis (n= 24), with emesis (n= 19) and with hyperemesis (n= 8). Serum free T4 and free T3 were higher in the hyperemesis group (P<0.01) and the emesis group (P<0.01), and serum TSH was suppressed to less than 0 1 mU/l in both groups, while serum hCG was not significantly different among these three groups.

However, serum thyroid‐stimulating activity was remarkably high in the hyperemesis group (P<0.01). Thus the ratio of thyroid‐stimulating activity to hCG was higher in the hyperemesis group (P < 0.05) and the emesis group (P < 0.05) compared with that in the group without emesis. These thyroid‐stimulating activities were abolished by treatment of the serum with anti‐hCG antibody. Two of eight women with hyperemesis, who had the highest free T4 and thyroid‐stimulating activity/hCG ratio, showed overt clinical symptoms of thyrotoxicosis; all the symptoms disappeared in association with a fall in thyroid‐stimulating activity and free T4.

CONCLUSION Clinical thyrotoxicosis is caused by circulating hCG with higher biological activity in pregnant women with hyperemesis. A new clinical entity of‘gestational thyrotoxicosis’is proposed and tentative characteristics are discussed.
Age and gender influence the severity of thyroid‐associated ophthalmopathy: a study of 101 patients attending a combined thyroid‐eye clinic
Authors: Perros P. , Crombie A. L. , Matthews J. N. S. , Kendall‐Taylor P.
Published: March 2008

BACKGROUND The pathogenesis of thyroid‐associated ophthalmopathy is thought to be autoimmune, although environmental and genetic factors are also considered to be important. As the morbidity of thyroid‐associated ophthalmopathy is considerable and treatment often unsatisfactory, there a need to identify possible predisposing factors.

OBJECTIVE The study was undertaken in order to ascertain the relationship between age, gender and severity of thyroid‐associated ophthalmopathy.

PATIENTS One hundred and one consecutive patients with thyroid‐associated ophthalmopathy who presented over a period of 5 years to a combined thyroid‐eye clinic.

METHODS Patients were assessed by grading their inflammatory signs and degree of diplopia, and by measurement of exophthalmos, palpebral aperture, differential intraocular pressure, and visual acuity. On the basis of the above an ophthalmopathy index was devised to grade the overall severity of eye disease.

RESULTS The mean age was 49.2 years (SD 13.4), the female‐to‐male ratio was 405, and mean ophthalmopathy index 6.49 (SD 3.3). Optic nerve compression was present in 9–9% of patients. There was a positive relationship between age and ophthalmopathy index (P<0.001); after correcting for age, males had an average ophthalmopathy index 41 % greater than that of females.

CONCLUSION There is an association between severity of thyroid‐associated ophthalmopathy and (i) advancing age and (ii) female‐to‐male ratio, which has not been previously described. Patients over the age of 60 (particularly males) with Graves'disease appear to be at risk of developing severe eye disease.
Characterization of a novel mutant human thyroid hormone receptor β in a family with hereditary thyroid hormone resistance
Authors: Sakurai Akihiro , Miyamoto Takahide , Hughes Ieuan A. , DeGroot Leslie J.
Published: March 2008

OBJECTIVE We wished to determine the abnormality responsible for Generalired Resistance to Thyroid Hormone in a family with this syndrome.

DESIGN Molecular biological studies were performed on a mutant human thyroid hormone receptor beta (hTRβ) cloned from fibroblasts of the patient.

PATIENTS The patient is from a previously reported family with typical features of Generalized Resistance to Thyroid Hormone, demonstrating goitre, elevated thyroid hormone levels, slightly elevated TSH, and retarded bone age.

MEASUREMENTS A cDNA for hTRβ1 was cloned using specific oligonucleotide primers from fibroblast DNA. A mutant hTRβ1 expression vector was constructed, and an in‐vitro expressed mutant receptor was tested for T3 binding. Receptor binding to DNA was studied in a DNA cellulose assay and gel mobility shift assay.

RESULTS Two mutations were found in the cloned hTRβ. One was silent but the second changed arginine 438 to histidine. The mutation was present in RNA and genomic DNA, as shown by allele‐specific amplification. The mutated receptor had reduced T3 binding affinity but demonstrated normal binding in a DNA cellulose assay and In a gel mobility shift assay. The receptor did not have altered heat sensitivity.

CONCLUSIONS In the T sibship with Generalized Resistance to Thyroid Hormone, resistance to thyroid hormone is apparently produced by a substitution of a histidine for arginine at amino acid 438, which causes reduced binding of receptor to T3, although the receptor remains able to bind to DNA and, for this reason, functions as a dominant negative in affected subjects who are heterorygous with one normal and one mutated allele.
The early effects of radioiodine therapy for hyperthyroidism on biochemical indices of bone turnover
Authors: MacLeod Jean M. , McHardy K. C. , Harvey R. D. , Duncan A. , Reid I. W. , Bewsher P. D. , Robins S. P.
Published: March 2008

OBJECTIVE We investigated the early changes following radioiodine therapy for hyperthyroidism, in biochemical indices of bone synthesis and degradation, and their relationship to circulating thyroid hormone concentrations.

DESIGN Prospective follow‐up over the first 12 weeks after radioiodine therapy.

PATIENTS Six women with clinical and biochemical evidence of hyperthyroidism.

MEASUREMENTS Serum Concentrations of T4, free T3 and osteocalcin, and urinary excretion of the pyridinium cross‐links, pyridinaline and deoxypyridinaline, measured before and weekly for 12 weeks after administration of radioiodine therapy.

RESULTS Biochemical indices of bone metabolism were elevated prior to treatment. There was a brisk reduction in circulating thyroid hormones levels paralleled by a similar fall In pyridinlum cross‐llnk excretion, which had returned to normal in five patients by the end of the study. There was a positive correlation between pyridinium cross‐link excretion and thyroid hormone concentrations. There was no significant change in serum osteocalcin.

CONCLUSIONS Treatment of hyperthyroidism results in prompt correction of the associated increased rate of bone collagen degradation suggesting that effective early correction of hyperthyroidism is desirable to limit its detrimental effect on skeletal mass.