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 An undetectable postoperative serum cortisol has been regarded as a definition of cure in Cushing’s disease. However, we noted disease recurrence amongst patients with Cushing’s disease despite undetectable postoperative cortisol levels, and this led us to audit our data. We have also previously assessed surgical outcome for acromegaly and microprolactinoma for a single surgeon. The aims of this study were two-fold: (i) to investigate the treatment and surgical outcome of patients with Cushing’s disease. In particular, we wished to compare the data with outcome for other pituitary tumours in our centre; and (ii) to determine whether undetectable cortisol following surgery is predictive of long-term cure for Cushing’s disease.

patients and methods We performed a retrospective audit of 97 patients; mean age 39·1 (range: 14–82) years, 78/97 (80·4%) female, mean follow-up 92 months (range: 6 months to 29 years), with Cushing’s disease seen in our unit between 1969 and 1998. We documented diagnostic investigation, immediate surgical outcome and disease recurrence in these patients.

results All patients had elevated urinary free cortisol (mean 1270·6 nmol/l, range: 327–3245 nmol/l). In total, 95·5% of patients did not suppress with low-dose dexamethasone suppression testing. Hypokalaemia (K   50% following corticotrophic releasing hormone (CRH) administration. There was no significant (> 3) gradient in ACTH or cortisol following CRH during inferior petrosal sinus sampling in 27·3% of patients who had the test. A pituitary tumour was demonstrated on imaging in 55·8% of patients; 10·3% were macroadenomas. Mortality rate following trans-sphenoidal surgery was 1%. Following surgery, the immediate postoperative remission rate (undetectable postoperative cortisol) was 68·5%. However, 11·5% of these patients developed disease recurrence during a mean follow-up period of 36·3 months. Considering microadenomas, Cushing’s disease patients had an immediate postoperative remission rate of 63·2% which is significantly lower (P < 0·05) compared to a remission rate of 91·1% in acromegaly. Additionally, new postoperative gonadotrophin deficiency (13·9%) and TSH deficiency (25·8%) was higher in patients with Cushing’s disease compared to patients with acromegaly or microprolactinoma. Immediate postoperative remission rates improved from 50% in the first decade of a surgeon’s career to consistently above 60% in the second and third decades, demonstrating a trend which may be attributed to surgical experience.

conclusions (i) Despite strict criteria for immediate postoperative remission and recurrence, undetectable postoperative cortisol is not always predictive of long-term remission. (ii) Despite an aggressive surgical approach, immediate postoperative remission rates for Cushing’s disease are lower compared to other microadenomas. The development of new pituitary hormonal deficiency following surgery is also commoner than that seen amongst other microadenomas. These data have important implications for the follow-up of patients with Cushing’s disease.

Undetectable postoperative cortisol does not always predict long‐term remission in Cushing’s disease: a single centre audit*

Summary
OBJECTIVE We audited our practice of insulin tolerance testing (ITT) in terms of safety and technical success. We reviewed the results of those tests performed over a 12-month period. By relating peak Cortisol response to 0900 h screening Cortisol level, we determined whether we could reduce the number of tests performed.

DESIGN The results of all ITTs performed on our unit between 1 January and 31 December 1991 were reviewed.

PATIENTS AND MEASUREMENTS Patients were pre-screened by measurement of serum Cortisol and thyroxine, and recording of an electrocardiogram. A subnormal serum thyroxine (<58 nmoi/l), 0900 h serum Cortisol (<100 nmol/l) or an abnormal ECG were taken as contraindications to the test. Minimum glucose and maximum Cortisol levels were recorded, along with peak GH responses when measured. The peak Cortisol response was compared to the screening and basal Cortisol levels.

RESULTS A total of 161 tests were performed, 135 of which fulfilled our inclusion criteria. The test was technically successful in all but 5 of these; a significant adverse event occurred in one patient with full recovery after reversal of hypoglycaemia. Thirty-two patients had a suboptimal serum Cortisol response to hypoglycaemia: screening Cortisol level ranged from 128 to 493 nmol/l and 0900 h serum Cortisol measured prior to the ITT from 97 to 431 nmol/l. The lowest level of screening Cortisol above which all patients would be expected to achieve the normal peak Cortisol of 580 nmol/l or over is therefore 494 nmol/l. If this cut-off level had been adopted, 10 (8%) ITTs need not have been performed if their only purpose had been to assess Cortisol reserve. Altering the criterion for the necessary peak Cortisol to 500 nmol/l did not affect the number of ITTs required. Our lower limit for testing could not be revised upwards from 100 nmol/l. Adequacy of Cortisol reserve did not predict a normal GH response to insulin-induced hypoglycaemia.

CONCLUSIONS When performed in an experienced endocrine unit with adequate supervision, the insulin tolerance test is a safe procedure. According to the current sample, fewer tests would be performed without detriment to patient care if those with a screening Cortisol of greater than 500 nmol/l did not proceed to testing, unless the purpose of the test was also to exclude GH deficiency. A lower limit of 100 nmol/l appears reasonable and need not be revised upwards.

An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year

Reduction of pituitary-tumour size in patients with prolactinomas and acromegaly treated with bromocriptine with or without radiotherapy

This study explores the clinical and endocrine implications of hyperinsulinaemia in the polycystic ovary syndrome (PCOS). Oral glucose tolerance tests were performed on 34 lean and 19 obese women with PCOS and on 13 lean women with normal ovaries. Insulin measurements were compared with basal gonadotrophins, androgens, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein 1 (IGFBP-1). Unselected lean women with PCOS were found to have fasting hyperinsulinaemia and the raised serum insulin concentrations were associated with menstrual disturbance and hyperandrogenaemia. In addition, serum insulin concentrations in lean women with PCOS correlated positively with serum IGF-I and negatively with serum IGFBP-1 concentrations. Ovarian stimulation by insulin appears to be independent of luteinizing hormone (LH) and is an important feature in 30% of lean women with PCOS.

Effects of luteinizing hormone, insulin, insulin-like growth factor-I and insulin-like growth factor small binding protein 1 in the polycystic ovary syndrome.

Synthetic CRF-41 has been given to 43 patients with hypothalamic, pituitary or adrenal diseases and contrasted with the responses in 20 normal subjects. In the normal subjects the mean increment in serum cortisol (+/- SE) was 276 +/- 38 nmol/l; the increments showed a significant negative correlation with the basal serum cortisol levels (r = -0.56; P less than 0.02). The mean peak serum cortisol was 662 +/- 34 nmol/l and the mean peak corticosterone was 28.6 +/- 3.8 nmol/l. There was a significant positive correlation between the peak serum corticosterone and cortisol concentrations (r = 0.84; P less than 0.0001). Dexamethasone pretreatment abolished the rise in cortisol in response to CRF-41. The peak serum cortisol following CRF-41 was not significantly different between the normal subjects and those patients with pituitary disease who had normal cortisol responses to insulin-induced hypoglycaemia. However, in individual patients the peak cortisol levels induced by hypoglycaemia were greater than, but significantly correlated with, those induced by 100 micrograms of CRF-41. Seven patients were ACTH deficient in response to hypoglycaemia, and of these six responded normally to CRF-41. Only one of these patients had a lesion clearly originating in the hypothalamus; four had pituitary tumours with suprasellar extensions and the remaining patient had idiopathic GH and ACTH deficiency. Our data suggest that these patients have a functional defect of ACTH secretion due to the failure of CRF to reach the corticotroph. Of the four patients with pituitary-dependent Cushing's disease who were on no treatment at the time of testing, three showed an exaggerated and one a normal response to CRF-41. These normal or enhanced responses of hypercortisolaemic patients with Cushing's syndrome contrast with the complete inhibition of the responses to CRF-41 in normal subjects given dexamethasone. In the treated patients with Cushing's syndrome and normal serum cortisol levels, those with pituitary-dependent disease showed an enhanced ACTH response to CRF-41 as compared with the ectopic ACTH group, but there was some overlap between the two groups. Acromegalic patients did not show a GH response to CRF-41. We conclude that administration of CRF-41 is a safe new method for investigating disorders of the hypothalamo-pituitary axis.

J. A. H. Wass

Papers

Undetectable postoperative cortisol does not always predict long‐term remission in Cushing’s disease: a single centre audit*

An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year

Reduction of pituitary-tumour size in patients with prolactinomas and acromegaly treated with bromocriptine with or without radiotherapy

Effects of luteinizing hormone, insulin, insulin-like growth factor-I and insulin-like growth factor small binding protein 1 in the polycystic ovary syndrome.

Corticotrophin releasing factor: responses in normal subjects and patients with disorders of the hypothalamus and pituitary