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.

In normal adolescents there is a pubertal fall in circulating levels of sex hormone binding globulin (SHBG) in both sexes which is not explained by classically accepted mechanisms of control of SHBG. Recent in vitro and in vivo evidence has suggested that SHBG is inversely regulated by insulin. In view of this we have compared SHBG levels in 80 adolescent subjects with Type 1 diabetes to those in 61 normal adolescents. In both normals and in Type 1 diabetic subjects there was a pubertal fall in SHBG levels. Contrary to expectations, SHBG levels were not elevated in those with diabetes, but prepubertally were significantly lower in both sexes (boys mean +/- SD, 70 +/- 28 nmol l-1, normals 130 +/- 52 nmol l-1, p less than 0.001; girls, 61 +/- 17 nmol l-1, normals 110 +/- 23 nmol l-1, p = 0.01). In pubertal subjects no differences in SHBG levels were seen between the two groups, or between either sex within any group. In subjects with Type 1 diabetes SHBG levels were unrelated to metabolic control as reflected by HbA1 but were inversely related to pubertal stage (r = 0.55, p less than 0.001). In prepubertal subjects with diabetes, in whom abnormal SHBG levels were found, these levels were weakly related to insulin dose (r = 0.33, p less than 0.05); no such relationship was found in the other groups. The significance of the abnormal SHBG levels in prepubertal children with diabetes and its relationship to any irregularities of their sexual development is unclear.

Sex Hormone Binding Globulin Levels in Adolescent Subjects with Diabetes Mellitus

A patient is described with tumours in the region of the pineal gland and anterior hypothalamus associated with high levels of hCG beta in the serum and cerebrospinal fluid (CSF). He presented aged 19, with hypopituitarism, but persistent secondary sexual characteristics. LH immunoreactivity in serum was due to the hCG beta which probably caused the elevated level of testosterone. Following cranial irradiation the tumour became undetectable and hCG beta was eradicated from the serum and CSF. The patient later died because of an intramedullary metastasis of choriocarcinoma in the cervical spinal cord. The endocrine details of six previously reported intracranial neoplasms which have been shown to secrete hCG beta are reviewed. Only two of these involved the pineal region. Chorionic gonadotrophin production by this tumour enabled early detection of its recurrence. It is unclear how often precocious puberty is caused by tumours producing hCG beta, but patients presenting either with that problem or a pineal tumour should have circulating hCG beta measured.

hCG beta producing pineal choriocarcinoma.

Wass JAH, Lytras N, Besser GM. Somatostatin octapeptide (SMS 201-995) in the medical treatment of acromegaly.Parenteral somatostatin has been used to suppress growth hormone secretion in acromegalic patients, but long-term treatment is hampered by its short half-life of a few minutes in the circulation. An octapeptide analogue of somatostatin (SMS 201-995) has recently been developed that has greater potency and selectivity in suppressing growth hormone than the native hormone. In this study somatostatin and somatostatin octapeptide infusions were compared in 13 patients with active acromegaly. The octapeptide had a longer duration of action in the suppression of growth hormone than native somatostatin. A twice daily dose of 100 μg significantly suppressed growth hormone during the day. Prolactin was not suppressed, even in hyperprolactinaemic patients, and suppression of insulin was of short duration. Two patients had diarrhoea, but this disappeared when treatment with the octapeptide was stopped. Somato...

Somatostatin octapeptide (SMS 201-995) in the medical treatment of acromegaly.

SUMMARY
Acromegaly secondary to the secretion of ectopic growth hormone releasing hormone (GHRH) is rare. We have documented the presentation and unusual clinical course of a patient with a disseminated GHRH-secreting bronchial carcinoid tumour associated with acromegaly over a 17-year period. Recurrent widespread metastatic lesions have been treated over a 10-year period by repeated cycles of the nitrosourea CCNU and 5-fluorouracil with evidence of tumour regression and reduction of circulating growth hormone (GH) and urinary 5HIAA excretion. This cytotoxic regimen, which has been well tolerated, may prove valuable in the management of disseminated carcinoid tumours.

Successful treatment by chemotherapy for acromegaly associated with ectopic growth hormone releasing hormone secretion from a carcinoid tumour.

A specific radioimmunoassay for the beta-chain of human chorionic gonadotrophin irHCG beta has demonstrated HCG-like material to be present in craniopharyngioma cyst fluid in nine consecutive patients with craniopharyngioma. There was no detectable LH/HCG bioactivity as assessed using testosterone production from isolated Leydig cells from rat testis in seven samples tested. One patient was also found to have measurable irHCG beta in the cerebrospinal fluid (CSF), which fell to undetectable levels following surgery; in this patient, there was clinical evidence that the cyst fluid had leaked into the CSF pre-operatively. Immunocytochemical staining for HCG beta and intact HCG was positive in five of the tumours. irHCG beta was not measurable in the serum of any of the patients.

J. A. H. Wass

Papers

Sex Hormone Binding Globulin Levels in Adolescent Subjects with Diabetes Mellitus

hCG beta producing pineal choriocarcinoma.

Somatostatin octapeptide (SMS 201-995) in the medical treatment of acromegaly.

Successful treatment by chemotherapy for acromegaly associated with ectopic growth hormone releasing hormone secretion from a carcinoid tumour.

Immunoreactive human chorionic gonadotrophin from the cyst fluid and CSF of patients with craniopharyngioma.