Dopamine agonists in the treatment of prolactinoma: are they still first choice?

Dopamine agonist therapy has been the cornerstone treatment for prolactinoma since the 1970s, replacing surgery in the primary management of this condition. These agents are effective in the management of prolactin excess, have a low side-effect profile, and in some cases may even be curative. However, recent studies of high dose dopamine agonists used in Parkinson's disease have raised the possibility that these drugs may be associated with cardiac valvulopathy. This paper discusses the modern use of dopamine agonists in a patient with prolactinoma.

The impact of ethnicity on the presentation of polycystic ovarian syndrome.

The effect of ethnicity on the prevalence and presentation of polycystic ovarian syndrome (PCOS) was examined in a cross-sectional study of women with clinical - and ultrasound - diagnosed PCOS. European, Maori and Pacific Island women were seen in proportion to the general population, whereas Indian women were over-represented and Chinese women under-represented. European and Maori women were more likely to present with hirsutism than other ethnic groups (43% versus 25%, p < 0.05), while European women were less likely to present with infertility (46% versus 68%, p < 0.01). The Pacific Island women had little or no acne but other signs of PCOS were similar among ethnic groups. Although less than 10% of patients were referred with obesity, the majority of PCOS women were overweight on examination. Maori and Pacific Island women were more obese and had the highest rates of insulin resistance and lipid abnormalities. The adverse metabolic profile of many of these women, particularly the Maori and Pacific Islanders, is very likely to predispose them to early cardiovascular disease.

Inhibin: a candidate gene for premature ovarian failure.

Premature ovarian failure (POF) occurs in 1% of all women, and in 0.1% of women under the age of 30 years. The mechanisms that give rise to POF are largely unknown. Inhibin has a role in regulating the pituitary secretion of FSH, and is therefore a potential candidate gene for ovarian failure. Using single-stranded conformation polymorphism (SSCP) and DNA sequencing, DNA samples were screened from 43 women with POF for mutations in the three inhibin genes. Two variants were found: a 1032C-->T transition in the INHssA gene in one patient, and a 769G-->A transition in the INHalpha gene in three patients. The INHssA variant appears to be a polymorphism, as there was no change in the amino acid sequence of the gene product. The INHalpha variant resulted in a non-conservative amino acid change, with a substitution from alanine to threonine. This alanine is highly conserved across species, and has the potential to affect receptor binding. The INHalpha variant is significantly associated with POF (3/43 patients; 7%) compared with control samples (1/150 normal controls; 0.7%) (Fisher's exact test, P < 0.035). Further analysis of the inhibin gene in POF patients and matched controls will determine its role in the aetiology of POF.

Potential role for growth hormone in human lactation insufficiency.

In order to evaluate the galactopoietic response to rhGH in mothers of normal babies with idiopathic lactation insufficiency arising in the early postpartum period, we performed a preliminary, randomised, single blind trial of 3 different doses of hGH: either 0.05, 0.1, or 0.2 IU/kg/day to a maximum of 16 IU/day, for 7 days. Total 24-hour milk production was determined in each mother 1 day prior to initiating therapy and on the last day of therapy. Milk production rose by 36.0 +/- 12.6% in the group receiving 0.2 IU/kg/day (n = 6) but by only 4.7 +/- 9.7%, (p < 0.04) in the combined lower dose group (n = 10). In conclusion, these data suggest that moderate dose hGH therapy in mothers with lactation insufficiency can improve galactopoiesis.

Insulin-like growth factors and their binding proteins in plasma and milk after growth hormone-stimulated galactopoiesis in normally lactating women.

We performed a double-blind randomized placebo-controlled trial of recombinant human growth hormone (hGH) in normally lactating women (N = 8 per group) to investigate the endocrine mode of action of the galactopoietic effect of this hormone. Insulin-like growth factors I (IGF-I) and II (IGF-II) and their binding proteins (IGFBP-1, IGFBP-2 and IGFBP-3) were measured by radioimmunoassay in plasma and milk samples collected throughout the study. All assays were validated for human plasma and milk. Human GH treatment (0.1 IU.kg-1 body wt.day-1 for 7 days) increased plasma concentrations of IGF-I from 22.1 +/- 1.3 nmol/l (mean +/- SEM) to 59.7 +/- 2.5 nmol/l (p < 0.01). At the end of the study the increase in plasma IGF-I correlated significantly with the increase in milk volume (r = 0.67, p < 0.005, N = 16). The IGF-I levels were considerably lower in milk, with 0.14 +/- 0.03 nmol/l before and 0.31 +/- 0.04 nmol/l after hGH treatment. The increase in milk IGF-I levels (134.0 +/- 14.5%) with hGH treatment was significant (p < 0.01) and plasma and milk IGF-I concentrations correlated significantly when considering all samples of the study (r = 0.45, p < 0.001, N = 56). The concentrations of IGF-II were not changed significantly with hGH treatment in plasma (52.5 +/- 2.5 nmol/l before and 42.6 +/- 3.9 nmol/l after treatment) or milk (2.1 +/- 0.29 nmol/l before and 2.3 +/- 0.49 nmol/l after hGH treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone stimulates galactopoiesis in healthy lactating women.

Sixteen normally lactating women underwent a double-blind randomized placebo-controlled trial of recombinant human growth hormone (hGH) to assess the effect of hGH on milk production in early lactation. Milk volumes were measured by test weighing procedures of the infants and removal of residual milk on a control day and after 7 days of treatment with recombinant hGH (0.1 IU.kg-1 body weight.d-1) or placebo treatment. Although all women were lactating normally before the study commenced, milk volume in 8 hGH treated mothers was increased (p < 0.02) by 18.5 +/- 1.4% (mean +/- SEM) compared to 11.6 +/- 2.0% in the placebo-treated group (N = 8). No adverse effects were seen with hGH treatment and no major changes noted in milk constituents. The hGH concentrations in milk were low and did not change with therapy. Plasma concentrations of IGF-1 increased significantly within 24 h of hGH treatment and increased further towards the end of the trial to values of 2.6-fold above the pretreatment values. The concentration of IGF-1 in milk was approximately 100-fold lower than those observed in plasma and could only be reliably measured after size exclusion chromatography to remove the interfering influence of IGF binding proteins in the radioimmunoassay. All women treated with hGH showed a small increase in milk IGF-1 concentrations but the values remained within the range of values observed in women receiving the placebo treatment (1.2-4.4 micrograms/l). Growth hormone treatment increased milk volume in normal lactating women during early lactation.(ABSTRACT TRUNCATED AT 250 WORDS)

The blood pressure response to unilateral adrenalectomy in primary aldosteronism.

The factors determining the outcome of blood pressure after removal of the aldosterone-secreting adenoma in primary aldosteronism are largely unknown. We have studied the results of surgery in 21 patients with this disorder, all of whom were investigated and treated in a single referral centre, and evaluated the contributions of clinical, biochemical and pathological factors to blood pressure outcome. Blood pressure before surgery was high (mean 210/121 mmHg), but after an average period of 5.4 years 12 patients (60 per cent) were considered by their primary physician not to require antihypertensive medication and a further seven had reduced drug requirements. In only two patients was arterial pressure unimproved by surgery. Blood pressure recordings within six months of surgery were not a good predictor of later levels. Of the clinical, electrolyte, hormone and pathological features assessed, only the systolic pressure before surgery, and abnormalities in the optic fundi, correlated statistically with final blood pressure ranking. There was no relationship between the severity of vascular changes in the adrenal or kidney biopsy tissue and final blood pressure. These results show that while the blood pressure response to the removal of a single adrenal adenoma is usually good, it is not possible to predict accurately the final blood pressure response using these criteria.

Successful treatment of scleroderma renal crisis with enalapril.

A patient with scleroderma renal crisis is described. At presentation he had severe hypertension, deteriorating renal function, microangiopathic haemolytic anaemia, and elevated levels of renin, aldosterone and noradrenaline. Enalapril controlled blood pressure, stabilized renal function, lowered aldosterone and noradrenaline levels, and improved peripheral circulation. It appears that converting-enzyme inhibitors can favourably alter the outlook of this otherwise fatal disorder.

The effect of peripheral catecholamine concentrations on the pituitary-adrenal response to corticotrophin releasing factor in man.

To evaluate the effect of changes in plasma catecholamines on the pituitary-adrenal response to ovine corticotrophin releasing factor (CRF) in normal man, the response to CRF alone (10 subjects) was compared responses after infusions of adrenaline (6 subjects), noradrenaline (6 subjects) and after oral administration of the alpha 2 agonist clonidine (10 subjects). Compared to control levels, plasma adrenaline and noradrenaline concentrations were increased three- and four-fold respectively by exogenous infusions, whereas plasma noradrenaline was significantly lowered by clonidine. Despite these changes in plasma catecholamine levels, the responses of plasma ACTH, cortisol and aldosterone to CRF did not differ significantly from control (CRF alone) in any of the three studies. Neither clonidine pretreatment nor catecholamine infusions altered basal levels of plasma ACTH, cortisol or aldosterone and no effect of CRF or catecholamine manipulations on plasma arginine vasopressin concentration was observed. These results show that modulation of peripheral plasma catecholamine levels within physiological limits does not affect CRF-stimulated release of ACTH or the adrenal response in normal man.

Augmentation of the response to CRF in man: relative contributions of endogenous angiotensin and vasopressin.

The plasma ACTH response to corticotrophin releasing factor (CRF) was studied in seven normal individuals. Five subjects were restudied following 4 d of salt restriction which resulted in raised endogenous plasma angiotensin II secretion. In a third experiment six subjects were given CRF following pre-infusion of hypertonic saline which significantly increased endogenous plasma vasopressin (AVP) levels. We were unable to demonstrate that high endogenous plasma AII levels were associated with a significant change in the plasma ACTH or cortisol responses to CRF. However there was an almost three-fold increase in the ACTH response when endogenous plasma AVP was elevated by hypertonic saline. It is concluded that AVP is likely to be of physiological importance in potentiating the ACTH response to CRF and that AVP and CRF together may provide a better test of pituitary ACTH secretion than either peptide alone.