Bile salt biotransformations by human intestinal bacteria.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. The classical symptoms are those of hyperandrogenism (hirsutism, persistant acne, androgen dependent alopecia) together with symptoms of anovulation (infertility, amenorrhoea, irregular dysfunctional uterine bleeding).1In the last 10 to 15 years, the use of high resolution pelvic ultrasonography has greatly facilitated identification of polycystic ovaries in women with hirsutism or menstrual disturbance. It is now clear that the range of presenting symptoms of women with polycystic ovaries includes not only non-hirsute women with oligomenorrhoea or amenorrhoea but also hirsute subjects with regular, ovulatory cycles. PCOS occurs in nearly 75% of cases of anovulatory infertility and over 80% of subjects with hirsutism.1 The typical biochemical features of PCOS include hyperandrogenaemia and an increase of serum luteinising hormone (LH) (with normal follicle stimulating hormone) but PCOS is also associated with a characteristic metabolic syndrome that includes hyperinsulinaemia, insulin resistance, and dyslipidaemia.1-4 These features are linked to a significantly increased risk of type II (non-insulin-dependent) diabetes in later life and women with PCOS may also have a greater chance of developing premature cardiovascular disease.3 5 6 

The presence of polycystic ovaries is necessary for the development of the syndrome but not all women with polycystic ovaries have PCOS. The typical …

Polycystic ovary syndrome.

Various tumours, classically specified as either neuroendocrine or non-neuroendocrine, contain high numbers of somatostatin receptors, which enable in vivo localization of the primary tumour and its metastases by scintigraphy with the radiolabelled somatostatin analogue octreotide. In addition granulomas and autoimmune processes can be visualized because of local accumulation of somatostatin receptor-positive activated mononuclear leucocytes. In many instances a positive scintigram predicts a favourable response to treatment with octreotide. It is tempting to speculate that octreotide labelled with an appropriate radionuclide might be used in cancer therapy. The successful application of radiolabelled octreotide in scintigraphy indicates the possible usefulness of other radiolabelled peptides, either native peptides or derivatives of these, in, for example, nuclear oncology. The small size of these peptides, e.g. bombesin and substance P, is of the utmost importance for a relatively fast blood clearance, thus leading to low background radioactivity. In this way peptides are powerful alternatives to (fragments of) monoclonal antibodies, the application of which to scintigraphic localization of specific cell surface antigen-bearing tumours is plagued by slow blood clearance and, hence, high background levels.

/pdf/somatostatin-receptor-scintigraphy-with-111in-dtpa-d-phe1-4zjyz1r6jz.pdf

Somatostatin receptor scintigraphy with [111In-DTPA-d-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61375-1.pdf

Cushing's syndrome

I. Introduction IN THE adult ovary, folliculogenesis starts when follicles leave the pool of resting follicles (RF) to enter the growth phase. From there, the early growing follicle undergoes a developmental process including a dramatic course of cellular proliferation and differentiation. In primates, only one follicle commonly reaches the preovulatory stage every cycle; most follicles fail to complete this maturation scheme, dying in the process termed atresia. In recent years, a picture has emerged depicting the classic endocrine control of ovarian function by LH and FSH, entangled in a maze of regulatory systems hinging on cell-cell interactions between follicular cells, via action of a variety of molecules (1–3). Different types of cell-cell interactions have been described. In paracrine regulations, a molecule synthesized by one cellular type is released into the interstitial milieu to act directly on another cellular type. In autocrine regulations, molecules synthesized by one cellular type are rel...

/pdf/regulation-of-ovarian-follicular-development-in-primates-4srrm0fi7f.pdf

Regulation of ovarian follicular development in primates: facts and hypotheses.

SUMMARY
objective A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We have looked at the use of an 123I-labelled Tyr3-octreotlde analogue of somatostatin In the visualization and functional characterization of growth hormone-secreting pituitary adenomas.

patients Fifteen patients with biochemically-proven acromegaly were scanned using this agent. In eight of these we also assessed acute GH responses to octreotide in order to correlate these responses with tumour uptake characteristics

measures Planar and single-photon-emlsslon computerized tomographic (SPECT) images of the head were obtained using a gamma-camera at 10 minutes, and 4 and 24 hours, after injection of the radiopharmaceutical. Blood for serum GH was sampled for 12 hours after administration of a single dose of 100 μ g octreotide.

results Twelve of the acromegalic subjects showed significant uptake of the radiopharmaceutical in the pituitary fossa. Of the eight patients In whom we assessed acute GH responses, five demonstrated a significant fall in GH in response to octreotide. These subjects also showed positive uptake in the pituitary on scanning. The three patients who had no fall in GH had no uptake on scanning

conclusions Uptake of 123I-labelled Tyr3-octreotide in the pituitary fossa appears to correlate closely with the presence of a therapeutic response to octreotide.

Pituitary imaging using a labelled somatostatin analogue in acromegaly.

Octreotide therapy in acromegaly is associated with an increased prevalence of gall stones, which may be the result of an inhibition of gall bladder motility. Gall stone prevalence in untreated acromegalic patients relative to the general population is unknown, however, and the presence of gall stones and gall bladder motility in these patients and in acromegalic patients receiving octreotide was therefore examined. Thirty four percent of 39 patients who had taken octreotide for a mean of 20 months had gall stones compared with 16% of 38 patients who had not been treated with octreotide (p < 0.005). In a subgroup of 21 patients studied prospectively over 4 to 18 months, two patients developed stones. No patient had symptoms referrable to their gall stones. In 31 untreated acromegalic patients, the mean fasting gall bladder volume was similar to that in normal subjects. Maximal percentage emptying, however, was impaired (34 v 64%, p < 0.001) and the mean postprandial residual gall bladder volume increased (21.7 v 9.0 ml, p < 0.001). Treatment with octreotide increased the mean postprandial residual volume further to 36.8 ml (p < 0.001). Gall bladder emptying in untreated acromegalic subjects is impaired. Octreotide further increases postprandial residual gall bladder volume and this may be a factor in the increased gall stone prevalence seen in these patients.

https://gut.bmj.com/content/gutjnl/34/2/270.full.pdf

Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly.

SUMMARY
Fifteen patients (12 male) with large pituitary tumours and serum prolactin levels below 1000 mU/1 were given dopamine agonist therapy (bromocriptine, mesulergine or pergolide) for a mean of 9 months (range 3–36 months) Serum prolactin became undetectable in all Despite this, significant suprasellar extensions and any associated neurological defect remained in 14 patients, who therefore were referred for surgery In one patient there was evidence of spontaneous pituitary infarction unrelated to dopamine agonist therapy At operation 12 patients had apparently functionless pituitary adenomas which failed to immunostain for prolactin, one had an epidermoid cyst and one a Rathke's pouch cyst We conclude that patients with large pituitary tumours and only a mildly elevated serum prolactin are unlikely to have prolactinomas, and that such tumours are not likely to show significant tumour shrinkage with medical treatment with dopamine agonists

The effect of dopamine agonist therapy on large functionless pituitary tumours

SUMMARY
A 41-year-old man presented with Cushing's syndrome and the biochemical features of ectopic ACTH production. Investigation revealed mediastinal metastases from a medullary carcinoma of the thyroid. The peripheral plasma contained grossly elevated levels of bombesin-like immunoreactivity (irBombesin) as well as calcitonin; blood sampling via a venous catheter confirmed a gradient of irBombesin, but not of ACTH, in the mediastinal vein draining the tumour. On extraction the tumour contained a bombesin-like peptide, but not vasopressin or corticotrophin releasing factor and only very low levels of ACTH; immunohistochemical studies showed positive immunostaining for bombesin and calcitonin but none for ACTH or CRF. No ACTH was released from dispersed tumour cells in vitro. However an extract of the tumour stimulated ACTH release in vitro from perifused dispersed rat anterior pituitary cells. This is the first reported case of Cushing's syndrome due to ectopic production of a bombesin-like peptide, causing excessive pituitary ACTH secretion.

Pituitary acth dependent cushing's syndrome due to ectopic production of a bombesin‐like peptide by a medullary carcinoma of the thyroid

SUMMARY
Fourteen patients presented with arrested pubertal development associated with prolactin-secreting pituitary tumours; serum prolactin ranged from 4000–104300 mU/1 in the ten females and 920–68000 in four males. Skull X-ray showed a markedly expanded pituitary fossa in eight patients. CT scan and/or air encephalography showed macroadenomas in nine, of whom seven had large suprasellar extensions to their tumours, yet only five had complained of headache and only two had visual field defects. All were treated with bromocriptine (7.5–60 mg/day) which lowered prolactin substantially in all and into the normal range in 11 (range < 60–3090, median 105 mU/1). Puberty thereafter progressed spontaneously in 13, but in one patient, whose prolactin did not suppress completely, menarche could be induced only with clomiphene. Anterior pituitary function improved on bromocriptine. In seven patients with macroadenomas, tumour shrinkage into the pituitary fossa was complete and in two others incomplete shrinkage was followed by transsphenoidal hypophysec-tomy. Seven patients received pituitary irradiation, six after bromocriptine-induced shrinkage and one after transsphenoidal surgery. At follow-up 6 months to 10 years (median 5 years) after presentation,' ten remain on bromocriptine with a suppressed serum prolactin, one has a normal prolactin after surgery, and three are off bromocriptine with residual hyperprolactinae-mia (418–4680 mU/1). To date, four females have become pregnant and one male has fathered two children.

Prolactinomas are an important, albeit rare, cause of arrested puberty and should therefore be sought. Most patients respond well to bromocriptine, with or without pituitary irradiation.

J. A. H. Wass

Papers

Pituitary imaging using a labelled somatostatin analogue in acromegaly.

Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly.

The effect of dopamine agonist therapy on large functionless pituitary tumours

Pituitary acth dependent cushing's syndrome due to ectopic production of a bombesin‐like peptide by a medullary carcinoma of the thyroid

Prolactinomas presenting as primary amenorrhoea and delayed or arrested puberty: response to medical therapy