G. M. Besser

Inhibition of gastrin and gastric-acid secretion by growth-hormone release-inhibiting hormone

Abstract The hypothalamic polypeptide growth-hormone release-inhibiting hormone (G.H.-R.I.H.) inhibited gastrin release in all subjects studied. In normal subjects and in patients with acromegaly during a standard food stimulus a G.H.- R.I.H. infusion completely suppressed gastrin release, and immediately after the infusion was stopped gastrin levels rose sharply to exceed control values. Two patients with pernicious anaemia demonstrated a rapid fall in plasma-gastrin during G.H.-R.I.H. infusion, and in a patient with Zollinger-Ellison syndrome a 20-minute G.H.-R.I.H. infusion greatly lowered plasma-gastrin concentrations and almost totally suppressed gastric-acid production.

Long-term Treatment of Galactorrhoea and Hypogonadism with Bromocriptine

Seventeen women and four men with galactorrhoea and associated hypogonadism have been treated with bromocriptine for 2 to 28 months. In 18 patients the gonadal status became normal as the galactorrhoea improved. The gonadally unresponsive patients had either pituitary tumours or premature menopause. Prolactin levels fell with treatment; withdrawal of the drug was associated with an increase in serum prolactin and a recurrence of the galactorrhoea and hypogonadism. Two patients tried to become pregnant on treatment and both succeeded. Raised prolactin levels appear to block the actions of the gonadotrophins at a gonadal level rather than prevent their synthesis or release; lowering prolactin secretion with bromocriptine allows resumption of normal gonadal function. Bromocriptine appears to be the treatment of choice for inappropriate lactation in association with hypogonadism on a long-term basis.

HORMONAL AND METABOLIC RESPONSES TO AN ENKEPHALIN ANALOGUE IN NORMAL MAN

An enkephalin analogue [D-Ala2, MePhe4, Met(o)-ol] enkephalin (DAMME), given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin. There was also a small fall in total glucagon and gastric inhibitory peptide (G.I.P.) and a rise in thyrotrophin. beta-Lipotrophin, motilin, vasoactive intestinal peptide, insulin, gastrin, and pancreatic glucagon were unchanged. Blood-glycerol increased, and blood lactate, alanine, and glucose fell. Prior administration of the opiate antagonist, naloxone, attenuated the hormonal responses to DAMME. This enkephalin analogue produces endocrine and metabolic changes in man which may be mediated through opiate-binding receptors both within and outside the brain. The enkephalins and related substances may provide an important link between perception, behaviour, and neuroendocrine regulation of hormone secretion and metabolism.

INCREASED β-ENDORPHIN BUT NOT MET-ENKEPHALIN LEVELS IN HUMAN CEREBROSPINAL FLUID AFTER ACUPUNCTURE FOR RECURRENT PAIN

Low-frequency electroacupuncture effectively alleviated recurrent pain in 10 patients. Basal levels of beta-endorphin and met-enkephalin in the lumbar cerebrospinal fluid (CSF) of these patients were not different from those in pain-free control subjects. After electroacupuncture in the patients with pain CSF beta-endorphin levels rose significantly in all subjects, but met-enkephalin levels were unchanged. These results suggest that the analgesia observed after electroacupuncture in patients with recurrent pain may be mediated by the release into the CSF of the endogenous opiate, beta-endorphin.

DIAGNOSIS AND MANAGEMENT OF ACTH‐DEPENDENT CUSHING'S SYNDROME: COMPARISON OF THE FEATURES IN ECTOPIC AND PITUITARY ACTH PRODUCTION

The clinical features, diagnosis and management of 16 consecutive patients with ectopic ACTH production are described and biochemical data are compared with those of 48 consecutive patients with pituitary‐dependent Cushings disease. In 10 cases the ectopic ACTH secreting tumour was completely occult to routine clinical and radiological investigation, and no basal or dynamic investigation of adrenal‐pituitary function was able clearly to differentiate these patients from those with Cushings disease. High dose dexamethasone suppression testing assessed by plasma cortisol was usually helpful but unexpected responses were seen in both diagnostic groups; the metyrapone test yielded no useful information and should now be abandoned. Hypokalaemia was seen in all patients with ectopic ACTH production but in only 10% of those with Cushings disease who were not on diuretics at presentation. Successful diagnosis and tumour localization was most frequently achieved by a combination of CT scanning of the chest and abdomen and venous catheter sampling for ACTH. All patients in whom the ectopic ACTH‐secreting tumour was obvious at presentation died of their primary tumour within 8 months, whereas seven of the 10 patients with occult tumours at presentation are alive 1·5–16·5 years later, and appear cured. Occult ectopic ACTH secretion may be impossible to distinguish from pituitary Cushings disease. Multiple and repeated investigations are often required to make this differential diagnosis, essential for appropriate therapy.

Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successfuI treatment

OBJECTIVE We tested the hypothesis that in Cushings disease, ACTH secretion from the normal pituitary surrounding an ACTH‐secreting adenoma is inhibited and hence removal of the entire adenoma should result in an undetectable serum cortisol in the immediate post‐operative period.

Long-term treatment of acromegaly with bromocriptine.

Seventy-three patients with active acromegaly were treated for three to 25 months with bromocriptine 10-60 mg/day. Seventy-one patients showed symptomatic and objective clinical improvement. This included reduction in excessive sweating, hand and foot size, and the number of headaches; improved facial appearance; and increased energy and libido. Abnormal visual fields became normal in two patients, one of whom had concomitant radiotherapy. Mean circulating growth hormone levels, obtained by averaging serial samples through the day, fell by more than 7 microng/l or became undetectable in 58 patients (79%) but did not reach normal values: only 15 patients had mean levels on treatment of 5 microng/l or less. Twenty-three patients were diabetic before treatment, and glucose tolerance became normal in 15 and improved in a further five. Provided the drug was started slowly side effects were minor when compared with the considerable clinical benefit obtained.

Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure

OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer‐term outcome for patients not offered further treatment when post‐operative levels of GH < 5 mU/l were achieved.

Gonadotrophin-releasing Hormone Therapy in Hypogonadal Males with Hypothalamic or Pituitary Dysfunction

Subcutaneous self-administration of synthetic gonadotrophin-releasing hormone 500 μg eight-hourly for up to one year by 12 male patients (five prepubertal) with clinical hypogonadism due to hypothalamic or pituitary disease resulted in the synthesis and continued release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). There was a rise in circulating androgen levels in all patients. Improvements in pubertal ratings were seen in some prepubertal patients. Potency returned in the adults and spermatogenesis was induced and maintained in the four patients who had received treatment for more than four months, total counts reaching between 7·8 and 432 × 106 spermatozoa. A fall in the FSH response to the releasing hormone occurred during spermatogenesis though LH was little affected. During the initial weeks of therapy FSH secretion usually occurred before that of LH though LH secretion was greater as treatment continued. FSH secretion also persisted for longer when treatment was stopped.

Luteinizing Hormone and Follicle Stimulating Hormone-Releasing Hormone Test in Patients with Hypothalamic Pituitary-Gonadal Dysfunction

A standard intravenous 100 μg luteinizing hormone/follicle stimulating hormone-releasing hormone (LH/FSH-RH) test was used to assess the pituitary gonadotrophin responses in 155 patients with a variety of diseases of the hypothalamic-pituitary-gonadal axis. In all but nine patients there was an increase in circulating levels of either LH or FSH in response to the releasing hormone though 137 (88%) were clinically hypogonadal. It was not possible with this test to distinguish between hypothalamic and pituitary causes of hypogonadotrophic hypogonadism, since a variety of LH and FSH responses emerged within the disease groups. However, primary gonadal failure characteristically resulted in exaggerated gonadotrophin response. The potential therapeutic use of the gonadotrophin releasing decapeptide is suggested in certain patients with hypogonadotrophic hypogonadism.