bluuebunny/crossref_metadata_2025 huggingface dataset:
THE STEROID RESPONSE TO CONTROLLED ADRENAL STIMULATION IN CONGENITAL ADRENAL HYPERPLASIA
Authors: CONWAY D. I. , ANDERSON D. C. , BU'LOCK D. E.
Published: March 2008

Adrenal steroidogenesis has been studied in vivo in eleven patients aged 13–68 years with 21‐hydroxylase deficiency, in one patient with 11β‐hydroxylase deficiency and in ten female control subjects. Serum levels of the Δ5 3β‐hydroxysteroids, pregnenolone (Pe), 17α‐hydroxypregnenolone (17Pe), dehydroepian‐drosterone (DHEA) and androstenediol (Adiol) and their Δ4 3‐keto counterparts, progesterone (Po), 17α‐hydroxyprogesterone (17Po) androstenedione (Adione) and testosterone as well as of 11‐deoxycortisol and cortisol were measured during acute adrenal suppression with dexamethasone followed by stimulation with synthetic 1–24 ACTH.

In the seven patients with 21‐hydroxylase deficiency who were on adequate glucocorticoid therapy, grossly exaggerated responses of 17Po and Po to ACTH were nevertheless preserved. In contrast, there was a grossly subnormal response of 17Pe, DHEA and Adiol to ACTH, and low basal levels of DHEA‐sulphate. In the untreated patients the response of 17Pe and DHEA was normal. The Adione response was exaggerated in untreated and normal in treated cases. Similar findings obtained in the patient with 11β‐hydroxylase deficiency who was studied after 6 weeks without replacement therapy. Our findings demonstrate that production of adrenal steroids that are associated with the adrenarche is not exaggerated in untreated CAH, and is grossly suppressed in treated cases. These findings are compatible with the hypothesis that intra‐adrenal cortisol may initiate and/or maintain production of the Δ5 steroids by the zona reticularis that occurs in the human adrenarche.
THE ACUTE CHANGES IN THYROID STIMULATING IMMUNOGLOBULINS, THYROGLOBULIN AND THYROGLOBULIN ANTIBODIES FOLLOWING SUBTOTAL THYROIDECTOMY*
Authors: BECH KARINE , FELDT‐RASMUSSEN ULLA , BLIDDAL H. , DATE J. , BLICHERT‐TOFT M.
Published: March 2008

The acute changes in thyroid adenylate cyclase stimulating immunoglobulins (TACSI), TSH binding inhibiting immunoglobulins (TBII), thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) in serum after subtotal thyroidectomy were studied in thirteen patients with Graves' disease (GD) and thirteen patients with non‐toxic goitre (NG).

Prior to operation eight patients with GD were TACSI positive (mean ± SEM: 135·18%) and within 8 h following surgery TACSI increased and became positive in all thirteen patients (mean 172 ± 20%). There was a parallel increase in Tg and a decline in TgAb. A secondary rise in TACSI was observed 3–4 days after operation followed by a gradual fall which was associated with an increase in TgAb reaching a maximum 10 days after surgery. TACSI were still detectable 1 month postoperatively, but had disappeared by 3 months.

In four of nine patients with GD TBII were present prior to operation. Immediately after surgery TBII decreased significantly (P < 0·05) and two of the four patients who were TBII positive became permanently negative, while the other two patients remained positive. A transient increase of the mean TBII levels was observed 5 days after surgery.

Two of thirteen patients with NG were TACSI positive before operation and no significant changes were observed after surgery. The mean levels were significantly lower than in GD. Tg was measurable in eleven patients and showed a lower increase than in GD following surgery. TgAb were present in two patients prior to operation but disappeared in one and in the other one the changes following surgery were similar to the changes in GD.
SIZE HETEROGENEITY OF IMMUNOREACTIVE PROLACTIN IN HYPERPROLACTINAEMIC SERUM
Authors: SOONG Y. K. , FERGUSON K. M. , McGARRICK G. , JEFFCOATE S. L.
Published: March 2008

Thirty‐five samples of serum with levels of immunoreactive prolactin greater than 500 mu/l have been fractionated by gel filtration. In samples from seven normal subjects with elevated prolactin levels following TRH or insulin stimulation and samples from twelve patients with prolactin levels greater than 1500 mu/l, over 80% of the immunoreactive material eluted in the position of native or ‘little’ prolactin. In eleven out of sixteen samples containing 500 to 1500 mu/l the proportion of ‘little’ prolactin was less than 80% and more than 20% eluted as ‘big‐big’ prolactin. It appears therefore that patients with moderately elevated levels of immunoreactive prolactin may not have genuine hyperprolactinaemia.
SERUM THYROGLOBULIN IN NORMAL AND HYPOTHYROID NEONATES
Authors: BLACK E. G. , BODDEN S. J. , HULSE J. A. , HOFFENBERG R.
Published: March 2008

Thyroglobulin (Tg) is secreted only by the thyroid gland and its presence in serum should therefore indicate the presence of functioning thyroid tissue. We have measured Tg in cord and heelprick serum samples from 230 newborn infants with no thyroid disease and in forty‐seven infants with suspected neonatal hypothyroidism. In the euthyroid group, well full‐term infants showed an increase in Tg post‐natally which was not seen in ill full‐term or pre‐term neonates. Thyroid hormones were lower and TSH higher in the ill and pre‐term groups, which, in conjunction with the lack of increase in Tg, suggests impaired thyroid secretion in these groups.

Of the forty‐seven hypothyroid infants (low T4 with raised TSH) thirty‐five had measurable Tg; twenty‐eight of these had thyroid scans, and twenty‐seven showed the presence of thyroid tissue. Of twelve infants without measurable Tg seven were scanned; four showed no thyroid uptake, in the other three thyroid tissue was demonstrable; two of these had a positive family history of goitrous hypothyroidism.

It appears that many infants with biochemical hypothyroidism (low T4 and high TSH) have functioning thyroid tissue (measurable Tg and positive scan). Adequate thyroid hormone replacement therapy should be instituted in all cases, but assessment of therapy at a later stage of childhood may establish whether the prognosis for the group with functioning thyroid tissue, especially for mental impairment, is different from those without demonstrable thyroid function.
CUSHING'S SYNDROME IN PREGNANCY—TREATMENT WITH METYRAPONE
Authors: GORMLEY M. J. J. , HADDEN D. R. , KENNEDY T. L. , MONTGOMERY D.A.D. , MURNAGHAN G. A. , SHERIDAN B.
Published: March 2008

A 23‐year‐old female presented with severe Cushing's syndrome in the 23rd week of pregnancy. Investigations showed plasma cortisol 770 nmol/l (08.00 h) and 850 nmol/l (23.00 h); plasma ACTH was 10 ng/l (08.00 h) and 27 ng/l (23.00 h); urinary free cortisol excretion was 2460 nmol/24 h. Dexamethasone 2 mg 6‐hourly for 48 h suppressed the 08.00 h plasma cortisol only to 680 nmol/l. Abdominal C.T. scan showed a right adrenal adenoma. The patient was treated with metyrapone and a good clinical improvement ensued. Plasma cortisol was reduced to 300–500 nmol/l. Despite ultrasonographic evidence of normal fetal growth, urinary oestriol excretion was markedly deficient. Prior to the spontaneous onset of labour, there was a marked rise in plasma cortisol despite continuous metyrapone treatment. A normal female infant was born at 37 weeks' gestation. The maternal adrenal adenoma was subsequently removed. The deficiency of oestriol synthesis during the pregnancy may be explained by metyrapone‐induced inhibition of C19‐hydroxylation.
A COMPARATIVE STUDY OF THE EFFECT OF OESTROGEN SUBSTITUTION THERAPY ON BREAST DEVELOPMENT IN GIRLS WITH HYPO—AND HYPERGONADOTROPHIC HYPOGONADISM
Authors: PERTZELAN A. , YALON L. , KAULI R. , LARON Z.
Published: March 2008

During treatment of girls with oestrogen deficiency we observed different patterns of breast development in response to therapy.

The forty‐five girls studied fell into four groups: Group A, gonadal dysgenesis; Group B, isolated gonadotrophin deficiency; Group C, multiple pituitary hormone deficiencies; Group D, congenital adrenal hyperplasia (17‐alpha‐hydroxylase deficiency).

Treatment with oestrogen was given in an identical manner to all. In the patients with gonadal dysgenesis, in whom the hypothalamic‐pituitary function was normal, treatment led to full breast development. In isolated gonadotrophin deficiency and multiple pituitary hormone deficiency breast development was incomplete even after 3 years or more of oestrogen treatment. The conspicuous difference in the hormonal status is that the latter two groups lack gonadotrophins, while in gonadal dysgenesis these hormones are grossly elevated. Our conclusion is that gonadotrophins play an important role in mammary gland development, a finding not previously described.

In the girl with 17‐alpha‐hydroxylase deficiency we observed that cortisol was necessary, in addition to sex hormones, for normal breast development.
THE EFFECT OF PUBERTY AND SHORT‐TERM ORAL ADMINISTRATION OF TESTOSTERONE UNDECANOATE ON GH TESTS AND SEX‐STEROID RELATED PLASMA COMPOUNDS IN GH DEFICIENT PATIENTS
Authors: DROP S. L. S. , SABBE‐CLAUS L. , VISSER H. K. A.
Published: March 2008

In twelve boys and two girls, with idiopathic (partial) growth hormone deficiency diagnosed at prepubertal age, we studied the effect of spontaneous puberty (six patients) as well as the effect of sex‐steroid priming (eight patients). Six boys received testosterone undecanoate and two girls ethinyloestradiol for 5 days.

Two pubertal patients showed a normal GH response, the patients primed with testosterone or oestrogen did not, despite a distinct effect on sex‐steroid related plasma compounds.

Reevaluation of GH status appears to be worthwhile in GH deficient patients presenting with short stature, growth deceleration at an early pubertal age and delayed sexual maturation. Sex‐steroid priming is unlikely to alter the outcome of GH testing, whenever marked growth deceleration is evident at prepubertal age.
STEROIDOGENESIS IN VITRO BY HUMAN OVARIAN FOLLICLES DURING THE PROCESS OF ATRESIA
Authors: MORI TAKAHIDE , FUJITA YASUHIKO , NIHNOBU KENJI , EZAKI YOJIRO , KUBO KIYOSHI , NISHIMURA TOSHIO
Published: March 2008

Slices of each of the six antral follicles at different stages of atresia isolated from ovaries of six patients with or without pretreatment with HCG before laparotomy, were incubated with [1–14C] acetate. Incorporation into progestins, androgens and oestrogens was assessed by the reverse dilution technique with recrystallization to constant specific activity.

The greatest incorporation into androstenedione without any incorporation into progesterone was commonly observed throughout the morphologically denned three stages of atresia. In the first stage atretic follicles, characterized by coexistence of normally developed thecal cells with degenerating granulosa cells, a minute incorporation into oestradiol was identified. In the second stage atretic follicles, showing hyperplasia and hypertrophy of thecal cells without granulosa cells, an increased incorporation into androgens was shown. Treatment with HCG induced similar but much pronounced changes in function and morphology. In the third stage atretic follicles, with subsiding thecal cells, a diminished incorporation into androstenedione was observed with 17‐hydroxyprogesterone being the only other steroid formed in this stage. The observed qualitative and quantitative changes of steroidogenesis in vitro may be functional reflections of structural changes during the atretic process.
HYPERPARATHYROIDISM DUE TO A CYSTIC PARATHYROID ADENOMA AFTER IRRADIATION OF THE NECK
Authors: VALENTA LUBOMIR J. , EISENBERG HARVEY , FISHMAN ARNOLD , ELIAS ALAN N. , PEZZLO FRANK , GORDON MARVIN
Published: March 2008

A 48‐year‐old female with hypercalcaemia diagnosed 3 years prior to admission is described. The patient underwent x‐ray therapy of the neck for keloid scars 35 years prior to the diagnosis of hypercalcaemia. The hypercalcaemia was found to be the result of primary hyperparathyroidism. A cystic parathyroid adenoma was identified during surgery and was, on microscopic examination, composed of oxyphil cells rich in mitochondria. The cystic fluid contained 360 times higher C‐terminal PTH than peripheral serum and almost 4000 times higher PTH as intact 1–84 amino acid residue species. We concluded that previous X‐ray irradiation was related to the pathogenesis of the patient's parathyroid adenoma. The mild nature of the patient's hyperparathyroidism was possibly related to the composition of the tumour of oxyphil cells, known to be a poorly functioning variant of the parathyroid cell. Since parathyroid‘cysts’are obviously necrotic parathyroid adenomas, aspiration of the cysts alone cannot be expected to be curative and, therefore, it is recommended to treat cystic parathyroid adenomas by surgical extirpation.
PLASMA STEROID CONCENTRATIONS IN PATIENTS WITH HYPOPITUITARISM AND KALLMAN'S SYNDROME: EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY
Authors: SAGEL J. , LEVINE J. H. , MATHUR R. S. , ROSEBROCK G. , GONZALEZ J. , VILLIER C. DE , NAIR R. M. G.
Published: March 2008

To determine the adrenal contribution to plasma concentrations of steroids potentially derived from both the adrenal and the testes, plasma levels of pregnenolone (Δ5P), progesterone (P), dehydroepiandrosterone and its sulphate (DHA and DHAS) and androstenedione (Δ4A) were measured in four men with isolated gonadotrophin deficiency and anosmia (Kallman's syndrome). A comparison of these levels with those seen in ten patients with both adrenal and testicular failure (hypopituitarism) and in sixteen normal age‐matched men was made.

As expected, the basal plasma levels of most steroids were low in patients with hypopituitarism. An exception was the normal Δ5P levels in most patients. In the patients with Kallman's syndrome both DHA and Δ5P were elevated whereas Δ4A and P were low.

When expressed as ratios, Δ5P/P was increased in both groups. DHA/Δ4A was increased in Kallman's syndrome but not in hypopituitarism. Following ACTH infusion, no significant changes in these ratios were observed.

To determine whether testosterone deficiency was in part responsible for the abnormal Δ5/Δ4 ratios, three patients with hypopituitarism and two with Kallman's syndrome were treated for 3 months with intramuscular testosterone. A decrease in the DHA/Δ4A ratio was seen in all patients and a decrease in Δ5P/P in all but one patient. In most cases these changes were produced by a fall in the Δ5 steroids as well as an increase in Δ4 steroids.

These findings suggest that a defect in the metabolism of Δ5 steroids exists in patients with hypopituitarism and Kallman's syndrome. In hypopituitarism the defect involves the metabolism of Δ5P to both DHA and P. In Kallman's syndrome only the metabolism of Δ5P to P is defective. Testosterone therapy alone or in combination with other appropriate hormonal replacement increases the metabolism of Δ5 to Δ4 steroids.
EFFECT OF METOCLOPRAMIDE AND LISURIDE ON HYPOPHYSEAL AND GONADAL FUNCTION IN MEN
Authors: GRÄF K.‐J. , SCHMIDT‐GOLLWITZER M. , HOROWSKI R. , DOROW R.
Published: March 2008

The effects of chronic treatment over 7 weeks with metoclopramide and lisuride alone as well as the combination of both drugs were studied on basal and TRH/LHRH stimulated serum PRL, testosterone, LH, FSH, GH, and TSH concentrations. The study was conducted under double‐blind placebo‐controlled conditions and included twenty‐four healthy male volunteers. In addition, repeated seminal fluid analyses were performed before, during and after treatment. While the known PRL‐stimulatory effect of metoclopramide and the PRL‐lowering effect of lisuride could be confirmed, we were unable to demonstrate any substance‐related effects on the other hypophyseal or gonadal hormones. In contrast to previously published data no adverse effects of metoclopramide on sperm analysis could be demonstrated.
THE EFFECT OF IODIZED OIL ON GOITRE SIZE, THYROID FUNCTION AND THE DEVELOPMENT OF THE JOD BASEDOW PHENOMENON*
Authors: MABERLY G. F. , CORCORAN J. M. , EASTMAN C. J.
Published: March 2008

In the Lubok Antu district of Sarawak, Malaysia, 240 subjects with 75% prevalence of goitre were studied before and at intervals of 1 and 2 years following iodized oil injection. After 1 year the prevalence of goitre was reduced to 33%, but 2 years after injection, goitres had regrown in fourteen subjects (6%). The mean urinary iodine concentration was low initially at 0±17±0±08 (SD) μmol/l, consistent with iodine deficiency, and rose to a level of 2±6 ± 2±5 μmol/l at 1 year, before falling to 0±46 ± 0±38 μmol/l, again consistent with deficiency. Such a rapid depletion of iodine may be related to the high consumption of cassava. Before injection serum TSH concentrations showed a wide scatter from normal up to 62 mU/l and at 1 year, serum TSH concentrations were undetectable. At 2 years serum TSH was again detectable in 50% of subjects with levels up to 8±6 mu/l. During the 2 years, there was a progressive rise in the mean serum T4 concentration from 92 ± 22 (SD) nmol/l to 110 ± 22 nmol/l (P < 0±05). Serum T3 concentrations rose serially in all subjects from a pre‐injection mean of 1±9 ± 0±3 nmol/l to 2±5 ± 0±9 nmol/l (P < 0±001) and then fell significantly below the baseline level to a mean of 1±7 ± 0±6 nmol/l 2 years after injection (P < 0±01). The mean serum rT3 levels followed the same trend. At 1 or 2 years following injection, eight subjects were clinically hyperthyroid. Four of these consented to venesection and hyperthyroidism was confirmed biochemically. These data reveal that:

goitres decreased rapidly in size in response to iodized oil injection;

2 significant though incomplete depletion of the iodine stores occurred within 2 years of injection;

the consistent increase in serum T3 was associated with a fall in serum TSH to undetectable levels;

the prevalence of the Jod Basedow phenomenon was l±7%.

These data suggest the need for closer biochemical monitoring of subjects receiving massive doses of iodine and a reappraisal of the use of iodized oil in the treatment of endemic goitre.
OPIATE MODULATION OF THE PITUITARY‐ADRENAL AXIS: EFFECTS OF STRESS AND CIRCADIAN RHYTHM
Authors: GROSSMAN A. , GAILLARD R. C. , McCARTNEY P. , REES LESLEY H. , BESSER G. M.
Published: March 2008

The opiate control of the pituitary‐adrenal axis has been investigated in normal subjects. The infusion of 1 mg of the met‐enkephalin analogue, DAMME, led to a fall in circulating cortisol in spite of a fall in blood pressure. Conversely, 16 mg of the opiate antagonist, naloxone led to brisk and pronounced elevations in plasma ACTH, lipotrophin (LPH) and cortisol. The rise above basal levels was consistent, irrespective of whether the infusion was given at 09.00, 18.00, or 23.00 h; the peak response obtained was significantly less at 23.00 h than at either 09.00 or 18.00 h. Finally, insulin‐induced hypoglycaemia (0.15 u/kg) or naloxone (25 mg) produced a similar rise in plasma cortisol which was no different when the two stimuli were combined.

It is suggested that there is a constant tonic inhibition of the pituitary‐adrenal axis by endogenous opiates throughout 24 h, and that the circadian rhythm of ACTH/LPH secretion is not due to changes in opiate tone. However, disinhibition of this tone is likely to be responsible, at least in part, for the rise in cortisol in response to hypoglycaemic stress.
HYPERMINERALOCORTICISM WITHOUT EXCESSIVE ALDOSTERONE SECRETION: AN ADRENAL CARCINOMA PRODUCING DEOXYCORTICOSTERONE
Authors: KELLY WILLIAM F. , O'HARE MICHAEL J. , LOIZOU SOZOS , DAVIES DEREK , LAING IAN
Published: March 2008

A 51‐year‐old female was thought to have Conn's syndrome because she had hypertension, hypokalaemia and low plasma renin activity. The cause was not aldosterone excess, but there was an adrenal cortical carcinoma producing 11‐deoxycorticosterone (DOC) in extremely large quantities, with ineffective 1 l/?‐steroid hydroxylation. Plasma and urinary aldosterone levels were within the normal range. Blood levels of other steroids including those on the pathways of formation of glucocorticoids and sex steroids were unaffected. The tumour was cultured in vitro and shown by high performance liquid chromatography (HPLC) to produce predominantly DOC from tritiated pregnenolone, with no detectable aldosterone, in agreement with the in vivo results.
CHANGES IN CIRCULATING SOMATOMEDIN‐C LEVELS IN BROMOCRIPTINE‐TREATED ACROMEGALY
Authors: WASS J. A. H. , CLEMMONS D. R. , UNDERWOOD L. E. , BARROW I. , BESSER G. M. , WYK J. J. VAN
Published: March 2008

To determine whether the improvement in clinical status of patients with active acromegaly correlates with a reduction of circulating somatomedin‐C, serum immunoreactive somatomedin‐C was measured in twenty‐seven patients before and during bromocriptine therapy. The patients were assessed using a clinical and metabolic score which included both subjective criteria of improved sweating and facial features, and objective criteria of a reduction in ring circumference and the area under the glucose tolerance curve. Using this, together with the change in GH levels before and during bromocriptine therapy, the patients could be divided into three groups. In one group, there was no clinical improvement, a less than 30% decline in somatomedin‐C, and in four of six patients no significant decline in GH. In both the other groups there was clinical improvement and a greater than 30% decrease in somatomedin‐C. In one of these two groups, however GH did not decline, while in the other it was reduced significantly. The results suggest that during bromocriptine treatment of acromegaly, serum somatomedin‐C concentrations correlate better with clinical status than does serum GH. Since some patients have no significant fall in GH but show both clinical improvement and a reduction in somatomedin‐C, it seems likely that in some patients bromocriptine may improve acromegaly by a mechanism other than a simple decrease in total immunoreactive GH secretion.
PRODUCTION OF NON‐STIMULATORY IMMUNOGLOBULINS THAT INHIBIT TSH BINDING IN Graves' DISEASE AFTER RADIOIODINE ADMINISTRATION
Authors: BECH KARINE , BLIDDAL HENNING , SIERSBÆK‐NIELSEN KAJ , FRIIS THORKILD
Published: March 2008

The effect of a single dose of 131I upon thyroid stimulating immunoglobulins has been studied in twenty‐two patients with Graves' disease. The thyroid stimulating immunoglobulins were assessed by parallel measurements of thyrotrophin receptor binding inhibitory immunoglobulins (TBII) and of thyroid adenylate cyclase stimulating immunoglobulins (TACSI) in serum by radioreceptor assay and stimulation of adenylate cyclase respectively.

Prior to 131I therapy TBII were present in fourteen and TACSI in sixteen patients; seventeen were positive in one of the assays and thirteen in both assays. After radioiodine the level of both TACSI and TBII increased in most patients, but in six patients 131I therapy appeared to lead to a dissociation between the TBII and TACSI. After 12 months, nine patients were still positive in both assays, and twenty‐one in one of the assays.

In total, five patients developed hypothyroidism within 1 year after radioiodine. The TBII levels were significantly higher both before and 3 months after therapy in these patients than in those who remained euthyroid. Two of the hypothyroid patients developed non‐stimulatory TSH binding inhibitory antibodies.

The present study thus confirms that radioiodine therapy is followed by an increase of TBII and TACSI in most patients with Graves' disease. The level of TBII can probably provide a marker for development of hypothyroidism following 131I therapy and might be involved in its pathogenesis.
AN IMPROVED RADIORECEPTOR ASSAY FOR TSH RECEPTOR ANTIBODIES
Authors: SHEWRING G. , SMITH B. REES
Published: March 2008

An improved receptor assay for TSH receptor antibodies is described in which detergent‐solubilized TSH receptors and 125I‐labelled TSH are used. Normal human serum and immunoglobulin concentrates from normal serum showed little effect on the interaction between labelled TSH and detergent‐solubilized receptors whereas immunoglobulin concentrates from some Graves' sera caused marked inhibition of TSH binding. Precipitation with polyethylene glycol was the most convenient way of preparing immunoglobulin concentrates and using this technique the assay could be completed in a few hours. The coefficient of inter assay variation at 51% inhibition of labelled TSH binding was 3.7% and analysis of serum samples from patients with Graves' disease (n= 42), Hashimoto's disease (n= 26), multinodular goitre (n= 9), rheumatoid arthritis (n= 10) and normal donors (n= 35) suggested that the assay could detect TSH receptor antibodies in about 80% of patients (treated and untreated) with Graves' disease.
PUBERTAL MATURATION OF THE LH STIMULATORY RESPONSE TO CLOMIPHENE CITRATE IN CONGENITAL VIRILIZING ADRENAL HYPERPLASIA*
Authors: MOREIRA AYRTON CUSTÓDIO , VERÍSSIMO JOSÉ MOACIR TABOSA , FOSS MILTON CESAR , IAZIGI NASSIM , MACIEL LEA MARIA ZANINI , PIMENTA WALKYRIA DE PAULA , RODRIGUES JOSÉ ANTUNES , SANTORO JOSÉ ROMANO
Published: March 2008

To determine the LH release response to clomiphene citrate in children with virilizing congenital adrenal hyperplasia (CAH), we examined six patients with glucocorticoid‐treated virilizing CAH, five girls and one boy, chonological age (CA) 4 years 2 months‐15 years 9 months and bone age (BA) range 8–18 years. All the patients but one, were treated with nocturnal dexamethasone. Their ages at the onset of treatment ranged from 2 years 6 months to 13 years 8 months. An additional boy (CA = 4 years 3 months and BA = 7–8 years) was studied 10 days after removal of a virilizing adrenal adenoma. Clomiphene citrate (3mg/kg/day) was administered orally in two doses/day for 8 days. Venous blood was collected on days 0, 4, 6 and 8. Two patients were also studied in consecutive years. In three patients no increase was noted over the basal levels of LH, but in the others LH rose during clomiphene administration. In two patients studied in consecutive years, there was detectable shift of LH release pattern. The basal LH levels and the sum of responses (day 4, 6 and 8) to clomiphene citrate and particularly their decimal logarithms were statistically significantly correlated with their respective BA. These results confirm that previous prolonged exposure to elevated concentrations of adrenal sex steroids, in children with treated virilizing CAH, may induce precocious maturation of the hypothalamic pubertal mechanism of LH secretion. This maturation was closely correlated with the degree of skeletal maturation.
THYROID ABNORMALITIES IN PATIENTS WITH MYOTONIC DYSTROPHY
Authors: STEINBECK KATE S. , CARTER JOHN N.
Published: March 2008

Myotonic dystrophy (MD) is a systemic genetic disorder predominantly affecting musculature. Although endocrine disturbances have been described, data relating to thyroid gland involvement are sparse and conflicting. To further investigate this aspect, twenty MD patients and twenty age‐and sex‐matched controls were studied. All were clinically euthyroid and there were no significant differences between circulating levels (mean ± SD) of T4 (101±5 ± 28±2 v. 103±8 ± 27±7 nmol/1), T3 (1±86 ± 0±57 v. 2±15 ± 0±47 nmol/1), rT3 (0±39 ± 0±14 v. 0±42 ± 0±09) nmol/1) or TSH (2±6 ±0±5 v. 2±4 ± 0±8 mu/1) or between T3 resin uptakes (97 ± 8 v. 98 ± 11%). TSH responses following TRH stimulation were significantly less in the MD patients (323 ± 141 ± 529 ± 240%; P < 0±0025). The mean maximum TSH levels achieved were 6±7 ± 3±6 mu/1 (MD) and 17±1 ±7±2 mu/1 (controls); P < 0±005. Two patients had multinodular goitres (MNG) and one a single thyroid nodule. Thyroid scans were normal except for patchy uptake in the two MNG patients. There was no abnormal incidence of circulating thyroid microsomal or thyroglobulin antibodies, and thyrotrophin binding inhibitory immunoglobulin levels were normal in four patients. It is concluded that in MD: 1 palpable thyroid gland abnormalities occur with increased frequency, 15% (three/twenty) in the present study and 20% (twenty/102 case reports) from a review of the literature; 2 TSH responses to TRH are significantly reduced; 3 circulating thyroid hormone levels are usually normal.
AN ACTH‐SECRETING PITUITARY TUMOUR ARISING IN A PATIENT WITH CONGENITAL ADRENAL HYPERPLASIA
Authors: HORROCKS P. M. , FRANKS S. , HOCKLEY A. D. , ROLFE E. B. , NOORDEN SUSAN VAN , LONDON D. R.
Published: March 2008

The case reported is of a 46‐year‐old woman who had congenital adrenal hyperplasia due to a 21‐hydroxylase deficiency, and in whom there was the development of an ACTH secreting pituitary tumour. The patient was untreated with glucocorticoids until the age of 32 years when she presented with infertility. She next presented with amenorrhoea at the age of 44 years when she was found to have an enlarged pituitary fossa. Despite treatment with bromocriptine and adequate doses of dexamethasone, the tumour enlarged and required operative treatment 1 year later. Before and after operation, plasma ACTH levels were between 300 and 400 ng/1, immunocytochemistry showed staining for ACTH and other structurally related pro‐opiocortin peptides but for no other hormones, and the tumour secreted large amounts of ACTH in vitro. The report of this case is to our knowledge the first account of a feedback tumour in congenital adrenal hyperplasia and provides yet another reason why patients with this condition should be treated, and good control achieved.
AN IMPROVED METHOD FOR THE ESTIMATION OF RELATIVE BINDING CONSTANTS OF T4 AND ITS ANALOGUES WITH SERUM PROTEINS
Authors: MIDGLEY J. E. M. , WILKINS T. A.
Published: March 2008

A new method is reported for the determination of the binding constants of homologous ligands relative to that of the parent ligand. The technique minimizes the effects of random and bias errors inherent in absolute methods and obviates the need to quantitate the radiolabelled tracer concentration. In addition, it is likely to be of general applicability for monovalent proteins. The method has been applied in the determination of the binding constant (relative to that of T4) of the T4‐analogue tracer used in the Amerlex® free T4 radioimmunoassay, in respect of its binding to both T4 binding globulin and prealbumin. The binding constants of the analogue (relative to T4) were approximately 3% for both proteins. These levels were judged unlikely to interfere significantly with the measurement of free T4 in serum samples from patients with very wide variations in concentration of either T4 binding globulin or prealbumin.
TISSUE CONCENTRATIONS OF LEVONORGESTREL IN WOMEN USING A LEVONORGESTREL‐RELEASING IUD
Authors: NILSSON C. G. , HAUKKAMAA M. , VIEROLA H. , LUUKKAINEN T. , ARCANGELI P.
Published: March 2008

Thirteen women who were scheduled for hysterectomy volunteered for the study. Nine women had a levonorgestrel‐releasing intrauterine contraceptive device inserted between 36 and 49 days prior to surgery and four women were on oral levonorgestrel treatment for 7 days prior to surgery. After the surgical removal of the uterus, samples of endometrial, myometrial, fallopian tube and fat tissue were obtained. Methods for measuring tissue concentrations of levonorgestrel were developed and the uptake of levonorgestrel by fat tissue in vitro was studied. The concentrations of levonorgestrel in myometrial, fallopian tube and fat tissue were all of the same order, of between 1 and 5 ng/g of wet weight of tissue, in both the intrauterine device group and the orally treated group. In the endometrium the levonorgestrel concentrations were many‐fold higher in the intrauterine device group. The in vitro experiments showed a rapid uptake of levonorgestrel and an unsaturability of the fat tissue by the steroid at the concentrations used. The fat tissue concentrations of levonorgestrel correlated with the plasma concentrations.
EFFECTS OF TSH ON cAMP LEVELS AND THYROID HORMONE RELEASE IN HUMAN THYROID‘AUTONOMOUS’NODULES: RELATIONSHIP WITH IODOTHYRONINE AND IODINE CONTENT IN THYROGLOBULIN
Authors: TOCCAFONDI R. , ROTELLA C. M. , TANINI ANNALISA , ATERINI S. , BORRELLI D. , And L. LODDI , ARCANGELI P.
Published: March 2008

The effect of TSH on the adenylate cyclase‐cAMP system and in vitro iodothyronine release, together with the iodothyronine and iodine content of 19s thyroglobulin, were studied in seven clinically euthyroid patients with autonomous thyroid nodules. Basal cAMP and cGMP content together with phosphodiesterase and protein‐kinase activities were normal in nodular, and suppressed in extranodular tissue. TSH‐dependent cAMP accumulation was reduced in nodular tissue, but normal in the suppressed extranodular tissue. In vitro TSH‐dependent iodothyronine release from nodular and extranodular tissue was absent. Thyroxine and iodine content of thyroglobulin extracted from nodular tissue was reduced, while triodothyronine content was normal but with a low T4/T3 ratio. In extranodular tissue T3, T4 and iodine contents were reduced. In conclusion, autonomous thyroid nodules produced a poorly iodinated thyroglobulin leading to preferential T3 secretion with increased circulating free thyroid hormones even in clinically euthyroid patients.
SALIVARY CORTISOL ASSAYS FOR ASSESSING PITUITARY‐ADRENAL RESERVE
Authors: PETERS J. R. , WALKER R. F. , And D. RIAD‐FAHMY , HALL R.
Published: March 2008

Cortisol concentrations were determined in matched samples of plasma and saliva from patients and healthy volunteers throughout the course of standard tests of pituitary and adrenal reserve. During insulin tolerance tests the percentage incremental changes in cortisol concentrations in saliva were strictly comparable with those in plasma and showed less inter‐subject variance. The clinical decision taken with regard to the integrity of the pituitary‐adrenal axis was the same whether plasma or salivary cortisol was measured. In the short tetracosactrin test changes in salivary cortisol reflected those in plasma and patients with loss of adrenal responsiveness would have been diagnosed as such using either measurement. In normal subjects, the circadian rhythm in salivary cortisol concentrations exactly paralleled that in plasma. Absence of the circadian rhythm in cases of hypercortisolism was seen as well in saliva as in plasma. Assays for salivary cortisol therefore provide information which is as clinically useful as that of plasma determinations. Since salivary cortisol concentrations were shown to reflect the free, biologically active fraction in plasma, salivary assay may, in selected cases, provide results of greater diagnostic significance than plasma total concentrations.
SLEEP‐ASSOCIATED GONADOTROPHIN AND OESTRADIOL PATTERNS IN GIRLS WITH PRECOCIOUS SEXUAL DEVELOPMENT
Authors: MATTHEWS M. J. , PARKER D. C. , REBAR R. W. , JONES K. L. , ROSSMAN L. , CAREY D. E. , YEN S. S. C.
Published: March 2008

Circulating concentrations of gonadotrophins and oestradiol (E2) during sleep were examined in six girls aged 5–10 years with precocious sexual development. All subjects exhibited nocturnal increments of LH and/or FSH. Gonadotrophin secretion appeared to vary from pulsatile release to random oscillations. Three subjects with LH pulses of greater than 5 miu/ml and a concomitant FSH rise had a temporal elevation of E2 during sleep. The other three subjects with pulses of either LH or FSH of less than 5 miu/ml had no nocturnal rise in E2. These data suggest that the nocturnal elevation of E2 results from pituitary release of both LH and FSH, leads to premature sexual development, and may be occasioned by inappropriate timing of hypothalamic gonadotrophin‐releasing hormone (LHRH) secretion.
ACANTHOSIS NIGRICANS, HIRSUTISM, INSULIN RESISTANCE AND INSULIN RECEPTOR DEFECT
Authors: LEME CARLOS EDUARDO , WAJCHENBERG BERNARDO LÉO , LERÁRIO ANTONIO CARLOS , GOLDMAN JAYME , BORGES JOÑO LINDOLFO CUNHA
Published: March 2008

A 24‐year‐old negress with the triad of acanthosis nigricans, hirsutism associated with polycystic ovaries and insulin resistance is reported. Metabolic studies were done 3 years after a bilateral ovarian wedge resection. Partial remission of the hirsutism and return of menstrual cycles occurred after surgery. Extreme resistance to endogenous and exogenous insulin was observed. Three studies of insulin receptors on circulating red blood cells (RBC) showed abnormal inhibition‐competition curves, characterized by increased percentage insulin binding at higher unlabelled insulin levels. Scatchard plots suggested an apparent increase in the number of low affinity receptors. Despite the changes in receptor‐insulin interaction, the defect does not seem to explain the insulin resistance since binding of insulin to a target tissue (RBC) appeared to be quantitatively normal at physiological insulin levels, suggesting a simultaneous post receptor defect.
THYROTROPHIN BINDING INHIBITION BY ANTI‐THYROTROPHIN RECEPTOR ANTIBODIES IN GRAVES' DISEASE WHICH IS NOT REFLECTED BY 1.6 M AMMONIUM SULPHATE PRECIPITATES
Authors: DE BRUIN T. W. A. , VAN DER HEIDE D. , QUERIDO A.
Published: March 2008

In ten patients with Graves' disease before, during and after treatment and three patients in remission, we have compared the TSH‐binding inhibition caused by serum, by 1.6 M ammonium sulphate precipitates from serum and by the fractions (19S, 7S and 4S) obtained after G‐200 gel chromatography of serum and ammonium sulphate precipitates.

Five out of ten patients had a positive thyrotrophin‐binding inhibitor immunoglobulin (TBII) index before treatment, three of whom relapsed. The binding inhibition caused by 7S fractions from ammonium sulphate precipitates of the ten untreated patients could be correlated with their TBII index (r= 0.9, P<0.001).

By contrast, the 7S fractions prepared directly from the sera of the same ten patients all showed marked TSH‐binding inhibition (P<0–001) when compared with normal plasma 7S, and no correlation with the TBII index could be demonstrated (r= 0.21, P>0.05).

It is concluded that ammonium sulphate precipitates, which are used to calculate the TBII index, do not reflect the presence of anti‐TSH receptor antibodies in serum accurately in all patients.
TRILOSTANE AND THE NORMAL HYPOTHALAMIC‐PITUITARY‐TESTICULAR AXIS
Authors: SEMPLE C. G. , WEIR S. W. , THOMSON J. A. , BEASTALL G. H.
Published: March 2008

Trilostane, a competitive inhibitor of the 3β‐hydroxysteroid dehydrogenase enzyme system, has adrenal blocking activity and has been used to treat Cushing's syndrome and other diseases. To investigate its effect on the normal human hypothalamic‐pituitary‐testicular axis, trilostane (initially 240 mg/day) was given to ten healthy adult males, the dose increasing at weekly intervals by 240 mg/day up to 960 mg/day. When chromatography was used to remove trilostane and metabolites from the assay system, serum testosterone was found to fall on trilostane therapy (P<0.01) and this was accompanied by a rise in LH (P<0.01). The responses of FSH and LH to LHRH were unaffected by treatment. It is concluded that trilostane inhibits human testicular 3β‐hydroxy‐steroid dehydrogenase and male patients on trilostane should be monitored for sexual dysfunction and impairment of testicular steroidogenesis.
CARDIOVASCULAR RESPONSES IN HYPERTHYROIDISM BEFORE AND DURING 0‐ADRENOCEPTOR BLOCKADE: EVIDENCE AGAINST ADRENERGIC HYPERSENSITIVITY
Authors: FORFAR J. COLIN , SAWERS J. STEWART A. , TOFT ANTHONY D.
Published: March 2008

The relationship between the sympathetic nervous system and cardiovascular responses has been studied indirectly in ten hyperthyroid patients and age matched euthyroid controls. Nyctohemeral variations in heart rate, and heart rate and blood pressure responses to exercise were measured before and during β‐blockade with slow‐release propranolol. Both groups showed a parallel variation in heart rate over 24 h, with an increase in heart rate in the hyperthyroid group that was the same during the day (27·9 ± 0·95 beats/min) and during the night (26·7 ± 0·75 beats/min). Similarly, the increase in resting heart rate (32·7 ± 4·4 beats/min) in the hyperthyroid group was close to the increase in peak exercise‐induced heart rate (25·0 ± 4·7 beats/min). Adequate β‐blockade was achieved in all subjects as evidenced by a percentage reduction in peak exercise heart rate of 25–45%. Propranolol caused a greater reduction in daytime than night‐time heart rate in both groups and blunted the response to exercise. Following β‐3‐blockade, the mean percentage reduction in heart rate and systolic blood pressure during exercise, and heart rate responses over 24 h were similar in hyperthyroid and euthyroid groups. The closest correlation between thyroid hormone levels and heart rate was that of serum total tri‐iodothyronine (T3) and nocturnal heart rate during β‐bockade (r = 0.92; P < 0·001). It is concluded that excess circulating thyroid hormones exert a direct effect on the cardiovascular system additive to the sympathetic nervous system and that there is no evidence of adrenergic hypersensitivity in hyperthyroidism.
INCREASED PLASMA RENIN ACTIVITY IN TYPE 1 DIABETES WITH MICROVASCULAR DISEASE
Authors: DRURY P. L. , BODANSKY H. J. , ODDIE C. J. , CUDWORTH A. G. , EDWARDS C. R. W.
Published: March 2008

Plasma renin activity was measured in thirty‐one subjects with Type 1 diabetes and proliferative retinopathy, and in seventeen matched diabetic subjects without evidence of any complications of their disease. The two groups were comparable for age, sex, smoking habits and duration of diabetes. Systolic and diastolic blood pressures were significantly higher in the patients with retinopathy (P < 0·025 and P= 0·05 respectively) and HbA1 was greater (P < 0·005) than in the patients without complications. Plasma renin activity, both lying and standing, was higher in the patients with retinopathy than in the uncomplicated group (P < 0·05 for each). There were no correlations between plasma renin activity and mean blood pressure, HbA1 or fasting blood glucose. These findings raise the possibility that the renin‐angiotensin system might be implicated in the pathogenesis of diabetic microvascular disease.
HYPER‐RESPONSIVENESS OF ALDOSTERONE TO METOCLOPRAMIDE IN ALDOSTERONISM
Authors: GNIADEK T. C. , GREKIN R. J. , GROSS M. D. , VILLAREAL J. Z.
Published: March 2008

Metoclopramide, a dopamine antagonist, stimulates aldosterone secretion in normal man. We studied the response of plasma aldosterone, plasma renin activity, cortisol, sodium, potassium and serum prolactin to a 10‐mg intravenous dose of metoclopramide in six dexamethasone suppressed patients with aldosteronism (four with adrenal adenoma, two with bilateral adrenal hyper‐plasia) and in six dexamethasone suppressed normal male volunteers. All subjects were studied on an ad libitum sodium diet. Patients were supplemented with oral potassium prior to study.

Sodium and potassium were not different between groups and did not change following metoclopramide. Cortisol was suppressed to less than 3 μg/dl throughout the study in all subjects. Basal plasma renin activity was significantly lower in the patients as compared with controls (P < 0·05), and did not change in either group following metoclopramide.

Basal aldosterone levels were not significantly different in patients as compared with controls, although patients did tend to have higher levels. The incremental and integrated response of aldosterone to metoclopramide in patients was significantly greater than controls (P < 0·01). The percentage increase in aldosterone was greater than controls in five of the six patients.

Basal prolactin was higher in the patients than in the controls. All subjects had a significant rise in prolactin to metoclopramide (P < 0·05). Five of six patients had an increased response of prolactin when compared to the controls and the four female patients had a significantly greater rise in prolactin as compared to the normals (P < 0·01).

These data suggest that increased dopaminergic activity plays a compensatory role in inhibiting aldosterone secretion in patients with aldosteronism. It appears unlikely that a decrease of dopaminergic inhibition is involved in the pathogenesis of aldosteronism due to either adenoma or bilateral hyperplasia.
VARIATIONS IN CLINICAL, HORMONAL AND SEROLOGICAL EXPRESSIONS OF CHRONIC LYMPHOCYTIC THYROIDITIS (CLT) IN CHILDREN AND ADOLESCENTS
Authors: DE PAPENDIECK LAURA GRUñEIRO , IORCANSKY SONIA , RIVAROLA M. A. , BERGADÁ C.
Published: March 2008

A diagnosis of chronic lymphocytic thyroiditis (CLT) was made in forty‐two children and adolescents according to Fisher's criteria. The age of the group ranged between 4±3 and 18±5 years. On the basis of serum TSH, T4 and RAI uptake, three groups of patients were distinguished at the time of diagnosis: 1, euthyroid group (n= 3) with normal TSH and T4; 2, hypothyroid group (n= 36) with high values of TSH, where three subgroups were distinguished: (a) compensated hypothyroidism (n= 14) with normal T4, (b) overt hypothy‐roidism with high or normal RAI uptake and low T4 (n= 19), (c) overt hypothyroidism with low RAI uptake and low T4 (n= 3); 3, Hyperthyroid group (n= 3) with high T4. In CLT, variability is a feature not only of the initial presentation, but also of the subsequent evolution of the disease. Sixteen patients were followed for periods between 4 months and 6 years. Thyroid function did not change in six. Six patients with compensated or overt hypothyroidism improved, four became euthyroid with normal basal TSH and T4 values, however, all three tested had an exaggerated response to TRH. Three patients who were initially hyperthyroid progressed to a state of compensated hypothyroidism. One patient with overt hypothyroidism on presentation developed hyperthyroidism after 15 months and became hypothyroid once more 8 months later. The variable clinical course of CLT is characteristic of immunological disturbances.
ALDOSTERONE IN SUSTAINED ESSENTIAL HYPERTENSION
Authors: SAFAR M. E. , SIMON A. Ch. , DARD S. A. , PARLIER H. R. , PAULEAU N. E. , VINCENT M. L. , SASSARD J. E.
Published: March 2008

Plasma aldosterone (PA), plasma renin activity (PRA), extracellular fluid volume (EFV) and hepatic blood flow were measured in forty‐four patients with sustained essential hypertension and compared with forty‐two normotensive controls of same age and sex. All patients had inulin clearances within the normal range and balanced sodium intake and urinary output. In hypertensives, PA, PRA, EFV and hepatic blood flow were within normal ranges; the log‐ratio PA: PRA was significantly elevated (P < 0·001). In normotensives, a negative relationship was observed between PA and EFV (r= ‐0·55; P <0·001) while a positive relationship was observed between PA and PRA (=+0·70; P < 0·001). In hypertensives, the two relationships were disrupted or less significant: for a given value of EFV, PA was more elevated in hypertensives than in normotensives; for a given value of PRA, PA was more elevated in hypertensives than in normotensives. The results could not be explained on the basis of a disturbance in hepatic blood flow and/or in the metabolic clearance rate of aldosterone. The study provided evidence that, in patients with sustained essential hypertension and equilibrated sodium balance, there is an excess of plasma aldosterone relative to the levels of extracellular fluid volume and plasma renin activity. The excess is probably related to an abnormality in the adrenal secretion.
T3 HYPERTHYROIDISM AND THYROID CANCER
Authors: KRUTER REGINA H. E. , LIEDTKE MONIKA , DE CASTRO J. A. SISSON , GROSS J. L.
Published: March 2008

The authors present an unusual case of T3 hyperthyroidism caused by a well‐differentiated thyroid follicular carcinoma and its large skull metastasis. They suggest iodine deficiency as being the single major factor in the aetiology of both disorders.